COVID-19 Updates

Many women who got a COVID-19 vaccine have reported heavier bleeding during their periods since they had the shots.

A team of researchers investigated the trend and set out to find out who among the vaccinated were more likely to experience the menstruation changes.

The researchers were led by Katharine M.N. Lee, PhD, MS, of the division of public health sciences at Washington University in St. Louis. Their findings were published ahead of print in Science Advances.

The investigators analyzed more than 139,000 responses from an online survey from both currently and formerly menstruating women.

They found that, among people who have regular periods, about the same percentage had heavier bleeding after they got a COVID vaccine as had no change in bleeding after the vaccine (44% vs. 42%, respectively).

“A much smaller portion had lighter periods,” they write.

The phenomenon has been difficult to study because questions about changes in menstruation are not a standard part of vaccine trials.

Date of last period is often tracked in clinical trials to make sure a participant is not pregnant, but the questions about periods often stop there.

Additionally, periods are different for everyone and can be influenced by all sorts of environmental factors, so making associations regarding exposures is problematic.
 

No changes found to fertility

The authors emphasized that, generally, changes to menstrual bleeding are not uncommon nor dangerous. They also emphasized that the changes in bleeding don’t mean changes to fertility.

The uterine reproductive system is flexible when the body is under stress, they note.

“We know that running a marathon may influence hormone concentrations in the short term while not rendering that person infertile,” the authors write.

However, they acknowledge that investigating these reports is critical in building trust in medicine.

This report includes information that hasn’t been available through the clinical trial follow-up process.

For instance, the authors write, “To the best of our knowledge, our work is the first to examine breakthrough bleeding after vaccination in either pre- or postmenopausal people.”

Reports of changes to periods after vaccination started emerging in 2021. But without data, reports were largely dismissed, fueling criticism from those waging campaigns against COVID vaccines.

Dr. Lee and colleagues gathered data from those who responded to the online survey and detailed some trends.

People who were bleeding more heavily after vaccination were more likely to be older, Hispanic, had vaccine side effects of fever and fatigue, had been pregnant at some point, or had given birth.

People with regular periods who had endometriosis, prolonged bleeding during their periods, polycystic ovarian syndrome (PCOS) or fibroids were also more likely to have increased bleeding after a COVID vaccine.
 

Breakthrough bleeding

For people who don’t menstruate, but have not reached menopause, breakthrough bleeding happened more often in women who had been pregnant and/or had given birth.

Among respondents who were postmenopausal, breakthrough bleeding happened more often in younger people and/or those who are Hispanic.

More than a third of the respondents (39%) who use gender-affirming hormones that eliminate menstruation reported breakthrough bleeding after vaccination.

The majority of premenopausal people on long-acting, reversible contraception (71%) and the majority of postmenopausal respondents (66%) had breakthrough bleeding as well.

The authors note that you can’t compare the percentages who report these experiences in the survey with the incidence of those who would experience changes in menstrual bleeding in the general population.

The nature of the online survey means it may be naturally biased because the people who responded may be more often those who noted some change in their own menstrual experiences, particularly if that involved discomfort, pain, or fear.

Researchers also acknowledge that Black, Indigenous, Latinx, and other respondents of color are underrepresented in this research and that represents a limitation in the work.

Alison Edelman, MD, MPH, with the department of obstetrics and gynecology at Oregon Health & Science University in Portland, was not involved with Dr. Lee and associates’ study but has also studied the relationship between COVID vaccines and menstruation.

Her team’s study found that COVID vaccination is associated with a small change in time between periods but not length of periods.

She said about the work by Dr. Lee and colleagues, “This work really elevates the voices of the public and what they’re experiencing.”

The association makes sense, Dr. Edelman says, in that the reproductive system and the immune system talk to each other and inflammation in the immune system is going to be noticed by the system governing periods.

Lack of data on the relationship between exposures and menstruation didn’t start with COVID. “There has been a signal in the population before with other vaccines that’s been dismissed,” she said.

Tracking menstruation information in clinical trials can help physicians counsel women on what may be coming with any vaccine and alleviate fears and vaccine hesitancy, Dr. Edelman explained. It can also help vaccine developers know what to include in information about their product.

“When you are counseled about what to expect, it’s not as scary. That provides trust in the system,” she said. She likened it to original lack of data on whether COVID-19 vaccines would affect pregnancy.

“We have great science now that COVID vaccine does not affect fertility and [vaccine] does not impact pregnancy.”

Another important aspect of this paper is that it included subgroups not studied before regarding menstruation and breakthrough bleeding, such as those taking gender-affirming hormones, she added.

Menstruation has been often overlooked as important in clinical trial exposures but Dr. Edelman hopes this recent attention and question will escalate and prompt more research.

“I’m hoping with the immense outpouring from the public about how important this is, that future studies will look at this a little bit better,” she says.

She said when the National Institutes of Health opened up funding for trials on COVID-19 vaccines and menstruation, researchers got flooded with requests from women to share their stories.

“As a researcher – I’ve been doing research for over 20 years – that’s not something that usually happens. I would love to have that happen for every research project.”

The authors and Dr. Edelman declare that they have no competing interests. This research was supported in part by the University of Illinois Beckman Institute for Advanced Science and Technology, the University of Illinois Interdisciplinary Health Sciences Institute, the National Institutes of Health, the Foundation for Barnes-Jewish Hospital, and the Siteman Cancer Center.

Many women who got a COVID-19 vaccine have reported heavier bleeding during their periods since they had the shots.

A team of researchers investigated the trend and set out to find out who among the vaccinated were more likely to experience the menstruation changes.

The researchers were led by Katharine M.N. Lee, PhD, MS, of the division of public health sciences at Washington University in St. Louis. Their findings were published ahead of print in Science Advances.

The investigators analyzed more than 139,000 responses from an online survey from both currently and formerly menstruating women.

They found that, among people who have regular periods, about the same percentage had heavier bleeding after they got a COVID vaccine as had no change in bleeding after the vaccine (44% vs. 42%, respectively).

“A much smaller portion had lighter periods,” they write.

The phenomenon has been difficult to study because questions about changes in menstruation are not a standard part of vaccine trials.

Date of last period is often tracked in clinical trials to make sure a participant is not pregnant, but the questions about periods often stop there.

Additionally, periods are different for everyone and can be influenced by all sorts of environmental factors, so making associations regarding exposures is problematic.
 

No changes found to fertility

The authors emphasized that, generally, changes to menstrual bleeding are not uncommon nor dangerous. They also emphasized that the changes in bleeding don’t mean changes to fertility.

The uterine reproductive system is flexible when the body is under stress, they note.

“We know that running a marathon may influence hormone concentrations in the short term while not rendering that person infertile,” the authors write.

However, they acknowledge that investigating these reports is critical in building trust in medicine.

This report includes information that hasn’t been available through the clinical trial follow-up process.

For instance, the authors write, “To the best of our knowledge, our work is the first to examine breakthrough bleeding after vaccination in either pre- or postmenopausal people.”

Reports of changes to periods after vaccination started emerging in 2021. But without data, reports were largely dismissed, fueling criticism from those waging campaigns against COVID vaccines.

Dr. Lee and colleagues gathered data from those who responded to the online survey and detailed some trends.

People who were bleeding more heavily after vaccination were more likely to be older, Hispanic, had vaccine side effects of fever and fatigue, had been pregnant at some point, or had given birth.

People with regular periods who had endometriosis, prolonged bleeding during their periods, polycystic ovarian syndrome (PCOS) or fibroids were also more likely to have increased bleeding after a COVID vaccine.
 

Breakthrough bleeding

For people who don’t menstruate, but have not reached menopause, breakthrough bleeding happened more often in women who had been pregnant and/or had given birth.

Among respondents who were postmenopausal, breakthrough bleeding happened more often in younger people and/or those who are Hispanic.

More than a third of the respondents (39%) who use gender-affirming hormones that eliminate menstruation reported breakthrough bleeding after vaccination.

The majority of premenopausal people on long-acting, reversible contraception (71%) and the majority of postmenopausal respondents (66%) had breakthrough bleeding as well.

The authors note that you can’t compare the percentages who report these experiences in the survey with the incidence of those who would experience changes in menstrual bleeding in the general population.

The nature of the online survey means it may be naturally biased because the people who responded may be more often those who noted some change in their own menstrual experiences, particularly if that involved discomfort, pain, or fear.

Researchers also acknowledge that Black, Indigenous, Latinx, and other respondents of color are underrepresented in this research and that represents a limitation in the work.

Alison Edelman, MD, MPH, with the department of obstetrics and gynecology at Oregon Health & Science University in Portland, was not involved with Dr. Lee and associates’ study but has also studied the relationship between COVID vaccines and menstruation.

Her team’s study found that COVID vaccination is associated with a small change in time between periods but not length of periods.

She said about the work by Dr. Lee and colleagues, “This work really elevates the voices of the public and what they’re experiencing.”

The association makes sense, Dr. Edelman says, in that the reproductive system and the immune system talk to each other and inflammation in the immune system is going to be noticed by the system governing periods.

Lack of data on the relationship between exposures and menstruation didn’t start with COVID. “There has been a signal in the population before with other vaccines that’s been dismissed,” she said.

Tracking menstruation information in clinical trials can help physicians counsel women on what may be coming with any vaccine and alleviate fears and vaccine hesitancy, Dr. Edelman explained. It can also help vaccine developers know what to include in information about their product.

“When you are counseled about what to expect, it’s not as scary. That provides trust in the system,” she said. She likened it to original lack of data on whether COVID-19 vaccines would affect pregnancy.

“We have great science now that COVID vaccine does not affect fertility and [vaccine] does not impact pregnancy.”

Another important aspect of this paper is that it included subgroups not studied before regarding menstruation and breakthrough bleeding, such as those taking gender-affirming hormones, she added.

Menstruation has been often overlooked as important in clinical trial exposures but Dr. Edelman hopes this recent attention and question will escalate and prompt more research.

“I’m hoping with the immense outpouring from the public about how important this is, that future studies will look at this a little bit better,” she says.

She said when the National Institutes of Health opened up funding for trials on COVID-19 vaccines and menstruation, researchers got flooded with requests from women to share their stories.

“As a researcher – I’ve been doing research for over 20 years – that’s not something that usually happens. I would love to have that happen for every research project.”

The authors and Dr. Edelman declare that they have no competing interests. This research was supported in part by the University of Illinois Beckman Institute for Advanced Science and Technology, the University of Illinois Interdisciplinary Health Sciences Institute, the National Institutes of Health, the Foundation for Barnes-Jewish Hospital, and the Siteman Cancer Center.

Many women who got a COVID-19 vaccine have reported heavier bleeding during their periods since they had the shots.

A team of researchers investigated the trend and set out to find out who among the vaccinated were more likely to experience the menstruation changes.

The researchers were led by Katharine M.N. Lee, PhD, MS, of the division of public health sciences at Washington University in St. Louis. Their findings were published ahead of print in Science Advances.

The investigators analyzed more than 139,000 responses from an online survey from both currently and formerly menstruating women.

They found that, among people who have regular periods, about the same percentage had heavier bleeding after they got a COVID vaccine as had no change in bleeding after the vaccine (44% vs. 42%, respectively).

“A much smaller portion had lighter periods,” they write.

The phenomenon has been difficult to study because questions about changes in menstruation are not a standard part of vaccine trials.

Date of last period is often tracked in clinical trials to make sure a participant is not pregnant, but the questions about periods often stop there.

Additionally, periods are different for everyone and can be influenced by all sorts of environmental factors, so making associations regarding exposures is problematic.
 

No changes found to fertility

The authors emphasized that, generally, changes to menstrual bleeding are not uncommon nor dangerous. They also emphasized that the changes in bleeding don’t mean changes to fertility.

The uterine reproductive system is flexible when the body is under stress, they note.

“We know that running a marathon may influence hormone concentrations in the short term while not rendering that person infertile,” the authors write.

However, they acknowledge that investigating these reports is critical in building trust in medicine.

This report includes information that hasn’t been available through the clinical trial follow-up process.

For instance, the authors write, “To the best of our knowledge, our work is the first to examine breakthrough bleeding after vaccination in either pre- or postmenopausal people.”

Reports of changes to periods after vaccination started emerging in 2021. But without data, reports were largely dismissed, fueling criticism from those waging campaigns against COVID vaccines.

Dr. Lee and colleagues gathered data from those who responded to the online survey and detailed some trends.

People who were bleeding more heavily after vaccination were more likely to be older, Hispanic, had vaccine side effects of fever and fatigue, had been pregnant at some point, or had given birth.

People with regular periods who had endometriosis, prolonged bleeding during their periods, polycystic ovarian syndrome (PCOS) or fibroids were also more likely to have increased bleeding after a COVID vaccine.
 

Breakthrough bleeding

For people who don’t menstruate, but have not reached menopause, breakthrough bleeding happened more often in women who had been pregnant and/or had given birth.

Among respondents who were postmenopausal, breakthrough bleeding happened more often in younger people and/or those who are Hispanic.

More than a third of the respondents (39%) who use gender-affirming hormones that eliminate menstruation reported breakthrough bleeding after vaccination.

The majority of premenopausal people on long-acting, reversible contraception (71%) and the majority of postmenopausal respondents (66%) had breakthrough bleeding as well.

The authors note that you can’t compare the percentages who report these experiences in the survey with the incidence of those who would experience changes in menstrual bleeding in the general population.

The nature of the online survey means it may be naturally biased because the people who responded may be more often those who noted some change in their own menstrual experiences, particularly if that involved discomfort, pain, or fear.

Researchers also acknowledge that Black, Indigenous, Latinx, and other respondents of color are underrepresented in this research and that represents a limitation in the work.

Alison Edelman, MD, MPH, with the department of obstetrics and gynecology at Oregon Health & Science University in Portland, was not involved with Dr. Lee and associates’ study but has also studied the relationship between COVID vaccines and menstruation.

Her team’s study found that COVID vaccination is associated with a small change in time between periods but not length of periods.

She said about the work by Dr. Lee and colleagues, “This work really elevates the voices of the public and what they’re experiencing.”

The association makes sense, Dr. Edelman says, in that the reproductive system and the immune system talk to each other and inflammation in the immune system is going to be noticed by the system governing periods.

Lack of data on the relationship between exposures and menstruation didn’t start with COVID. “There has been a signal in the population before with other vaccines that’s been dismissed,” she said.

Tracking menstruation information in clinical trials can help physicians counsel women on what may be coming with any vaccine and alleviate fears and vaccine hesitancy, Dr. Edelman explained. It can also help vaccine developers know what to include in information about their product.

“When you are counseled about what to expect, it’s not as scary. That provides trust in the system,” she said. She likened it to original lack of data on whether COVID-19 vaccines would affect pregnancy.

“We have great science now that COVID vaccine does not affect fertility and [vaccine] does not impact pregnancy.”

Another important aspect of this paper is that it included subgroups not studied before regarding menstruation and breakthrough bleeding, such as those taking gender-affirming hormones, she added.

Menstruation has been often overlooked as important in clinical trial exposures but Dr. Edelman hopes this recent attention and question will escalate and prompt more research.

“I’m hoping with the immense outpouring from the public about how important this is, that future studies will look at this a little bit better,” she says.

She said when the National Institutes of Health opened up funding for trials on COVID-19 vaccines and menstruation, researchers got flooded with requests from women to share their stories.

“As a researcher – I’ve been doing research for over 20 years – that’s not something that usually happens. I would love to have that happen for every research project.”

The authors and Dr. Edelman declare that they have no competing interests. This research was supported in part by the University of Illinois Beckman Institute for Advanced Science and Technology, the University of Illinois Interdisciplinary Health Sciences Institute, the National Institutes of Health, the Foundation for Barnes-Jewish Hospital, and the Siteman Cancer Center.

Priapism is a disorder that occurs when the penis maintains a prolonged erection in the absence of appropriate stimulation. The disorder is typically divided into subgroups based on arterial flow: low flow (ischemic) and high flow (nonischemic). Ischemic priapism is the most common form and results from venous congestion due to obstructed outflow and inability of cavernous smooth muscle to contract, resulting in compartment syndrome, tissue hypoxia, hypercapnia, and acidosis.¹ Conditions that result in hypercoagulable states and hyperviscosity are associated with ischemic priapism. COVID-19 is well known to cause an acute respiratory illness and systemic inflammatory response and has been increasingly associated with coagulopathy. Studies have shown that 20% to 55% of patients admitted to the hospital for COVID-19 show objective laboratory evidence of a hypercoagulable state.²

To date, there are 6 reported cases of priapism occurring in the setting of COVID-19 with all cases demonstrating the ischemic subtype. The onset of priapism from the beginning of infectious symptoms ranged from 2 days to more than a month. Five of the cases occurred in patients with critical COVID-19 and 1 in the setting of mild disease.^3-8 Two critically ill patients did not receive treatment for their ischemic priapism as they were transitioned to expectant management and/or comfort measures.Most were treated with cavernosal blood aspiration and intracavernosal injections of phenylephrine or ethylephrine. Some patients were managed with prophylactic doses of anticoagulation after the identification of priapism; others were transitioned to therapeutic doses. Two patients were followed postdischarge; one patient reported normal nighttime erections with sexual desire 2 weeks postdischarge, and another patient, who underwent a bilateral T-shunt procedure after unsuccessful phenylephrine injections, reported complete erectile dysfunction at 3 months postdischarge.^4,7 There was a potentially confounding variable in 2 cases in which propofol infusions were used for sedation management in the setting of mechanical ventilation.^6,8 Propofol has been linked to priapism through its blockade of sympathetic activation resulting in persistent relaxation of cavernosal smooth muscle.⁹ We present a unique case of COVID-19–associated ischemic priapism as our patient had moderate rather than critical COVID-19.

