I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m²) seen in the pediatric emergency department with tachycardia, O₂ saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.¹

She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.

Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”

The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.²

Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?

Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.

Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.³

Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.

Implementation challenges

The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.

Summary

Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.⁴ Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.

2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.

3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.

4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.

I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m²) seen in the pediatric emergency department with tachycardia, O₂ saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.¹

She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.

Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”

The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.²

Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?

Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.

Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.³

Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.

Implementation challenges

The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.

Summary

Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.⁴ Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.

2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.

3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.

4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.

I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m²) seen in the pediatric emergency department with tachycardia, O₂ saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.¹

She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.

Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”

The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.²

Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?

Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.

Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.³

Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.

Implementation challenges

The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.

Summary

Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.⁴ Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.

2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.

3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.

4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.

With deer hunting season underway or starting in states across the United States, people should wear a mask and gloves when handling deer to prevent coronavirus transmission, experts say.

A recent study by researchers at Penn State University found that more than 80% of the deer sampled during last year’s hunting season in counties across Iowa tested positive for COVID-19. Overall, a third of the deer sampled between September 2020 and January 2021 tested positive.

“The findings suggest that white-tailed deer may be a reservoir for the virus to continually circulate and raise concerns about the emergence of new strains that may prove a threat to wildlife and, possibly, to humans,” the researchers said in a statement.

The deer were likely infected due to “multiple human-to-deer spillover events and deer-to-deer transmission,” they noted.

Studies haven’t shown whether deer have infected humans, but public health experts are recommending that hunters and deer handlers consider possible transmission avenues, The Plain Dealer, a Cleveland newspaper, reported.

To limit deer-to-deer transmission, homeowners and hunters should avoid concentrating deer at backyard feeders or in hunting situations, according to the Ohio Department of Natural Resources Division of Wildlife. The department also urged people to not allow contact between wildlife and domestic animals, including pets and hunting dogs.

Eating venison shouldn’t be a concern if people cook the meat thoroughly, the newspaper reported. Until more is known, people should wear a mask and gloves when handling deer.

In the study, Penn State researchers examined 283 deer between December 2020 and January 2021. They took samples from lymph nodes in the head and neck as part of Iowa’s chronic wasting disease surveillance program.

“This is the first direct evidence of SARS-CoV-2 virus in any free-living species, and our findings have important implications for the ecology and long-term persistence of the virus,” Suresh Kuchipudi, PhD, associate director of the Animal Diagnostics Laboratory at Penn State, said in the statement.

“These include spillover to other free-living or captive animals and potential spillback to human hosts,” he said. “Of course, this highlights that many urgent steps are needed to monitor the spread of the virus in deer and prevent spillback to humans.”

The research team sequenced genomes from all the positive samples and identified 12 coronavirus lineages. The prominent ones corresponded to the same lineages found in humans at the time.

The U.S. Department of Agriculture has also inspected 480 samples this year from white-tailed deer in Illinois, Michigan, New York, and Pennsylvania. Researchers detected virus antibodies in 33% of samples, according to a statement from the department. The department has confirmed the virus in deer in Ohio as well.

Health officials have recommended that hunters also take precautions while around other people by getting vaccinated and wearing a mask, according to WMTV in Wisconsin.

“If someone comes to deer camp and they have COVID and other folks aren’t vaccinated, in that enclosed space with the laughing and good times that are had, the likelihood that those other hunters would be infected is pretty high,” Jeff Pothof, MD, an emergency medicine doctor at UW Health, told the news outlet.

“I think the biggest risk to deer hunters is going to be other hunters, not so much the deer,” he said.

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

With deer hunting season underway or starting in states across the United States, people should wear a mask and gloves when handling deer to prevent coronavirus transmission, experts say.

A recent study by researchers at Penn State University found that more than 80% of the deer sampled during last year’s hunting season in counties across Iowa tested positive for COVID-19. Overall, a third of the deer sampled between September 2020 and January 2021 tested positive.

“The findings suggest that white-tailed deer may be a reservoir for the virus to continually circulate and raise concerns about the emergence of new strains that may prove a threat to wildlife and, possibly, to humans,” the researchers said in a statement.

The deer were likely infected due to “multiple human-to-deer spillover events and deer-to-deer transmission,” they noted.

Studies haven’t shown whether deer have infected humans, but public health experts are recommending that hunters and deer handlers consider possible transmission avenues, The Plain Dealer, a Cleveland newspaper, reported.

