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Inflammation, thrombosis biomarkers tied to COVID-19 deaths
Their prospective cohort study of 1150 patients hospitalized with the disease in New York City also revealed a high proportion of racial and ethnic minorities, and confirmed high rates of critical illness and mortality.
“Of particular interest is the finding that over three quarters of critically ill patients required a ventilator and almost one third required renal dialysis support,” Max O’Donnell, MD, MPH, assistant professor of medicine and epidemiology at Columbia University in New York City, said in a press release.
O’Donnell and colleagues published the results of their study online today in The Lancet. It is the largest prospective cohort study published in the United States, they said.
“Although the clinical spectrum of disease has been characterised in reports from China and Italy, until now, detailed understanding of how the virus is affecting critically ill patients in the US has been limited to reports from a small number of cases,” said Natalie Yip, MD, assistant professor of medicine at Columbia University.
In the cohort, drawn from two NewYork-Presbyterian hospitals, the researchers focused on the 257 (22%) patients who required intensive care. When they estimated inflammation through interleukin-6 (IL-6) concentrations and thrombosis through D-dimer concentrations, they found a 10% increased risk for death with every 10% increase of IL-6 (adjusted hazard ratio [aHR], 1.11; 95% confidence interval [CI], 1.02–1.20) or D-dimer concentration (aHR, 1.10; 95% CI, 1.01–1.19).
“The association of mortality with higher concentrations of IL-6 and d-dimer is particularly relevant for two reasons,” write Giacomo Grasselli, from the Fondazione IRCCS Ca’ Granda Ospediale Maggiore Policlinico, and Alberto Zanella, from the University of Milan, Italy, in an accompanying commentary.
“First, it confirms the key pathogenic role played by the activation of systemic inflammation and endothelial-vascular damage in the development of organ dysfunction,” they write. “Second, it provides the rationale for the design of clinical trials for measuring the efficacy of treatment with immunomodulating and anticoagulant drugs.”
Seventeen percent of patients received interleukin receptor antagonists and 26% received corticosteroids, but the authors did not report any data on the effects of these treatments, or any data about anticoagulant therapies administered.
Severe disease common
The study also highlighted a high proportion of ethnic and racial minorities. Sixty-two percent of the critically ill patients were Hispanic or Latinx, 19% Black, 32% White, and 3% Asian.
Their median age was 62 years and 67% were men. Eighty-two percent had at least one chronic illness, most commonly hypertension (63%), followed by diabetes (36%). Forty-six percent were obese.
As of April 28, 2020, 101 (39%) of the critically ill patients had died following a median of 9 days (interquartile range (IQR), 5–15) in the hospital and 94 (37%) remained hospitalized. Of the 203 patients who received invasive mechanical ventilation, 84 (41%) had died.
The poor prognosis of patients requiring ventilation is consistent with data from a report on patients treated in National Health Service intensive care units in England, Wales, and Northern Ireland through May 15. Overall, 11,292 patients with COVID-19 required critical care, and 4855 needed advanced respiratory support. Approximately half of the patients receiving mechanical ventilation had died 30 days after starting critical care.
In the New York study, patients spent an average of 18 days on a ventilator (IQR, 9–28 days). This is a longer period than reported in smaller studies of cases from Washington state, but corresponds with a recent report from Italy, the researchers said.
Remarkably, O’Donnell and colleagues report that almost a third (31%) of critically ill patients developed severe kidney damage and required dialysis.
Mortality was associated with several baseline factors, including older age (aHR, 1.31 [95% CI, 1.09–1.57] per 10-year increase), chronic cardiac disease (aHR, 1.76; 95% CI, 1.08–2·86), and chronic pulmonary disease (aHR, 2.94; 95% CI, 1.48–5.84).
Authors of the New York study reported financial relationships to ICE Neurosystems, ALung Technologies, Baxter, BREETHE, Xenios, Hemovent, Gilead Sciences, Amazon, and Karyopharm Therapeutics. Grasselli reports personal fees from Biotest, Draeger, Fisher & Paykel, Maquet, Merck Sharp & Dohme, and Pfizer, all outside the area of work commented on here. Zanella has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Their prospective cohort study of 1150 patients hospitalized with the disease in New York City also revealed a high proportion of racial and ethnic minorities, and confirmed high rates of critical illness and mortality.
“Of particular interest is the finding that over three quarters of critically ill patients required a ventilator and almost one third required renal dialysis support,” Max O’Donnell, MD, MPH, assistant professor of medicine and epidemiology at Columbia University in New York City, said in a press release.
O’Donnell and colleagues published the results of their study online today in The Lancet. It is the largest prospective cohort study published in the United States, they said.
“Although the clinical spectrum of disease has been characterised in reports from China and Italy, until now, detailed understanding of how the virus is affecting critically ill patients in the US has been limited to reports from a small number of cases,” said Natalie Yip, MD, assistant professor of medicine at Columbia University.
In the cohort, drawn from two NewYork-Presbyterian hospitals, the researchers focused on the 257 (22%) patients who required intensive care. When they estimated inflammation through interleukin-6 (IL-6) concentrations and thrombosis through D-dimer concentrations, they found a 10% increased risk for death with every 10% increase of IL-6 (adjusted hazard ratio [aHR], 1.11; 95% confidence interval [CI], 1.02–1.20) or D-dimer concentration (aHR, 1.10; 95% CI, 1.01–1.19).
“The association of mortality with higher concentrations of IL-6 and d-dimer is particularly relevant for two reasons,” write Giacomo Grasselli, from the Fondazione IRCCS Ca’ Granda Ospediale Maggiore Policlinico, and Alberto Zanella, from the University of Milan, Italy, in an accompanying commentary.
“First, it confirms the key pathogenic role played by the activation of systemic inflammation and endothelial-vascular damage in the development of organ dysfunction,” they write. “Second, it provides the rationale for the design of clinical trials for measuring the efficacy of treatment with immunomodulating and anticoagulant drugs.”
Seventeen percent of patients received interleukin receptor antagonists and 26% received corticosteroids, but the authors did not report any data on the effects of these treatments, or any data about anticoagulant therapies administered.
Severe disease common
The study also highlighted a high proportion of ethnic and racial minorities. Sixty-two percent of the critically ill patients were Hispanic or Latinx, 19% Black, 32% White, and 3% Asian.
Their median age was 62 years and 67% were men. Eighty-two percent had at least one chronic illness, most commonly hypertension (63%), followed by diabetes (36%). Forty-six percent were obese.
As of April 28, 2020, 101 (39%) of the critically ill patients had died following a median of 9 days (interquartile range (IQR), 5–15) in the hospital and 94 (37%) remained hospitalized. Of the 203 patients who received invasive mechanical ventilation, 84 (41%) had died.
The poor prognosis of patients requiring ventilation is consistent with data from a report on patients treated in National Health Service intensive care units in England, Wales, and Northern Ireland through May 15. Overall, 11,292 patients with COVID-19 required critical care, and 4855 needed advanced respiratory support. Approximately half of the patients receiving mechanical ventilation had died 30 days after starting critical care.
In the New York study, patients spent an average of 18 days on a ventilator (IQR, 9–28 days). This is a longer period than reported in smaller studies of cases from Washington state, but corresponds with a recent report from Italy, the researchers said.
Remarkably, O’Donnell and colleagues report that almost a third (31%) of critically ill patients developed severe kidney damage and required dialysis.
Mortality was associated with several baseline factors, including older age (aHR, 1.31 [95% CI, 1.09–1.57] per 10-year increase), chronic cardiac disease (aHR, 1.76; 95% CI, 1.08–2·86), and chronic pulmonary disease (aHR, 2.94; 95% CI, 1.48–5.84).
Authors of the New York study reported financial relationships to ICE Neurosystems, ALung Technologies, Baxter, BREETHE, Xenios, Hemovent, Gilead Sciences, Amazon, and Karyopharm Therapeutics. Grasselli reports personal fees from Biotest, Draeger, Fisher & Paykel, Maquet, Merck Sharp & Dohme, and Pfizer, all outside the area of work commented on here. Zanella has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Their prospective cohort study of 1150 patients hospitalized with the disease in New York City also revealed a high proportion of racial and ethnic minorities, and confirmed high rates of critical illness and mortality.
“Of particular interest is the finding that over three quarters of critically ill patients required a ventilator and almost one third required renal dialysis support,” Max O’Donnell, MD, MPH, assistant professor of medicine and epidemiology at Columbia University in New York City, said in a press release.
O’Donnell and colleagues published the results of their study online today in The Lancet. It is the largest prospective cohort study published in the United States, they said.
“Although the clinical spectrum of disease has been characterised in reports from China and Italy, until now, detailed understanding of how the virus is affecting critically ill patients in the US has been limited to reports from a small number of cases,” said Natalie Yip, MD, assistant professor of medicine at Columbia University.
In the cohort, drawn from two NewYork-Presbyterian hospitals, the researchers focused on the 257 (22%) patients who required intensive care. When they estimated inflammation through interleukin-6 (IL-6) concentrations and thrombosis through D-dimer concentrations, they found a 10% increased risk for death with every 10% increase of IL-6 (adjusted hazard ratio [aHR], 1.11; 95% confidence interval [CI], 1.02–1.20) or D-dimer concentration (aHR, 1.10; 95% CI, 1.01–1.19).
“The association of mortality with higher concentrations of IL-6 and d-dimer is particularly relevant for two reasons,” write Giacomo Grasselli, from the Fondazione IRCCS Ca’ Granda Ospediale Maggiore Policlinico, and Alberto Zanella, from the University of Milan, Italy, in an accompanying commentary.
“First, it confirms the key pathogenic role played by the activation of systemic inflammation and endothelial-vascular damage in the development of organ dysfunction,” they write. “Second, it provides the rationale for the design of clinical trials for measuring the efficacy of treatment with immunomodulating and anticoagulant drugs.”
Seventeen percent of patients received interleukin receptor antagonists and 26% received corticosteroids, but the authors did not report any data on the effects of these treatments, or any data about anticoagulant therapies administered.
Severe disease common
The study also highlighted a high proportion of ethnic and racial minorities. Sixty-two percent of the critically ill patients were Hispanic or Latinx, 19% Black, 32% White, and 3% Asian.
Their median age was 62 years and 67% were men. Eighty-two percent had at least one chronic illness, most commonly hypertension (63%), followed by diabetes (36%). Forty-six percent were obese.
As of April 28, 2020, 101 (39%) of the critically ill patients had died following a median of 9 days (interquartile range (IQR), 5–15) in the hospital and 94 (37%) remained hospitalized. Of the 203 patients who received invasive mechanical ventilation, 84 (41%) had died.
The poor prognosis of patients requiring ventilation is consistent with data from a report on patients treated in National Health Service intensive care units in England, Wales, and Northern Ireland through May 15. Overall, 11,292 patients with COVID-19 required critical care, and 4855 needed advanced respiratory support. Approximately half of the patients receiving mechanical ventilation had died 30 days after starting critical care.
In the New York study, patients spent an average of 18 days on a ventilator (IQR, 9–28 days). This is a longer period than reported in smaller studies of cases from Washington state, but corresponds with a recent report from Italy, the researchers said.
Remarkably, O’Donnell and colleagues report that almost a third (31%) of critically ill patients developed severe kidney damage and required dialysis.
Mortality was associated with several baseline factors, including older age (aHR, 1.31 [95% CI, 1.09–1.57] per 10-year increase), chronic cardiac disease (aHR, 1.76; 95% CI, 1.08–2·86), and chronic pulmonary disease (aHR, 2.94; 95% CI, 1.48–5.84).
Authors of the New York study reported financial relationships to ICE Neurosystems, ALung Technologies, Baxter, BREETHE, Xenios, Hemovent, Gilead Sciences, Amazon, and Karyopharm Therapeutics. Grasselli reports personal fees from Biotest, Draeger, Fisher & Paykel, Maquet, Merck Sharp & Dohme, and Pfizer, all outside the area of work commented on here. Zanella has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Maskomania: Masks and COVID-19
A comprehensive review
On April 3, the Centers for Disease Control and Prevention issued an advisory that the general public wear cloth face masks when outside, particularly those residing in areas with significant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) community transmission.1 Recent research reveals several factors related to the nature of the virus as well as the epidemiologic spread of the illness that may have led to this decision.
However, controversy still prevails whether this recommendation will alleviate or aggravate disease progression. With many hospitals across America lacking sufficient personal protective equipment (PPE) and scrambling for supplies, universal masking may create more chaos, especially with certain states imposing monetary fines on individuals spotted outdoors without a mask. With new information being discovered each day about COVID-19, it is more imperative than ever to update existing strategies and formulate more effective methods to flatten the curve.
Airborne vs. droplet transmission
According to a scientific brief released by the World Health Organization, there have been studies with mixed evidence and opinions regarding the presence of COVID-19 ribonucleic acid (RNA) in air samples.2 In medRxiv, Santarpia et al., from the University of Nebraska Medical Center, Omaha, detected viral RNA in samples taken from beneath a patient’s bed and from a window ledge, both areas in which neither the patient nor health care personnel had any direct contact. They also found that 66.7% of air samples taken from a hospital hallway carried virus-containing particles.3 It is worth noting that certain aerosol-generating procedures (AGP) may increase the likelihood of airborne dissemination. Whether airborne transmission is a major mode of COVID-19 spread in the community and routine clinical settings (with no aerosol-generating procedures) is still a debatable question without a definitive answer.
We should consider the epidemiology of COVID-19 thus far in the pandemic to determine if transmission patterns are more consistent with that of other common respiratory viral pathogens or more consistent with that of the agents we classically consider to be transmitted by the airborne route (measles, varicella zoster virus, and Mycobacterium tuberculosis). The attack rates in various settings (household, health care, and the public) as well as the expected number of secondary cases from a single infected individual in a susceptible population (R0) are more consistent with those of a droplet spread pathogen.
For measles, the R0 is 12-18, and the secondary household attack rates are ≥ 90%. In case of the varicella zoster virus, the R0 is ~10, and the secondary household attack rate is 85%. The R0 for pulmonary tuberculosis is up to 10 (per year) and the secondary household attack rate has been reported to be >50%. With COVID-19, the R0 appears to be around 2.5-3 and secondary household attack rates are ~ 10% from data available so far, similar to that of influenza viruses. This discrepancy suggests that droplet transmission may be more likely. The dichotomy of airborne versus droplet mode of spread may be better described as a continuum, as pointed out in a recent article in the JAMA. Infectious droplets form turbulent gas clouds allowing the virus particles to travel further and remain in the air longer.4 The necessary precautions for an airborne illness should be chosen over droplet precautions, especially when there is concern for an AGP.
Universal masking: Risks and benefits
The idea of universal masking has been debated extensively since the initial stages of the COVID-19 pandemic. According to public health authorities, significant exposure is defined as “face-to-face contact within 6 feet with a patient with symptomatic COVID-19” in the range of a few minutes up to 30 minutes.5 The researchers wrote in the New England Journal of Medicine that the chance of catching COVID-19 from a passing interaction in a public space is therefore minimal, and it may seem unnecessary to wear a mask at all times in public.
As reported in Science, randomized clinical studies performed on other viruses in the past have shown no added protection conferred by wearing a mask, though small sample sizes and noncompliance are limiting factors to their validity.6 On the contrary, mask wearing has been enforced in many parts of Asia, including Hong Kong and Singapore with promising results.5 Leung et al. stated in The Lancet that the lack of proof that masks are effective should not rule them as ineffective. Also, universal masking would reduce the stigma around symptomatic individuals covering their faces. It has become a cultural phenomenon in many southeast Asian countries and has been cited as one of the reasons for relatively successful containment in Singapore, South Korea, and Taiwan. The most important benefit of universal masking is protection attained by preventing spread from asymptomatic, mildly symptomatic, and presymptomatic carriers.7
In a study in the New England Journal of Medicine that estimated viral loads during various stages of COVID-19, researchers found that asymptomatic patients had similar viral loads to symptomatic patients, thereby suggesting high potential for transmission.8 Furthermore, numerous cases are being reported concerning the spread of illness from asymptomatic carriers.9-12 In an outbreak at a skilled nursing facility in Washington outlined in MMWR, 13 of 23 residents with positive test results were asymptomatic at the time of testing, and of those, 3 never developed any symptoms.12
Many hospitals are now embracing the policy of universal masking. A mask is a critical component of the personal protective equipment (PPE) clinicians need when caring for symptomatic patients with respiratory viral infections, in conjunction with a gown, gloves, and eye protection. Masking in this context is already part of routine operations in most hospitals. There are two scenarios in which there may be possible benefits. One scenario is the lower likelihood of transmission from asymptomatic and minimally symptomatic health care workers with COVID-19 to other providers and patients. The other less plausible benefit of universal masking among health care workers is that it may provide some protection in the possibility of caring for an unrecognized COVID-19 patient. However, universal masking should be coupled with other favorable practices like temperature checks and symptom screening on a daily basis to avail the maximum benefit from masking. Despite varied opinions on the outcomes of universal masking, this measure helps improve health care workers’ safety, psychological well-being, trust in their hospital, and decreases anxiety of acquiring the illness.
Efficacy of various types of masks
With the possibility of airborne transmission of the virus, are cloth masks as recommended by the CDC truly helpful in preventing infection? A study in the Journal of Medical Virology demonstrates 99.98%, 97.14%, and 95.15% efficacy for N95, surgical, and homemade masks, respectively, in blocking the avian influenza virus (comparable to coronavirus in size and physical characteristics). The homemade mask was created using one layer of polyester cloth and a four-layered kitchen filter paper.13
N95 masks (equivalent to FFP/P2 in European countries) are made of electrostatically charged polypropylene microfibers designed to filter particles measuring 100-300nm in diameter with 95% efficacy. A single SARS-CoV-2 molecule measures 125 nm approximately. N99 (FFP3) and N100 (P3) masks are also available, though not as widely used, with 99% and 99.7% efficacy respectively for the same size range. Though cloth masks are the clear-cut last resort for medical professionals, a few studies state no clinically proven difference in protection between surgical masks and N95 respirators.14,15 Even aerosolized droplets (< 5 mcm) were found to be blocked by surgical masks in a Nature Medicine study in which 4/10 subjects tested positive for coronavirus in exhaled breath samples without masks and 0/10 subjects with masks.16
On the contrary, an Annals of Internal Medicine study of four COVID-19 positive subjects that “neither surgical masks nor cloth masks effectively filtered SARS-CoV-2 during coughs of infected patients.” In fact, more contamination was found on the outer surface of the masks when compared to the inner surface, probably owing to the masks’ aerodynamic properties.17 Because of limitations present in the above-mentioned studies, further research is necessary to conclusively determine which types of masks are efficacious in preventing infection by the virus. In a scarcity of surgical masks and respirators for health care personnel, suboptimal masks can be of some use provided there is adherent use, minimal donning and doffing, and it is to be accompanied by adequate hand washing practices.14
In case of severe infections with high viral loads or patients undergoing aerosol-generating procedures, powered air-purifying respirators (PAPRs) also are advisable as they confer greater protection than N95 respirators, according to a study in the Annals of Work Exposures and Health. Despite being more comfortable for long-term use and accommodative of facial hair, their use is limited because of high cost and difficult maintenance.18 3-D printing also is being used to combat the current shortage of masks worldwide. However, a study from the International Journal of Oral & Maxillofacial Surgery reported that virologic testing for leakage between the two reusable components and contamination of the components themselves after one or multiple disinfection cycles is essential before application in real-life situations.19
Ongoing issues
WHO estimates a monthly requirement of nearly 90 million masks exclusively for health care workers to protect themselves against COVID-19.20 In spite of increasing the production rate by 40%, if the general public hoards masks and respirators, the results could be disastrous. Personal protective equipment is currently at 100 times the usual demand and 20 times the usual cost, with stocks backlogged by 4-6 months. The appropriate order of priority in distribution to health care professionals first, followed by those caring for infected patients is critical.20 In a survey conducted by the Association for Professionals in Infection Control and Epidemiology, results revealed that 48% of the U.S. health care facilities that responded were either out or nearly out of respirators as of March 25. 21
The gravest risk behind the universal masking policy is the likely depletion of medical resources.22 A possible solution to this issue could be to modify the policy to stagger the requirement based on the severity of community transmission in that area of residence. In the article appropriately titled “Rational use of face masks in the COVID-19 pandemic” published in The Lancet Respiratory Medicine, researchers described how the Chinese population was classified into moderate, low, and very-low risk of infection categories and advised to wear a surgical or disposable mask, disposable mask, and no mask respectively.23 This curbs widespread panic and eagerness by the general public to stock up on essential medical equipment when it may not even be necessary.
Reuse, extended use, and sterilization
Several studies have been conducted to identify the viability of the COVID-19 on various surfaces.24-25 The CDC and National Institute for Occupational Safety and Health (NIOSH) guidelines state that an N95 respirator can be used up to 8 hours with intermittent or continuous use, though this number is not fixed and heavily depends upon the extent of exposure, risk of contamination, and frequency of donning and doffing26,27. Though traditionally meant for single-time usage, after 8 hours, the mask can be decontaminated and reused. The CDC defines extended use as the “practice of wearing the same N95 respirator for repeated close-contact encounters with several patients, without removing the respirator between patient encounters.” Reuse is defined as “using the same N95 respirator for multiple encounters with patients but removing it (‘doffing’) after each encounter. The respirator is stored in between encounters to be put on again (‘donned’) prior to the next encounter with a patient.”
It has been established that extended use is more advisable than reuse given the lower risk of self-inoculation. Furthermore, health care professionals are urged to wear a cleanable face shield or disposable mask over the respirator to minimize contamination and practice diligent hand hygiene before and after handling the respirator. N95 respirators are to be discarded following aerosol-generating procedures or if they come in contact with blood, respiratory secretions, or bodily fluids. They should also be discarded in case of close contact with an infected patient or if they cause breathing difficulties to the wearer.27 This may not always be possible given the unprecedented shortage of PPE, hence decontamination techniques and repurposing are the need of the hour.
In Anesthesia & Analgesia, Naveen Nathan, MD, of Northwestern University, Chicago, recommends recycling four masks in a series, using one per day, keeping the mask in a dry, clean environment, and then repeating use of the first mask on the 5th day, the second on the 6th day, and so forth. This ensures clearance of the virus particles by the next use. Alternatively, respirators can be sterilized between uses by heating to 70º C (158º F) for 30 minutes. Liquid disinfectants such as alcohol and bleach as well as ultraviolet rays in sunlight tend to damage masks.28 Steam sterilization is the most commonly utilized technique in hospitals. Other methods, described by the N95/PPE Working Group, report include gamma irradiation at 20kGy (2MRad) for large-scale sterilization (though the facilities may not be widely available), vaporized hydrogen peroxide, ozone decontamination, ultraviolet germicidal irradiation, and ethylene oxide.29 Though a discussion on various considerations of decontamination techniques is out of the scope of this article, detailed guidelines have been published by the CDC30 and the COVID-19 Healthcare Coalition.30
Conclusion
A recent startling discovery reported on in Emerging Infectious Diseases suggests that the basic COVID-19 reproductive number (R0) is actually much higher than previously thought. Using expanded data, updated epidemiologic parameters, and the current outbreak dynamics in Wuhan, the team came to the conclusion that the R0 for the novel coronavirus is actually 5.7 (95% CI 3.8-8.9), compared with an initial estimate of 2.2-2.7.31 Concern for transmissibility demands heightened prevention strategies until more data evolves. The latest recommendation by the CDC regarding cloth masking in the public may help slow the progression of the pandemic. However, it is of paramount importance to keep in mind that masks alone are not enough to control the disease and must be coupled with other nonpharmacologic interventions such as social distancing, quarantining/isolation, and diligent hand hygiene.
Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Bharathidasan is a recent medical graduate from India with an interest in public health and community research; she plans to pursue residency training in the United States. Ms. Freshman is currently the regional director of infection prevention for WellSpan Health and has 35 years of experience in nursing. Dr. Palabindala is the medical director, utilization management and physician advisory services, at the University of Mississippi Medical Center, Jackson. He is an associate professor of medicine and academic hospitalist in the UMMC School of Medicine.
References
1. Centers for Disease Control and Prevention. Recommendation regarding the use of cloth face coverings.
2. World Health Organization. Modes of transmission of virus causing COVID-19 : implications for IPC precaution recommendations. Sci Br. 2020 Mar 29:1-3.
3. Santarpia JL et al. Transmission potential of SARS-CoV-2 in viral shedding observed at the University of Nebraska Medical Center. 2020 Mar 26. medRxiv. 2020;2020.03.23.20039446.
4. Bourouiba L. Turbulent gas clouds and respiratory pathogen emissions: Potential implications for reducing transmission of COVID-19. JAMA. 2020 Mar 26. doi: 10.1001/jama.2020.4756.
5. Klompas M et al. Universal masking in hospitals in the Covid-19 era. N Engl J Med. 2020 Apr 1. doi: 10.1056/NEJMp2006372.
6. Servick K. Would everyone wearing face masks help us slow the pandemic? Science 2020 Mar 28. doi: 10.1126/science.abb9371.
7. Leung CC et al. Mass masking in the COVID-19 epidemic: People need guidance. Lancet 2020 Mar 21;395(10228):945. doi: 10.1016/S0140-6736(20)30520-1.
8. Zou L et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020 Mar 19;382(12):1177-9.
9. Pan X et al. Asymptomatic cases in a family cluster with SARS-CoV-2 infection. Lancet Infect Dis. 2020 Apr;20(4):410-1.
10. Bai Y et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020 Feb 21;323(14):1406-7.
11. Wei WE et al. Presymptomatic transmission of SARS-CoV-2 – Singapore, Jan. 23–March 16, 2020. MMWR Morb Mortal Wkly Rep 2020;69:411-5.
12. Kimball A et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility – King County, Washington, March 2020. 2020 Apr 3. MMWR Morb Mortal Wkly Rep 2020;69:377-81.
13. Ma Q-X et al. Potential utilities of mask wearing and instant hand hygiene for fighting SARS-CoV-2. J Med Virol. 2020 Mar 31;10.1002/jmv.25805. doi: 10.1002/jmv.25805.
14. Abd-Elsayed A et al. Utility of substandard face mask options for health care workers during the COVID-19 pandemic. Anesth Analg. 2020 Mar 31;10.1213/ANE.0000000000004841. doi: 10.1213/ANE.0000000000004841.
15. Long Y et al. Effectiveness of N95 respirators versus surgical masks against influenza: A systematic review and meta-analysis. J Evid Based Med. 2020 Mar 13;10.1111/jebm.12381. doi: 10.1111/jebm.12381.
16. Leung NHL et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nat Med. 2020 May;26(5):676-80.
17. Bae S et al. Effectiveness of surgical and cotton masks in blocking SARS-CoV-2: A controlled comparison in 4 patients. Ann Intern Med. 2020 Apr 6;M20-1342. doi: 10.7326/M20-1342.
18. Brosseau LM. Are powered air purifying respirators a solution for protecting healthcare workers from emerging aerosol-transmissible diseases? Ann Work Expo Health. 2020 Apr 30;64(4):339-41.
19. Swennen GRJ et al. Custom-made 3D-printed face masks in case of pandemic crisis situations with a lack of commercially available FFP2/3 masks. Int J Oral Maxillofac Surg. 2020 May;49(5):673-7.
20. Mahase E. Coronavirus: Global stocks of protective gear are depleted, with demand at “100 times” normal level, WHO warns. BMJ. 2020 Feb 10;368:m543. doi: 10.1136/bmj.m543.
21. National survey shows dire shortages of PPE, hand sanitizer across the U.S. 2020 Mar 27. Association for Professionals in Infection Control and Epidemiology (APIC) press briefing.
22. Wu HL et al. Facemask shortage and the novel coronavirus disease (COVID-19) outbreak: Reflections on public health measures. EClinicalMedicine. 2020 Apr 3:100329. doi: 10.1016/j.eclinm.2020.100329.
23. Feng S et al. Rational use of face masks in the COVID-19 pandemic. Lancet Respir Med. 2020 May;8(5):434-6.
24. Chin AWH et al. Stability of SARS-CoV-2 in different environmental. The Lancet Microbe. 2020 May 1;5247(20):2004973. doi. org/10.1016/S2666-5247(20)30003-3.
25. van Doremalen N et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020 Apr 16;382(16):1564-7.
26. NIOSH – Workplace Safety and Health Topics: Recommended guidance for extended use and limited reuse of n95 filtering facepiece respirators in healthcare settings.
27. Centers for Disease Control and Prevention. COVID-19 decontamination and reuse of filtering facepiece respirators. 2020 Apr 15.
28. Nathan N. Waste not, want not: The re-usability of N95 masks. Anesth Analg. 2020 Mar 31.doi: 10.1213/ane.0000000000004843.
29. European Centre for Disease Prevention and Control technical report. Cloth masks and mask sterilisation as options in case of shortage of surgical masks and respirators. 2020 Mar.
30. N95/PPE Working Group report. Evaluation of decontamination techniques for the reuse of N95 respirators. 2020 Apr 3;2:1-7.
31. Sanche Set al. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020 Jul. doi. org/10.3201/eid2607.200282.
A comprehensive review
A comprehensive review
On April 3, the Centers for Disease Control and Prevention issued an advisory that the general public wear cloth face masks when outside, particularly those residing in areas with significant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) community transmission.1 Recent research reveals several factors related to the nature of the virus as well as the epidemiologic spread of the illness that may have led to this decision.
However, controversy still prevails whether this recommendation will alleviate or aggravate disease progression. With many hospitals across America lacking sufficient personal protective equipment (PPE) and scrambling for supplies, universal masking may create more chaos, especially with certain states imposing monetary fines on individuals spotted outdoors without a mask. With new information being discovered each day about COVID-19, it is more imperative than ever to update existing strategies and formulate more effective methods to flatten the curve.
Airborne vs. droplet transmission
According to a scientific brief released by the World Health Organization, there have been studies with mixed evidence and opinions regarding the presence of COVID-19 ribonucleic acid (RNA) in air samples.2 In medRxiv, Santarpia et al., from the University of Nebraska Medical Center, Omaha, detected viral RNA in samples taken from beneath a patient’s bed and from a window ledge, both areas in which neither the patient nor health care personnel had any direct contact. They also found that 66.7% of air samples taken from a hospital hallway carried virus-containing particles.3 It is worth noting that certain aerosol-generating procedures (AGP) may increase the likelihood of airborne dissemination. Whether airborne transmission is a major mode of COVID-19 spread in the community and routine clinical settings (with no aerosol-generating procedures) is still a debatable question without a definitive answer.
We should consider the epidemiology of COVID-19 thus far in the pandemic to determine if transmission patterns are more consistent with that of other common respiratory viral pathogens or more consistent with that of the agents we classically consider to be transmitted by the airborne route (measles, varicella zoster virus, and Mycobacterium tuberculosis). The attack rates in various settings (household, health care, and the public) as well as the expected number of secondary cases from a single infected individual in a susceptible population (R0) are more consistent with those of a droplet spread pathogen.
For measles, the R0 is 12-18, and the secondary household attack rates are ≥ 90%. In case of the varicella zoster virus, the R0 is ~10, and the secondary household attack rate is 85%. The R0 for pulmonary tuberculosis is up to 10 (per year) and the secondary household attack rate has been reported to be >50%. With COVID-19, the R0 appears to be around 2.5-3 and secondary household attack rates are ~ 10% from data available so far, similar to that of influenza viruses. This discrepancy suggests that droplet transmission may be more likely. The dichotomy of airborne versus droplet mode of spread may be better described as a continuum, as pointed out in a recent article in the JAMA. Infectious droplets form turbulent gas clouds allowing the virus particles to travel further and remain in the air longer.4 The necessary precautions for an airborne illness should be chosen over droplet precautions, especially when there is concern for an AGP.
Universal masking: Risks and benefits
The idea of universal masking has been debated extensively since the initial stages of the COVID-19 pandemic. According to public health authorities, significant exposure is defined as “face-to-face contact within 6 feet with a patient with symptomatic COVID-19” in the range of a few minutes up to 30 minutes.5 The researchers wrote in the New England Journal of Medicine that the chance of catching COVID-19 from a passing interaction in a public space is therefore minimal, and it may seem unnecessary to wear a mask at all times in public.
As reported in Science, randomized clinical studies performed on other viruses in the past have shown no added protection conferred by wearing a mask, though small sample sizes and noncompliance are limiting factors to their validity.6 On the contrary, mask wearing has been enforced in many parts of Asia, including Hong Kong and Singapore with promising results.5 Leung et al. stated in The Lancet that the lack of proof that masks are effective should not rule them as ineffective. Also, universal masking would reduce the stigma around symptomatic individuals covering their faces. It has become a cultural phenomenon in many southeast Asian countries and has been cited as one of the reasons for relatively successful containment in Singapore, South Korea, and Taiwan. The most important benefit of universal masking is protection attained by preventing spread from asymptomatic, mildly symptomatic, and presymptomatic carriers.7
In a study in the New England Journal of Medicine that estimated viral loads during various stages of COVID-19, researchers found that asymptomatic patients had similar viral loads to symptomatic patients, thereby suggesting high potential for transmission.8 Furthermore, numerous cases are being reported concerning the spread of illness from asymptomatic carriers.9-12 In an outbreak at a skilled nursing facility in Washington outlined in MMWR, 13 of 23 residents with positive test results were asymptomatic at the time of testing, and of those, 3 never developed any symptoms.12
Many hospitals are now embracing the policy of universal masking. A mask is a critical component of the personal protective equipment (PPE) clinicians need when caring for symptomatic patients with respiratory viral infections, in conjunction with a gown, gloves, and eye protection. Masking in this context is already part of routine operations in most hospitals. There are two scenarios in which there may be possible benefits. One scenario is the lower likelihood of transmission from asymptomatic and minimally symptomatic health care workers with COVID-19 to other providers and patients. The other less plausible benefit of universal masking among health care workers is that it may provide some protection in the possibility of caring for an unrecognized COVID-19 patient. However, universal masking should be coupled with other favorable practices like temperature checks and symptom screening on a daily basis to avail the maximum benefit from masking. Despite varied opinions on the outcomes of universal masking, this measure helps improve health care workers’ safety, psychological well-being, trust in their hospital, and decreases anxiety of acquiring the illness.
Efficacy of various types of masks
With the possibility of airborne transmission of the virus, are cloth masks as recommended by the CDC truly helpful in preventing infection? A study in the Journal of Medical Virology demonstrates 99.98%, 97.14%, and 95.15% efficacy for N95, surgical, and homemade masks, respectively, in blocking the avian influenza virus (comparable to coronavirus in size and physical characteristics). The homemade mask was created using one layer of polyester cloth and a four-layered kitchen filter paper.13
N95 masks (equivalent to FFP/P2 in European countries) are made of electrostatically charged polypropylene microfibers designed to filter particles measuring 100-300nm in diameter with 95% efficacy. A single SARS-CoV-2 molecule measures 125 nm approximately. N99 (FFP3) and N100 (P3) masks are also available, though not as widely used, with 99% and 99.7% efficacy respectively for the same size range. Though cloth masks are the clear-cut last resort for medical professionals, a few studies state no clinically proven difference in protection between surgical masks and N95 respirators.14,15 Even aerosolized droplets (< 5 mcm) were found to be blocked by surgical masks in a Nature Medicine study in which 4/10 subjects tested positive for coronavirus in exhaled breath samples without masks and 0/10 subjects with masks.16
On the contrary, an Annals of Internal Medicine study of four COVID-19 positive subjects that “neither surgical masks nor cloth masks effectively filtered SARS-CoV-2 during coughs of infected patients.” In fact, more contamination was found on the outer surface of the masks when compared to the inner surface, probably owing to the masks’ aerodynamic properties.17 Because of limitations present in the above-mentioned studies, further research is necessary to conclusively determine which types of masks are efficacious in preventing infection by the virus. In a scarcity of surgical masks and respirators for health care personnel, suboptimal masks can be of some use provided there is adherent use, minimal donning and doffing, and it is to be accompanied by adequate hand washing practices.14
In case of severe infections with high viral loads or patients undergoing aerosol-generating procedures, powered air-purifying respirators (PAPRs) also are advisable as they confer greater protection than N95 respirators, according to a study in the Annals of Work Exposures and Health. Despite being more comfortable for long-term use and accommodative of facial hair, their use is limited because of high cost and difficult maintenance.18 3-D printing also is being used to combat the current shortage of masks worldwide. However, a study from the International Journal of Oral & Maxillofacial Surgery reported that virologic testing for leakage between the two reusable components and contamination of the components themselves after one or multiple disinfection cycles is essential before application in real-life situations.19
Ongoing issues
WHO estimates a monthly requirement of nearly 90 million masks exclusively for health care workers to protect themselves against COVID-19.20 In spite of increasing the production rate by 40%, if the general public hoards masks and respirators, the results could be disastrous. Personal protective equipment is currently at 100 times the usual demand and 20 times the usual cost, with stocks backlogged by 4-6 months. The appropriate order of priority in distribution to health care professionals first, followed by those caring for infected patients is critical.20 In a survey conducted by the Association for Professionals in Infection Control and Epidemiology, results revealed that 48% of the U.S. health care facilities that responded were either out or nearly out of respirators as of March 25. 21
The gravest risk behind the universal masking policy is the likely depletion of medical resources.22 A possible solution to this issue could be to modify the policy to stagger the requirement based on the severity of community transmission in that area of residence. In the article appropriately titled “Rational use of face masks in the COVID-19 pandemic” published in The Lancet Respiratory Medicine, researchers described how the Chinese population was classified into moderate, low, and very-low risk of infection categories and advised to wear a surgical or disposable mask, disposable mask, and no mask respectively.23 This curbs widespread panic and eagerness by the general public to stock up on essential medical equipment when it may not even be necessary.
Reuse, extended use, and sterilization
Several studies have been conducted to identify the viability of the COVID-19 on various surfaces.24-25 The CDC and National Institute for Occupational Safety and Health (NIOSH) guidelines state that an N95 respirator can be used up to 8 hours with intermittent or continuous use, though this number is not fixed and heavily depends upon the extent of exposure, risk of contamination, and frequency of donning and doffing26,27. Though traditionally meant for single-time usage, after 8 hours, the mask can be decontaminated and reused. The CDC defines extended use as the “practice of wearing the same N95 respirator for repeated close-contact encounters with several patients, without removing the respirator between patient encounters.” Reuse is defined as “using the same N95 respirator for multiple encounters with patients but removing it (‘doffing’) after each encounter. The respirator is stored in between encounters to be put on again (‘donned’) prior to the next encounter with a patient.”
It has been established that extended use is more advisable than reuse given the lower risk of self-inoculation. Furthermore, health care professionals are urged to wear a cleanable face shield or disposable mask over the respirator to minimize contamination and practice diligent hand hygiene before and after handling the respirator. N95 respirators are to be discarded following aerosol-generating procedures or if they come in contact with blood, respiratory secretions, or bodily fluids. They should also be discarded in case of close contact with an infected patient or if they cause breathing difficulties to the wearer.27 This may not always be possible given the unprecedented shortage of PPE, hence decontamination techniques and repurposing are the need of the hour.
In Anesthesia & Analgesia, Naveen Nathan, MD, of Northwestern University, Chicago, recommends recycling four masks in a series, using one per day, keeping the mask in a dry, clean environment, and then repeating use of the first mask on the 5th day, the second on the 6th day, and so forth. This ensures clearance of the virus particles by the next use. Alternatively, respirators can be sterilized between uses by heating to 70º C (158º F) for 30 minutes. Liquid disinfectants such as alcohol and bleach as well as ultraviolet rays in sunlight tend to damage masks.28 Steam sterilization is the most commonly utilized technique in hospitals. Other methods, described by the N95/PPE Working Group, report include gamma irradiation at 20kGy (2MRad) for large-scale sterilization (though the facilities may not be widely available), vaporized hydrogen peroxide, ozone decontamination, ultraviolet germicidal irradiation, and ethylene oxide.29 Though a discussion on various considerations of decontamination techniques is out of the scope of this article, detailed guidelines have been published by the CDC30 and the COVID-19 Healthcare Coalition.30
Conclusion
A recent startling discovery reported on in Emerging Infectious Diseases suggests that the basic COVID-19 reproductive number (R0) is actually much higher than previously thought. Using expanded data, updated epidemiologic parameters, and the current outbreak dynamics in Wuhan, the team came to the conclusion that the R0 for the novel coronavirus is actually 5.7 (95% CI 3.8-8.9), compared with an initial estimate of 2.2-2.7.31 Concern for transmissibility demands heightened prevention strategies until more data evolves. The latest recommendation by the CDC regarding cloth masking in the public may help slow the progression of the pandemic. However, it is of paramount importance to keep in mind that masks alone are not enough to control the disease and must be coupled with other nonpharmacologic interventions such as social distancing, quarantining/isolation, and diligent hand hygiene.
Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Bharathidasan is a recent medical graduate from India with an interest in public health and community research; she plans to pursue residency training in the United States. Ms. Freshman is currently the regional director of infection prevention for WellSpan Health and has 35 years of experience in nursing. Dr. Palabindala is the medical director, utilization management and physician advisory services, at the University of Mississippi Medical Center, Jackson. He is an associate professor of medicine and academic hospitalist in the UMMC School of Medicine.
References
1. Centers for Disease Control and Prevention. Recommendation regarding the use of cloth face coverings.
2. World Health Organization. Modes of transmission of virus causing COVID-19 : implications for IPC precaution recommendations. Sci Br. 2020 Mar 29:1-3.
3. Santarpia JL et al. Transmission potential of SARS-CoV-2 in viral shedding observed at the University of Nebraska Medical Center. 2020 Mar 26. medRxiv. 2020;2020.03.23.20039446.
4. Bourouiba L. Turbulent gas clouds and respiratory pathogen emissions: Potential implications for reducing transmission of COVID-19. JAMA. 2020 Mar 26. doi: 10.1001/jama.2020.4756.
5. Klompas M et al. Universal masking in hospitals in the Covid-19 era. N Engl J Med. 2020 Apr 1. doi: 10.1056/NEJMp2006372.
6. Servick K. Would everyone wearing face masks help us slow the pandemic? Science 2020 Mar 28. doi: 10.1126/science.abb9371.
7. Leung CC et al. Mass masking in the COVID-19 epidemic: People need guidance. Lancet 2020 Mar 21;395(10228):945. doi: 10.1016/S0140-6736(20)30520-1.
8. Zou L et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020 Mar 19;382(12):1177-9.
9. Pan X et al. Asymptomatic cases in a family cluster with SARS-CoV-2 infection. Lancet Infect Dis. 2020 Apr;20(4):410-1.
10. Bai Y et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020 Feb 21;323(14):1406-7.
11. Wei WE et al. Presymptomatic transmission of SARS-CoV-2 – Singapore, Jan. 23–March 16, 2020. MMWR Morb Mortal Wkly Rep 2020;69:411-5.
12. Kimball A et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility – King County, Washington, March 2020. 2020 Apr 3. MMWR Morb Mortal Wkly Rep 2020;69:377-81.
13. Ma Q-X et al. Potential utilities of mask wearing and instant hand hygiene for fighting SARS-CoV-2. J Med Virol. 2020 Mar 31;10.1002/jmv.25805. doi: 10.1002/jmv.25805.
14. Abd-Elsayed A et al. Utility of substandard face mask options for health care workers during the COVID-19 pandemic. Anesth Analg. 2020 Mar 31;10.1213/ANE.0000000000004841. doi: 10.1213/ANE.0000000000004841.
15. Long Y et al. Effectiveness of N95 respirators versus surgical masks against influenza: A systematic review and meta-analysis. J Evid Based Med. 2020 Mar 13;10.1111/jebm.12381. doi: 10.1111/jebm.12381.
16. Leung NHL et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nat Med. 2020 May;26(5):676-80.
17. Bae S et al. Effectiveness of surgical and cotton masks in blocking SARS-CoV-2: A controlled comparison in 4 patients. Ann Intern Med. 2020 Apr 6;M20-1342. doi: 10.7326/M20-1342.
18. Brosseau LM. Are powered air purifying respirators a solution for protecting healthcare workers from emerging aerosol-transmissible diseases? Ann Work Expo Health. 2020 Apr 30;64(4):339-41.
19. Swennen GRJ et al. Custom-made 3D-printed face masks in case of pandemic crisis situations with a lack of commercially available FFP2/3 masks. Int J Oral Maxillofac Surg. 2020 May;49(5):673-7.
20. Mahase E. Coronavirus: Global stocks of protective gear are depleted, with demand at “100 times” normal level, WHO warns. BMJ. 2020 Feb 10;368:m543. doi: 10.1136/bmj.m543.
21. National survey shows dire shortages of PPE, hand sanitizer across the U.S. 2020 Mar 27. Association for Professionals in Infection Control and Epidemiology (APIC) press briefing.
22. Wu HL et al. Facemask shortage and the novel coronavirus disease (COVID-19) outbreak: Reflections on public health measures. EClinicalMedicine. 2020 Apr 3:100329. doi: 10.1016/j.eclinm.2020.100329.
23. Feng S et al. Rational use of face masks in the COVID-19 pandemic. Lancet Respir Med. 2020 May;8(5):434-6.
24. Chin AWH et al. Stability of SARS-CoV-2 in different environmental. The Lancet Microbe. 2020 May 1;5247(20):2004973. doi. org/10.1016/S2666-5247(20)30003-3.
25. van Doremalen N et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020 Apr 16;382(16):1564-7.
26. NIOSH – Workplace Safety and Health Topics: Recommended guidance for extended use and limited reuse of n95 filtering facepiece respirators in healthcare settings.
27. Centers for Disease Control and Prevention. COVID-19 decontamination and reuse of filtering facepiece respirators. 2020 Apr 15.
28. Nathan N. Waste not, want not: The re-usability of N95 masks. Anesth Analg. 2020 Mar 31.doi: 10.1213/ane.0000000000004843.
29. European Centre for Disease Prevention and Control technical report. Cloth masks and mask sterilisation as options in case of shortage of surgical masks and respirators. 2020 Mar.
30. N95/PPE Working Group report. Evaluation of decontamination techniques for the reuse of N95 respirators. 2020 Apr 3;2:1-7.
31. Sanche Set al. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020 Jul. doi. org/10.3201/eid2607.200282.
On April 3, the Centers for Disease Control and Prevention issued an advisory that the general public wear cloth face masks when outside, particularly those residing in areas with significant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) community transmission.1 Recent research reveals several factors related to the nature of the virus as well as the epidemiologic spread of the illness that may have led to this decision.
However, controversy still prevails whether this recommendation will alleviate or aggravate disease progression. With many hospitals across America lacking sufficient personal protective equipment (PPE) and scrambling for supplies, universal masking may create more chaos, especially with certain states imposing monetary fines on individuals spotted outdoors without a mask. With new information being discovered each day about COVID-19, it is more imperative than ever to update existing strategies and formulate more effective methods to flatten the curve.
Airborne vs. droplet transmission
According to a scientific brief released by the World Health Organization, there have been studies with mixed evidence and opinions regarding the presence of COVID-19 ribonucleic acid (RNA) in air samples.2 In medRxiv, Santarpia et al., from the University of Nebraska Medical Center, Omaha, detected viral RNA in samples taken from beneath a patient’s bed and from a window ledge, both areas in which neither the patient nor health care personnel had any direct contact. They also found that 66.7% of air samples taken from a hospital hallway carried virus-containing particles.3 It is worth noting that certain aerosol-generating procedures (AGP) may increase the likelihood of airborne dissemination. Whether airborne transmission is a major mode of COVID-19 spread in the community and routine clinical settings (with no aerosol-generating procedures) is still a debatable question without a definitive answer.