Case Presentation

A 67-year-old male patient presented to the emergency department for a painful erection of 34-hour duration. The patient had been exposed to COVID-19 roughly 2 months prior. Since the exposure, he had experienced headache, nonproductive cough, sore throat, and decreased appetite with weight loss. His medical history included hypertension, thoracic aortic aneurysm, B-cell type chronic lymphocytic leukemia (CLL), and obstructive sleep apnea. Daily outpatient medications included atenolol 100 mg, hydrochlorothiazide 25 mg, and omeprazole 20 mg. The patient stopped tobacco use about 30 years previously. He reported no alcohol consumption or illicit drug use and had no previous episodes of prolonged erection.

The patient was afebrile, hemodynamically stable, and had an oxygen saturation of 92% on room air. Physical examination revealed clear breath sounds and an erect circumcised penis without any lesions, discoloration, or skin necrosis. Laboratory data were remarkable for the following values: 125,660 cells/μL white blood cells (WBCs), 13.82 × 10³/ μL neutrophils, 110.58 × 10³/μL lymphocytes, 1.26 × 10³/μL monocytes, no blasts, 9.4 gm/dL hemoglobin, 100.3 fl mean corpuscular volume, 417,000 cells/μL platelets, 23,671 ng/mL D-dimer, 29.6 seconds activated partial thromboplastin time (aPTT), 16.3 seconds prothrombin time, 743 mg/dL fibrinogen, 474 U/L lactate dehydrogenase, and 202.1 mg/dL haptoglobin. A nasopharyngeal reverse transcription polymerase chain reaction test resulted positive for the SARS-CoV-2 virus, and subsequent chest X-ray revealed bilateral, hazy opacities predominantly in a peripheral distribution. Computed tomography (CT) angiogram of the chest did not reveal pulmonary emboli, pneumothorax, effusions, or lobar consolidation. However, it displayed bilateral ground-glass opacities with interstitial consolidation worst in the upper lobes. Corporal aspiration and blood gas analysis revealed a pH of 7.05, Pco₂ of 64 mm Hg, and Po₂ of 33 mm Hg.

Differential Diagnosis

The first consideration in the differential diagnosis of priapism is to differentiate between ischemic and nonischemic. Based on the abnormal blood gas results above, this case clearly falls within the ischemic spectrum. Ischemic priapism secondary to CLL-induced hyperleukocytosis was considered. It has been noted that up to 20% of priapism cases in adults are related to hematologic disorders.¹⁰ While it is not uncommon to see hyperleukocytosis (total WBC count > 100 × 10⁹/L) in CLL, leukostasis is rare with most reports demonstrating WBC counts > 1000 × 10⁹/L.¹¹ Hematology, vascular surgery, and urology services were consulted and agreed that ischemic priapism was due to microthrombi or pelvic vein thrombosis secondary to COVID-19–associated coagulopathy (CAC) was the most likely etiology.

Treatment

After corporal aspiration, intracorporal phenylephrine was administered. Diluted phenylephrine (100 ug/mL) was injected every 5 to 10 minutes while intermittently aspirating and irrigating multiple sites along the lateral length of the penile shaft. This initial procedure reduced the erection from 100% to 30% rigidity, with repeat blood gas analysis revealing minimal improvement. CT of the abdomen and pelvis with IV contrast revealed no evidence of pelvic thrombi. A second round of phenylephrine injections were administered, resulting in detumescence. The patient was treated with 2 to 3 L/min of oxygen supplementation via nasal cannula, a 5-day course of remdesivir and low-intensity heparin drip. Following the initial low-intensity heparin drip, the patient transitioned to therapeutic enoxaparin and subsequently was discharged on apixaban for a 3-month course. Since discharge, the patient followed up with hematology. He tolerated and completed the anticoagulation regimen without any recurrences of priapism or residual deficits.

Discussion

Recent studies have overwhelmingly analyzed the incidence and presentation of thrombotic complications in critically ill patients with COVID-19. CAC has been postulated to result from endotheliopathy along with immune cell activation and propagation of coagulation. While COVID-19 has been noted to create lung injury through binding angiotensin-converting enzyme 2 receptors expressed on alveolar pneumocytes, it increasingly has been found to affect endothelial cells throughout the body. Recent postmortem analyses have demonstrated direct viral infection of endothelial cells with consequent diffuse endothelial inflammation, as evidenced by viral inclusions, sequestered immune cells, and endothelial apoptosis.^12,13 Manifestations of this endotheliopathy have been delineated through various studies.

An early retrospective study in Wuhan, China, illustrated that 36% of the first 99 patients hospitalized with COVID-19 demonstrated an elevated D-dimer, 6% an elevated aPTT, and 5% an elevated prothrombin time.¹⁴ Another retrospective study conducted in Wuhan found a 25% incidence of venous thromboembolic complications in critically ill patients with severe COVID-19.¹⁵ In the Netherlands, a study reported the incidence of arterial and venous thrombotic complications to be 31% in 184 critically ill patients with COVID-19, with 81% of these cases involving pulmonary emboli.¹⁶

To our knowledge, our patient is the seventh reported case of ischemic priapism occurring in the setting of a COVID-19 infection, and the first to have occurred in its moderate form. Ischemic priapism is often a consequence of penile venous outflow obstruction and resultant stasis of hypoxic blood.⁷ The prothrombotic state induced by CAC has been proposed to cause the obstruction of small emissary veins in the subtunical space and in turn lead to venous stasis, which propagates the formation of ischemic priapism.⁸ Furthermore, 4 of the previously reported cases shared laboratory data on their patients, and all demonstrated elevated D-dimer and fibrinogen levels, which strengthens this hypothesis.^3,5,7,8 CLL presents a potential confounding variable in this case; however, as we have reviewed earlier, the risk of leukostasis at WBC counts < 1000 × 10⁹/L is very low.¹¹ It is also probable that the patient had some level of immune dysregulation secondary to CLL, leading to his prolonged course and slow clearance of the virus.

Conclusions

Although only a handful of CAC cases leading to ischemic priapism have been reported, the true incidence may be much higher. While our case highlights the importance of considering COVID-19 infection in the differential diagnosis of ischemic priapism, more research is needed to understand incidence and definitively establish a causative relationship.

Priapism is a disorder that occurs when the penis maintains a prolonged erection in the absence of appropriate stimulation. The disorder is typically divided into subgroups based on arterial flow: low flow (ischemic) and high flow (nonischemic). Ischemic priapism is the most common form and results from venous congestion due to obstructed outflow and inability of cavernous smooth muscle to contract, resulting in compartment syndrome, tissue hypoxia, hypercapnia, and acidosis.¹ Conditions that result in hypercoagulable states and hyperviscosity are associated with ischemic priapism. COVID-19 is well known to cause an acute respiratory illness and systemic inflammatory response and has been increasingly associated with coagulopathy. Studies have shown that 20% to 55% of patients admitted to the hospital for COVID-19 show objective laboratory evidence of a hypercoagulable state.²

To date, there are 6 reported cases of priapism occurring in the setting of COVID-19 with all cases demonstrating the ischemic subtype. The onset of priapism from the beginning of infectious symptoms ranged from 2 days to more than a month. Five of the cases occurred in patients with critical COVID-19 and 1 in the setting of mild disease.^3-8 Two critically ill patients did not receive treatment for their ischemic priapism as they were transitioned to expectant management and/or comfort measures.Most were treated with cavernosal blood aspiration and intracavernosal injections of phenylephrine or ethylephrine. Some patients were managed with prophylactic doses of anticoagulation after the identification of priapism; others were transitioned to therapeutic doses. Two patients were followed postdischarge; one patient reported normal nighttime erections with sexual desire 2 weeks postdischarge, and another patient, who underwent a bilateral T-shunt procedure after unsuccessful phenylephrine injections, reported complete erectile dysfunction at 3 months postdischarge.^4,7 There was a potentially confounding variable in 2 cases in which propofol infusions were used for sedation management in the setting of mechanical ventilation.^6,8 Propofol has been linked to priapism through its blockade of sympathetic activation resulting in persistent relaxation of cavernosal smooth muscle.⁹ We present a unique case of COVID-19–associated ischemic priapism as our patient had moderate rather than critical COVID-19.

Case Presentation

A 67-year-old male patient presented to the emergency department for a painful erection of 34-hour duration. The patient had been exposed to COVID-19 roughly 2 months prior. Since the exposure, he had experienced headache, nonproductive cough, sore throat, and decreased appetite with weight loss. His medical history included hypertension, thoracic aortic aneurysm, B-cell type chronic lymphocytic leukemia (CLL), and obstructive sleep apnea. Daily outpatient medications included atenolol 100 mg, hydrochlorothiazide 25 mg, and omeprazole 20 mg. The patient stopped tobacco use about 30 years previously. He reported no alcohol consumption or illicit drug use and had no previous episodes of prolonged erection.

The patient was afebrile, hemodynamically stable, and had an oxygen saturation of 92% on room air. Physical examination revealed clear breath sounds and an erect circumcised penis without any lesions, discoloration, or skin necrosis. Laboratory data were remarkable for the following values: 125,660 cells/μL white blood cells (WBCs), 13.82 × 10³/ μL neutrophils, 110.58 × 10³/μL lymphocytes, 1.26 × 10³/μL monocytes, no blasts, 9.4 gm/dL hemoglobin, 100.3 fl mean corpuscular volume, 417,000 cells/μL platelets, 23,671 ng/mL D-dimer, 29.6 seconds activated partial thromboplastin time (aPTT), 16.3 seconds prothrombin time, 743 mg/dL fibrinogen, 474 U/L lactate dehydrogenase, and 202.1 mg/dL haptoglobin. A nasopharyngeal reverse transcription polymerase chain reaction test resulted positive for the SARS-CoV-2 virus, and subsequent chest X-ray revealed bilateral, hazy opacities predominantly in a peripheral distribution. Computed tomography (CT) angiogram of the chest did not reveal pulmonary emboli, pneumothorax, effusions, or lobar consolidation. However, it displayed bilateral ground-glass opacities with interstitial consolidation worst in the upper lobes. Corporal aspiration and blood gas analysis revealed a pH of 7.05, Pco₂ of 64 mm Hg, and Po₂ of 33 mm Hg.

Differential Diagnosis

The first consideration in the differential diagnosis of priapism is to differentiate between ischemic and nonischemic. Based on the abnormal blood gas results above, this case clearly falls within the ischemic spectrum. Ischemic priapism secondary to CLL-induced hyperleukocytosis was considered. It has been noted that up to 20% of priapism cases in adults are related to hematologic disorders.¹⁰ While it is not uncommon to see hyperleukocytosis (total WBC count > 100 × 10⁹/L) in CLL, leukostasis is rare with most reports demonstrating WBC counts > 1000 × 10⁹/L.¹¹ Hematology, vascular surgery, and urology services were consulted and agreed that ischemic priapism was due to microthrombi or pelvic vein thrombosis secondary to COVID-19–associated coagulopathy (CAC) was the most likely etiology.

Treatment

After corporal aspiration, intracorporal phenylephrine was administered. Diluted phenylephrine (100 ug/mL) was injected every 5 to 10 minutes while intermittently aspirating and irrigating multiple sites along the lateral length of the penile shaft. This initial procedure reduced the erection from 100% to 30% rigidity, with repeat blood gas analysis revealing minimal improvement. CT of the abdomen and pelvis with IV contrast revealed no evidence of pelvic thrombi. A second round of phenylephrine injections were administered, resulting in detumescence. The patient was treated with 2 to 3 L/min of oxygen supplementation via nasal cannula, a 5-day course of remdesivir and low-intensity heparin drip. Following the initial low-intensity heparin drip, the patient transitioned to therapeutic enoxaparin and subsequently was discharged on apixaban for a 3-month course. Since discharge, the patient followed up with hematology. He tolerated and completed the anticoagulation regimen without any recurrences of priapism or residual deficits.

Discussion

Recent studies have overwhelmingly analyzed the incidence and presentation of thrombotic complications in critically ill patients with COVID-19. CAC has been postulated to result from endotheliopathy along with immune cell activation and propagation of coagulation. While COVID-19 has been noted to create lung injury through binding angiotensin-converting enzyme 2 receptors expressed on alveolar pneumocytes, it increasingly has been found to affect endothelial cells throughout the body. Recent postmortem analyses have demonstrated direct viral infection of endothelial cells with consequent diffuse endothelial inflammation, as evidenced by viral inclusions, sequestered immune cells, and endothelial apoptosis.^12,13 Manifestations of this endotheliopathy have been delineated through various studies.

An early retrospective study in Wuhan, China, illustrated that 36% of the first 99 patients hospitalized with COVID-19 demonstrated an elevated D-dimer, 6% an elevated aPTT, and 5% an elevated prothrombin time.¹⁴ Another retrospective study conducted in Wuhan found a 25% incidence of venous thromboembolic complications in critically ill patients with severe COVID-19.¹⁵ In the Netherlands, a study reported the incidence of arterial and venous thrombotic complications to be 31% in 184 critically ill patients with COVID-19, with 81% of these cases involving pulmonary emboli.¹⁶

To our knowledge, our patient is the seventh reported case of ischemic priapism occurring in the setting of a COVID-19 infection, and the first to have occurred in its moderate form. Ischemic priapism is often a consequence of penile venous outflow obstruction and resultant stasis of hypoxic blood.⁷ The prothrombotic state induced by CAC has been proposed to cause the obstruction of small emissary veins in the subtunical space and in turn lead to venous stasis, which propagates the formation of ischemic priapism.⁸ Furthermore, 4 of the previously reported cases shared laboratory data on their patients, and all demonstrated elevated D-dimer and fibrinogen levels, which strengthens this hypothesis.^3,5,7,8 CLL presents a potential confounding variable in this case; however, as we have reviewed earlier, the risk of leukostasis at WBC counts < 1000 × 10⁹/L is very low.¹¹ It is also probable that the patient had some level of immune dysregulation secondary to CLL, leading to his prolonged course and slow clearance of the virus.

Conclusions

Although only a handful of CAC cases leading to ischemic priapism have been reported, the true incidence may be much higher. While our case highlights the importance of considering COVID-19 infection in the differential diagnosis of ischemic priapism, more research is needed to understand incidence and definitively establish a causative relationship.

Priapism is a disorder that occurs when the penis maintains a prolonged erection in the absence of appropriate stimulation. The disorder is typically divided into subgroups based on arterial flow: low flow (ischemic) and high flow (nonischemic). Ischemic priapism is the most common form and results from venous congestion due to obstructed outflow and inability of cavernous smooth muscle to contract, resulting in compartment syndrome, tissue hypoxia, hypercapnia, and acidosis.¹ Conditions that result in hypercoagulable states and hyperviscosity are associated with ischemic priapism. COVID-19 is well known to cause an acute respiratory illness and systemic inflammatory response and has been increasingly associated with coagulopathy. Studies have shown that 20% to 55% of patients admitted to the hospital for COVID-19 show objective laboratory evidence of a hypercoagulable state.²

To date, there are 6 reported cases of priapism occurring in the setting of COVID-19 with all cases demonstrating the ischemic subtype. The onset of priapism from the beginning of infectious symptoms ranged from 2 days to more than a month. Five of the cases occurred in patients with critical COVID-19 and 1 in the setting of mild disease.^3-8 Two critically ill patients did not receive treatment for their ischemic priapism as they were transitioned to expectant management and/or comfort measures.Most were treated with cavernosal blood aspiration and intracavernosal injections of phenylephrine or ethylephrine. Some patients were managed with prophylactic doses of anticoagulation after the identification of priapism; others were transitioned to therapeutic doses. Two patients were followed postdischarge; one patient reported normal nighttime erections with sexual desire 2 weeks postdischarge, and another patient, who underwent a bilateral T-shunt procedure after unsuccessful phenylephrine injections, reported complete erectile dysfunction at 3 months postdischarge.^4,7 There was a potentially confounding variable in 2 cases in which propofol infusions were used for sedation management in the setting of mechanical ventilation.^6,8 Propofol has been linked to priapism through its blockade of sympathetic activation resulting in persistent relaxation of cavernosal smooth muscle.⁹ We present a unique case of COVID-19–associated ischemic priapism as our patient had moderate rather than critical COVID-19.

Case Presentation

A 67-year-old male patient presented to the emergency department for a painful erection of 34-hour duration. The patient had been exposed to COVID-19 roughly 2 months prior. Since the exposure, he had experienced headache, nonproductive cough, sore throat, and decreased appetite with weight loss. His medical history included hypertension, thoracic aortic aneurysm, B-cell type chronic lymphocytic leukemia (CLL), and obstructive sleep apnea. Daily outpatient medications included atenolol 100 mg, hydrochlorothiazide 25 mg, and omeprazole 20 mg. The patient stopped tobacco use about 30 years previously. He reported no alcohol consumption or illicit drug use and had no previous episodes of prolonged erection.

The patient was afebrile, hemodynamically stable, and had an oxygen saturation of 92% on room air. Physical examination revealed clear breath sounds and an erect circumcised penis without any lesions, discoloration, or skin necrosis. Laboratory data were remarkable for the following values: 125,660 cells/μL white blood cells (WBCs), 13.82 × 10³/ μL neutrophils, 110.58 × 10³/μL lymphocytes, 1.26 × 10³/μL monocytes, no blasts, 9.4 gm/dL hemoglobin, 100.3 fl mean corpuscular volume, 417,000 cells/μL platelets, 23,671 ng/mL D-dimer, 29.6 seconds activated partial thromboplastin time (aPTT), 16.3 seconds prothrombin time, 743 mg/dL fibrinogen, 474 U/L lactate dehydrogenase, and 202.1 mg/dL haptoglobin. A nasopharyngeal reverse transcription polymerase chain reaction test resulted positive for the SARS-CoV-2 virus, and subsequent chest X-ray revealed bilateral, hazy opacities predominantly in a peripheral distribution. Computed tomography (CT) angiogram of the chest did not reveal pulmonary emboli, pneumothorax, effusions, or lobar consolidation. However, it displayed bilateral ground-glass opacities with interstitial consolidation worst in the upper lobes. Corporal aspiration and blood gas analysis revealed a pH of 7.05, Pco₂ of 64 mm Hg, and Po₂ of 33 mm Hg.

