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Antifungal drug appears safe for pregnancy
Treatment with the according to results from a large registry study in Denmark.
Physicians have been reluctant to prescribe the drug during pregnancy because of the limited safety data. The drug has not been associated with any signs of fetal toxicity in animal studies, but only one study – in 54 pregnancies – has examined the issue in humans and did not identify an increased fetal risk, according to Niklas Worm Andersson, MD, of the department of clinical pharmacology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, and coauthors.
The retrospective, nationwide cohort study analyzed exposure to oral and tropical terbinafine in a large pregnancy registry and found no increase in the risk of major malformations or spontaneous abortions in exposed versus unexposed pregnancies. The study was published in JAMA Dermatology.
Still, these results fell short of certainty, the authors noted. “Although our results may provide reassurance for pregnancies exposed to oral terbinafine by reporting no overall increased risk of major malformations, we cannot exclude a potential increased risk of a specific malformation,” they wrote.
“To our knowledge, this is by far the largest, most statistically rigorous study in the literature regarding this topic,” Jenny E. Murase, MD, of the department of dermatology at the University of California, San Francisco, and Mary Kathryn Abel, a medical student at UCSF, wrote in an accompanying editorial. They described the study as “a substantial contribution to the nearly absent literature regarding the use of terbinafine during pregnancy. Among the antifungal medications, it is possible that terbinafine is the safest one currently available for use in pregnancy, particularly of the oral formulations.”
However, since asymptomatic onychomycosis “is typically a cosmetic, rather than medical, concern, waiting until after pregnancy to initiate therapy is reasonable. ... It is important to acknowledge the uncertainty in this field and question the appropriateness of treating non–life-threatening diseases during pregnancy and lactation,” they wrote.
The Danish researchers drew from a registry of 1,650,649 pregnancies between 1997 and 2016, which included 891 pregnancies exposed to oral terbinafine, and 3,174 exposed to topical terbinafine. Matched outcome analyses compared the exposed pregnancies with up to 40,650 controls unexposed during pregnancy.
Propensity-matched comparisons showed no increased risk of major malformations for oral terbinafine exposure versus no exposure (odds ratio, 1.01; 95% confidence interval, 0.63-1.62) or topical exposure versus no exposure (OR, 1.08; 95% CI, 0.81-1.44). There was also no difference in oral versus topical exposure (OR, 1.18; 95% CI, 0.61-2.29).
With respect to spontaneous abortions, there was no significant association with oral terbinafine (hazard ratio, 1.06; 95% CI, 0.86-1.32) or topical terbinafine (HR, 1.04; 95% CI, 0.88-1.21), compared with unexposed pregnancies, or oral over topical terbinafine-exposed pregnancies (HR, 1.19; 95% CI, 0.84-1.70).
The study is limited by the fact that it was conducted in a Danish population, and the data relied on filled prescriptions for determining exposure, which did not account for adherence. Residual confounding is possible because of the retrospective nature of the study, the authors pointed out.
No source of funding was disclosed. One of the authors has received grants and personal fees from Novartis. Dr. Murase has received fees from Sanofi Genzyme, Dermira, UCB, Regeneron, Ferndale, and UpToDate.
SOURCES: Andersson NW et al. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2020.0142; Murase JE, Abel MK. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2019.5036.
Treatment with the according to results from a large registry study in Denmark.
Physicians have been reluctant to prescribe the drug during pregnancy because of the limited safety data. The drug has not been associated with any signs of fetal toxicity in animal studies, but only one study – in 54 pregnancies – has examined the issue in humans and did not identify an increased fetal risk, according to Niklas Worm Andersson, MD, of the department of clinical pharmacology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, and coauthors.
The retrospective, nationwide cohort study analyzed exposure to oral and tropical terbinafine in a large pregnancy registry and found no increase in the risk of major malformations or spontaneous abortions in exposed versus unexposed pregnancies. The study was published in JAMA Dermatology.
Still, these results fell short of certainty, the authors noted. “Although our results may provide reassurance for pregnancies exposed to oral terbinafine by reporting no overall increased risk of major malformations, we cannot exclude a potential increased risk of a specific malformation,” they wrote.
“To our knowledge, this is by far the largest, most statistically rigorous study in the literature regarding this topic,” Jenny E. Murase, MD, of the department of dermatology at the University of California, San Francisco, and Mary Kathryn Abel, a medical student at UCSF, wrote in an accompanying editorial. They described the study as “a substantial contribution to the nearly absent literature regarding the use of terbinafine during pregnancy. Among the antifungal medications, it is possible that terbinafine is the safest one currently available for use in pregnancy, particularly of the oral formulations.”
However, since asymptomatic onychomycosis “is typically a cosmetic, rather than medical, concern, waiting until after pregnancy to initiate therapy is reasonable. ... It is important to acknowledge the uncertainty in this field and question the appropriateness of treating non–life-threatening diseases during pregnancy and lactation,” they wrote.
The Danish researchers drew from a registry of 1,650,649 pregnancies between 1997 and 2016, which included 891 pregnancies exposed to oral terbinafine, and 3,174 exposed to topical terbinafine. Matched outcome analyses compared the exposed pregnancies with up to 40,650 controls unexposed during pregnancy.
Propensity-matched comparisons showed no increased risk of major malformations for oral terbinafine exposure versus no exposure (odds ratio, 1.01; 95% confidence interval, 0.63-1.62) or topical exposure versus no exposure (OR, 1.08; 95% CI, 0.81-1.44). There was also no difference in oral versus topical exposure (OR, 1.18; 95% CI, 0.61-2.29).
With respect to spontaneous abortions, there was no significant association with oral terbinafine (hazard ratio, 1.06; 95% CI, 0.86-1.32) or topical terbinafine (HR, 1.04; 95% CI, 0.88-1.21), compared with unexposed pregnancies, or oral over topical terbinafine-exposed pregnancies (HR, 1.19; 95% CI, 0.84-1.70).
The study is limited by the fact that it was conducted in a Danish population, and the data relied on filled prescriptions for determining exposure, which did not account for adherence. Residual confounding is possible because of the retrospective nature of the study, the authors pointed out.
No source of funding was disclosed. One of the authors has received grants and personal fees from Novartis. Dr. Murase has received fees from Sanofi Genzyme, Dermira, UCB, Regeneron, Ferndale, and UpToDate.
SOURCES: Andersson NW et al. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2020.0142; Murase JE, Abel MK. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2019.5036.
Treatment with the according to results from a large registry study in Denmark.
Physicians have been reluctant to prescribe the drug during pregnancy because of the limited safety data. The drug has not been associated with any signs of fetal toxicity in animal studies, but only one study – in 54 pregnancies – has examined the issue in humans and did not identify an increased fetal risk, according to Niklas Worm Andersson, MD, of the department of clinical pharmacology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, and coauthors.
The retrospective, nationwide cohort study analyzed exposure to oral and tropical terbinafine in a large pregnancy registry and found no increase in the risk of major malformations or spontaneous abortions in exposed versus unexposed pregnancies. The study was published in JAMA Dermatology.
Still, these results fell short of certainty, the authors noted. “Although our results may provide reassurance for pregnancies exposed to oral terbinafine by reporting no overall increased risk of major malformations, we cannot exclude a potential increased risk of a specific malformation,” they wrote.
“To our knowledge, this is by far the largest, most statistically rigorous study in the literature regarding this topic,” Jenny E. Murase, MD, of the department of dermatology at the University of California, San Francisco, and Mary Kathryn Abel, a medical student at UCSF, wrote in an accompanying editorial. They described the study as “a substantial contribution to the nearly absent literature regarding the use of terbinafine during pregnancy. Among the antifungal medications, it is possible that terbinafine is the safest one currently available for use in pregnancy, particularly of the oral formulations.”
However, since asymptomatic onychomycosis “is typically a cosmetic, rather than medical, concern, waiting until after pregnancy to initiate therapy is reasonable. ... It is important to acknowledge the uncertainty in this field and question the appropriateness of treating non–life-threatening diseases during pregnancy and lactation,” they wrote.
The Danish researchers drew from a registry of 1,650,649 pregnancies between 1997 and 2016, which included 891 pregnancies exposed to oral terbinafine, and 3,174 exposed to topical terbinafine. Matched outcome analyses compared the exposed pregnancies with up to 40,650 controls unexposed during pregnancy.
Propensity-matched comparisons showed no increased risk of major malformations for oral terbinafine exposure versus no exposure (odds ratio, 1.01; 95% confidence interval, 0.63-1.62) or topical exposure versus no exposure (OR, 1.08; 95% CI, 0.81-1.44). There was also no difference in oral versus topical exposure (OR, 1.18; 95% CI, 0.61-2.29).
With respect to spontaneous abortions, there was no significant association with oral terbinafine (hazard ratio, 1.06; 95% CI, 0.86-1.32) or topical terbinafine (HR, 1.04; 95% CI, 0.88-1.21), compared with unexposed pregnancies, or oral over topical terbinafine-exposed pregnancies (HR, 1.19; 95% CI, 0.84-1.70).
The study is limited by the fact that it was conducted in a Danish population, and the data relied on filled prescriptions for determining exposure, which did not account for adherence. Residual confounding is possible because of the retrospective nature of the study, the authors pointed out.
No source of funding was disclosed. One of the authors has received grants and personal fees from Novartis. Dr. Murase has received fees from Sanofi Genzyme, Dermira, UCB, Regeneron, Ferndale, and UpToDate.
SOURCES: Andersson NW et al. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2020.0142; Murase JE, Abel MK. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2019.5036.
FROM JAMA DERMATOLOGY
HIV free 30 months after stem cell transplant, is the London patient cured?
A patient with HIV remission induced by stem cell transplantation continues to be disease free at the 30-month mark.
The individual, referred to as the London patient, received allogeneic hematopoietic stem cell transplantation (allo-HSCT) for stage IVB Hodgkin lymphoma. The transplant donor was homozygous for the CCR5 delta-32 mutation, which confers immunity to HIV because there’s no point of entry for the virus into immune cells.
After extensive sampling of various tissues, including gut, lymph node, blood, semen, and cerebrospinal fluid (CSF), Ravindra Kumar Gupta, MD, PhD, and colleagues found no detectable virus that was competent to replicate. However, they reported that the testing did detect some “fossilized” remnants of HIV DNA persisting in certain tissues.
The results were shared in a video presentation of the research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.
The London patient’s HIV status had been reported the previous year at CROI 2019, but only blood samples were used in that analysis.
In a commentary accompanying the simultaneously published study in the Lancet, Jennifer Zerbato, PhD, and Sharon Lewin, FRACP, PHD, FAAHMS, asked: “A key question now for the area of HIV cure is how soon can one know if someone has been cured of HIV?
“We will need more than a handful of patients cured of HIV to really understand the duration of follow-up needed and the likelihood of an unexpected late rebound in virus replication,” continued Dr. Zerbato, of the University of Melbourne, and Dr. Lewin, of the Royal Melbourne Hospital and Monash University, also in Melbourne.
In their ongoing analysis of data from the London patient, Dr. Gupta, a virologist at the University of Cambridge (England), and associates constructed a mathematical model that maps the probability for lifetime remission or cure of HIV against several factors, including the degree of chimerism achieved with the stem cell transplant.
In this model, when chimerism reaches 80% in total HIV target cells, the probability of remission for life is 98%; when donor chimerism reaches 90%, the probability of lifetime remission is greater than 99%. Peripheral T-cell chimerism in the London patient has held steady at 99%.
Dr. Gupta and associates obtained some testing opportunistically: A PET-CT scan revealed an axillary lymph node that was biopsied after it was found to have avid radiotracer uptake. Similarly, the CSF sample was obtained in the course of a work-up for some neurologic symptoms that the London patient was having.
In contrast to the first patient who achieved ongoing HIV remission from a pair of stem cell transplants received over 13 years ago – the Berlin patient – the London patient did not receive whole-body radiation, but rather underwent a reduced-intensity conditioning regimen. The London patient experienced a bout of gut graft-versus-host disease (GVHD) about 2 months after his transplant, but has been free of GVHD in the interval. He hasn’t taken cytotoxic agents or any GVHD prophylaxis since 6 months post transplant.
Though there’s no sign of HIV that’s competent to replicate, “the London patient has shown somewhat slow CD4 reconstitution,” said Dr. Gupta and coauthors in discussing the results.
The patient had a reactivation of Epstein-Barr virus (EBV) about 21 months after analytic treatment interruption (ATI) of antiretroviral therapy that was managed without any specific treatment, but he hasn’t experienced any opportunistic infections. However, his CD4 count didn’t rebound to pretransplant levels until 28 months after ATI. At that point, his CD4 count was 430 cells per mcL, or 23.5% of total T cells. The CD4:CD8 ratio was 0.86; normal range is 1.5-2.5.
The researchers used quantitative real-time polymerase chain reaction (rt-PCR) to look for packaging site and envelope (env) DNA fragments, and droplet digital PCR to quantify HIV-1 DNA.
The patient’s HIV-1 plasma load measured at 30 months post ATI on an ultrasensitive assay was below the lower limit of detection (less than 1 copy per mL). Semen viremia measured at 21 months was also below the lower limit of detection, as was CSF measured at 25 months.
Samples were taken from the patient’s rectum, cecum, sigmoid colon, and terminal ileum during a colonoscopy conducted 22 months post ATI; all tested negative for HIV DNA via droplet digital PCR.
The lymph node had large numbers of EBV-positive cells and was positive for HIV-1 env and long-terminal repeat by double-drop PCR, but no integrase DNA was detected. Additionally, no intact proviral DNA was found on assay.
Dr. Gupta and associates speculated that “EBV reactivation could have triggered EBV-specific CD4 and CD8 T-cell responses and proliferation, potentially including CD4 T cells containing HIV-1 DNA.” Supporting this hypothesis, EBV-specific CD8 T-cell responses in peripheral blood were “robust,” and the researchers also saw some CD4 response.
“Similar to the Berlin patient, highly sensitive tests showed very low levels of so-called fossilized HIV-1 DNA in some tissue samples from the London patient. Residual HIV-1 DNA and axillary lymph node tissue could represent a defective clone that expanded during hyperplasia within the lymph note sampled,” noted Dr. Gupta and coauthors.
Responses of CD4 and CD8 T cells to HIV have also remained below the limit of detection, though cytomegalovirus-specific responses persist in the London patient.
As with the Berlin patient, standard enzyme-linked immunosorbent assay (ELISA) testing has remained positive in the London patient. “Standard ELISA testing, therefore, cannot be used as a marker for cure, although more work needs to be done to assess the role of detuned low-avidity antibody assays in defining cure,” noted Dr. Gupta and associates.
The ongoing follow-up plan for the London patient is to obtain viral load testing twice yearly up to 5 years post ATI, and then obtain yearly tests for a total of 10 years. Ongoing testing will confirm the investigators’ belief that “these findings probably represent the second recorded HIV-1 cure after CCR5 delta-32/delta-32 allo-HSCT, with evidence of residual low-level HIV-1 DNA.”
Dr. Zerbato and Dr. Lewin advised cautious optimism and ongoing surveillance: “In view of the many cells sampled in this case, and the absence of any intact virus, is the London patient truly cured? The additional data provided in this follow-up case report is certainly exciting and encouraging but, in the end, only time will tell.”
Dr. Gupta reported being a consultant for ViiV Healthcare and Gilead Sciences; several coauthors also reported financial relationships with pharmaceutical companies. The work was funded by amfAR, the American Foundation for AIDS Research, and the Wellcome Trust. Dr. Lewin reported grants from the National Health and Medical Research Council of Australia, the National Institutes of Health, the American Foundation for AIDS Research, Gilead Sciences, Merck, ViiV Healthcare, Leidos, the Wellcome Trust, the Australian Centre for HIV and Hepatitis Virology Research, and the Melbourne HIV Cure Consortium. Dr. Zerbato reported grants from the Melbourne HIV Cure Consortium,
SOURCE: Gupta R et al. Lancet. 2020 Mar 10. doi: 10.1016/ S2352-3018(20)30069-2.
A patient with HIV remission induced by stem cell transplantation continues to be disease free at the 30-month mark.
The individual, referred to as the London patient, received allogeneic hematopoietic stem cell transplantation (allo-HSCT) for stage IVB Hodgkin lymphoma. The transplant donor was homozygous for the CCR5 delta-32 mutation, which confers immunity to HIV because there’s no point of entry for the virus into immune cells.
After extensive sampling of various tissues, including gut, lymph node, blood, semen, and cerebrospinal fluid (CSF), Ravindra Kumar Gupta, MD, PhD, and colleagues found no detectable virus that was competent to replicate. However, they reported that the testing did detect some “fossilized” remnants of HIV DNA persisting in certain tissues.
The results were shared in a video presentation of the research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.
The London patient’s HIV status had been reported the previous year at CROI 2019, but only blood samples were used in that analysis.
In a commentary accompanying the simultaneously published study in the Lancet, Jennifer Zerbato, PhD, and Sharon Lewin, FRACP, PHD, FAAHMS, asked: “A key question now for the area of HIV cure is how soon can one know if someone has been cured of HIV?
“We will need more than a handful of patients cured of HIV to really understand the duration of follow-up needed and the likelihood of an unexpected late rebound in virus replication,” continued Dr. Zerbato, of the University of Melbourne, and Dr. Lewin, of the Royal Melbourne Hospital and Monash University, also in Melbourne.
