Clinician Reviews

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

This article was updated 4/13/21.

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

This article was updated 4/13/21.

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

This article was updated 4/13/21.

Loss of smell, loss of taste, dyspnea, and fatigue are the four most common symptoms that health care professionals in Sweden report 8 months after mild COVID-19 illness, new evidence reveals.

Approximately 1 in 10 health care workers experience one or more moderate to severe symptoms that negatively affect their quality of life, according to the study.

Nenad Cavoski/Getty Images

“We see that a substantial portion of health care workers suffer from long-term symptoms after mild COVID-19,” senior author Charlotte Thålin, MD, PhD, said in an interview. She added that loss of smell and taste “may seem trivial, but have a negative impact on work, social, and home life in the long run.”

The study is noteworthy not only for tracking the COVID-19-related experiences of health care workers over time, but also for what it did not find. There was no increased prevalence of cognitive issues – including memory or concentration – that others have linked to what’s often called long-haul COVID-19.

The research letter was published online April 7, 2021, in JAMA.

“Even if you are young and previously healthy, a mild COVID-19 infection may result in long-term consequences,” said Dr. Thålin, from the department of clinical sciences at Danderyd Hospital, Karolinska Institute, Stockholm.

The researchers did not observe an increased risk for long-term symptoms after asymptomatic COVID-19.
 

Adding to existing evidence

This research letter “adds to the growing body of literature showing that people recovering from COVID have reported a diverse array of symptoms lasting for months after initial infection,” Lekshmi Santhosh, MD, said in an interview. She is physician faculty lead at the University of California, San Francisco Post-COVID OPTIMAL Clinic.

Previous research revealed severe long-term symptoms, including heart palpitations and neurologic impairments, among people hospitalized with COVID-19. However, “there is limited data on the long-term effects after mild COVID-19, and these studies are often hampered by selection bias and without proper control groups,” Dr. Thålin said.

The absence of these more severe symptoms after mild COVID-19 is “reassuring,” she added.

The current findings are part of the ongoing COMMUNITY (COVID-19 Biomarker and Immunity) study looking at long-term immunity. Health care professionals enrolled in the research between April 15 and May 8, 2020, and have initial blood tests repeated every 4 months.

Dr. Thålin, lead author Sebastian Havervall, MD, and their colleagues compared symptom reporting between 323 hospital employees who had mild COVID-19 at least 8 months earlier with 1,072 employees who did not have COVID-19 throughout the study.

The results show that 26% of those who had COVID-19 previously had at least one moderate to severe symptom that lasted more than 2 months, compared with 9% in the control group.

The group with a history of mild COVID-19 was a median 43 years old and 83% were women. The controls were a median 47 years old and 86% were women.

“These data mirror what we have seen across long-term cohorts of patients with COVID-19 infection. Notably, mild illness among previously healthy individuals may be associated with long-term persistent symptoms,” Sarah Jolley, MD, a pulmonologist specializing in critical care at the University of Colorado Hospital in Aurora and director of the Post-COVID Clinic, said in an interview.

“In this cohort, similar to others, this seems to be more pronounced in women,” Dr. Jolley added.
 

Key findings on functioning

At 8 months, using a smartphone app, participants reported presence, duration, and severity of 23 predefined symptoms. Researchers used the Sheehan Disability Scale to gauge functional impairment.

A total of 11% participants reported at least one symptom that negatively affected work or social or home life at 8 months versus only 2% of the control group.

Seropositive participants were almost two times more likely to report that their long-term symptoms moderately to markedly disrupted their work life, 8% versus 4% of seronegative healthcare workers (relative risk, 1.8; 95%; confidence interval, 1.2-2.9).

Disruptions to a social life from long-term symptoms were 2.5 times more likely in the seropositive group. A total 15% of this cohort reported moderate to marked effects, compared with 6% of the seronegative group (RR, 2.5; 95% CI, 1.8-3.6).

The researchers also inquired about home life disruptions, which were reported by 12% of the seropositive health care workers and 5% of the seronegative participants (RR, 2.3; 95% CI, 1.6-3.4).

The study’s findings “tracks with a lot of the other work we’re seeing,” David Putrino, PT, PhD, director of rehabilitation innovation at Mount Sinai Health System in New York, said in an interview. He and his colleagues are responsible for managing the rehabilitation of patients with long COVID.

Interestingly, the proportion of people with persistent symptoms might be underestimated in this research, Dr. Putrino said. “Antibodies are not an entirely reliable biomarker. So what the researchers are using here is the most conservative measure of who may have had the virus.”

Potential recall bias and the subjective rating of symptoms were possible limitations of the study.

When asked to speculate why researchers did not find higher levels of cognitive dysfunction, Dr. Putrino said that self-reports are generally less reliable than measures like the Montreal Cognitive Assessment for detecting cognitive impairment.

Furthermore, unlike many of the people with long-haul COVID-19 whom he treats clinically – ones who are “really struggling” – the health care workers studied in Sweden are functioning well enough to perform their duties at the hospital, so the study population may not represent the population at large.
 

More research required

“More research needs to be conducted to investigate the mechanisms underlying these persistent symptoms, and several centers, including UCSF, are conducting research into why this might be,” Dr. Santhosh said.

Dr. Thålin and colleagues plan to continue following participants. “The primary aim of the COMMUNITY study is to investigate long-term immunity after COVID-19, but we will also look into possible underlying pathophysiological mechanisms behind COVID-19–related long-term symptoms,” she said.

“I hope to see that taste and smell will return,” Dr. Thålin added.

“We’re really just starting to understand the long-term effects of COVID-19,” Putrino said. “This is something we’re going to see a lot of moving forward.”

Dr. Thålin, Dr. Santhosh, Dr. Jolley, and Dr. Putrino disclosed no relevant financial relationships. The research was funded by grants from the Knut and Alice Wallenberg Foundation, Jonas and Christina af Jochnick Foundation, Leif Lundblad Family Foundation, Region Stockholm, and Erling-Persson Family Foundation.

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

Loss of smell, loss of taste, dyspnea, and fatigue are the four most common symptoms that health care professionals in Sweden report 8 months after mild COVID-19 illness, new evidence reveals.

Approximately 1 in 10 health care workers experience one or more moderate to severe symptoms that negatively affect their quality of life, according to the study.

Nenad Cavoski/Getty Images

“We see that a substantial portion of health care workers suffer from long-term symptoms after mild COVID-19,” senior author Charlotte Thålin, MD, PhD, said in an interview. She added that loss of smell and taste “may seem trivial, but have a negative impact on work, social, and home life in the long run.”

The study is noteworthy not only for tracking the COVID-19-related experiences of health care workers over time, but also for what it did not find. There was no increased prevalence of cognitive issues – including memory or concentration – that others have linked to what’s often called long-haul COVID-19.

The research letter was published online April 7, 2021, in JAMA.

“Even if you are young and previously healthy, a mild COVID-19 infection may result in long-term consequences,” said Dr. Thålin, from the department of clinical sciences at Danderyd Hospital, Karolinska Institute, Stockholm.

The researchers did not observe an increased risk for long-term symptoms after asymptomatic COVID-19.
 

Adding to existing evidence

This research letter “adds to the growing body of literature showing that people recovering from COVID have reported a diverse array of symptoms lasting for months after initial infection,” Lekshmi Santhosh, MD, said in an interview. She is physician faculty lead at the University of California, San Francisco Post-COVID OPTIMAL Clinic.

Previous research revealed severe long-term symptoms, including heart palpitations and neurologic impairments, among people hospitalized with COVID-19. However, “there is limited data on the long-term effects after mild COVID-19, and these studies are often hampered by selection bias and without proper control groups,” Dr. Thålin said.

The absence of these more severe symptoms after mild COVID-19 is “reassuring,” she added.

The current findings are part of the ongoing COMMUNITY (COVID-19 Biomarker and Immunity) study looking at long-term immunity. Health care professionals enrolled in the research between April 15 and May 8, 2020, and have initial blood tests repeated every 4 months.

Dr. Thålin, lead author Sebastian Havervall, MD, and their colleagues compared symptom reporting between 323 hospital employees who had mild COVID-19 at least 8 months earlier with 1,072 employees who did not have COVID-19 throughout the study.

The results show that 26% of those who had COVID-19 previously had at least one moderate to severe symptom that lasted more than 2 months, compared with 9% in the control group.

The group with a history of mild COVID-19 was a median 43 years old and 83% were women. The controls were a median 47 years old and 86% were women.

“These data mirror what we have seen across long-term cohorts of patients with COVID-19 infection. Notably, mild illness among previously healthy individuals may be associated with long-term persistent symptoms,” Sarah Jolley, MD, a pulmonologist specializing in critical care at the University of Colorado Hospital in Aurora and director of the Post-COVID Clinic, said in an interview.

“In this cohort, similar to others, this seems to be more pronounced in women,” Dr. Jolley added.
 

Key findings on functioning

At 8 months, using a smartphone app, participants reported presence, duration, and severity of 23 predefined symptoms. Researchers used the Sheehan Disability Scale to gauge functional impairment.

A total of 11% participants reported at least one symptom that negatively affected work or social or home life at 8 months versus only 2% of the control group.

Seropositive participants were almost two times more likely to report that their long-term symptoms moderately to markedly disrupted their work life, 8% versus 4% of seronegative healthcare workers (relative risk, 1.8; 95%; confidence interval, 1.2-2.9).

Disruptions to a social life from long-term symptoms were 2.5 times more likely in the seropositive group. A total 15% of this cohort reported moderate to marked effects, compared with 6% of the seronegative group (RR, 2.5; 95% CI, 1.8-3.6).

The researchers also inquired about home life disruptions, which were reported by 12% of the seropositive health care workers and 5% of the seronegative participants (RR, 2.3; 95% CI, 1.6-3.4).

The study’s findings “tracks with a lot of the other work we’re seeing,” David Putrino, PT, PhD, director of rehabilitation innovation at Mount Sinai Health System in New York, said in an interview. He and his colleagues are responsible for managing the rehabilitation of patients with long COVID.

Interestingly, the proportion of people with persistent symptoms might be underestimated in this research, Dr. Putrino said. “Antibodies are not an entirely reliable biomarker. So what the researchers are using here is the most conservative measure of who may have had the virus.”

Potential recall bias and the subjective rating of symptoms were possible limitations of the study.

When asked to speculate why researchers did not find higher levels of cognitive dysfunction, Dr. Putrino said that self-reports are generally less reliable than measures like the Montreal Cognitive Assessment for detecting cognitive impairment.

Furthermore, unlike many of the people with long-haul COVID-19 whom he treats clinically – ones who are “really struggling” – the health care workers studied in Sweden are functioning well enough to perform their duties at the hospital, so the study population may not represent the population at large.
 

More research required

“More research needs to be conducted to investigate the mechanisms underlying these persistent symptoms, and several centers, including UCSF, are conducting research into why this might be,” Dr. Santhosh said.

Dr. Thålin and colleagues plan to continue following participants. “The primary aim of the COMMUNITY study is to investigate long-term immunity after COVID-19, but we will also look into possible underlying pathophysiological mechanisms behind COVID-19–related long-term symptoms,” she said.

“I hope to see that taste and smell will return,” Dr. Thålin added.

“We’re really just starting to understand the long-term effects of COVID-19,” Putrino said. “This is something we’re going to see a lot of moving forward.”

Dr. Thålin, Dr. Santhosh, Dr. Jolley, and Dr. Putrino disclosed no relevant financial relationships. The research was funded by grants from the Knut and Alice Wallenberg Foundation, Jonas and Christina af Jochnick Foundation, Leif Lundblad Family Foundation, Region Stockholm, and Erling-Persson Family Foundation.

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

Loss of smell, loss of taste, dyspnea, and fatigue are the four most common symptoms that health care professionals in Sweden report 8 months after mild COVID-19 illness, new evidence reveals.

Approximately 1 in 10 health care workers experience one or more moderate to severe symptoms that negatively affect their quality of life, according to the study.

Nenad Cavoski/Getty Images

“We see that a substantial portion of health care workers suffer from long-term symptoms after mild COVID-19,” senior author Charlotte Thålin, MD, PhD, said in an interview. She added that loss of smell and taste “may seem trivial, but have a negative impact on work, social, and home life in the long run.”

The study is noteworthy not only for tracking the COVID-19-related experiences of health care workers over time, but also for what it did not find. There was no increased prevalence of cognitive issues – including memory or concentration – that others have linked to what’s often called long-haul COVID-19.

The research letter was published online April 7, 2021, in JAMA.

“Even if you are young and previously healthy, a mild COVID-19 infection may result in long-term consequences,” said Dr. Thålin, from the department of clinical sciences at Danderyd Hospital, Karolinska Institute, Stockholm.

The researchers did not observe an increased risk for long-term symptoms after asymptomatic COVID-19.
 