We should consider the epidemiology of COVID-19 thus far in the pandemic to determine if transmission patterns are more consistent with that of other common respiratory viral pathogens or more consistent with that of the agents we classically consider to be transmitted by the airborne route (measles, varicella zoster virus, and Mycobacterium tuberculosis). The attack rates in various settings (household, health care, and the public) as well as the expected number of secondary cases from a single infected individual in a susceptible population (R0) are more consistent with those of a droplet spread pathogen.
For measles, the R0 is 12-18, and the secondary household attack rates are ≥ 90%. In case of the varicella zoster virus, the R0 is ~10, and the secondary household attack rate is 85%. The R0 for pulmonary tuberculosis is up to 10 (per year) and the secondary household attack rate has been reported to be >50%. With COVID-19, the R0 appears to be around 2.5-3 and secondary household attack rates are ~ 10% from data available so far, similar to that of influenza viruses. This discrepancy suggests that droplet transmission may be more likely. The dichotomy of airborne versus droplet mode of spread may be better described as a continuum, as pointed out in a recent article in the JAMA. Infectious droplets form turbulent gas clouds allowing the virus particles to travel further and remain in the air longer.4 The necessary precautions for an airborne illness should be chosen over droplet precautions, especially when there is concern for an AGP.
Universal masking: Risks and benefits
The idea of universal masking has been debated extensively since the initial stages of the COVID-19 pandemic. According to public health authorities, significant exposure is defined as “face-to-face contact within 6 feet with a patient with symptomatic COVID-19” in the range of a few minutes up to 30 minutes.5 The researchers wrote in the New England Journal of Medicine that the chance of catching COVID-19 from a passing interaction in a public space is therefore minimal, and it may seem unnecessary to wear a mask at all times in public.
As reported in Science, randomized clinical studies performed on other viruses in the past have shown no added protection conferred by wearing a mask, though small sample sizes and noncompliance are limiting factors to their validity.6 On the contrary, mask wearing has been enforced in many parts of Asia, including Hong Kong and Singapore with promising results.5 Leung et al. stated in The Lancet that the lack of proof that masks are effective should not rule them as ineffective. Also, universal masking would reduce the stigma around symptomatic individuals covering their faces. It has become a cultural phenomenon in many southeast Asian countries and has been cited as one of the reasons for relatively successful containment in Singapore, South Korea, and Taiwan. The most important benefit of universal masking is protection attained by preventing spread from asymptomatic, mildly symptomatic, and presymptomatic carriers.7
In a study in the New England Journal of Medicine that estimated viral loads during various stages of COVID-19, researchers found that asymptomatic patients had similar viral loads to symptomatic patients, thereby suggesting high potential for transmission.8 Furthermore, numerous cases are being reported concerning the spread of illness from asymptomatic carriers.9-12 In an outbreak at a skilled nursing facility in Washington outlined in MMWR, 13 of 23 residents with positive test results were asymptomatic at the time of testing, and of those, 3 never developed any symptoms.12
Many hospitals are now embracing the policy of universal masking. A mask is a critical component of the personal protective equipment (PPE) clinicians need when caring for symptomatic patients with respiratory viral infections, in conjunction with a gown, gloves, and eye protection. Masking in this context is already part of routine operations in most hospitals. There are two scenarios in which there may be possible benefits. One scenario is the lower likelihood of transmission from asymptomatic and minimally symptomatic health care workers with COVID-19 to other providers and patients. The other less plausible benefit of universal masking among health care workers is that it may provide some protection in the possibility of caring for an unrecognized COVID-19 patient. However, universal masking should be coupled with other favorable practices like temperature checks and symptom screening on a daily basis to avail the maximum benefit from masking. Despite varied opinions on the outcomes of universal masking, this measure helps improve health care workers’ safety, psychological well-being, trust in their hospital, and decreases anxiety of acquiring the illness.
Efficacy of various types of masks
With the possibility of airborne transmission of the virus, are cloth masks as recommended by the CDC truly helpful in preventing infection? A study in the Journal of Medical Virology demonstrates 99.98%, 97.14%, and 95.15% efficacy for N95, surgical, and homemade masks, respectively, in blocking the avian influenza virus (comparable to coronavirus in size and physical characteristics). The homemade mask was created using one layer of polyester cloth and a four-layered kitchen filter paper.13
N95 masks (equivalent to FFP/P2 in European countries) are made of electrostatically charged polypropylene microfibers designed to filter particles measuring 100-300nm in diameter with 95% efficacy. A single SARS-CoV-2 molecule measures 125 nm approximately. N99 (FFP3) and N100 (P3) masks are also available, though not as widely used, with 99% and 99.7% efficacy respectively for the same size range. Though cloth masks are the clear-cut last resort for medical professionals, a few studies state no clinically proven difference in protection between surgical masks and N95 respirators.14,15 Even aerosolized droplets (< 5 mcm) were found to be blocked by surgical masks in a Nature Medicine study in which 4/10 subjects tested positive for coronavirus in exhaled breath samples without masks and 0/10 subjects with masks.16
On the contrary, an Annals of Internal Medicine study of four COVID-19 positive subjects that “neither surgical masks nor cloth masks effectively filtered SARS-CoV-2 during coughs of infected patients.” In fact, more contamination was found on the outer surface of the masks when compared to the inner surface, probably owing to the masks’ aerodynamic properties.17 Because of limitations present in the above-mentioned studies, further research is necessary to conclusively determine which types of masks are efficacious in preventing infection by the virus. In a scarcity of surgical masks and respirators for health care personnel, suboptimal masks can be of some use provided there is adherent use, minimal donning and doffing, and it is to be accompanied by adequate hand washing practices.14
In case of severe infections with high viral loads or patients undergoing aerosol-generating procedures, powered air-purifying respirators (PAPRs) also are advisable as they confer greater protection than N95 respirators, according to a study in the Annals of Work Exposures and Health. Despite being more comfortable for long-term use and accommodative of facial hair, their use is limited because of high cost and difficult maintenance.18 3-D printing also is being used to combat the current shortage of masks worldwide. However, a study from the International Journal of Oral & Maxillofacial Surgery reported that virologic testing for leakage between the two reusable components and contamination of the components themselves after one or multiple disinfection cycles is essential before application in real-life situations.19
Ongoing issues
WHO estimates a monthly requirement of nearly 90 million masks exclusively for health care workers to protect themselves against COVID-19.20 In spite of increasing the production rate by 40%, if the general public hoards masks and respirators, the results could be disastrous. Personal protective equipment is currently at 100 times the usual demand and 20 times the usual cost, with stocks backlogged by 4-6 months. The appropriate order of priority in distribution to health care professionals first, followed by those caring for infected patients is critical.20 In a survey conducted by the Association for Professionals in Infection Control and Epidemiology, results revealed that 48% of the U.S. health care facilities that responded were either out or nearly out of respirators as of March 25. 21
The gravest risk behind the universal masking policy is the likely depletion of medical resources.22 A possible solution to this issue could be to modify the policy to stagger the requirement based on the severity of community transmission in that area of residence. In the article appropriately titled “Rational use of face masks in the COVID-19 pandemic” published in The Lancet Respiratory Medicine, researchers described how the Chinese population was classified into moderate, low, and very-low risk of infection categories and advised to wear a surgical or disposable mask, disposable mask, and no mask respectively.23 This curbs widespread panic and eagerness by the general public to stock up on essential medical equipment when it may not even be necessary.
Reuse, extended use, and sterilization
Several studies have been conducted to identify the viability of the COVID-19 on various surfaces.24-25 The CDC and National Institute for Occupational Safety and Health (NIOSH) guidelines state that an N95 respirator can be used up to 8 hours with intermittent or continuous use, though this number is not fixed and heavily depends upon the extent of exposure, risk of contamination, and frequency of donning and doffing26,27. Though traditionally meant for single-time usage, after 8 hours, the mask can be decontaminated and reused. The CDC defines extended use as the “practice of wearing the same N95 respirator for repeated close-contact encounters with several patients, without removing the respirator between patient encounters.” Reuse is defined as “using the same N95 respirator for multiple encounters with patients but removing it (‘doffing’) after each encounter. The respirator is stored in between encounters to be put on again (‘donned’) prior to the next encounter with a patient.”
It has been established that extended use is more advisable than reuse given the lower risk of self-inoculation. Furthermore, health care professionals are urged to wear a cleanable face shield or disposable mask over the respirator to minimize contamination and practice diligent hand hygiene before and after handling the respirator. N95 respirators are to be discarded following aerosol-generating procedures or if they come in contact with blood, respiratory secretions, or bodily fluids. They should also be discarded in case of close contact with an infected patient or if they cause breathing difficulties to the wearer.27 This may not always be possible given the unprecedented shortage of PPE, hence decontamination techniques and repurposing are the need of the hour.
In Anesthesia & Analgesia, Naveen Nathan, MD, of Northwestern University, Chicago, recommends recycling four masks in a series, using one per day, keeping the mask in a dry, clean environment, and then repeating use of the first mask on the 5th day, the second on the 6th day, and so forth. This ensures clearance of the virus particles by the next use. Alternatively, respirators can be sterilized between uses by heating to 70º C (158º F) for 30 minutes. Liquid disinfectants such as alcohol and bleach as well as ultraviolet rays in sunlight tend to damage masks.28 Steam sterilization is the most commonly utilized technique in hospitals. Other methods, described by the N95/PPE Working Group, report include gamma irradiation at 20kGy (2MRad) for large-scale sterilization (though the facilities may not be widely available), vaporized hydrogen peroxide, ozone decontamination, ultraviolet germicidal irradiation, and ethylene oxide.29 Though a discussion on various considerations of decontamination techniques is out of the scope of this article, detailed guidelines have been published by the CDC30 and the COVID-19 Healthcare Coalition.30
Conclusion
A recent startling discovery reported on in Emerging Infectious Diseases suggests that the basic COVID-19 reproductive number (R0) is actually much higher than previously thought. Using expanded data, updated epidemiologic parameters, and the current outbreak dynamics in Wuhan, the team came to the conclusion that the R0 for the novel coronavirus is actually 5.7 (95% CI 3.8-8.9), compared with an initial estimate of 2.2-2.7.31 Concern for transmissibility demands heightened prevention strategies until more data evolves. The latest recommendation by the CDC regarding cloth masking in the public may help slow the progression of the pandemic. However, it is of paramount importance to keep in mind that masks alone are not enough to control the disease and must be coupled with other nonpharmacologic interventions such as social distancing, quarantining/isolation, and diligent hand hygiene.
Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals. Dr. Bharathidasan is a recent medical graduate from India with an interest in public health and community research; she plans to pursue residency training in the United States. Ms. Freshman is currently the regional director of infection prevention for WellSpan Health and has 35 years of experience in nursing. Dr. Palabindala is the medical director, utilization management and physician advisory services, at the University of Mississippi Medical Center, Jackson. He is an associate professor of medicine and academic hospitalist in the UMMC School of Medicine.
References
1. Centers for Disease Control and Prevention. Recommendation regarding the use of cloth face coverings.
2. World Health Organization. Modes of transmission of virus causing COVID-19 : implications for IPC precaution recommendations. Sci Br. 2020 Mar 29:1-3.
3. Santarpia JL et al. Transmission potential of SARS-CoV-2 in viral shedding observed at the University of Nebraska Medical Center. 2020 Mar 26. medRxiv. 2020;2020.03.23.20039446.
4. Bourouiba L. Turbulent gas clouds and respiratory pathogen emissions: Potential implications for reducing transmission of COVID-19. JAMA. 2020 Mar 26. doi: 10.1001/jama.2020.4756.
5. Klompas M et al. Universal masking in hospitals in the Covid-19 era. N Engl J Med. 2020 Apr 1. doi: 10.1056/NEJMp2006372.
6. Servick K. Would everyone wearing face masks help us slow the pandemic? Science 2020 Mar 28. doi: 10.1126/science.abb9371.
7. Leung CC et al. Mass masking in the COVID-19 epidemic: People need guidance. Lancet 2020 Mar 21;395(10228):945. doi: 10.1016/S0140-6736(20)30520-1.
8. Zou L et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020 Mar 19;382(12):1177-9.
9. Pan X et al. Asymptomatic cases in a family cluster with SARS-CoV-2 infection. Lancet Infect Dis. 2020 Apr;20(4):410-1.
10. Bai Y et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020 Feb 21;323(14):1406-7.
11. Wei WE et al. Presymptomatic transmission of SARS-CoV-2 – Singapore, Jan. 23–March 16, 2020. MMWR Morb Mortal Wkly Rep 2020;69:411-5.
12. Kimball A et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility – King County, Washington, March 2020. 2020 Apr 3. MMWR Morb Mortal Wkly Rep 2020;69:377-81.
13. Ma Q-X et al. Potential utilities of mask wearing and instant hand hygiene for fighting SARS-CoV-2. J Med Virol. 2020 Mar 31;10.1002/jmv.25805. doi: 10.1002/jmv.25805.
14. Abd-Elsayed A et al. Utility of substandard face mask options for health care workers during the COVID-19 pandemic. Anesth Analg. 2020 Mar 31;10.1213/ANE.0000000000004841. doi: 10.1213/ANE.0000000000004841.
15. Long Y et al. Effectiveness of N95 respirators versus surgical masks against influenza: A systematic review and meta-analysis. J Evid Based Med. 2020 Mar 13;10.1111/jebm.12381. doi: 10.1111/jebm.12381.
16. Leung NHL et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nat Med. 2020 May;26(5):676-80.
17. Bae S et al. Effectiveness of surgical and cotton masks in blocking SARS-CoV-2: A controlled comparison in 4 patients. Ann Intern Med. 2020 Apr 6;M20-1342. doi: 10.7326/M20-1342.
18. Brosseau LM. Are powered air purifying respirators a solution for protecting healthcare workers from emerging aerosol-transmissible diseases? Ann Work Expo Health. 2020 Apr 30;64(4):339-41.
19. Swennen GRJ et al. Custom-made 3D-printed face masks in case of pandemic crisis situations with a lack of commercially available FFP2/3 masks. Int J Oral Maxillofac Surg. 2020 May;49(5):673-7.
20. Mahase E. Coronavirus: Global stocks of protective gear are depleted, with demand at “100 times” normal level, WHO warns. BMJ. 2020 Feb 10;368:m543. doi: 10.1136/bmj.m543.
21. National survey shows dire shortages of PPE, hand sanitizer across the U.S. 2020 Mar 27. Association for Professionals in Infection Control and Epidemiology (APIC) press briefing.
22. Wu HL et al. Facemask shortage and the novel coronavirus disease (COVID-19) outbreak: Reflections on public health measures. EClinicalMedicine. 2020 Apr 3:100329. doi: 10.1016/j.eclinm.2020.100329.
23. Feng S et al. Rational use of face masks in the COVID-19 pandemic. Lancet Respir Med. 2020 May;8(5):434-6.
24. Chin AWH et al. Stability of SARS-CoV-2 in different environmental. The Lancet Microbe. 2020 May 1;5247(20):2004973. doi. org/10.1016/S2666-5247(20)30003-3.
25. van Doremalen N et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020 Apr 16;382(16):1564-7.
26. NIOSH – Workplace Safety and Health Topics: Recommended guidance for extended use and limited reuse of n95 filtering facepiece respirators in healthcare settings.
27. Centers for Disease Control and Prevention. COVID-19 decontamination and reuse of filtering facepiece respirators. 2020 Apr 15.
28. Nathan N. Waste not, want not: The re-usability of N95 masks. Anesth Analg. 2020 Mar 31.doi: 10.1213/ane.0000000000004843.
29. European Centre for Disease Prevention and Control technical report. Cloth masks and mask sterilisation as options in case of shortage of surgical masks and respirators. 2020 Mar.
30. N95/PPE Working Group report. Evaluation of decontamination techniques for the reuse of N95 respirators. 2020 Apr 3;2:1-7.
31. Sanche Set al. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020 Jul. doi. org/10.3201/eid2607.200282.
Today’s top news highlights: COVID-19 in kids, addiction-related suicide
Here are the stories our MDedge editors across specialties think you need to know about today:
COVID-19 in kids
Children and young adults in all age groups can develop severe illess after SARS-CoV-2 infection, but infants and teens are most likely to be hospitalized, according to retrospective data from 177 children and young adults at a single center. “One patient had features consistent with the recently emerged Kawasaki disease–like presentation with hyperinflammatory state, hypotension, and profound myocardial depression,” Roberta L. DeBiasi, MD, of Children’s National Hospital, Washington, and colleagues reported in the Journal of Pediatrics. READ MORE
Avoiding ageism in COVID resource allocation
The American Geriatrics Society has issued new policy recommendations for resource allocation during the COVID-19 pandemic that are aimed at protecting seniors for ageism. When allocating scarce resources in an emergency, officials should equally weigh in-hospital survival and severe comorbidities contributing to short-term mortality, the group wrote. “Age per se should never be used as a means for a categorical exclusion from therapeutic interventions that represent the standard of care. ... Likewise, specific age-based cutoffs should not be used in resource allocation strategies,” AGS officials wrote in the statement. READ MORE
Preventing addiction-related suicide
Individuals with substance use disorders are at a significant risk for suicide, but there have been few evidence-based options for their treatment. Now a single intervention is showing promise for this high-risk group. In a large, multicenter randomized effectiveness study, a single 3-hour-long group psychosocial intervention resulted in significantly improved knowledge and attitudes regarding suicide that persisted at 6 months of follow-up. The intervention to prevent future suicide was designed specifically for patients who were in intensive outpatient programs for addiction treatment. “We’ve shown that suicide prevention in intensive outpatient program addiction groups is feasible, easy to train, and highly rated by counselors, and I’d say it’s very adaptable, easy to go national in almost any addiction treatment program, right out of the box,” said Richard K. Ries, MD, director of outpatient psychiatry as well as the psychiatry addiction division at Harborview Medical Center. READ MORE
TNF inhibitors may hamper COVID-19 severity
Early evidence from the COVID-19 Global Rheumatology Alliance Registry has produced an intriguing result: Patients on tumor necrosis factor inhibitors for their rheumatic disease are less likely to require hospitalization when infected with COVID-19. The registry data also show that taking hydroxychloroquine or other antimalarials at the time of COVID-19 infection had no impact on hospitalization. “A strength of the global registry has been that it provides timely data that’s been very helpful for rheumatologists to rapidly dispel misinformation that has been spread about hydroxychloroquine, especially statements about lupus patients not getting COVID-19. We know from these data that’s not true,” said Jinoos Yazdany, MD, professor of medicine at the University of California, San Francisco, and chief of rheumatology at San Francisco General Hospital. READ MORE
Audrey Hepburn’s lessons in pandemic grace
There are a lot of new skills required for praticing medicine during the COVID-19 pandemic. In his latest MDedge column, Jeffrey Benabio, MD, explains that grace is one of them. Dr. Benabio, director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego, looks to Audrey Hepburn for inspiration. “Effort is also required for telephone and video visits,” he writes. “In them, our doctor-patient connection is diminished – no matter how high definition, it’s a virtual affair. Ms. Hepburn would no doubt take the time to ensure she appeared professional, well lit, with a pleasing background. She’d plan for the call to be done in a quiet location and without distraction.” READ MORE
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
COVID-19 in kids
Children and young adults in all age groups can develop severe illess after SARS-CoV-2 infection, but infants and teens are most likely to be hospitalized, according to retrospective data from 177 children and young adults at a single center. “One patient had features consistent with the recently emerged Kawasaki disease–like presentation with hyperinflammatory state, hypotension, and profound myocardial depression,” Roberta L. DeBiasi, MD, of Children’s National Hospital, Washington, and colleagues reported in the Journal of Pediatrics. READ MORE
Avoiding ageism in COVID resource allocation
The American Geriatrics Society has issued new policy recommendations for resource allocation during the COVID-19 pandemic that are aimed at protecting seniors for ageism. When allocating scarce resources in an emergency, officials should equally weigh in-hospital survival and severe comorbidities contributing to short-term mortality, the group wrote. “Age per se should never be used as a means for a categorical exclusion from therapeutic interventions that represent the standard of care. ... Likewise, specific age-based cutoffs should not be used in resource allocation strategies,” AGS officials wrote in the statement. READ MORE
Preventing addiction-related suicide
Individuals with substance use disorders are at a significant risk for suicide, but there have been few evidence-based options for their treatment. Now a single intervention is showing promise for this high-risk group. In a large, multicenter randomized effectiveness study, a single 3-hour-long group psychosocial intervention resulted in significantly improved knowledge and attitudes regarding suicide that persisted at 6 months of follow-up. The intervention to prevent future suicide was designed specifically for patients who were in intensive outpatient programs for addiction treatment. “We’ve shown that suicide prevention in intensive outpatient program addiction groups is feasible, easy to train, and highly rated by counselors, and I’d say it’s very adaptable, easy to go national in almost any addiction treatment program, right out of the box,” said Richard K. Ries, MD, director of outpatient psychiatry as well as the psychiatry addiction division at Harborview Medical Center. READ MORE
TNF inhibitors may hamper COVID-19 severity
Early evidence from the COVID-19 Global Rheumatology Alliance Registry has produced an intriguing result: Patients on tumor necrosis factor inhibitors for their rheumatic disease are less likely to require hospitalization when infected with COVID-19. The registry data also show that taking hydroxychloroquine or other antimalarials at the time of COVID-19 infection had no impact on hospitalization. “A strength of the global registry has been that it provides timely data that’s been very helpful for rheumatologists to rapidly dispel misinformation that has been spread about hydroxychloroquine, especially statements about lupus patients not getting COVID-19. We know from these data that’s not true,” said Jinoos Yazdany, MD, professor of medicine at the University of California, San Francisco, and chief of rheumatology at San Francisco General Hospital. READ MORE
Audrey Hepburn’s lessons in pandemic grace
There are a lot of new skills required for praticing medicine during the COVID-19 pandemic. In his latest MDedge column, Jeffrey Benabio, MD, explains that grace is one of them. Dr. Benabio, director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego, looks to Audrey Hepburn for inspiration. “Effort is also required for telephone and video visits,” he writes. “In them, our doctor-patient connection is diminished – no matter how high definition, it’s a virtual affair. Ms. Hepburn would no doubt take the time to ensure she appeared professional, well lit, with a pleasing background. She’d plan for the call to be done in a quiet location and without distraction.” READ MORE
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
COVID-19 in kids
Children and young adults in all age groups can develop severe illess after SARS-CoV-2 infection, but infants and teens are most likely to be hospitalized, according to retrospective data from 177 children and young adults at a single center. “One patient had features consistent with the recently emerged Kawasaki disease–like presentation with hyperinflammatory state, hypotension, and profound myocardial depression,” Roberta L. DeBiasi, MD, of Children’s National Hospital, Washington, and colleagues reported in the Journal of Pediatrics. READ MORE
Avoiding ageism in COVID resource allocation
The American Geriatrics Society has issued new policy recommendations for resource allocation during the COVID-19 pandemic that are aimed at protecting seniors for ageism. When allocating scarce resources in an emergency, officials should equally weigh in-hospital survival and severe comorbidities contributing to short-term mortality, the group wrote. “Age per se should never be used as a means for a categorical exclusion from therapeutic interventions that represent the standard of care. ... Likewise, specific age-based cutoffs should not be used in resource allocation strategies,” AGS officials wrote in the statement. READ MORE
Preventing addiction-related suicide
Individuals with substance use disorders are at a significant risk for suicide, but there have been few evidence-based options for their treatment. Now a single intervention is showing promise for this high-risk group. In a large, multicenter randomized effectiveness study, a single 3-hour-long group psychosocial intervention resulted in significantly improved knowledge and attitudes regarding suicide that persisted at 6 months of follow-up. The intervention to prevent future suicide was designed specifically for patients who were in intensive outpatient programs for addiction treatment. “We’ve shown that suicide prevention in intensive outpatient program addiction groups is feasible, easy to train, and highly rated by counselors, and I’d say it’s very adaptable, easy to go national in almost any addiction treatment program, right out of the box,” said Richard K. Ries, MD, director of outpatient psychiatry as well as the psychiatry addiction division at Harborview Medical Center. READ MORE
TNF inhibitors may hamper COVID-19 severity
Early evidence from the COVID-19 Global Rheumatology Alliance Registry has produced an intriguing result: Patients on tumor necrosis factor inhibitors for their rheumatic disease are less likely to require hospitalization when infected with COVID-19. The registry data also show that taking hydroxychloroquine or other antimalarials at the time of COVID-19 infection had no impact on hospitalization. “A strength of the global registry has been that it provides timely data that’s been very helpful for rheumatologists to rapidly dispel misinformation that has been spread about hydroxychloroquine, especially statements about lupus patients not getting COVID-19. We know from these data that’s not true,” said Jinoos Yazdany, MD, professor of medicine at the University of California, San Francisco, and chief of rheumatology at San Francisco General Hospital. READ MORE
Audrey Hepburn’s lessons in pandemic grace
There are a lot of new skills required for praticing medicine during the COVID-19 pandemic. In his latest MDedge column, Jeffrey Benabio, MD, explains that grace is one of them. Dr. Benabio, director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego, looks to Audrey Hepburn for inspiration. “Effort is also required for telephone and video visits,” he writes. “In them, our doctor-patient connection is diminished – no matter how high definition, it’s a virtual affair. Ms. Hepburn would no doubt take the time to ensure she appeared professional, well lit, with a pleasing background. She’d plan for the call to be done in a quiet location and without distraction.” READ MORE
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
3 new latent TB preventive regimens dramatically cut Tx time
References
- Sterling TR, Njie G, Zenner D, et al. Guidelines for the treatment of latent tubercular infection: recommendations from the National Tuberculosis Controllers Association and the CDC, 2020. MMWR Recomm Rep. 2020;69:1-11.