In their ongoing analysis of data from the London patient, Dr. Gupta, a virologist at the University of Cambridge (England), and associates constructed a mathematical model that maps the probability for lifetime remission or cure of HIV against several factors, including the degree of chimerism achieved with the stem cell transplant.
In this model, when chimerism reaches 80% in total HIV target cells, the probability of remission for life is 98%; when donor chimerism reaches 90%, the probability of lifetime remission is greater than 99%. Peripheral T-cell chimerism in the London patient has held steady at 99%.
Dr. Gupta and associates obtained some testing opportunistically: A PET-CT scan revealed an axillary lymph node that was biopsied after it was found to have avid radiotracer uptake. Similarly, the CSF sample was obtained in the course of a work-up for some neurologic symptoms that the London patient was having.
In contrast to the first patient who achieved ongoing HIV remission from a pair of stem cell transplants received over 13 years ago – the Berlin patient – the London patient did not receive whole-body radiation, but rather underwent a reduced-intensity conditioning regimen. The London patient experienced a bout of gut graft-versus-host disease (GVHD) about 2 months after his transplant, but has been free of GVHD in the interval. He hasn’t taken cytotoxic agents or any GVHD prophylaxis since 6 months post transplant.
Though there’s no sign of HIV that’s competent to replicate, “the London patient has shown somewhat slow CD4 reconstitution,” said Dr. Gupta and coauthors in discussing the results.
The patient had a reactivation of Epstein-Barr virus (EBV) about 21 months after analytic treatment interruption (ATI) of antiretroviral therapy that was managed without any specific treatment, but he hasn’t experienced any opportunistic infections. However, his CD4 count didn’t rebound to pretransplant levels until 28 months after ATI. At that point, his CD4 count was 430 cells per mcL, or 23.5% of total T cells. The CD4:CD8 ratio was 0.86; normal range is 1.5-2.5.
The researchers used quantitative real-time polymerase chain reaction (rt-PCR) to look for packaging site and envelope (env) DNA fragments, and droplet digital PCR to quantify HIV-1 DNA.
The patient’s HIV-1 plasma load measured at 30 months post ATI on an ultrasensitive assay was below the lower limit of detection (less than 1 copy per mL). Semen viremia measured at 21 months was also below the lower limit of detection, as was CSF measured at 25 months.
Samples were taken from the patient’s rectum, cecum, sigmoid colon, and terminal ileum during a colonoscopy conducted 22 months post ATI; all tested negative for HIV DNA via droplet digital PCR.
The lymph node had large numbers of EBV-positive cells and was positive for HIV-1 env and long-terminal repeat by double-drop PCR, but no integrase DNA was detected. Additionally, no intact proviral DNA was found on assay.
Dr. Gupta and associates speculated that “EBV reactivation could have triggered EBV-specific CD4 and CD8 T-cell responses and proliferation, potentially including CD4 T cells containing HIV-1 DNA.” Supporting this hypothesis, EBV-specific CD8 T-cell responses in peripheral blood were “robust,” and the researchers also saw some CD4 response.
“Similar to the Berlin patient, highly sensitive tests showed very low levels of so-called fossilized HIV-1 DNA in some tissue samples from the London patient. Residual HIV-1 DNA and axillary lymph node tissue could represent a defective clone that expanded during hyperplasia within the lymph note sampled,” noted Dr. Gupta and coauthors.
Responses of CD4 and CD8 T cells to HIV have also remained below the limit of detection, though cytomegalovirus-specific responses persist in the London patient.
As with the Berlin patient, standard enzyme-linked immunosorbent assay (ELISA) testing has remained positive in the London patient. “Standard ELISA testing, therefore, cannot be used as a marker for cure, although more work needs to be done to assess the role of detuned low-avidity antibody assays in defining cure,” noted Dr. Gupta and associates.
The ongoing follow-up plan for the London patient is to obtain viral load testing twice yearly up to 5 years post ATI, and then obtain yearly tests for a total of 10 years. Ongoing testing will confirm the investigators’ belief that “these findings probably represent the second recorded HIV-1 cure after CCR5 delta-32/delta-32 allo-HSCT, with evidence of residual low-level HIV-1 DNA.”
Dr. Zerbato and Dr. Lewin advised cautious optimism and ongoing surveillance: “In view of the many cells sampled in this case, and the absence of any intact virus, is the London patient truly cured? The additional data provided in this follow-up case report is certainly exciting and encouraging but, in the end, only time will tell.”
Dr. Gupta reported being a consultant for ViiV Healthcare and Gilead Sciences; several coauthors also reported financial relationships with pharmaceutical companies. The work was funded by amfAR, the American Foundation for AIDS Research, and the Wellcome Trust. Dr. Lewin reported grants from the National Health and Medical Research Council of Australia, the National Institutes of Health, the American Foundation for AIDS Research, Gilead Sciences, Merck, ViiV Healthcare, Leidos, the Wellcome Trust, the Australian Centre for HIV and Hepatitis Virology Research, and the Melbourne HIV Cure Consortium. Dr. Zerbato reported grants from the Melbourne HIV Cure Consortium,
SOURCE: Gupta R et al. Lancet. 2020 Mar 10. doi: 10.1016/ S2352-3018(20)30069-2.
A patient with HIV remission induced by stem cell transplantation continues to be disease free at the 30-month mark.
The individual, referred to as the London patient, received allogeneic hematopoietic stem cell transplantation (allo-HSCT) for stage IVB Hodgkin lymphoma. The transplant donor was homozygous for the CCR5 delta-32 mutation, which confers immunity to HIV because there’s no point of entry for the virus into immune cells.
After extensive sampling of various tissues, including gut, lymph node, blood, semen, and cerebrospinal fluid (CSF), Ravindra Kumar Gupta, MD, PhD, and colleagues found no detectable virus that was competent to replicate. However, they reported that the testing did detect some “fossilized” remnants of HIV DNA persisting in certain tissues.
The results were shared in a video presentation of the research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.
The London patient’s HIV status had been reported the previous year at CROI 2019, but only blood samples were used in that analysis.
In a commentary accompanying the simultaneously published study in the Lancet, Jennifer Zerbato, PhD, and Sharon Lewin, FRACP, PHD, FAAHMS, asked: “A key question now for the area of HIV cure is how soon can one know if someone has been cured of HIV?
“We will need more than a handful of patients cured of HIV to really understand the duration of follow-up needed and the likelihood of an unexpected late rebound in virus replication,” continued Dr. Zerbato, of the University of Melbourne, and Dr. Lewin, of the Royal Melbourne Hospital and Monash University, also in Melbourne.
In their ongoing analysis of data from the London patient, Dr. Gupta, a virologist at the University of Cambridge (England), and associates constructed a mathematical model that maps the probability for lifetime remission or cure of HIV against several factors, including the degree of chimerism achieved with the stem cell transplant.
In this model, when chimerism reaches 80% in total HIV target cells, the probability of remission for life is 98%; when donor chimerism reaches 90%, the probability of lifetime remission is greater than 99%. Peripheral T-cell chimerism in the London patient has held steady at 99%.
Dr. Gupta and associates obtained some testing opportunistically: A PET-CT scan revealed an axillary lymph node that was biopsied after it was found to have avid radiotracer uptake. Similarly, the CSF sample was obtained in the course of a work-up for some neurologic symptoms that the London patient was having.
In contrast to the first patient who achieved ongoing HIV remission from a pair of stem cell transplants received over 13 years ago – the Berlin patient – the London patient did not receive whole-body radiation, but rather underwent a reduced-intensity conditioning regimen. The London patient experienced a bout of gut graft-versus-host disease (GVHD) about 2 months after his transplant, but has been free of GVHD in the interval. He hasn’t taken cytotoxic agents or any GVHD prophylaxis since 6 months post transplant.
Though there’s no sign of HIV that’s competent to replicate, “the London patient has shown somewhat slow CD4 reconstitution,” said Dr. Gupta and coauthors in discussing the results.
The patient had a reactivation of Epstein-Barr virus (EBV) about 21 months after analytic treatment interruption (ATI) of antiretroviral therapy that was managed without any specific treatment, but he hasn’t experienced any opportunistic infections. However, his CD4 count didn’t rebound to pretransplant levels until 28 months after ATI. At that point, his CD4 count was 430 cells per mcL, or 23.5% of total T cells. The CD4:CD8 ratio was 0.86; normal range is 1.5-2.5.
The researchers used quantitative real-time polymerase chain reaction (rt-PCR) to look for packaging site and envelope (env) DNA fragments, and droplet digital PCR to quantify HIV-1 DNA.
The patient’s HIV-1 plasma load measured at 30 months post ATI on an ultrasensitive assay was below the lower limit of detection (less than 1 copy per mL). Semen viremia measured at 21 months was also below the lower limit of detection, as was CSF measured at 25 months.
Samples were taken from the patient’s rectum, cecum, sigmoid colon, and terminal ileum during a colonoscopy conducted 22 months post ATI; all tested negative for HIV DNA via droplet digital PCR.
The lymph node had large numbers of EBV-positive cells and was positive for HIV-1 env and long-terminal repeat by double-drop PCR, but no integrase DNA was detected. Additionally, no intact proviral DNA was found on assay.
Dr. Gupta and associates speculated that “EBV reactivation could have triggered EBV-specific CD4 and CD8 T-cell responses and proliferation, potentially including CD4 T cells containing HIV-1 DNA.” Supporting this hypothesis, EBV-specific CD8 T-cell responses in peripheral blood were “robust,” and the researchers also saw some CD4 response.
“Similar to the Berlin patient, highly sensitive tests showed very low levels of so-called fossilized HIV-1 DNA in some tissue samples from the London patient. Residual HIV-1 DNA and axillary lymph node tissue could represent a defective clone that expanded during hyperplasia within the lymph note sampled,” noted Dr. Gupta and coauthors.
Responses of CD4 and CD8 T cells to HIV have also remained below the limit of detection, though cytomegalovirus-specific responses persist in the London patient.
As with the Berlin patient, standard enzyme-linked immunosorbent assay (ELISA) testing has remained positive in the London patient. “Standard ELISA testing, therefore, cannot be used as a marker for cure, although more work needs to be done to assess the role of detuned low-avidity antibody assays in defining cure,” noted Dr. Gupta and associates.
The ongoing follow-up plan for the London patient is to obtain viral load testing twice yearly up to 5 years post ATI, and then obtain yearly tests for a total of 10 years. Ongoing testing will confirm the investigators’ belief that “these findings probably represent the second recorded HIV-1 cure after CCR5 delta-32/delta-32 allo-HSCT, with evidence of residual low-level HIV-1 DNA.”
Dr. Zerbato and Dr. Lewin advised cautious optimism and ongoing surveillance: “In view of the many cells sampled in this case, and the absence of any intact virus, is the London patient truly cured? The additional data provided in this follow-up case report is certainly exciting and encouraging but, in the end, only time will tell.”
Dr. Gupta reported being a consultant for ViiV Healthcare and Gilead Sciences; several coauthors also reported financial relationships with pharmaceutical companies. The work was funded by amfAR, the American Foundation for AIDS Research, and the Wellcome Trust. Dr. Lewin reported grants from the National Health and Medical Research Council of Australia, the National Institutes of Health, the American Foundation for AIDS Research, Gilead Sciences, Merck, ViiV Healthcare, Leidos, the Wellcome Trust, the Australian Centre for HIV and Hepatitis Virology Research, and the Melbourne HIV Cure Consortium. Dr. Zerbato reported grants from the Melbourne HIV Cure Consortium,
SOURCE: Gupta R et al. Lancet. 2020 Mar 10. doi: 10.1016/ S2352-3018(20)30069-2.
FROM CROI 2020
Testosterone therapy linked to CV risk in men with HIV
Men with HIV are likely prone to the same cardiovascular risks from testosterone therapy as other men, according to new research.
There’s no reason to think they weren’t, but it hadn’t been demonstrated until now, and men with HIV are already at increased risk for cardiovascular disease. The take-home message is that “it would be prudent for clinicians to monitor closely for cardiovascular risk factors and recommend intervention to lower cardiovascular risk among men with HIV on or considering testosterone therapy,” lead investigator Sabina Haberlen, PhD, an assistant scientist in the infectious disease epidemiology division of Johns Hopkins University, Baltimore, said in a poster that was presented as part of the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because concerns about the spread of COVID-19.
Testosterone therapy is common among middle-aged and older men with HIV to counter the hypogonadism associated with infection. The investigators turned to the Multicenter AIDS Cohort Study – a 30-year, four-city study of HIV-1 infection in men who have sex with men – to gauge its effect.
The 300 men in the study had a baseline coronary CT angiogram in 2010-2013 and a repeat study a mean of 4.5 years later. They had no history of coronary interventions or kidney dysfunction at baseline and were aged 40-70 years, with a median age of 51 years. About 70% reported never using testosterone, 8% were former users before entering the study, 7% started using testosterone between the two CTs, and 15% entered the study on testosterone and stayed on it.
Adjusting for age, race, cardiovascular risk factors, baseline serum testosterone levels, and other potential confounders, the risk of significant coronary artery calcium (CAC) progression was 2 times greater among continuous users (P = .03) and 2.4 times greater among new users (P = .01), compared with former users, who the investigators used as a control group because, at some point, they too had indications for testosterone replacement and so were more medically similar than never users.
The risk of noncalcified plaque volume progression was also more than twice as high among ongoing users, and elevated, although not significantly so, among ongoing users.
In short, “our findings are similar to those on subclinical atherosclerotic progression” in trials of older men in the general population on testosterone replacement, Dr. Haberlen said.
About half the subjects were white, 41% were at high risk for cardiovascular disease, 91% were on antiretroviral therapy, and 81% had undetectable HIV viral loads. Median total testosterone was 606 ng/dL. CAC progression was defined by incident CAC, at least a 10 Agatston unit/year increase if the baseline CAC score was 1-100, and a 10% or more annual increase if the baseline score was above 100.
Lower baseline serum testosterone was also associated with an increased risk of CAC progression, although not progression of noncalcified plaques.
The work was funded by the National Institutes of Health. Dr. Haberlen didn’t report any relevant disclosures.
SOURCE: Haberlen S et al. CROI 2020, Abstract 662.
Men with HIV are likely prone to the same cardiovascular risks from testosterone therapy as other men, according to new research.
There’s no reason to think they weren’t, but it hadn’t been demonstrated until now, and men with HIV are already at increased risk for cardiovascular disease. The take-home message is that “it would be prudent for clinicians to monitor closely for cardiovascular risk factors and recommend intervention to lower cardiovascular risk among men with HIV on or considering testosterone therapy,” lead investigator Sabina Haberlen, PhD, an assistant scientist in the infectious disease epidemiology division of Johns Hopkins University, Baltimore, said in a poster that was presented as part of the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because concerns about the spread of COVID-19.
Testosterone therapy is common among middle-aged and older men with HIV to counter the hypogonadism associated with infection. The investigators turned to the Multicenter AIDS Cohort Study – a 30-year, four-city study of HIV-1 infection in men who have sex with men – to gauge its effect.
The 300 men in the study had a baseline coronary CT angiogram in 2010-2013 and a repeat study a mean of 4.5 years later. They had no history of coronary interventions or kidney dysfunction at baseline and were aged 40-70 years, with a median age of 51 years. About 70% reported never using testosterone, 8% were former users before entering the study, 7% started using testosterone between the two CTs, and 15% entered the study on testosterone and stayed on it.
Adjusting for age, race, cardiovascular risk factors, baseline serum testosterone levels, and other potential confounders, the risk of significant coronary artery calcium (CAC) progression was 2 times greater among continuous users (P = .03) and 2.4 times greater among new users (P = .01), compared with former users, who the investigators used as a control group because, at some point, they too had indications for testosterone replacement and so were more medically similar than never users.
The risk of noncalcified plaque volume progression was also more than twice as high among ongoing users, and elevated, although not significantly so, among ongoing users.
In short, “our findings are similar to those on subclinical atherosclerotic progression” in trials of older men in the general population on testosterone replacement, Dr. Haberlen said.
About half the subjects were white, 41% were at high risk for cardiovascular disease, 91% were on antiretroviral therapy, and 81% had undetectable HIV viral loads. Median total testosterone was 606 ng/dL. CAC progression was defined by incident CAC, at least a 10 Agatston unit/year increase if the baseline CAC score was 1-100, and a 10% or more annual increase if the baseline score was above 100.
Lower baseline serum testosterone was also associated with an increased risk of CAC progression, although not progression of noncalcified plaques.
The work was funded by the National Institutes of Health. Dr. Haberlen didn’t report any relevant disclosures.
SOURCE: Haberlen S et al. CROI 2020, Abstract 662.
Men with HIV are likely prone to the same cardiovascular risks from testosterone therapy as other men, according to new research.
There’s no reason to think they weren’t, but it hadn’t been demonstrated until now, and men with HIV are already at increased risk for cardiovascular disease. The take-home message is that “it would be prudent for clinicians to monitor closely for cardiovascular risk factors and recommend intervention to lower cardiovascular risk among men with HIV on or considering testosterone therapy,” lead investigator Sabina Haberlen, PhD, an assistant scientist in the infectious disease epidemiology division of Johns Hopkins University, Baltimore, said in a poster that was presented as part of the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because concerns about the spread of COVID-19.
Testosterone therapy is common among middle-aged and older men with HIV to counter the hypogonadism associated with infection. The investigators turned to the Multicenter AIDS Cohort Study – a 30-year, four-city study of HIV-1 infection in men who have sex with men – to gauge its effect.