Differential Diagnosis

The first consideration in the differential diagnosis of priapism is to differentiate between ischemic and nonischemic. Based on the abnormal blood gas results above, this case clearly falls within the ischemic spectrum. Ischemic priapism secondary to CLL-induced hyperleukocytosis was considered. It has been noted that up to 20% of priapism cases in adults are related to hematologic disorders.¹⁰ While it is not uncommon to see hyperleukocytosis (total WBC count > 100 × 10⁹/L) in CLL, leukostasis is rare with most reports demonstrating WBC counts > 1000 × 10⁹/L.¹¹ Hematology, vascular surgery, and urology services were consulted and agreed that ischemic priapism was due to microthrombi or pelvic vein thrombosis secondary to COVID-19–associated coagulopathy (CAC) was the most likely etiology.

Treatment

After corporal aspiration, intracorporal phenylephrine was administered. Diluted phenylephrine (100 ug/mL) was injected every 5 to 10 minutes while intermittently aspirating and irrigating multiple sites along the lateral length of the penile shaft. This initial procedure reduced the erection from 100% to 30% rigidity, with repeat blood gas analysis revealing minimal improvement. CT of the abdomen and pelvis with IV contrast revealed no evidence of pelvic thrombi. A second round of phenylephrine injections were administered, resulting in detumescence. The patient was treated with 2 to 3 L/min of oxygen supplementation via nasal cannula, a 5-day course of remdesivir and low-intensity heparin drip. Following the initial low-intensity heparin drip, the patient transitioned to therapeutic enoxaparin and subsequently was discharged on apixaban for a 3-month course. Since discharge, the patient followed up with hematology. He tolerated and completed the anticoagulation regimen without any recurrences of priapism or residual deficits.

Discussion

Recent studies have overwhelmingly analyzed the incidence and presentation of thrombotic complications in critically ill patients with COVID-19. CAC has been postulated to result from endotheliopathy along with immune cell activation and propagation of coagulation. While COVID-19 has been noted to create lung injury through binding angiotensin-converting enzyme 2 receptors expressed on alveolar pneumocytes, it increasingly has been found to affect endothelial cells throughout the body. Recent postmortem analyses have demonstrated direct viral infection of endothelial cells with consequent diffuse endothelial inflammation, as evidenced by viral inclusions, sequestered immune cells, and endothelial apoptosis.^12,13 Manifestations of this endotheliopathy have been delineated through various studies.

An early retrospective study in Wuhan, China, illustrated that 36% of the first 99 patients hospitalized with COVID-19 demonstrated an elevated D-dimer, 6% an elevated aPTT, and 5% an elevated prothrombin time.¹⁴ Another retrospective study conducted in Wuhan found a 25% incidence of venous thromboembolic complications in critically ill patients with severe COVID-19.¹⁵ In the Netherlands, a study reported the incidence of arterial and venous thrombotic complications to be 31% in 184 critically ill patients with COVID-19, with 81% of these cases involving pulmonary emboli.¹⁶

To our knowledge, our patient is the seventh reported case of ischemic priapism occurring in the setting of a COVID-19 infection, and the first to have occurred in its moderate form. Ischemic priapism is often a consequence of penile venous outflow obstruction and resultant stasis of hypoxic blood.⁷ The prothrombotic state induced by CAC has been proposed to cause the obstruction of small emissary veins in the subtunical space and in turn lead to venous stasis, which propagates the formation of ischemic priapism.⁸ Furthermore, 4 of the previously reported cases shared laboratory data on their patients, and all demonstrated elevated D-dimer and fibrinogen levels, which strengthens this hypothesis.^3,5,7,8 CLL presents a potential confounding variable in this case; however, as we have reviewed earlier, the risk of leukostasis at WBC counts < 1000 × 10⁹/L is very low.¹¹ It is also probable that the patient had some level of immune dysregulation secondary to CLL, leading to his prolonged course and slow clearance of the virus.

Conclusions

Although only a handful of CAC cases leading to ischemic priapism have been reported, the true incidence may be much higher. While our case highlights the importance of considering COVID-19 infection in the differential diagnosis of ischemic priapism, more research is needed to understand incidence and definitively establish a causative relationship.

Treatment with oral sabizabulin (Veru Pharmaceuticals) cut the risk for death by more than 55% in hospitalized patients with COVID-19, an interim analysis of a phase 3 placebo-controlled trial found.

Sabizabulin treatment consistently and significantly reduced deaths across patient subgroups “regardless of standard of care treatment received, baseline World Health Organization scores, age, comorbidities, vaccination status, COVID-19 variant, or geography,” study investigator Mitchell Steiner, MD, chairman, president, and CEO of Veru, said in a news release.

The company has submitted an emergency use authorization request to the U.S. Food and Drug Administration to use sabizabulin to treat COVID-19.

The analysis was published online in NEJM Evidence.

Sabizabulin, originally developed to treat metastatic castration-resistant prostate cancer, is a novel, investigational, oral microtubule disruptor with dual antiviral and anti-inflammatory activities. Given the drug’s mechanism, researchers at Veru thought that sabizabulin could help treat lung inflammation in patients with COVID-19 as well.

Findings of the interim analysis are based on 150 adults hospitalized with moderate to severe COVID-19 at high risk for acute respiratory distress syndrome and death. The patients were randomly allocated to receive 9 mg oral sabizabulin (n = 98) or placebo (n = 52) once daily for up to 21 days.

Overall, the mortality rate was 20.2% in the sabizabulin group vs. 45.1% in the placebo group. Compared with placebo, treatment with sabizabulin led to a 24.9–percentage point absolute reduction and a 55.2% relative reduction in death (odds ratio, 3.23; P = .0042).

The key secondary endpoint of mortality through day 29 also favored sabizabulin over placebo, with a mortality rate of 17% vs. 35.3%. In this scenario, treatment with sabizabulin resulted in an absolute reduction in deaths of 18.3 percentage points and a relative reduction of 51.8%.

Sabizabulin led to a significant 43% relative reduction in ICU days, a 49% relative reduction in days on mechanical ventilation, and a 26% relative reduction in days in the hospital, compared with placebo.

Adverse and serious adverse events were also lower in the sabizabulin group (61.5%) than the placebo group (78.3%).

The data are “pretty impressive and in a group of patients that we really have limited things to offer,” Aaron Glatt, MD, a spokesperson for the Infectious Diseases Society of America and chief of infectious diseases and hospital epidemiologist at Mount Sinai South Nassau in Oceanside, N.Y., said in an interview. “This is an interim analysis and obviously we’d like to see more data, but it certainly is something that is novel and quite interesting.”

David Boulware, MD, MPH, an infectious disease expert at the University of Minnesota, Minneapolis, told the New York Times that the large number of deaths in the placebo group seemed “rather high” and that the final analysis might reveal a more modest benefit for sabizabulin.

“I would be skeptical” that the reduced risk for death remains 55%, he noted.

The study was funded by Veru Pharmaceuticals. Several authors are employed by the company or have financial relationships with the company.

A version of this article first appeared on Medscape.com.

Treatment with oral sabizabulin (Veru Pharmaceuticals) cut the risk for death by more than 55% in hospitalized patients with COVID-19, an interim analysis of a phase 3 placebo-controlled trial found.

Sabizabulin treatment consistently and significantly reduced deaths across patient subgroups “regardless of standard of care treatment received, baseline World Health Organization scores, age, comorbidities, vaccination status, COVID-19 variant, or geography,” study investigator Mitchell Steiner, MD, chairman, president, and CEO of Veru, said in a news release.

The company has submitted an emergency use authorization request to the U.S. Food and Drug Administration to use sabizabulin to treat COVID-19.

The analysis was published online in NEJM Evidence.

Sabizabulin, originally developed to treat metastatic castration-resistant prostate cancer, is a novel, investigational, oral microtubule disruptor with dual antiviral and anti-inflammatory activities. Given the drug’s mechanism, researchers at Veru thought that sabizabulin could help treat lung inflammation in patients with COVID-19 as well.

Findings of the interim analysis are based on 150 adults hospitalized with moderate to severe COVID-19 at high risk for acute respiratory distress syndrome and death. The patients were randomly allocated to receive 9 mg oral sabizabulin (n = 98) or placebo (n = 52) once daily for up to 21 days.

Overall, the mortality rate was 20.2% in the sabizabulin group vs. 45.1% in the placebo group. Compared with placebo, treatment with sabizabulin led to a 24.9–percentage point absolute reduction and a 55.2% relative reduction in death (odds ratio, 3.23; P = .0042).

The key secondary endpoint of mortality through day 29 also favored sabizabulin over placebo, with a mortality rate of 17% vs. 35.3%. In this scenario, treatment with sabizabulin resulted in an absolute reduction in deaths of 18.3 percentage points and a relative reduction of 51.8%.

Sabizabulin led to a significant 43% relative reduction in ICU days, a 49% relative reduction in days on mechanical ventilation, and a 26% relative reduction in days in the hospital, compared with placebo.

Adverse and serious adverse events were also lower in the sabizabulin group (61.5%) than the placebo group (78.3%).

The data are “pretty impressive and in a group of patients that we really have limited things to offer,” Aaron Glatt, MD, a spokesperson for the Infectious Diseases Society of America and chief of infectious diseases and hospital epidemiologist at Mount Sinai South Nassau in Oceanside, N.Y., said in an interview. “This is an interim analysis and obviously we’d like to see more data, but it certainly is something that is novel and quite interesting.”

David Boulware, MD, MPH, an infectious disease expert at the University of Minnesota, Minneapolis, told the New York Times that the large number of deaths in the placebo group seemed “rather high” and that the final analysis might reveal a more modest benefit for sabizabulin.

“I would be skeptical” that the reduced risk for death remains 55%, he noted.

The study was funded by Veru Pharmaceuticals. Several authors are employed by the company or have financial relationships with the company.

A version of this article first appeared on Medscape.com.

Treatment with oral sabizabulin (Veru Pharmaceuticals) cut the risk for death by more than 55% in hospitalized patients with COVID-19, an interim analysis of a phase 3 placebo-controlled trial found.

Sabizabulin treatment consistently and significantly reduced deaths across patient subgroups “regardless of standard of care treatment received, baseline World Health Organization scores, age, comorbidities, vaccination status, COVID-19 variant, or geography,” study investigator Mitchell Steiner, MD, chairman, president, and CEO of Veru, said in a news release.

The company has submitted an emergency use authorization request to the U.S. Food and Drug Administration to use sabizabulin to treat COVID-19.

The analysis was published online in NEJM Evidence.

Sabizabulin, originally developed to treat metastatic castration-resistant prostate cancer, is a novel, investigational, oral microtubule disruptor with dual antiviral and anti-inflammatory activities. Given the drug’s mechanism, researchers at Veru thought that sabizabulin could help treat lung inflammation in patients with COVID-19 as well.

Findings of the interim analysis are based on 150 adults hospitalized with moderate to severe COVID-19 at high risk for acute respiratory distress syndrome and death. The patients were randomly allocated to receive 9 mg oral sabizabulin (n = 98) or placebo (n = 52) once daily for up to 21 days.

Overall, the mortality rate was 20.2% in the sabizabulin group vs. 45.1% in the placebo group. Compared with placebo, treatment with sabizabulin led to a 24.9–percentage point absolute reduction and a 55.2% relative reduction in death (odds ratio, 3.23; P = .0042).

The key secondary endpoint of mortality through day 29 also favored sabizabulin over placebo, with a mortality rate of 17% vs. 35.3%. In this scenario, treatment with sabizabulin resulted in an absolute reduction in deaths of 18.3 percentage points and a relative reduction of 51.8%.

Sabizabulin led to a significant 43% relative reduction in ICU days, a 49% relative reduction in days on mechanical ventilation, and a 26% relative reduction in days in the hospital, compared with placebo.

Adverse and serious adverse events were also lower in the sabizabulin group (61.5%) than the placebo group (78.3%).

The data are “pretty impressive and in a group of patients that we really have limited things to offer,” Aaron Glatt, MD, a spokesperson for the Infectious Diseases Society of America and chief of infectious diseases and hospital epidemiologist at Mount Sinai South Nassau in Oceanside, N.Y., said in an interview. “This is an interim analysis and obviously we’d like to see more data, but it certainly is something that is novel and quite interesting.”

David Boulware, MD, MPH, an infectious disease expert at the University of Minnesota, Minneapolis, told the New York Times that the large number of deaths in the placebo group seemed “rather high” and that the final analysis might reveal a more modest benefit for sabizabulin.

“I would be skeptical” that the reduced risk for death remains 55%, he noted.

The study was funded by Veru Pharmaceuticals. Several authors are employed by the company or have financial relationships with the company.

A version of this article first appeared on Medscape.com.

Body clocks and the shifting risks of stroke

Health care professionals, we’re sure, are no strangers to rotating shifts. And, as practitioners of the shiftly arts, you should know new research shows that working those kinds of hours can have lasting effects on your health. And it’s all based on your sleep-wake cycle.

Wildpixel/thinkstockphotos.com

In a study published in Neurobiology of Sleep and Circadian Rhythms, investigators at Texas A&M University looked at the effects of working these kinds of shifts for a long period of time and then returning to a regular 24-hour cycle later in life. The study piggybacks on a previous study, which showed that rats on shift schedules had more severe stroke outcomes than those who were on a 24-hour cycle.

The current study demonstrates that working rotating shifts does have a lasting effect, by way of messing with the sleep-wake cycle. Based on the research, the rats that performed those kinds of shifts never got back to a normal schedule. When strokes occurred, outcomes were much worse, and the females had a higher mortality rate and more severe functional deficits than the males.

Now for the “good” news: Even if you’re among those who haven’t worked a rotating shift, you may not be safe either.

People who have regular working hours have a tendency to take work home and stay up late, especially with so many moving to a remote-work model. And if you’re staying up late on the weekends you’re producing what lead author David J. Earnest, PhD, called “social jet lag,” which messes with your circadian rhythm to wind you down for sleep. All of these things can lead to the same kind of effects that working rotating shifts has on your health, he said in a written statement.

How do you combat this? Dr. Earnest recommended creating a sleep schedule and setting regular mealtimes. Also ease up on high-fat foods, drinking, and smoking. The connection between your brain and gut also could play a part in how severe a stroke can be.

So continue to work hard, but not too hard.

Got 3 minutes? You got time for culture

Much like a Krabby Patty, art is good for your soul. Seriously, staring at a 500-year-old painting may not seem like much, but research has proven time and again that going to a museum and looking at paintings by long-dead artists you probably know better as pizza-eating superhero turtles improves mood, stress, and well-being.

National Gallery of Art/rawpixel

A couple of years ago, however, museums and art galleries ran into a big virus-shaped problem. You may have heard of it. All of a sudden it became a very bad idea for people to gather together in one building and huddle around the Mona Lisa, which, by the way, is a lot smaller in person than you might expect. But, rather than sit around with a bunch of priceless art for an indeterminate amount of time, museums brought their exhibits to the Internet so that people from all over the world could see great works from their couches.

This is absolutely a good thing for public access, but do these virtual art exhibits provide the same health benefits as going to a museum in person? That’s what a group of European researchers aimed to find out, and in a study published in Frontiers of Psychology, that’s exactly what they found.

Their directive to the 84 study participants was simple: Take a well-being survey, engage with either of a pair of online exhibits (a Monet painting and a display of Japanese culinary traditions) for just 3 minutes, then take another well-being assessment. The results were quite clear: Even just a couple of minutes of viewing art online improved all the well-being categories on the survey, such as lowering anxiety, negative mood, and loneliness, as well as increasing subjective well-being. Also, the more beautiful or meaningful a person found the art, the more their mood and well-being improved.

The researchers noted that these results could help access in places where access to art is limited, such as waiting rooms, hospitals, and rural areas. Let’s just hope it sticks to that, and that big businesses don’t take notice. Just imagine them plastering ads with classic Renaissance artworks. After all, art makes you feel good, and you know what else feels good on a hot summer day? An ice-cold Coca-Cola! By the way, we’re taking offers, advertising agencies. The LOTME staff can absolutely be bought.

Appetite for etymology

Today on “It’s a Thing,” we examine various states of hunger and what they should be called. Our first guest is that historically hungry royal person, King Henry VIII of England. Your majesty, have you ever been “hangry?”

PxHere

KH8: First, let me thank you for inviting me on the show, Maurice. I’m a huge fan. A recent study done in the United Kingdom and Austria showed that “hunger is associated with greater levels of anger and irritability, as well as lower levels of pleasure,” according to a Eurekalert statement. So, yes, I have been “hangry.”

Maurice: Now to our next guest. Martha Stewart, can you add anything about that study?

Martha: Happy to, Maurice. The 64 participants used a smartphone app to record their hunger levels and emotional states five times a day for 21 days. It’s the first time that “hanger” was studied outside a lab, and it showed that hunger “was associated with 37% of the variance in irritability, 34% of the variance in anger, and 38% of the variance in pleasure recorded by the participants,” the investigators said in that statement.

Maurice: It’s official, then. Hangry is a thing, and we don’t need to put it in quotes anymore. Now let’s meet our third and final guest, Betty Crocker. Betty, I’m told you have a study to plug.

Betty: That’s right, Mo. Researchers at Tel Aviv University looked at survey data from almost 3,000 men and women and found that men ate 17% more food during the warmer months (March to September) than they did the rest of the year. Among women, however, caloric intake did not change.

KH8: I saw that study. Didn’t they put 27 people out in the sun and then take blood samples?

Betty: Indeed they did, Hank. After 25 minutes of sun exposure, the 13 men felt hungrier than before, but the 14 women did not. The men also had higher levels of ghrelin, an appetite-stimulating hormone, than the women.