Adding to existing evidence

This research letter “adds to the growing body of literature showing that people recovering from COVID have reported a diverse array of symptoms lasting for months after initial infection,” Lekshmi Santhosh, MD, said in an interview. She is physician faculty lead at the University of California, San Francisco Post-COVID OPTIMAL Clinic.

Previous research revealed severe long-term symptoms, including heart palpitations and neurologic impairments, among people hospitalized with COVID-19. However, “there is limited data on the long-term effects after mild COVID-19, and these studies are often hampered by selection bias and without proper control groups,” Dr. Thålin said.

The absence of these more severe symptoms after mild COVID-19 is “reassuring,” she added.

The current findings are part of the ongoing COMMUNITY (COVID-19 Biomarker and Immunity) study looking at long-term immunity. Health care professionals enrolled in the research between April 15 and May 8, 2020, and have initial blood tests repeated every 4 months.

Dr. Thålin, lead author Sebastian Havervall, MD, and their colleagues compared symptom reporting between 323 hospital employees who had mild COVID-19 at least 8 months earlier with 1,072 employees who did not have COVID-19 throughout the study.

The results show that 26% of those who had COVID-19 previously had at least one moderate to severe symptom that lasted more than 2 months, compared with 9% in the control group.

The group with a history of mild COVID-19 was a median 43 years old and 83% were women. The controls were a median 47 years old and 86% were women.

“These data mirror what we have seen across long-term cohorts of patients with COVID-19 infection. Notably, mild illness among previously healthy individuals may be associated with long-term persistent symptoms,” Sarah Jolley, MD, a pulmonologist specializing in critical care at the University of Colorado Hospital in Aurora and director of the Post-COVID Clinic, said in an interview.

“In this cohort, similar to others, this seems to be more pronounced in women,” Dr. Jolley added.
 

Key findings on functioning

At 8 months, using a smartphone app, participants reported presence, duration, and severity of 23 predefined symptoms. Researchers used the Sheehan Disability Scale to gauge functional impairment.

A total of 11% participants reported at least one symptom that negatively affected work or social or home life at 8 months versus only 2% of the control group.

Seropositive participants were almost two times more likely to report that their long-term symptoms moderately to markedly disrupted their work life, 8% versus 4% of seronegative healthcare workers (relative risk, 1.8; 95%; confidence interval, 1.2-2.9).

Disruptions to a social life from long-term symptoms were 2.5 times more likely in the seropositive group. A total 15% of this cohort reported moderate to marked effects, compared with 6% of the seronegative group (RR, 2.5; 95% CI, 1.8-3.6).

The researchers also inquired about home life disruptions, which were reported by 12% of the seropositive health care workers and 5% of the seronegative participants (RR, 2.3; 95% CI, 1.6-3.4).

The study’s findings “tracks with a lot of the other work we’re seeing,” David Putrino, PT, PhD, director of rehabilitation innovation at Mount Sinai Health System in New York, said in an interview. He and his colleagues are responsible for managing the rehabilitation of patients with long COVID.

Interestingly, the proportion of people with persistent symptoms might be underestimated in this research, Dr. Putrino said. “Antibodies are not an entirely reliable biomarker. So what the researchers are using here is the most conservative measure of who may have had the virus.”

Potential recall bias and the subjective rating of symptoms were possible limitations of the study.

When asked to speculate why researchers did not find higher levels of cognitive dysfunction, Dr. Putrino said that self-reports are generally less reliable than measures like the Montreal Cognitive Assessment for detecting cognitive impairment.

Furthermore, unlike many of the people with long-haul COVID-19 whom he treats clinically – ones who are “really struggling” – the health care workers studied in Sweden are functioning well enough to perform their duties at the hospital, so the study population may not represent the population at large.
 

More research required

“More research needs to be conducted to investigate the mechanisms underlying these persistent symptoms, and several centers, including UCSF, are conducting research into why this might be,” Dr. Santhosh said.

Dr. Thålin and colleagues plan to continue following participants. “The primary aim of the COMMUNITY study is to investigate long-term immunity after COVID-19, but we will also look into possible underlying pathophysiological mechanisms behind COVID-19–related long-term symptoms,” she said.

“I hope to see that taste and smell will return,” Dr. Thålin added.

“We’re really just starting to understand the long-term effects of COVID-19,” Putrino said. “This is something we’re going to see a lot of moving forward.”

Dr. Thålin, Dr. Santhosh, Dr. Jolley, and Dr. Putrino disclosed no relevant financial relationships. The research was funded by grants from the Knut and Alice Wallenberg Foundation, Jonas and Christina af Jochnick Foundation, Leif Lundblad Family Foundation, Region Stockholm, and Erling-Persson Family Foundation.

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

A 74-year-old woman presented to the dermatology clinic for follow-up 3 months after the surgical excision of a basal cell carcinoma on her left jawline. During this postop period, the patient developed new-onset hirsutism. She appeared to be in otherwise good health.

Family and personal medical history were unremarkable. Her medication regimen included aspirin 81 mg/d and a daily multivitamin. The patient was postmenopausal and had a body mass index of 28 and a history of acid reflux and osteoarthritis.

Physical examination of the patient’s scalp showed male-pattern alopecia (FIGURE 1A). She also had coarse terminal hairs on her forearms and back, as well as on her chin (FIGURE 1B).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Dx: Androgen-secreting ovarian tumor

Based on the distribution of terminal hairs and marked change over 3 months, as well as the male-pattern alopecia, a diagnosis of androgen excess was suspected. Laboratory work-up, including thyroid-stimulating hormone, dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone, luteinizing hormone, prolactin, complete blood count, and complete metabolic panel, was within normal limits. Pelvic ultrasound of the ovaries and abdominal computed tomography (CT) of the adrenal glands were also normal.

Further testing showed an elevated testosterone level of 464 ng/dL (reference range: 2-45 ng/dL) and an elevated free testosterone level of 66.8 ng/dL (reference range: 0.2-3.7 ng/dL). These levels pointed to an androgen-secreting ovarian tumor; the androgen excess was likely the cause of her hirsutism.

Hirsutism or hypertrichosis?

Hirsutism, a common disorder affecting up to 8% of women, is defined by excess terminal hairs that appear in a male pattern in women due to production of excess androgens.¹ This should be distinguished from hypertrichosis, which is generalized excessive hair growth not caused by androgen excess.

Hirsutism is more often associated with adrenal or ovarian tumors in postmenopausal patients.

Testosterone and DHEAS—produced in the ovaries and adrenal glands, respectively—contribute to the development of hirsutism.¹ Hirsutism is more often associated with adrenal or ovarian tumors in postmenopausal patients.² Generalized hypertrichosis can be associated with porphyria cutanea tarda, severe anorexia nervosa, and rarely, malignancies; it also can be secondary to certain agents, such as cyclosporin, phenytoin, and minoxidil.

While hirsutism is associated with hyperandrogenemia, its degree correlates poorly with serum levels. Notably, about half of women with hirsutism have been found to have normal levels of circulating androgens.¹ Severe signs of hyperandrogenemia include rapid onset of symptoms, signs of virilization, and a palpable abdominal or pelvic mass.³

Continue to: Is the patient pre- or postmenopausal?

Is the patient pre- or postmenopausal? Polycystic ovary syndrome (PCOS) accounts for up to three-fourths of premenopausal hirsutism.³ The likelihood of hirsutism is actually decreased in postmenopausal women because estrogen levels can drop abruptly after menopause. That said, conditions linked to hirsutism in postmenopausal women include adrenal hyperplasia, thyroid dysfunction, Cushing syndrome, and least frequently, androgen-secreting tumors (seen in this patient). (Hirsutism can also be idiopathic or iatrogenic [medications].)

Methods for detection

Research suggests that when a female patient is given a diagnosis of hirsutism, it’s important to explore possible underlying ovarian and/or adrenal tumors and adult-onset adrenal hyperplasia.¹ The following tests and procedure can be helpful:

Serum testosterone and DHEAS. Levels of total testosterone > 200 ng/dL and/or DHEAS > 700 ng/dL are strongly indicative of androgen-secreting tumors.¹

Imaging—including ultrasound, CT, or magnetic resonance imaging—can be used for evaluation of the adrenal glands and ovaries. However, imaging is often unable to identify these small tumors.⁴

Selective venous catheterization can be useful in the localization and lateralization of an androgen-secreting tumor, although a nondiagnostic result with this technique is not uncommon.⁴

Continue to: Dynamic hormonal testing

Dynamic hormonal testing may assist in determining the pathology of disease but not laterality.² For example, testing for gonadotropin-releasing hormone agonists can be helpful because the constant administration of such agonists can lead to ovarian suppression without affecting adrenal androgen secretion.⁵

Testing with oral dexamethasone may induce adrenal hormonal depression of androgens and subsequent estradiol through aromatase conversion, which can help rule out an ovarian source.⁶ Exogenous administration of follicle-stimulating hormone or luteinizing hormone can further differentiate the source from ovarian theca or granulosa cell production.⁴

Treatment varies

The specific etiology of a patient’s hirsutism dictates the most appropriate treatment. For example, medication-induced hirsutism often requires discontinuation of the offending agent, whereas PCOS would necessitate appropriate nonpharmacologic and pharmacologic interventions.

For our patient, the elevated testosterone and free testosterone levels with normal DHEAS strongly suggested the presence of an androgen-secreting ovarian tumor. These findings led to a referral for bilateral salpingo-oophorectomy. The surgical gross appearance of the patient’s ovaries was unremarkable, but gross dissection and pathology of the ovaries (which were not postoperatively identified to determine laterality) showed one was larger (2.7 × 1.5 × 0.8 cm vs 3.2 × 1.4 × 1.2 cm).

The larger ovary contained an area of brown induration measuring 2.3 × 1.1 × 1.1 cm. This area corresponded to abundant eosinophilic cytoplasm with nuclear, rich, round-cell proliferation, consistent with the diagnosis of a benign ovarian Leydig cell tumor (FIGURE 2). Thus, the bilateral salpingo-oophorectomy was both diagnostic and therapeutic.

Six weeks after the surgery, blood work showed normalization of testosterone and free testosterone levels. The patient’s hirsutism completely resolved over the course of the next several months.

A 74-year-old woman presented to the dermatology clinic for follow-up 3 months after the surgical excision of a basal cell carcinoma on her left jawline. During this postop period, the patient developed new-onset hirsutism. She appeared to be in otherwise good health.

Family and personal medical history were unremarkable. Her medication regimen included aspirin 81 mg/d and a daily multivitamin. The patient was postmenopausal and had a body mass index of 28 and a history of acid reflux and osteoarthritis.

Physical examination of the patient’s scalp showed male-pattern alopecia (FIGURE 1A). She also had coarse terminal hairs on her forearms and back, as well as on her chin (FIGURE 1B).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Dx: Androgen-secreting ovarian tumor

Based on the distribution of terminal hairs and marked change over 3 months, as well as the male-pattern alopecia, a diagnosis of androgen excess was suspected. Laboratory work-up, including thyroid-stimulating hormone, dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone, luteinizing hormone, prolactin, complete blood count, and complete metabolic panel, was within normal limits. Pelvic ultrasound of the ovaries and abdominal computed tomography (CT) of the adrenal glands were also normal.

Further testing showed an elevated testosterone level of 464 ng/dL (reference range: 2-45 ng/dL) and an elevated free testosterone level of 66.8 ng/dL (reference range: 0.2-3.7 ng/dL). These levels pointed to an androgen-secreting ovarian tumor; the androgen excess was likely the cause of her hirsutism.

Hirsutism or hypertrichosis?

Hirsutism, a common disorder affecting up to 8% of women, is defined by excess terminal hairs that appear in a male pattern in women due to production of excess androgens.¹ This should be distinguished from hypertrichosis, which is generalized excessive hair growth not caused by androgen excess.

Hirsutism is more often associated with adrenal or ovarian tumors in postmenopausal patients.

Testosterone and DHEAS—produced in the ovaries and adrenal glands, respectively—contribute to the development of hirsutism.¹ Hirsutism is more often associated with adrenal or ovarian tumors in postmenopausal patients.² Generalized hypertrichosis can be associated with porphyria cutanea tarda, severe anorexia nervosa, and rarely, malignancies; it also can be secondary to certain agents, such as cyclosporin, phenytoin, and minoxidil.

While hirsutism is associated with hyperandrogenemia, its degree correlates poorly with serum levels. Notably, about half of women with hirsutism have been found to have normal levels of circulating androgens.¹ Severe signs of hyperandrogenemia include rapid onset of symptoms, signs of virilization, and a palpable abdominal or pelvic mass.³

Continue to: Is the patient pre- or postmenopausal?