The 300 men in the study had a baseline coronary CT angiogram in 2010-2013 and a repeat study a mean of 4.5 years later. They had no history of coronary interventions or kidney dysfunction at baseline and were aged 40-70 years, with a median age of 51 years. About 70% reported never using testosterone, 8% were former users before entering the study, 7% started using testosterone between the two CTs, and 15% entered the study on testosterone and stayed on it.
Adjusting for age, race, cardiovascular risk factors, baseline serum testosterone levels, and other potential confounders, the risk of significant coronary artery calcium (CAC) progression was 2 times greater among continuous users (P = .03) and 2.4 times greater among new users (P = .01), compared with former users, who the investigators used as a control group because, at some point, they too had indications for testosterone replacement and so were more medically similar than never users.
The risk of noncalcified plaque volume progression was also more than twice as high among ongoing users, and elevated, although not significantly so, among ongoing users.
In short, “our findings are similar to those on subclinical atherosclerotic progression” in trials of older men in the general population on testosterone replacement, Dr. Haberlen said.
About half the subjects were white, 41% were at high risk for cardiovascular disease, 91% were on antiretroviral therapy, and 81% had undetectable HIV viral loads. Median total testosterone was 606 ng/dL. CAC progression was defined by incident CAC, at least a 10 Agatston unit/year increase if the baseline CAC score was 1-100, and a 10% or more annual increase if the baseline score was above 100.
Lower baseline serum testosterone was also associated with an increased risk of CAC progression, although not progression of noncalcified plaques.
The work was funded by the National Institutes of Health. Dr. Haberlen didn’t report any relevant disclosures.
SOURCE: Haberlen S et al. CROI 2020, Abstract 662.
FROM CROI 2020
Descovy safety no match for cost savings with generic Truvada, study says
Economically, the modest safety benefit of tenofovir alafenamide-emtricitabine (Descovy) for HIV preexposure prophylaxis won’t justify paying thousands of dollars more for it when tenofovir disoproxil fumarate-emtricitabine (Truvada) becomes available as a generic in a year or so, according to a population level cost-effectiveness analysis presented at the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers held a virtual meeting because of concerns about the spread of COVID-19.
Those benefits will translate to a health savings worth only a few hundred dollars over the likely generic price, said investigators led by Rochelle Walensky, MD, and infectious disease physician and professor of medicine at Harvard Medical School, Boston.
In a press statement, Gilead, which makes both medications, said it “strongly believes that the analysis ... is flawed, leading to inaccurate conclusions that severely underestimate the value of Descovy. The method and validation of the models, incomplete clinical data analyzed and the assumptions around potential pricing associated with a generic alternative to Truvada ... are inadequate to enable a sufficiently robust analysis.”
The company did not go into details about what exactly might have been off about the analysis.
Approved in Oct. 2019, tenofovir alafenamide-emtricitabine (also known as F/TAF) is the first new option for HIV preexposure prophylaxis (PrEP) since tenofovir disoproxil fumarate-emtricitabine (F/TDF) was approved in 2012; F/TDF is going off patent soon.
Amid a robust marketing campaign, the new medication has already captured 25% of the PrEP market, and Gilead expects up to 45% of patients to switch to F/TAF before generic F/TDF becomes available.
That worries the investigators. “At the current FSS [Federal Supply Schedule] price of $16,600 per year,” a nationwide PrEP program that uses F/TAF “would consume the entire $900.8 million federal budget for HIV prevention several times over ... If branded F/TAF drives out generic F/TDF,” rates of PrEP coverage “could decrease, and F/TAF could end up causing more avoidable HIV transmissions” than it prevents. “Given the very small, albeit statistically significant, differences in surrogate [safety] markers, without evidence of clinical significance, there is no urgency and no reason to switch PrEP regimens now,” they said. Both medications were equally effective in preventing HIV transmission in Gilead’s head-to-head phase 3 trial, but there was an a mean of about a 4 mL/min difference in estimated glomerular filtration rate at week 48 and about a 2% difference in hip and spine density at week 96, both favoring F/TAF. Marketing highlights those differences.
The investigators wanted to see how much they are worth, so they estimated savings from a possibly lower rate of bone fractures and renal failure with F/TAF and juxtaposed it with its cost and the anticipated cost of generic F/TDF at half-price, $8,300/patient-year.
They gave F/TAF the benefit of the doubt, skewing their model toward maximal harm and cost from F/TDF toxicity, and omitting the cost of increased lipid levels, weight gain, and other possible F/TAF adverse events.
In the end, they concluded that “the improved safety of F/TAF is worth no more than an additional $370 per person per year” over generic F/TDF based on toxicity differences. “
The team calculated that F/TAF would prevent a maximum of 2,101 fractures and 25 cases of end-stage renal disease among 123,610 U.S. men who have sex with men treated for 5 years. That translated to an incremental cost-effectiveness ratio of more than $7 million per quality-adjusted life-year, far above the $100,000 threshold considered acceptable in the United States.
“In the presence of a generic alternative, the current price of F/TAF would have to be reduced by over $7,900/year for F/TAF to satisfy generally accepted standards of societal value. If F/TDF can achieve the 75% price reduction that is commonly observed when generic competition ensues (that is, a cost of $4,150/year), the F/TAF price would need to be no higher than $4,520 to demonstrate value on the basis of cost-effectiveness,” the investigators said.
For older patients at unusually high risk for renal disease or bone-related adverse events, the switch from F/TDF to F/TAF would have greater clinical effect and benefit. Even in this population, however, it would be difficult to defend a price greater than $800 over the cost of the generic alternative,” they said.
“The message seems clear that the current cost of F/TAF does not justify wholesale conversion to F/TAF as the first-line agent for all PrEP-eligible patients,” said Carlos del Rio, MD, and Wendy Armstrong, MD, infectious disease professors at Emory University, Atlanta, in an editorial. “For PrEP-eligible persons at low risk for fracture and renal disease, it is very hard to justify use of F/TAF knowing that F/TDF will soon be generic” (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M20-0799).
“Successful PrEP scale-up in other countries was made possible by drug costs that are less than $100/month in most countries. In the United States, without drastic reductions in the cost of PrEP, which may be achievable with generic F/TDF ... we will fail to avert otherwise preventable new HIV transmissions,” they said.
The study was simultaneously published online (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478).
The work was funded by the National Institutes of Health and Massachusetts General Hospital. The investigators and editorialists didn’t have any industry disclosures.
SOURCE: Walensky RP et al. Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478.
Economically, the modest safety benefit of tenofovir alafenamide-emtricitabine (Descovy) for HIV preexposure prophylaxis won’t justify paying thousands of dollars more for it when tenofovir disoproxil fumarate-emtricitabine (Truvada) becomes available as a generic in a year or so, according to a population level cost-effectiveness analysis presented at the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers held a virtual meeting because of concerns about the spread of COVID-19.
Those benefits will translate to a health savings worth only a few hundred dollars over the likely generic price, said investigators led by Rochelle Walensky, MD, and infectious disease physician and professor of medicine at Harvard Medical School, Boston.
In a press statement, Gilead, which makes both medications, said it “strongly believes that the analysis ... is flawed, leading to inaccurate conclusions that severely underestimate the value of Descovy. The method and validation of the models, incomplete clinical data analyzed and the assumptions around potential pricing associated with a generic alternative to Truvada ... are inadequate to enable a sufficiently robust analysis.”
The company did not go into details about what exactly might have been off about the analysis.
Approved in Oct. 2019, tenofovir alafenamide-emtricitabine (also known as F/TAF) is the first new option for HIV preexposure prophylaxis (PrEP) since tenofovir disoproxil fumarate-emtricitabine (F/TDF) was approved in 2012; F/TDF is going off patent soon.
Amid a robust marketing campaign, the new medication has already captured 25% of the PrEP market, and Gilead expects up to 45% of patients to switch to F/TAF before generic F/TDF becomes available.
That worries the investigators. “At the current FSS [Federal Supply Schedule] price of $16,600 per year,” a nationwide PrEP program that uses F/TAF “would consume the entire $900.8 million federal budget for HIV prevention several times over ... If branded F/TAF drives out generic F/TDF,” rates of PrEP coverage “could decrease, and F/TAF could end up causing more avoidable HIV transmissions” than it prevents. “Given the very small, albeit statistically significant, differences in surrogate [safety] markers, without evidence of clinical significance, there is no urgency and no reason to switch PrEP regimens now,” they said. Both medications were equally effective in preventing HIV transmission in Gilead’s head-to-head phase 3 trial, but there was an a mean of about a 4 mL/min difference in estimated glomerular filtration rate at week 48 and about a 2% difference in hip and spine density at week 96, both favoring F/TAF. Marketing highlights those differences.
The investigators wanted to see how much they are worth, so they estimated savings from a possibly lower rate of bone fractures and renal failure with F/TAF and juxtaposed it with its cost and the anticipated cost of generic F/TDF at half-price, $8,300/patient-year.
They gave F/TAF the benefit of the doubt, skewing their model toward maximal harm and cost from F/TDF toxicity, and omitting the cost of increased lipid levels, weight gain, and other possible F/TAF adverse events.
In the end, they concluded that “the improved safety of F/TAF is worth no more than an additional $370 per person per year” over generic F/TDF based on toxicity differences. “
The team calculated that F/TAF would prevent a maximum of 2,101 fractures and 25 cases of end-stage renal disease among 123,610 U.S. men who have sex with men treated for 5 years. That translated to an incremental cost-effectiveness ratio of more than $7 million per quality-adjusted life-year, far above the $100,000 threshold considered acceptable in the United States.
“In the presence of a generic alternative, the current price of F/TAF would have to be reduced by over $7,900/year for F/TAF to satisfy generally accepted standards of societal value. If F/TDF can achieve the 75% price reduction that is commonly observed when generic competition ensues (that is, a cost of $4,150/year), the F/TAF price would need to be no higher than $4,520 to demonstrate value on the basis of cost-effectiveness,” the investigators said.
For older patients at unusually high risk for renal disease or bone-related adverse events, the switch from F/TDF to F/TAF would have greater clinical effect and benefit. Even in this population, however, it would be difficult to defend a price greater than $800 over the cost of the generic alternative,” they said.
“The message seems clear that the current cost of F/TAF does not justify wholesale conversion to F/TAF as the first-line agent for all PrEP-eligible patients,” said Carlos del Rio, MD, and Wendy Armstrong, MD, infectious disease professors at Emory University, Atlanta, in an editorial. “For PrEP-eligible persons at low risk for fracture and renal disease, it is very hard to justify use of F/TAF knowing that F/TDF will soon be generic” (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M20-0799).
“Successful PrEP scale-up in other countries was made possible by drug costs that are less than $100/month in most countries. In the United States, without drastic reductions in the cost of PrEP, which may be achievable with generic F/TDF ... we will fail to avert otherwise preventable new HIV transmissions,” they said.
The study was simultaneously published online (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478).
The work was funded by the National Institutes of Health and Massachusetts General Hospital. The investigators and editorialists didn’t have any industry disclosures.
SOURCE: Walensky RP et al. Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478.
Economically, the modest safety benefit of tenofovir alafenamide-emtricitabine (Descovy) for HIV preexposure prophylaxis won’t justify paying thousands of dollars more for it when tenofovir disoproxil fumarate-emtricitabine (Truvada) becomes available as a generic in a year or so, according to a population level cost-effectiveness analysis presented at the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers held a virtual meeting because of concerns about the spread of COVID-19.
Those benefits will translate to a health savings worth only a few hundred dollars over the likely generic price, said investigators led by Rochelle Walensky, MD, and infectious disease physician and professor of medicine at Harvard Medical School, Boston.
In a press statement, Gilead, which makes both medications, said it “strongly believes that the analysis ... is flawed, leading to inaccurate conclusions that severely underestimate the value of Descovy. The method and validation of the models, incomplete clinical data analyzed and the assumptions around potential pricing associated with a generic alternative to Truvada ... are inadequate to enable a sufficiently robust analysis.”
The company did not go into details about what exactly might have been off about the analysis.
Approved in Oct. 2019, tenofovir alafenamide-emtricitabine (also known as F/TAF) is the first new option for HIV preexposure prophylaxis (PrEP) since tenofovir disoproxil fumarate-emtricitabine (F/TDF) was approved in 2012; F/TDF is going off patent soon.
Amid a robust marketing campaign, the new medication has already captured 25% of the PrEP market, and Gilead expects up to 45% of patients to switch to F/TAF before generic F/TDF becomes available.
That worries the investigators. “At the current FSS [Federal Supply Schedule] price of $16,600 per year,” a nationwide PrEP program that uses F/TAF “would consume the entire $900.8 million federal budget for HIV prevention several times over ... If branded F/TAF drives out generic F/TDF,” rates of PrEP coverage “could decrease, and F/TAF could end up causing more avoidable HIV transmissions” than it prevents. “Given the very small, albeit statistically significant, differences in surrogate [safety] markers, without evidence of clinical significance, there is no urgency and no reason to switch PrEP regimens now,” they said. Both medications were equally effective in preventing HIV transmission in Gilead’s head-to-head phase 3 trial, but there was an a mean of about a 4 mL/min difference in estimated glomerular filtration rate at week 48 and about a 2% difference in hip and spine density at week 96, both favoring F/TAF. Marketing highlights those differences.
The investigators wanted to see how much they are worth, so they estimated savings from a possibly lower rate of bone fractures and renal failure with F/TAF and juxtaposed it with its cost and the anticipated cost of generic F/TDF at half-price, $8,300/patient-year.
They gave F/TAF the benefit of the doubt, skewing their model toward maximal harm and cost from F/TDF toxicity, and omitting the cost of increased lipid levels, weight gain, and other possible F/TAF adverse events.
In the end, they concluded that “the improved safety of F/TAF is worth no more than an additional $370 per person per year” over generic F/TDF based on toxicity differences. “
The team calculated that F/TAF would prevent a maximum of 2,101 fractures and 25 cases of end-stage renal disease among 123,610 U.S. men who have sex with men treated for 5 years. That translated to an incremental cost-effectiveness ratio of more than $7 million per quality-adjusted life-year, far above the $100,000 threshold considered acceptable in the United States.
“In the presence of a generic alternative, the current price of F/TAF would have to be reduced by over $7,900/year for F/TAF to satisfy generally accepted standards of societal value. If F/TDF can achieve the 75% price reduction that is commonly observed when generic competition ensues (that is, a cost of $4,150/year), the F/TAF price would need to be no higher than $4,520 to demonstrate value on the basis of cost-effectiveness,” the investigators said.
For older patients at unusually high risk for renal disease or bone-related adverse events, the switch from F/TDF to F/TAF would have greater clinical effect and benefit. Even in this population, however, it would be difficult to defend a price greater than $800 over the cost of the generic alternative,” they said.
“The message seems clear that the current cost of F/TAF does not justify wholesale conversion to F/TAF as the first-line agent for all PrEP-eligible patients,” said Carlos del Rio, MD, and Wendy Armstrong, MD, infectious disease professors at Emory University, Atlanta, in an editorial. “For PrEP-eligible persons at low risk for fracture and renal disease, it is very hard to justify use of F/TAF knowing that F/TDF will soon be generic” (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M20-0799).
“Successful PrEP scale-up in other countries was made possible by drug costs that are less than $100/month in most countries. In the United States, without drastic reductions in the cost of PrEP, which may be achievable with generic F/TDF ... we will fail to avert otherwise preventable new HIV transmissions,” they said.
The study was simultaneously published online (Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478).
The work was funded by the National Institutes of Health and Massachusetts General Hospital. The investigators and editorialists didn’t have any industry disclosures.
SOURCE: Walensky RP et al. Ann Intern Med. 2020 Mar 10. doi: 10.7326/M19-3478.
FROM CROI 2020
Some infected patients could show COVID-19 symptoms after quarantine
Although a 14-day quarantine after exposure to novel coronavirus is “well supported” by evidence, some infected individuals will not become symptomatic until after that period, according to authors of a recent analysis published in Annals of Internal Medicine.
Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will develop symptoms by day 12 of the infection, which is within the 14-day period of active monitoring currently recommended by the Centers for Disease Control and Prevention, the authors wrote.
However, an estimated 101 out of 10,000 cases could become symptomatic after the end of that 14-day monitoring period, they cautioned.
“Our analyses do not preclude that estimate from being higher,” said the investigators, led by Stephen A. Lauer, PhD, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore.
The analysis, based on 181 confirmed cases of coronavirus disease 2019 (COVID-19) that were documented outside of the outbreak epicenter, Wuhan, China, makes “more conservative assumptions” about the window of symptom onset and potential for continued exposure, compared with analyses in previous studies, the researchers wrote.
The estimated incubation period for SARS-CoV-2 in the 181-patient study was a median of 5.1 days, which is comparable with previous estimates based on COVID-19 cases outside of Wuhan and consistent with other known human coronavirus diseases, such as SARS, which had a reported mean incubation period of 5 days, Dr. Lauer and colleagues noted.
Symptoms developed within 11.5 days for 97.5% of patients in the study.
Whether it’s acceptable to have 101 out of 10,000 cases becoming symptomatic beyond the recommended quarantine window depends on two factors, according to the authors. The first is the expected infection risk in the population that is being monitored, and the second is “judgment about the cost of missing cases,” wrote the authors.