Maurice: To sum all this up, then, we’ve got angry and hungry officially combining to make hangry, and now it looks like the sun is causing hunger in men, which makes them … sungry?

Martha: It’s a thing.

Chicken cutlets with a side of COVID

You stopped at the drive through at McDonald’s on the way home from work, and while you’re looking for something sweet in the refrigerator for dessert, you see that chicken breast that expires today.

Richard Franki/MDedge News

Freezing meat that’s about to expire might be your go-to so it doesn’t go to waste, but it’s been found that SARS-CoV-2 can live in meat that’s been in the refrigerator or freezer for more than a month.

Researchers exposed chicken, beef, pork, and salmon to surrogate viruses that are similar to COVID but not as harmful and stored them in freezers at –4° F and in the refrigerator at 39.2° F. “We even found that the viruses could be cultured after [being frozen for] that length of time,” lead author Emily Bailey, PhD, of Campbell University in Buies Creek, N.C., said in Study Finds.

The team began its research after hearing of COVID-19 outbreaks where there were no reports of community transmission, such as in Southeast Asia. Tracing eventually led to packaged meats as the culprits in those cases. SARS-CoV-2 is able to replicate in the gut, as well as the respiratory tract, so it could affect the gut before respiratory symptoms start. It is crucial to ensure cross contamination doesn’t occur, and inadequate sanitation prior to packaging needs to be addressed, the investigators said.

Honestly, we didn’t think anything could survive in a freezer for that long, but SARS-CoV-2 is a fighter.

Body clocks and the shifting risks of stroke

Health care professionals, we’re sure, are no strangers to rotating shifts. And, as practitioners of the shiftly arts, you should know new research shows that working those kinds of hours can have lasting effects on your health. And it’s all based on your sleep-wake cycle.

Wildpixel/thinkstockphotos.com

In a study published in Neurobiology of Sleep and Circadian Rhythms, investigators at Texas A&M University looked at the effects of working these kinds of shifts for a long period of time and then returning to a regular 24-hour cycle later in life. The study piggybacks on a previous study, which showed that rats on shift schedules had more severe stroke outcomes than those who were on a 24-hour cycle.

The current study demonstrates that working rotating shifts does have a lasting effect, by way of messing with the sleep-wake cycle. Based on the research, the rats that performed those kinds of shifts never got back to a normal schedule. When strokes occurred, outcomes were much worse, and the females had a higher mortality rate and more severe functional deficits than the males.

Now for the “good” news: Even if you’re among those who haven’t worked a rotating shift, you may not be safe either.

People who have regular working hours have a tendency to take work home and stay up late, especially with so many moving to a remote-work model. And if you’re staying up late on the weekends you’re producing what lead author David J. Earnest, PhD, called “social jet lag,” which messes with your circadian rhythm to wind you down for sleep. All of these things can lead to the same kind of effects that working rotating shifts has on your health, he said in a written statement.

How do you combat this? Dr. Earnest recommended creating a sleep schedule and setting regular mealtimes. Also ease up on high-fat foods, drinking, and smoking. The connection between your brain and gut also could play a part in how severe a stroke can be.

So continue to work hard, but not too hard.

Got 3 minutes? You got time for culture

Much like a Krabby Patty, art is good for your soul. Seriously, staring at a 500-year-old painting may not seem like much, but research has proven time and again that going to a museum and looking at paintings by long-dead artists you probably know better as pizza-eating superhero turtles improves mood, stress, and well-being.

National Gallery of Art/rawpixel

A couple of years ago, however, museums and art galleries ran into a big virus-shaped problem. You may have heard of it. All of a sudden it became a very bad idea for people to gather together in one building and huddle around the Mona Lisa, which, by the way, is a lot smaller in person than you might expect. But, rather than sit around with a bunch of priceless art for an indeterminate amount of time, museums brought their exhibits to the Internet so that people from all over the world could see great works from their couches.

This is absolutely a good thing for public access, but do these virtual art exhibits provide the same health benefits as going to a museum in person? That’s what a group of European researchers aimed to find out, and in a study published in Frontiers of Psychology, that’s exactly what they found.

Their directive to the 84 study participants was simple: Take a well-being survey, engage with either of a pair of online exhibits (a Monet painting and a display of Japanese culinary traditions) for just 3 minutes, then take another well-being assessment. The results were quite clear: Even just a couple of minutes of viewing art online improved all the well-being categories on the survey, such as lowering anxiety, negative mood, and loneliness, as well as increasing subjective well-being. Also, the more beautiful or meaningful a person found the art, the more their mood and well-being improved.

The researchers noted that these results could help access in places where access to art is limited, such as waiting rooms, hospitals, and rural areas. Let’s just hope it sticks to that, and that big businesses don’t take notice. Just imagine them plastering ads with classic Renaissance artworks. After all, art makes you feel good, and you know what else feels good on a hot summer day? An ice-cold Coca-Cola! By the way, we’re taking offers, advertising agencies. The LOTME staff can absolutely be bought.

Appetite for etymology

Today on “It’s a Thing,” we examine various states of hunger and what they should be called. Our first guest is that historically hungry royal person, King Henry VIII of England. Your majesty, have you ever been “hangry?”

PxHere

KH8: First, let me thank you for inviting me on the show, Maurice. I’m a huge fan. A recent study done in the United Kingdom and Austria showed that “hunger is associated with greater levels of anger and irritability, as well as lower levels of pleasure,” according to a Eurekalert statement. So, yes, I have been “hangry.”

Maurice: Now to our next guest. Martha Stewart, can you add anything about that study?

Martha: Happy to, Maurice. The 64 participants used a smartphone app to record their hunger levels and emotional states five times a day for 21 days. It’s the first time that “hanger” was studied outside a lab, and it showed that hunger “was associated with 37% of the variance in irritability, 34% of the variance in anger, and 38% of the variance in pleasure recorded by the participants,” the investigators said in that statement.

Maurice: It’s official, then. Hangry is a thing, and we don’t need to put it in quotes anymore. Now let’s meet our third and final guest, Betty Crocker. Betty, I’m told you have a study to plug.

Betty: That’s right, Mo. Researchers at Tel Aviv University looked at survey data from almost 3,000 men and women and found that men ate 17% more food during the warmer months (March to September) than they did the rest of the year. Among women, however, caloric intake did not change.

KH8: I saw that study. Didn’t they put 27 people out in the sun and then take blood samples?

Betty: Indeed they did, Hank. After 25 minutes of sun exposure, the 13 men felt hungrier than before, but the 14 women did not. The men also had higher levels of ghrelin, an appetite-stimulating hormone, than the women.

Maurice: To sum all this up, then, we’ve got angry and hungry officially combining to make hangry, and now it looks like the sun is causing hunger in men, which makes them … sungry?

Martha: It’s a thing.

Chicken cutlets with a side of COVID

You stopped at the drive through at McDonald’s on the way home from work, and while you’re looking for something sweet in the refrigerator for dessert, you see that chicken breast that expires today.

Richard Franki/MDedge News

Freezing meat that’s about to expire might be your go-to so it doesn’t go to waste, but it’s been found that SARS-CoV-2 can live in meat that’s been in the refrigerator or freezer for more than a month.

Researchers exposed chicken, beef, pork, and salmon to surrogate viruses that are similar to COVID but not as harmful and stored them in freezers at –4° F and in the refrigerator at 39.2° F. “We even found that the viruses could be cultured after [being frozen for] that length of time,” lead author Emily Bailey, PhD, of Campbell University in Buies Creek, N.C., said in Study Finds.

The team began its research after hearing of COVID-19 outbreaks where there were no reports of community transmission, such as in Southeast Asia. Tracing eventually led to packaged meats as the culprits in those cases. SARS-CoV-2 is able to replicate in the gut, as well as the respiratory tract, so it could affect the gut before respiratory symptoms start. It is crucial to ensure cross contamination doesn’t occur, and inadequate sanitation prior to packaging needs to be addressed, the investigators said.

Honestly, we didn’t think anything could survive in a freezer for that long, but SARS-CoV-2 is a fighter.

Body clocks and the shifting risks of stroke

Health care professionals, we’re sure, are no strangers to rotating shifts. And, as practitioners of the shiftly arts, you should know new research shows that working those kinds of hours can have lasting effects on your health. And it’s all based on your sleep-wake cycle.

Wildpixel/thinkstockphotos.com

In a study published in Neurobiology of Sleep and Circadian Rhythms, investigators at Texas A&M University looked at the effects of working these kinds of shifts for a long period of time and then returning to a regular 24-hour cycle later in life. The study piggybacks on a previous study, which showed that rats on shift schedules had more severe stroke outcomes than those who were on a 24-hour cycle.

The current study demonstrates that working rotating shifts does have a lasting effect, by way of messing with the sleep-wake cycle. Based on the research, the rats that performed those kinds of shifts never got back to a normal schedule. When strokes occurred, outcomes were much worse, and the females had a higher mortality rate and more severe functional deficits than the males.

Now for the “good” news: Even if you’re among those who haven’t worked a rotating shift, you may not be safe either.

People who have regular working hours have a tendency to take work home and stay up late, especially with so many moving to a remote-work model. And if you’re staying up late on the weekends you’re producing what lead author David J. Earnest, PhD, called “social jet lag,” which messes with your circadian rhythm to wind you down for sleep. All of these things can lead to the same kind of effects that working rotating shifts has on your health, he said in a written statement.

How do you combat this? Dr. Earnest recommended creating a sleep schedule and setting regular mealtimes. Also ease up on high-fat foods, drinking, and smoking. The connection between your brain and gut also could play a part in how severe a stroke can be.

So continue to work hard, but not too hard.

Got 3 minutes? You got time for culture

Much like a Krabby Patty, art is good for your soul. Seriously, staring at a 500-year-old painting may not seem like much, but research has proven time and again that going to a museum and looking at paintings by long-dead artists you probably know better as pizza-eating superhero turtles improves mood, stress, and well-being.

National Gallery of Art/rawpixel

A couple of years ago, however, museums and art galleries ran into a big virus-shaped problem. You may have heard of it. All of a sudden it became a very bad idea for people to gather together in one building and huddle around the Mona Lisa, which, by the way, is a lot smaller in person than you might expect. But, rather than sit around with a bunch of priceless art for an indeterminate amount of time, museums brought their exhibits to the Internet so that people from all over the world could see great works from their couches.

This is absolutely a good thing for public access, but do these virtual art exhibits provide the same health benefits as going to a museum in person? That’s what a group of European researchers aimed to find out, and in a study published in Frontiers of Psychology, that’s exactly what they found.

Their directive to the 84 study participants was simple: Take a well-being survey, engage with either of a pair of online exhibits (a Monet painting and a display of Japanese culinary traditions) for just 3 minutes, then take another well-being assessment. The results were quite clear: Even just a couple of minutes of viewing art online improved all the well-being categories on the survey, such as lowering anxiety, negative mood, and loneliness, as well as increasing subjective well-being. Also, the more beautiful or meaningful a person found the art, the more their mood and well-being improved.

The researchers noted that these results could help access in places where access to art is limited, such as waiting rooms, hospitals, and rural areas. Let’s just hope it sticks to that, and that big businesses don’t take notice. Just imagine them plastering ads with classic Renaissance artworks. After all, art makes you feel good, and you know what else feels good on a hot summer day? An ice-cold Coca-Cola! By the way, we’re taking offers, advertising agencies. The LOTME staff can absolutely be bought.

Appetite for etymology

Today on “It’s a Thing,” we examine various states of hunger and what they should be called. Our first guest is that historically hungry royal person, King Henry VIII of England. Your majesty, have you ever been “hangry?”

PxHere

KH8: First, let me thank you for inviting me on the show, Maurice. I’m a huge fan. A recent study done in the United Kingdom and Austria showed that “hunger is associated with greater levels of anger and irritability, as well as lower levels of pleasure,” according to a Eurekalert statement. So, yes, I have been “hangry.”

Maurice: Now to our next guest. Martha Stewart, can you add anything about that study?

Martha: Happy to, Maurice. The 64 participants used a smartphone app to record their hunger levels and emotional states five times a day for 21 days. It’s the first time that “hanger” was studied outside a lab, and it showed that hunger “was associated with 37% of the variance in irritability, 34% of the variance in anger, and 38% of the variance in pleasure recorded by the participants,” the investigators said in that statement.

Maurice: It’s official, then. Hangry is a thing, and we don’t need to put it in quotes anymore. Now let’s meet our third and final guest, Betty Crocker. Betty, I’m told you have a study to plug.

Betty: That’s right, Mo. Researchers at Tel Aviv University looked at survey data from almost 3,000 men and women and found that men ate 17% more food during the warmer months (March to September) than they did the rest of the year. Among women, however, caloric intake did not change.

KH8: I saw that study. Didn’t they put 27 people out in the sun and then take blood samples?

Betty: Indeed they did, Hank. After 25 minutes of sun exposure, the 13 men felt hungrier than before, but the 14 women did not. The men also had higher levels of ghrelin, an appetite-stimulating hormone, than the women.

Maurice: To sum all this up, then, we’ve got angry and hungry officially combining to make hangry, and now it looks like the sun is causing hunger in men, which makes them … sungry?

Martha: It’s a thing.

Chicken cutlets with a side of COVID

You stopped at the drive through at McDonald’s on the way home from work, and while you’re looking for something sweet in the refrigerator for dessert, you see that chicken breast that expires today.

Richard Franki/MDedge News

Freezing meat that’s about to expire might be your go-to so it doesn’t go to waste, but it’s been found that SARS-CoV-2 can live in meat that’s been in the refrigerator or freezer for more than a month.

Researchers exposed chicken, beef, pork, and salmon to surrogate viruses that are similar to COVID but not as harmful and stored them in freezers at –4° F and in the refrigerator at 39.2° F. “We even found that the viruses could be cultured after [being frozen for] that length of time,” lead author Emily Bailey, PhD, of Campbell University in Buies Creek, N.C., said in Study Finds.

The team began its research after hearing of COVID-19 outbreaks where there were no reports of community transmission, such as in Southeast Asia. Tracing eventually led to packaged meats as the culprits in those cases. SARS-CoV-2 is able to replicate in the gut, as well as the respiratory tract, so it could affect the gut before respiratory symptoms start. It is crucial to ensure cross contamination doesn’t occur, and inadequate sanitation prior to packaging needs to be addressed, the investigators said.

Honestly, we didn’t think anything could survive in a freezer for that long, but SARS-CoV-2 is a fighter.

Americans could soon have a fourth option for COVID-19 vaccines after the Food and Drug Administration granted emergency use authorization to a two-shot vaccine from Novavax on July 13.

The vaccine is authorized for adults only. Should the Centers for Disease Control and Prevention follow suit and approve its use, Novavax would join Moderna, Pfizer and Johnson & Johnson on the U.S. market. A CDC panel of advisors is expected to consider the new entry on July 19.

The Novavax vaccine is only for those who have not yet been vaccinated at all.

“Today’s authorization offers adults in the United States who have not yet received a COVID-19 vaccine another option that meets the FDA’s rigorous standards for safety, effectiveness and manufacturing quality needed to support emergency use authorization,” FDA Commissioner Robert Califf, MD, said in a statement. “COVID-19 vaccines remain the best preventive measure against severe disease caused by COVID-19 and I encourage anyone who is eligible for, but has not yet received a COVID-19 vaccine, to consider doing so.”

The Novavax vaccine is protein-based, making it different than mRNA vaccines from Pfizer and Moderna. It contains harmless elements of actual coronavirus spike protein and an ingredient known as a adjuvant that enhances the patient’s immune response.

Clinical trials found the vaccine to be 90.4% effective in preventing mild, moderate or severe COVID-19. Only 17 patients out of 17,200 developed COVID-19 after receiving both doses.

The FDA said, however, that Novavax’s vaccine did show evidence of increased risk of myocarditis – inflammation of the heart – and pericarditis, inflammation of tissue surrounding the heart. In most people both disorders began within 10 days.

A version of this article first appeared on WebMD.com.

Americans could soon have a fourth option for COVID-19 vaccines after the Food and Drug Administration granted emergency use authorization to a two-shot vaccine from Novavax on July 13.

The vaccine is authorized for adults only. Should the Centers for Disease Control and Prevention follow suit and approve its use, Novavax would join Moderna, Pfizer and Johnson & Johnson on the U.S. market. A CDC panel of advisors is expected to consider the new entry on July 19.

The Novavax vaccine is only for those who have not yet been vaccinated at all.

“Today’s authorization offers adults in the United States who have not yet received a COVID-19 vaccine another option that meets the FDA’s rigorous standards for safety, effectiveness and manufacturing quality needed to support emergency use authorization,” FDA Commissioner Robert Califf, MD, said in a statement. “COVID-19 vaccines remain the best preventive measure against severe disease caused by COVID-19 and I encourage anyone who is eligible for, but has not yet received a COVID-19 vaccine, to consider doing so.”

The Novavax vaccine is protein-based, making it different than mRNA vaccines from Pfizer and Moderna. It contains harmless elements of actual coronavirus spike protein and an ingredient known as a adjuvant that enhances the patient’s immune response.

Clinical trials found the vaccine to be 90.4% effective in preventing mild, moderate or severe COVID-19. Only 17 patients out of 17,200 developed COVID-19 after receiving both doses.

The FDA said, however, that Novavax’s vaccine did show evidence of increased risk of myocarditis – inflammation of the heart – and pericarditis, inflammation of tissue surrounding the heart. In most people both disorders began within 10 days.

A version of this article first appeared on WebMD.com.

Americans could soon have a fourth option for COVID-19 vaccines after the Food and Drug Administration granted emergency use authorization to a two-shot vaccine from Novavax on July 13.