To limit deer-to-deer transmission, homeowners and hunters should avoid concentrating deer at backyard feeders or in hunting situations, according to the Ohio Department of Natural Resources Division of Wildlife. The department also urged people to not allow contact between wildlife and domestic animals, including pets and hunting dogs.

Eating venison shouldn’t be a concern if people cook the meat thoroughly, the newspaper reported. Until more is known, people should wear a mask and gloves when handling deer.

In the study, Penn State researchers examined 283 deer between December 2020 and January 2021. They took samples from lymph nodes in the head and neck as part of Iowa’s chronic wasting disease surveillance program.

“This is the first direct evidence of SARS-CoV-2 virus in any free-living species, and our findings have important implications for the ecology and long-term persistence of the virus,” Suresh Kuchipudi, PhD, associate director of the Animal Diagnostics Laboratory at Penn State, said in the statement.

“These include spillover to other free-living or captive animals and potential spillback to human hosts,” he said. “Of course, this highlights that many urgent steps are needed to monitor the spread of the virus in deer and prevent spillback to humans.”

The research team sequenced genomes from all the positive samples and identified 12 coronavirus lineages. The prominent ones corresponded to the same lineages found in humans at the time.

The U.S. Department of Agriculture has also inspected 480 samples this year from white-tailed deer in Illinois, Michigan, New York, and Pennsylvania. Researchers detected virus antibodies in 33% of samples, according to a statement from the department. The department has confirmed the virus in deer in Ohio as well.

Health officials have recommended that hunters also take precautions while around other people by getting vaccinated and wearing a mask, according to WMTV in Wisconsin.

“If someone comes to deer camp and they have COVID and other folks aren’t vaccinated, in that enclosed space with the laughing and good times that are had, the likelihood that those other hunters would be infected is pretty high,” Jeff Pothof, MD, an emergency medicine doctor at UW Health, told the news outlet.

“I think the biggest risk to deer hunters is going to be other hunters, not so much the deer,” he said.

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

With deer hunting season underway or starting in states across the United States, people should wear a mask and gloves when handling deer to prevent coronavirus transmission, experts say.

A recent study by researchers at Penn State University found that more than 80% of the deer sampled during last year’s hunting season in counties across Iowa tested positive for COVID-19. Overall, a third of the deer sampled between September 2020 and January 2021 tested positive.

“The findings suggest that white-tailed deer may be a reservoir for the virus to continually circulate and raise concerns about the emergence of new strains that may prove a threat to wildlife and, possibly, to humans,” the researchers said in a statement.

The deer were likely infected due to “multiple human-to-deer spillover events and deer-to-deer transmission,” they noted.

Studies haven’t shown whether deer have infected humans, but public health experts are recommending that hunters and deer handlers consider possible transmission avenues, The Plain Dealer, a Cleveland newspaper, reported.

To limit deer-to-deer transmission, homeowners and hunters should avoid concentrating deer at backyard feeders or in hunting situations, according to the Ohio Department of Natural Resources Division of Wildlife. The department also urged people to not allow contact between wildlife and domestic animals, including pets and hunting dogs.

Eating venison shouldn’t be a concern if people cook the meat thoroughly, the newspaper reported. Until more is known, people should wear a mask and gloves when handling deer.

In the study, Penn State researchers examined 283 deer between December 2020 and January 2021. They took samples from lymph nodes in the head and neck as part of Iowa’s chronic wasting disease surveillance program.

“This is the first direct evidence of SARS-CoV-2 virus in any free-living species, and our findings have important implications for the ecology and long-term persistence of the virus,” Suresh Kuchipudi, PhD, associate director of the Animal Diagnostics Laboratory at Penn State, said in the statement.

“These include spillover to other free-living or captive animals and potential spillback to human hosts,” he said. “Of course, this highlights that many urgent steps are needed to monitor the spread of the virus in deer and prevent spillback to humans.”

The research team sequenced genomes from all the positive samples and identified 12 coronavirus lineages. The prominent ones corresponded to the same lineages found in humans at the time.

The U.S. Department of Agriculture has also inspected 480 samples this year from white-tailed deer in Illinois, Michigan, New York, and Pennsylvania. Researchers detected virus antibodies in 33% of samples, according to a statement from the department. The department has confirmed the virus in deer in Ohio as well.