In an interview, Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau, Oceanside, N.Y., said that in practical terms, the results suggest that the majority of patients with COVID-19 will be identified within 14 days, with an “outside chance” of an infected individual leaving quarantine and transmitting virus for a short period of time before becoming symptomatic.
“I think the proper message to give those patients [who are asymptomatic upon leaving quarantine] is, ‘after 14 days, we’re pretty sure you’re out of the woods, but should you get any symptoms, immediately requarantine yourself and seek medical care,” he said.
Study coauthor Kyra H. Grantz, a doctoral graduate student at the Johns Hopkins Bloomberg School of Public Health, said that extending a quarantine beyond 14 days might be considered in the highest-risk scenarios, though the benefits of doing so would have to be weighed against the costs to public health and to the individuals under quarantine.
“Our estimate of the incubation period definitely supports the 14-day recommendation that the CDC has been using,” she said in an interview.
Dr. Grantz emphasized that the estimate of 101 out of 10,000 cases developing symptoms after day 14 of active monitoring – representing the 99th percentile of cases – assumes the “most conservative, worst-case scenario” in a population that is fully infected.
“If you’re looking at a following a cohort of 1,000 people whom you think may have been exposed, only a certain percentage will be infected, and only a certain percentage of those will even develop symptoms – before we get to this idea of how many people would we miss,” she said.
The study was supported by the Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the Alexander von Humboldt Foundation. Four authors reported disclosures related to those entities, and the remaining five reported no conflicts of interest.
SOURCE: Lauer SA et al. Ann Intern Med. 2020 Mar 9. doi:10.1101/2020.02.02.20020016.
Although a 14-day quarantine after exposure to novel coronavirus is “well supported” by evidence, some infected individuals will not become symptomatic until after that period, according to authors of a recent analysis published in Annals of Internal Medicine.
Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will develop symptoms by day 12 of the infection, which is within the 14-day period of active monitoring currently recommended by the Centers for Disease Control and Prevention, the authors wrote.
However, an estimated 101 out of 10,000 cases could become symptomatic after the end of that 14-day monitoring period, they cautioned.
“Our analyses do not preclude that estimate from being higher,” said the investigators, led by Stephen A. Lauer, PhD, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore.
The analysis, based on 181 confirmed cases of coronavirus disease 2019 (COVID-19) that were documented outside of the outbreak epicenter, Wuhan, China, makes “more conservative assumptions” about the window of symptom onset and potential for continued exposure, compared with analyses in previous studies, the researchers wrote.
The estimated incubation period for SARS-CoV-2 in the 181-patient study was a median of 5.1 days, which is comparable with previous estimates based on COVID-19 cases outside of Wuhan and consistent with other known human coronavirus diseases, such as SARS, which had a reported mean incubation period of 5 days, Dr. Lauer and colleagues noted.
Symptoms developed within 11.5 days for 97.5% of patients in the study.
Whether it’s acceptable to have 101 out of 10,000 cases becoming symptomatic beyond the recommended quarantine window depends on two factors, according to the authors. The first is the expected infection risk in the population that is being monitored, and the second is “judgment about the cost of missing cases,” wrote the authors.
In an interview, Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau, Oceanside, N.Y., said that in practical terms, the results suggest that the majority of patients with COVID-19 will be identified within 14 days, with an “outside chance” of an infected individual leaving quarantine and transmitting virus for a short period of time before becoming symptomatic.
“I think the proper message to give those patients [who are asymptomatic upon leaving quarantine] is, ‘after 14 days, we’re pretty sure you’re out of the woods, but should you get any symptoms, immediately requarantine yourself and seek medical care,” he said.
Study coauthor Kyra H. Grantz, a doctoral graduate student at the Johns Hopkins Bloomberg School of Public Health, said that extending a quarantine beyond 14 days might be considered in the highest-risk scenarios, though the benefits of doing so would have to be weighed against the costs to public health and to the individuals under quarantine.
“Our estimate of the incubation period definitely supports the 14-day recommendation that the CDC has been using,” she said in an interview.
Dr. Grantz emphasized that the estimate of 101 out of 10,000 cases developing symptoms after day 14 of active monitoring – representing the 99th percentile of cases – assumes the “most conservative, worst-case scenario” in a population that is fully infected.
“If you’re looking at a following a cohort of 1,000 people whom you think may have been exposed, only a certain percentage will be infected, and only a certain percentage of those will even develop symptoms – before we get to this idea of how many people would we miss,” she said.
The study was supported by the Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the Alexander von Humboldt Foundation. Four authors reported disclosures related to those entities, and the remaining five reported no conflicts of interest.
SOURCE: Lauer SA et al. Ann Intern Med. 2020 Mar 9. doi:10.1101/2020.02.02.20020016.
Although a 14-day quarantine after exposure to novel coronavirus is “well supported” by evidence, some infected individuals will not become symptomatic until after that period, according to authors of a recent analysis published in Annals of Internal Medicine.
Most individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will develop symptoms by day 12 of the infection, which is within the 14-day period of active monitoring currently recommended by the Centers for Disease Control and Prevention, the authors wrote.
However, an estimated 101 out of 10,000 cases could become symptomatic after the end of that 14-day monitoring period, they cautioned.
“Our analyses do not preclude that estimate from being higher,” said the investigators, led by Stephen A. Lauer, PhD, MD, of Johns Hopkins Bloomberg School of Public Health, Baltimore.
The analysis, based on 181 confirmed cases of coronavirus disease 2019 (COVID-19) that were documented outside of the outbreak epicenter, Wuhan, China, makes “more conservative assumptions” about the window of symptom onset and potential for continued exposure, compared with analyses in previous studies, the researchers wrote.
The estimated incubation period for SARS-CoV-2 in the 181-patient study was a median of 5.1 days, which is comparable with previous estimates based on COVID-19 cases outside of Wuhan and consistent with other known human coronavirus diseases, such as SARS, which had a reported mean incubation period of 5 days, Dr. Lauer and colleagues noted.
Symptoms developed within 11.5 days for 97.5% of patients in the study.
Whether it’s acceptable to have 101 out of 10,000 cases becoming symptomatic beyond the recommended quarantine window depends on two factors, according to the authors. The first is the expected infection risk in the population that is being monitored, and the second is “judgment about the cost of missing cases,” wrote the authors.
In an interview, Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau, Oceanside, N.Y., said that in practical terms, the results suggest that the majority of patients with COVID-19 will be identified within 14 days, with an “outside chance” of an infected individual leaving quarantine and transmitting virus for a short period of time before becoming symptomatic.
“I think the proper message to give those patients [who are asymptomatic upon leaving quarantine] is, ‘after 14 days, we’re pretty sure you’re out of the woods, but should you get any symptoms, immediately requarantine yourself and seek medical care,” he said.
Study coauthor Kyra H. Grantz, a doctoral graduate student at the Johns Hopkins Bloomberg School of Public Health, said that extending a quarantine beyond 14 days might be considered in the highest-risk scenarios, though the benefits of doing so would have to be weighed against the costs to public health and to the individuals under quarantine.
“Our estimate of the incubation period definitely supports the 14-day recommendation that the CDC has been using,” she said in an interview.
Dr. Grantz emphasized that the estimate of 101 out of 10,000 cases developing symptoms after day 14 of active monitoring – representing the 99th percentile of cases – assumes the “most conservative, worst-case scenario” in a population that is fully infected.
“If you’re looking at a following a cohort of 1,000 people whom you think may have been exposed, only a certain percentage will be infected, and only a certain percentage of those will even develop symptoms – before we get to this idea of how many people would we miss,” she said.
The study was supported by the Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the Alexander von Humboldt Foundation. Four authors reported disclosures related to those entities, and the remaining five reported no conflicts of interest.
SOURCE: Lauer SA et al. Ann Intern Med. 2020 Mar 9. doi:10.1101/2020.02.02.20020016.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point: Some individuals who are infected with the novel coronavirus could become symptomatic after the active 14-day quarantine period.
Major finding: The median incubation period was 5.1 days, with 97.5% of patients developing symptoms within 11.5 days, implying that 101 of every 10,000 cases (99th percentile) would develop symptoms beyond the quarantine period.
Study details: Analysis of 181 confirmed COVID-19 cases identified outside of the outbreak epicenter, Wuhan, China.
Disclosures: The study was supported by the U.S. Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the Alexander von Humboldt Foundation. Four authors reported disclosures related to those entities, and the remaining five reported no conflicts of interest.
Source: Lauer SA et al. Ann Intern Med. 2020 Mar 9. doi: 10.1101/2020.02.02.20020016.
Rotavirus vaccination is not a risk factor for type 1 diabetes
published in JAMA Pediatrics.
Previous findings from a number of studies have indicated a possible association between rotavirus and type 1 diabetes, according to Jason M. Glanz, PhD, and colleagues. “Epidemiologic data suggest an association between gastrointestinal infection and incidence of type 1 diabetes in children followed from birth to age 10 years. Given these findings, it is biologically plausible that live, attenuated rotavirus vaccine could either increase or decrease the risk for type 1 diabetes in early childhood,” they wrote.
To examine the association between rotavirus vaccination and the incidence of type 1 diabetes in a cohort of U.S. children, Dr. Glanz, a senior investigator at the Kaiser Permanente Colorado Institute for Health Research in Aurora, and colleagues retrospectively analyzed data from seven health care organizations that participate in the Vaccine Safety Datalink.
The researchers identified children born between 2006 and 2014 who had continuous enrollment from age 6 weeks to 2 years. They excluded children with a medical contraindication to vaccination or fewer than two well-child visits by age 12 months. They followed children until a type 1 diabetes diagnosis, disenrollment, or Dec. 31, 2017. The researchers adjusted for sex, birth year, mother’s age, birth weight, gestational age, and race or ethnicity.
The cohort included 386,937 children who were followed up a median of 5.4 years for a total person-time follow-up of 2,253,879 years. In all, 386,937 children (93.1%) were fully exposed to rotavirus vaccination; 15,765 (4.1%) were partially exposed to rotavirus vaccination, meaning that they received some, but not all, vaccine doses; and 11,003 (2.8%) were unexposed to rotavirus vaccination but had received all other recommended vaccines.
There were 464 cases of type 1 diabetes in the cohort, with an incidence rate of 20 cases per 100,000 person-years in the fully exposed group, 31.2 cases per 100,000 person-years in the partially exposed group, and 22.4 cases per 100,000 person-years in the unexposed group.
The incidence of type 1 diabetes was not significantly different across the rotavirus vaccine–exposure groups. The researchers reported that, compared with children unexposed to rotavirus vaccination, the adjusted hazard ratio for children fully exposed to rotavirus vaccination was 1.03 (95% confidence interval, 0.62-1.72), and for those partially exposed to the vaccination, it was 1.50 (95% CI, 0.81-2.77).
“Since licensure, rotavirus vaccination has been associated with a reduction in morbidity and mortality due to rotavirus infection in the United States and worldwide. ... Although rotavirus vaccination may not prevent type 1 diabetes, these results should provide additional reassurance to the public that rotavirus vaccination can be safely administered to infants,” they wrote.
The limited follow-up duration and relatively small proportion of patients unexposed to rotavirus vaccination are limitations of the study, the authors noted.
The Centers for Disease Control and Prevention funded the study. Several authors reported having received grants from the CDC. One author received grants from the National Institute of Diabetes and Digestive and Kidney Diseases, and another from pharmaceutical companies not involved in the study.
SOURCE: Glanz JM et al. JAMA Pediatr. 2020 Mar 9. doi: 10.1001/jamapediatrics.2019.6324.
published in JAMA Pediatrics.
Previous findings from a number of studies have indicated a possible association between rotavirus and type 1 diabetes, according to Jason M. Glanz, PhD, and colleagues. “Epidemiologic data suggest an association between gastrointestinal infection and incidence of type 1 diabetes in children followed from birth to age 10 years. Given these findings, it is biologically plausible that live, attenuated rotavirus vaccine could either increase or decrease the risk for type 1 diabetes in early childhood,” they wrote.
To examine the association between rotavirus vaccination and the incidence of type 1 diabetes in a cohort of U.S. children, Dr. Glanz, a senior investigator at the Kaiser Permanente Colorado Institute for Health Research in Aurora, and colleagues retrospectively analyzed data from seven health care organizations that participate in the Vaccine Safety Datalink.
The researchers identified children born between 2006 and 2014 who had continuous enrollment from age 6 weeks to 2 years. They excluded children with a medical contraindication to vaccination or fewer than two well-child visits by age 12 months. They followed children until a type 1 diabetes diagnosis, disenrollment, or Dec. 31, 2017. The researchers adjusted for sex, birth year, mother’s age, birth weight, gestational age, and race or ethnicity.
The cohort included 386,937 children who were followed up a median of 5.4 years for a total person-time follow-up of 2,253,879 years. In all, 386,937 children (93.1%) were fully exposed to rotavirus vaccination; 15,765 (4.1%) were partially exposed to rotavirus vaccination, meaning that they received some, but not all, vaccine doses; and 11,003 (2.8%) were unexposed to rotavirus vaccination but had received all other recommended vaccines.
There were 464 cases of type 1 diabetes in the cohort, with an incidence rate of 20 cases per 100,000 person-years in the fully exposed group, 31.2 cases per 100,000 person-years in the partially exposed group, and 22.4 cases per 100,000 person-years in the unexposed group.
The incidence of type 1 diabetes was not significantly different across the rotavirus vaccine–exposure groups. The researchers reported that, compared with children unexposed to rotavirus vaccination, the adjusted hazard ratio for children fully exposed to rotavirus vaccination was 1.03 (95% confidence interval, 0.62-1.72), and for those partially exposed to the vaccination, it was 1.50 (95% CI, 0.81-2.77).
“Since licensure, rotavirus vaccination has been associated with a reduction in morbidity and mortality due to rotavirus infection in the United States and worldwide. ... Although rotavirus vaccination may not prevent type 1 diabetes, these results should provide additional reassurance to the public that rotavirus vaccination can be safely administered to infants,” they wrote.
The limited follow-up duration and relatively small proportion of patients unexposed to rotavirus vaccination are limitations of the study, the authors noted.
The Centers for Disease Control and Prevention funded the study. Several authors reported having received grants from the CDC. One author received grants from the National Institute of Diabetes and Digestive and Kidney Diseases, and another from pharmaceutical companies not involved in the study.
SOURCE: Glanz JM et al. JAMA Pediatr. 2020 Mar 9. doi: 10.1001/jamapediatrics.2019.6324.
published in JAMA Pediatrics.
Previous findings from a number of studies have indicated a possible association between rotavirus and type 1 diabetes, according to Jason M. Glanz, PhD, and colleagues. “Epidemiologic data suggest an association between gastrointestinal infection and incidence of type 1 diabetes in children followed from birth to age 10 years. Given these findings, it is biologically plausible that live, attenuated rotavirus vaccine could either increase or decrease the risk for type 1 diabetes in early childhood,” they wrote.
To examine the association between rotavirus vaccination and the incidence of type 1 diabetes in a cohort of U.S. children, Dr. Glanz, a senior investigator at the Kaiser Permanente Colorado Institute for Health Research in Aurora, and colleagues retrospectively analyzed data from seven health care organizations that participate in the Vaccine Safety Datalink.
The researchers identified children born between 2006 and 2014 who had continuous enrollment from age 6 weeks to 2 years. They excluded children with a medical contraindication to vaccination or fewer than two well-child visits by age 12 months. They followed children until a type 1 diabetes diagnosis, disenrollment, or Dec. 31, 2017. The researchers adjusted for sex, birth year, mother’s age, birth weight, gestational age, and race or ethnicity.
The cohort included 386,937 children who were followed up a median of 5.4 years for a total person-time follow-up of 2,253,879 years. In all, 386,937 children (93.1%) were fully exposed to rotavirus vaccination; 15,765 (4.1%) were partially exposed to rotavirus vaccination, meaning that they received some, but not all, vaccine doses; and 11,003 (2.8%) were unexposed to rotavirus vaccination but had received all other recommended vaccines.
There were 464 cases of type 1 diabetes in the cohort, with an incidence rate of 20 cases per 100,000 person-years in the fully exposed group, 31.2 cases per 100,000 person-years in the partially exposed group, and 22.4 cases per 100,000 person-years in the unexposed group.
The incidence of type 1 diabetes was not significantly different across the rotavirus vaccine–exposure groups. The researchers reported that, compared with children unexposed to rotavirus vaccination, the adjusted hazard ratio for children fully exposed to rotavirus vaccination was 1.03 (95% confidence interval, 0.62-1.72), and for those partially exposed to the vaccination, it was 1.50 (95% CI, 0.81-2.77).
“Since licensure, rotavirus vaccination has been associated with a reduction in morbidity and mortality due to rotavirus infection in the United States and worldwide. ... Although rotavirus vaccination may not prevent type 1 diabetes, these results should provide additional reassurance to the public that rotavirus vaccination can be safely administered to infants,” they wrote.
The limited follow-up duration and relatively small proportion of patients unexposed to rotavirus vaccination are limitations of the study, the authors noted.
The Centers for Disease Control and Prevention funded the study. Several authors reported having received grants from the CDC. One author received grants from the National Institute of Diabetes and Digestive and Kidney Diseases, and another from pharmaceutical companies not involved in the study.
SOURCE: Glanz JM et al. JAMA Pediatr. 2020 Mar 9. doi: 10.1001/jamapediatrics.2019.6324.