The vaccine is authorized for adults only. Should the Centers for Disease Control and Prevention follow suit and approve its use, Novavax would join Moderna, Pfizer and Johnson & Johnson on the U.S. market. A CDC panel of advisors is expected to consider the new entry on July 19.

The Novavax vaccine is only for those who have not yet been vaccinated at all.

“Today’s authorization offers adults in the United States who have not yet received a COVID-19 vaccine another option that meets the FDA’s rigorous standards for safety, effectiveness and manufacturing quality needed to support emergency use authorization,” FDA Commissioner Robert Califf, MD, said in a statement. “COVID-19 vaccines remain the best preventive measure against severe disease caused by COVID-19 and I encourage anyone who is eligible for, but has not yet received a COVID-19 vaccine, to consider doing so.”

The Novavax vaccine is protein-based, making it different than mRNA vaccines from Pfizer and Moderna. It contains harmless elements of actual coronavirus spike protein and an ingredient known as a adjuvant that enhances the patient’s immune response.

Clinical trials found the vaccine to be 90.4% effective in preventing mild, moderate or severe COVID-19. Only 17 patients out of 17,200 developed COVID-19 after receiving both doses.

The FDA said, however, that Novavax’s vaccine did show evidence of increased risk of myocarditis – inflammation of the heart – and pericarditis, inflammation of tissue surrounding the heart. In most people both disorders began within 10 days.

A version of this article first appeared on WebMD.com.

The COVID-19 vaccination effort in the youngest children has begun much more slowly than the most recent rollout for older children, according to the Centers for Disease Control and Prevention.

Almost 263,000 children under age 5 years were vaccinated in the first 2 weeks after final approval on June 18, compared with the over 3 million children aged 5-11 years who received their first dose during the 2 weeks after approval in early November of 2021, based on CDC data last updated on July 7.

That approval, of course, came between the Delta and Omicron surges, when awareness was higher. The low initial uptake among those under age 5, however, was not unexpected by the Biden administration. “That number in and of itself is very much in line with our expectation, and we’re eager to continue working closely with partners to build on this start,” a senior administration official told ABC News.

With approval of the vaccine occurring after the school year was over, parents’ thoughts have been focused more on vacations and less on vaccinations. “Even before these vaccines officially became available, this was going to be a different rollout; it was going to take more time,” the official explained.
 

Incidence measures continue on different paths

New COVID-19 cases dropped during the latest reporting week (July 1-7), returning to the downward trend that began in late May and then stopped for 1 week (June 24-30), when cases were up by 12.4%, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Children also represent a smaller share of cases, probably because of underreporting. “There has been a notable decline in the portion of reported weekly COVID-19 cases that are children,” the two groups said in their weekly COVID report. Although “cases are likely increasingly underreported for all age groups, this decline indicates that children are disproportionately undercounted in reported COVID-19 cases.”

Other measures, however, have been rising slowly but steadily since the spring. New admissions of patients aged 0-17 years with confirmed COVID, which were down to 0.13 per 100,000 population in early April, had climbed to 0.39 per 100,000 by July 7, the CDC said on its COVID Data Tracker.

Emergency department visits continue to show the same upward trend, despite a small decline in early June. A COVID diagnosis was involved in just 0.5% of ED visits in children aged 0-11 years on March 26, but by July 6 the rate was 4.7%. Increases were not as high among older children: From 0.3% on March 26 to 2.5% on July 6 for those aged 12-15 and from 0.3% to 2.4% for 16- and 17-year-olds, according to the CDC.

[email protected]

The COVID-19 vaccination effort in the youngest children has begun much more slowly than the most recent rollout for older children, according to the Centers for Disease Control and Prevention.

Almost 263,000 children under age 5 years were vaccinated in the first 2 weeks after final approval on June 18, compared with the over 3 million children aged 5-11 years who received their first dose during the 2 weeks after approval in early November of 2021, based on CDC data last updated on July 7.

That approval, of course, came between the Delta and Omicron surges, when awareness was higher. The low initial uptake among those under age 5, however, was not unexpected by the Biden administration. “That number in and of itself is very much in line with our expectation, and we’re eager to continue working closely with partners to build on this start,” a senior administration official told ABC News.

With approval of the vaccine occurring after the school year was over, parents’ thoughts have been focused more on vacations and less on vaccinations. “Even before these vaccines officially became available, this was going to be a different rollout; it was going to take more time,” the official explained.
 

Incidence measures continue on different paths

New COVID-19 cases dropped during the latest reporting week (July 1-7), returning to the downward trend that began in late May and then stopped for 1 week (June 24-30), when cases were up by 12.4%, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Children also represent a smaller share of cases, probably because of underreporting. “There has been a notable decline in the portion of reported weekly COVID-19 cases that are children,” the two groups said in their weekly COVID report. Although “cases are likely increasingly underreported for all age groups, this decline indicates that children are disproportionately undercounted in reported COVID-19 cases.”

Other measures, however, have been rising slowly but steadily since the spring. New admissions of patients aged 0-17 years with confirmed COVID, which were down to 0.13 per 100,000 population in early April, had climbed to 0.39 per 100,000 by July 7, the CDC said on its COVID Data Tracker.

Emergency department visits continue to show the same upward trend, despite a small decline in early June. A COVID diagnosis was involved in just 0.5% of ED visits in children aged 0-11 years on March 26, but by July 6 the rate was 4.7%. Increases were not as high among older children: From 0.3% on March 26 to 2.5% on July 6 for those aged 12-15 and from 0.3% to 2.4% for 16- and 17-year-olds, according to the CDC.

[email protected]

The COVID-19 vaccination effort in the youngest children has begun much more slowly than the most recent rollout for older children, according to the Centers for Disease Control and Prevention.

Almost 263,000 children under age 5 years were vaccinated in the first 2 weeks after final approval on June 18, compared with the over 3 million children aged 5-11 years who received their first dose during the 2 weeks after approval in early November of 2021, based on CDC data last updated on July 7.

That approval, of course, came between the Delta and Omicron surges, when awareness was higher. The low initial uptake among those under age 5, however, was not unexpected by the Biden administration. “That number in and of itself is very much in line with our expectation, and we’re eager to continue working closely with partners to build on this start,” a senior administration official told ABC News.

With approval of the vaccine occurring after the school year was over, parents’ thoughts have been focused more on vacations and less on vaccinations. “Even before these vaccines officially became available, this was going to be a different rollout; it was going to take more time,” the official explained.
 

Incidence measures continue on different paths

New COVID-19 cases dropped during the latest reporting week (July 1-7), returning to the downward trend that began in late May and then stopped for 1 week (June 24-30), when cases were up by 12.4%, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Children also represent a smaller share of cases, probably because of underreporting. “There has been a notable decline in the portion of reported weekly COVID-19 cases that are children,” the two groups said in their weekly COVID report. Although “cases are likely increasingly underreported for all age groups, this decline indicates that children are disproportionately undercounted in reported COVID-19 cases.”

Other measures, however, have been rising slowly but steadily since the spring. New admissions of patients aged 0-17 years with confirmed COVID, which were down to 0.13 per 100,000 population in early April, had climbed to 0.39 per 100,000 by July 7, the CDC said on its COVID Data Tracker.

Emergency department visits continue to show the same upward trend, despite a small decline in early June. A COVID diagnosis was involved in just 0.5% of ED visits in children aged 0-11 years on March 26, but by July 6 the rate was 4.7%. Increases were not as high among older children: From 0.3% on March 26 to 2.5% on July 6 for those aged 12-15 and from 0.3% to 2.4% for 16- and 17-year-olds, according to the CDC.

[email protected]

The picture around the BA.4 and BA.5 subvariants of Omicron has been really confusing in that the pair is driving up cases but global COVID-19 deaths remain at their lowest level since the beginning of the pandemic. I wanted to explain what is happening with these subvariants, in that the picture seems to be one of antibody evasion without the dodging of cellular immunity. Explaining the two components of the immune response – antibodies versus cellular immune responses – can help us understand where we are in the pandemic and future booster options.

These two subvariants of Omicron, as of July 5, make up more than half of the COVID-19 strains in the United States and are expected to keep increasing. One of two reasons can lead to a variant or subvariant becoming dominant strain: increased transmissibility or evasion of antibodies.

Although BA.4 and BA.5 could be more transmissible than other subvariants of Omicron (which is already very transmissible), this has not yet been established in experiments showing increased affinity for the human receptor or in animal models. What we do know is that BA.4 and BA.5 seem to evade neutralizing antibodies conferred by the vaccines or even prior BA.1 infection (an earlier subvariant of Omicron), which could be the reason we are seeing so many reinfections now. Of note, BA.1 infection conferred antibodies that protected against subsequent BA.2 infection, so we did not see the same spike in cases in the United States with BA.2 (after a large BA.1 spike over the winter) earlier this spring.

Okay, so isn’t evasion of antibodies a bad thing? Of course it is but, luckily, our immune system is “redundant” and doesn›t just rely on antibodies to protect us from infection. In fact, antibodies (such as IgA, which is the mucosal antibody most prevalent in the nose and mouth, and IgG, which is the most prevalent antibody in the bloodstream) are our first line of COVID-19 defense in the nasal mucosa. Therefore, mild upper respiratory infections will be common as BA.4/BA.5 evade our nasal antibodies. Luckily, the rate of severe disease is remaining low throughout the world, probably because of the high amounts of cellular immunity to the virus. B and T cells are our protectors from severe disease.

For instance, two-dose vaccines are still conferring high rates of protection from severe disease with the BA.4 and BA.5 variants, with 87% protection against hospitalization per South Africa data. This is probably attributable to the fact that T-cell immunity from the vaccines remains protective across variants “from Alpha to Omicron,” as described by a recent and elegant paper.

Data from Qatar show that natural infection (even occurring up to 14 months ago) remains very protective (97.3%) against severe disease with the current circulating subvariants, including BA.4 and BA.5. Again, this is probably attributable to T cells which specifically amplify in response to a piece of the virus and help recruit cells to attack the pathogen directly.

The original BA.1 subvariant of Omicron has 26-32 mutations along its spike protein that differ from the “ancestral strain,” and BA.4 and BA.5 variants have a few more. Our T-cell response, even across a mutated spike protein, is so robust that we have not seen Omicron yet able to evade the many T cells (which we produce from the vaccines or infection) that descend upon the mutated virus to fight severe disease. Antibody-producing memory B cells, generated by the vaccines (or prior infection), have been shown to actually adapt their immune response to the variant to which they are exposed.

Therefore, the story of the BA.4 and BA.5 subvariants seems to remain about antibodies vs. cellular immunity. Our immunity in the United States is growing and is from both vaccination and natural infection, with 78.3% of the population having had at least one dose of the vaccine and at least 60% of adults (and 75% of children 0-18) having been exposed to the virus by February 2022, per the Centers for Disease Control and Prevention (with exposure probably much higher now in July 2022 after subsequent Omicron subvariants waves).

So, what about Omicron-specific boosters? A booster shot will just raise antibodies temporarily, but their effectiveness wanes several months later. Moreover, a booster shot against the ancestral strain is not very effective in neutralizing BA.4 and BA.5 (with a prior BA.1 Omicron infection being more effective than a booster). Luckily, Pfizer has promised a BA.4/BA.5-specific mRNA vaccine by October, and Moderna has promised a bivalent vaccine containing BA.4/BA.5 mRNA sequences around the same time. A vaccine that specifically increases antibodies against the most prevalent circulating strain should be important as a booster for those who are predisposed to severe breakthrough infections (for example, those with immunocompromise or older individuals with multiple comorbidities). Moreover, BA.4/BA.5–specific booster vaccines may help prevent mild infections for many individuals. Finally, any booster (or exposure) should diversify and broaden T-cell responses to the virus, and a booster shot will also expand the potency of B cells, making them better able to respond to the newest subvariants as we continue to live with COVID-19.
 

Monica Gandhi, MD, MPH, is an infectious diseases doctor, professor of medicine, and associate chief in the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco.

A version of this article first appeared on Medscape.com.

The picture around the BA.4 and BA.5 subvariants of Omicron has been really confusing in that the pair is driving up cases but global COVID-19 deaths remain at their lowest level since the beginning of the pandemic. I wanted to explain what is happening with these subvariants, in that the picture seems to be one of antibody evasion without the dodging of cellular immunity. Explaining the two components of the immune response – antibodies versus cellular immune responses – can help us understand where we are in the pandemic and future booster options.

These two subvariants of Omicron, as of July 5, make up more than half of the COVID-19 strains in the United States and are expected to keep increasing. One of two reasons can lead to a variant or subvariant becoming dominant strain: increased transmissibility or evasion of antibodies.

Although BA.4 and BA.5 could be more transmissible than other subvariants of Omicron (which is already very transmissible), this has not yet been established in experiments showing increased affinity for the human receptor or in animal models. What we do know is that BA.4 and BA.5 seem to evade neutralizing antibodies conferred by the vaccines or even prior BA.1 infection (an earlier subvariant of Omicron), which could be the reason we are seeing so many reinfections now. Of note, BA.1 infection conferred antibodies that protected against subsequent BA.2 infection, so we did not see the same spike in cases in the United States with BA.2 (after a large BA.1 spike over the winter) earlier this spring.

Okay, so isn’t evasion of antibodies a bad thing? Of course it is but, luckily, our immune system is “redundant” and doesn›t just rely on antibodies to protect us from infection. In fact, antibodies (such as IgA, which is the mucosal antibody most prevalent in the nose and mouth, and IgG, which is the most prevalent antibody in the bloodstream) are our first line of COVID-19 defense in the nasal mucosa. Therefore, mild upper respiratory infections will be common as BA.4/BA.5 evade our nasal antibodies. Luckily, the rate of severe disease is remaining low throughout the world, probably because of the high amounts of cellular immunity to the virus. B and T cells are our protectors from severe disease.

For instance, two-dose vaccines are still conferring high rates of protection from severe disease with the BA.4 and BA.5 variants, with 87% protection against hospitalization per South Africa data. This is probably attributable to the fact that T-cell immunity from the vaccines remains protective across variants “from Alpha to Omicron,” as described by a recent and elegant paper.

Data from Qatar show that natural infection (even occurring up to 14 months ago) remains very protective (97.3%) against severe disease with the current circulating subvariants, including BA.4 and BA.5. Again, this is probably attributable to T cells which specifically amplify in response to a piece of the virus and help recruit cells to attack the pathogen directly.

The original BA.1 subvariant of Omicron has 26-32 mutations along its spike protein that differ from the “ancestral strain,” and BA.4 and BA.5 variants have a few more. Our T-cell response, even across a mutated spike protein, is so robust that we have not seen Omicron yet able to evade the many T cells (which we produce from the vaccines or infection) that descend upon the mutated virus to fight severe disease. Antibody-producing memory B cells, generated by the vaccines (or prior infection), have been shown to actually adapt their immune response to the variant to which they are exposed.

Therefore, the story of the BA.4 and BA.5 subvariants seems to remain about antibodies vs. cellular immunity. Our immunity in the United States is growing and is from both vaccination and natural infection, with 78.3% of the population having had at least one dose of the vaccine and at least 60% of adults (and 75% of children 0-18) having been exposed to the virus by February 2022, per the Centers for Disease Control and Prevention (with exposure probably much higher now in July 2022 after subsequent Omicron subvariants waves).

So, what about Omicron-specific boosters? A booster shot will just raise antibodies temporarily, but their effectiveness wanes several months later. Moreover, a booster shot against the ancestral strain is not very effective in neutralizing BA.4 and BA.5 (with a prior BA.1 Omicron infection being more effective than a booster). Luckily, Pfizer has promised a BA.4/BA.5-specific mRNA vaccine by October, and Moderna has promised a bivalent vaccine containing BA.4/BA.5 mRNA sequences around the same time. A vaccine that specifically increases antibodies against the most prevalent circulating strain should be important as a booster for those who are predisposed to severe breakthrough infections (for example, those with immunocompromise or older individuals with multiple comorbidities). Moreover, BA.4/BA.5–specific booster vaccines may help prevent mild infections for many individuals. Finally, any booster (or exposure) should diversify and broaden T-cell responses to the virus, and a booster shot will also expand the potency of B cells, making them better able to respond to the newest subvariants as we continue to live with COVID-19.
 

Monica Gandhi, MD, MPH, is an infectious diseases doctor, professor of medicine, and associate chief in the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco.

A version of this article first appeared on Medscape.com.

The picture around the BA.4 and BA.5 subvariants of Omicron has been really confusing in that the pair is driving up cases but global COVID-19 deaths remain at their lowest level since the beginning of the pandemic. I wanted to explain what is happening with these subvariants, in that the picture seems to be one of antibody evasion without the dodging of cellular immunity. Explaining the two components of the immune response – antibodies versus cellular immune responses – can help us understand where we are in the pandemic and future booster options.

These two subvariants of Omicron, as of July 5, make up more than half of the COVID-19 strains in the United States and are expected to keep increasing. One of two reasons can lead to a variant or subvariant becoming dominant strain: increased transmissibility or evasion of antibodies.

Although BA.4 and BA.5 could be more transmissible than other subvariants of Omicron (which is already very transmissible), this has not yet been established in experiments showing increased affinity for the human receptor or in animal models. What we do know is that BA.4 and BA.5 seem to evade neutralizing antibodies conferred by the vaccines or even prior BA.1 infection (an earlier subvariant of Omicron), which could be the reason we are seeing so many reinfections now. Of note, BA.1 infection conferred antibodies that protected against subsequent BA.2 infection, so we did not see the same spike in cases in the United States with BA.2 (after a large BA.1 spike over the winter) earlier this spring.

Okay, so isn’t evasion of antibodies a bad thing? Of course it is but, luckily, our immune system is “redundant” and doesn›t just rely on antibodies to protect us from infection. In fact, antibodies (such as IgA, which is the mucosal antibody most prevalent in the nose and mouth, and IgG, which is the most prevalent antibody in the bloodstream) are our first line of COVID-19 defense in the nasal mucosa. Therefore, mild upper respiratory infections will be common as BA.4/BA.5 evade our nasal antibodies. Luckily, the rate of severe disease is remaining low throughout the world, probably because of the high amounts of cellular immunity to the virus. B and T cells are our protectors from severe disease.