Health officials have recommended that hunters also take precautions while around other people by getting vaccinated and wearing a mask, according to WMTV in Wisconsin.

“If someone comes to deer camp and they have COVID and other folks aren’t vaccinated, in that enclosed space with the laughing and good times that are had, the likelihood that those other hunters would be infected is pretty high,” Jeff Pothof, MD, an emergency medicine doctor at UW Health, told the news outlet.

“I think the biggest risk to deer hunters is going to be other hunters, not so much the deer,” he said.

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

A systematic review of studies of infections found no evidence of airborne transmission of respiratory or enteric pathogens in public washrooms, but some experts disagree with the study’s conclusions. The study was published in Science of the Total Environment.

Sotiris Vardoulakis, PhD, of the Australian National University, Canberra, and colleagues reviewed studies of infections associated with public washrooms.

The researchers used keywords to identify potential articles. After screening study abstracts to ensure that only publicly available washrooms with toilets, sinks, and hand dryers were included, 65 studies remained. The investigators excluded washrooms on public transportation (ships, planes, trains, and buses).

“What most of the studies concluded was that what’s really important is to have good hand hygiene and proper maintenance and ventilation of washrooms,” Dr. Vardoulakis said in an interview. “So if the hand washing and drying is effective in the first place, it’s unlikely that the bathroom air or surfaces will pose an infectious disease transmission risk.”

There has been ongoing debate on whether electric hand dryers or paper towels are better. Some studies focused on hygiene. Others focused on the environmental cost of paper towels. One concern is that air dryers might spread germs further.

One study focused on the idea that the air recirculation from electric dryers may spread infective aerosols. Another study determined that the Airblade filters in some electric dryers clean more than 99% of the bacteria. The first study, published in Mayo Clinic Proceedings by Cunrui Huang, MMed, MSPH, and colleagues, concluded that “drying hands thoroughly with single-use, disposable paper towels is the preferred method of hand drying in terms of hand hygiene.” Many people prefer to use paper towels because they can be used as a barrier when opening the washroom door.

Dr. Vardoulakis dismissed the air-versus-paper debate, saying, “If the hand washing and drying is effective in the first place, it’s unlikely that the bathroom air or surfaces will pose an infectious disease transmission risk.”

Although Dr. Vardoulakis’ review did not find that public washrooms pose a risk for infection, other researchers have shown that some settings do pose problems. For example, toilet plumes are thought to have contributed to the 2003 outbreak of severe acute respiratory syndrome at the Amoy Gardens housing complex in Hong Kong and nearby buildings by aerosolization of fecal waste. Also, norovirus has long been shown to be transmitted by aerosolized particles in vomitus or stool.

Rodney E. Rohde, PhD, professor and chair, clinical lab science program, Texas State University, San Marcos, expressed concern about this systematic review in an interview with this news organization. “I believe one of the major limitations is that studies which involved restrooms on planes, hotels, camping (those camp kids are nasty), and other similar public-access restrooms MUST be included in this type of review. I also believe they excluded restrooms from low-income/rural areas. WHAT? Their ultimate conclusions seem to be in line with the most current understanding about hand hygiene (including drying without devices that create strong air currents, which may create widespread emission of microbes).”

In an interview, Emanuel Goldman, PhD, professor of microbiology, biochemistry, and molecular genetics, New Jersey Medical School, Newark, focused on the COVID-specific aspects of the review. “The chances are less than 1 in 10,000 of getting COVID from a fomite, and that’s very conservative,” he said. “I think it’s a lot lower than that. The virus is fragile. It dies very quickly outside of a human host.” He emphasized, “virtually no infectious virus has been found on fomites over the last 2 years. ... A big mistake in a lot of papers is they confuse viral RNA with the virus. It’s not the same. Viral RNA is the genetic material of the virus, but it also is the ghost of the virus after the virus is dead, and that’s what people are finding. They’re finding the ghost of the virus.”

Because “studies show that the transfer from a surface to fingers is in the neighborhood of 10% efficiency” and one’s fingers also kill the virus, “transmission through your fingers is not easy,” Dr. Goldman said. “You’ve got to really work at it to deliberately infect yourself” with COVID from a fomite.

Dr. Rohde’s conclusion about Dr. Vardoulakis’s review? “So, the question may be, have there been enough studies, in general, of these other areas to include in a review? Otherwise, can we really generalize from this study? I don’t think so.”