FROM JAMA PEDIATRICS
Key clinical point: Rotavirus vaccination is not associated with the incidence of type 1 diabetes and can be safely administered to infants.
Major finding: Compared with children unexposed to rotavirus vaccination, the adjusted hazard ratio for developing type 1 diabetes for children fully exposed to the vaccination was 1.03 (95% confidence interval, 0.62-1.72), and for those partially exposed to it, the aHR was 1.50 (95% CI, 0.81-2.77).
Study details: A retrospective cohort study of 386,937 children using data from the Vaccine Safety Datalink.
Disclosures: The Centers for Disease Control and Prevention funded the study. Several authors reported having received grants from the CDC. One author received grants from the National Institute of Diabetes and Digestive and Kidney Diseases, and another from pharmaceutical companies not involved in the study.
Source: Glanz JM et al. JAMA Pediatr. 2020 Mar 9. doi: 10.1001/jamapediatrics.2019.6324.
Flu activity declines again but remains high
Outpatient visits to health care providers for influenza-like illness dropped from 5.5% the previous week to 5.3% of all visits for the week ending Feb. 29, the Centers for Disease Control and Prevention said on March 6.
The national baseline rate of 2.4% was first reached during the week of Nov. 9, 2019 – marking the start of flu season – and has remained at or above that level for 17 consecutive weeks. Last year’s season, which also was the longest in a decade, lasted 21 consecutive weeks but started 2 weeks later than the current season and had a lower outpatient-visit rate (4.5%) for the last week of February, CDC data show.
This season’s earlier start could mean that even a somewhat steep decline in visits to below the baseline rate – marking the end of the season – might take 5 or 6 weeks and would make 2019-2020 even longer than 2018-2019.
The activity situation on the state level reflects the small national decline. For the week ending Feb. 29, there were 33 states at level 10 on the CDC’s 1-10 activity scale, compared with 37 the week before, and a total of 40 in the “high” range of 8-10, compared with 43 the week before, the CDC’s influenza division reported.
The other main measure of influenza activity, percentage of respiratory specimens testing positive, also declined for the third week in a row and is now at 24.3% after reaching a high of 30.3% during the week of Feb. 2-8, the influenza division said.
The overall cumulative hospitalization rate continues to remain at a fairly typical 57.9 per 100,000 population, but rates for school-aged children (84.9 per 100,000) and young adults (31.2 per 100,000) are among the highest ever recorded at this point in the season. Mortality among children – now at 136 for 2019-2020 – is higher than for any season since reporting began in 2004, with the exception of the 2009 pandemic, the CDC said.
Outpatient visits to health care providers for influenza-like illness dropped from 5.5% the previous week to 5.3% of all visits for the week ending Feb. 29, the Centers for Disease Control and Prevention said on March 6.
The national baseline rate of 2.4% was first reached during the week of Nov. 9, 2019 – marking the start of flu season – and has remained at or above that level for 17 consecutive weeks. Last year’s season, which also was the longest in a decade, lasted 21 consecutive weeks but started 2 weeks later than the current season and had a lower outpatient-visit rate (4.5%) for the last week of February, CDC data show.
This season’s earlier start could mean that even a somewhat steep decline in visits to below the baseline rate – marking the end of the season – might take 5 or 6 weeks and would make 2019-2020 even longer than 2018-2019.
The activity situation on the state level reflects the small national decline. For the week ending Feb. 29, there were 33 states at level 10 on the CDC’s 1-10 activity scale, compared with 37 the week before, and a total of 40 in the “high” range of 8-10, compared with 43 the week before, the CDC’s influenza division reported.
The other main measure of influenza activity, percentage of respiratory specimens testing positive, also declined for the third week in a row and is now at 24.3% after reaching a high of 30.3% during the week of Feb. 2-8, the influenza division said.
The overall cumulative hospitalization rate continues to remain at a fairly typical 57.9 per 100,000 population, but rates for school-aged children (84.9 per 100,000) and young adults (31.2 per 100,000) are among the highest ever recorded at this point in the season. Mortality among children – now at 136 for 2019-2020 – is higher than for any season since reporting began in 2004, with the exception of the 2009 pandemic, the CDC said.
Outpatient visits to health care providers for influenza-like illness dropped from 5.5% the previous week to 5.3% of all visits for the week ending Feb. 29, the Centers for Disease Control and Prevention said on March 6.
The national baseline rate of 2.4% was first reached during the week of Nov. 9, 2019 – marking the start of flu season – and has remained at or above that level for 17 consecutive weeks. Last year’s season, which also was the longest in a decade, lasted 21 consecutive weeks but started 2 weeks later than the current season and had a lower outpatient-visit rate (4.5%) for the last week of February, CDC data show.
This season’s earlier start could mean that even a somewhat steep decline in visits to below the baseline rate – marking the end of the season – might take 5 or 6 weeks and would make 2019-2020 even longer than 2018-2019.
The activity situation on the state level reflects the small national decline. For the week ending Feb. 29, there were 33 states at level 10 on the CDC’s 1-10 activity scale, compared with 37 the week before, and a total of 40 in the “high” range of 8-10, compared with 43 the week before, the CDC’s influenza division reported.
The other main measure of influenza activity, percentage of respiratory specimens testing positive, also declined for the third week in a row and is now at 24.3% after reaching a high of 30.3% during the week of Feb. 2-8, the influenza division said.
The overall cumulative hospitalization rate continues to remain at a fairly typical 57.9 per 100,000 population, but rates for school-aged children (84.9 per 100,000) and young adults (31.2 per 100,000) are among the highest ever recorded at this point in the season. Mortality among children – now at 136 for 2019-2020 – is higher than for any season since reporting began in 2004, with the exception of the 2009 pandemic, the CDC said.
Novel coronavirus may cause environmental contamination through fecal shedding
The toilet bowl, sink, and bathroom door handle of an isolation room housing a patient with the novel coronavirus tested positive for the virus, raising the possibility that viral shedding in the stool could represent another route of transmission, investigators reported.
Air outlet fans and other room sites also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), though an anteroom, a corridor, and most personal protective equipment (PPE) worn by health care providers tested negative, according to the researchers, led by Sean Wei Xiang Ong, MBBS, of the National Centre for Infectious Diseases, Singapore.
Taken together, these findings suggest a “need for strict adherence to environmental and hand hygiene” to combat significant environmental contamination through respiratory droplets and fecal shedding, Dr. Ong and colleagues wrote in JAMA.
Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau in New York, said these results demonstrate that SARS-CoV-2 is “clearly capable” of contaminating bathroom sinks and toilets.
“That wouldn’t have been the first place I would have thought of, before this study,” he said in an interview. “You need to pay attention to cleaning the bathrooms, which we obviously do, but that’s an important reminder.”
The report by Dr. Ong and coauthors included a total of three patients housed in airborne infection isolation rooms in a dedicated SARS-CoV-2 outbreak center in Singapore. For each patient, surface samples were taken from 26 sites in the isolation room, an anteroom, and a bathroom. Samples were also taken from PPE on physicians as they left the patient rooms.
Samples for the first patient, taken right after routine cleaning, were all negative, according to researchers. That room was sampled twice, on days 4 and 10 of the illness, while the patient was still symptomatic. Likewise, for the second patient, postcleaning samples were negative; those samples were taken 2 days after cleaning.
However, for the third patient, samples were taken before routine cleaning. In this case, Dr. Ong and colleagues said 13 of 15 room sites (87%) were positive, including air outlet fans, while 3 of 5 toilet sites (60%) were positive as well, though no contamination was found in the anteroom, corridor, or in air samples.
That patient had two stool samples that were positive for SARS-CoV-2, but no diarrhea, authors said, and had upper respiratory tract involvement without pneumonia.
The fact that swabs of the air exhaust outlets tested positive suggests that virus-laden droplets could be “displaced by airflows” and end up on vents or other equipment, Dr. Ong and coauthors reported.
All PPE samples tested negative, except for the front of one shoe.
“The risk of transmission from contaminated footwear is likely low, as evidenced by negative results in the anteroom and corridor,” they wrote.
While this study included only a small number of patients, Dr. Glatt said the findings represent an important and useful contribution to the literature on coronavirus disease 2019 (COVID-19).
“Every day we’re getting more information, and each little piece of the puzzle helps us in the overall management of individuals with COVID-19,” he said in the interview. “They’re adding to our ability to manage, control, and mitigate further spread of the disease.”
Funding for the study came from the National Medical Research Council in Singapore and DSO National Laboratories. Dr. Ong and colleagues reported no conflicts of interest.
SOURCE: Ong SWX et al. JAMA. 2020 Mar 4. doi: 10.1001/jama.2020.3227.
The toilet bowl, sink, and bathroom door handle of an isolation room housing a patient with the novel coronavirus tested positive for the virus, raising the possibility that viral shedding in the stool could represent another route of transmission, investigators reported.
Air outlet fans and other room sites also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), though an anteroom, a corridor, and most personal protective equipment (PPE) worn by health care providers tested negative, according to the researchers, led by Sean Wei Xiang Ong, MBBS, of the National Centre for Infectious Diseases, Singapore.
Taken together, these findings suggest a “need for strict adherence to environmental and hand hygiene” to combat significant environmental contamination through respiratory droplets and fecal shedding, Dr. Ong and colleagues wrote in JAMA.
Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau in New York, said these results demonstrate that SARS-CoV-2 is “clearly capable” of contaminating bathroom sinks and toilets.
“That wouldn’t have been the first place I would have thought of, before this study,” he said in an interview. “You need to pay attention to cleaning the bathrooms, which we obviously do, but that’s an important reminder.”
The report by Dr. Ong and coauthors included a total of three patients housed in airborne infection isolation rooms in a dedicated SARS-CoV-2 outbreak center in Singapore. For each patient, surface samples were taken from 26 sites in the isolation room, an anteroom, and a bathroom. Samples were also taken from PPE on physicians as they left the patient rooms.
Samples for the first patient, taken right after routine cleaning, were all negative, according to researchers. That room was sampled twice, on days 4 and 10 of the illness, while the patient was still symptomatic. Likewise, for the second patient, postcleaning samples were negative; those samples were taken 2 days after cleaning.
However, for the third patient, samples were taken before routine cleaning. In this case, Dr. Ong and colleagues said 13 of 15 room sites (87%) were positive, including air outlet fans, while 3 of 5 toilet sites (60%) were positive as well, though no contamination was found in the anteroom, corridor, or in air samples.
That patient had two stool samples that were positive for SARS-CoV-2, but no diarrhea, authors said, and had upper respiratory tract involvement without pneumonia.
The fact that swabs of the air exhaust outlets tested positive suggests that virus-laden droplets could be “displaced by airflows” and end up on vents or other equipment, Dr. Ong and coauthors reported.
All PPE samples tested negative, except for the front of one shoe.
“The risk of transmission from contaminated footwear is likely low, as evidenced by negative results in the anteroom and corridor,” they wrote.
While this study included only a small number of patients, Dr. Glatt said the findings represent an important and useful contribution to the literature on coronavirus disease 2019 (COVID-19).
“Every day we’re getting more information, and each little piece of the puzzle helps us in the overall management of individuals with COVID-19,” he said in the interview. “They’re adding to our ability to manage, control, and mitigate further spread of the disease.”
Funding for the study came from the National Medical Research Council in Singapore and DSO National Laboratories. Dr. Ong and colleagues reported no conflicts of interest.
SOURCE: Ong SWX et al. JAMA. 2020 Mar 4. doi: 10.1001/jama.2020.3227.
The toilet bowl, sink, and bathroom door handle of an isolation room housing a patient with the novel coronavirus tested positive for the virus, raising the possibility that viral shedding in the stool could represent another route of transmission, investigators reported.
Air outlet fans and other room sites also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), though an anteroom, a corridor, and most personal protective equipment (PPE) worn by health care providers tested negative, according to the researchers, led by Sean Wei Xiang Ong, MBBS, of the National Centre for Infectious Diseases, Singapore.
Taken together, these findings suggest a “need for strict adherence to environmental and hand hygiene” to combat significant environmental contamination through respiratory droplets and fecal shedding, Dr. Ong and colleagues wrote in JAMA.
Aaron Eli Glatt, MD, chair of medicine at Mount Sinai South Nassau in New York, said these results demonstrate that SARS-CoV-2 is “clearly capable” of contaminating bathroom sinks and toilets.
“That wouldn’t have been the first place I would have thought of, before this study,” he said in an interview. “You need to pay attention to cleaning the bathrooms, which we obviously do, but that’s an important reminder.”
The report by Dr. Ong and coauthors included a total of three patients housed in airborne infection isolation rooms in a dedicated SARS-CoV-2 outbreak center in Singapore. For each patient, surface samples were taken from 26 sites in the isolation room, an anteroom, and a bathroom. Samples were also taken from PPE on physicians as they left the patient rooms.
Samples for the first patient, taken right after routine cleaning, were all negative, according to researchers. That room was sampled twice, on days 4 and 10 of the illness, while the patient was still symptomatic. Likewise, for the second patient, postcleaning samples were negative; those samples were taken 2 days after cleaning.
However, for the third patient, samples were taken before routine cleaning. In this case, Dr. Ong and colleagues said 13 of 15 room sites (87%) were positive, including air outlet fans, while 3 of 5 toilet sites (60%) were positive as well, though no contamination was found in the anteroom, corridor, or in air samples.
That patient had two stool samples that were positive for SARS-CoV-2, but no diarrhea, authors said, and had upper respiratory tract involvement without pneumonia.
The fact that swabs of the air exhaust outlets tested positive suggests that virus-laden droplets could be “displaced by airflows” and end up on vents or other equipment, Dr. Ong and coauthors reported.
All PPE samples tested negative, except for the front of one shoe.
“The risk of transmission from contaminated footwear is likely low, as evidenced by negative results in the anteroom and corridor,” they wrote.
While this study included only a small number of patients, Dr. Glatt said the findings represent an important and useful contribution to the literature on coronavirus disease 2019 (COVID-19).
“Every day we’re getting more information, and each little piece of the puzzle helps us in the overall management of individuals with COVID-19,” he said in the interview. “They’re adding to our ability to manage, control, and mitigate further spread of the disease.”
Funding for the study came from the National Medical Research Council in Singapore and DSO National Laboratories. Dr. Ong and colleagues reported no conflicts of interest.
SOURCE: Ong SWX et al. JAMA. 2020 Mar 4. doi: 10.1001/jama.2020.3227.
FROM JAMA
Telehealth seen as a key tool to help fight COVID-19
Telehealth is increasingly being viewed as a key way to help fight the COVID-19 outbreak in the United States. Recognizing the potential of this technology to slow the spread of the disease, the House of Representatives included a provision in an $8.3 billion emergency response bill it approved today that would temporarily lift restrictions on Medicare telehealth coverage to assist in the efforts to contain the virus.
Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention (CDC), said that hospitals should be prepared to use telehealth as one of their tools in fighting the outbreak, according to a recent news release from the American Hospital Association (AHA).
Congress is responding to that need by including the service in the new coronavirus legislation now headed to the Senate, after the funding bill was approved in a 415-2 vote by the House.
The bill empowers the Secretary of Health and Human Services (HHS) to “waive or modify application of certain Medicare requirements with respect to telehealth services furnished during certain emergency periods.”
While the measure adds telehealth to the waiver authority that the HHS secretary currently has during national emergencies, it’s only for the coronavirus crisis in this case, Krista Drobac, executive director of the Alliance for Connected Care, told Medscape Medical News.
The waiver would apply to originating sites of telehealth visits, she noted. Thus Medicare coverage of telemedicine would be expanded beyond rural areas.
In addition, the waiver would allow coverage of virtual visits conducted on smartphones with audio and video capabilities. A “qualified provider,” as defined by the legislation, would be a practitioner who has an established relationship with the patient or who is in the same practice as the provider who has that relationship.
An advantage of telehealth, proponents say, is that it can enable people who believe they have COVID-19 to be seen at home rather than visit offices or emergency departments (EDs) where they might spread the disease or be in proximity to others who have it.
In an editorial published March 2 in Modern Healthcare, medical directors from Stanford Medicine, MedStar Health, and Intermountain Healthcare also noted that telehealth can give patients 24/7 access to care, allow surveillance of patients at risk while keeping them at home, ensure that treatment in hospitals is reserved for high-need patients, and enable providers to triage and screen more patients than can be handled in brick-and-mortar care settings.
However, telehealth screening would allow physicians only to judge whether a patient’s symptoms might be indicative of COVID-19, the Alliance for Connected Care, a telehealth advocacy group, noted in a letter to Congressional leaders. Patients would still have to be seen in person to be tested for the disease.
The group, which represents technology companies, health insurers, pharmacies, and other healthcare players, has been lobbying Congress to include telehealth in federal funds to combat the outbreak.
The American Telemedicine Association (ATA) also supports this goal, ATA President Joseph Kvedar, MD, told Medscape Medical News. And the authors of the Modern Healthcare editorial also advocated for this legislative solution. Because the fatality rate for COVID-19 is significantly higher for older people than for other age groups, they noted, telehealth should be an economically viable option for all seniors.
The Centers for Medicare and Medicaid Services (CMS) long covered telemedicine only in rural areas and only when initiated in healthcare settings. Recently, however, CMS loosened its approach to some extent. Virtual “check-in visits” can now be initiated from any location, including home, to determine whether a Medicare patient needs to be seen in the office. In addition, CMS allows Medicare Advantage plans to offer telemedicine as a core benefit.