- USPSTF. Latent tuberculosis screening [final recommendation statement]. Published September 6, 2016. www.uspreventiveservicestaskforce.org/uspstf/recommendation/latent-tuberculosis-infection-screening. Accessed May 19, 2020.
- CDC. Tuberculosis (TB): data and statistics. Updated September 6, 2019. www.cdc.gov/tb/statistics/default.htm. Accessed May 19, 2020.
References
- Sterling TR, Njie G, Zenner D, et al. Guidelines for the treatment of latent tubercular infection: recommendations from the National Tuberculosis Controllers Association and the CDC, 2020. MMWR Recomm Rep. 2020;69:1-11.
- USPSTF. Latent tuberculosis screening [final recommendation statement]. Published September 6, 2016. www.uspreventiveservicestaskforce.org/uspstf/recommendation/latent-tuberculosis-infection-screening. Accessed May 19, 2020.
- CDC. Tuberculosis (TB): data and statistics. Updated September 6, 2019. www.cdc.gov/tb/statistics/default.htm. Accessed May 19, 2020.
References
- Sterling TR, Njie G, Zenner D, et al. Guidelines for the treatment of latent tubercular infection: recommendations from the National Tuberculosis Controllers Association and the CDC, 2020. MMWR Recomm Rep. 2020;69:1-11.
- USPSTF. Latent tuberculosis screening [final recommendation statement]. Published September 6, 2016. www.uspreventiveservicestaskforce.org/uspstf/recommendation/latent-tuberculosis-infection-screening. Accessed May 19, 2020.
- CDC. Tuberculosis (TB): data and statistics. Updated September 6, 2019. www.cdc.gov/tb/statistics/default.htm. Accessed May 19, 2020.
Vitamin D: A low-hanging fruit in COVID-19?
Mainstream media outlets have been flooded recently with reports speculating on what role, if any, vitamin D may play in reducing the severity of COVID-19 infection.
as well as mortality, with the further suggestion of an effect of vitamin D on the immune response to infection.
But other studies question such a link, including any association between vitamin D concentration and differences in COVID-19 severity by ethnic group.
And while some researchers and clinicians believe people should get tested to see if they have adequate vitamin D levels during this pandemic – in particular frontline health care workers – most doctors say the best way to ensure that people have adequate levels of vitamin D during COVID-19 is to simply take supplements at currently recommended levels.
This is especially important given the fact that, during “lockdown” scenarios, many people are spending more time than usual indoors.
Clifford Rosen, MD, senior scientist at Maine Medical Center’s Research Institute in Scarborough, has been researching vitamin D for 25 years.
“There’s no randomized, controlled trial for sure, and that’s the gold standard,” he said in an interview, and “the observational data are so confounded, it’s difficult to know.”
Whether from diet or supplementation, having adequate vitamin D is important, especially for those at the highest risk of COVID-19, he said. Still, robust data supporting a role of vitamin D in prevention of COVID-19, or as any kind of “therapy” for the infection, are currently lacking.
Rose Anne Kenny, MD, professor of medical gerontology at Trinity College Dublin, recently coauthored an article detailing an inverse association between vitamin D levels and mortality from COVID-19 across countries in Europe.
“At no stage are any of us saying this is a given, but there’s a probability that [vitamin D] – a low-hanging fruit – is a contributory factor and we can do something about it now,” she said in an interview.
Dr. Kenny is calling for the Irish government to formally change their recommendations. “We call on the Irish government to update guidelines as a matter of urgency and encourage all adults to take [vitamin D] supplements during the COVID-19 crisis.” Northern Ireland, part of the United Kingdom, also has not yet made this recommendation, she said.
Meanwhile, Harpreet S. Bajaj, MD, MPH, a practicing endocrinologist from Mount Sinai Hospital, Toronto, said: “Vitamin D could have any of three potential roles in risk for COVID-19 and/or its severity: no role, simply a marker, or a causal factor.”
Dr. Bajaj said – as did Dr. Rosen and Dr. Kenny – that randomized, controlled trials (RCTs) are sorely needed to help ascertain whether there is a specific role of vitamin D.
“Until then, we should continue to follow established public health recommendations for vitamin D supplementation, in addition to following COVID-19 prevention guidance and evolving guidelines for COVID-19 treatment.”
What is the role of vitamin D fortification?
In their study in the Irish Medical Journal, Dr. Kenny and colleagues noted that, in Europe, despite being sunny, Spain and Northern Italy had high rates of vitamin D deficiency and have experienced some of the highest COVID-19 infection and mortality rates in the world.
But these countries do not formally fortify foods or recommend supplementation with vitamin D.
Conversely, the northern countries of Norway, Finland, and Sweden had higher vitamin D levels despite less UVB sunlight exposure, as a result of common supplementation and formal fortification of foods. These Nordic countries also had lower levels of COVID-19 infection and mortality.
Overall, the correlation between low vitamin D levels and mortality from COVID-19 was statistically significant (P = .046), the investigators reported.
“Optimizing vitamin D status to recommendations by national and international public health agencies will certainly have ... potential benefits for COVID-19,” they concluded.
“We’re not saying there aren’t any confounders. This can absolutely be the case, but this [finding] needs to be in the mix of evidence,” Dr. Kenny said.
Dr. Kenny also noted that countries in the Southern Hemisphere have been seeing a relatively low mortality from COVID-19, although she acknowledged the explanation could be that the virus spread later to those countries.
Dr. Rosen has doubts on this issue, too.
“Sure, vitamin D supplementation may have worked for [Nordic countries], their COVID-19 has been better controlled, but there’s no causality here; there’s another step to actually prove this. Other factors might be at play,” he said.
“Look at Brazil, it’s at the equator but the disease is devastating the country. Right now, I just don’t believe it.”
Does vitamin D have a role to play in immune modulation?
One theory currently circulating is that, if vitamin D does have any role to play in modulating response to COVID-19, this may be via a blunting of the immune system reaction to the virus.
In a recent preprint study, Ali Daneshkhah, PhD, and colleagues from Northwestern University, Chicago, interrogated hospital data from China, France, Germany, Italy, Iran, South Korea, Spain, Switzerland, the United Kingdom, and the United States.
Specifically, the risk of severe COVID-19 cases among patients with severe vitamin D deficiency was 17.3%, whereas the equivalent figure for patients with normal vitamin D levels was 14.6% (a reduction of 15.6%).
“This potential effect may be attributed to vitamin D’s ability to suppress the adaptive immune system, regulating cytokine levels and thereby reducing the risk of developing severe COVID-19,” said the researchers.
Likewise, JoAnn E. Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, in a recent commentary, noted evidence from an observational study from three South Asian hospitals, in which the prevalence of vitamin D deficiency was much higher among those with severe COVID-19 illness compared with those with mild illness.
“We also know that vitamin D has an immune-modulating effect and can lower inflammation, and this may be relevant to the respiratory response during COVID-19 and the cytokine storm that’s been demonstrated,” she noted.
Dr. Rosen said he is willing to listen on the issue of a potential role of vitamin D in immune modulation.
“I’ve been a huge skeptic from the get-go, and loudly criticized the data for doing nothing. I am surprised at myself for saying there might be some effect,” he said.
“Clearly most people don’t get this [cytokine storm] but of those that do, it’s unclear why they do. Maybe if you are vitamin D sufficient, it might have some impact down the road on your response to an infection,” Dr. Rosen said. “Vitamin D may induce proteins important in modulating the function of macrophages of the immune system.”
Ethnic minorities disproportionately affected
It is also well recognized that COVID-19 disproportionately affects black and Asian minority ethnic individuals.
But on the issue of vitamin D in this context, one recent peer-reviewed study using UK Biobank data found no evidence to support a potential role for vitamin D concentration to explain susceptibility to COVID-19 infection either overall or in explaining differences between ethnic groups.
“Vitamin D is unlikely to be the underlying mechanism for the higher risk observed in black and minority ethnic individuals, and vitamin D supplements are unlikely to provide an effective intervention,” Claire Hastie, PhD, of the University of Glasgow and colleagues concluded.
But this hasn’t stopped two endocrinologists from appealing to members of the British Association of Physicians of Indian Origin (BAPIO) to get their vitamin D levels tested.
The black and Asian minority ethnic population, “especially frontline staff, should get their Vitamin D3 levels checked and get appropriate replacement as required,” said Parag Singhal, MD, of Weston General Hospital, Weston-Super-Mare, England, and David C. Anderson, a retired endocrinologist, said in a letter to BAPIO members.
Indeed, they suggested a booster dose of 100,000 IU as a one-off for black and Asian minority ethnic health care staff that should raise vitamin D levels for 2-3 months. They referred to a systematic review that concludes that “single vitamin D3 doses ≥300,000 IU are most effective at improving vitamin D status ... for up to 3 months”.
Commenting on the idea, Dr. Rosen remarked that, in general, the high-dose 50,000-500,000 IU given as a one-off does not confer any greater benefit than a single dose of 1,000 IU per day, except that the blood levels go up quicker and higher.
“Really there is no evidence that getting to super-high levels of vitamin D confer a greater benefit than normal levels,” he said. “So if health care workers suspect vitamin D deficiency, daily doses of 1,000 IU seem reasonable; even if they miss doses, the blood levels are relatively stable.”
On the specific question of vitamin D needs in ethnic minorities, Dr. Rosen said while such individuals do have lower serum levels of vitamin D, the issue is whether there are meaningful clinical implications related to this.
“The real question is whether [ethnic minority individuals] have physiologically adapted for this in other ways because these low levels have been so for thousands of years. In fact, African Americans have lower vitamin D levels but they absolutely have better bones than [whites],” he pointed out.
Testing and governmental recommendations during COVID-19
The U.S. National Institutes of Health in general advises 400 IU to 800 IU per day intake of vitamin D, depending on age, with those over 70 years requiring the highest daily dose. This will result in blood levels that are sufficient to maintain bone health and normal calcium metabolism in healthy people. There are no additional recommendations specific to vitamin D intake during the COVID-19 pandemic, however.
And Dr. Rosen pointed out that there is no evidence for mass screening of vitamin D levels among the U.S. population.
“U.S. public health guidance was pre-COVID, and I think high-risk individuals might want to think about their levels; for example, someone with inflammatory bowel disease or liver or pancreatic disease. These people are at higher risk anyway, and it could be because their vitamin D is low,” he said.
“Skip the test and ensure you are getting adequate levels of vitamin D whether via diet or supplement [400-800 IU per day],” he suggested. “It won’t harm.”
The U.K.’s Public Health England (PHE) clarified its advice on vitamin D supplementation during COVID-19. Alison Tedstone, PhD, chief nutritionist at PHE, said: “Many people are spending more time indoors and may not get all the vitamin D they need from sunlight. To protect their bone and muscle health, they should consider taking a daily supplement containing 10 micrograms [400 IU] of vitamin D.”
However, “there is no sufficient evidence to support recommending Vitamin D for reducing the risk of COVID-19,” she stressed.
Dr. Bajaj is on the advisory board of Medscape Diabetes & Endocrinology. He has ties with Amgen, AstraZeneca Boehringer Ingelheim, Janssen, Merck, Novo Nordisk, Sanofi, Eli Lilly,Valeant, Canadian Collaborative Research Network, CMS Knowledge Translation, Diabetes Canada Scientific Group, LMC Healthcare,mdBriefCase,Medscape, andMeducom. Dr. Kenny, Dr. Rosen, and Dr. Singhal have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Mainstream media outlets have been flooded recently with reports speculating on what role, if any, vitamin D may play in reducing the severity of COVID-19 infection.
as well as mortality, with the further suggestion of an effect of vitamin D on the immune response to infection.
But other studies question such a link, including any association between vitamin D concentration and differences in COVID-19 severity by ethnic group.
And while some researchers and clinicians believe people should get tested to see if they have adequate vitamin D levels during this pandemic – in particular frontline health care workers – most doctors say the best way to ensure that people have adequate levels of vitamin D during COVID-19 is to simply take supplements at currently recommended levels.
This is especially important given the fact that, during “lockdown” scenarios, many people are spending more time than usual indoors.
Clifford Rosen, MD, senior scientist at Maine Medical Center’s Research Institute in Scarborough, has been researching vitamin D for 25 years.
“There’s no randomized, controlled trial for sure, and that’s the gold standard,” he said in an interview, and “the observational data are so confounded, it’s difficult to know.”
Whether from diet or supplementation, having adequate vitamin D is important, especially for those at the highest risk of COVID-19, he said. Still, robust data supporting a role of vitamin D in prevention of COVID-19, or as any kind of “therapy” for the infection, are currently lacking.
Rose Anne Kenny, MD, professor of medical gerontology at Trinity College Dublin, recently coauthored an article detailing an inverse association between vitamin D levels and mortality from COVID-19 across countries in Europe.
“At no stage are any of us saying this is a given, but there’s a probability that [vitamin D] – a low-hanging fruit – is a contributory factor and we can do something about it now,” she said in an interview.
Dr. Kenny is calling for the Irish government to formally change their recommendations. “We call on the Irish government to update guidelines as a matter of urgency and encourage all adults to take [vitamin D] supplements during the COVID-19 crisis.” Northern Ireland, part of the United Kingdom, also has not yet made this recommendation, she said.
Meanwhile, Harpreet S. Bajaj, MD, MPH, a practicing endocrinologist from Mount Sinai Hospital, Toronto, said: “Vitamin D could have any of three potential roles in risk for COVID-19 and/or its severity: no role, simply a marker, or a causal factor.”
Dr. Bajaj said – as did Dr. Rosen and Dr. Kenny – that randomized, controlled trials (RCTs) are sorely needed to help ascertain whether there is a specific role of vitamin D.
“Until then, we should continue to follow established public health recommendations for vitamin D supplementation, in addition to following COVID-19 prevention guidance and evolving guidelines for COVID-19 treatment.”
What is the role of vitamin D fortification?
In their study in the Irish Medical Journal, Dr. Kenny and colleagues noted that, in Europe, despite being sunny, Spain and Northern Italy had high rates of vitamin D deficiency and have experienced some of the highest COVID-19 infection and mortality rates in the world.
But these countries do not formally fortify foods or recommend supplementation with vitamin D.
Conversely, the northern countries of Norway, Finland, and Sweden had higher vitamin D levels despite less UVB sunlight exposure, as a result of common supplementation and formal fortification of foods. These Nordic countries also had lower levels of COVID-19 infection and mortality.
Overall, the correlation between low vitamin D levels and mortality from COVID-19 was statistically significant (P = .046), the investigators reported.
“Optimizing vitamin D status to recommendations by national and international public health agencies will certainly have ... potential benefits for COVID-19,” they concluded.
“We’re not saying there aren’t any confounders. This can absolutely be the case, but this [finding] needs to be in the mix of evidence,” Dr. Kenny said.
Dr. Kenny also noted that countries in the Southern Hemisphere have been seeing a relatively low mortality from COVID-19, although she acknowledged the explanation could be that the virus spread later to those countries.
Dr. Rosen has doubts on this issue, too.
“Sure, vitamin D supplementation may have worked for [Nordic countries], their COVID-19 has been better controlled, but there’s no causality here; there’s another step to actually prove this. Other factors might be at play,” he said.
“Look at Brazil, it’s at the equator but the disease is devastating the country. Right now, I just don’t believe it.”
Does vitamin D have a role to play in immune modulation?
One theory currently circulating is that, if vitamin D does have any role to play in modulating response to COVID-19, this may be via a blunting of the immune system reaction to the virus.
In a recent preprint study, Ali Daneshkhah, PhD, and colleagues from Northwestern University, Chicago, interrogated hospital data from China, France, Germany, Italy, Iran, South Korea, Spain, Switzerland, the United Kingdom, and the United States.
Specifically, the risk of severe COVID-19 cases among patients with severe vitamin D deficiency was 17.3%, whereas the equivalent figure for patients with normal vitamin D levels was 14.6% (a reduction of 15.6%).
“This potential effect may be attributed to vitamin D’s ability to suppress the adaptive immune system, regulating cytokine levels and thereby reducing the risk of developing severe COVID-19,” said the researchers.
Likewise, JoAnn E. Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, in a recent commentary, noted evidence from an observational study from three South Asian hospitals, in which the prevalence of vitamin D deficiency was much higher among those with severe COVID-19 illness compared with those with mild illness.
“We also know that vitamin D has an immune-modulating effect and can lower inflammation, and this may be relevant to the respiratory response during COVID-19 and the cytokine storm that’s been demonstrated,” she noted.
Dr. Rosen said he is willing to listen on the issue of a potential role of vitamin D in immune modulation.
“I’ve been a huge skeptic from the get-go, and loudly criticized the data for doing nothing. I am surprised at myself for saying there might be some effect,” he said.
“Clearly most people don’t get this [cytokine storm] but of those that do, it’s unclear why they do. Maybe if you are vitamin D sufficient, it might have some impact down the road on your response to an infection,” Dr. Rosen said. “Vitamin D may induce proteins important in modulating the function of macrophages of the immune system.”
Ethnic minorities disproportionately affected
It is also well recognized that COVID-19 disproportionately affects black and Asian minority ethnic individuals.
But on the issue of vitamin D in this context, one recent peer-reviewed study using UK Biobank data found no evidence to support a potential role for vitamin D concentration to explain susceptibility to COVID-19 infection either overall or in explaining differences between ethnic groups.
“Vitamin D is unlikely to be the underlying mechanism for the higher risk observed in black and minority ethnic individuals, and vitamin D supplements are unlikely to provide an effective intervention,” Claire Hastie, PhD, of the University of Glasgow and colleagues concluded.
But this hasn’t stopped two endocrinologists from appealing to members of the British Association of Physicians of Indian Origin (BAPIO) to get their vitamin D levels tested.
The black and Asian minority ethnic population, “especially frontline staff, should get their Vitamin D3 levels checked and get appropriate replacement as required,” said Parag Singhal, MD, of Weston General Hospital, Weston-Super-Mare, England, and David C. Anderson, a retired endocrinologist, said in a letter to BAPIO members.
Indeed, they suggested a booster dose of 100,000 IU as a one-off for black and Asian minority ethnic health care staff that should raise vitamin D levels for 2-3 months. They referred to a systematic review that concludes that “single vitamin D3 doses ≥300,000 IU are most effective at improving vitamin D status ... for up to 3 months”.
Commenting on the idea, Dr. Rosen remarked that, in general, the high-dose 50,000-500,000 IU given as a one-off does not confer any greater benefit than a single dose of 1,000 IU per day, except that the blood levels go up quicker and higher.
“Really there is no evidence that getting to super-high levels of vitamin D confer a greater benefit than normal levels,” he said. “So if health care workers suspect vitamin D deficiency, daily doses of 1,000 IU seem reasonable; even if they miss doses, the blood levels are relatively stable.”
On the specific question of vitamin D needs in ethnic minorities, Dr. Rosen said while such individuals do have lower serum levels of vitamin D, the issue is whether there are meaningful clinical implications related to this.
“The real question is whether [ethnic minority individuals] have physiologically adapted for this in other ways because these low levels have been so for thousands of years. In fact, African Americans have lower vitamin D levels but they absolutely have better bones than [whites],” he pointed out.
Testing and governmental recommendations during COVID-19
The U.S. National Institutes of Health in general advises 400 IU to 800 IU per day intake of vitamin D, depending on age, with those over 70 years requiring the highest daily dose. This will result in blood levels that are sufficient to maintain bone health and normal calcium metabolism in healthy people. There are no additional recommendations specific to vitamin D intake during the COVID-19 pandemic, however.
And Dr. Rosen pointed out that there is no evidence for mass screening of vitamin D levels among the U.S. population.
“U.S. public health guidance was pre-COVID, and I think high-risk individuals might want to think about their levels; for example, someone with inflammatory bowel disease or liver or pancreatic disease. These people are at higher risk anyway, and it could be because their vitamin D is low,” he said.
“Skip the test and ensure you are getting adequate levels of vitamin D whether via diet or supplement [400-800 IU per day],” he suggested. “It won’t harm.”
The U.K.’s Public Health England (PHE) clarified its advice on vitamin D supplementation during COVID-19. Alison Tedstone, PhD, chief nutritionist at PHE, said: “Many people are spending more time indoors and may not get all the vitamin D they need from sunlight. To protect their bone and muscle health, they should consider taking a daily supplement containing 10 micrograms [400 IU] of vitamin D.”
However, “there is no sufficient evidence to support recommending Vitamin D for reducing the risk of COVID-19,” she stressed.
Dr. Bajaj is on the advisory board of Medscape Diabetes & Endocrinology. He has ties with Amgen, AstraZeneca Boehringer Ingelheim, Janssen, Merck, Novo Nordisk, Sanofi, Eli Lilly,Valeant, Canadian Collaborative Research Network, CMS Knowledge Translation, Diabetes Canada Scientific Group, LMC Healthcare,mdBriefCase,Medscape, andMeducom. Dr. Kenny, Dr. Rosen, and Dr. Singhal have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Mainstream media outlets have been flooded recently with reports speculating on what role, if any, vitamin D may play in reducing the severity of COVID-19 infection.
as well as mortality, with the further suggestion of an effect of vitamin D on the immune response to infection.
But other studies question such a link, including any association between vitamin D concentration and differences in COVID-19 severity by ethnic group.
And while some researchers and clinicians believe people should get tested to see if they have adequate vitamin D levels during this pandemic – in particular frontline health care workers – most doctors say the best way to ensure that people have adequate levels of vitamin D during COVID-19 is to simply take supplements at currently recommended levels.
This is especially important given the fact that, during “lockdown” scenarios, many people are spending more time than usual indoors.
Clifford Rosen, MD, senior scientist at Maine Medical Center’s Research Institute in Scarborough, has been researching vitamin D for 25 years.