Is the patient pre- or postmenopausal? Polycystic ovary syndrome (PCOS) accounts for up to three-fourths of premenopausal hirsutism.³ The likelihood of hirsutism is actually decreased in postmenopausal women because estrogen levels can drop abruptly after menopause. That said, conditions linked to hirsutism in postmenopausal women include adrenal hyperplasia, thyroid dysfunction, Cushing syndrome, and least frequently, androgen-secreting tumors (seen in this patient). (Hirsutism can also be idiopathic or iatrogenic [medications].)

Methods for detection

Research suggests that when a female patient is given a diagnosis of hirsutism, it’s important to explore possible underlying ovarian and/or adrenal tumors and adult-onset adrenal hyperplasia.¹ The following tests and procedure can be helpful:

Serum testosterone and DHEAS. Levels of total testosterone > 200 ng/dL and/or DHEAS > 700 ng/dL are strongly indicative of androgen-secreting tumors.¹

Imaging—including ultrasound, CT, or magnetic resonance imaging—can be used for evaluation of the adrenal glands and ovaries. However, imaging is often unable to identify these small tumors.⁴

Selective venous catheterization can be useful in the localization and lateralization of an androgen-secreting tumor, although a nondiagnostic result with this technique is not uncommon.⁴

Continue to: Dynamic hormonal testing

Dynamic hormonal testing may assist in determining the pathology of disease but not laterality.² For example, testing for gonadotropin-releasing hormone agonists can be helpful because the constant administration of such agonists can lead to ovarian suppression without affecting adrenal androgen secretion.⁵

Testing with oral dexamethasone may induce adrenal hormonal depression of androgens and subsequent estradiol through aromatase conversion, which can help rule out an ovarian source.⁶ Exogenous administration of follicle-stimulating hormone or luteinizing hormone can further differentiate the source from ovarian theca or granulosa cell production.⁴

Treatment varies

The specific etiology of a patient’s hirsutism dictates the most appropriate treatment. For example, medication-induced hirsutism often requires discontinuation of the offending agent, whereas PCOS would necessitate appropriate nonpharmacologic and pharmacologic interventions.

For our patient, the elevated testosterone and free testosterone levels with normal DHEAS strongly suggested the presence of an androgen-secreting ovarian tumor. These findings led to a referral for bilateral salpingo-oophorectomy. The surgical gross appearance of the patient’s ovaries was unremarkable, but gross dissection and pathology of the ovaries (which were not postoperatively identified to determine laterality) showed one was larger (2.7 × 1.5 × 0.8 cm vs 3.2 × 1.4 × 1.2 cm).

The larger ovary contained an area of brown induration measuring 2.3 × 1.1 × 1.1 cm. This area corresponded to abundant eosinophilic cytoplasm with nuclear, rich, round-cell proliferation, consistent with the diagnosis of a benign ovarian Leydig cell tumor (FIGURE 2). Thus, the bilateral salpingo-oophorectomy was both diagnostic and therapeutic.

Six weeks after the surgery, blood work showed normalization of testosterone and free testosterone levels. The patient’s hirsutism completely resolved over the course of the next several months.

A 74-year-old woman presented to the dermatology clinic for follow-up 3 months after the surgical excision of a basal cell carcinoma on her left jawline. During this postop period, the patient developed new-onset hirsutism. She appeared to be in otherwise good health.

Family and personal medical history were unremarkable. Her medication regimen included aspirin 81 mg/d and a daily multivitamin. The patient was postmenopausal and had a body mass index of 28 and a history of acid reflux and osteoarthritis.

Physical examination of the patient’s scalp showed male-pattern alopecia (FIGURE 1A). She also had coarse terminal hairs on her forearms and back, as well as on her chin (FIGURE 1B).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Dx: Androgen-secreting ovarian tumor

Based on the distribution of terminal hairs and marked change over 3 months, as well as the male-pattern alopecia, a diagnosis of androgen excess was suspected. Laboratory work-up, including thyroid-stimulating hormone, dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone, luteinizing hormone, prolactin, complete blood count, and complete metabolic panel, was within normal limits. Pelvic ultrasound of the ovaries and abdominal computed tomography (CT) of the adrenal glands were also normal.

Further testing showed an elevated testosterone level of 464 ng/dL (reference range: 2-45 ng/dL) and an elevated free testosterone level of 66.8 ng/dL (reference range: 0.2-3.7 ng/dL). These levels pointed to an androgen-secreting ovarian tumor; the androgen excess was likely the cause of her hirsutism.

Hirsutism or hypertrichosis?

Hirsutism, a common disorder affecting up to 8% of women, is defined by excess terminal hairs that appear in a male pattern in women due to production of excess androgens.¹ This should be distinguished from hypertrichosis, which is generalized excessive hair growth not caused by androgen excess.

Hirsutism is more often associated with adrenal or ovarian tumors in postmenopausal patients.

Testosterone and DHEAS—produced in the ovaries and adrenal glands, respectively—contribute to the development of hirsutism.¹ Hirsutism is more often associated with adrenal or ovarian tumors in postmenopausal patients.² Generalized hypertrichosis can be associated with porphyria cutanea tarda, severe anorexia nervosa, and rarely, malignancies; it also can be secondary to certain agents, such as cyclosporin, phenytoin, and minoxidil.

While hirsutism is associated with hyperandrogenemia, its degree correlates poorly with serum levels. Notably, about half of women with hirsutism have been found to have normal levels of circulating androgens.¹ Severe signs of hyperandrogenemia include rapid onset of symptoms, signs of virilization, and a palpable abdominal or pelvic mass.³

Continue to: Is the patient pre- or postmenopausal?

Is the patient pre- or postmenopausal? Polycystic ovary syndrome (PCOS) accounts for up to three-fourths of premenopausal hirsutism.³ The likelihood of hirsutism is actually decreased in postmenopausal women because estrogen levels can drop abruptly after menopause. That said, conditions linked to hirsutism in postmenopausal women include adrenal hyperplasia, thyroid dysfunction, Cushing syndrome, and least frequently, androgen-secreting tumors (seen in this patient). (Hirsutism can also be idiopathic or iatrogenic [medications].)

Methods for detection

Research suggests that when a female patient is given a diagnosis of hirsutism, it’s important to explore possible underlying ovarian and/or adrenal tumors and adult-onset adrenal hyperplasia.¹ The following tests and procedure can be helpful:

Serum testosterone and DHEAS. Levels of total testosterone > 200 ng/dL and/or DHEAS > 700 ng/dL are strongly indicative of androgen-secreting tumors.¹

Imaging—including ultrasound, CT, or magnetic resonance imaging—can be used for evaluation of the adrenal glands and ovaries. However, imaging is often unable to identify these small tumors.⁴

Selective venous catheterization can be useful in the localization and lateralization of an androgen-secreting tumor, although a nondiagnostic result with this technique is not uncommon.⁴

Continue to: Dynamic hormonal testing

Dynamic hormonal testing may assist in determining the pathology of disease but not laterality.² For example, testing for gonadotropin-releasing hormone agonists can be helpful because the constant administration of such agonists can lead to ovarian suppression without affecting adrenal androgen secretion.⁵

Testing with oral dexamethasone may induce adrenal hormonal depression of androgens and subsequent estradiol through aromatase conversion, which can help rule out an ovarian source.⁶ Exogenous administration of follicle-stimulating hormone or luteinizing hormone can further differentiate the source from ovarian theca or granulosa cell production.⁴

Treatment varies

The specific etiology of a patient’s hirsutism dictates the most appropriate treatment. For example, medication-induced hirsutism often requires discontinuation of the offending agent, whereas PCOS would necessitate appropriate nonpharmacologic and pharmacologic interventions.

For our patient, the elevated testosterone and free testosterone levels with normal DHEAS strongly suggested the presence of an androgen-secreting ovarian tumor. These findings led to a referral for bilateral salpingo-oophorectomy. The surgical gross appearance of the patient’s ovaries was unremarkable, but gross dissection and pathology of the ovaries (which were not postoperatively identified to determine laterality) showed one was larger (2.7 × 1.5 × 0.8 cm vs 3.2 × 1.4 × 1.2 cm).

The larger ovary contained an area of brown induration measuring 2.3 × 1.1 × 1.1 cm. This area corresponded to abundant eosinophilic cytoplasm with nuclear, rich, round-cell proliferation, consistent with the diagnosis of a benign ovarian Leydig cell tumor (FIGURE 2). Thus, the bilateral salpingo-oophorectomy was both diagnostic and therapeutic.

Six weeks after the surgery, blood work showed normalization of testosterone and free testosterone levels. The patient’s hirsutism completely resolved over the course of the next several months.

Approximately 40,000 children in the United States have lost a parent to COVID-19, based on data from a combination of death counts and simulation models.

dtiberio/iStock/Getty Images

The scale of mortality from COVID-19 among adults in the United States merits efforts to monitor how many children have lost a parent as a result of the pandemic, wrote Rachel Kidman, PhD, of Stony Brook (N.Y.) University and colleagues.

In a study published in JAMA Pediatrics, the researchers used kinship networks of White and Black individuals in the United States to estimate parental bereavement. They combined deaths from COVID-19 as of February 2021 and combined them with excess deaths, and estimated future bereavement based on a herd immunity scenario.

Overall, the model suggested that each death from COVID-19 results in potential parental bereavement for 0.78 children aged 0-17 years, representing an increase of 17.5%-20.2% in parental bereavement. The model indicated that, as of February 2021, 37,337 children aged 0-17 years had lost a parent to COVID-19, including 11,366 children age 0-9 years and 31,661 children and teens aged 10-17 years. A total of 20,600 of these children were non-Hispanic White and 7,600 were Black. Black children accounted for 20% of the bereaved children, although they account for approximately 14% of children aged 0-17 years in the United States, the researchers noted.

Including the excess death estimate, which refers to the difference between observed and expected deaths for the remainder of the pandemic, raised the total bereaved children to 43,000. A future mortality scenario using a total of 1,500,000 deaths from COVID-19 based on a natural herd immunity strategy increased the total estimate of bereaved children to 116,922.

The study findings were limited by several factors including the lack of data on nonparental primary caregivers, and the use of demographic models rather than survey or administrative data, the researchers noted.

However, the huge number of children who have experienced the death of a parent because of COVID-19 emphasizes the need for reforms to address health, educational, and economic impacts of this mass bereavement on children and teens, they said.

“Parentally bereaved children will also need targeted support to help with grief, particularly during this period of heightened social isolation,” they emphasized.

Establishment of a national child bereavement cohort could identify children early in the bereavement process to help ensure that they are connected to local supportive care and monitored for health and behavior problems, the researchers said. In addition, such a cohort could be used as a basis for a longitudinal study of the impact of mass parental bereavement during a unique period of social isolation and economic uncertainty, they concluded.
 

Study spotlights gaps in mental health care

The study is an important reminder of how COVID-19 has disrupted children’s lives, said Herschel Lessin, MD, of Children’s Medical Group in Poughkeepsie, N.Y., in an interview. Losing a parent because of COVID-19 is one more tragedy on the list of social and emotional disasters the pandemic has wrought on children, he said.

“There has to be some sort of national response to help children through all of this, not just one item at a time,” Dr. Lessin said. However, the management of children’s mental health in the United States has been subpar for decades, he noted, with few clinicians trained to specialize in treating behavioral and mental health issues in children. Consequently, more general pediatricians will continue to be faced with the mental health issues of bereaved children who desperately need support, he said.

Money remains a key barrier, as it keeps qualified clinicians from entering the field of pediatric mental and behavioral health, and even where there are mental health providers, most do not take insurance and have long waiting lists, Dr. Lessin noted.

General pediatricians were seeing more patients with ADHD, anxiety, and depression before the advent of COVID-19, though most are not trained in managing these conditions, said Dr. Lessin. “Approximately 25%-30% of my visits now are mental health related, and the pandemic will make it geometrically worse,” he said.

The current study, with its dramatic estimates of the number of children who have lost a parent because of COVID-19, may bring attention to the fact that more training and money are needed to support mental health programs for children, he said.

Lead author Dr. Kidman had no financial conflicts to disclose. The study was supported by grants to corresponding author Ashton M. Verdery, PhD, from the National Institute on Aging and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Lessin had no financial conflicts but serves on the Pediatric News editorial advisory board.

SOURCE: Kidman R et al. JAMA Pediatr. .

Approximately 40,000 children in the United States have lost a parent to COVID-19, based on data from a combination of death counts and simulation models.

dtiberio/iStock/Getty Images

The scale of mortality from COVID-19 among adults in the United States merits efforts to monitor how many children have lost a parent as a result of the pandemic, wrote Rachel Kidman, PhD, of Stony Brook (N.Y.) University and colleagues.

In a study published in JAMA Pediatrics, the researchers used kinship networks of White and Black individuals in the United States to estimate parental bereavement. They combined deaths from COVID-19 as of February 2021 and combined them with excess deaths, and estimated future bereavement based on a herd immunity scenario.