Are healthcare systems prepared?
Some large healthcare systems such as Stanford, MedStar, and Intermountain are already using telehealth to diagnose and treat patients who have traditional influenza. Telehealth providers at Stanford estimate that almost 50% of these patients are being prescribed the antiviral drug Tamiflu.
It’s unclear whether other healthcare systems are this well prepared to offer telehealth on a large scale. But, according to an AHA survey, Kvedar noted, three quarters of AHA members are engaged in some form of telehealth.
Drobac said “it wouldn’t require too much effort” to ramp up a wide-scale telehealth program that could help reduce the impact of the outbreak. “The technology is there,” she noted. “You need a HIPAA-compliant telehealth platform, but there are so many out there.”
Kvedar agreed. To begin with, he said, hospitals might sequester patients who visit the ED with COVID-19 symptoms in a video-equipped “isolation room.” Staff members could then do the patient intake from a different location in the hospital.
He admitted that this approach would be infeasible if a lot of patients arrived in EDs with coronavirus symptoms. However, Kvedar noted, “All the tools are in place to go well beyond that. American Well, Teladoc, and others are all offering ways to get out in front of this. There are plenty of vendors out there, and most people have a connected cell phone that you can do a video call on.”
Hospital leaders would have to decide whether to embrace telehealth, which would mean less use of services in their institutions, he said. “But it would be for the greater good of the public.”
Kvedar recalled that there was some use of telehealth in the New York area after 9/11. Telehealth was also used in the aftermath of Hurricane Katrina in 2005. But the ATA president, who is also vice president of connected health at Partners HealthCare in Boston, noted that the COVID-19 outbreak is the first public health emergency to occur in the era of Skype and smartphones.
If Congress does ultimately authorize CMS to cover telehealth across the board during this emergency, might that lead to a permanent change in Medicare coverage policy? Kvedar wouldn’t venture an opinion. “However, the current CMS leadership has been incredibly telehealth friendly,” he said. “So it’s possible they would [embrace a lifting of restrictions]. As patients get a sense of this modality of care and how convenient it is for them, they’ll start asking for more.”
Meanwhile, he said, the telehealth opportunity goes beyond video visits with doctors to mitigate the outbreak. Telehealth data could also be used to track disease spread, similar to how researchers have studied Google searches to predict the spread of the flu, he noted.
Teladoc, a major telehealth vendor, recently told stock analysts it’s already working with the CDC on disease surveillance, according to a report in FierceHealthcare.
This article first appeared on Medscape.com.
Telehealth is increasingly being viewed as a key way to help fight the COVID-19 outbreak in the United States. Recognizing the potential of this technology to slow the spread of the disease, the House of Representatives included a provision in an $8.3 billion emergency response bill it approved today that would temporarily lift restrictions on Medicare telehealth coverage to assist in the efforts to contain the virus.
Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention (CDC), said that hospitals should be prepared to use telehealth as one of their tools in fighting the outbreak, according to a recent news release from the American Hospital Association (AHA).
Congress is responding to that need by including the service in the new coronavirus legislation now headed to the Senate, after the funding bill was approved in a 415-2 vote by the House.
The bill empowers the Secretary of Health and Human Services (HHS) to “waive or modify application of certain Medicare requirements with respect to telehealth services furnished during certain emergency periods.”
While the measure adds telehealth to the waiver authority that the HHS secretary currently has during national emergencies, it’s only for the coronavirus crisis in this case, Krista Drobac, executive director of the Alliance for Connected Care, told Medscape Medical News.
The waiver would apply to originating sites of telehealth visits, she noted. Thus Medicare coverage of telemedicine would be expanded beyond rural areas.
In addition, the waiver would allow coverage of virtual visits conducted on smartphones with audio and video capabilities. A “qualified provider,” as defined by the legislation, would be a practitioner who has an established relationship with the patient or who is in the same practice as the provider who has that relationship.
An advantage of telehealth, proponents say, is that it can enable people who believe they have COVID-19 to be seen at home rather than visit offices or emergency departments (EDs) where they might spread the disease or be in proximity to others who have it.
In an editorial published March 2 in Modern Healthcare, medical directors from Stanford Medicine, MedStar Health, and Intermountain Healthcare also noted that telehealth can give patients 24/7 access to care, allow surveillance of patients at risk while keeping them at home, ensure that treatment in hospitals is reserved for high-need patients, and enable providers to triage and screen more patients than can be handled in brick-and-mortar care settings.
However, telehealth screening would allow physicians only to judge whether a patient’s symptoms might be indicative of COVID-19, the Alliance for Connected Care, a telehealth advocacy group, noted in a letter to Congressional leaders. Patients would still have to be seen in person to be tested for the disease.
The group, which represents technology companies, health insurers, pharmacies, and other healthcare players, has been lobbying Congress to include telehealth in federal funds to combat the outbreak.
The American Telemedicine Association (ATA) also supports this goal, ATA President Joseph Kvedar, MD, told Medscape Medical News. And the authors of the Modern Healthcare editorial also advocated for this legislative solution. Because the fatality rate for COVID-19 is significantly higher for older people than for other age groups, they noted, telehealth should be an economically viable option for all seniors.
The Centers for Medicare and Medicaid Services (CMS) long covered telemedicine only in rural areas and only when initiated in healthcare settings. Recently, however, CMS loosened its approach to some extent. Virtual “check-in visits” can now be initiated from any location, including home, to determine whether a Medicare patient needs to be seen in the office. In addition, CMS allows Medicare Advantage plans to offer telemedicine as a core benefit.
Are healthcare systems prepared?
Some large healthcare systems such as Stanford, MedStar, and Intermountain are already using telehealth to diagnose and treat patients who have traditional influenza. Telehealth providers at Stanford estimate that almost 50% of these patients are being prescribed the antiviral drug Tamiflu.
It’s unclear whether other healthcare systems are this well prepared to offer telehealth on a large scale. But, according to an AHA survey, Kvedar noted, three quarters of AHA members are engaged in some form of telehealth.
Drobac said “it wouldn’t require too much effort” to ramp up a wide-scale telehealth program that could help reduce the impact of the outbreak. “The technology is there,” she noted. “You need a HIPAA-compliant telehealth platform, but there are so many out there.”
Kvedar agreed. To begin with, he said, hospitals might sequester patients who visit the ED with COVID-19 symptoms in a video-equipped “isolation room.” Staff members could then do the patient intake from a different location in the hospital.
He admitted that this approach would be infeasible if a lot of patients arrived in EDs with coronavirus symptoms. However, Kvedar noted, “All the tools are in place to go well beyond that. American Well, Teladoc, and others are all offering ways to get out in front of this. There are plenty of vendors out there, and most people have a connected cell phone that you can do a video call on.”
Hospital leaders would have to decide whether to embrace telehealth, which would mean less use of services in their institutions, he said. “But it would be for the greater good of the public.”
Kvedar recalled that there was some use of telehealth in the New York area after 9/11. Telehealth was also used in the aftermath of Hurricane Katrina in 2005. But the ATA president, who is also vice president of connected health at Partners HealthCare in Boston, noted that the COVID-19 outbreak is the first public health emergency to occur in the era of Skype and smartphones.
If Congress does ultimately authorize CMS to cover telehealth across the board during this emergency, might that lead to a permanent change in Medicare coverage policy? Kvedar wouldn’t venture an opinion. “However, the current CMS leadership has been incredibly telehealth friendly,” he said. “So it’s possible they would [embrace a lifting of restrictions]. As patients get a sense of this modality of care and how convenient it is for them, they’ll start asking for more.”
Meanwhile, he said, the telehealth opportunity goes beyond video visits with doctors to mitigate the outbreak. Telehealth data could also be used to track disease spread, similar to how researchers have studied Google searches to predict the spread of the flu, he noted.
Teladoc, a major telehealth vendor, recently told stock analysts it’s already working with the CDC on disease surveillance, according to a report in FierceHealthcare.
This article first appeared on Medscape.com.
Telehealth is increasingly being viewed as a key way to help fight the COVID-19 outbreak in the United States. Recognizing the potential of this technology to slow the spread of the disease, the House of Representatives included a provision in an $8.3 billion emergency response bill it approved today that would temporarily lift restrictions on Medicare telehealth coverage to assist in the efforts to contain the virus.
Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention (CDC), said that hospitals should be prepared to use telehealth as one of their tools in fighting the outbreak, according to a recent news release from the American Hospital Association (AHA).
Congress is responding to that need by including the service in the new coronavirus legislation now headed to the Senate, after the funding bill was approved in a 415-2 vote by the House.
The bill empowers the Secretary of Health and Human Services (HHS) to “waive or modify application of certain Medicare requirements with respect to telehealth services furnished during certain emergency periods.”
While the measure adds telehealth to the waiver authority that the HHS secretary currently has during national emergencies, it’s only for the coronavirus crisis in this case, Krista Drobac, executive director of the Alliance for Connected Care, told Medscape Medical News.
The waiver would apply to originating sites of telehealth visits, she noted. Thus Medicare coverage of telemedicine would be expanded beyond rural areas.
In addition, the waiver would allow coverage of virtual visits conducted on smartphones with audio and video capabilities. A “qualified provider,” as defined by the legislation, would be a practitioner who has an established relationship with the patient or who is in the same practice as the provider who has that relationship.
An advantage of telehealth, proponents say, is that it can enable people who believe they have COVID-19 to be seen at home rather than visit offices or emergency departments (EDs) where they might spread the disease or be in proximity to others who have it.
In an editorial published March 2 in Modern Healthcare, medical directors from Stanford Medicine, MedStar Health, and Intermountain Healthcare also noted that telehealth can give patients 24/7 access to care, allow surveillance of patients at risk while keeping them at home, ensure that treatment in hospitals is reserved for high-need patients, and enable providers to triage and screen more patients than can be handled in brick-and-mortar care settings.
However, telehealth screening would allow physicians only to judge whether a patient’s symptoms might be indicative of COVID-19, the Alliance for Connected Care, a telehealth advocacy group, noted in a letter to Congressional leaders. Patients would still have to be seen in person to be tested for the disease.
The group, which represents technology companies, health insurers, pharmacies, and other healthcare players, has been lobbying Congress to include telehealth in federal funds to combat the outbreak.
The American Telemedicine Association (ATA) also supports this goal, ATA President Joseph Kvedar, MD, told Medscape Medical News. And the authors of the Modern Healthcare editorial also advocated for this legislative solution. Because the fatality rate for COVID-19 is significantly higher for older people than for other age groups, they noted, telehealth should be an economically viable option for all seniors.
The Centers for Medicare and Medicaid Services (CMS) long covered telemedicine only in rural areas and only when initiated in healthcare settings. Recently, however, CMS loosened its approach to some extent. Virtual “check-in visits” can now be initiated from any location, including home, to determine whether a Medicare patient needs to be seen in the office. In addition, CMS allows Medicare Advantage plans to offer telemedicine as a core benefit.
Are healthcare systems prepared?
Some large healthcare systems such as Stanford, MedStar, and Intermountain are already using telehealth to diagnose and treat patients who have traditional influenza. Telehealth providers at Stanford estimate that almost 50% of these patients are being prescribed the antiviral drug Tamiflu.
It’s unclear whether other healthcare systems are this well prepared to offer telehealth on a large scale. But, according to an AHA survey, Kvedar noted, three quarters of AHA members are engaged in some form of telehealth.
Drobac said “it wouldn’t require too much effort” to ramp up a wide-scale telehealth program that could help reduce the impact of the outbreak. “The technology is there,” she noted. “You need a HIPAA-compliant telehealth platform, but there are so many out there.”
Kvedar agreed. To begin with, he said, hospitals might sequester patients who visit the ED with COVID-19 symptoms in a video-equipped “isolation room.” Staff members could then do the patient intake from a different location in the hospital.
He admitted that this approach would be infeasible if a lot of patients arrived in EDs with coronavirus symptoms. However, Kvedar noted, “All the tools are in place to go well beyond that. American Well, Teladoc, and others are all offering ways to get out in front of this. There are plenty of vendors out there, and most people have a connected cell phone that you can do a video call on.”
Hospital leaders would have to decide whether to embrace telehealth, which would mean less use of services in their institutions, he said. “But it would be for the greater good of the public.”
Kvedar recalled that there was some use of telehealth in the New York area after 9/11. Telehealth was also used in the aftermath of Hurricane Katrina in 2005. But the ATA president, who is also vice president of connected health at Partners HealthCare in Boston, noted that the COVID-19 outbreak is the first public health emergency to occur in the era of Skype and smartphones.
If Congress does ultimately authorize CMS to cover telehealth across the board during this emergency, might that lead to a permanent change in Medicare coverage policy? Kvedar wouldn’t venture an opinion. “However, the current CMS leadership has been incredibly telehealth friendly,” he said. “So it’s possible they would [embrace a lifting of restrictions]. As patients get a sense of this modality of care and how convenient it is for them, they’ll start asking for more.”
Meanwhile, he said, the telehealth opportunity goes beyond video visits with doctors to mitigate the outbreak. Telehealth data could also be used to track disease spread, similar to how researchers have studied Google searches to predict the spread of the flu, he noted.
Teladoc, a major telehealth vendor, recently told stock analysts it’s already working with the CDC on disease surveillance, according to a report in FierceHealthcare.
This article first appeared on Medscape.com.
COVID-19 and public health preparedness in the United States
Background
On Dec. 31, 2019, the Chinese city of Wuhan reported an outbreak of pneumonia from an unknown cause. The outbreak was found to be linked to the Hunan seafood market because of a shared history of exposure by many patients. After a full-scale investigation, China’s Center for Disease Control activated a level 2 emergency response on Jan. 4, 2020. A novel coronavirus was officially identified as a causative pathogen for the outbreak.1
Coronavirus, first discovered in the 1960s, is a respiratory RNA virus, most commonly associated with the “common cold.” However, we have had two highly pathogenic forms of coronavirus that originated from animal reservoirs, leading to global epidemics. This includes SARS-CoV in 2002-2004 and MERS-CoV in 2012 with more than 10,000 combined cases. The primary host has been bats, but mammals like camels, cattle, cats, and palm civets have been intermediate hosts in previous epidemics.2
The International Committee on Taxonomy of Viruses named the 2019-nCoV officially as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease, COVID-19, on Feb. 11, 2020.3 Currently, the presentation includes fever, cough, trouble breathing, fatigue, and, rarely, watery diarrhea. More severe presentations include respiratory failure and death. Based on the incubation period of illness for Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses, as well as observational data from reports of travel-related COVID-19, CDC estimates that symptoms of COVID-19 occur within 2-14 days after exposure. Asymptomatic transmission is also documented in some cases.4
On Jan. 13, the first case of COVID-19 outside of China was identified in Thailand. On Jan. 21, the first case of COVID-19 was identified in the United States. On Jan. 23, Chinese authorities suspended travel in and out of Wuhan, followed by other cities in the Hubei Province, leading to a quarantine of 50 million people. By Jan. 30, the World Health Organization had identified COVID-19 as the highest level of an epidemic alert referred to as a PHEIC: Public Health Emergency of International Concern. On Feb. 2, the first death outside China from coronavirus was reported in the Philippines. As of March 4 there have been 95,000 confirmed cases and 3,246 deaths globally. Within China, there have been 80,200 cases with 2,981 deaths.5
Cases have now been diagnosed in increasing numbers in Italy, Japan, South Korea, Iran, and 76 countries. Of note, the fatalities were of patients already in critical condition, who were typically older (more than 60 years old, especially more than 80) and immunocompromised with comorbid conditions (cardiovascular disease, diabetes, chronic respiratory disease, cancer).6 To put this in perspective, since 2010, CDC reports 140,000-810,000 hospitalizations and 12,000-61,000 deaths from the influenza virus annually in the US.7
The current situation in the United States
In the United States, as of March 4, 2020, there are currently 152 confirmed cases in 16 states. The first U.S. case of coronavirus without any of the travel-related and exposure risk factors was identified on Feb. 27 in California, indicating the first instance of community spread.8 The first death was reported in Washington state on Feb. 28, after which the state’s governor declared a state of emergency.9 On March 1, Washington state health officials investigated an outbreak of coronavirus at a long-term nursing facility in which two people tested positive for the disease, heralding the probable first nosocomial transmission of the virus in the United States. Since then, there have been 10 deaths in Washington state related to the coronavirus.
Current interventions in the United States
The U.S. Centers for Disease Control and Prevention is leading a multiagency effort to combat the COVID-19 potential pandemic. A Feb. 24 report in Morbidity and Mortality Weekly Report revealed that 1,336 CDC staff members have been involved in the COVID-19 response.10 CDC staff members have been deployed to 39 locations in the United States and internationally. CDC staff members are working with state and local health departments and other public health authorities to assist with case identification, contact tracing, evaluation of persons under investigation (PUI) for COVID-19, and medical management of cases, as well as with research and academic institutions to understand the virulence, risk for transmission, and other characteristics of this novel virus. The CDC is also working with other agencies of the U.S. government including the U.S. Department of Defense, Department of Health & Human Services and the U.S. Department of State to safely evacuate U.S. citizens, residents, and their families from international locations with high incidence and transmission of COVID-19.