“There’s no randomized, controlled trial for sure, and that’s the gold standard,” he said in an interview, and “the observational data are so confounded, it’s difficult to know.”
Whether from diet or supplementation, having adequate vitamin D is important, especially for those at the highest risk of COVID-19, he said. Still, robust data supporting a role of vitamin D in prevention of COVID-19, or as any kind of “therapy” for the infection, are currently lacking.
Rose Anne Kenny, MD, professor of medical gerontology at Trinity College Dublin, recently coauthored an article detailing an inverse association between vitamin D levels and mortality from COVID-19 across countries in Europe.
“At no stage are any of us saying this is a given, but there’s a probability that [vitamin D] – a low-hanging fruit – is a contributory factor and we can do something about it now,” she said in an interview.
Dr. Kenny is calling for the Irish government to formally change their recommendations. “We call on the Irish government to update guidelines as a matter of urgency and encourage all adults to take [vitamin D] supplements during the COVID-19 crisis.” Northern Ireland, part of the United Kingdom, also has not yet made this recommendation, she said.
Meanwhile, Harpreet S. Bajaj, MD, MPH, a practicing endocrinologist from Mount Sinai Hospital, Toronto, said: “Vitamin D could have any of three potential roles in risk for COVID-19 and/or its severity: no role, simply a marker, or a causal factor.”
Dr. Bajaj said – as did Dr. Rosen and Dr. Kenny – that randomized, controlled trials (RCTs) are sorely needed to help ascertain whether there is a specific role of vitamin D.
“Until then, we should continue to follow established public health recommendations for vitamin D supplementation, in addition to following COVID-19 prevention guidance and evolving guidelines for COVID-19 treatment.”
What is the role of vitamin D fortification?
In their study in the Irish Medical Journal, Dr. Kenny and colleagues noted that, in Europe, despite being sunny, Spain and Northern Italy had high rates of vitamin D deficiency and have experienced some of the highest COVID-19 infection and mortality rates in the world.
But these countries do not formally fortify foods or recommend supplementation with vitamin D.
Conversely, the northern countries of Norway, Finland, and Sweden had higher vitamin D levels despite less UVB sunlight exposure, as a result of common supplementation and formal fortification of foods. These Nordic countries also had lower levels of COVID-19 infection and mortality.
Overall, the correlation between low vitamin D levels and mortality from COVID-19 was statistically significant (P = .046), the investigators reported.
“Optimizing vitamin D status to recommendations by national and international public health agencies will certainly have ... potential benefits for COVID-19,” they concluded.
“We’re not saying there aren’t any confounders. This can absolutely be the case, but this [finding] needs to be in the mix of evidence,” Dr. Kenny said.
Dr. Kenny also noted that countries in the Southern Hemisphere have been seeing a relatively low mortality from COVID-19, although she acknowledged the explanation could be that the virus spread later to those countries.
Dr. Rosen has doubts on this issue, too.
“Sure, vitamin D supplementation may have worked for [Nordic countries], their COVID-19 has been better controlled, but there’s no causality here; there’s another step to actually prove this. Other factors might be at play,” he said.
“Look at Brazil, it’s at the equator but the disease is devastating the country. Right now, I just don’t believe it.”
Does vitamin D have a role to play in immune modulation?
One theory currently circulating is that, if vitamin D does have any role to play in modulating response to COVID-19, this may be via a blunting of the immune system reaction to the virus.
In a recent preprint study, Ali Daneshkhah, PhD, and colleagues from Northwestern University, Chicago, interrogated hospital data from China, France, Germany, Italy, Iran, South Korea, Spain, Switzerland, the United Kingdom, and the United States.
Specifically, the risk of severe COVID-19 cases among patients with severe vitamin D deficiency was 17.3%, whereas the equivalent figure for patients with normal vitamin D levels was 14.6% (a reduction of 15.6%).
“This potential effect may be attributed to vitamin D’s ability to suppress the adaptive immune system, regulating cytokine levels and thereby reducing the risk of developing severe COVID-19,” said the researchers.
Likewise, JoAnn E. Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, in a recent commentary, noted evidence from an observational study from three South Asian hospitals, in which the prevalence of vitamin D deficiency was much higher among those with severe COVID-19 illness compared with those with mild illness.
“We also know that vitamin D has an immune-modulating effect and can lower inflammation, and this may be relevant to the respiratory response during COVID-19 and the cytokine storm that’s been demonstrated,” she noted.
Dr. Rosen said he is willing to listen on the issue of a potential role of vitamin D in immune modulation.
“I’ve been a huge skeptic from the get-go, and loudly criticized the data for doing nothing. I am surprised at myself for saying there might be some effect,” he said.
“Clearly most people don’t get this [cytokine storm] but of those that do, it’s unclear why they do. Maybe if you are vitamin D sufficient, it might have some impact down the road on your response to an infection,” Dr. Rosen said. “Vitamin D may induce proteins important in modulating the function of macrophages of the immune system.”
Ethnic minorities disproportionately affected
It is also well recognized that COVID-19 disproportionately affects black and Asian minority ethnic individuals.
But on the issue of vitamin D in this context, one recent peer-reviewed study using UK Biobank data found no evidence to support a potential role for vitamin D concentration to explain susceptibility to COVID-19 infection either overall or in explaining differences between ethnic groups.
“Vitamin D is unlikely to be the underlying mechanism for the higher risk observed in black and minority ethnic individuals, and vitamin D supplements are unlikely to provide an effective intervention,” Claire Hastie, PhD, of the University of Glasgow and colleagues concluded.
But this hasn’t stopped two endocrinologists from appealing to members of the British Association of Physicians of Indian Origin (BAPIO) to get their vitamin D levels tested.
The black and Asian minority ethnic population, “especially frontline staff, should get their Vitamin D3 levels checked and get appropriate replacement as required,” said Parag Singhal, MD, of Weston General Hospital, Weston-Super-Mare, England, and David C. Anderson, a retired endocrinologist, said in a letter to BAPIO members.
Indeed, they suggested a booster dose of 100,000 IU as a one-off for black and Asian minority ethnic health care staff that should raise vitamin D levels for 2-3 months. They referred to a systematic review that concludes that “single vitamin D3 doses ≥300,000 IU are most effective at improving vitamin D status ... for up to 3 months”.
Commenting on the idea, Dr. Rosen remarked that, in general, the high-dose 50,000-500,000 IU given as a one-off does not confer any greater benefit than a single dose of 1,000 IU per day, except that the blood levels go up quicker and higher.
“Really there is no evidence that getting to super-high levels of vitamin D confer a greater benefit than normal levels,” he said. “So if health care workers suspect vitamin D deficiency, daily doses of 1,000 IU seem reasonable; even if they miss doses, the blood levels are relatively stable.”
On the specific question of vitamin D needs in ethnic minorities, Dr. Rosen said while such individuals do have lower serum levels of vitamin D, the issue is whether there are meaningful clinical implications related to this.
“The real question is whether [ethnic minority individuals] have physiologically adapted for this in other ways because these low levels have been so for thousands of years. In fact, African Americans have lower vitamin D levels but they absolutely have better bones than [whites],” he pointed out.
Testing and governmental recommendations during COVID-19
The U.S. National Institutes of Health in general advises 400 IU to 800 IU per day intake of vitamin D, depending on age, with those over 70 years requiring the highest daily dose. This will result in blood levels that are sufficient to maintain bone health and normal calcium metabolism in healthy people. There are no additional recommendations specific to vitamin D intake during the COVID-19 pandemic, however.
And Dr. Rosen pointed out that there is no evidence for mass screening of vitamin D levels among the U.S. population.
“U.S. public health guidance was pre-COVID, and I think high-risk individuals might want to think about their levels; for example, someone with inflammatory bowel disease or liver or pancreatic disease. These people are at higher risk anyway, and it could be because their vitamin D is low,” he said.
“Skip the test and ensure you are getting adequate levels of vitamin D whether via diet or supplement [400-800 IU per day],” he suggested. “It won’t harm.”
The U.K.’s Public Health England (PHE) clarified its advice on vitamin D supplementation during COVID-19. Alison Tedstone, PhD, chief nutritionist at PHE, said: “Many people are spending more time indoors and may not get all the vitamin D they need from sunlight. To protect their bone and muscle health, they should consider taking a daily supplement containing 10 micrograms [400 IU] of vitamin D.”
However, “there is no sufficient evidence to support recommending Vitamin D for reducing the risk of COVID-19,” she stressed.
Dr. Bajaj is on the advisory board of Medscape Diabetes & Endocrinology. He has ties with Amgen, AstraZeneca Boehringer Ingelheim, Janssen, Merck, Novo Nordisk, Sanofi, Eli Lilly,Valeant, Canadian Collaborative Research Network, CMS Knowledge Translation, Diabetes Canada Scientific Group, LMC Healthcare,mdBriefCase,Medscape, andMeducom. Dr. Kenny, Dr. Rosen, and Dr. Singhal have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Antibody testing suggests COVID-19 cases are being missed
The number of COVID-19 infections in the community may be “substantially greater” than totals confirmed by authorities, based on SARS-CoV-2 antibody testing among a random sample of adults in Los Angeles County, Calif.
Testing of 863 people on April 10-11 revealed that 35 (4.06%) were positive for SARS-CoV-2–specific antibodies (IgM or IgG), and after adjustment for test sensitivity and specificity, the weighted prevalence for the entire sample was 4.65%, Neeraj Sood, PhD, of the University of Southern California, Los Angeles, and associates wrote in JAMA.
The estimate of 4.65% “implies that approximately 367,000 adults [in Los Angeles County] had SARS-CoV-2 antibodies, which is substantially greater than the 8,430 cumulative number of confirmed infections in the county on April 10,” they wrote.
It also suggests that fatality rates based on the larger number of infections may be lower than rates based on confirmed cases. “In addition, contact tracing methods to limit the spread of infection will face considerable challenges,” Dr. Sood and associates said.
Test positivity varied by race/ethnicity, sex, and income. The proportion of non-Hispanic blacks with a positive result was 6.94%, compared with 4.42% for non-Hispanic whites, 2.10% for Hispanics, and 3.85% for others. Men were much more likely than women to be positive for SARS-CoV-2: 5.18% vs. 3.31%, the investigators said.
Household income favored the middle ground. Those individuals making less than $50,000 a year had a positivity rate of 5.14% and those with an income of $100,000 or more had a rate of 4.90%, but only 1.58% of those making $50,000-$99,999 tested positive, they reported.
The authors reported numerous sources of nonprofit organization support.
SOURCE: Sood N et al. JAMA 2020 May 18. doi: 10.1001/jama.2020.8279.
The number of COVID-19 infections in the community may be “substantially greater” than totals confirmed by authorities, based on SARS-CoV-2 antibody testing among a random sample of adults in Los Angeles County, Calif.
Testing of 863 people on April 10-11 revealed that 35 (4.06%) were positive for SARS-CoV-2–specific antibodies (IgM or IgG), and after adjustment for test sensitivity and specificity, the weighted prevalence for the entire sample was 4.65%, Neeraj Sood, PhD, of the University of Southern California, Los Angeles, and associates wrote in JAMA.
The estimate of 4.65% “implies that approximately 367,000 adults [in Los Angeles County] had SARS-CoV-2 antibodies, which is substantially greater than the 8,430 cumulative number of confirmed infections in the county on April 10,” they wrote.
It also suggests that fatality rates based on the larger number of infections may be lower than rates based on confirmed cases. “In addition, contact tracing methods to limit the spread of infection will face considerable challenges,” Dr. Sood and associates said.
Test positivity varied by race/ethnicity, sex, and income. The proportion of non-Hispanic blacks with a positive result was 6.94%, compared with 4.42% for non-Hispanic whites, 2.10% for Hispanics, and 3.85% for others. Men were much more likely than women to be positive for SARS-CoV-2: 5.18% vs. 3.31%, the investigators said.
Household income favored the middle ground. Those individuals making less than $50,000 a year had a positivity rate of 5.14% and those with an income of $100,000 or more had a rate of 4.90%, but only 1.58% of those making $50,000-$99,999 tested positive, they reported.
The authors reported numerous sources of nonprofit organization support.
SOURCE: Sood N et al. JAMA 2020 May 18. doi: 10.1001/jama.2020.8279.
The number of COVID-19 infections in the community may be “substantially greater” than totals confirmed by authorities, based on SARS-CoV-2 antibody testing among a random sample of adults in Los Angeles County, Calif.
Testing of 863 people on April 10-11 revealed that 35 (4.06%) were positive for SARS-CoV-2–specific antibodies (IgM or IgG), and after adjustment for test sensitivity and specificity, the weighted prevalence for the entire sample was 4.65%, Neeraj Sood, PhD, of the University of Southern California, Los Angeles, and associates wrote in JAMA.
The estimate of 4.65% “implies that approximately 367,000 adults [in Los Angeles County] had SARS-CoV-2 antibodies, which is substantially greater than the 8,430 cumulative number of confirmed infections in the county on April 10,” they wrote.
It also suggests that fatality rates based on the larger number of infections may be lower than rates based on confirmed cases. “In addition, contact tracing methods to limit the spread of infection will face considerable challenges,” Dr. Sood and associates said.
Test positivity varied by race/ethnicity, sex, and income. The proportion of non-Hispanic blacks with a positive result was 6.94%, compared with 4.42% for non-Hispanic whites, 2.10% for Hispanics, and 3.85% for others. Men were much more likely than women to be positive for SARS-CoV-2: 5.18% vs. 3.31%, the investigators said.
Household income favored the middle ground. Those individuals making less than $50,000 a year had a positivity rate of 5.14% and those with an income of $100,000 or more had a rate of 4.90%, but only 1.58% of those making $50,000-$99,999 tested positive, they reported.
The authors reported numerous sources of nonprofit organization support.
SOURCE: Sood N et al. JAMA 2020 May 18. doi: 10.1001/jama.2020.8279.
FROM JAMA
COVID-19 in kids: Severe illness most common in infants, teens
Children and young adults in all age groups can develop severe illness after SARS-CoV-2 infection, but the oldest and youngest appear most likely to be hospitalized and possibly critically ill, based on data from a retrospective cohort study of 177 pediatric patients seen at a single center.
“Although children and young adults clearly are susceptible to SARS-CoV-2 infection, attention has focused primarily on their potential role in influencing spread and community transmission rather than the potential severity of infection in children and young adults themselves,” wrote Roberta L. DeBiasi, MD, chief of the division of pediatric infectious diseases at Children’s National Hospital, Washington, and colleagues.
In a study published in the Journal of Pediatrics, the researchers reviewed data from 44 hospitalized and 133 non-hospitalized children and young adults infected with SARS-CoV-2. Of the 44 hospitalized patients, 35 were noncritically ill and 9 were critically ill. The study population ranged from 0.1-34 years of age, with a median of 10 years, which was similar between hospitalized and nonhospitalized patients. However, the median age of critically ill patients was significantly higher, compared with noncritically ill patients (17 years vs. 4 years). All age groups were represented in all cohorts. “However, we noted a bimodal distribution of patients less than 1 year of age and patients greater than 15 years of age representing the largest proportion of patients within the SARS-CoV-2–infected hospitalized and critically ill cohorts,” the researchers noted. Children less than 1 year and adolescents/young adults over 15 years each represented 32% of the 44 hospitalized patients.
Overall, 39% of the 177 patients had underlying medical conditions, the most frequent of which was asthma (20%), which was not significantly more common between hospitalized/nonhospitalized patients or critically ill/noncritically ill patients. Patients also presented with neurologic conditions (6%), diabetes (3%), obesity (2%), cardiac conditions (3%), hematologic conditions (3%) and oncologic conditions (1%). Underlying conditions occurred more commonly in the hospitalized cohort (63%) than in the nonhospitalized cohort (32%).
Neurologic disorders, cardiac conditions, hematologic conditions, and oncologic conditions were significantly more common in hospitalized patients, but not significantly more common among those critically ill versus noncritically ill.
About 76% of the patients presented with respiratory symptoms including rhinorrhea, congestion, sore throat, cough, or shortness of breath – with or without fever; 66% had fevers; and 48% had both respiratory symptoms and fever. Shortness of breath was significantly more common among hospitalized patients versus nonhospitalized patients (26% vs. 12%), but less severe respiratory symptoms were significantly more common among nonhospitalized patients, the researchers noted.
Other symptoms – such as diarrhea, vomiting, chest pain, and loss of sense or smell occurred in a small percentage of patients – but were not more likely to occur in any of the cohorts.
Among the critically ill patients, eight of nine needed some level of respiratory support, and four were on ventilators.
“One patient had features consistent with the recently emerged Kawasaki disease–like presentation with hyperinflammatory state, hypotension, and profound myocardial depression,” Dr. DiBiasi and associates noted.
The researchers found coinfection with routine coronavirus, respiratory syncytial virus, or rhinovirus/enterovirus in 4 of 63 (6%) patients, but the clinical impact of these coinfections are unclear.
The study findings were limited by several factors including the retrospective design and the ongoing transmission of COVID-19 in the Washington area, the researchers noted. “One potential bias of this study is our regional role in providing critical care for young adults age 21-35 years with COVID-19.” In addition, “we plan to address the role of race and ethnicity after validation of current administrative data and have elected to defer this analysis until completed.”
“Our findings highlight the potential for severe disease in this age group and inform other regions to anticipate and prepare their COVID-19 response to include a significant burden of hospitalized and critically ill children and young adults. As SARS-CoV-2 spreads within the United States, regional differences may be apparent based on virus and host factors that are yet to be identified,” Dr. DeBiasi and colleagues concluded.
Robin Steinhorn, MD, serves as an associate editor for the Journal of Pediatrics. The other researchers declared no conflicts of interest.
SOURCE: DeBiasi RL et al. J Pediatr. 2020 May 6. doi: 10.1016/j.jpeds.2020.05.007.
This article was updated 5/19/20.
Children and young adults in all age groups can develop severe illness after SARS-CoV-2 infection, but the oldest and youngest appear most likely to be hospitalized and possibly critically ill, based on data from a retrospective cohort study of 177 pediatric patients seen at a single center.
“Although children and young adults clearly are susceptible to SARS-CoV-2 infection, attention has focused primarily on their potential role in influencing spread and community transmission rather than the potential severity of infection in children and young adults themselves,” wrote Roberta L. DeBiasi, MD, chief of the division of pediatric infectious diseases at Children’s National Hospital, Washington, and colleagues.
In a study published in the Journal of Pediatrics, the researchers reviewed data from 44 hospitalized and 133 non-hospitalized children and young adults infected with SARS-CoV-2. Of the 44 hospitalized patients, 35 were noncritically ill and 9 were critically ill. The study population ranged from 0.1-34 years of age, with a median of 10 years, which was similar between hospitalized and nonhospitalized patients. However, the median age of critically ill patients was significantly higher, compared with noncritically ill patients (17 years vs. 4 years). All age groups were represented in all cohorts. “However, we noted a bimodal distribution of patients less than 1 year of age and patients greater than 15 years of age representing the largest proportion of patients within the SARS-CoV-2–infected hospitalized and critically ill cohorts,” the researchers noted. Children less than 1 year and adolescents/young adults over 15 years each represented 32% of the 44 hospitalized patients.
Overall, 39% of the 177 patients had underlying medical conditions, the most frequent of which was asthma (20%), which was not significantly more common between hospitalized/nonhospitalized patients or critically ill/noncritically ill patients. Patients also presented with neurologic conditions (6%), diabetes (3%), obesity (2%), cardiac conditions (3%), hematologic conditions (3%) and oncologic conditions (1%). Underlying conditions occurred more commonly in the hospitalized cohort (63%) than in the nonhospitalized cohort (32%).
Neurologic disorders, cardiac conditions, hematologic conditions, and oncologic conditions were significantly more common in hospitalized patients, but not significantly more common among those critically ill versus noncritically ill.
About 76% of the patients presented with respiratory symptoms including rhinorrhea, congestion, sore throat, cough, or shortness of breath – with or without fever; 66% had fevers; and 48% had both respiratory symptoms and fever. Shortness of breath was significantly more common among hospitalized patients versus nonhospitalized patients (26% vs. 12%), but less severe respiratory symptoms were significantly more common among nonhospitalized patients, the researchers noted.
Other symptoms – such as diarrhea, vomiting, chest pain, and loss of sense or smell occurred in a small percentage of patients – but were not more likely to occur in any of the cohorts.
Among the critically ill patients, eight of nine needed some level of respiratory support, and four were on ventilators.
“One patient had features consistent with the recently emerged Kawasaki disease–like presentation with hyperinflammatory state, hypotension, and profound myocardial depression,” Dr. DiBiasi and associates noted.
The researchers found coinfection with routine coronavirus, respiratory syncytial virus, or rhinovirus/enterovirus in 4 of 63 (6%) patients, but the clinical impact of these coinfections are unclear.
The study findings were limited by several factors including the retrospective design and the ongoing transmission of COVID-19 in the Washington area, the researchers noted. “One potential bias of this study is our regional role in providing critical care for young adults age 21-35 years with COVID-19.” In addition, “we plan to address the role of race and ethnicity after validation of current administrative data and have elected to defer this analysis until completed.”
“Our findings highlight the potential for severe disease in this age group and inform other regions to anticipate and prepare their COVID-19 response to include a significant burden of hospitalized and critically ill children and young adults. As SARS-CoV-2 spreads within the United States, regional differences may be apparent based on virus and host factors that are yet to be identified,” Dr. DeBiasi and colleagues concluded.
Robin Steinhorn, MD, serves as an associate editor for the Journal of Pediatrics. The other researchers declared no conflicts of interest.
SOURCE: DeBiasi RL et al. J Pediatr. 2020 May 6. doi: 10.1016/j.jpeds.2020.05.007.
This article was updated 5/19/20.
Children and young adults in all age groups can develop severe illness after SARS-CoV-2 infection, but the oldest and youngest appear most likely to be hospitalized and possibly critically ill, based on data from a retrospective cohort study of 177 pediatric patients seen at a single center.
“Although children and young adults clearly are susceptible to SARS-CoV-2 infection, attention has focused primarily on their potential role in influencing spread and community transmission rather than the potential severity of infection in children and young adults themselves,” wrote Roberta L. DeBiasi, MD, chief of the division of pediatric infectious diseases at Children’s National Hospital, Washington, and colleagues.
In a study published in the Journal of Pediatrics, the researchers reviewed data from 44 hospitalized and 133 non-hospitalized children and young adults infected with SARS-CoV-2. Of the 44 hospitalized patients, 35 were noncritically ill and 9 were critically ill. The study population ranged from 0.1-34 years of age, with a median of 10 years, which was similar between hospitalized and nonhospitalized patients. However, the median age of critically ill patients was significantly higher, compared with noncritically ill patients (17 years vs. 4 years). All age groups were represented in all cohorts. “However, we noted a bimodal distribution of patients less than 1 year of age and patients greater than 15 years of age representing the largest proportion of patients within the SARS-CoV-2–infected hospitalized and critically ill cohorts,” the researchers noted. Children less than 1 year and adolescents/young adults over 15 years each represented 32% of the 44 hospitalized patients.
Overall, 39% of the 177 patients had underlying medical conditions, the most frequent of which was asthma (20%), which was not significantly more common between hospitalized/nonhospitalized patients or critically ill/noncritically ill patients. Patients also presented with neurologic conditions (6%), diabetes (3%), obesity (2%), cardiac conditions (3%), hematologic conditions (3%) and oncologic conditions (1%). Underlying conditions occurred more commonly in the hospitalized cohort (63%) than in the nonhospitalized cohort (32%).
Neurologic disorders, cardiac conditions, hematologic conditions, and oncologic conditions were significantly more common in hospitalized patients, but not significantly more common among those critically ill versus noncritically ill.
About 76% of the patients presented with respiratory symptoms including rhinorrhea, congestion, sore throat, cough, or shortness of breath – with or without fever; 66% had fevers; and 48% had both respiratory symptoms and fever. Shortness of breath was significantly more common among hospitalized patients versus nonhospitalized patients (26% vs. 12%), but less severe respiratory symptoms were significantly more common among nonhospitalized patients, the researchers noted.