Overall, the model suggested that each death from COVID-19 results in potential parental bereavement for 0.78 children aged 0-17 years, representing an increase of 17.5%-20.2% in parental bereavement. The model indicated that, as of February 2021, 37,337 children aged 0-17 years had lost a parent to COVID-19, including 11,366 children age 0-9 years and 31,661 children and teens aged 10-17 years. A total of 20,600 of these children were non-Hispanic White and 7,600 were Black. Black children accounted for 20% of the bereaved children, although they account for approximately 14% of children aged 0-17 years in the United States, the researchers noted.

Including the excess death estimate, which refers to the difference between observed and expected deaths for the remainder of the pandemic, raised the total bereaved children to 43,000. A future mortality scenario using a total of 1,500,000 deaths from COVID-19 based on a natural herd immunity strategy increased the total estimate of bereaved children to 116,922.

The study findings were limited by several factors including the lack of data on nonparental primary caregivers, and the use of demographic models rather than survey or administrative data, the researchers noted.

However, the huge number of children who have experienced the death of a parent because of COVID-19 emphasizes the need for reforms to address health, educational, and economic impacts of this mass bereavement on children and teens, they said.

“Parentally bereaved children will also need targeted support to help with grief, particularly during this period of heightened social isolation,” they emphasized.

Establishment of a national child bereavement cohort could identify children early in the bereavement process to help ensure that they are connected to local supportive care and monitored for health and behavior problems, the researchers said. In addition, such a cohort could be used as a basis for a longitudinal study of the impact of mass parental bereavement during a unique period of social isolation and economic uncertainty, they concluded.
 

Study spotlights gaps in mental health care

The study is an important reminder of how COVID-19 has disrupted children’s lives, said Herschel Lessin, MD, of Children’s Medical Group in Poughkeepsie, N.Y., in an interview. Losing a parent because of COVID-19 is one more tragedy on the list of social and emotional disasters the pandemic has wrought on children, he said.

“There has to be some sort of national response to help children through all of this, not just one item at a time,” Dr. Lessin said. However, the management of children’s mental health in the United States has been subpar for decades, he noted, with few clinicians trained to specialize in treating behavioral and mental health issues in children. Consequently, more general pediatricians will continue to be faced with the mental health issues of bereaved children who desperately need support, he said.

Money remains a key barrier, as it keeps qualified clinicians from entering the field of pediatric mental and behavioral health, and even where there are mental health providers, most do not take insurance and have long waiting lists, Dr. Lessin noted.

General pediatricians were seeing more patients with ADHD, anxiety, and depression before the advent of COVID-19, though most are not trained in managing these conditions, said Dr. Lessin. “Approximately 25%-30% of my visits now are mental health related, and the pandemic will make it geometrically worse,” he said.

The current study, with its dramatic estimates of the number of children who have lost a parent because of COVID-19, may bring attention to the fact that more training and money are needed to support mental health programs for children, he said.

Lead author Dr. Kidman had no financial conflicts to disclose. The study was supported by grants to corresponding author Ashton M. Verdery, PhD, from the National Institute on Aging and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Lessin had no financial conflicts but serves on the Pediatric News editorial advisory board.

SOURCE: Kidman R et al. JAMA Pediatr. .

Approximately 40,000 children in the United States have lost a parent to COVID-19, based on data from a combination of death counts and simulation models.

dtiberio/iStock/Getty Images

The scale of mortality from COVID-19 among adults in the United States merits efforts to monitor how many children have lost a parent as a result of the pandemic, wrote Rachel Kidman, PhD, of Stony Brook (N.Y.) University and colleagues.

In a study published in JAMA Pediatrics, the researchers used kinship networks of White and Black individuals in the United States to estimate parental bereavement. They combined deaths from COVID-19 as of February 2021 and combined them with excess deaths, and estimated future bereavement based on a herd immunity scenario.

Overall, the model suggested that each death from COVID-19 results in potential parental bereavement for 0.78 children aged 0-17 years, representing an increase of 17.5%-20.2% in parental bereavement. The model indicated that, as of February 2021, 37,337 children aged 0-17 years had lost a parent to COVID-19, including 11,366 children age 0-9 years and 31,661 children and teens aged 10-17 years. A total of 20,600 of these children were non-Hispanic White and 7,600 were Black. Black children accounted for 20% of the bereaved children, although they account for approximately 14% of children aged 0-17 years in the United States, the researchers noted.

Including the excess death estimate, which refers to the difference between observed and expected deaths for the remainder of the pandemic, raised the total bereaved children to 43,000. A future mortality scenario using a total of 1,500,000 deaths from COVID-19 based on a natural herd immunity strategy increased the total estimate of bereaved children to 116,922.

The study findings were limited by several factors including the lack of data on nonparental primary caregivers, and the use of demographic models rather than survey or administrative data, the researchers noted.

However, the huge number of children who have experienced the death of a parent because of COVID-19 emphasizes the need for reforms to address health, educational, and economic impacts of this mass bereavement on children and teens, they said.

“Parentally bereaved children will also need targeted support to help with grief, particularly during this period of heightened social isolation,” they emphasized.

Establishment of a national child bereavement cohort could identify children early in the bereavement process to help ensure that they are connected to local supportive care and monitored for health and behavior problems, the researchers said. In addition, such a cohort could be used as a basis for a longitudinal study of the impact of mass parental bereavement during a unique period of social isolation and economic uncertainty, they concluded.
 

Study spotlights gaps in mental health care

The study is an important reminder of how COVID-19 has disrupted children’s lives, said Herschel Lessin, MD, of Children’s Medical Group in Poughkeepsie, N.Y., in an interview. Losing a parent because of COVID-19 is one more tragedy on the list of social and emotional disasters the pandemic has wrought on children, he said.

“There has to be some sort of national response to help children through all of this, not just one item at a time,” Dr. Lessin said. However, the management of children’s mental health in the United States has been subpar for decades, he noted, with few clinicians trained to specialize in treating behavioral and mental health issues in children. Consequently, more general pediatricians will continue to be faced with the mental health issues of bereaved children who desperately need support, he said.

Money remains a key barrier, as it keeps qualified clinicians from entering the field of pediatric mental and behavioral health, and even where there are mental health providers, most do not take insurance and have long waiting lists, Dr. Lessin noted.

General pediatricians were seeing more patients with ADHD, anxiety, and depression before the advent of COVID-19, though most are not trained in managing these conditions, said Dr. Lessin. “Approximately 25%-30% of my visits now are mental health related, and the pandemic will make it geometrically worse,” he said.

The current study, with its dramatic estimates of the number of children who have lost a parent because of COVID-19, may bring attention to the fact that more training and money are needed to support mental health programs for children, he said.

Lead author Dr. Kidman had no financial conflicts to disclose. The study was supported by grants to corresponding author Ashton M. Verdery, PhD, from the National Institute on Aging and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Lessin had no financial conflicts but serves on the Pediatric News editorial advisory board.

SOURCE: Kidman R et al. JAMA Pediatr. .

Following a recent article in the Guardian, the Internet has erupted with tales of periods gone awry. The stress and loss of normalcy over the last year appears to have altered cycles and amplified the premenstrual syndrome (PMS) symptoms many women experience. And after the piece published, many responded on social media with the same sentiment: “So, it’s not just me?”

Women have experienced the loss of their period, excessive and prolonged bleeding, severe mood swings, and irritability, according to the Guardian article. London-based gynecologist Anita Mitra, MBChB, PhD, took an informal survey and found that 65% of 5,677 respondents had noticed a change in their menstrual cycle, the Guardian reported. Another survey, which was posted on medRxiv but hasn’t been peer reviewed yet, found 53% of the 749 respondents had noticed a change in their menstrual cycle, including increased cycle length.

“The pandemic in itself has made more stress for women,” said Karen Carlson, MD, obstetrician and gynecologist at Nebraska Medicine. There’s preliminary evidence that the cycling progesterone and estrogen experienced by reproductive age women actually offers a protective effect against COVID-19, which is good news. But Dr. Carlson said that because they are less likely than men and the elderly to become seriously ill, many women have taken on a lot of the additional responsibilities brought on by the pandemic. They often juggle homeschooling and elder care in addition to the ubiquitous stressors of isolation and concerns around personal health.

“Abnormal bleeding is the most common reason people present to the gynecologist,” Dr. Carlson said in an interview. But in recent months, Dr. Carlson said she’s seen a slight uptick in these issues, and there might have been even more women presenting to their physicians if the pandemic hadn’t also suppressed access to care.

Stress, or rather the cortisol it causes the body to produce, is the culprit for disrupted cycles. It can suppress pituitary hormones that stimulate ovulation. “Some women don’t feel right because they are stuck in the one phase of the cycle,” Dr. Carlson said. They may go months without a period and when they do eventually shed their uterine lining the bleeding goes on for a while.

Some irregularity in a person’s cycle is a normal response to stress and even likely, given the last year. However, bleeding for more than 2 weeks or irregularity for more than 3 months could point to something more serious like an infection or cancer, Dr. Carlson said. Getting a clear history so you know when you need to do blood and hormone workups is critical.
 

Anxiety and depression amplified

For some women it’s not bleeding that’s a problem, rather their PMS has become crippling. And some of their significant others have noticed drastic changes in their mood. In the Guardian article, one woman said she’d gone from feeling withdrawn during her period to being totally unreachable and experiencing intense anxiety.

Maureen Whelihan, MD, a gynecologist in Palm Beach, Fla., said that, for the majority of her patients under 39 years of age, these feelings aren’t a hormone issue, but a stress and neuroreceptor issue. She says she’s seen approximately a 30% increase in mood disorders since the start of the pandemic. Even though many of her patients are cycling relatively normally, their anxiety and depression have been amplified.

Caroline Gurvich, PhD, a neuroscientist at Monash University in Melbourne, attributes this to the loss of typical coping mechanisms. “Having changes to the support system and routine and things that would keep them mentally healthy can exacerbate PMS,” she said in an interview. Dr. Gurvich’s advice is to build routines into the pandemic lifestyle. Normal wake and sleep times, healthy eating, and practices that bring happiness can be “crucial to keeping those PMS systems as controlled as possible.”

Telehealth has made it much easier to access some patients struggling with PMS and offer them the medication or counseling they need, Dr. Carlson said. But that approach doesn’t work for everyone. “I feel like there are a lot of silent sufferers,” she said.

This is where screening practices like the Patient Health Questionnaire-9 are so critical, according to Dr. Whelihan, who screens every patient as part of their routine iPad check-in process. Even in a normal year, “I think one-third of gynecology is psychiatry,” she said in an interview. She finds many of the patients struggling with excessive PMS symptoms, both during the pandemic and before, benefit from a child-sized dose of antidepressant. This may allow them to get to a place where they can make impactful routine decisions about exercise or sleep, and then taper off the antidepressant.

It may also be important for clinicians to help patients make the initial connection between their worsening mood or cognitive function and their period. Knowing their feelings of stress, irritability, fogginess, or being withdrawn are linked to their hormone cycle and possibly worsened by the stress of the pandemic can be helpful, Dr. Gurvich said. “If they become conscious of how they are feeling it can be helpful for management of these stressful symptoms,” she said.

Following a recent article in the Guardian, the Internet has erupted with tales of periods gone awry. The stress and loss of normalcy over the last year appears to have altered cycles and amplified the premenstrual syndrome (PMS) symptoms many women experience. And after the piece published, many responded on social media with the same sentiment: “So, it’s not just me?”

Women have experienced the loss of their period, excessive and prolonged bleeding, severe mood swings, and irritability, according to the Guardian article. London-based gynecologist Anita Mitra, MBChB, PhD, took an informal survey and found that 65% of 5,677 respondents had noticed a change in their menstrual cycle, the Guardian reported. Another survey, which was posted on medRxiv but hasn’t been peer reviewed yet, found 53% of the 749 respondents had noticed a change in their menstrual cycle, including increased cycle length.

“The pandemic in itself has made more stress for women,” said Karen Carlson, MD, obstetrician and gynecologist at Nebraska Medicine. There’s preliminary evidence that the cycling progesterone and estrogen experienced by reproductive age women actually offers a protective effect against COVID-19, which is good news. But Dr. Carlson said that because they are less likely than men and the elderly to become seriously ill, many women have taken on a lot of the additional responsibilities brought on by the pandemic. They often juggle homeschooling and elder care in addition to the ubiquitous stressors of isolation and concerns around personal health.

“Abnormal bleeding is the most common reason people present to the gynecologist,” Dr. Carlson said in an interview. But in recent months, Dr. Carlson said she’s seen a slight uptick in these issues, and there might have been even more women presenting to their physicians if the pandemic hadn’t also suppressed access to care.

Stress, or rather the cortisol it causes the body to produce, is the culprit for disrupted cycles. It can suppress pituitary hormones that stimulate ovulation. “Some women don’t feel right because they are stuck in the one phase of the cycle,” Dr. Carlson said. They may go months without a period and when they do eventually shed their uterine lining the bleeding goes on for a while.