Specific real-time updated guidance has been developed and posted online for health care settings for patient management, infection control and prevention, laboratory testing, environmental cleaning, worker safety, and international travel. The CDC has developed communications materials in English and Spanish for communities and guidance for health care settings, public health, laboratories, schools, and businesses to prepare for a potential pandemic. Travel advisories to countries affected by the epidemic are regularly updated to inform travelers and clinicians about current health issues that need to be considered before travel.11 A level 3 travel notice (avoid all nonessential travel) for China has been in effect since Jan. 27, and on Feb. 29 this was upgraded to a level 4 travel notice.12 Airport screening has been implemented in the 11 U.S. international airports to which flights from China have been diverted, and a total of 46,016 air travelers had been screened by Feb. 23. Incoming passengers are screened for fever, cough, and shortness of breath.
Currently, the CDC has a comprehensive algorithm for further investigation of a PUI – fever, cough, shortness of breath, and a history of travel to areas with increased coronavirus circulation within 14 days of onset of symptoms, OR a close household contact of a confirmed case. When there is a PUI, the current protocol indicates health care providers should alert a local or state health department official. After the health department completes a case investigation, the CDC will help transport specimens (upper respiratory and lower respiratory specimens, and sometimes stool or urine) as soon as possible to the centralized lab for polymerase chain reaction (PCR) testing.13 CDC laboratories are currently using real-time reverse transcription–PCR (RT-PCR). The CDC is also developing a serologic test to assist with surveillance for SARS-CoV-2 circulation in the U.S. population. There is also a safe repository of viral isolates set up to help with sharing of isolates with academic institutions for research purposes.14
At hospitals and outpatient offices in the United States, we are preparing for potential cases by reminding frontline health care workers to routinely ask about travel history in addition to relevant symptoms. By eliciting the history early, they should be able to identify and isolate PUIs, appropriately minimizing exposure. Some facilities are displaying signage in waiting rooms to alert patients to provide relevant history, helping to improve triage. COVID-19 symptoms are like those of influenza (e.g., fever, cough, and shortness of breath), and the current outbreak is occurring during a time of year when respiratory illnesses from influenza and other viruses are highly prevalent. To prevent influenza and possible unnecessary evaluation for COVID-19, all persons aged 6 months and older are strongly encouraged to receive an annual influenza vaccine.
To decrease the risk for respiratory disease, persons can practice recommended preventive measures. Persons ill with symptoms of COVID-19 who have had contact with a person with COVID-19, or recent travel to countries with apparent community spread, should proactively communicate with their health care provider before showing up at the health care facility to help make arrangements to prevent possible transmission in the health care setting. In a medical emergency, they should inform emergency medical personnel about possible COVID-19 exposure. If found positive, the current recommendation is to place patients on airborne isolation. N95 masks are being recommended for health care professionals. Hospitals are reinforcing effective infection control procedures, updating pandemic preparedness protocols, and ensuring adequate supplies in the case of an enormous influx of patients.15
Challenges and opportunities
Many challenges present in the process of getting prepared for a potential outbreak. Personal protective equipment such as N-95 masks are in short supply, as they are in high demand in the general public.16 The CDC currently does not recommend that members of the general public use face masks, given low levels of circulation of SARS-CoV-2 currently in the United States. The CDC has developed several documents regarding infection control, hospital preparedness assessments, personal protective equipment (PPE) supply planning, clinical evaluation and management, and respirator conservation strategies.
The RT-PCR test developed by the CDC has had some setbacks, with recent testing kits showing “inconclusive results.” The testing was initially available only through the CDC lab in Atlanta, with a 48-hour turnaround. This led to potential delays in diagnosis and the timely isolation and treatment of infected patients. On March 3, the CDC broadened the guidelines for coronavirus testing, allowing clinicians to order a test for any patients who have symptoms of COVID-19 infection. The greatest need is for decentralized testing in local and state labs, as well as validated testing in local hospitals and commercial labs. The ability to develop and scale-up diagnostic abilities is critically important.
There is also concern about overwhelming hospitals with a strain on the availability of beds, ventilators, and airborne isolation rooms. The CDC is recommending leveraging telehealth tools to direct people to the right level of health care for their medical needs. Hospitalization should only be for the sickest patients.17
Funding for a pandemic response is of paramount importance. Proposed 2021 federal budget cuts include $2.9 billion in cuts to the National Institutes of Health, and $708 million in cuts to the CDC, which makes the situation look especially worrisome as we face a potentially severe pandemic. The Infectious Diseases Society of America identifies antimicrobial resistance, NIH research, global health security, global HIV epidemic, and CDC vaccine programs as five “deeply underfunded” areas in the federal budget.18
The NIH has recently begun the first randomized clinical trial, treating patients at the University of Nebraska with laboratory-confirmed SARS-CoV-2 with a broad-spectrum antiviral drug called remdesivir. Patients from the Diamond Princess Cruise ship are also participating in this clinical trial. This study will hopefully shed light on potential treatments for coronavirus to stop or alleviate the consequences in real time. Similar clinical trials are also occurring in China.19
Vaccine development is underway in many public and private research facilities, but it will take approximately 6-18 months before they will be available for use. In the absence of a vaccine or therapeutic, community mitigation measures are the primary method to respond to the widespread transmission, and supportive care is the current medical treatment. In the case of a pandemic, the mitigation measures might include school dismissals and social distancing in other settings, like suspension of mass gatherings, telework and remote-meeting options in workplaces.
Many respected medical journals in the United States have made access to SARS-CoV-2 articles and literature readily and freely available, which is a remarkable step. Multiple societies and journals have made information available in real time and have used media effectively (e.g., podcasts, e-learning) to disseminate information to the general public. Articles have been made available in other languages, including Chinese.
Conclusions
In summary, there have been 3,280 total deaths attributable to SARS-CoV-2 to date globally, mostly among geriatric patients with comorbidities. To provide some perspective on the statistics, influenza has killed almost 14,000 patients this season alone (much more than coronavirus). COVID-19 is undoubtedly a global public health threat. We in the U.S. health care system are taking swift public health actions, including isolation of patients and contacts to prevent secondary spread, but it is unclear if this is enough to stop an outbreak from becoming a pandemic.
The CDC is warning of significant social and economic disruption in the coming weeks, with more expected community spread and confirmed cases. It is challenging to prepare for a pandemic when the transmission dynamics are not clearly known, the duration of infectiousness is not well defined, and asymptomatic transmission is a possibility. It is time for the public to be informed from trusted sources and avoid unverified information, especially on social media which can lead to confusion and panic. The spread of COVID-19 infection in the United States is inevitable, and there must be sufficient, well-coordinated planning that can curtail the spread and reduce the impact.
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. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson. Ms. Sathya Areti is a 3rd-year medical student at the Virginia Commonwealth University School of Medicine (class of 2021), planning to apply into Internal Medicine-Pediatrics. Dr. Swetha Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is also a member of the Wellspan Pharmacy and Therapeutics committee.
References
1. Phelan AL et al. The novel coronavirus originating in Wuhan, China: Challenges for global health governance. JAMA. 2020;323(8):709-10. doi: 10.1001/jama.2020.1097.
2. del Rio C, Malani PN. 2019 Novel coronavirus – Important information for clinicians. JAMA. Published online Feb. 5, 2020. doi: 10.1001/jama.2020.1490.
3. Gorbalenya AE et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group. bioRxiv. Published Jan. 1, 2020. doi: 10.1101/2020.02.07.937862.
4. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.
5. Coronavirus disease 2019 (COVID-19). Situation Report – 40. Published Feb. 29, 2020.
6. Kaiyuan Sun, et al. Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population level observational study, Feb. 20, 2020. Lancet Digital Health 2020. doi: 10.1016/S2589-7500(20)30026-1.
7. Rolfes MA et al. Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness. Influenza Other Respir Viruses. 2018;12(1):132-7. doi: 10.1111/irv.12486.
8. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.
9. Jablon R, Baumann L. Washington governor declares state of emergency over virus. AP News. Published Feb. 29, 2020.
10. Jernigan DB, CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-219. doi: 10.15585/mmwr.mm6908e1.
11. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb 24, 2020.
12. Hines M. Coronavirus: Travel advisory for Italy, South Korea raised to level 4, ‘Do Not Travel’. USA Today. Published Feb. 29, 2020.
13. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb. 24, 2020.
14. CDC Tests for COVID-19. Centers for Disease Control and Prevention. Published Feb. 25, 2020.
15. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-19. doi: 10.15585/mmwr.mm6908e1.
16. Gunia A. The global shortage of medical masks won’t be easing soon. Time. Published Feb. 27, 2020.
17. CDC in action: Preparing communities for potential spread of COVID-19. Centers for Disease Control and Prevention. Published Feb. 23, 2020.
18. Kadets L. White House budget cuts vital domestic and global public health programs. IDSA Home. Published 2020.
19. NIH clinical trial of remdesivir to treat COVID-19 begins. National Institutes of Health. Feb. 25, 2020.
Background
On Dec. 31, 2019, the Chinese city of Wuhan reported an outbreak of pneumonia from an unknown cause. The outbreak was found to be linked to the Hunan seafood market because of a shared history of exposure by many patients. After a full-scale investigation, China’s Center for Disease Control activated a level 2 emergency response on Jan. 4, 2020. A novel coronavirus was officially identified as a causative pathogen for the outbreak.1
Coronavirus, first discovered in the 1960s, is a respiratory RNA virus, most commonly associated with the “common cold.” However, we have had two highly pathogenic forms of coronavirus that originated from animal reservoirs, leading to global epidemics. This includes SARS-CoV in 2002-2004 and MERS-CoV in 2012 with more than 10,000 combined cases. The primary host has been bats, but mammals like camels, cattle, cats, and palm civets have been intermediate hosts in previous epidemics.2
The International Committee on Taxonomy of Viruses named the 2019-nCoV officially as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease, COVID-19, on Feb. 11, 2020.3 Currently, the presentation includes fever, cough, trouble breathing, fatigue, and, rarely, watery diarrhea. More severe presentations include respiratory failure and death. Based on the incubation period of illness for Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses, as well as observational data from reports of travel-related COVID-19, CDC estimates that symptoms of COVID-19 occur within 2-14 days after exposure. Asymptomatic transmission is also documented in some cases.4
On Jan. 13, the first case of COVID-19 outside of China was identified in Thailand. On Jan. 21, the first case of COVID-19 was identified in the United States. On Jan. 23, Chinese authorities suspended travel in and out of Wuhan, followed by other cities in the Hubei Province, leading to a quarantine of 50 million people. By Jan. 30, the World Health Organization had identified COVID-19 as the highest level of an epidemic alert referred to as a PHEIC: Public Health Emergency of International Concern. On Feb. 2, the first death outside China from coronavirus was reported in the Philippines. As of March 4 there have been 95,000 confirmed cases and 3,246 deaths globally. Within China, there have been 80,200 cases with 2,981 deaths.5
Cases have now been diagnosed in increasing numbers in Italy, Japan, South Korea, Iran, and 76 countries. Of note, the fatalities were of patients already in critical condition, who were typically older (more than 60 years old, especially more than 80) and immunocompromised with comorbid conditions (cardiovascular disease, diabetes, chronic respiratory disease, cancer).6 To put this in perspective, since 2010, CDC reports 140,000-810,000 hospitalizations and 12,000-61,000 deaths from the influenza virus annually in the US.7
The current situation in the United States
In the United States, as of March 4, 2020, there are currently 152 confirmed cases in 16 states. The first U.S. case of coronavirus without any of the travel-related and exposure risk factors was identified on Feb. 27 in California, indicating the first instance of community spread.8 The first death was reported in Washington state on Feb. 28, after which the state’s governor declared a state of emergency.9 On March 1, Washington state health officials investigated an outbreak of coronavirus at a long-term nursing facility in which two people tested positive for the disease, heralding the probable first nosocomial transmission of the virus in the United States. Since then, there have been 10 deaths in Washington state related to the coronavirus.
Current interventions in the United States
The U.S. Centers for Disease Control and Prevention is leading a multiagency effort to combat the COVID-19 potential pandemic. A Feb. 24 report in Morbidity and Mortality Weekly Report revealed that 1,336 CDC staff members have been involved in the COVID-19 response.10 CDC staff members have been deployed to 39 locations in the United States and internationally. CDC staff members are working with state and local health departments and other public health authorities to assist with case identification, contact tracing, evaluation of persons under investigation (PUI) for COVID-19, and medical management of cases, as well as with research and academic institutions to understand the virulence, risk for transmission, and other characteristics of this novel virus. The CDC is also working with other agencies of the U.S. government including the U.S. Department of Defense, Department of Health & Human Services and the U.S. Department of State to safely evacuate U.S. citizens, residents, and their families from international locations with high incidence and transmission of COVID-19.
Specific real-time updated guidance has been developed and posted online for health care settings for patient management, infection control and prevention, laboratory testing, environmental cleaning, worker safety, and international travel. The CDC has developed communications materials in English and Spanish for communities and guidance for health care settings, public health, laboratories, schools, and businesses to prepare for a potential pandemic. Travel advisories to countries affected by the epidemic are regularly updated to inform travelers and clinicians about current health issues that need to be considered before travel.11 A level 3 travel notice (avoid all nonessential travel) for China has been in effect since Jan. 27, and on Feb. 29 this was upgraded to a level 4 travel notice.12 Airport screening has been implemented in the 11 U.S. international airports to which flights from China have been diverted, and a total of 46,016 air travelers had been screened by Feb. 23. Incoming passengers are screened for fever, cough, and shortness of breath.
Currently, the CDC has a comprehensive algorithm for further investigation of a PUI – fever, cough, shortness of breath, and a history of travel to areas with increased coronavirus circulation within 14 days of onset of symptoms, OR a close household contact of a confirmed case. When there is a PUI, the current protocol indicates health care providers should alert a local or state health department official. After the health department completes a case investigation, the CDC will help transport specimens (upper respiratory and lower respiratory specimens, and sometimes stool or urine) as soon as possible to the centralized lab for polymerase chain reaction (PCR) testing.13 CDC laboratories are currently using real-time reverse transcription–PCR (RT-PCR). The CDC is also developing a serologic test to assist with surveillance for SARS-CoV-2 circulation in the U.S. population. There is also a safe repository of viral isolates set up to help with sharing of isolates with academic institutions for research purposes.14
At hospitals and outpatient offices in the United States, we are preparing for potential cases by reminding frontline health care workers to routinely ask about travel history in addition to relevant symptoms. By eliciting the history early, they should be able to identify and isolate PUIs, appropriately minimizing exposure. Some facilities are displaying signage in waiting rooms to alert patients to provide relevant history, helping to improve triage. COVID-19 symptoms are like those of influenza (e.g., fever, cough, and shortness of breath), and the current outbreak is occurring during a time of year when respiratory illnesses from influenza and other viruses are highly prevalent. To prevent influenza and possible unnecessary evaluation for COVID-19, all persons aged 6 months and older are strongly encouraged to receive an annual influenza vaccine.
To decrease the risk for respiratory disease, persons can practice recommended preventive measures. Persons ill with symptoms of COVID-19 who have had contact with a person with COVID-19, or recent travel to countries with apparent community spread, should proactively communicate with their health care provider before showing up at the health care facility to help make arrangements to prevent possible transmission in the health care setting. In a medical emergency, they should inform emergency medical personnel about possible COVID-19 exposure. If found positive, the current recommendation is to place patients on airborne isolation. N95 masks are being recommended for health care professionals. Hospitals are reinforcing effective infection control procedures, updating pandemic preparedness protocols, and ensuring adequate supplies in the case of an enormous influx of patients.15
Challenges and opportunities
Many challenges present in the process of getting prepared for a potential outbreak. Personal protective equipment such as N-95 masks are in short supply, as they are in high demand in the general public.16 The CDC currently does not recommend that members of the general public use face masks, given low levels of circulation of SARS-CoV-2 currently in the United States. The CDC has developed several documents regarding infection control, hospital preparedness assessments, personal protective equipment (PPE) supply planning, clinical evaluation and management, and respirator conservation strategies.
The RT-PCR test developed by the CDC has had some setbacks, with recent testing kits showing “inconclusive results.” The testing was initially available only through the CDC lab in Atlanta, with a 48-hour turnaround. This led to potential delays in diagnosis and the timely isolation and treatment of infected patients. On March 3, the CDC broadened the guidelines for coronavirus testing, allowing clinicians to order a test for any patients who have symptoms of COVID-19 infection. The greatest need is for decentralized testing in local and state labs, as well as validated testing in local hospitals and commercial labs. The ability to develop and scale-up diagnostic abilities is critically important.
There is also concern about overwhelming hospitals with a strain on the availability of beds, ventilators, and airborne isolation rooms. The CDC is recommending leveraging telehealth tools to direct people to the right level of health care for their medical needs. Hospitalization should only be for the sickest patients.17
Funding for a pandemic response is of paramount importance. Proposed 2021 federal budget cuts include $2.9 billion in cuts to the National Institutes of Health, and $708 million in cuts to the CDC, which makes the situation look especially worrisome as we face a potentially severe pandemic. The Infectious Diseases Society of America identifies antimicrobial resistance, NIH research, global health security, global HIV epidemic, and CDC vaccine programs as five “deeply underfunded” areas in the federal budget.18
The NIH has recently begun the first randomized clinical trial, treating patients at the University of Nebraska with laboratory-confirmed SARS-CoV-2 with a broad-spectrum antiviral drug called remdesivir. Patients from the Diamond Princess Cruise ship are also participating in this clinical trial. This study will hopefully shed light on potential treatments for coronavirus to stop or alleviate the consequences in real time. Similar clinical trials are also occurring in China.19
Vaccine development is underway in many public and private research facilities, but it will take approximately 6-18 months before they will be available for use. In the absence of a vaccine or therapeutic, community mitigation measures are the primary method to respond to the widespread transmission, and supportive care is the current medical treatment. In the case of a pandemic, the mitigation measures might include school dismissals and social distancing in other settings, like suspension of mass gatherings, telework and remote-meeting options in workplaces.