For instance, two-dose vaccines are still conferring high rates of protection from severe disease with the BA.4 and BA.5 variants, with 87% protection against hospitalization per South Africa data. This is probably attributable to the fact that T-cell immunity from the vaccines remains protective across variants “from Alpha to Omicron,” as described by a recent and elegant paper.

Data from Qatar show that natural infection (even occurring up to 14 months ago) remains very protective (97.3%) against severe disease with the current circulating subvariants, including BA.4 and BA.5. Again, this is probably attributable to T cells which specifically amplify in response to a piece of the virus and help recruit cells to attack the pathogen directly.

The original BA.1 subvariant of Omicron has 26-32 mutations along its spike protein that differ from the “ancestral strain,” and BA.4 and BA.5 variants have a few more. Our T-cell response, even across a mutated spike protein, is so robust that we have not seen Omicron yet able to evade the many T cells (which we produce from the vaccines or infection) that descend upon the mutated virus to fight severe disease. Antibody-producing memory B cells, generated by the vaccines (or prior infection), have been shown to actually adapt their immune response to the variant to which they are exposed.

Therefore, the story of the BA.4 and BA.5 subvariants seems to remain about antibodies vs. cellular immunity. Our immunity in the United States is growing and is from both vaccination and natural infection, with 78.3% of the population having had at least one dose of the vaccine and at least 60% of adults (and 75% of children 0-18) having been exposed to the virus by February 2022, per the Centers for Disease Control and Prevention (with exposure probably much higher now in July 2022 after subsequent Omicron subvariants waves).

So, what about Omicron-specific boosters? A booster shot will just raise antibodies temporarily, but their effectiveness wanes several months later. Moreover, a booster shot against the ancestral strain is not very effective in neutralizing BA.4 and BA.5 (with a prior BA.1 Omicron infection being more effective than a booster). Luckily, Pfizer has promised a BA.4/BA.5-specific mRNA vaccine by October, and Moderna has promised a bivalent vaccine containing BA.4/BA.5 mRNA sequences around the same time. A vaccine that specifically increases antibodies against the most prevalent circulating strain should be important as a booster for those who are predisposed to severe breakthrough infections (for example, those with immunocompromise or older individuals with multiple comorbidities). Moreover, BA.4/BA.5–specific booster vaccines may help prevent mild infections for many individuals. Finally, any booster (or exposure) should diversify and broaden T-cell responses to the virus, and a booster shot will also expand the potency of B cells, making them better able to respond to the newest subvariants as we continue to live with COVID-19.
 

Monica Gandhi, MD, MPH, is an infectious diseases doctor, professor of medicine, and associate chief in the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco.

A version of this article first appeared on Medscape.com.

Researchers published the study covered in this summary on medRxiv.org as a preprint that has not yet been peer reviewed.

Key takeaways

• The study results suggest that obesity may accelerate waning of antibody response to SARS-CoV-2 vaccination and increased breakthrough infections with COVID-19.
• The findings documented evidence of reduced neutralizing antibody capacity 6 months after primary vaccination in people with severe obesity.
• This was a large study involving about more than 3.5 million people who had received at least two doses of COVID-19 vaccine, including more than 650,000 with obesity.

Why this matters

• Obesity is associated with comorbidities that independently increase the risk for severe COVID-19, including type 2 diabetes, chronic kidney disease, and heart failure.
• The authors concluded that additional or more frequent booster doses are likely to be required to maintain protection among people with obesity against COVID-19.

Study design

• Prospective longitudinal study of the incidence and severity of COVID-19 infections and immune responses in a cohort of more than 3.5 million adults from a Scottish healthcare database who received two or three doses of COVID-19 vaccine. The data came from the study, centered at the University of Edinburgh.
• About 16% had obesity with a body mass index of 30-39.9 kg/m², and an additional 3% had severe obesity with a BMI of 40 or greater.
• Although not specified in this preprint, another said that the vaccines administered in Scotland have been the Pfizer-BioNTech and Oxford-AstraZeneca formulations.

Key results

• Between Sept. 14, 2020, and March 19, 2022, 10,983 people (0.3% of the total cohort; 6.0 events per 1,000 person-years) had severe COVID-19, consisting of 9,733 who were hospitalized and 2,207 who died (957 of those hospitalized also died).
• People with obesity or severe obesity were at higher risk of hospitalization or death from COVID-19 after both a second and third (booster) dose of vaccine.
• Compared with those with normal weight, those with severe obesity (BMI higher than 40) were at significantly increased risk for severe COVID-19 after a second vaccine dose, with an adjusted rate ratio 1.76, whereas those with standard obesity (BMI, 30-40) were at a modestly but significantly increased risk with an adjusted rate ratio of 1.11.
• Breakthrough infections after the second dose for those with severe obesity, obesity, and normal weight occurred on average at 10 weeks, 15 weeks, and 20 weeks, respectively.
• Interaction testing showed that vaccine effectiveness significantly diminished over time across BMI groups, and protection waned more rapidly as BMI increased.
• Results from immunophenotyping studies run in a subgroup of several dozen subjects with severe obesity or normal weight showed significant decrements in the robustness of antibody responses in those with severe obesity 6 months after a second or third vaccine dose.

Limitations

• The authors did not specify any limitations.

Disclosures

• The study received no commercial funding.
• One author received funding from Wellcome.

This is a summary of a preprint research study , “Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity,” published by researchers primarily at the University of Cambridge (England), on medRxiv. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.



A version of this article first appeared on Medscape.com.

Researchers published the study covered in this summary on medRxiv.org as a preprint that has not yet been peer reviewed.

Key takeaways

• The study results suggest that obesity may accelerate waning of antibody response to SARS-CoV-2 vaccination and increased breakthrough infections with COVID-19.
• The findings documented evidence of reduced neutralizing antibody capacity 6 months after primary vaccination in people with severe obesity.
• This was a large study involving about more than 3.5 million people who had received at least two doses of COVID-19 vaccine, including more than 650,000 with obesity.

Why this matters

• Obesity is associated with comorbidities that independently increase the risk for severe COVID-19, including type 2 diabetes, chronic kidney disease, and heart failure.
• The authors concluded that additional or more frequent booster doses are likely to be required to maintain protection among people with obesity against COVID-19.

Study design

• Prospective longitudinal study of the incidence and severity of COVID-19 infections and immune responses in a cohort of more than 3.5 million adults from a Scottish healthcare database who received two or three doses of COVID-19 vaccine. The data came from the study, centered at the University of Edinburgh.
• About 16% had obesity with a body mass index of 30-39.9 kg/m², and an additional 3% had severe obesity with a BMI of 40 or greater.
• Although not specified in this preprint, another said that the vaccines administered in Scotland have been the Pfizer-BioNTech and Oxford-AstraZeneca formulations.

Key results

• Between Sept. 14, 2020, and March 19, 2022, 10,983 people (0.3% of the total cohort; 6.0 events per 1,000 person-years) had severe COVID-19, consisting of 9,733 who were hospitalized and 2,207 who died (957 of those hospitalized also died).
• People with obesity or severe obesity were at higher risk of hospitalization or death from COVID-19 after both a second and third (booster) dose of vaccine.
• Compared with those with normal weight, those with severe obesity (BMI higher than 40) were at significantly increased risk for severe COVID-19 after a second vaccine dose, with an adjusted rate ratio 1.76, whereas those with standard obesity (BMI, 30-40) were at a modestly but significantly increased risk with an adjusted rate ratio of 1.11.
• Breakthrough infections after the second dose for those with severe obesity, obesity, and normal weight occurred on average at 10 weeks, 15 weeks, and 20 weeks, respectively.
• Interaction testing showed that vaccine effectiveness significantly diminished over time across BMI groups, and protection waned more rapidly as BMI increased.
• Results from immunophenotyping studies run in a subgroup of several dozen subjects with severe obesity or normal weight showed significant decrements in the robustness of antibody responses in those with severe obesity 6 months after a second or third vaccine dose.

Limitations

• The authors did not specify any limitations.

Disclosures

• The study received no commercial funding.
• One author received funding from Wellcome.

This is a summary of a preprint research study , “Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity,” published by researchers primarily at the University of Cambridge (England), on medRxiv. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.



A version of this article first appeared on Medscape.com.

Researchers published the study covered in this summary on medRxiv.org as a preprint that has not yet been peer reviewed.

Key takeaways

• The study results suggest that obesity may accelerate waning of antibody response to SARS-CoV-2 vaccination and increased breakthrough infections with COVID-19.
• The findings documented evidence of reduced neutralizing antibody capacity 6 months after primary vaccination in people with severe obesity.
• This was a large study involving about more than 3.5 million people who had received at least two doses of COVID-19 vaccine, including more than 650,000 with obesity.

Why this matters

• Obesity is associated with comorbidities that independently increase the risk for severe COVID-19, including type 2 diabetes, chronic kidney disease, and heart failure.
• The authors concluded that additional or more frequent booster doses are likely to be required to maintain protection among people with obesity against COVID-19.

Study design

• Prospective longitudinal study of the incidence and severity of COVID-19 infections and immune responses in a cohort of more than 3.5 million adults from a Scottish healthcare database who received two or three doses of COVID-19 vaccine. The data came from the study, centered at the University of Edinburgh.
• About 16% had obesity with a body mass index of 30-39.9 kg/m², and an additional 3% had severe obesity with a BMI of 40 or greater.
• Although not specified in this preprint, another said that the vaccines administered in Scotland have been the Pfizer-BioNTech and Oxford-AstraZeneca formulations.

Key results

• Between Sept. 14, 2020, and March 19, 2022, 10,983 people (0.3% of the total cohort; 6.0 events per 1,000 person-years) had severe COVID-19, consisting of 9,733 who were hospitalized and 2,207 who died (957 of those hospitalized also died).
• People with obesity or severe obesity were at higher risk of hospitalization or death from COVID-19 after both a second and third (booster) dose of vaccine.
• Compared with those with normal weight, those with severe obesity (BMI higher than 40) were at significantly increased risk for severe COVID-19 after a second vaccine dose, with an adjusted rate ratio 1.76, whereas those with standard obesity (BMI, 30-40) were at a modestly but significantly increased risk with an adjusted rate ratio of 1.11.
• Breakthrough infections after the second dose for those with severe obesity, obesity, and normal weight occurred on average at 10 weeks, 15 weeks, and 20 weeks, respectively.
• Interaction testing showed that vaccine effectiveness significantly diminished over time across BMI groups, and protection waned more rapidly as BMI increased.
• Results from immunophenotyping studies run in a subgroup of several dozen subjects with severe obesity or normal weight showed significant decrements in the robustness of antibody responses in those with severe obesity 6 months after a second or third vaccine dose.

Limitations

• The authors did not specify any limitations.

Disclosures

• The study received no commercial funding.
• One author received funding from Wellcome.

This is a summary of a preprint research study , “Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity,” published by researchers primarily at the University of Cambridge (England), on medRxiv. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.



A version of this article first appeared on Medscape.com.

Among scientists, the existence of long COVID-19 in children and adolescents has been the subject of debate. Two published studies have drawn attention to long COVID-19 signs and symptoms in these patients.

Published by a Mexican multidisciplinary group in Scientific Reports, the first study is a systematic review and meta-analysis. It identified mood symptoms as the most prevalent clinical manifestations of long COVID-19 in children and adolescents. These symptoms included sadness, tension, anger, depression, and anxiety (16.50%); fatigue (9.66%); and sleep disorders (8.42%).

The second study, LongCOVIDKidsDK, was conducted in Denmark. It compared 11,000 children younger than 14 years who had tested positive for COVID-19 with 33,000 children who had no history of COVID-19. The study was published in The Lancet Child and Adolescent Health.
 

Definitions are changing

In their meta-analysis, the researchers estimated the prevalence and counted signs and symptoms of long COVID-19, as defined by the United Kingdom’s National Institute for Health and Care Excellence. Long COVID-19 was defined as the presence of one or more symptoms more than 4 weeks after SARS-CoV-2 infection. For search terms, the researchers used “COVID-19,” “COVID,” “SARSCOV-2,” “coronavirus,” “long COVID,” “postCOVID,” “PASC,” “long-haulers,” “prolonged,” “post-acute,” “persistent,” “convalescent,” “sequelae,” and “postviral.”

Of the 8,373 citations returned by the search as of Feb. 10, 2022, 21 prospective studies, 2 of them on preprint servers, met the authors’ selection criteria. Those studies included a total of 80,071 children and adolescents younger than 18 years.

In the meta-analysis, the prevalence of long COVID-19 among children and adolescents was reported to be 25.24% (95% confidence interval, 18.17-33.02; I2, 99.61%), regardless of whether the case had been asymptomatic, mild, moderate, severe, or serious. For patients who had been hospitalized, the prevalence was 29.19% (95% CI, 17.83-41.98; I2, 80.84%).

These numbers, while striking, are not the focus of the study, according to first author Sandra Lopez-Leon, MD, PhD, associate professor of pharmacoepidemiology at Rutgers University, New Brunswick, N.J. “It’s important that we don’t focus on that 25%,” she said in an interview. “It’s a disease that we’re learning about, we’re at a time when the definitions are still changing, and, depending on when it is measured, a different number will be given. The message we want to give is that long COVID-19 exists, it’s happening in children and adolescents, and patients need this recognition. And also to show that it can affect the whole body.”

The study showed that the children and adolescents who presented with SARS-CoV-2 infection were at higher risk of subsequent long dyspnea, anosmia/ageusia, or fever, compared with control persons.

In total, in the studies that were included, more than 40 long-term clinical manifestations associated with COVID-19 in the pediatric population were identified.

The most common symptoms among children aged 0-3 years were mood swings, skin rashes, and stomachaches. In 4- to 11-year-olds, the most common symptoms were mood swings, trouble remembering or concentrating, and skin rashes. In 12- to 14-year-olds, they were fatigue, mood swings, and trouble remembering or concentrating. These data are based on parent responses.

The list of signs and symptoms also includes headache, respiratory symptoms, cognitive symptoms (such as decreased concentration, learning difficulties, confusion, and memory loss), loss of appetite, and smell disorder (hyposmia, anosmia, hyperosmia, parosmia, and phantom smell).

In the studies, the prevalence of the following symptoms was less than 5%: hyperhidrosis, chest pain, dizziness, cough, myalgia/arthralgia, changes in body weight, taste disorder, otalgia (tinnitus, ear pain, vertigo), ophthalmologic symptoms (conjunctivitis, dry eye, blurred vision, photophobia, pain), dermatologic symptoms (dry skin, itchy skin, rashes, hives, hair loss), urinary symptoms, abdominal pain, throat pain, chest tightness, variations in heart rate, palpitations, constipation, dysphonia, fever, diarrhea, vomiting/nausea, menstrual changes, neurological abnormalities, speech disorders, and dysphagia.

The authors made it clear that the frequency and severity of these symptoms can fluctuate from one patient to another.

“The meta-analysis is important because it brings together 21 studies selected from more than 8,000 articles – and in them, a large number of children – to study the most common manifestations of long COVID-19,” Gabriela Ensinck, MD, head of the infectious diseases department at the Víctor J. Vilela Children’s Hospital in Rosario, Argentina, told this news organization. Dr. Ensinck did not participate in the study. “The important thing here is that long COVID-19 exists in pediatrics. And that it is a prolongation of signs or symptoms over time, a time for which there is no single definition.”

“It’s a snapshot of all the symptoms that can remain after COVID-19,” Dr. Lopez-Leon explained. “The meta-analysis seeks to see if there’s an association between having had COVID-19 and having the symptoms, but at no time does it speak of causality.”

The prevalence of symptoms largely depends on the time since the onset of acute COVID-19. Most symptoms improve over time. In the studies that were included in the meta-analysis, the follow-up time varied between 1 and 13 months. It is important to understand what symptoms are associated with each period after the onset of infection, the authors said.
 

Danish parent survey

The Danish study LongCOVIDKidsDK followed the World Health Organization criteria for long COVID-19 and included children and adolescents aged 0-14 years who received a diagnosis of COVID-19 and who experienced symptoms that lasted at least 2 months.

Between July 20, 2021, and Sept. 15, 2021, a questionnaire was sent to 38,152 case patients and 147,212 control persons. Of this group, 10,997 (28.8%) case patients and 33,016 (22.4%) control persons answered the survey.

Children who had been diagnosed with SARS-CoV-2 infection were more likely to experience long-lasting symptoms than children who had never been diagnosed. Approximately one-third of children with a positive SARS-CoV-2 test experienced symptoms that were not present before infection. Children who experienced long-lasting symptoms included 40% of children diagnosed with COVID-19 and 27% of control persons aged 0-3 years, 38% of case patients and 34% of control persons aged 4-11 years, and 46% of case patients and 41% of control persons aged 12-14 years.

Interestingly, those diagnosed with COVID-19 reported fewer psychological and social problems than those in the control group. Among the oldest (aged 12-14 years), quality of life scores were higher and anxiety scores were lower for those who had tested positive for SARS-CoV-2.
 

More information needed

Given the diversity of symptoms in the meta-analysis and the LongCOVIDKidsDK study, a multidisciplinary approach is imperative. Dr. Lopez-Leon suggests that there is a need to raise awareness among parents, clinicians, researchers, and the health system about the conditions that can occur after COVID-19. Clinicians must better understand the sequelae to provide targeted care and treatment. The authors of the Danish study recommend establishing clinics for long COVID-19 with multispecialty care.