Some irregularity in a person’s cycle is a normal response to stress and even likely, given the last year. However, bleeding for more than 2 weeks or irregularity for more than 3 months could point to something more serious like an infection or cancer, Dr. Carlson said. Getting a clear history so you know when you need to do blood and hormone workups is critical.
 

Anxiety and depression amplified

For some women it’s not bleeding that’s a problem, rather their PMS has become crippling. And some of their significant others have noticed drastic changes in their mood. In the Guardian article, one woman said she’d gone from feeling withdrawn during her period to being totally unreachable and experiencing intense anxiety.

Maureen Whelihan, MD, a gynecologist in Palm Beach, Fla., said that, for the majority of her patients under 39 years of age, these feelings aren’t a hormone issue, but a stress and neuroreceptor issue. She says she’s seen approximately a 30% increase in mood disorders since the start of the pandemic. Even though many of her patients are cycling relatively normally, their anxiety and depression have been amplified.

Caroline Gurvich, PhD, a neuroscientist at Monash University in Melbourne, attributes this to the loss of typical coping mechanisms. “Having changes to the support system and routine and things that would keep them mentally healthy can exacerbate PMS,” she said in an interview. Dr. Gurvich’s advice is to build routines into the pandemic lifestyle. Normal wake and sleep times, healthy eating, and practices that bring happiness can be “crucial to keeping those PMS systems as controlled as possible.”

Telehealth has made it much easier to access some patients struggling with PMS and offer them the medication or counseling they need, Dr. Carlson said. But that approach doesn’t work for everyone. “I feel like there are a lot of silent sufferers,” she said.

This is where screening practices like the Patient Health Questionnaire-9 are so critical, according to Dr. Whelihan, who screens every patient as part of their routine iPad check-in process. Even in a normal year, “I think one-third of gynecology is psychiatry,” she said in an interview. She finds many of the patients struggling with excessive PMS symptoms, both during the pandemic and before, benefit from a child-sized dose of antidepressant. This may allow them to get to a place where they can make impactful routine decisions about exercise or sleep, and then taper off the antidepressant.

It may also be important for clinicians to help patients make the initial connection between their worsening mood or cognitive function and their period. Knowing their feelings of stress, irritability, fogginess, or being withdrawn are linked to their hormone cycle and possibly worsened by the stress of the pandemic can be helpful, Dr. Gurvich said. “If they become conscious of how they are feeling it can be helpful for management of these stressful symptoms,” she said.

Following a recent article in the Guardian, the Internet has erupted with tales of periods gone awry. The stress and loss of normalcy over the last year appears to have altered cycles and amplified the premenstrual syndrome (PMS) symptoms many women experience. And after the piece published, many responded on social media with the same sentiment: “So, it’s not just me?”

Women have experienced the loss of their period, excessive and prolonged bleeding, severe mood swings, and irritability, according to the Guardian article. London-based gynecologist Anita Mitra, MBChB, PhD, took an informal survey and found that 65% of 5,677 respondents had noticed a change in their menstrual cycle, the Guardian reported. Another survey, which was posted on medRxiv but hasn’t been peer reviewed yet, found 53% of the 749 respondents had noticed a change in their menstrual cycle, including increased cycle length.

“The pandemic in itself has made more stress for women,” said Karen Carlson, MD, obstetrician and gynecologist at Nebraska Medicine. There’s preliminary evidence that the cycling progesterone and estrogen experienced by reproductive age women actually offers a protective effect against COVID-19, which is good news. But Dr. Carlson said that because they are less likely than men and the elderly to become seriously ill, many women have taken on a lot of the additional responsibilities brought on by the pandemic. They often juggle homeschooling and elder care in addition to the ubiquitous stressors of isolation and concerns around personal health.

“Abnormal bleeding is the most common reason people present to the gynecologist,” Dr. Carlson said in an interview. But in recent months, Dr. Carlson said she’s seen a slight uptick in these issues, and there might have been even more women presenting to their physicians if the pandemic hadn’t also suppressed access to care.

Stress, or rather the cortisol it causes the body to produce, is the culprit for disrupted cycles. It can suppress pituitary hormones that stimulate ovulation. “Some women don’t feel right because they are stuck in the one phase of the cycle,” Dr. Carlson said. They may go months without a period and when they do eventually shed their uterine lining the bleeding goes on for a while.

Some irregularity in a person’s cycle is a normal response to stress and even likely, given the last year. However, bleeding for more than 2 weeks or irregularity for more than 3 months could point to something more serious like an infection or cancer, Dr. Carlson said. Getting a clear history so you know when you need to do blood and hormone workups is critical.
 

Anxiety and depression amplified

For some women it’s not bleeding that’s a problem, rather their PMS has become crippling. And some of their significant others have noticed drastic changes in their mood. In the Guardian article, one woman said she’d gone from feeling withdrawn during her period to being totally unreachable and experiencing intense anxiety.

Maureen Whelihan, MD, a gynecologist in Palm Beach, Fla., said that, for the majority of her patients under 39 years of age, these feelings aren’t a hormone issue, but a stress and neuroreceptor issue. She says she’s seen approximately a 30% increase in mood disorders since the start of the pandemic. Even though many of her patients are cycling relatively normally, their anxiety and depression have been amplified.

Caroline Gurvich, PhD, a neuroscientist at Monash University in Melbourne, attributes this to the loss of typical coping mechanisms. “Having changes to the support system and routine and things that would keep them mentally healthy can exacerbate PMS,” she said in an interview. Dr. Gurvich’s advice is to build routines into the pandemic lifestyle. Normal wake and sleep times, healthy eating, and practices that bring happiness can be “crucial to keeping those PMS systems as controlled as possible.”

Telehealth has made it much easier to access some patients struggling with PMS and offer them the medication or counseling they need, Dr. Carlson said. But that approach doesn’t work for everyone. “I feel like there are a lot of silent sufferers,” she said.

This is where screening practices like the Patient Health Questionnaire-9 are so critical, according to Dr. Whelihan, who screens every patient as part of their routine iPad check-in process. Even in a normal year, “I think one-third of gynecology is psychiatry,” she said in an interview. She finds many of the patients struggling with excessive PMS symptoms, both during the pandemic and before, benefit from a child-sized dose of antidepressant. This may allow them to get to a place where they can make impactful routine decisions about exercise or sleep, and then taper off the antidepressant.

It may also be important for clinicians to help patients make the initial connection between their worsening mood or cognitive function and their period. Knowing their feelings of stress, irritability, fogginess, or being withdrawn are linked to their hormone cycle and possibly worsened by the stress of the pandemic can be helpful, Dr. Gurvich said. “If they become conscious of how they are feeling it can be helpful for management of these stressful symptoms,” she said.

The Diagnosis: Cutaneous B-cell Lymphoma 

Histopathology revealed a dense and diffuse lymphocytic infiltrate throughout the dermis with occasional individual cell necrosis. On closer inspection, the infiltrate consisted of intermediate-sized lymphocytes, some with a vesiculated nucleus and ample amount of cytoplasm, while others contained hyperchromatic nuclei (Figure 1). These cells stained strongly positive for B-cell marker (CD20), while only a few mature lymphocytes demonstrated T-cell phenotype (CD3)(Figure 2).  

Although the patient recounted a 3-month history of lower leg edema, he also reported that the rash began a few weeks after his diagnosis of systemic B-cell follicular lymphoma. Throughout this time, he was seen by various physicians who attributed the edema and skin changes to chronic stasis, peripheral venous insufficiency, and diabetic peripheral neuropathy. His primary care physician prescribed an antifungal lotion, which he discontinued on his own due to lack of improvement. Upon arrival to the emergency department, he was started on intravenous cefazolin and subcutaneous heparin. Doppler ultrasonography of the legs was ordered to rule out a deep venous thrombosis. Dermatology was consulted and proceeded with a punch biopsy to investigate for cutaneous B-cell lymphoma (BCL) with a plan to follow up as an outpatient for results upon discharge. He also was prescribed triamcinolone ointment 0.1% twice daily for symptomatic relief. 

The patient's left axillary lymph node was biopsied for pathologic evaluation. Immunohistochemical staining revealed expression of B-cell markers CD20, CD79a, and PAX5, along with the antiapoptotic markers BCL-2 and BCL-6. Fluorescence in situ hybridization displayed gene rearrangements of BCL-2, BCL-6, and t(14;18)/IgH-BCL2 in the majority of cells. CD3 and CD5 immunostains were negative, indicating that T cells were not involved in this process. Flow cytometry identified a monoclonal κ B-cell population in 40% to 50% of the total cells, which co-expressed CD10, CD19, CD22, and CD38; the cells were negative for CD5, CD20, and CD23. Cell size was variably enlarged and CD71 positive, otherwise known as transferrin receptor 1, indicating the mediation of iron transport into cells of erythroid lineage that is necessary for proliferation.¹ Bone marrow core biopsy did not identify features of bone marrow involvement by the lymphoma. Based on these results, the patient was diagnosed with systemic B-cell follicular lymphoma grade 3b stage IIIA. Oncology initiated a systemic chemotherapy regimen with obinutuzumab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone. 

Skin involvement in B-cell follicular lymphoma can be primary or secondary. Although all subtypes of BCL can have secondary cutaneous involvement, it is most common in advanced-stage disease (stages III or IV).² Cutaneous manifestations of primary cutaneous follicle-center lymphoma (PCFCL) and systemic/nodal follicular lymphoma secondarily involving the skin can be difficult to distinguish clinically and histopathologically; both appear as solitary or grouped plaques and nodules most commonly on the head, neck, or trunk, and rarely on the legs.³ Although the pathologic features of these two diagnoses can seem almost identical, it is important to differentiate them due to their differing prognosis and management. Patients with follicular lymphoma involving the skin are more likely than those with PCFCL to develop lymphadenopathy and B symptoms.³ Primary cutaneous follicle-center lymphoma also generally runs an indolent course and requires local therapy, while secondary involvement of the skin due to systemic/nodal follicular lymphoma has a worse prognosis and requires systemic chemotherapy treatment.⁴ 

Immunohistochemical markers are the most helpful tool used to distinguish PCFCL from systemic/nodal follicular lymphoma involving the skin. Tumors of B-cell origin are expected to express associated B-cell markers such as CD20, CD79a, and PAX5²; BCL-6, a marker of germinal center cells, also is expected to stain positive.² CD10 is positive in a majority of cases with a follicular growth pattern, while those with a diffuse pattern of growth may have a negative stain.² The most valuable histopathologic indicator differentiating primary and secondary skin involvement is the intensity of BCL-2 expression.⁵ The prognostic significance of the t(14;18)/IgH-BCL2 rearrangement is controversial, with rearrangement identified in more than 75% of systemic/nodal follicular lymphoma cases and less commonly found in PCFCL, with one report arguing an incidence ranging from 1% to 40%.⁵ 

A comprehensive history and physical examination are necessary to develop a differential diagnosis. Our patient's lower leg edema and extensive medical history made the diagnosis more complicated. Pitting edema was present on physical examination, making elephantiasis nostras verrucosa less likely, as it would instead present with nonpitting edema and a woody feel.⁶ Our patient did not have epidemiologic exposure to filariasis through foreign travel and did not present with any classic signs or symptoms of lymphatic filariasis, such as fever, eosinophilia, chyluria, or hydrocele.⁷ Although a negative history of HIV makes Kaposi sarcoma and bacillary angiomatosis less likely diagnoses, a biopsy would be useful to rule out these conditions. Positive inguinal lymphadenopathy present on physical examination may have contributed to lymphatic flow obstruction leading to the leg lymphedema in our patient. 

The Diagnosis: Cutaneous B-cell Lymphoma 

Histopathology revealed a dense and diffuse lymphocytic infiltrate throughout the dermis with occasional individual cell necrosis. On closer inspection, the infiltrate consisted of intermediate-sized lymphocytes, some with a vesiculated nucleus and ample amount of cytoplasm, while others contained hyperchromatic nuclei (Figure 1). These cells stained strongly positive for B-cell marker (CD20), while only a few mature lymphocytes demonstrated T-cell phenotype (CD3)(Figure 2).  

Although the patient recounted a 3-month history of lower leg edema, he also reported that the rash began a few weeks after his diagnosis of systemic B-cell follicular lymphoma. Throughout this time, he was seen by various physicians who attributed the edema and skin changes to chronic stasis, peripheral venous insufficiency, and diabetic peripheral neuropathy. His primary care physician prescribed an antifungal lotion, which he discontinued on his own due to lack of improvement. Upon arrival to the emergency department, he was started on intravenous cefazolin and subcutaneous heparin. Doppler ultrasonography of the legs was ordered to rule out a deep venous thrombosis. Dermatology was consulted and proceeded with a punch biopsy to investigate for cutaneous B-cell lymphoma (BCL) with a plan to follow up as an outpatient for results upon discharge. He also was prescribed triamcinolone ointment 0.1% twice daily for symptomatic relief. 