Many respected medical journals in the United States have made access to SARS-CoV-2 articles and literature readily and freely available, which is a remarkable step. Multiple societies and journals have made information available in real time and have used media effectively (e.g., podcasts, e-learning) to disseminate information to the general public. Articles have been made available in other languages, including Chinese.
Conclusions
In summary, there have been 3,280 total deaths attributable to SARS-CoV-2 to date globally, mostly among geriatric patients with comorbidities. To provide some perspective on the statistics, influenza has killed almost 14,000 patients this season alone (much more than coronavirus). COVID-19 is undoubtedly a global public health threat. We in the U.S. health care system are taking swift public health actions, including isolation of patients and contacts to prevent secondary spread, but it is unclear if this is enough to stop an outbreak from becoming a pandemic.
The CDC is warning of significant social and economic disruption in the coming weeks, with more expected community spread and confirmed cases. It is challenging to prepare for a pandemic when the transmission dynamics are not clearly known, the duration of infectiousness is not well defined, and asymptomatic transmission is a possibility. It is time for the public to be informed from trusted sources and avoid unverified information, especially on social media which can lead to confusion and panic. The spread of COVID-19 infection in the United States is inevitable, and there must be sufficient, well-coordinated planning that can curtail the spread and reduce the impact.
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. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson. Ms. Sathya Areti is a 3rd-year medical student at the Virginia Commonwealth University School of Medicine (class of 2021), planning to apply into Internal Medicine-Pediatrics. Dr. Swetha Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is also a member of the Wellspan Pharmacy and Therapeutics committee.
References
1. Phelan AL et al. The novel coronavirus originating in Wuhan, China: Challenges for global health governance. JAMA. 2020;323(8):709-10. doi: 10.1001/jama.2020.1097.
2. del Rio C, Malani PN. 2019 Novel coronavirus – Important information for clinicians. JAMA. Published online Feb. 5, 2020. doi: 10.1001/jama.2020.1490.
3. Gorbalenya AE et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group. bioRxiv. Published Jan. 1, 2020. doi: 10.1101/2020.02.07.937862.
4. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.
5. Coronavirus disease 2019 (COVID-19). Situation Report – 40. Published Feb. 29, 2020.
6. Kaiyuan Sun, et al. Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population level observational study, Feb. 20, 2020. Lancet Digital Health 2020. doi: 10.1016/S2589-7500(20)30026-1.
7. Rolfes MA et al. Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness. Influenza Other Respir Viruses. 2018;12(1):132-7. doi: 10.1111/irv.12486.
8. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.
9. Jablon R, Baumann L. Washington governor declares state of emergency over virus. AP News. Published Feb. 29, 2020.
10. Jernigan DB, CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-219. doi: 10.15585/mmwr.mm6908e1.
11. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb 24, 2020.
12. Hines M. Coronavirus: Travel advisory for Italy, South Korea raised to level 4, ‘Do Not Travel’. USA Today. Published Feb. 29, 2020.
13. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb. 24, 2020.
14. CDC Tests for COVID-19. Centers for Disease Control and Prevention. Published Feb. 25, 2020.
15. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-19. doi: 10.15585/mmwr.mm6908e1.
16. Gunia A. The global shortage of medical masks won’t be easing soon. Time. Published Feb. 27, 2020.
17. CDC in action: Preparing communities for potential spread of COVID-19. Centers for Disease Control and Prevention. Published Feb. 23, 2020.
18. Kadets L. White House budget cuts vital domestic and global public health programs. IDSA Home. Published 2020.
19. NIH clinical trial of remdesivir to treat COVID-19 begins. National Institutes of Health. Feb. 25, 2020.
Background
On Dec. 31, 2019, the Chinese city of Wuhan reported an outbreak of pneumonia from an unknown cause. The outbreak was found to be linked to the Hunan seafood market because of a shared history of exposure by many patients. After a full-scale investigation, China’s Center for Disease Control activated a level 2 emergency response on Jan. 4, 2020. A novel coronavirus was officially identified as a causative pathogen for the outbreak.1
Coronavirus, first discovered in the 1960s, is a respiratory RNA virus, most commonly associated with the “common cold.” However, we have had two highly pathogenic forms of coronavirus that originated from animal reservoirs, leading to global epidemics. This includes SARS-CoV in 2002-2004 and MERS-CoV in 2012 with more than 10,000 combined cases. The primary host has been bats, but mammals like camels, cattle, cats, and palm civets have been intermediate hosts in previous epidemics.2
The International Committee on Taxonomy of Viruses named the 2019-nCoV officially as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease, COVID-19, on Feb. 11, 2020.3 Currently, the presentation includes fever, cough, trouble breathing, fatigue, and, rarely, watery diarrhea. More severe presentations include respiratory failure and death. Based on the incubation period of illness for Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses, as well as observational data from reports of travel-related COVID-19, CDC estimates that symptoms of COVID-19 occur within 2-14 days after exposure. Asymptomatic transmission is also documented in some cases.4
On Jan. 13, the first case of COVID-19 outside of China was identified in Thailand. On Jan. 21, the first case of COVID-19 was identified in the United States. On Jan. 23, Chinese authorities suspended travel in and out of Wuhan, followed by other cities in the Hubei Province, leading to a quarantine of 50 million people. By Jan. 30, the World Health Organization had identified COVID-19 as the highest level of an epidemic alert referred to as a PHEIC: Public Health Emergency of International Concern. On Feb. 2, the first death outside China from coronavirus was reported in the Philippines. As of March 4 there have been 95,000 confirmed cases and 3,246 deaths globally. Within China, there have been 80,200 cases with 2,981 deaths.5
Cases have now been diagnosed in increasing numbers in Italy, Japan, South Korea, Iran, and 76 countries. Of note, the fatalities were of patients already in critical condition, who were typically older (more than 60 years old, especially more than 80) and immunocompromised with comorbid conditions (cardiovascular disease, diabetes, chronic respiratory disease, cancer).6 To put this in perspective, since 2010, CDC reports 140,000-810,000 hospitalizations and 12,000-61,000 deaths from the influenza virus annually in the US.7
The current situation in the United States
In the United States, as of March 4, 2020, there are currently 152 confirmed cases in 16 states. The first U.S. case of coronavirus without any of the travel-related and exposure risk factors was identified on Feb. 27 in California, indicating the first instance of community spread.8 The first death was reported in Washington state on Feb. 28, after which the state’s governor declared a state of emergency.9 On March 1, Washington state health officials investigated an outbreak of coronavirus at a long-term nursing facility in which two people tested positive for the disease, heralding the probable first nosocomial transmission of the virus in the United States. Since then, there have been 10 deaths in Washington state related to the coronavirus.
Current interventions in the United States
The U.S. Centers for Disease Control and Prevention is leading a multiagency effort to combat the COVID-19 potential pandemic. A Feb. 24 report in Morbidity and Mortality Weekly Report revealed that 1,336 CDC staff members have been involved in the COVID-19 response.10 CDC staff members have been deployed to 39 locations in the United States and internationally. CDC staff members are working with state and local health departments and other public health authorities to assist with case identification, contact tracing, evaluation of persons under investigation (PUI) for COVID-19, and medical management of cases, as well as with research and academic institutions to understand the virulence, risk for transmission, and other characteristics of this novel virus. The CDC is also working with other agencies of the U.S. government including the U.S. Department of Defense, Department of Health & Human Services and the U.S. Department of State to safely evacuate U.S. citizens, residents, and their families from international locations with high incidence and transmission of COVID-19.
Specific real-time updated guidance has been developed and posted online for health care settings for patient management, infection control and prevention, laboratory testing, environmental cleaning, worker safety, and international travel. The CDC has developed communications materials in English and Spanish for communities and guidance for health care settings, public health, laboratories, schools, and businesses to prepare for a potential pandemic. Travel advisories to countries affected by the epidemic are regularly updated to inform travelers and clinicians about current health issues that need to be considered before travel.11 A level 3 travel notice (avoid all nonessential travel) for China has been in effect since Jan. 27, and on Feb. 29 this was upgraded to a level 4 travel notice.12 Airport screening has been implemented in the 11 U.S. international airports to which flights from China have been diverted, and a total of 46,016 air travelers had been screened by Feb. 23. Incoming passengers are screened for fever, cough, and shortness of breath.
Currently, the CDC has a comprehensive algorithm for further investigation of a PUI – fever, cough, shortness of breath, and a history of travel to areas with increased coronavirus circulation within 14 days of onset of symptoms, OR a close household contact of a confirmed case. When there is a PUI, the current protocol indicates health care providers should alert a local or state health department official. After the health department completes a case investigation, the CDC will help transport specimens (upper respiratory and lower respiratory specimens, and sometimes stool or urine) as soon as possible to the centralized lab for polymerase chain reaction (PCR) testing.13 CDC laboratories are currently using real-time reverse transcription–PCR (RT-PCR). The CDC is also developing a serologic test to assist with surveillance for SARS-CoV-2 circulation in the U.S. population. There is also a safe repository of viral isolates set up to help with sharing of isolates with academic institutions for research purposes.14
At hospitals and outpatient offices in the United States, we are preparing for potential cases by reminding frontline health care workers to routinely ask about travel history in addition to relevant symptoms. By eliciting the history early, they should be able to identify and isolate PUIs, appropriately minimizing exposure. Some facilities are displaying signage in waiting rooms to alert patients to provide relevant history, helping to improve triage. COVID-19 symptoms are like those of influenza (e.g., fever, cough, and shortness of breath), and the current outbreak is occurring during a time of year when respiratory illnesses from influenza and other viruses are highly prevalent. To prevent influenza and possible unnecessary evaluation for COVID-19, all persons aged 6 months and older are strongly encouraged to receive an annual influenza vaccine.
To decrease the risk for respiratory disease, persons can practice recommended preventive measures. Persons ill with symptoms of COVID-19 who have had contact with a person with COVID-19, or recent travel to countries with apparent community spread, should proactively communicate with their health care provider before showing up at the health care facility to help make arrangements to prevent possible transmission in the health care setting. In a medical emergency, they should inform emergency medical personnel about possible COVID-19 exposure. If found positive, the current recommendation is to place patients on airborne isolation. N95 masks are being recommended for health care professionals. Hospitals are reinforcing effective infection control procedures, updating pandemic preparedness protocols, and ensuring adequate supplies in the case of an enormous influx of patients.15
Challenges and opportunities
Many challenges present in the process of getting prepared for a potential outbreak. Personal protective equipment such as N-95 masks are in short supply, as they are in high demand in the general public.16 The CDC currently does not recommend that members of the general public use face masks, given low levels of circulation of SARS-CoV-2 currently in the United States. The CDC has developed several documents regarding infection control, hospital preparedness assessments, personal protective equipment (PPE) supply planning, clinical evaluation and management, and respirator conservation strategies.
The RT-PCR test developed by the CDC has had some setbacks, with recent testing kits showing “inconclusive results.” The testing was initially available only through the CDC lab in Atlanta, with a 48-hour turnaround. This led to potential delays in diagnosis and the timely isolation and treatment of infected patients. On March 3, the CDC broadened the guidelines for coronavirus testing, allowing clinicians to order a test for any patients who have symptoms of COVID-19 infection. The greatest need is for decentralized testing in local and state labs, as well as validated testing in local hospitals and commercial labs. The ability to develop and scale-up diagnostic abilities is critically important.
There is also concern about overwhelming hospitals with a strain on the availability of beds, ventilators, and airborne isolation rooms. The CDC is recommending leveraging telehealth tools to direct people to the right level of health care for their medical needs. Hospitalization should only be for the sickest patients.17
Funding for a pandemic response is of paramount importance. Proposed 2021 federal budget cuts include $2.9 billion in cuts to the National Institutes of Health, and $708 million in cuts to the CDC, which makes the situation look especially worrisome as we face a potentially severe pandemic. The Infectious Diseases Society of America identifies antimicrobial resistance, NIH research, global health security, global HIV epidemic, and CDC vaccine programs as five “deeply underfunded” areas in the federal budget.18
The NIH has recently begun the first randomized clinical trial, treating patients at the University of Nebraska with laboratory-confirmed SARS-CoV-2 with a broad-spectrum antiviral drug called remdesivir. Patients from the Diamond Princess Cruise ship are also participating in this clinical trial. This study will hopefully shed light on potential treatments for coronavirus to stop or alleviate the consequences in real time. Similar clinical trials are also occurring in China.19
Vaccine development is underway in many public and private research facilities, but it will take approximately 6-18 months before they will be available for use. In the absence of a vaccine or therapeutic, community mitigation measures are the primary method to respond to the widespread transmission, and supportive care is the current medical treatment. In the case of a pandemic, the mitigation measures might include school dismissals and social distancing in other settings, like suspension of mass gatherings, telework and remote-meeting options in workplaces.
Many respected medical journals in the United States have made access to SARS-CoV-2 articles and literature readily and freely available, which is a remarkable step. Multiple societies and journals have made information available in real time and have used media effectively (e.g., podcasts, e-learning) to disseminate information to the general public. Articles have been made available in other languages, including Chinese.
Conclusions
In summary, there have been 3,280 total deaths attributable to SARS-CoV-2 to date globally, mostly among geriatric patients with comorbidities. To provide some perspective on the statistics, influenza has killed almost 14,000 patients this season alone (much more than coronavirus). COVID-19 is undoubtedly a global public health threat. We in the U.S. health care system are taking swift public health actions, including isolation of patients and contacts to prevent secondary spread, but it is unclear if this is enough to stop an outbreak from becoming a pandemic.
The CDC is warning of significant social and economic disruption in the coming weeks, with more expected community spread and confirmed cases. It is challenging to prepare for a pandemic when the transmission dynamics are not clearly known, the duration of infectiousness is not well defined, and asymptomatic transmission is a possibility. It is time for the public to be informed from trusted sources and avoid unverified information, especially on social media which can lead to confusion and panic. The spread of COVID-19 infection in the United States is inevitable, and there must be sufficient, well-coordinated planning that can curtail the spread and reduce the impact.
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. Palabindala is hospital medicine division chief at the University of Mississippi Medical Center, Jackson. Ms. Sathya Areti is a 3rd-year medical student at the Virginia Commonwealth University School of Medicine (class of 2021), planning to apply into Internal Medicine-Pediatrics. Dr. Swetha Areti is currently working as a hospitalist at Wellspan Chambersburg Hospital and is also a member of the Wellspan Pharmacy and Therapeutics committee.
References
1. Phelan AL et al. The novel coronavirus originating in Wuhan, China: Challenges for global health governance. JAMA. 2020;323(8):709-10. doi: 10.1001/jama.2020.1097.
2. del Rio C, Malani PN. 2019 Novel coronavirus – Important information for clinicians. JAMA. Published online Feb. 5, 2020. doi: 10.1001/jama.2020.1490.
3. Gorbalenya AE et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group. bioRxiv. Published Jan. 1, 2020. doi: 10.1101/2020.02.07.937862.
4. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.
5. Coronavirus disease 2019 (COVID-19). Situation Report – 40. Published Feb. 29, 2020.
6. Kaiyuan Sun, et al. Early epidemiological analysis of the coronavirus disease 2019 outbreak based on crowdsourced data: a population level observational study, Feb. 20, 2020. Lancet Digital Health 2020. doi: 10.1016/S2589-7500(20)30026-1.
7. Rolfes MA et al. Annual estimates of the burden of seasonal influenza in the United States: A tool for strengthening influenza surveillance and preparedness. Influenza Other Respir Viruses. 2018;12(1):132-7. doi: 10.1111/irv.12486.
8. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020;69:216-19. doi: 10.15585/mmwr.mm6908e1.
9. Jablon R, Baumann L. Washington governor declares state of emergency over virus. AP News. Published Feb. 29, 2020.
10. Jernigan DB, CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-219. doi: 10.15585/mmwr.mm6908e1.
11. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb 24, 2020.
12. Hines M. Coronavirus: Travel advisory for Italy, South Korea raised to level 4, ‘Do Not Travel’. USA Today. Published Feb. 29, 2020.
13. Information for health departments on reporting a person under investigation (PUI) or laboratory-confirmed case for COVID-19. Centers for Disease Control and Prevention. Published Feb. 24, 2020.
14. CDC Tests for COVID-19. Centers for Disease Control and Prevention. Published Feb. 25, 2020.
15. Jernigan DB. CDC COVID-19 response team. Update: Public health response to the coronavirus disease 2019 outbreak – United States, Feb. 24, 2020. MMWR Morbidity and Mortality Weekly Report 2020; 69:216-19. doi: 10.15585/mmwr.mm6908e1.
16. Gunia A. The global shortage of medical masks won’t be easing soon. Time. Published Feb. 27, 2020.
17. CDC in action: Preparing communities for potential spread of COVID-19. Centers for Disease Control and Prevention. Published Feb. 23, 2020.
18. Kadets L. White House budget cuts vital domestic and global public health programs. IDSA Home. Published 2020.
19. NIH clinical trial of remdesivir to treat COVID-19 begins. National Institutes of Health. Feb. 25, 2020.