Maren J. Heilskov Rytter, PhD, associate professor of clinical medicine at the University of Copenhagen, wrote an editorial in The Lancet Child and Adolescent Health about the Danish study. Until it is clarified whether SARS-CoV-2 does indeed cause persistent symptoms, she wrote, “it seems excessive and premature to establish specific multidisciplinary clinics for children with long COVID-19.”

Dr. Rytter highlighted the difficulty of interpreting LongCOVIDKidsDK data, owing to recall bias, the failure to exclude other causes of symptoms in the cases analyzed, and the number of symptoms in the control persons. In addition, the data analyzed in Denmark are of limited clinical relevance, she said, given a greater presence of mild symptoms and, paradoxically, a higher quality of life.

She concluded, “In the majority of children with nonspecific symptoms after COVID-19, the symptoms presented are more likely to have been caused by something other than COVID-19, and if they are related to COVID-19, they are likely to go away over time.”

Dr. Ensinck, who is coauthor of the Argentine Ministry of Health’s guide for long COVID-19 monitoring for children and adolescents and who represented the Infectious Diseases Committee of the Argentine Society of Pediatrics, highlighted another aspect of the problem. “What should be taken into account in these data is to see how much the confinement contributed. Children are the ones who suffered the most in the period in which schools were closed; they could not meet their peers, they had sick relatives, they felt fear. … all this must be taken into account.”

There is as yet no agreement on how to define and diagnose long COVID-19 in adults, a population that has been studied more closely. Part of the problem is that long COVID-19 has been linked to more than 200 symptoms, which can range in severity from inconvenient to debilitating, can last for months or years, and can recur, sometimes months after apparent recovery. Thus, there are still disparate answers to basic questions about the syndrome’s frequency and its effects on vaccination, reinfection, and the latest variant of SARS-CoV-2.

This article has been translated from the Medscape Spanish edition. A version appeared on Medscape.com.

Among scientists, the existence of long COVID-19 in children and adolescents has been the subject of debate. Two published studies have drawn attention to long COVID-19 signs and symptoms in these patients.

Published by a Mexican multidisciplinary group in Scientific Reports, the first study is a systematic review and meta-analysis. It identified mood symptoms as the most prevalent clinical manifestations of long COVID-19 in children and adolescents. These symptoms included sadness, tension, anger, depression, and anxiety (16.50%); fatigue (9.66%); and sleep disorders (8.42%).

The second study, LongCOVIDKidsDK, was conducted in Denmark. It compared 11,000 children younger than 14 years who had tested positive for COVID-19 with 33,000 children who had no history of COVID-19. The study was published in The Lancet Child and Adolescent Health.
 

Definitions are changing

In their meta-analysis, the researchers estimated the prevalence and counted signs and symptoms of long COVID-19, as defined by the United Kingdom’s National Institute for Health and Care Excellence. Long COVID-19 was defined as the presence of one or more symptoms more than 4 weeks after SARS-CoV-2 infection. For search terms, the researchers used “COVID-19,” “COVID,” “SARSCOV-2,” “coronavirus,” “long COVID,” “postCOVID,” “PASC,” “long-haulers,” “prolonged,” “post-acute,” “persistent,” “convalescent,” “sequelae,” and “postviral.”

Of the 8,373 citations returned by the search as of Feb. 10, 2022, 21 prospective studies, 2 of them on preprint servers, met the authors’ selection criteria. Those studies included a total of 80,071 children and adolescents younger than 18 years.

In the meta-analysis, the prevalence of long COVID-19 among children and adolescents was reported to be 25.24% (95% confidence interval, 18.17-33.02; I2, 99.61%), regardless of whether the case had been asymptomatic, mild, moderate, severe, or serious. For patients who had been hospitalized, the prevalence was 29.19% (95% CI, 17.83-41.98; I2, 80.84%).

These numbers, while striking, are not the focus of the study, according to first author Sandra Lopez-Leon, MD, PhD, associate professor of pharmacoepidemiology at Rutgers University, New Brunswick, N.J. “It’s important that we don’t focus on that 25%,” she said in an interview. “It’s a disease that we’re learning about, we’re at a time when the definitions are still changing, and, depending on when it is measured, a different number will be given. The message we want to give is that long COVID-19 exists, it’s happening in children and adolescents, and patients need this recognition. And also to show that it can affect the whole body.”

The study showed that the children and adolescents who presented with SARS-CoV-2 infection were at higher risk of subsequent long dyspnea, anosmia/ageusia, or fever, compared with control persons.

In total, in the studies that were included, more than 40 long-term clinical manifestations associated with COVID-19 in the pediatric population were identified.

The most common symptoms among children aged 0-3 years were mood swings, skin rashes, and stomachaches. In 4- to 11-year-olds, the most common symptoms were mood swings, trouble remembering or concentrating, and skin rashes. In 12- to 14-year-olds, they were fatigue, mood swings, and trouble remembering or concentrating. These data are based on parent responses.

The list of signs and symptoms also includes headache, respiratory symptoms, cognitive symptoms (such as decreased concentration, learning difficulties, confusion, and memory loss), loss of appetite, and smell disorder (hyposmia, anosmia, hyperosmia, parosmia, and phantom smell).

In the studies, the prevalence of the following symptoms was less than 5%: hyperhidrosis, chest pain, dizziness, cough, myalgia/arthralgia, changes in body weight, taste disorder, otalgia (tinnitus, ear pain, vertigo), ophthalmologic symptoms (conjunctivitis, dry eye, blurred vision, photophobia, pain), dermatologic symptoms (dry skin, itchy skin, rashes, hives, hair loss), urinary symptoms, abdominal pain, throat pain, chest tightness, variations in heart rate, palpitations, constipation, dysphonia, fever, diarrhea, vomiting/nausea, menstrual changes, neurological abnormalities, speech disorders, and dysphagia.

The authors made it clear that the frequency and severity of these symptoms can fluctuate from one patient to another.

“The meta-analysis is important because it brings together 21 studies selected from more than 8,000 articles – and in them, a large number of children – to study the most common manifestations of long COVID-19,” Gabriela Ensinck, MD, head of the infectious diseases department at the Víctor J. Vilela Children’s Hospital in Rosario, Argentina, told this news organization. Dr. Ensinck did not participate in the study. “The important thing here is that long COVID-19 exists in pediatrics. And that it is a prolongation of signs or symptoms over time, a time for which there is no single definition.”

“It’s a snapshot of all the symptoms that can remain after COVID-19,” Dr. Lopez-Leon explained. “The meta-analysis seeks to see if there’s an association between having had COVID-19 and having the symptoms, but at no time does it speak of causality.”

The prevalence of symptoms largely depends on the time since the onset of acute COVID-19. Most symptoms improve over time. In the studies that were included in the meta-analysis, the follow-up time varied between 1 and 13 months. It is important to understand what symptoms are associated with each period after the onset of infection, the authors said.
 

Danish parent survey

The Danish study LongCOVIDKidsDK followed the World Health Organization criteria for long COVID-19 and included children and adolescents aged 0-14 years who received a diagnosis of COVID-19 and who experienced symptoms that lasted at least 2 months.

Between July 20, 2021, and Sept. 15, 2021, a questionnaire was sent to 38,152 case patients and 147,212 control persons. Of this group, 10,997 (28.8%) case patients and 33,016 (22.4%) control persons answered the survey.

Children who had been diagnosed with SARS-CoV-2 infection were more likely to experience long-lasting symptoms than children who had never been diagnosed. Approximately one-third of children with a positive SARS-CoV-2 test experienced symptoms that were not present before infection. Children who experienced long-lasting symptoms included 40% of children diagnosed with COVID-19 and 27% of control persons aged 0-3 years, 38% of case patients and 34% of control persons aged 4-11 years, and 46% of case patients and 41% of control persons aged 12-14 years.

Interestingly, those diagnosed with COVID-19 reported fewer psychological and social problems than those in the control group. Among the oldest (aged 12-14 years), quality of life scores were higher and anxiety scores were lower for those who had tested positive for SARS-CoV-2.
 

More information needed

Given the diversity of symptoms in the meta-analysis and the LongCOVIDKidsDK study, a multidisciplinary approach is imperative. Dr. Lopez-Leon suggests that there is a need to raise awareness among parents, clinicians, researchers, and the health system about the conditions that can occur after COVID-19. Clinicians must better understand the sequelae to provide targeted care and treatment. The authors of the Danish study recommend establishing clinics for long COVID-19 with multispecialty care.

Maren J. Heilskov Rytter, PhD, associate professor of clinical medicine at the University of Copenhagen, wrote an editorial in The Lancet Child and Adolescent Health about the Danish study. Until it is clarified whether SARS-CoV-2 does indeed cause persistent symptoms, she wrote, “it seems excessive and premature to establish specific multidisciplinary clinics for children with long COVID-19.”

Dr. Rytter highlighted the difficulty of interpreting LongCOVIDKidsDK data, owing to recall bias, the failure to exclude other causes of symptoms in the cases analyzed, and the number of symptoms in the control persons. In addition, the data analyzed in Denmark are of limited clinical relevance, she said, given a greater presence of mild symptoms and, paradoxically, a higher quality of life.

She concluded, “In the majority of children with nonspecific symptoms after COVID-19, the symptoms presented are more likely to have been caused by something other than COVID-19, and if they are related to COVID-19, they are likely to go away over time.”

Dr. Ensinck, who is coauthor of the Argentine Ministry of Health’s guide for long COVID-19 monitoring for children and adolescents and who represented the Infectious Diseases Committee of the Argentine Society of Pediatrics, highlighted another aspect of the problem. “What should be taken into account in these data is to see how much the confinement contributed. Children are the ones who suffered the most in the period in which schools were closed; they could not meet their peers, they had sick relatives, they felt fear. … all this must be taken into account.”

There is as yet no agreement on how to define and diagnose long COVID-19 in adults, a population that has been studied more closely. Part of the problem is that long COVID-19 has been linked to more than 200 symptoms, which can range in severity from inconvenient to debilitating, can last for months or years, and can recur, sometimes months after apparent recovery. Thus, there are still disparate answers to basic questions about the syndrome’s frequency and its effects on vaccination, reinfection, and the latest variant of SARS-CoV-2.

This article has been translated from the Medscape Spanish edition. A version appeared on Medscape.com.

Among scientists, the existence of long COVID-19 in children and adolescents has been the subject of debate. Two published studies have drawn attention to long COVID-19 signs and symptoms in these patients.

Published by a Mexican multidisciplinary group in Scientific Reports, the first study is a systematic review and meta-analysis. It identified mood symptoms as the most prevalent clinical manifestations of long COVID-19 in children and adolescents. These symptoms included sadness, tension, anger, depression, and anxiety (16.50%); fatigue (9.66%); and sleep disorders (8.42%).

The second study, LongCOVIDKidsDK, was conducted in Denmark. It compared 11,000 children younger than 14 years who had tested positive for COVID-19 with 33,000 children who had no history of COVID-19. The study was published in The Lancet Child and Adolescent Health.
 

Definitions are changing

In their meta-analysis, the researchers estimated the prevalence and counted signs and symptoms of long COVID-19, as defined by the United Kingdom’s National Institute for Health and Care Excellence. Long COVID-19 was defined as the presence of one or more symptoms more than 4 weeks after SARS-CoV-2 infection. For search terms, the researchers used “COVID-19,” “COVID,” “SARSCOV-2,” “coronavirus,” “long COVID,” “postCOVID,” “PASC,” “long-haulers,” “prolonged,” “post-acute,” “persistent,” “convalescent,” “sequelae,” and “postviral.”

Of the 8,373 citations returned by the search as of Feb. 10, 2022, 21 prospective studies, 2 of them on preprint servers, met the authors’ selection criteria. Those studies included a total of 80,071 children and adolescents younger than 18 years.

In the meta-analysis, the prevalence of long COVID-19 among children and adolescents was reported to be 25.24% (95% confidence interval, 18.17-33.02; I2, 99.61%), regardless of whether the case had been asymptomatic, mild, moderate, severe, or serious. For patients who had been hospitalized, the prevalence was 29.19% (95% CI, 17.83-41.98; I2, 80.84%).

These numbers, while striking, are not the focus of the study, according to first author Sandra Lopez-Leon, MD, PhD, associate professor of pharmacoepidemiology at Rutgers University, New Brunswick, N.J. “It’s important that we don’t focus on that 25%,” she said in an interview. “It’s a disease that we’re learning about, we’re at a time when the definitions are still changing, and, depending on when it is measured, a different number will be given. The message we want to give is that long COVID-19 exists, it’s happening in children and adolescents, and patients need this recognition. And also to show that it can affect the whole body.”

The study showed that the children and adolescents who presented with SARS-CoV-2 infection were at higher risk of subsequent long dyspnea, anosmia/ageusia, or fever, compared with control persons.

In total, in the studies that were included, more than 40 long-term clinical manifestations associated with COVID-19 in the pediatric population were identified.

The most common symptoms among children aged 0-3 years were mood swings, skin rashes, and stomachaches. In 4- to 11-year-olds, the most common symptoms were mood swings, trouble remembering or concentrating, and skin rashes. In 12- to 14-year-olds, they were fatigue, mood swings, and trouble remembering or concentrating. These data are based on parent responses.

The list of signs and symptoms also includes headache, respiratory symptoms, cognitive symptoms (such as decreased concentration, learning difficulties, confusion, and memory loss), loss of appetite, and smell disorder (hyposmia, anosmia, hyperosmia, parosmia, and phantom smell).

In the studies, the prevalence of the following symptoms was less than 5%: hyperhidrosis, chest pain, dizziness, cough, myalgia/arthralgia, changes in body weight, taste disorder, otalgia (tinnitus, ear pain, vertigo), ophthalmologic symptoms (conjunctivitis, dry eye, blurred vision, photophobia, pain), dermatologic symptoms (dry skin, itchy skin, rashes, hives, hair loss), urinary symptoms, abdominal pain, throat pain, chest tightness, variations in heart rate, palpitations, constipation, dysphonia, fever, diarrhea, vomiting/nausea, menstrual changes, neurological abnormalities, speech disorders, and dysphagia.

The authors made it clear that the frequency and severity of these symptoms can fluctuate from one patient to another.

“The meta-analysis is important because it brings together 21 studies selected from more than 8,000 articles – and in them, a large number of children – to study the most common manifestations of long COVID-19,” Gabriela Ensinck, MD, head of the infectious diseases department at the Víctor J. Vilela Children’s Hospital in Rosario, Argentina, told this news organization. Dr. Ensinck did not participate in the study. “The important thing here is that long COVID-19 exists in pediatrics. And that it is a prolongation of signs or symptoms over time, a time for which there is no single definition.”

“It’s a snapshot of all the symptoms that can remain after COVID-19,” Dr. Lopez-Leon explained. “The meta-analysis seeks to see if there’s an association between having had COVID-19 and having the symptoms, but at no time does it speak of causality.”

The prevalence of symptoms largely depends on the time since the onset of acute COVID-19. Most symptoms improve over time. In the studies that were included in the meta-analysis, the follow-up time varied between 1 and 13 months. It is important to understand what symptoms are associated with each period after the onset of infection, the authors said.
 

Danish parent survey

The Danish study LongCOVIDKidsDK followed the World Health Organization criteria for long COVID-19 and included children and adolescents aged 0-14 years who received a diagnosis of COVID-19 and who experienced symptoms that lasted at least 2 months.

Between July 20, 2021, and Sept. 15, 2021, a questionnaire was sent to 38,152 case patients and 147,212 control persons. Of this group, 10,997 (28.8%) case patients and 33,016 (22.4%) control persons answered the survey.

Children who had been diagnosed with SARS-CoV-2 infection were more likely to experience long-lasting symptoms than children who had never been diagnosed. Approximately one-third of children with a positive SARS-CoV-2 test experienced symptoms that were not present before infection. Children who experienced long-lasting symptoms included 40% of children diagnosed with COVID-19 and 27% of control persons aged 0-3 years, 38% of case patients and 34% of control persons aged 4-11 years, and 46% of case patients and 41% of control persons aged 12-14 years.

Interestingly, those diagnosed with COVID-19 reported fewer psychological and social problems than those in the control group. Among the oldest (aged 12-14 years), quality of life scores were higher and anxiety scores were lower for those who had tested positive for SARS-CoV-2.
 

More information needed

Given the diversity of symptoms in the meta-analysis and the LongCOVIDKidsDK study, a multidisciplinary approach is imperative. Dr. Lopez-Leon suggests that there is a need to raise awareness among parents, clinicians, researchers, and the health system about the conditions that can occur after COVID-19. Clinicians must better understand the sequelae to provide targeted care and treatment. The authors of the Danish study recommend establishing clinics for long COVID-19 with multispecialty care.

Maren J. Heilskov Rytter, PhD, associate professor of clinical medicine at the University of Copenhagen, wrote an editorial in The Lancet Child and Adolescent Health about the Danish study. Until it is clarified whether SARS-CoV-2 does indeed cause persistent symptoms, she wrote, “it seems excessive and premature to establish specific multidisciplinary clinics for children with long COVID-19.”

Dr. Rytter highlighted the difficulty of interpreting LongCOVIDKidsDK data, owing to recall bias, the failure to exclude other causes of symptoms in the cases analyzed, and the number of symptoms in the control persons. In addition, the data analyzed in Denmark are of limited clinical relevance, she said, given a greater presence of mild symptoms and, paradoxically, a higher quality of life.

She concluded, “In the majority of children with nonspecific symptoms after COVID-19, the symptoms presented are more likely to have been caused by something other than COVID-19, and if they are related to COVID-19, they are likely to go away over time.”

Dr. Ensinck, who is coauthor of the Argentine Ministry of Health’s guide for long COVID-19 monitoring for children and adolescents and who represented the Infectious Diseases Committee of the Argentine Society of Pediatrics, highlighted another aspect of the problem. “What should be taken into account in these data is to see how much the confinement contributed. Children are the ones who suffered the most in the period in which schools were closed; they could not meet their peers, they had sick relatives, they felt fear. … all this must be taken into account.”