The patient's left axillary lymph node was biopsied for pathologic evaluation. Immunohistochemical staining revealed expression of B-cell markers CD20, CD79a, and PAX5, along with the antiapoptotic markers BCL-2 and BCL-6. Fluorescence in situ hybridization displayed gene rearrangements of BCL-2, BCL-6, and t(14;18)/IgH-BCL2 in the majority of cells. CD3 and CD5 immunostains were negative, indicating that T cells were not involved in this process. Flow cytometry identified a monoclonal κ B-cell population in 40% to 50% of the total cells, which co-expressed CD10, CD19, CD22, and CD38; the cells were negative for CD5, CD20, and CD23. Cell size was variably enlarged and CD71 positive, otherwise known as transferrin receptor 1, indicating the mediation of iron transport into cells of erythroid lineage that is necessary for proliferation.¹ Bone marrow core biopsy did not identify features of bone marrow involvement by the lymphoma. Based on these results, the patient was diagnosed with systemic B-cell follicular lymphoma grade 3b stage IIIA. Oncology initiated a systemic chemotherapy regimen with obinutuzumab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone. 

Skin involvement in B-cell follicular lymphoma can be primary or secondary. Although all subtypes of BCL can have secondary cutaneous involvement, it is most common in advanced-stage disease (stages III or IV).² Cutaneous manifestations of primary cutaneous follicle-center lymphoma (PCFCL) and systemic/nodal follicular lymphoma secondarily involving the skin can be difficult to distinguish clinically and histopathologically; both appear as solitary or grouped plaques and nodules most commonly on the head, neck, or trunk, and rarely on the legs.³ Although the pathologic features of these two diagnoses can seem almost identical, it is important to differentiate them due to their differing prognosis and management. Patients with follicular lymphoma involving the skin are more likely than those with PCFCL to develop lymphadenopathy and B symptoms.³ Primary cutaneous follicle-center lymphoma also generally runs an indolent course and requires local therapy, while secondary involvement of the skin due to systemic/nodal follicular lymphoma has a worse prognosis and requires systemic chemotherapy treatment.⁴ 

Immunohistochemical markers are the most helpful tool used to distinguish PCFCL from systemic/nodal follicular lymphoma involving the skin. Tumors of B-cell origin are expected to express associated B-cell markers such as CD20, CD79a, and PAX5²; BCL-6, a marker of germinal center cells, also is expected to stain positive.² CD10 is positive in a majority of cases with a follicular growth pattern, while those with a diffuse pattern of growth may have a negative stain.² The most valuable histopathologic indicator differentiating primary and secondary skin involvement is the intensity of BCL-2 expression.⁵ The prognostic significance of the t(14;18)/IgH-BCL2 rearrangement is controversial, with rearrangement identified in more than 75% of systemic/nodal follicular lymphoma cases and less commonly found in PCFCL, with one report arguing an incidence ranging from 1% to 40%.⁵ 

A comprehensive history and physical examination are necessary to develop a differential diagnosis. Our patient's lower leg edema and extensive medical history made the diagnosis more complicated. Pitting edema was present on physical examination, making elephantiasis nostras verrucosa less likely, as it would instead present with nonpitting edema and a woody feel.⁶ Our patient did not have epidemiologic exposure to filariasis through foreign travel and did not present with any classic signs or symptoms of lymphatic filariasis, such as fever, eosinophilia, chyluria, or hydrocele.⁷ Although a negative history of HIV makes Kaposi sarcoma and bacillary angiomatosis less likely diagnoses, a biopsy would be useful to rule out these conditions. Positive inguinal lymphadenopathy present on physical examination may have contributed to lymphatic flow obstruction leading to the leg lymphedema in our patient. 

The Diagnosis: Cutaneous B-cell Lymphoma 

Histopathology revealed a dense and diffuse lymphocytic infiltrate throughout the dermis with occasional individual cell necrosis. On closer inspection, the infiltrate consisted of intermediate-sized lymphocytes, some with a vesiculated nucleus and ample amount of cytoplasm, while others contained hyperchromatic nuclei (Figure 1). These cells stained strongly positive for B-cell marker (CD20), while only a few mature lymphocytes demonstrated T-cell phenotype (CD3)(Figure 2).  

Although the patient recounted a 3-month history of lower leg edema, he also reported that the rash began a few weeks after his diagnosis of systemic B-cell follicular lymphoma. Throughout this time, he was seen by various physicians who attributed the edema and skin changes to chronic stasis, peripheral venous insufficiency, and diabetic peripheral neuropathy. His primary care physician prescribed an antifungal lotion, which he discontinued on his own due to lack of improvement. Upon arrival to the emergency department, he was started on intravenous cefazolin and subcutaneous heparin. Doppler ultrasonography of the legs was ordered to rule out a deep venous thrombosis. Dermatology was consulted and proceeded with a punch biopsy to investigate for cutaneous B-cell lymphoma (BCL) with a plan to follow up as an outpatient for results upon discharge. He also was prescribed triamcinolone ointment 0.1% twice daily for symptomatic relief. 

The patient's left axillary lymph node was biopsied for pathologic evaluation. Immunohistochemical staining revealed expression of B-cell markers CD20, CD79a, and PAX5, along with the antiapoptotic markers BCL-2 and BCL-6. Fluorescence in situ hybridization displayed gene rearrangements of BCL-2, BCL-6, and t(14;18)/IgH-BCL2 in the majority of cells. CD3 and CD5 immunostains were negative, indicating that T cells were not involved in this process. Flow cytometry identified a monoclonal κ B-cell population in 40% to 50% of the total cells, which co-expressed CD10, CD19, CD22, and CD38; the cells were negative for CD5, CD20, and CD23. Cell size was variably enlarged and CD71 positive, otherwise known as transferrin receptor 1, indicating the mediation of iron transport into cells of erythroid lineage that is necessary for proliferation.¹ Bone marrow core biopsy did not identify features of bone marrow involvement by the lymphoma. Based on these results, the patient was diagnosed with systemic B-cell follicular lymphoma grade 3b stage IIIA. Oncology initiated a systemic chemotherapy regimen with obinutuzumab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone. 

Skin involvement in B-cell follicular lymphoma can be primary or secondary. Although all subtypes of BCL can have secondary cutaneous involvement, it is most common in advanced-stage disease (stages III or IV).² Cutaneous manifestations of primary cutaneous follicle-center lymphoma (PCFCL) and systemic/nodal follicular lymphoma secondarily involving the skin can be difficult to distinguish clinically and histopathologically; both appear as solitary or grouped plaques and nodules most commonly on the head, neck, or trunk, and rarely on the legs.³ Although the pathologic features of these two diagnoses can seem almost identical, it is important to differentiate them due to their differing prognosis and management. Patients with follicular lymphoma involving the skin are more likely than those with PCFCL to develop lymphadenopathy and B symptoms.³ Primary cutaneous follicle-center lymphoma also generally runs an indolent course and requires local therapy, while secondary involvement of the skin due to systemic/nodal follicular lymphoma has a worse prognosis and requires systemic chemotherapy treatment.⁴ 

Immunohistochemical markers are the most helpful tool used to distinguish PCFCL from systemic/nodal follicular lymphoma involving the skin. Tumors of B-cell origin are expected to express associated B-cell markers such as CD20, CD79a, and PAX5²; BCL-6, a marker of germinal center cells, also is expected to stain positive.² CD10 is positive in a majority of cases with a follicular growth pattern, while those with a diffuse pattern of growth may have a negative stain.² The most valuable histopathologic indicator differentiating primary and secondary skin involvement is the intensity of BCL-2 expression.⁵ The prognostic significance of the t(14;18)/IgH-BCL2 rearrangement is controversial, with rearrangement identified in more than 75% of systemic/nodal follicular lymphoma cases and less commonly found in PCFCL, with one report arguing an incidence ranging from 1% to 40%.⁵ 

A comprehensive history and physical examination are necessary to develop a differential diagnosis. Our patient's lower leg edema and extensive medical history made the diagnosis more complicated. Pitting edema was present on physical examination, making elephantiasis nostras verrucosa less likely, as it would instead present with nonpitting edema and a woody feel.⁶ Our patient did not have epidemiologic exposure to filariasis through foreign travel and did not present with any classic signs or symptoms of lymphatic filariasis, such as fever, eosinophilia, chyluria, or hydrocele.⁷ Although a negative history of HIV makes Kaposi sarcoma and bacillary angiomatosis less likely diagnoses, a biopsy would be useful to rule out these conditions. Positive inguinal lymphadenopathy present on physical examination may have contributed to lymphatic flow obstruction leading to the leg lymphedema in our patient. 

Public health officials in the Midwest and Northeast are sounding the alarm about steep new increases in COVID-19 cases in children.
 

South_agency/Getty Images

The increases seem to be driven by greater circulation of more contagious variants, just as children and teens have returned to in-person activities such as sports, parties, and classes.

“I can just tell you from my 46 years in the business, I’ve never seen dynamic transmission in kids like we’re seeing right now, younger kids,” said Michael Osterholm, PhD, who directs the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis.

In earlier surges, children – especially younger children – played only minor roles in transmitting the infection. When they were diagnosed with COVID-19, their symptoms tended to be mild or even absent, and for reasons that aren’t well understood, they haven’t usually been the first cases in households or clusters. 

Now, as more SARS-CoV-2 variants have begun to dominate, and seniors gain protection from vaccines, that pattern may be changing. Infectious disease experts are watching to see if COVID-19 will start to spread in a pattern more similar to influenza, with children becoming infected first and bringing the infection home to their parents.
 

Michigan sees jump in cases

Governors in some hard-hit states are pleading with a pandemic-weary public to keep up mask-wearing and social distancing and avoid unnecessary travel and large gatherings in order to protect in-person classes. 

In Michigan, many schools reopened and youth sports resumed just as the more contagious B.1.1.7 variant spread widely. There, cases are rising among all age groups, but the largest number of new COVID-19 cases is among children aged 10-19, the first time that’s happened since the start of the pandemic.

Over the month of March, incidence in this age group had more than doubled in the state. Cases among younger children – infants through 9-year-olds – are also going up, increasing by more than 230% since Feb. 19, according to data from the Michigan Department of Health and Human Services. 

The increases have prompted some schools to pause in-person learning for a time after spring break to slow transmission, according to Natasha Bagdasarian, MD, senior public health physician with the Michigan health department in Ann Arbor.

In Minnesota, on a recent call with reporters, Ruth Lynfield, MD, state epidemiologist, said the B.1.1.7 variant, which has rapidly risen in the state, has a higher attack rate among children than that of earlier versions of the virus, meaning they’re more likely to be infected when exposed.

“We certainly get the sense that youth are what we might refer to as the leading edge of the spread of variants,” she said.

Dr. Lynfield said they were tracking cases spreading through youth sports, classrooms, and daycare centers.

In Massachusetts, the largest number of new COVID-19 infections in the last 2 weeks of March was among children and teens. Massachusetts has the fifth-highest number of recorded B.1.1.7 cases in the United States, according to CDC data.

Although most COVID-19 cases in children and teens are mild, the disease can be severe for those who have underlying medical conditions. Even in healthy children, it can trigger a serious postviral syndrome called MIS-C that requires hospitalization. 

Emerging studies show that children, like adults, can develop the lingering symptoms of long COVID-19. Recent data from the United Kingdom show 10%-15% of children younger than 16 infected with COVID-19 still had at least one symptom 5 weeks later.

Dr. Osterholm said it remains to be seen whether more cases in children will also mean a rise in more serious outcomes for children, as it has in Europe and Israel.

In Israel, the B.1.1.7 variant arrived at the end of December and became dominant in January. By the end of January, Hadassah Ein Kerem Medical Center in Jerusalem had four patients in its newly opened pediatric COVID-19 ICU unit. They ranged in age from 13 days to 2 years.

By early February, the Ministry of Health warned the country’s doctors to prepare for an “imminent upward trend” in pediatric COVID-19 cases. They notified hospitals to be ready to open more ICU beds for children with COVID-19, according to Cyrille Cohen, PhD, head of the laboratory of immunotherapy at Bar-Ilan University in Ramat Gan, Israel.

On March 31, French President Emmanuel Macron ordered France into its third national lockdown and closed schools for 3 weeks to try to hold off a third wave of COVID-19. President Macron had been a staunch defender of keeping schools open, but said the closure was necessary. 

“It is the best solution to slow down the virus,” he said, according to Reuters.

German Chancellor Angela Merkel recently announced a new lockdown for Germany as the spread of the variants has led to rising cases there.