Dr. Goldman is not worried about COVID transmission in public bathrooms. His summation: “I think indoor dining is more risky than anything else right now.”

The study was funded by Dyson Technology. Dr. Vardoulakis is a member of the Dyson scientific advisory board.

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

A systematic review of studies of infections found no evidence of airborne transmission of respiratory or enteric pathogens in public washrooms, but some experts disagree with the study’s conclusions. The study was published in Science of the Total Environment.

Sotiris Vardoulakis, PhD, of the Australian National University, Canberra, and colleagues reviewed studies of infections associated with public washrooms.

The researchers used keywords to identify potential articles. After screening study abstracts to ensure that only publicly available washrooms with toilets, sinks, and hand dryers were included, 65 studies remained. The investigators excluded washrooms on public transportation (ships, planes, trains, and buses).

“What most of the studies concluded was that what’s really important is to have good hand hygiene and proper maintenance and ventilation of washrooms,” Dr. Vardoulakis said in an interview. “So if the hand washing and drying is effective in the first place, it’s unlikely that the bathroom air or surfaces will pose an infectious disease transmission risk.”

There has been ongoing debate on whether electric hand dryers or paper towels are better. Some studies focused on hygiene. Others focused on the environmental cost of paper towels. One concern is that air dryers might spread germs further.

One study focused on the idea that the air recirculation from electric dryers may spread infective aerosols. Another study determined that the Airblade filters in some electric dryers clean more than 99% of the bacteria. The first study, published in Mayo Clinic Proceedings by Cunrui Huang, MMed, MSPH, and colleagues, concluded that “drying hands thoroughly with single-use, disposable paper towels is the preferred method of hand drying in terms of hand hygiene.” Many people prefer to use paper towels because they can be used as a barrier when opening the washroom door.

Dr. Vardoulakis dismissed the air-versus-paper debate, saying, “If the hand washing and drying is effective in the first place, it’s unlikely that the bathroom air or surfaces will pose an infectious disease transmission risk.”

Although Dr. Vardoulakis’ review did not find that public washrooms pose a risk for infection, other researchers have shown that some settings do pose problems. For example, toilet plumes are thought to have contributed to the 2003 outbreak of severe acute respiratory syndrome at the Amoy Gardens housing complex in Hong Kong and nearby buildings by aerosolization of fecal waste. Also, norovirus has long been shown to be transmitted by aerosolized particles in vomitus or stool.

Rodney E. Rohde, PhD, professor and chair, clinical lab science program, Texas State University, San Marcos, expressed concern about this systematic review in an interview with this news organization. “I believe one of the major limitations is that studies which involved restrooms on planes, hotels, camping (those camp kids are nasty), and other similar public-access restrooms MUST be included in this type of review. I also believe they excluded restrooms from low-income/rural areas. WHAT? Their ultimate conclusions seem to be in line with the most current understanding about hand hygiene (including drying without devices that create strong air currents, which may create widespread emission of microbes).”

In an interview, Emanuel Goldman, PhD, professor of microbiology, biochemistry, and molecular genetics, New Jersey Medical School, Newark, focused on the COVID-specific aspects of the review. “The chances are less than 1 in 10,000 of getting COVID from a fomite, and that’s very conservative,” he said. “I think it’s a lot lower than that. The virus is fragile. It dies very quickly outside of a human host.” He emphasized, “virtually no infectious virus has been found on fomites over the last 2 years. ... A big mistake in a lot of papers is they confuse viral RNA with the virus. It’s not the same. Viral RNA is the genetic material of the virus, but it also is the ghost of the virus after the virus is dead, and that’s what people are finding. They’re finding the ghost of the virus.”

Because “studies show that the transfer from a surface to fingers is in the neighborhood of 10% efficiency” and one’s fingers also kill the virus, “transmission through your fingers is not easy,” Dr. Goldman said. “You’ve got to really work at it to deliberately infect yourself” with COVID from a fomite.

Dr. Rohde’s conclusion about Dr. Vardoulakis’s review? “So, the question may be, have there been enough studies, in general, of these other areas to include in a review? Otherwise, can we really generalize from this study? I don’t think so.”

Dr. Goldman is not worried about COVID transmission in public bathrooms. His summation: “I think indoor dining is more risky than anything else right now.”

The study was funded by Dyson Technology. Dr. Vardoulakis is a member of the Dyson scientific advisory board.