Other symptoms – such as diarrhea, vomiting, chest pain, and loss of sense or smell occurred in a small percentage of patients – but were not more likely to occur in any of the cohorts.
Among the critically ill patients, eight of nine needed some level of respiratory support, and four were on ventilators.
“One patient had features consistent with the recently emerged Kawasaki disease–like presentation with hyperinflammatory state, hypotension, and profound myocardial depression,” Dr. DiBiasi and associates noted.
The researchers found coinfection with routine coronavirus, respiratory syncytial virus, or rhinovirus/enterovirus in 4 of 63 (6%) patients, but the clinical impact of these coinfections are unclear.
The study findings were limited by several factors including the retrospective design and the ongoing transmission of COVID-19 in the Washington area, the researchers noted. “One potential bias of this study is our regional role in providing critical care for young adults age 21-35 years with COVID-19.” In addition, “we plan to address the role of race and ethnicity after validation of current administrative data and have elected to defer this analysis until completed.”
“Our findings highlight the potential for severe disease in this age group and inform other regions to anticipate and prepare their COVID-19 response to include a significant burden of hospitalized and critically ill children and young adults. As SARS-CoV-2 spreads within the United States, regional differences may be apparent based on virus and host factors that are yet to be identified,” Dr. DeBiasi and colleagues concluded.
Robin Steinhorn, MD, serves as an associate editor for the Journal of Pediatrics. The other researchers declared no conflicts of interest.
SOURCE: DeBiasi RL et al. J Pediatr. 2020 May 6. doi: 10.1016/j.jpeds.2020.05.007.
This article was updated 5/19/20.
FROM THE JOURNAL OF PEDIATRICS
Today's top news highlights
Dermatologic changes with COVID-19: What we do and don’t know
From qurantine toes to patients with chilblains, the skin manifestaions of COVID-19 are being seen and documented. "It was once hypothesized that Coronaviridae was the cause of Kawasaki disease. Then that got debunked. But these cases now raise the question of whether Kawasaki disease may be virally mediated. Is it an immune reaction to an infectious trigger? Is it actually Coronaviridae that triggers it?" READ MORE
Glucose control linked to COVID-19 outcomes in largest study yet
The strong link between glucose control and COVID-19 outcomes has been reaffirmed in the largest study thus far of hospitalized patients with preexisting type 2 diabetes, according to findings published in Cell Metabolism. “We were surprised to see such favorable outcomes in the well-controlled blood glucose group among patients with COVID-19 and preexisting type 2 diabetes,” senior author Hongliang Li said in a statement. READ MORE
FDA approves pomalidomide for Kaposi sarcoma
The FDA has granted accelerated approval to pomalidomide for the treatment of AIDS-related Kaposi sarcoma that is resistant to HAART or that occurs in HIV-negative patients. Pomalidomide is the only oral agent and first new treatment option for Kaposi sarcoma in more than 20 years, according to the company. READ MORE
ER docs ask, 'Where are our patients?'
Across the country, the number of patients arriving in EDs with acute ST-elevation MI, stroke, trauma, and other highest-acuity presentations is down substantially. But the volume of patients with more routine, bread-and-butter conditions typically seen in EDs is down even more, noted Donald M. Yealy, MD, professor and chair of the department of emergency medicine at the University of Pittsburgh. He is concerned for a coming “tsunami of untreated illness," adding that "the safest place in the world to be right now is the ED." READ MORE
Obesity can shift severe COVID-19 to younger groups
The younger an ICU patient with severe COVID-19 is, the more obese that patient tends to be, according to a new analysis published in The Lancet. "If you’re very, very overweight, don’t think that if you’re 35 you’re that much safer than your mother or grandparents or others in their 60s or 70s,” noted David Kass, MD, a professor of cardiology and medicine at Johns Hopkins University School of Medicine in Baltimore. READ MORE
Many hydroxychloroquine prophylaxis trials lack ECG screening
As of April 30, 155 randomized, control trials listed on clinicaltrials.gov had designs that intended to randomize a total of more than 85,000 healthy people to receive hydroxychloroquine or chloroquine, in some cases in combination with azithromycin, to test their efficacy and safety for COVID-19 prophylaxis. All three agents potentially produce lengthening of the corrected QT interval (QTc), Michael H. Gollob, MD, said in an article posted by JAAC. If this happens in a person who starts treatment with a QTc on the high end, the incremental prolongation could push their heart rhythm into a range where their risk for a life-threatening arrhythmia becomes substantial, said Dr. Gollob. “It is ... inexcusable that clinical investigators would dare to include healthy individuals ... without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. READ MORE
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Dermatologic changes with COVID-19: What we do and don’t know
From qurantine toes to patients with chilblains, the skin manifestaions of COVID-19 are being seen and documented. "It was once hypothesized that Coronaviridae was the cause of Kawasaki disease. Then that got debunked. But these cases now raise the question of whether Kawasaki disease may be virally mediated. Is it an immune reaction to an infectious trigger? Is it actually Coronaviridae that triggers it?" READ MORE
Glucose control linked to COVID-19 outcomes in largest study yet
The strong link between glucose control and COVID-19 outcomes has been reaffirmed in the largest study thus far of hospitalized patients with preexisting type 2 diabetes, according to findings published in Cell Metabolism. “We were surprised to see such favorable outcomes in the well-controlled blood glucose group among patients with COVID-19 and preexisting type 2 diabetes,” senior author Hongliang Li said in a statement. READ MORE
FDA approves pomalidomide for Kaposi sarcoma
The FDA has granted accelerated approval to pomalidomide for the treatment of AIDS-related Kaposi sarcoma that is resistant to HAART or that occurs in HIV-negative patients. Pomalidomide is the only oral agent and first new treatment option for Kaposi sarcoma in more than 20 years, according to the company. READ MORE
ER docs ask, 'Where are our patients?'
Across the country, the number of patients arriving in EDs with acute ST-elevation MI, stroke, trauma, and other highest-acuity presentations is down substantially. But the volume of patients with more routine, bread-and-butter conditions typically seen in EDs is down even more, noted Donald M. Yealy, MD, professor and chair of the department of emergency medicine at the University of Pittsburgh. He is concerned for a coming “tsunami of untreated illness," adding that "the safest place in the world to be right now is the ED." READ MORE
Obesity can shift severe COVID-19 to younger groups
The younger an ICU patient with severe COVID-19 is, the more obese that patient tends to be, according to a new analysis published in The Lancet. "If you’re very, very overweight, don’t think that if you’re 35 you’re that much safer than your mother or grandparents or others in their 60s or 70s,” noted David Kass, MD, a professor of cardiology and medicine at Johns Hopkins University School of Medicine in Baltimore. READ MORE
Many hydroxychloroquine prophylaxis trials lack ECG screening
As of April 30, 155 randomized, control trials listed on clinicaltrials.gov had designs that intended to randomize a total of more than 85,000 healthy people to receive hydroxychloroquine or chloroquine, in some cases in combination with azithromycin, to test their efficacy and safety for COVID-19 prophylaxis. All three agents potentially produce lengthening of the corrected QT interval (QTc), Michael H. Gollob, MD, said in an article posted by JAAC. If this happens in a person who starts treatment with a QTc on the high end, the incremental prolongation could push their heart rhythm into a range where their risk for a life-threatening arrhythmia becomes substantial, said Dr. Gollob. “It is ... inexcusable that clinical investigators would dare to include healthy individuals ... without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. READ MORE
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Dermatologic changes with COVID-19: What we do and don’t know
From qurantine toes to patients with chilblains, the skin manifestaions of COVID-19 are being seen and documented. "It was once hypothesized that Coronaviridae was the cause of Kawasaki disease. Then that got debunked. But these cases now raise the question of whether Kawasaki disease may be virally mediated. Is it an immune reaction to an infectious trigger? Is it actually Coronaviridae that triggers it?" READ MORE
Glucose control linked to COVID-19 outcomes in largest study yet
The strong link between glucose control and COVID-19 outcomes has been reaffirmed in the largest study thus far of hospitalized patients with preexisting type 2 diabetes, according to findings published in Cell Metabolism. “We were surprised to see such favorable outcomes in the well-controlled blood glucose group among patients with COVID-19 and preexisting type 2 diabetes,” senior author Hongliang Li said in a statement. READ MORE
FDA approves pomalidomide for Kaposi sarcoma
The FDA has granted accelerated approval to pomalidomide for the treatment of AIDS-related Kaposi sarcoma that is resistant to HAART or that occurs in HIV-negative patients. Pomalidomide is the only oral agent and first new treatment option for Kaposi sarcoma in more than 20 years, according to the company. READ MORE
ER docs ask, 'Where are our patients?'
Across the country, the number of patients arriving in EDs with acute ST-elevation MI, stroke, trauma, and other highest-acuity presentations is down substantially. But the volume of patients with more routine, bread-and-butter conditions typically seen in EDs is down even more, noted Donald M. Yealy, MD, professor and chair of the department of emergency medicine at the University of Pittsburgh. He is concerned for a coming “tsunami of untreated illness," adding that "the safest place in the world to be right now is the ED." READ MORE
Obesity can shift severe COVID-19 to younger groups
The younger an ICU patient with severe COVID-19 is, the more obese that patient tends to be, according to a new analysis published in The Lancet. "If you’re very, very overweight, don’t think that if you’re 35 you’re that much safer than your mother or grandparents or others in their 60s or 70s,” noted David Kass, MD, a professor of cardiology and medicine at Johns Hopkins University School of Medicine in Baltimore. READ MORE
Many hydroxychloroquine prophylaxis trials lack ECG screening
As of April 30, 155 randomized, control trials listed on clinicaltrials.gov had designs that intended to randomize a total of more than 85,000 healthy people to receive hydroxychloroquine or chloroquine, in some cases in combination with azithromycin, to test their efficacy and safety for COVID-19 prophylaxis. All three agents potentially produce lengthening of the corrected QT interval (QTc), Michael H. Gollob, MD, said in an article posted by JAAC. If this happens in a person who starts treatment with a QTc on the high end, the incremental prolongation could push their heart rhythm into a range where their risk for a life-threatening arrhythmia becomes substantial, said Dr. Gollob. “It is ... inexcusable that clinical investigators would dare to include healthy individuals ... without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. READ MORE
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Dermatologic changes with COVID-19: What we know and don’t know
The dermatologic manifestations associated with SARS-CoV-2 are many and varied, with new information virtually daily. Graeme Lipper, MD, a member of the Medscape Dermatology advisory board, discussed what we know and what is still to be learned with Lindy Fox, MD, a professor of dermatology at University of California, San Francisco (UCSF) and a member of the American Academy of Dermatology’s COVID-19 Registry task force.
Graeme M. Lipper, MD
Earlier this spring, before there was any real talk about skin manifestations of COVID, my partner called me in to see an unusual case. His patient was a healthy 20-year-old who had just come back from college and had tender, purple discoloration and swelling on his toes. I shrugged and said “looks like chilblains,” but there was something weird about the case. It seemed more severe, with areas of blistering and erosions, and the discomfort was unusual for run-of-the-mill pernio. This young man had experienced a cough and shortness of breath a few weeks earlier but those symptoms had resolved when we saw him.
That evening, I was on a derm social media site and saw a series of pictures from Italy that blew me away. All of these pictures looked just like this kid’s toes. That’s the first I heard of “COVID toes,” but now they seem to be everywhere. How would you describe this presentation, and how does it differ from typical chilblains?
Lindy P. Fox, MD
I am so proud of dermatologists around the world who have really jumped into action to examine the pathophysiology and immunology behind these findings.
Your experience matches mine. Like you, I first heard about these pernio- or chilblains-like lesions when Europe was experiencing its surge in cases. And while it does indeed look like chilblains, I think the reality is that it is more severe and symptomatic than we would expect. I think your observation is exactly right. There are certainly clinicians who do not believe that this is an association with COVID-19 because the testing is often negative. But to my mind, there are just too many cases at the wrong time of year, all happening concomitantly, and simultaneous with a new virus for me to accept that they are not somehow related.
Dr. Lipper: Some have referred to this as “quarantine toes,” the result of more people at home and walking around barefoot. That doesn’t seem to make a whole lot of sense because it’s happening in both warm and cold climates.
Others have speculated that there is another, unrelated circulating virus causing these pernio cases, but that seems far-fetched.
But the idea of a reporting bias – more patients paying attention to these lesions because they’ve read something in the mass media or seen a report on television and are concerned, and thus present with mild lesions they might otherwise have ignored – may be contributing somewhat. But even that cannot be the sole reason behind the increase.
Dr. Fox: Agree.
Evaluation of the patient with chilblains – then and now
Dr. Lipper: In the past, how did you perform a workup for someone with chilblains?
Dr. Fox: Pre-COVID – and I think we all have divided our world into pre- and post-COVID – the most common thing that I’d be looking for would be a clotting disorder or an autoimmune disease, typically lupus. So I take a good history, review of systems, and look at the skin for signs of lupus or other autoimmune connective tissue diseases. My lab workup is probably limited to an antinuclear antibody (ANA). If the findings are severe and recurrent, I might check for hypercoagulability with an antiphospholipid antibody panel. But that was usually it unless there was something in the history or physical exam that would lead me to look for something less common – for example, cryoglobulins or an underlying hematologic disease that would lead to a predominance of lesions in acral sites.
My approach was the same. In New England, where I practice, I also always look at environmental factors. We would sometimes see chilblains in someone from a warmer climate who came home to the Northeast to ski.
Dr. Lipper: Now, in the post-COVID world, how do you assess these patients? What has changed?
Dr. Fox: That’s a great question. To be frank, our focus now is on not missing a secondary consequence of COVID infection that we might not have picked up before. I’m the first to admit that the workup that we have been doing at UCSF is extremely comprehensive. We may be ordering tests that don’t need to be done. But until we know better what might and might not be affected by COVID, we don’t actually have a sense of whether they’re worth looking for or not.
Right now, my workup includes nasal swab polymerase chain reaction (PCR) for COVID, as well as IgG and IgM serology if available. We have IgG easily available to us. IgM needs approval; at UCSF, it is primarily done in neonates as of now. I also do a workup for autoimmunity and cold-associated disease, which includes an ANA, rheumatoid factor, cryoglobulin, and cold agglutinins.
Because of reported concerns about hypercoagulability in COVID patients, particularly in those who are doing poorly in the hospital, we look for elevations in d-dimers and fibrinogen. We check antiphospholipid antibodies, anticardiolipin antibodies, erythrocyte sedimentation rate, and C-reactive protein. That is probably too much of a workup for the healthy young person, but as of yet, we are just unable to say that those things are universally normal.
There has also been concern that complement may be involved in patients who do poorly and tend to clot a lot. So we are also checking C3, C4, and CH50.
To date, in my patients who have had this workup, I have found one with a positive ANA that was significant (1:320) who also had low complements.
There have been a couple of patients at my institution, not my own patients, who are otherwise fine but have some slight elevation in d-dimers.
Dr. Lipper: Is COVID toes more than one condition?
Some of the initial reports of finger/toe cyanosis out of China were very alarming, with many patients developing skin necrosis or even gangrene. These were critically ill adults with pneumonia and blood markers of disseminated intravascular coagulation, and five out of seven died. In contrast, the cases of pseudo-pernio reported in Europe, and now the United States, seem to be much milder, usually occurring late in the illness or in asymptomatic young people. Do you think these are two different conditions?
Dr. Fox: I believe you have hit the nail on the head. I think it is really important that we don’t confuse those two things. In the inpatient setting, we are clearly seeing patients with a prothrombotic state with associated retiform purpura. For nondermatologists, that usually means star-like, stellate-like, or even lacy purpuric changes with potential for necrosis of the skin. In hospitalized patients, the fingers and toes are usually affected but, interestingly, also the buttocks. When these lesions are biopsied, as has been done by our colleague at Weill Cornell Medicine, New York, Joanna Harp, MD, we tend to find thrombosis.
A study of endothelial cell function in patients with COVID-19, published in the Lancet tried to determine whether viral particles could be found in endothelial cells. And the investigators did indeed find these particles. So it appears that the virus is endothelially active, and this might provide some insight into the thromboses seen in hospitalized patients. These patients can develop purple necrotic toes that may progress to gangrene. But that is completely different from what we’re seeing when we say pernio-like or chilblains-like lesions.
The chilblains-like lesions come in several forms. They may be purple, red bumps, often involving the tops of the toes and sometimes the bottom of the feet. Some have been described as target-like or erythema multiforme–like. In others, there may not be individual discrete lesions but rather a redness or bluish, purplish discoloration accompanied by edema of the entire toe or several toes.
Biopsies that I am aware of have identified features consistent with an inflammatory process, all of which can be seen in a typical biopsy of pernio. You can sometimes see lymphocytes surrounding a vessel (called lymphocytic vasculitis) that may damage a vessel and cause a small clot, but the primary process is an inflammatory rather than thrombotic one. You may get a clot in a little tiny vessel secondary to inflammation, and that may lead to some blisters or little areas of necrosis. But you’re not going to see digital necrosis and gangrene. I think that’s an important distinction.
The patients who get the pernio-like lesions are typically children or young adults and are otherwise healthy. Half of them didn’t even have COVID symptoms. If they did have COVID symptoms they were typically mild. So we think the pernio-like lesions are most often occurring in the late stage of the disease and now represent a secondary inflammatory response.
Managing COVID toes
Dr. Lipper: One question I’ve been struggling with is, what do we tell these otherwise healthy patients with purple toes, especially those with no other symptoms? Many of them are testing SARS-CoV-2 negative, both with viral swabs and serologies. Some have suggestive histories like known COVID exposure, recent cough, or travel to high-risk areas. Do we tell them they’re at risk of transmitting the virus? Should they self-quarantine, and for how long? Is there any consensus emerging?
Dr. Fox: This is a good opportunity to plug the American Academy of Dermatology’s COVID-19 Registry, which is run by Esther Freeman, MD, at Massachusetts General Hospital. She has done a phenomenal job in helping us figure out the answers to these exact questions.
I’d encourage any clinicians who have a suspected COVID patient with a skin finding, whether or not infection is confirmed with testing, to enter information about that patient into the registry. That is the only way we will figure out evidence-based answers to a lot of the questions that we’re talking about today.
Based on working with the registry, we know that, rarely, patients who develop pernio-like changes will do so before they get COVID symptoms or at the same time as more typical symptoms. Some patients with these findings are PCR positive, and it is therefore theoretically possible that you could be shedding virus while you’re having the pernio toes. However, more commonly – and this is the experience of most of my colleagues and what we’re seeing at UCSF – pernio is a later finding and most patients are no longer shedding the virus. It appears that pseudo-pernio is an immune reaction and most people are not actively infectious at that point.
The only way to know for sure is to send patients for both PCR testing and antibody testing. If the PCR is negative, the most likely interpretation is that the person is no longer shedding virus, though there can be some false negatives. Therefore, these patients do not need to isolate outside of what I call their COVID pod – family or roommates who have probably been with them the whole time. Any transmission likely would have already occurred.
I tell people who call me concerned about their toes that I do think they should be given a workup for COVID. However, I reassure them that it is usually a good prognostic sign.
What is puzzling is that even in patients with pseudo-chilblains who have a clinical history consistent with COVID or exposure to a COVID-positive family member, antibody testing is often – in fact, most often – negative. There are many hypotheses as to why this is. Maybe the tests just aren’t good. Maybe people with mild disease don’t generate enough antibodies to be detected, Maybe we’re testing at the wrong time. Those are all things that we’re trying to figure out.
But currently, I tell patients that they do not need to strictly isolate. They should still practice social distancing, wear a mask, practice good hand hygiene, and do all of the careful things that we should all be doing. However, they can live within their home environment and be reassured that most likely they are in the convalescent stage.
Dr. Lipper: I find the antibody issue both fascinating and confusing.
In my practice, we’ve noticed a range of symptoms associated with pseudo-pernio. Some people barely realize it’s there and only called because they saw a headline in the news. Others complain of severe burning, throbbing, or itching that keeps them up at night and can sometimes last for weeks. Are there any treatments that seem to help?
Dr. Fox: We can start by saying, as you note, that a lot of patients don’t need interventions. They want reassurance that their toes aren’t going to fall off, that nothing terrible is going to happen to them, and often that’s enough. So far, many patients have contacted us just because they heard about the link between what they were seeing on their feet and COVID. They were likely toward the end of any other symptoms they may have had. But moving forward, I think we’re going to be seeing patients at the more active stage as the public is more aware of this finding.
Most of the time we can manage with clobetasol ointment and low-dose aspirin. I wouldn’t give aspirin to a young child with a high fever, but otherwise I think aspirin is not harmful. A paper published in Mayo Clinic Proceedings in 2014, before COVID, by Jonathan Cappel, MD, and David Wetter, MD, provides a nice therapeutic algorithm. Assuming that the findings we are seeing now are inflammatory, then I think that algorithm should apply. Nifedipine 20-60 mg/day is an option. Hydroxychloroquine, a maximum of 5 mg/kg per day, is an option. I have used hydroxychloroquine most commonly, pre-COVID, in patients who have symptomatic pernio.
I also use pentoxifylline 400 mg three times a day, which has a slight anti-inflammatory effect, when I think a blood vessel is incidentally involved or the patient has a predisposition to clotting. Nicotinamide 500 mg three times a day can be used, though I have not used it.
Some topical options are nitroglycerin, tacrolimus, and minoxidil.
However, during this post-COVID period, I have not come across many with pseudo-pernio who needed anything more than a topical steroid and some aspirin. But I do know of other physicians who have been taking care of patients with much more symptomatic disease.
Dr. Lipper: That is a comprehensive list. You’ve mentioned some options that I’ve wondered about, especially pentoxifylline, which I have found to be very helpful for livedoid vasculopathy. I should note that these are all off-label uses.
Let’s talk about some other suspected skin manifestations of COVID. A prospective nationwide study in Spain of 375 patients reported on a number of different skin manifestations of COVID.
You’re part of a team doing critically important work with the American Academy of Dermatology COVID-19 Dermatology Registry. I know it’s early going, but what are some of the other common skin presentations you’re finding?
Dr. Fox: I’m glad you brought up that paper out of Spain. I think it is really good and does highlight the difference in acute versus convalescent cutaneous manifestations and prognosis. It confirms what we’re seeing. Retiform purpura is an early finding associated with ill patients in the hospital. Pseudo pernio-like lesions tend to be later-stage and in younger, healthier patients.
Interestingly, the vesicular eruption that those investigators describe – monomorphic vesicles on the trunk and extremity – can occur in the more acute phase. That’s fascinating to me because widespread vesicular eruptions are not a thing that we commonly see. If it is not an autoimmune blistering disease, and not a drug-induced blistering process, then you’re really left with viral. Rickettsialpox can do that, as can primary varicella, disseminated herpes, disseminated zoster, and now COVID. So that’s intriguing.
I got called to see a patient yesterday who had symptoms of COVID about a month ago. She was not PCR tested at the time but she is now negative. She has a widespread eruption of tiny vesicles on an erythematous base. An IgG for COVID is positive. How do we decide whether her skin lesions have active virus in them?
The many dermatologic manifestations of COVID-19
Dr. Lipper: In the series in Spain, almost 1 out of 10 patients were found to have a widespread vesicular rash. And just under half had maculopapular exanthems. The information arising from the AAD registry will be of great interest and build on this paper.
In England, the National Health Service and the Paediatric Intensive Care Society recently put out a warning about an alarming number of children with COVID-19 who developed symptoms mimicking Kawasaki disease (high fever, abdominal pain, rash, swollen lymph nodes, mucositis, and conjunctivitis). These kids have systemic inflammation and vasculitis and are critically ill. That was followed by an alert from the New York City Health Department about cases there, which as of May 6 numbered 64. Another 25 children with similar findings have been identified in France.