“I think what we’re seeing here is this is going to play out over the country,” said Dr. Osterholm. “Before this time, we didn’t see major transmission in younger kids particularly K through eighth grade, and now we’re seeing that happening with many school outbreaks, particularly in the Northeast and in the Midwest.” He added that it will spread through southern states as well.
 

Fall surge all over again

“It’s starting to feel an awful lot like déjà vu, where the hospitalization numbers, the positivity rate, all of the metrics that we track are trending up significantly, and it’s feeling like the fall surge,” said Brian Peters, CEO of the Michigan Hospital Association. “It’s feeling in many ways like the initial surge a year ago.”

Mr. Peters said that in January and February, COVID-19 hospitalizations in Michigan were less than 1,000 a day. Recently, he said, there were 2,558 people hospitalized with COVID-19 in Michigan.

About half of adults aged 65 and older have been fully vaccinated in Michigan. That’s led to a dramatic drop in cases and hospitalizations among seniors, who are at highest risk of death. At the same time, Gov. Gretchen Whitmer and health officials with the Biden administration have encouraged schools to reopen for in-person learning, and extracurricular activities have largely resumed.

The same circumstances – students in classrooms, combined with the arrival of the variants – resulted in COVID-19 cases caused by the B.1.1.7 variant increasing  among younger age groups in the United Kingdom. 

When schools were locked down again, however, cases caused by variant and wild type viruses both dropped in children, suggesting that there wasn’t anything that made B.1.1.7 extra risky for children, but that the strain is more contagious for everyone. Sports, extracurricular activities, and classrooms offered the virus plenty of opportunities to spread.

In Michigan, Dr. Bagdasarian said the outbreaks in children started with winter sports.

“Not necessarily transmission on the field, but we’re really talking about social gatherings that were happening in and around sports,” like the pizza party to celebrate a team win, she said, “and I think those social gatherings were a big driver.”

“Outbreaks are trickling over into teams and trickling over into schools, which is exactly what we want to avoid,” she added.

Thus far, Michigan has been reserving vaccine doses for older adults but will open eligibility to anyone age 16 and older starting on April 6.

Until younger age groups can be vaccinated, Mr. Peters said people need to continue to be careful.

“We see people letting their guard down and it’s to be expected,” Mr. Peters said. “People have COVID fatigue, and they are eager to get together with their friends. We’re not out of the woods yet.”
 

Children ‘heavily impacted’

In Nebraska, Alice Sato, MD, PhD, hospital epidemiologist at Children’s Hospital and Medical Center in Omaha, said they saw an increase in MIS-C cases after the winter surges, and she’s watching the data carefully as COVID-19 cases tick up in other midwestern states.

Dr. Sato got so tired of hearing people compare COVID-19 to the flu that she pulled some numbers on pediatric deaths.

While COVID-19 fatality rates in children are much lower than they are for adults, at least 279 children have died across the United States since the start of the pandemic. The highest number of confirmed pediatric deaths recorded during any of the previous 10 flu seasons was 188, according to the CDC.

“So while children are relatively spared, they’re still heavily impacted,” said Dr. Sato.

She was thrilled to hear the recent news that the Pfizer vaccine works well in children aged 12-15, but because Pfizer’s cold-chain requirements make it one the trickiest to store, the Food and Drug Administration hasn’t given the go-ahead yet. She said it will be months before she has any to offer to teens in her state. 

In the meantime, genetic testing has shown that the variants are already circulating there.

“We really want parents and family members who are eligible to be vaccinated because that is a great way to protect children that I cannot vaccinate yet,” Dr. Sato said. “The best way for me to protect children is to prevent the adults around them from being infected.”

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

Public health officials in the Midwest and Northeast are sounding the alarm about steep new increases in COVID-19 cases in children.
 

South_agency/Getty Images

The increases seem to be driven by greater circulation of more contagious variants, just as children and teens have returned to in-person activities such as sports, parties, and classes.

“I can just tell you from my 46 years in the business, I’ve never seen dynamic transmission in kids like we’re seeing right now, younger kids,” said Michael Osterholm, PhD, who directs the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis.

In earlier surges, children – especially younger children – played only minor roles in transmitting the infection. When they were diagnosed with COVID-19, their symptoms tended to be mild or even absent, and for reasons that aren’t well understood, they haven’t usually been the first cases in households or clusters. 

Now, as more SARS-CoV-2 variants have begun to dominate, and seniors gain protection from vaccines, that pattern may be changing. Infectious disease experts are watching to see if COVID-19 will start to spread in a pattern more similar to influenza, with children becoming infected first and bringing the infection home to their parents.
 

Michigan sees jump in cases

Governors in some hard-hit states are pleading with a pandemic-weary public to keep up mask-wearing and social distancing and avoid unnecessary travel and large gatherings in order to protect in-person classes. 

In Michigan, many schools reopened and youth sports resumed just as the more contagious B.1.1.7 variant spread widely. There, cases are rising among all age groups, but the largest number of new COVID-19 cases is among children aged 10-19, the first time that’s happened since the start of the pandemic.

Over the month of March, incidence in this age group had more than doubled in the state. Cases among younger children – infants through 9-year-olds – are also going up, increasing by more than 230% since Feb. 19, according to data from the Michigan Department of Health and Human Services. 

The increases have prompted some schools to pause in-person learning for a time after spring break to slow transmission, according to Natasha Bagdasarian, MD, senior public health physician with the Michigan health department in Ann Arbor.

In Minnesota, on a recent call with reporters, Ruth Lynfield, MD, state epidemiologist, said the B.1.1.7 variant, which has rapidly risen in the state, has a higher attack rate among children than that of earlier versions of the virus, meaning they’re more likely to be infected when exposed.

“We certainly get the sense that youth are what we might refer to as the leading edge of the spread of variants,” she said.

Dr. Lynfield said they were tracking cases spreading through youth sports, classrooms, and daycare centers.

In Massachusetts, the largest number of new COVID-19 infections in the last 2 weeks of March was among children and teens. Massachusetts has the fifth-highest number of recorded B.1.1.7 cases in the United States, according to CDC data.

Although most COVID-19 cases in children and teens are mild, the disease can be severe for those who have underlying medical conditions. Even in healthy children, it can trigger a serious postviral syndrome called MIS-C that requires hospitalization. 

Emerging studies show that children, like adults, can develop the lingering symptoms of long COVID-19. Recent data from the United Kingdom show 10%-15% of children younger than 16 infected with COVID-19 still had at least one symptom 5 weeks later.

Dr. Osterholm said it remains to be seen whether more cases in children will also mean a rise in more serious outcomes for children, as it has in Europe and Israel.

In Israel, the B.1.1.7 variant arrived at the end of December and became dominant in January. By the end of January, Hadassah Ein Kerem Medical Center in Jerusalem had four patients in its newly opened pediatric COVID-19 ICU unit. They ranged in age from 13 days to 2 years.

By early February, the Ministry of Health warned the country’s doctors to prepare for an “imminent upward trend” in pediatric COVID-19 cases. They notified hospitals to be ready to open more ICU beds for children with COVID-19, according to Cyrille Cohen, PhD, head of the laboratory of immunotherapy at Bar-Ilan University in Ramat Gan, Israel.

On March 31, French President Emmanuel Macron ordered France into its third national lockdown and closed schools for 3 weeks to try to hold off a third wave of COVID-19. President Macron had been a staunch defender of keeping schools open, but said the closure was necessary. 

“It is the best solution to slow down the virus,” he said, according to Reuters.

German Chancellor Angela Merkel recently announced a new lockdown for Germany as the spread of the variants has led to rising cases there.

“I think what we’re seeing here is this is going to play out over the country,” said Dr. Osterholm. “Before this time, we didn’t see major transmission in younger kids particularly K through eighth grade, and now we’re seeing that happening with many school outbreaks, particularly in the Northeast and in the Midwest.” He added that it will spread through southern states as well.
 

Fall surge all over again

“It’s starting to feel an awful lot like déjà vu, where the hospitalization numbers, the positivity rate, all of the metrics that we track are trending up significantly, and it’s feeling like the fall surge,” said Brian Peters, CEO of the Michigan Hospital Association. “It’s feeling in many ways like the initial surge a year ago.”

Mr. Peters said that in January and February, COVID-19 hospitalizations in Michigan were less than 1,000 a day. Recently, he said, there were 2,558 people hospitalized with COVID-19 in Michigan.

About half of adults aged 65 and older have been fully vaccinated in Michigan. That’s led to a dramatic drop in cases and hospitalizations among seniors, who are at highest risk of death. At the same time, Gov. Gretchen Whitmer and health officials with the Biden administration have encouraged schools to reopen for in-person learning, and extracurricular activities have largely resumed.

The same circumstances – students in classrooms, combined with the arrival of the variants – resulted in COVID-19 cases caused by the B.1.1.7 variant increasing  among younger age groups in the United Kingdom. 

When schools were locked down again, however, cases caused by variant and wild type viruses both dropped in children, suggesting that there wasn’t anything that made B.1.1.7 extra risky for children, but that the strain is more contagious for everyone. Sports, extracurricular activities, and classrooms offered the virus plenty of opportunities to spread.

In Michigan, Dr. Bagdasarian said the outbreaks in children started with winter sports.

“Not necessarily transmission on the field, but we’re really talking about social gatherings that were happening in and around sports,” like the pizza party to celebrate a team win, she said, “and I think those social gatherings were a big driver.”

“Outbreaks are trickling over into teams and trickling over into schools, which is exactly what we want to avoid,” she added.

Thus far, Michigan has been reserving vaccine doses for older adults but will open eligibility to anyone age 16 and older starting on April 6.

Until younger age groups can be vaccinated, Mr. Peters said people need to continue to be careful.

“We see people letting their guard down and it’s to be expected,” Mr. Peters said. “People have COVID fatigue, and they are eager to get together with their friends. We’re not out of the woods yet.”
 

Children ‘heavily impacted’

In Nebraska, Alice Sato, MD, PhD, hospital epidemiologist at Children’s Hospital and Medical Center in Omaha, said they saw an increase in MIS-C cases after the winter surges, and she’s watching the data carefully as COVID-19 cases tick up in other midwestern states.

Dr. Sato got so tired of hearing people compare COVID-19 to the flu that she pulled some numbers on pediatric deaths.

While COVID-19 fatality rates in children are much lower than they are for adults, at least 279 children have died across the United States since the start of the pandemic. The highest number of confirmed pediatric deaths recorded during any of the previous 10 flu seasons was 188, according to the CDC.

“So while children are relatively spared, they’re still heavily impacted,” said Dr. Sato.

She was thrilled to hear the recent news that the Pfizer vaccine works well in children aged 12-15, but because Pfizer’s cold-chain requirements make it one the trickiest to store, the Food and Drug Administration hasn’t given the go-ahead yet. She said it will be months before she has any to offer to teens in her state. 

In the meantime, genetic testing has shown that the variants are already circulating there.

“We really want parents and family members who are eligible to be vaccinated because that is a great way to protect children that I cannot vaccinate yet,” Dr. Sato said. “The best way for me to protect children is to prevent the adults around them from being infected.”

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

Public health officials in the Midwest and Northeast are sounding the alarm about steep new increases in COVID-19 cases in children.
 

South_agency/Getty Images

The increases seem to be driven by greater circulation of more contagious variants, just as children and teens have returned to in-person activities such as sports, parties, and classes.

“I can just tell you from my 46 years in the business, I’ve never seen dynamic transmission in kids like we’re seeing right now, younger kids,” said Michael Osterholm, PhD, who directs the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis.

In earlier surges, children – especially younger children – played only minor roles in transmitting the infection. When they were diagnosed with COVID-19, their symptoms tended to be mild or even absent, and for reasons that aren’t well understood, they haven’t usually been the first cases in households or clusters. 

Now, as more SARS-CoV-2 variants have begun to dominate, and seniors gain protection from vaccines, that pattern may be changing. Infectious disease experts are watching to see if COVID-19 will start to spread in a pattern more similar to influenza, with children becoming infected first and bringing the infection home to their parents.
 

Michigan sees jump in cases

Governors in some hard-hit states are pleading with a pandemic-weary public to keep up mask-wearing and social distancing and avoid unnecessary travel and large gatherings in order to protect in-person classes. 

In Michigan, many schools reopened and youth sports resumed just as the more contagious B.1.1.7 variant spread widely. There, cases are rising among all age groups, but the largest number of new COVID-19 cases is among children aged 10-19, the first time that’s happened since the start of the pandemic.

Over the month of March, incidence in this age group had more than doubled in the state. Cases among younger children – infants through 9-year-olds – are also going up, increasing by more than 230% since Feb. 19, according to data from the Michigan Department of Health and Human Services. 

The increases have prompted some schools to pause in-person learning for a time after spring break to slow transmission, according to Natasha Bagdasarian, MD, senior public health physician with the Michigan health department in Ann Arbor.