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

A systematic review of studies of infections found no evidence of airborne transmission of respiratory or enteric pathogens in public washrooms, but some experts disagree with the study’s conclusions. The study was published in Science of the Total Environment.

Sotiris Vardoulakis, PhD, of the Australian National University, Canberra, and colleagues reviewed studies of infections associated with public washrooms.

The researchers used keywords to identify potential articles. After screening study abstracts to ensure that only publicly available washrooms with toilets, sinks, and hand dryers were included, 65 studies remained. The investigators excluded washrooms on public transportation (ships, planes, trains, and buses).

“What most of the studies concluded was that what’s really important is to have good hand hygiene and proper maintenance and ventilation of washrooms,” Dr. Vardoulakis said in an interview. “So if the hand washing and drying is effective in the first place, it’s unlikely that the bathroom air or surfaces will pose an infectious disease transmission risk.”

There has been ongoing debate on whether electric hand dryers or paper towels are better. Some studies focused on hygiene. Others focused on the environmental cost of paper towels. One concern is that air dryers might spread germs further.

One study focused on the idea that the air recirculation from electric dryers may spread infective aerosols. Another study determined that the Airblade filters in some electric dryers clean more than 99% of the bacteria. The first study, published in Mayo Clinic Proceedings by Cunrui Huang, MMed, MSPH, and colleagues, concluded that “drying hands thoroughly with single-use, disposable paper towels is the preferred method of hand drying in terms of hand hygiene.” Many people prefer to use paper towels because they can be used as a barrier when opening the washroom door.

Dr. Vardoulakis dismissed the air-versus-paper debate, saying, “If the hand washing and drying is effective in the first place, it’s unlikely that the bathroom air or surfaces will pose an infectious disease transmission risk.”

Although Dr. Vardoulakis’ review did not find that public washrooms pose a risk for infection, other researchers have shown that some settings do pose problems. For example, toilet plumes are thought to have contributed to the 2003 outbreak of severe acute respiratory syndrome at the Amoy Gardens housing complex in Hong Kong and nearby buildings by aerosolization of fecal waste. Also, norovirus has long been shown to be transmitted by aerosolized particles in vomitus or stool.

Rodney E. Rohde, PhD, professor and chair, clinical lab science program, Texas State University, San Marcos, expressed concern about this systematic review in an interview with this news organization. “I believe one of the major limitations is that studies which involved restrooms on planes, hotels, camping (those camp kids are nasty), and other similar public-access restrooms MUST be included in this type of review. I also believe they excluded restrooms from low-income/rural areas. WHAT? Their ultimate conclusions seem to be in line with the most current understanding about hand hygiene (including drying without devices that create strong air currents, which may create widespread emission of microbes).”

In an interview, Emanuel Goldman, PhD, professor of microbiology, biochemistry, and molecular genetics, New Jersey Medical School, Newark, focused on the COVID-specific aspects of the review. “The chances are less than 1 in 10,000 of getting COVID from a fomite, and that’s very conservative,” he said. “I think it’s a lot lower than that. The virus is fragile. It dies very quickly outside of a human host.” He emphasized, “virtually no infectious virus has been found on fomites over the last 2 years. ... A big mistake in a lot of papers is they confuse viral RNA with the virus. It’s not the same. Viral RNA is the genetic material of the virus, but it also is the ghost of the virus after the virus is dead, and that’s what people are finding. They’re finding the ghost of the virus.”

Because “studies show that the transfer from a surface to fingers is in the neighborhood of 10% efficiency” and one’s fingers also kill the virus, “transmission through your fingers is not easy,” Dr. Goldman said. “You’ve got to really work at it to deliberately infect yourself” with COVID from a fomite.

Dr. Rohde’s conclusion about Dr. Vardoulakis’s review? “So, the question may be, have there been enough studies, in general, of these other areas to include in a review? Otherwise, can we really generalize from this study? I don’t think so.”

Dr. Goldman is not worried about COVID transmission in public bathrooms. His summation: “I think indoor dining is more risky than anything else right now.”

The study was funded by Dyson Technology. Dr. Vardoulakis is a member of the Dyson scientific advisory board.

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

At its November meeting, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) voted against Biogen’s controversial Alzheimer’s drug aducanumab (Aduhelm), making it highly unlikely the drug will be recommended for approval at its December meeting.

In a news release issued Nov. 17, Biogen said the company received a “negative trend vote” on the aducanumab marketing authorization application in Europe.