There is as yet no agreement on how to define and diagnose long COVID-19 in adults, a population that has been studied more closely. Part of the problem is that long COVID-19 has been linked to more than 200 symptoms, which can range in severity from inconvenient to debilitating, can last for months or years, and can recur, sometimes months after apparent recovery. Thus, there are still disparate answers to basic questions about the syndrome’s frequency and its effects on vaccination, reinfection, and the latest variant of SARS-CoV-2.

This article has been translated from the Medscape Spanish edition. A version appeared on Medscape.com.

GLASGOW – Individuals given COVID-19 vaccination may experience a wide range of dermatologic reactions, some of which may be life-threatening, reveals a prospective Indian study that suggests histopathological assessment is key to understanding the cause.

Studying more than 130 patients who presented with vaccine-related dermatologic reactions, the researchers found that the most common acute adverse events were acute urticaria, generalized pruritus, and maculopapular rash.

Dermal hypersensitivity reactions occurred within 3 days of vaccination, which suggests the culprit is an immediate type 1 hypersensitivity reaction, said study presenter Alpana Mohta, MD, department of dermatology, Sardar Patel Medical College, Bikaner, Rajasthan, India. Most of the patients had received the AstraZeneca vaccine, she said.

The most common delayed events were pityriasis rosea and lichen planus, which occurred within 3-4 weeks of vaccination and could be a result of delayed hypersensitivity or a T cell–mediated skin reaction caused by “molecular mimicry with a viral epitope,” Dr. Mohta said.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 5.

Dr. Mohta said that, given the “surge” in the number of people who have been vaccinated, it is “imperative as dermatologists” to maintain a “very high index of suspicion to differentiate reactions caused by vaccination” from other causes, and a proper assessment should be performed in “every patient” who presents with a possible reaction.

She also emphasized that “since so many clinical [COVID-19] variants are being encountered,” histopathological assessment could “help in better understanding the underlying pathophysiology” of every reaction.

Dr. Mohta began her presentation by explaining that India is running one of the “world’s largest vaccination drives” for COVID-19, with almost 90% of adults fully vaccinated.

She added that studies have indicated that the incidence of cutaneous adverse reactions following COVID-19 vaccination ranges from 1.0% to 1.9% and that dermatologists have encountered a “plethora” of related reactions.

Dr. Mohta emphasized that the “myriad presentations” of these reactions means that correlating clinical and pathological findings is “key” to understanding the underlying pathophysiology.

She and her colleagues therefore conducted a prospective, hospital-based study of patients who self-reported mucocutaneous adverse reactions from April to December 2021, within 4 weeks of receiving a COVID-19 vaccine.

They gathered information on the patients’ signs and symptoms, as well as the date of vaccine administration and the type of vaccine given, alongside a detailed medical history, including previous allergies, prior COVID-19 infection, and any comorbidities.

The patients also underwent a clinical examination and laboratory investigations, and their cases were assessed by two senior dermatologists to determine whether the association between the adverse event and COVID-19 vaccination was likely causal.

Dr. Mohta said that 132 adult patients, with an average age of 38.2 years, were identified as having vaccine-related reactions.

This included 84 (63.6%) patients with a mild reaction, defined as resolving with symptomatic treatment; 43 (32.6%) patients with a moderate reaction, defined as extensive and lasting for more than 4 weeks; and five (3.8%) patients with severe reactions, defined as systemic and potentially life-threatening.

The mild group included 21 patients with acute urticaria, with a mean onset of 1.2 days following vaccination, as well as 20 cases of maculopapular rash, with a mean onset of 2.4 days; 18 cases of pityriasis rosea, with a mean onset of 17.4 days; and nine cases of eruptive pseudoangioma, with a mean onset of 3.5 days.

There were 16 cases of lichen planus in the moderate group, with a mean onset of 22.7 days after COVID-19 vaccination; nine cases of herpes zoster, with a mean onset of 15.3 days; and one case of pityriasis lichenoides et varioliformis acuta (PLEVA), among others.

The severe group included two cases of erythroderma, with a mean onset of 9 days after vaccination; one case of drug rash with eosinophilia and systemic symptoms (DRESS), with a mean onset of 20 days; and one case each of subacute cutaneous lupus erythematosus (SCLE) and bullous pemphigoid, with mean onsets of 15 days and 14 days, respectively.

Turning to the histopathological results, Dr. Mohta explained that only 57 patients from their cohort agreed to have a skin biopsy.

Results of those skin biopsies showed that 21 (36.8%) patients had vaccine-related eruption of papules and plaques, predominantly spongiotic dermatitis. This correlated with the clinical diagnoses of pityriasis rosea, maculopapular and papulosquamous rash, and DRESS.

Lichenoid and interface dermatitis were seen in 13 (22.8%) patients, which correlated with the clinical diagnoses of lichen planus, PLEVA, and SCLE. Eleven (19.3%) patients had a dermal hypersensitivity reaction, equated to the clinical diagnoses of urticaria, and eruptive pseudoangioma.

Dr. Mohta acknowledged that the study was limited by the inability to calculate the “true prevalence of vaccine-associated reactions,” and because immunohistochemistry was not performed.

Session chair Saleem Taibjee, MD, department of dermatology, Dorset County Hospital NHS Foundation Trust, Dorchester, United Kingdom, congratulated Dr. Mohta on her “very interesting” presentation, highlighting their “extensive experience in such a large cohort of patients.”

He asked what type of COVID-19 vaccines the patients had received, and whether Dr. Mohta could provide any “insights into which patients you can safely give the vaccine again to, and those [to whom] you may avoid giving further doses.”

Dr. Mohta said that the majority of the patients in the study received the AstraZeneca COVID-19 vaccine, as that was the one most commonly used in India at the time, with around 30 patients receiving the Indian Covishield version of the AstraZeneca vaccine. (The two-dose AstraZeneca vaccine, which is cheaper to manufacture and easier to store at typical refrigerated temperatures than mRNA-based vaccines, has been authorized by the World Health Organization, the European Medicines Agency, and over 50 countries but has not been authorized in the United States.)

She added that none of the patients in the study with mild-to-moderate skin reactions were advised against receiving further doses” but that those with severe reactions “were advised not to take any further doses.”

Consequently, in the case of mild reactions, “further doses are not a contraindication,” Dr. Mohta said, but patients with more severe reactions should be considered on a “case by case basis.”

A version of this article first appeared on Medscape.com.

GLASGOW – Individuals given COVID-19 vaccination may experience a wide range of dermatologic reactions, some of which may be life-threatening, reveals a prospective Indian study that suggests histopathological assessment is key to understanding the cause.

Studying more than 130 patients who presented with vaccine-related dermatologic reactions, the researchers found that the most common acute adverse events were acute urticaria, generalized pruritus, and maculopapular rash.

Dermal hypersensitivity reactions occurred within 3 days of vaccination, which suggests the culprit is an immediate type 1 hypersensitivity reaction, said study presenter Alpana Mohta, MD, department of dermatology, Sardar Patel Medical College, Bikaner, Rajasthan, India. Most of the patients had received the AstraZeneca vaccine, she said.

The most common delayed events were pityriasis rosea and lichen planus, which occurred within 3-4 weeks of vaccination and could be a result of delayed hypersensitivity or a T cell–mediated skin reaction caused by “molecular mimicry with a viral epitope,” Dr. Mohta said.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 5.

Dr. Mohta said that, given the “surge” in the number of people who have been vaccinated, it is “imperative as dermatologists” to maintain a “very high index of suspicion to differentiate reactions caused by vaccination” from other causes, and a proper assessment should be performed in “every patient” who presents with a possible reaction.

She also emphasized that “since so many clinical [COVID-19] variants are being encountered,” histopathological assessment could “help in better understanding the underlying pathophysiology” of every reaction.

Dr. Mohta began her presentation by explaining that India is running one of the “world’s largest vaccination drives” for COVID-19, with almost 90% of adults fully vaccinated.

She added that studies have indicated that the incidence of cutaneous adverse reactions following COVID-19 vaccination ranges from 1.0% to 1.9% and that dermatologists have encountered a “plethora” of related reactions.

Dr. Mohta emphasized that the “myriad presentations” of these reactions means that correlating clinical and pathological findings is “key” to understanding the underlying pathophysiology.

She and her colleagues therefore conducted a prospective, hospital-based study of patients who self-reported mucocutaneous adverse reactions from April to December 2021, within 4 weeks of receiving a COVID-19 vaccine.

They gathered information on the patients’ signs and symptoms, as well as the date of vaccine administration and the type of vaccine given, alongside a detailed medical history, including previous allergies, prior COVID-19 infection, and any comorbidities.

The patients also underwent a clinical examination and laboratory investigations, and their cases were assessed by two senior dermatologists to determine whether the association between the adverse event and COVID-19 vaccination was likely causal.

Dr. Mohta said that 132 adult patients, with an average age of 38.2 years, were identified as having vaccine-related reactions.

This included 84 (63.6%) patients with a mild reaction, defined as resolving with symptomatic treatment; 43 (32.6%) patients with a moderate reaction, defined as extensive and lasting for more than 4 weeks; and five (3.8%) patients with severe reactions, defined as systemic and potentially life-threatening.

The mild group included 21 patients with acute urticaria, with a mean onset of 1.2 days following vaccination, as well as 20 cases of maculopapular rash, with a mean onset of 2.4 days; 18 cases of pityriasis rosea, with a mean onset of 17.4 days; and nine cases of eruptive pseudoangioma, with a mean onset of 3.5 days.

There were 16 cases of lichen planus in the moderate group, with a mean onset of 22.7 days after COVID-19 vaccination; nine cases of herpes zoster, with a mean onset of 15.3 days; and one case of pityriasis lichenoides et varioliformis acuta (PLEVA), among others.

The severe group included two cases of erythroderma, with a mean onset of 9 days after vaccination; one case of drug rash with eosinophilia and systemic symptoms (DRESS), with a mean onset of 20 days; and one case each of subacute cutaneous lupus erythematosus (SCLE) and bullous pemphigoid, with mean onsets of 15 days and 14 days, respectively.

Turning to the histopathological results, Dr. Mohta explained that only 57 patients from their cohort agreed to have a skin biopsy.

Results of those skin biopsies showed that 21 (36.8%) patients had vaccine-related eruption of papules and plaques, predominantly spongiotic dermatitis. This correlated with the clinical diagnoses of pityriasis rosea, maculopapular and papulosquamous rash, and DRESS.

Lichenoid and interface dermatitis were seen in 13 (22.8%) patients, which correlated with the clinical diagnoses of lichen planus, PLEVA, and SCLE. Eleven (19.3%) patients had a dermal hypersensitivity reaction, equated to the clinical diagnoses of urticaria, and eruptive pseudoangioma.

Dr. Mohta acknowledged that the study was limited by the inability to calculate the “true prevalence of vaccine-associated reactions,” and because immunohistochemistry was not performed.

Session chair Saleem Taibjee, MD, department of dermatology, Dorset County Hospital NHS Foundation Trust, Dorchester, United Kingdom, congratulated Dr. Mohta on her “very interesting” presentation, highlighting their “extensive experience in such a large cohort of patients.”

He asked what type of COVID-19 vaccines the patients had received, and whether Dr. Mohta could provide any “insights into which patients you can safely give the vaccine again to, and those [to whom] you may avoid giving further doses.”

Dr. Mohta said that the majority of the patients in the study received the AstraZeneca COVID-19 vaccine, as that was the one most commonly used in India at the time, with around 30 patients receiving the Indian Covishield version of the AstraZeneca vaccine. (The two-dose AstraZeneca vaccine, which is cheaper to manufacture and easier to store at typical refrigerated temperatures than mRNA-based vaccines, has been authorized by the World Health Organization, the European Medicines Agency, and over 50 countries but has not been authorized in the United States.)

She added that none of the patients in the study with mild-to-moderate skin reactions were advised against receiving further doses” but that those with severe reactions “were advised not to take any further doses.”

Consequently, in the case of mild reactions, “further doses are not a contraindication,” Dr. Mohta said, but patients with more severe reactions should be considered on a “case by case basis.”

A version of this article first appeared on Medscape.com.

GLASGOW – Individuals given COVID-19 vaccination may experience a wide range of dermatologic reactions, some of which may be life-threatening, reveals a prospective Indian study that suggests histopathological assessment is key to understanding the cause.

Studying more than 130 patients who presented with vaccine-related dermatologic reactions, the researchers found that the most common acute adverse events were acute urticaria, generalized pruritus, and maculopapular rash.

Dermal hypersensitivity reactions occurred within 3 days of vaccination, which suggests the culprit is an immediate type 1 hypersensitivity reaction, said study presenter Alpana Mohta, MD, department of dermatology, Sardar Patel Medical College, Bikaner, Rajasthan, India. Most of the patients had received the AstraZeneca vaccine, she said.

The most common delayed events were pityriasis rosea and lichen planus, which occurred within 3-4 weeks of vaccination and could be a result of delayed hypersensitivity or a T cell–mediated skin reaction caused by “molecular mimicry with a viral epitope,” Dr. Mohta said.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 5.

Dr. Mohta said that, given the “surge” in the number of people who have been vaccinated, it is “imperative as dermatologists” to maintain a “very high index of suspicion to differentiate reactions caused by vaccination” from other causes, and a proper assessment should be performed in “every patient” who presents with a possible reaction.

She also emphasized that “since so many clinical [COVID-19] variants are being encountered,” histopathological assessment could “help in better understanding the underlying pathophysiology” of every reaction.

Dr. Mohta began her presentation by explaining that India is running one of the “world’s largest vaccination drives” for COVID-19, with almost 90% of adults fully vaccinated.

She added that studies have indicated that the incidence of cutaneous adverse reactions following COVID-19 vaccination ranges from 1.0% to 1.9% and that dermatologists have encountered a “plethora” of related reactions.

Dr. Mohta emphasized that the “myriad presentations” of these reactions means that correlating clinical and pathological findings is “key” to understanding the underlying pathophysiology.

She and her colleagues therefore conducted a prospective, hospital-based study of patients who self-reported mucocutaneous adverse reactions from April to December 2021, within 4 weeks of receiving a COVID-19 vaccine.

They gathered information on the patients’ signs and symptoms, as well as the date of vaccine administration and the type of vaccine given, alongside a detailed medical history, including previous allergies, prior COVID-19 infection, and any comorbidities.

The patients also underwent a clinical examination and laboratory investigations, and their cases were assessed by two senior dermatologists to determine whether the association between the adverse event and COVID-19 vaccination was likely causal.

Dr. Mohta said that 132 adult patients, with an average age of 38.2 years, were identified as having vaccine-related reactions.

This included 84 (63.6%) patients with a mild reaction, defined as resolving with symptomatic treatment; 43 (32.6%) patients with a moderate reaction, defined as extensive and lasting for more than 4 weeks; and five (3.8%) patients with severe reactions, defined as systemic and potentially life-threatening.

The mild group included 21 patients with acute urticaria, with a mean onset of 1.2 days following vaccination, as well as 20 cases of maculopapular rash, with a mean onset of 2.4 days; 18 cases of pityriasis rosea, with a mean onset of 17.4 days; and nine cases of eruptive pseudoangioma, with a mean onset of 3.5 days.

There were 16 cases of lichen planus in the moderate group, with a mean onset of 22.7 days after COVID-19 vaccination; nine cases of herpes zoster, with a mean onset of 15.3 days; and one case of pityriasis lichenoides et varioliformis acuta (PLEVA), among others.

The severe group included two cases of erythroderma, with a mean onset of 9 days after vaccination; one case of drug rash with eosinophilia and systemic symptoms (DRESS), with a mean onset of 20 days; and one case each of subacute cutaneous lupus erythematosus (SCLE) and bullous pemphigoid, with mean onsets of 15 days and 14 days, respectively.

Turning to the histopathological results, Dr. Mohta explained that only 57 patients from their cohort agreed to have a skin biopsy.

Results of those skin biopsies showed that 21 (36.8%) patients had vaccine-related eruption of papules and plaques, predominantly spongiotic dermatitis. This correlated with the clinical diagnoses of pityriasis rosea, maculopapular and papulosquamous rash, and DRESS.

Lichenoid and interface dermatitis were seen in 13 (22.8%) patients, which correlated with the clinical diagnoses of lichen planus, PLEVA, and SCLE. Eleven (19.3%) patients had a dermal hypersensitivity reaction, equated to the clinical diagnoses of urticaria, and eruptive pseudoangioma.

Dr. Mohta acknowledged that the study was limited by the inability to calculate the “true prevalence of vaccine-associated reactions,” and because immunohistochemistry was not performed.

Session chair Saleem Taibjee, MD, department of dermatology, Dorset County Hospital NHS Foundation Trust, Dorchester, United Kingdom, congratulated Dr. Mohta on her “very interesting” presentation, highlighting their “extensive experience in such a large cohort of patients.”

He asked what type of COVID-19 vaccines the patients had received, and whether Dr. Mohta could provide any “insights into which patients you can safely give the vaccine again to, and those [to whom] you may avoid giving further doses.”

Dr. Mohta said that the majority of the patients in the study received the AstraZeneca COVID-19 vaccine, as that was the one most commonly used in India at the time, with around 30 patients receiving the Indian Covishield version of the AstraZeneca vaccine. (The two-dose AstraZeneca vaccine, which is cheaper to manufacture and easier to store at typical refrigerated temperatures than mRNA-based vaccines, has been authorized by the World Health Organization, the European Medicines Agency, and over 50 countries but has not been authorized in the United States.)

She added that none of the patients in the study with mild-to-moderate skin reactions were advised against receiving further doses” but that those with severe reactions “were advised not to take any further doses.”

Consequently, in the case of mild reactions, “further doses are not a contraindication,” Dr. Mohta said, but patients with more severe reactions should be considered on a “case by case basis.”

A version of this article first appeared on Medscape.com.