In Minnesota, on a recent call with reporters, Ruth Lynfield, MD, state epidemiologist, said the B.1.1.7 variant, which has rapidly risen in the state, has a higher attack rate among children than that of earlier versions of the virus, meaning they’re more likely to be infected when exposed.

“We certainly get the sense that youth are what we might refer to as the leading edge of the spread of variants,” she said.

Dr. Lynfield said they were tracking cases spreading through youth sports, classrooms, and daycare centers.

In Massachusetts, the largest number of new COVID-19 infections in the last 2 weeks of March was among children and teens. Massachusetts has the fifth-highest number of recorded B.1.1.7 cases in the United States, according to CDC data.

Although most COVID-19 cases in children and teens are mild, the disease can be severe for those who have underlying medical conditions. Even in healthy children, it can trigger a serious postviral syndrome called MIS-C that requires hospitalization. 

Emerging studies show that children, like adults, can develop the lingering symptoms of long COVID-19. Recent data from the United Kingdom show 10%-15% of children younger than 16 infected with COVID-19 still had at least one symptom 5 weeks later.

Dr. Osterholm said it remains to be seen whether more cases in children will also mean a rise in more serious outcomes for children, as it has in Europe and Israel.

In Israel, the B.1.1.7 variant arrived at the end of December and became dominant in January. By the end of January, Hadassah Ein Kerem Medical Center in Jerusalem had four patients in its newly opened pediatric COVID-19 ICU unit. They ranged in age from 13 days to 2 years.

By early February, the Ministry of Health warned the country’s doctors to prepare for an “imminent upward trend” in pediatric COVID-19 cases. They notified hospitals to be ready to open more ICU beds for children with COVID-19, according to Cyrille Cohen, PhD, head of the laboratory of immunotherapy at Bar-Ilan University in Ramat Gan, Israel.

On March 31, French President Emmanuel Macron ordered France into its third national lockdown and closed schools for 3 weeks to try to hold off a third wave of COVID-19. President Macron had been a staunch defender of keeping schools open, but said the closure was necessary. 

“It is the best solution to slow down the virus,” he said, according to Reuters.

German Chancellor Angela Merkel recently announced a new lockdown for Germany as the spread of the variants has led to rising cases there.

“I think what we’re seeing here is this is going to play out over the country,” said Dr. Osterholm. “Before this time, we didn’t see major transmission in younger kids particularly K through eighth grade, and now we’re seeing that happening with many school outbreaks, particularly in the Northeast and in the Midwest.” He added that it will spread through southern states as well.
 

Fall surge all over again

“It’s starting to feel an awful lot like déjà vu, where the hospitalization numbers, the positivity rate, all of the metrics that we track are trending up significantly, and it’s feeling like the fall surge,” said Brian Peters, CEO of the Michigan Hospital Association. “It’s feeling in many ways like the initial surge a year ago.”

Mr. Peters said that in January and February, COVID-19 hospitalizations in Michigan were less than 1,000 a day. Recently, he said, there were 2,558 people hospitalized with COVID-19 in Michigan.

About half of adults aged 65 and older have been fully vaccinated in Michigan. That’s led to a dramatic drop in cases and hospitalizations among seniors, who are at highest risk of death. At the same time, Gov. Gretchen Whitmer and health officials with the Biden administration have encouraged schools to reopen for in-person learning, and extracurricular activities have largely resumed.

The same circumstances – students in classrooms, combined with the arrival of the variants – resulted in COVID-19 cases caused by the B.1.1.7 variant increasing  among younger age groups in the United Kingdom. 

When schools were locked down again, however, cases caused by variant and wild type viruses both dropped in children, suggesting that there wasn’t anything that made B.1.1.7 extra risky for children, but that the strain is more contagious for everyone. Sports, extracurricular activities, and classrooms offered the virus plenty of opportunities to spread.

In Michigan, Dr. Bagdasarian said the outbreaks in children started with winter sports.

“Not necessarily transmission on the field, but we’re really talking about social gatherings that were happening in and around sports,” like the pizza party to celebrate a team win, she said, “and I think those social gatherings were a big driver.”

“Outbreaks are trickling over into teams and trickling over into schools, which is exactly what we want to avoid,” she added.

Thus far, Michigan has been reserving vaccine doses for older adults but will open eligibility to anyone age 16 and older starting on April 6.

Until younger age groups can be vaccinated, Mr. Peters said people need to continue to be careful.

“We see people letting their guard down and it’s to be expected,” Mr. Peters said. “People have COVID fatigue, and they are eager to get together with their friends. We’re not out of the woods yet.”
 

Children ‘heavily impacted’

In Nebraska, Alice Sato, MD, PhD, hospital epidemiologist at Children’s Hospital and Medical Center in Omaha, said they saw an increase in MIS-C cases after the winter surges, and she’s watching the data carefully as COVID-19 cases tick up in other midwestern states.

Dr. Sato got so tired of hearing people compare COVID-19 to the flu that she pulled some numbers on pediatric deaths.

While COVID-19 fatality rates in children are much lower than they are for adults, at least 279 children have died across the United States since the start of the pandemic. The highest number of confirmed pediatric deaths recorded during any of the previous 10 flu seasons was 188, according to the CDC.

“So while children are relatively spared, they’re still heavily impacted,” said Dr. Sato.

She was thrilled to hear the recent news that the Pfizer vaccine works well in children aged 12-15, but because Pfizer’s cold-chain requirements make it one the trickiest to store, the Food and Drug Administration hasn’t given the go-ahead yet. She said it will be months before she has any to offer to teens in her state. 

In the meantime, genetic testing has shown that the variants are already circulating there.

“We really want parents and family members who are eligible to be vaccinated because that is a great way to protect children that I cannot vaccinate yet,” Dr. Sato said. “The best way for me to protect children is to prevent the adults around them from being infected.”

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

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

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

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

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

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

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

About 15 million doses of the Johnson & Johnson COVID-19 vaccine were ruined after workers at a manufacturing plant mixed up ingredients, The New York Times reported.

The Baltimore plant is operated by a company called Emergent BioSolutions, the Times said. The company works with both Johnson & Johnson and AstraZeneca.

The mistake has stopped shipments of the vaccine until the FDA investigates, the paper said. The mishap, however, does not affect doses of the J&J one-shot vaccine already delivered and being used.

The problem is that tens of millions of doses were supposed to come from the Baltimore plant.

The Associated Press reported that Emergent has had numerous problems with the FDA, with the agency citing the company for poorly trained employees, cracked vials and mold.

The records cover inspections at Emergent facilities, including Bayview, since 2017. Following a December 2017 inspection at an Emergent plant in Canton, Massachusetts, the FDA said the company hadn’t corrected “continued low level mold and yeast isolates” found in the facility. Nearly a year later, agency investigators questioned why Emergent had “an unwritten policy of not conducting routine compliance audits” at a separate plant in Baltimore, known as Camden, where an anthrax vaccine is filled into vials.

Meanwhile, in a statement, Johnson & Johnson said its own quality control process identified the problem in one batch of ingredients. The company said the Emergent plant in Baltimore is “not yet authorized to manufacture drug substance for our COVID-19 vaccine. This batch was never advanced to the filling and finishing stages of our manufacturing process.”

The company said it plans to still seek emergency use authorization for a different Emergent facility and will provide more experts on site at Emergent.

The Times reports that President Joe Biden’s team still believes the administration can meet its commitment to have enough vaccine doses to immunize every adult by the end of May.

Johnson & Johnson said it still plans to deliver an additional 24 million doses through April.

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

This article was updated 4/1/21.

About 15 million doses of the Johnson & Johnson COVID-19 vaccine were ruined after workers at a manufacturing plant mixed up ingredients, The New York Times reported.

The Baltimore plant is operated by a company called Emergent BioSolutions, the Times said. The company works with both Johnson & Johnson and AstraZeneca.

The mistake has stopped shipments of the vaccine until the FDA investigates, the paper said. The mishap, however, does not affect doses of the J&J one-shot vaccine already delivered and being used.

The problem is that tens of millions of doses were supposed to come from the Baltimore plant.

The Associated Press reported that Emergent has had numerous problems with the FDA, with the agency citing the company for poorly trained employees, cracked vials and mold.

The records cover inspections at Emergent facilities, including Bayview, since 2017. Following a December 2017 inspection at an Emergent plant in Canton, Massachusetts, the FDA said the company hadn’t corrected “continued low level mold and yeast isolates” found in the facility. Nearly a year later, agency investigators questioned why Emergent had “an unwritten policy of not conducting routine compliance audits” at a separate plant in Baltimore, known as Camden, where an anthrax vaccine is filled into vials.

Meanwhile, in a statement, Johnson & Johnson said its own quality control process identified the problem in one batch of ingredients. The company said the Emergent plant in Baltimore is “not yet authorized to manufacture drug substance for our COVID-19 vaccine. This batch was never advanced to the filling and finishing stages of our manufacturing process.”

The company said it plans to still seek emergency use authorization for a different Emergent facility and will provide more experts on site at Emergent.

The Times reports that President Joe Biden’s team still believes the administration can meet its commitment to have enough vaccine doses to immunize every adult by the end of May.

Johnson & Johnson said it still plans to deliver an additional 24 million doses through April.

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

This article was updated 4/1/21.

About 15 million doses of the Johnson & Johnson COVID-19 vaccine were ruined after workers at a manufacturing plant mixed up ingredients, The New York Times reported.

The Baltimore plant is operated by a company called Emergent BioSolutions, the Times said. The company works with both Johnson & Johnson and AstraZeneca.

The mistake has stopped shipments of the vaccine until the FDA investigates, the paper said. The mishap, however, does not affect doses of the J&J one-shot vaccine already delivered and being used.

The problem is that tens of millions of doses were supposed to come from the Baltimore plant.

The Associated Press reported that Emergent has had numerous problems with the FDA, with the agency citing the company for poorly trained employees, cracked vials and mold.

The records cover inspections at Emergent facilities, including Bayview, since 2017. Following a December 2017 inspection at an Emergent plant in Canton, Massachusetts, the FDA said the company hadn’t corrected “continued low level mold and yeast isolates” found in the facility. Nearly a year later, agency investigators questioned why Emergent had “an unwritten policy of not conducting routine compliance audits” at a separate plant in Baltimore, known as Camden, where an anthrax vaccine is filled into vials.

Meanwhile, in a statement, Johnson & Johnson said its own quality control process identified the problem in one batch of ingredients. The company said the Emergent plant in Baltimore is “not yet authorized to manufacture drug substance for our COVID-19 vaccine. This batch was never advanced to the filling and finishing stages of our manufacturing process.”

The company said it plans to still seek emergency use authorization for a different Emergent facility and will provide more experts on site at Emergent.

The Times reports that President Joe Biden’s team still believes the administration can meet its commitment to have enough vaccine doses to immunize every adult by the end of May.

Johnson & Johnson said it still plans to deliver an additional 24 million doses through April.

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

This article was updated 4/1/21.

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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

The Centers for Disease Control and Prevention has added several new medical conditions to its list of those that predispose adults to more severe COVID-19 illness.

Conditions that had previously been categorized as “might be” placing individuals at increased risk – but now are listed as high risk – include type 1 diabetes (in addition to type 2), moderate-to-severe asthma, liver disease, dementia or other neurologic conditions, stroke/cerebrovascular disease, HIV infection, cystic fibrosis, and overweight (in addition to obesity).

Substance use disorders, which hadn’t been previously listed, are now also considered high risk.  

The new list groups together certain categories, such as chronic lung diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc) and heart conditions (heart failure, coronary artery disease, hypertension, etc).

Both diabetes types are now grouped under “diabetes.”  

The added medical conditions were posted on the CDC website’s COVID-19 page on March 29.
 

Type 1 diabetes and other conditions now priority for vaccination

The CDC refers to the medical conditions list as phase 1c in regard to COVID-19 vaccine prioritization, which means that anyone with any of these conditions can now be prioritized for vaccination, following those in groups 1a (frontline essential workers and those in long-term care facilities) and 1b (people aged 65-74 years; other essential workers; and people aged 16-64 years with underlying conditions that increase the risk of serious, life-threatening complications from COVID-19).

But in many cases, multiple states have already either fully opened up vaccine eligibility to all adults or have created their own lists of underlying high-risk medical conditions, CDC spokeswoman Kristen Nordlund told this news organization.  

No conditions have been removed from the list.

In January, the American Diabetes Association and 18 other organizations sent a letter to the CDC requesting that type 1 diabetes be prioritized along with type 2, based on data from studies showing people with both types to be at high risk for severe COVID-19 illness.

Now, ADA says, “this updated guidance will help to address the fact that in many states, millions of people with type 1 diabetes have not been prioritized equally, slowing their access to critical vaccines.”

While awaiting this latest CDC move, ADA had been urging state governors to prioritize type 1 and type 2 diabetes equally. As of now, 38 states and the District of Columbia had either done so or announced that they would.

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