This is such a scary development, especially because children were supposed to be relatively “safe” from this virus. Any thoughts on who is at risk or why?
Dr. Fox: It’s very alarming. It appears that these cases look just like Kawasaki disease.
It was once hypothesized that Coronaviridae was the cause of Kawasaki disease. Then that got debunked. But these cases now raise the question of whether Kawasaki disease may be virally mediated. Is it an immune reaction to an infectious trigger? Is it actually Coronaviridae that triggers it?
As with these pernio cases, I think we’re going to learn about the pathophysiology of these diseases that we currently look at as secondary responses or immune reactions to unknown triggers. We’re going to learn a lot about them and about the immune system because of how this virus is acting on the immune system.
Dr. Lipper: As is the case with patients with pernio-like lesions, some of these children with Kawasaki-like disease are PCR negative for SARS-CoV-2. It will be interesting to see what happens with antibody testing in this population.
Dr. Fox: Agree. While some of the manufacturers of serology tests have claimed that they have very high sensitivity and specificity, that has not been my experience.
Dr. Lipper: I’ve had a number of patients with a clinical picture that strongly suggests COVID whose serology tests have been negative.
Dr. Fox: As have I. While this could be the result of faulty tests, my biggest worry is that it means that people with mild disease do not mount an antibody response. And if people who have disease can’t make antibodies, then there’s no herd immunity. If there’s no herd immunity, we’re stuck in lockdown until there’s a vaccine.
Dr. Lipper: That is a scary but real possibility. We need evidence – evidence like that provided by the AAD registry.
Dr. Fox: Agree. I look forward to sharing those results with you when we have them.
Dr. Lipper is a clinical assistant professor at the University of Vermont, Burlington, and a partner at Advanced DermCare in Danbury, Conn.
Dr. Fox is a professor in the department of dermatology at the University of California, San Francisco. She is a hospital-based dermatologist who specializes in the care of patients with complex skin conditions. She is immediate past president of the Medical Dermatology Society and current president of the Society of Dermatology Hospitalists.
This article was first published on Medscape.com.
The dermatologic manifestations associated with SARS-CoV-2 are many and varied, with new information virtually daily. Graeme Lipper, MD, a member of the Medscape Dermatology advisory board, discussed what we know and what is still to be learned with Lindy Fox, MD, a professor of dermatology at University of California, San Francisco (UCSF) and a member of the American Academy of Dermatology’s COVID-19 Registry task force.
Graeme M. Lipper, MD
Earlier this spring, before there was any real talk about skin manifestations of COVID, my partner called me in to see an unusual case. His patient was a healthy 20-year-old who had just come back from college and had tender, purple discoloration and swelling on his toes. I shrugged and said “looks like chilblains,” but there was something weird about the case. It seemed more severe, with areas of blistering and erosions, and the discomfort was unusual for run-of-the-mill pernio. This young man had experienced a cough and shortness of breath a few weeks earlier but those symptoms had resolved when we saw him.
That evening, I was on a derm social media site and saw a series of pictures from Italy that blew me away. All of these pictures looked just like this kid’s toes. That’s the first I heard of “COVID toes,” but now they seem to be everywhere. How would you describe this presentation, and how does it differ from typical chilblains?
Lindy P. Fox, MD
I am so proud of dermatologists around the world who have really jumped into action to examine the pathophysiology and immunology behind these findings.
Your experience matches mine. Like you, I first heard about these pernio- or chilblains-like lesions when Europe was experiencing its surge in cases. And while it does indeed look like chilblains, I think the reality is that it is more severe and symptomatic than we would expect. I think your observation is exactly right. There are certainly clinicians who do not believe that this is an association with COVID-19 because the testing is often negative. But to my mind, there are just too many cases at the wrong time of year, all happening concomitantly, and simultaneous with a new virus for me to accept that they are not somehow related.
Dr. Lipper: Some have referred to this as “quarantine toes,” the result of more people at home and walking around barefoot. That doesn’t seem to make a whole lot of sense because it’s happening in both warm and cold climates.
Others have speculated that there is another, unrelated circulating virus causing these pernio cases, but that seems far-fetched.
But the idea of a reporting bias – more patients paying attention to these lesions because they’ve read something in the mass media or seen a report on television and are concerned, and thus present with mild lesions they might otherwise have ignored – may be contributing somewhat. But even that cannot be the sole reason behind the increase.
Dr. Fox: Agree.
Evaluation of the patient with chilblains – then and now
Dr. Lipper: In the past, how did you perform a workup for someone with chilblains?
Dr. Fox: Pre-COVID – and I think we all have divided our world into pre- and post-COVID – the most common thing that I’d be looking for would be a clotting disorder or an autoimmune disease, typically lupus. So I take a good history, review of systems, and look at the skin for signs of lupus or other autoimmune connective tissue diseases. My lab workup is probably limited to an antinuclear antibody (ANA). If the findings are severe and recurrent, I might check for hypercoagulability with an antiphospholipid antibody panel. But that was usually it unless there was something in the history or physical exam that would lead me to look for something less common – for example, cryoglobulins or an underlying hematologic disease that would lead to a predominance of lesions in acral sites.
My approach was the same. In New England, where I practice, I also always look at environmental factors. We would sometimes see chilblains in someone from a warmer climate who came home to the Northeast to ski.
Dr. Lipper: Now, in the post-COVID world, how do you assess these patients? What has changed?
Dr. Fox: That’s a great question. To be frank, our focus now is on not missing a secondary consequence of COVID infection that we might not have picked up before. I’m the first to admit that the workup that we have been doing at UCSF is extremely comprehensive. We may be ordering tests that don’t need to be done. But until we know better what might and might not be affected by COVID, we don’t actually have a sense of whether they’re worth looking for or not.
Right now, my workup includes nasal swab polymerase chain reaction (PCR) for COVID, as well as IgG and IgM serology if available. We have IgG easily available to us. IgM needs approval; at UCSF, it is primarily done in neonates as of now. I also do a workup for autoimmunity and cold-associated disease, which includes an ANA, rheumatoid factor, cryoglobulin, and cold agglutinins.
Because of reported concerns about hypercoagulability in COVID patients, particularly in those who are doing poorly in the hospital, we look for elevations in d-dimers and fibrinogen. We check antiphospholipid antibodies, anticardiolipin antibodies, erythrocyte sedimentation rate, and C-reactive protein. That is probably too much of a workup for the healthy young person, but as of yet, we are just unable to say that those things are universally normal.
There has also been concern that complement may be involved in patients who do poorly and tend to clot a lot. So we are also checking C3, C4, and CH50.
To date, in my patients who have had this workup, I have found one with a positive ANA that was significant (1:320) who also had low complements.
There have been a couple of patients at my institution, not my own patients, who are otherwise fine but have some slight elevation in d-dimers.
Dr. Lipper: Is COVID toes more than one condition?
Some of the initial reports of finger/toe cyanosis out of China were very alarming, with many patients developing skin necrosis or even gangrene. These were critically ill adults with pneumonia and blood markers of disseminated intravascular coagulation, and five out of seven died. In contrast, the cases of pseudo-pernio reported in Europe, and now the United States, seem to be much milder, usually occurring late in the illness or in asymptomatic young people. Do you think these are two different conditions?
Dr. Fox: I believe you have hit the nail on the head. I think it is really important that we don’t confuse those two things. In the inpatient setting, we are clearly seeing patients with a prothrombotic state with associated retiform purpura. For nondermatologists, that usually means star-like, stellate-like, or even lacy purpuric changes with potential for necrosis of the skin. In hospitalized patients, the fingers and toes are usually affected but, interestingly, also the buttocks. When these lesions are biopsied, as has been done by our colleague at Weill Cornell Medicine, New York, Joanna Harp, MD, we tend to find thrombosis.
A study of endothelial cell function in patients with COVID-19, published in the Lancet tried to determine whether viral particles could be found in endothelial cells. And the investigators did indeed find these particles. So it appears that the virus is endothelially active, and this might provide some insight into the thromboses seen in hospitalized patients. These patients can develop purple necrotic toes that may progress to gangrene. But that is completely different from what we’re seeing when we say pernio-like or chilblains-like lesions.
The chilblains-like lesions come in several forms. They may be purple, red bumps, often involving the tops of the toes and sometimes the bottom of the feet. Some have been described as target-like or erythema multiforme–like. In others, there may not be individual discrete lesions but rather a redness or bluish, purplish discoloration accompanied by edema of the entire toe or several toes.
Biopsies that I am aware of have identified features consistent with an inflammatory process, all of which can be seen in a typical biopsy of pernio. You can sometimes see lymphocytes surrounding a vessel (called lymphocytic vasculitis) that may damage a vessel and cause a small clot, but the primary process is an inflammatory rather than thrombotic one. You may get a clot in a little tiny vessel secondary to inflammation, and that may lead to some blisters or little areas of necrosis. But you’re not going to see digital necrosis and gangrene. I think that’s an important distinction.
The patients who get the pernio-like lesions are typically children or young adults and are otherwise healthy. Half of them didn’t even have COVID symptoms. If they did have COVID symptoms they were typically mild. So we think the pernio-like lesions are most often occurring in the late stage of the disease and now represent a secondary inflammatory response.
Managing COVID toes
Dr. Lipper: One question I’ve been struggling with is, what do we tell these otherwise healthy patients with purple toes, especially those with no other symptoms? Many of them are testing SARS-CoV-2 negative, both with viral swabs and serologies. Some have suggestive histories like known COVID exposure, recent cough, or travel to high-risk areas. Do we tell them they’re at risk of transmitting the virus? Should they self-quarantine, and for how long? Is there any consensus emerging?
Dr. Fox: This is a good opportunity to plug the American Academy of Dermatology’s COVID-19 Registry, which is run by Esther Freeman, MD, at Massachusetts General Hospital. She has done a phenomenal job in helping us figure out the answers to these exact questions.
I’d encourage any clinicians who have a suspected COVID patient with a skin finding, whether or not infection is confirmed with testing, to enter information about that patient into the registry. That is the only way we will figure out evidence-based answers to a lot of the questions that we’re talking about today.
Based on working with the registry, we know that, rarely, patients who develop pernio-like changes will do so before they get COVID symptoms or at the same time as more typical symptoms. Some patients with these findings are PCR positive, and it is therefore theoretically possible that you could be shedding virus while you’re having the pernio toes. However, more commonly – and this is the experience of most of my colleagues and what we’re seeing at UCSF – pernio is a later finding and most patients are no longer shedding the virus. It appears that pseudo-pernio is an immune reaction and most people are not actively infectious at that point.
The only way to know for sure is to send patients for both PCR testing and antibody testing. If the PCR is negative, the most likely interpretation is that the person is no longer shedding virus, though there can be some false negatives. Therefore, these patients do not need to isolate outside of what I call their COVID pod – family or roommates who have probably been with them the whole time. Any transmission likely would have already occurred.
I tell people who call me concerned about their toes that I do think they should be given a workup for COVID. However, I reassure them that it is usually a good prognostic sign.
What is puzzling is that even in patients with pseudo-chilblains who have a clinical history consistent with COVID or exposure to a COVID-positive family member, antibody testing is often – in fact, most often – negative. There are many hypotheses as to why this is. Maybe the tests just aren’t good. Maybe people with mild disease don’t generate enough antibodies to be detected, Maybe we’re testing at the wrong time. Those are all things that we’re trying to figure out.
But currently, I tell patients that they do not need to strictly isolate. They should still practice social distancing, wear a mask, practice good hand hygiene, and do all of the careful things that we should all be doing. However, they can live within their home environment and be reassured that most likely they are in the convalescent stage.
Dr. Lipper: I find the antibody issue both fascinating and confusing.
In my practice, we’ve noticed a range of symptoms associated with pseudo-pernio. Some people barely realize it’s there and only called because they saw a headline in the news. Others complain of severe burning, throbbing, or itching that keeps them up at night and can sometimes last for weeks. Are there any treatments that seem to help?
Dr. Fox: We can start by saying, as you note, that a lot of patients don’t need interventions. They want reassurance that their toes aren’t going to fall off, that nothing terrible is going to happen to them, and often that’s enough. So far, many patients have contacted us just because they heard about the link between what they were seeing on their feet and COVID. They were likely toward the end of any other symptoms they may have had. But moving forward, I think we’re going to be seeing patients at the more active stage as the public is more aware of this finding.
Most of the time we can manage with clobetasol ointment and low-dose aspirin. I wouldn’t give aspirin to a young child with a high fever, but otherwise I think aspirin is not harmful. A paper published in Mayo Clinic Proceedings in 2014, before COVID, by Jonathan Cappel, MD, and David Wetter, MD, provides a nice therapeutic algorithm. Assuming that the findings we are seeing now are inflammatory, then I think that algorithm should apply. Nifedipine 20-60 mg/day is an option. Hydroxychloroquine, a maximum of 5 mg/kg per day, is an option. I have used hydroxychloroquine most commonly, pre-COVID, in patients who have symptomatic pernio.
I also use pentoxifylline 400 mg three times a day, which has a slight anti-inflammatory effect, when I think a blood vessel is incidentally involved or the patient has a predisposition to clotting. Nicotinamide 500 mg three times a day can be used, though I have not used it.
Some topical options are nitroglycerin, tacrolimus, and minoxidil.
However, during this post-COVID period, I have not come across many with pseudo-pernio who needed anything more than a topical steroid and some aspirin. But I do know of other physicians who have been taking care of patients with much more symptomatic disease.
Dr. Lipper: That is a comprehensive list. You’ve mentioned some options that I’ve wondered about, especially pentoxifylline, which I have found to be very helpful for livedoid vasculopathy. I should note that these are all off-label uses.
Let’s talk about some other suspected skin manifestations of COVID. A prospective nationwide study in Spain of 375 patients reported on a number of different skin manifestations of COVID.
You’re part of a team doing critically important work with the American Academy of Dermatology COVID-19 Dermatology Registry. I know it’s early going, but what are some of the other common skin presentations you’re finding?
Dr. Fox: I’m glad you brought up that paper out of Spain. I think it is really good and does highlight the difference in acute versus convalescent cutaneous manifestations and prognosis. It confirms what we’re seeing. Retiform purpura is an early finding associated with ill patients in the hospital. Pseudo pernio-like lesions tend to be later-stage and in younger, healthier patients.
Interestingly, the vesicular eruption that those investigators describe – monomorphic vesicles on the trunk and extremity – can occur in the more acute phase. That’s fascinating to me because widespread vesicular eruptions are not a thing that we commonly see. If it is not an autoimmune blistering disease, and not a drug-induced blistering process, then you’re really left with viral. Rickettsialpox can do that, as can primary varicella, disseminated herpes, disseminated zoster, and now COVID. So that’s intriguing.
I got called to see a patient yesterday who had symptoms of COVID about a month ago. She was not PCR tested at the time but she is now negative. She has a widespread eruption of tiny vesicles on an erythematous base. An IgG for COVID is positive. How do we decide whether her skin lesions have active virus in them?
The many dermatologic manifestations of COVID-19
Dr. Lipper: In the series in Spain, almost 1 out of 10 patients were found to have a widespread vesicular rash. And just under half had maculopapular exanthems. The information arising from the AAD registry will be of great interest and build on this paper.
In England, the National Health Service and the Paediatric Intensive Care Society recently put out a warning about an alarming number of children with COVID-19 who developed symptoms mimicking Kawasaki disease (high fever, abdominal pain, rash, swollen lymph nodes, mucositis, and conjunctivitis). These kids have systemic inflammation and vasculitis and are critically ill. That was followed by an alert from the New York City Health Department about cases there, which as of May 6 numbered 64. Another 25 children with similar findings have been identified in France.
This is such a scary development, especially because children were supposed to be relatively “safe” from this virus. Any thoughts on who is at risk or why?
Dr. Fox: It’s very alarming. It appears that these cases look just like Kawasaki disease.
It was once hypothesized that Coronaviridae was the cause of Kawasaki disease. Then that got debunked. But these cases now raise the question of whether Kawasaki disease may be virally mediated. Is it an immune reaction to an infectious trigger? Is it actually Coronaviridae that triggers it?
As with these pernio cases, I think we’re going to learn about the pathophysiology of these diseases that we currently look at as secondary responses or immune reactions to unknown triggers. We’re going to learn a lot about them and about the immune system because of how this virus is acting on the immune system.
Dr. Lipper: As is the case with patients with pernio-like lesions, some of these children with Kawasaki-like disease are PCR negative for SARS-CoV-2. It will be interesting to see what happens with antibody testing in this population.
Dr. Fox: Agree. While some of the manufacturers of serology tests have claimed that they have very high sensitivity and specificity, that has not been my experience.
Dr. Lipper: I’ve had a number of patients with a clinical picture that strongly suggests COVID whose serology tests have been negative.
Dr. Fox: As have I. While this could be the result of faulty tests, my biggest worry is that it means that people with mild disease do not mount an antibody response. And if people who have disease can’t make antibodies, then there’s no herd immunity. If there’s no herd immunity, we’re stuck in lockdown until there’s a vaccine.
Dr. Lipper: That is a scary but real possibility. We need evidence – evidence like that provided by the AAD registry.
Dr. Fox: Agree. I look forward to sharing those results with you when we have them.
Dr. Lipper is a clinical assistant professor at the University of Vermont, Burlington, and a partner at Advanced DermCare in Danbury, Conn.
Dr. Fox is a professor in the department of dermatology at the University of California, San Francisco. She is a hospital-based dermatologist who specializes in the care of patients with complex skin conditions. She is immediate past president of the Medical Dermatology Society and current president of the Society of Dermatology Hospitalists.
This article was first published on Medscape.com.
The dermatologic manifestations associated with SARS-CoV-2 are many and varied, with new information virtually daily. Graeme Lipper, MD, a member of the Medscape Dermatology advisory board, discussed what we know and what is still to be learned with Lindy Fox, MD, a professor of dermatology at University of California, San Francisco (UCSF) and a member of the American Academy of Dermatology’s COVID-19 Registry task force.
Graeme M. Lipper, MD
Earlier this spring, before there was any real talk about skin manifestations of COVID, my partner called me in to see an unusual case. His patient was a healthy 20-year-old who had just come back from college and had tender, purple discoloration and swelling on his toes. I shrugged and said “looks like chilblains,” but there was something weird about the case. It seemed more severe, with areas of blistering and erosions, and the discomfort was unusual for run-of-the-mill pernio. This young man had experienced a cough and shortness of breath a few weeks earlier but those symptoms had resolved when we saw him.
That evening, I was on a derm social media site and saw a series of pictures from Italy that blew me away. All of these pictures looked just like this kid’s toes. That’s the first I heard of “COVID toes,” but now they seem to be everywhere. How would you describe this presentation, and how does it differ from typical chilblains?
Lindy P. Fox, MD
I am so proud of dermatologists around the world who have really jumped into action to examine the pathophysiology and immunology behind these findings.
Your experience matches mine. Like you, I first heard about these pernio- or chilblains-like lesions when Europe was experiencing its surge in cases. And while it does indeed look like chilblains, I think the reality is that it is more severe and symptomatic than we would expect. I think your observation is exactly right. There are certainly clinicians who do not believe that this is an association with COVID-19 because the testing is often negative. But to my mind, there are just too many cases at the wrong time of year, all happening concomitantly, and simultaneous with a new virus for me to accept that they are not somehow related.
Dr. Lipper: Some have referred to this as “quarantine toes,” the result of more people at home and walking around barefoot. That doesn’t seem to make a whole lot of sense because it’s happening in both warm and cold climates.
Others have speculated that there is another, unrelated circulating virus causing these pernio cases, but that seems far-fetched.
But the idea of a reporting bias – more patients paying attention to these lesions because they’ve read something in the mass media or seen a report on television and are concerned, and thus present with mild lesions they might otherwise have ignored – may be contributing somewhat. But even that cannot be the sole reason behind the increase.
Dr. Fox: Agree.
Evaluation of the patient with chilblains – then and now
Dr. Lipper: In the past, how did you perform a workup for someone with chilblains?
Dr. Fox: Pre-COVID – and I think we all have divided our world into pre- and post-COVID – the most common thing that I’d be looking for would be a clotting disorder or an autoimmune disease, typically lupus. So I take a good history, review of systems, and look at the skin for signs of lupus or other autoimmune connective tissue diseases. My lab workup is probably limited to an antinuclear antibody (ANA). If the findings are severe and recurrent, I might check for hypercoagulability with an antiphospholipid antibody panel. But that was usually it unless there was something in the history or physical exam that would lead me to look for something less common – for example, cryoglobulins or an underlying hematologic disease that would lead to a predominance of lesions in acral sites.
My approach was the same. In New England, where I practice, I also always look at environmental factors. We would sometimes see chilblains in someone from a warmer climate who came home to the Northeast to ski.
Dr. Lipper: Now, in the post-COVID world, how do you assess these patients? What has changed?
Dr. Fox: That’s a great question. To be frank, our focus now is on not missing a secondary consequence of COVID infection that we might not have picked up before. I’m the first to admit that the workup that we have been doing at UCSF is extremely comprehensive. We may be ordering tests that don’t need to be done. But until we know better what might and might not be affected by COVID, we don’t actually have a sense of whether they’re worth looking for or not.
Right now, my workup includes nasal swab polymerase chain reaction (PCR) for COVID, as well as IgG and IgM serology if available. We have IgG easily available to us. IgM needs approval; at UCSF, it is primarily done in neonates as of now. I also do a workup for autoimmunity and cold-associated disease, which includes an ANA, rheumatoid factor, cryoglobulin, and cold agglutinins.
Because of reported concerns about hypercoagulability in COVID patients, particularly in those who are doing poorly in the hospital, we look for elevations in d-dimers and fibrinogen. We check antiphospholipid antibodies, anticardiolipin antibodies, erythrocyte sedimentation rate, and C-reactive protein. That is probably too much of a workup for the healthy young person, but as of yet, we are just unable to say that those things are universally normal.
There has also been concern that complement may be involved in patients who do poorly and tend to clot a lot. So we are also checking C3, C4, and CH50.
To date, in my patients who have had this workup, I have found one with a positive ANA that was significant (1:320) who also had low complements.
There have been a couple of patients at my institution, not my own patients, who are otherwise fine but have some slight elevation in d-dimers.
Dr. Lipper: Is COVID toes more than one condition?
Some of the initial reports of finger/toe cyanosis out of China were very alarming, with many patients developing skin necrosis or even gangrene. These were critically ill adults with pneumonia and blood markers of disseminated intravascular coagulation, and five out of seven died. In contrast, the cases of pseudo-pernio reported in Europe, and now the United States, seem to be much milder, usually occurring late in the illness or in asymptomatic young people. Do you think these are two different conditions?
Dr. Fox: I believe you have hit the nail on the head. I think it is really important that we don’t confuse those two things. In the inpatient setting, we are clearly seeing patients with a prothrombotic state with associated retiform purpura. For nondermatologists, that usually means star-like, stellate-like, or even lacy purpuric changes with potential for necrosis of the skin. In hospitalized patients, the fingers and toes are usually affected but, interestingly, also the buttocks. When these lesions are biopsied, as has been done by our colleague at Weill Cornell Medicine, New York, Joanna Harp, MD, we tend to find thrombosis.
A study of endothelial cell function in patients with COVID-19, published in the Lancet tried to determine whether viral particles could be found in endothelial cells. And the investigators did indeed find these particles. So it appears that the virus is endothelially active, and this might provide some insight into the thromboses seen in hospitalized patients. These patients can develop purple necrotic toes that may progress to gangrene. But that is completely different from what we’re seeing when we say pernio-like or chilblains-like lesions.
The chilblains-like lesions come in several forms. They may be purple, red bumps, often involving the tops of the toes and sometimes the bottom of the feet. Some have been described as target-like or erythema multiforme–like. In others, there may not be individual discrete lesions but rather a redness or bluish, purplish discoloration accompanied by edema of the entire toe or several toes.
Biopsies that I am aware of have identified features consistent with an inflammatory process, all of which can be seen in a typical biopsy of pernio. You can sometimes see lymphocytes surrounding a vessel (called lymphocytic vasculitis) that may damage a vessel and cause a small clot, but the primary process is an inflammatory rather than thrombotic one. You may get a clot in a little tiny vessel secondary to inflammation, and that may lead to some blisters or little areas of necrosis. But you’re not going to see digital necrosis and gangrene. I think that’s an important distinction.
The patients who get the pernio-like lesions are typically children or young adults and are otherwise healthy. Half of them didn’t even have COVID symptoms. If they did have COVID symptoms they were typically mild. So we think the pernio-like lesions are most often occurring in the late stage of the disease and now represent a secondary inflammatory response.
Managing COVID toes
Dr. Lipper: One question I’ve been struggling with is, what do we tell these otherwise healthy patients with purple toes, especially those with no other symptoms? Many of them are testing SARS-CoV-2 negative, both with viral swabs and serologies. Some have suggestive histories like known COVID exposure, recent cough, or travel to high-risk areas. Do we tell them they’re at risk of transmitting the virus? Should they self-quarantine, and for how long? Is there any consensus emerging?
Dr. Fox: This is a good opportunity to plug the American Academy of Dermatology’s COVID-19 Registry, which is run by Esther Freeman, MD, at Massachusetts General Hospital. She has done a phenomenal job in helping us figure out the answers to these exact questions.
I’d encourage any clinicians who have a suspected COVID patient with a skin finding, whether or not infection is confirmed with testing, to enter information about that patient into the registry. That is the only way we will figure out evidence-based answers to a lot of the questions that we’re talking about today.
Based on working with the registry, we know that, rarely, patients who develop pernio-like changes will do so before they get COVID symptoms or at the same time as more typical symptoms. Some patients with these findings are PCR positive, and it is therefore theoretically possible that you could be shedding virus while you’re having the pernio toes. However, more commonly – and this is the experience of most of my colleagues and what we’re seeing at UCSF – pernio is a later finding and most patients are no longer shedding the virus. It appears that pseudo-pernio is an immune reaction and most people are not actively infectious at that point.
The only way to know for sure is to send patients for both PCR testing and antibody testing. If the PCR is negative, the most likely interpretation is that the person is no longer shedding virus, though there can be some false negatives. Therefore, these patients do not need to isolate outside of what I call their COVID pod – family or roommates who have probably been with them the whole time. Any transmission likely would have already occurred.
I tell people who call me concerned about their toes that I do think they should be given a workup for COVID. However, I reassure them that it is usually a good prognostic sign.
What is puzzling is that even in patients with pseudo-chilblains who have a clinical history consistent with COVID or exposure to a COVID-positive family member, antibody testing is often – in fact, most often – negative. There are many hypotheses as to why this is. Maybe the tests just aren’t good. Maybe people with mild disease don’t generate enough antibodies to be detected, Maybe we’re testing at the wrong time. Those are all things that we’re trying to figure out.
But currently, I tell patients that they do not need to strictly isolate. They should still practice social distancing, wear a mask, practice good hand hygiene, and do all of the careful things that we should all be doing. However, they can live within their home environment and be reassured that most likely they are in the convalescent stage.
Dr. Lipper: I find the antibody issue both fascinating and confusing.
In my practice, we’ve noticed a range of symptoms associated with pseudo-pernio. Some people barely realize it’s there and only called because they saw a headline in the news. Others complain of severe burning, throbbing, or itching that keeps them up at night and can sometimes last for weeks. Are there any treatments that seem to help?
Dr. Fox: We can start by saying, as you note, that a lot of patients don’t need interventions. They want reassurance that their toes aren’t going to fall off, that nothing terrible is going to happen to them, and often that’s enough. So far, many patients have contacted us just because they heard about the link between what they were seeing on their feet and COVID. They were likely toward the end of any other symptoms they may have had. But moving forward, I think we’re going to be seeing patients at the more active stage as the public is more aware of this finding.
Most of the time we can manage with clobetasol ointment and low-dose aspirin. I wouldn’t give aspirin to a young child with a high fever, but otherwise I think aspirin is not harmful. A paper published in Mayo Clinic Proceedings in 2014, before COVID, by Jonathan Cappel, MD, and David Wetter, MD, provides a nice therapeutic algorithm. Assuming that the findings we are seeing now are inflammatory, then I think that algorithm should apply. Nifedipine 20-60 mg/day is an option. Hydroxychloroquine, a maximum of 5 mg/kg per day, is an option. I have used hydroxychloroquine most commonly, pre-COVID, in patients who have symptomatic pernio.
I also use pentoxifylline 400 mg three times a day, which has a slight anti-inflammatory effect, when I think a blood vessel is incidentally involved or the patient has a predisposition to clotting. Nicotinamide 500 mg three times a day can be used, though I have not used it.
Some topical options are nitroglycerin, tacrolimus, and minoxidil.
However, during this post-COVID period, I have not come across many with pseudo-pernio who needed anything more than a topical steroid and some aspirin. But I do know of other physicians who have been taking care of patients with much more symptomatic disease.
Dr. Lipper: That is a comprehensive list. You’ve mentioned some options that I’ve wondered about, especially pentoxifylline, which I have found to be very helpful for livedoid vasculopathy. I should note that these are all off-label uses.
Let’s talk about some other suspected skin manifestations of COVID. A prospective nationwide study in Spain of 375 patients reported on a number of different skin manifestations of COVID.
You’re part of a team doing critically important work with the American Academy of Dermatology COVID-19 Dermatology Registry. I know it’s early going, but what are some of the other common skin presentations you’re finding?
Dr. Fox: I’m glad you brought up that paper out of Spain. I think it is really good and does highlight the difference in acute versus convalescent cutaneous manifestations and prognosis. It confirms what we’re seeing. Retiform purpura is an early finding associated with ill patients in the hospital. Pseudo pernio-like lesions tend to be later-stage and in younger, healthier patients.
Interestingly, the vesicular eruption that those investigators describe – monomorphic vesicles on the trunk and extremity – can occur in the more acute phase. That’s fascinating to me because widespread vesicular eruptions are not a thing that we commonly see. If it is not an autoimmune blistering disease, and not a drug-induced blistering process, then you’re really left with viral. Rickettsialpox can do that, as can primary varicella, disseminated herpes, disseminated zoster, and now COVID. So that’s intriguing.
I got called to see a patient yesterday who had symptoms of COVID about a month ago. She was not PCR tested at the time but she is now negative. She has a widespread eruption of tiny vesicles on an erythematous base. An IgG for COVID is positive. How do we decide whether her skin lesions have active virus in them?
The many dermatologic manifestations of COVID-19
Dr. Lipper: In the series in Spain, almost 1 out of 10 patients were found to have a widespread vesicular rash. And just under half had maculopapular exanthems. The information arising from the AAD registry will be of great interest and build on this paper.
In England, the National Health Service and the Paediatric Intensive Care Society recently put out a warning about an alarming number of children with COVID-19 who developed symptoms mimicking Kawasaki disease (high fever, abdominal pain, rash, swollen lymph nodes, mucositis, and conjunctivitis). These kids have systemic inflammation and vasculitis and are critically ill. That was followed by an alert from the New York City Health Department about cases there, which as of May 6 numbered 64. Another 25 children with similar findings have been identified in France.
This is such a scary development, especially because children were supposed to be relatively “safe” from this virus. Any thoughts on who is at risk or why?
Dr. Fox: It’s very alarming. It appears that these cases look just like Kawasaki disease.
It was once hypothesized that Coronaviridae was the cause of Kawasaki disease. Then that got debunked. But these cases now raise the question of whether Kawasaki disease may be virally mediated. Is it an immune reaction to an infectious trigger? Is it actually Coronaviridae that triggers it?
As with these pernio cases, I think we’re going to learn about the pathophysiology of these diseases that we currently look at as secondary responses or immune reactions to unknown triggers. We’re going to learn a lot about them and about the immune system because of how this virus is acting on the immune system.
Dr. Lipper: As is the case with patients with pernio-like lesions, some of these children with Kawasaki-like disease are PCR negative for SARS-CoV-2. It will be interesting to see what happens with antibody testing in this population.
Dr. Fox: Agree. While some of the manufacturers of serology tests have claimed that they have very high sensitivity and specificity, that has not been my experience.
Dr. Lipper: I’ve had a number of patients with a clinical picture that strongly suggests COVID whose serology tests have been negative.
Dr. Fox: As have I. While this could be the result of faulty tests, my biggest worry is that it means that people with mild disease do not mount an antibody response. And if people who have disease can’t make antibodies, then there’s no herd immunity. If there’s no herd immunity, we’re stuck in lockdown until there’s a vaccine.
Dr. Lipper: That is a scary but real possibility. We need evidence – evidence like that provided by the AAD registry.
Dr. Fox: Agree. I look forward to sharing those results with you when we have them.
Dr. Lipper is a clinical assistant professor at the University of Vermont, Burlington, and a partner at Advanced DermCare in Danbury, Conn.
Dr. Fox is a professor in the department of dermatology at the University of California, San Francisco. She is a hospital-based dermatologist who specializes in the care of patients with complex skin conditions. She is immediate past president of the Medical Dermatology Society and current president of the Society of Dermatology Hospitalists.
This article was first published on Medscape.com.
Hazard pay included in new COVID-19 relief bill
Hazard pay for frontline health care workers – an idea that has been championed by President Donald J. Trump and Senate Minority Leader Chuck Schumer, among others – is included in a just-released COVID-19 relief package assembled by Democrats in the House of Representatives.
according to a report in the Washington Post.
But it is far from a done deal. “The Democrats’ spending bill is a Pelosi-led pipe dream written in private,” said House Republican Leader Kevin McCarthy (Calif.) in a Fox News interview posted May 12 on Facebook.
Senate Majority Leader Mitch McConnell condemned the package. “This is exactly the wrong approach,” he said in a prepared statement that instead laid out a variety of liability protections, which he said should be the first priority.
“We are not going to let health care heroes emerge from this crisis facing a tidal wave of medical malpractice lawsuits so that trial lawyers can line their pockets,” said Sen. McConnell, adding that his plan would “raise the liability threshold for COVID-related malpractice lawsuits.”
Ingrida Lusis, vice president of government affairs and health policy at the American Nurses Association, said in an interview that the ANA had lobbied for hazard pay and was told it would be in the next relief package.
“Though there is an inherent risk in the nursing profession, we think that this is really critical to ensuring that we have a workforce to meet the intense demands of this pandemic,” said Ms. Lusis.
“If health care workers are not treated and compensated appropriately for what they’re going through right now, then we may not have a next generation that will want to enter the field,” she said.
Various nursing organizations, nurses’ unions, and health care unions, such as the American Federation of State, County and Municipal Employees (AFSCME) and the Service Employees International Union, have advocated for hazard pay.
Physicians’ organizations have not been vocal on the issue, however. The American Medical Association, for instance, pushed for hazard pay for residents but has not made any further public statements. An AMA spokesman said that the group was monitoring the situation but declined further comment.
Multiple online petitions seeking hazard pay for health care workers have been circulated, including one seeking the same $600 bump for essential workers that was given out as part of unemployment benefits in the first COVID-19 relief package. More than 1.2 million had signed the petition as of May 12.
‘Heroes fund’
The president first suggested hazard pay for health care workers on March 30 Fox News broadcast. “These are really brave people,” he said, adding that the administration was considering different ways of boosting pay, primarily through hospitals.
“We are asking the hospitals to do it and to consider something, including bonuses,” said Trump. “If anybody’s entitled to it, they are.”
On April 7, Sen. Schumer proposed a “Heroes Fund.” It would give public, private, and tribal frontline employees – including doctors, nurses, first responders, and transit, grocery, and postal workers – a $13 per hour raise up to $25,000 in additional pay through Dec. 31 for workers earning up to $200,000 and $5,000 in additional pay for those earning more than $200,000. It would also provide a $15,000 signing bonus to those who agree to take on such a position.
Rep. Matt Cartwright (D-Pa.) introduced a bill in mid-April, the Coronavirus Frontline Workers Fair Pay Act (HR 6709), that would provide similar pay increases. Health care workers would receive an additional $13 per hour. It would be retroactive to Jan. 31, 2020, and would be available through the end of 2020.
Molly Kinder of the Brookings Institution, a self-described nonpartisan Washington policy institute, estimates that Sen. Schumer’s proposal would represent the equivalent of double-time pay for the average low-wage worker, a 50% pay increase for a mail carrier, a 20% boost for a pharmacist, and less than a 15% increase for a surgeon, as determined from median 2018 wages.
Before the House Democrats unveiled their bill, Isabel Soto of the center-right group American Action Forum estimated that a $13 per hour wage increase could cost $398.9 billion just from the end of March to the end of September. A great proportion of that amount – $264 billion – would go to some 10 million health care workers, Ms. Soto calculated.
Some already offering pay boost
A few states and hospital systems are already offering hazard pay.
On April 12, Massachusetts agreed to give about 6,500 AFSCME union members who work at state human services facilities and group homes a $5 or a $10 per hour pay increase, depending on duties. It was to stay in effect until at least May 30.
Maine Governor Janet Mills (D) also agreed to increase pay by $3-$5 an hour for AFSCME workers in state correctional and mental health facilities beginning March 29.
In New York City, the biggest hospital network, Northwell Health, in late April gave 45,000 workers – including nurses, physicians, respiratory therapists, environmental services workers, housekeepers, and people in outpatient and corporate roles – a lump sum bonus payment of up to $2,500 and 1 week of paid time off. The money came out of the system’s general fund.
“As an organization, we want to continue to support, motivate and inspire our team members,” said Northwell President and CEO Michael Dowling in a statement at the time.
On April 2, New York–Presbyterian Hospital’s chair of the department of surgery, Craig Smith, MD, announced that the facility was “providing a $1,250 bonus for everyone who has worked in or supported the COVID-19 front lines, for at least 1 week.”
Advocate Aurora, with 15 hospitals and 32,000 employees in Wisconsin, said in early April that it was giving increases of $6.25-$15.00 an hour at least through the end of May.
A version of this article originally appeared on Medscape.com.
Hazard pay for frontline health care workers – an idea that has been championed by President Donald J. Trump and Senate Minority Leader Chuck Schumer, among others – is included in a just-released COVID-19 relief package assembled by Democrats in the House of Representatives.
according to a report in the Washington Post.
But it is far from a done deal. “The Democrats’ spending bill is a Pelosi-led pipe dream written in private,” said House Republican Leader Kevin McCarthy (Calif.) in a Fox News interview posted May 12 on Facebook.
Senate Majority Leader Mitch McConnell condemned the package. “This is exactly the wrong approach,” he said in a prepared statement that instead laid out a variety of liability protections, which he said should be the first priority.
“We are not going to let health care heroes emerge from this crisis facing a tidal wave of medical malpractice lawsuits so that trial lawyers can line their pockets,” said Sen. McConnell, adding that his plan would “raise the liability threshold for COVID-related malpractice lawsuits.”
Ingrida Lusis, vice president of government affairs and health policy at the American Nurses Association, said in an interview that the ANA had lobbied for hazard pay and was told it would be in the next relief package.
“Though there is an inherent risk in the nursing profession, we think that this is really critical to ensuring that we have a workforce to meet the intense demands of this pandemic,” said Ms. Lusis.
“If health care workers are not treated and compensated appropriately for what they’re going through right now, then we may not have a next generation that will want to enter the field,” she said.
Various nursing organizations, nurses’ unions, and health care unions, such as the American Federation of State, County and Municipal Employees (AFSCME) and the Service Employees International Union, have advocated for hazard pay.
Physicians’ organizations have not been vocal on the issue, however. The American Medical Association, for instance, pushed for hazard pay for residents but has not made any further public statements. An AMA spokesman said that the group was monitoring the situation but declined further comment.
Multiple online petitions seeking hazard pay for health care workers have been circulated, including one seeking the same $600 bump for essential workers that was given out as part of unemployment benefits in the first COVID-19 relief package. More than 1.2 million had signed the petition as of May 12.
‘Heroes fund’
The president first suggested hazard pay for health care workers on March 30 Fox News broadcast. “These are really brave people,” he said, adding that the administration was considering different ways of boosting pay, primarily through hospitals.
“We are asking the hospitals to do it and to consider something, including bonuses,” said Trump. “If anybody’s entitled to it, they are.”
On April 7, Sen. Schumer proposed a “Heroes Fund.” It would give public, private, and tribal frontline employees – including doctors, nurses, first responders, and transit, grocery, and postal workers – a $13 per hour raise up to $25,000 in additional pay through Dec. 31 for workers earning up to $200,000 and $5,000 in additional pay for those earning more than $200,000. It would also provide a $15,000 signing bonus to those who agree to take on such a position.
Rep. Matt Cartwright (D-Pa.) introduced a bill in mid-April, the Coronavirus Frontline Workers Fair Pay Act (HR 6709), that would provide similar pay increases. Health care workers would receive an additional $13 per hour. It would be retroactive to Jan. 31, 2020, and would be available through the end of 2020.
Molly Kinder of the Brookings Institution, a self-described nonpartisan Washington policy institute, estimates that Sen. Schumer’s proposal would represent the equivalent of double-time pay for the average low-wage worker, a 50% pay increase for a mail carrier, a 20% boost for a pharmacist, and less than a 15% increase for a surgeon, as determined from median 2018 wages.
Before the House Democrats unveiled their bill, Isabel Soto of the center-right group American Action Forum estimated that a $13 per hour wage increase could cost $398.9 billion just from the end of March to the end of September. A great proportion of that amount – $264 billion – would go to some 10 million health care workers, Ms. Soto calculated.
Some already offering pay boost
A few states and hospital systems are already offering hazard pay.
On April 12, Massachusetts agreed to give about 6,500 AFSCME union members who work at state human services facilities and group homes a $5 or a $10 per hour pay increase, depending on duties. It was to stay in effect until at least May 30.
Maine Governor Janet Mills (D) also agreed to increase pay by $3-$5 an hour for AFSCME workers in state correctional and mental health facilities beginning March 29.
In New York City, the biggest hospital network, Northwell Health, in late April gave 45,000 workers – including nurses, physicians, respiratory therapists, environmental services workers, housekeepers, and people in outpatient and corporate roles – a lump sum bonus payment of up to $2,500 and 1 week of paid time off. The money came out of the system’s general fund.
“As an organization, we want to continue to support, motivate and inspire our team members,” said Northwell President and CEO Michael Dowling in a statement at the time.
On April 2, New York–Presbyterian Hospital’s chair of the department of surgery, Craig Smith, MD, announced that the facility was “providing a $1,250 bonus for everyone who has worked in or supported the COVID-19 front lines, for at least 1 week.”
Advocate Aurora, with 15 hospitals and 32,000 employees in Wisconsin, said in early April that it was giving increases of $6.25-$15.00 an hour at least through the end of May.
A version of this article originally appeared on Medscape.com.
Hazard pay for frontline health care workers – an idea that has been championed by President Donald J. Trump and Senate Minority Leader Chuck Schumer, among others – is included in a just-released COVID-19 relief package assembled by Democrats in the House of Representatives.
according to a report in the Washington Post.
But it is far from a done deal. “The Democrats’ spending bill is a Pelosi-led pipe dream written in private,” said House Republican Leader Kevin McCarthy (Calif.) in a Fox News interview posted May 12 on Facebook.
Senate Majority Leader Mitch McConnell condemned the package. “This is exactly the wrong approach,” he said in a prepared statement that instead laid out a variety of liability protections, which he said should be the first priority.
“We are not going to let health care heroes emerge from this crisis facing a tidal wave of medical malpractice lawsuits so that trial lawyers can line their pockets,” said Sen. McConnell, adding that his plan would “raise the liability threshold for COVID-related malpractice lawsuits.”
Ingrida Lusis, vice president of government affairs and health policy at the American Nurses Association, said in an interview that the ANA had lobbied for hazard pay and was told it would be in the next relief package.
“Though there is an inherent risk in the nursing profession, we think that this is really critical to ensuring that we have a workforce to meet the intense demands of this pandemic,” said Ms. Lusis.
“If health care workers are not treated and compensated appropriately for what they’re going through right now, then we may not have a next generation that will want to enter the field,” she said.
Various nursing organizations, nurses’ unions, and health care unions, such as the American Federation of State, County and Municipal Employees (AFSCME) and the Service Employees International Union, have advocated for hazard pay.
Physicians’ organizations have not been vocal on the issue, however. The American Medical Association, for instance, pushed for hazard pay for residents but has not made any further public statements. An AMA spokesman said that the group was monitoring the situation but declined further comment.
Multiple online petitions seeking hazard pay for health care workers have been circulated, including one seeking the same $600 bump for essential workers that was given out as part of unemployment benefits in the first COVID-19 relief package. More than 1.2 million had signed the petition as of May 12.
‘Heroes fund’
The president first suggested hazard pay for health care workers on March 30 Fox News broadcast. “These are really brave people,” he said, adding that the administration was considering different ways of boosting pay, primarily through hospitals.
“We are asking the hospitals to do it and to consider something, including bonuses,” said Trump. “If anybody’s entitled to it, they are.”
On April 7, Sen. Schumer proposed a “Heroes Fund.” It would give public, private, and tribal frontline employees – including doctors, nurses, first responders, and transit, grocery, and postal workers – a $13 per hour raise up to $25,000 in additional pay through Dec. 31 for workers earning up to $200,000 and $5,000 in additional pay for those earning more than $200,000. It would also provide a $15,000 signing bonus to those who agree to take on such a position.
Rep. Matt Cartwright (D-Pa.) introduced a bill in mid-April, the Coronavirus Frontline Workers Fair Pay Act (HR 6709), that would provide similar pay increases. Health care workers would receive an additional $13 per hour. It would be retroactive to Jan. 31, 2020, and would be available through the end of 2020.
Molly Kinder of the Brookings Institution, a self-described nonpartisan Washington policy institute, estimates that Sen. Schumer’s proposal would represent the equivalent of double-time pay for the average low-wage worker, a 50% pay increase for a mail carrier, a 20% boost for a pharmacist, and less than a 15% increase for a surgeon, as determined from median 2018 wages.
Before the House Democrats unveiled their bill, Isabel Soto of the center-right group American Action Forum estimated that a $13 per hour wage increase could cost $398.9 billion just from the end of March to the end of September. A great proportion of that amount – $264 billion – would go to some 10 million health care workers, Ms. Soto calculated.
Some already offering pay boost
A few states and hospital systems are already offering hazard pay.
On April 12, Massachusetts agreed to give about 6,500 AFSCME union members who work at state human services facilities and group homes a $5 or a $10 per hour pay increase, depending on duties. It was to stay in effect until at least May 30.
Maine Governor Janet Mills (D) also agreed to increase pay by $3-$5 an hour for AFSCME workers in state correctional and mental health facilities beginning March 29.
In New York City, the biggest hospital network, Northwell Health, in late April gave 45,000 workers – including nurses, physicians, respiratory therapists, environmental services workers, housekeepers, and people in outpatient and corporate roles – a lump sum bonus payment of up to $2,500 and 1 week of paid time off. The money came out of the system’s general fund.
“As an organization, we want to continue to support, motivate and inspire our team members,” said Northwell President and CEO Michael Dowling in a statement at the time.
On April 2, New York–Presbyterian Hospital’s chair of the department of surgery, Craig Smith, MD, announced that the facility was “providing a $1,250 bonus for everyone who has worked in or supported the COVID-19 front lines, for at least 1 week.”
Advocate Aurora, with 15 hospitals and 32,000 employees in Wisconsin, said in early April that it was giving increases of $6.25-$15.00 an hour at least through the end of May.
A version of this article originally appeared on Medscape.com.