“While we are disappointed with the trend vote, we strongly believe in the strength of our data and that aducanumab has the potential to make a positive and meaningful difference for people and families affected by Alzheimer’s disease [AD],” Priya Singhal, MD, MPH, head of global safety and regulatory sciences and interim head of research and development at Biogen, said in the release.

The EMA committee is expected to adopt a formal opinion on the marketing application at its December meeting (Dec. 13-16, 2021).

“Biogen will continue to engage with the EMA and CHMP as it considers next steps towards the goal of providing access to aducanumab to patients in Europe,” the company said.

At the recent Clinical Trials on Alzheimer’s Disease conference, Biogen announced new phase 3 findings that “provide further evidence of aducanumab’s effect on lowering amyloid beta plaque and downstream tau pathology, the two defining pathologies of Alzheimer’s disease,” the company said.
 

No clinically meaningful effect

In a statement from the nonprofit U.K. Science Media Centre, Prof. Robert Howard, from University College London, said the result of the CHMP vote “is absolutely the decision that we should have expected from the EMA’s expert advisory panel and is consistent with the FDA’s [U.S. Food and Drug Administration’s] Advisory Committee who voted unanimously 12 months ago against approval of aducanumab because of a lack of demonstrable efficacy in the pivotal phase 3 trials ENGAGE and EMERGE.”

“The FDA’s accelerated approval of aducanumab, solely on the grounds that it was reasonable to expect that reduction in amyloid would lead to improvement in the course of Alzheimer’s disease, despite all the evidence indicating no meaningful correlation between amyloid reduction and symptom improvement, has been highly controversial and has called into question the impartiality of the FDA and its staff,” Prof. Howard noted.

He anticipates that when the EMA panel meets in December they will not grant a license to aducanumab.

“Aducanumab is a treatment without convincing efficacy, with serious associated adverse effects and a high financial cost. On the basis of the available evidence and in the best interests of people with Alzheimer’s disease, their families and those who care for them, EMA and MHRA [Medicines and Healthcare products Regulatory Agency] should not approve a license for aducanumab,” Prof. Howard said.

Also weighing in, David Thomas, head of policy at Alzheimer’s Research UK, said the need for new AD treatments is “urgent,” but added that “it’s vital that regulators judge that any new treatment is safe and effective.”

“Results of aducanumab’s phase 3 trials, EMERGE and ENGAGE, have sparked much debate among the research community about how to judge the effectiveness of any new Alzheimer’s treatment,” Mr. Thomas noted.

“The FDA’s approval of aducanumab in the U.S. was based on the drug’s ability to clear the hallmark Alzheimer’s protein amyloid from the brain. As part of this approval the regulator now requires further trials to be carried out to ensure that aducanumab brings long-term improvement to people’s memory, thinking and day-to-day lives,” Mr. Thomas said.

EMA is now undertaking its own review of the data and “it’s important that we wait for the committee’s official recommendation, which is expected next month. In the meantime, we must continue to work at pace to ensure researchers are developing a broad pipeline of potential new treatments for diseases like Alzheimer’s, and that health systems like the NHS [National Health Service] will be ready to deliver them in the years ahead,” he added.
 

‘Reckless’ FDA decision

In related news, the Centers for Medicare and Medicaid Services (CMS) has announced that the Medicare Part B standard premium would rise to $170 per month for all enrollees, a 15% spike over the 2021 premium level.

“All Part B Medicare beneficiaries soon will be forced to bear significant financial burden as a direct result of the FDA’s reckless decision to approve aducanumab, a drug that has not been proven to provide any clinically meaningful benefit to Alzheimer’s patients but nevertheless carries an indefensible annual price tag set by Biogen at $56,000 per year for just the drug alone,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said in a statement.

“To protect the many Medicare beneficiaries who cannot afford the unacceptable 15% jump in Part B premiums, CMS must promptly announce that it will exclude aducanumab from coverage under the Medicare program until there is definitive evidence that the drug provides substantial evidence of cognitive benefit to Alzheimer’s disease patients,” Dr. Carome said.

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

At its November meeting, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) voted against Biogen’s controversial Alzheimer’s drug aducanumab (Aduhelm), making it highly unlikely the drug will be recommended for approval at its December meeting.

In a news release issued Nov. 17, Biogen said the company received a “negative trend vote” on the aducanumab marketing authorization application in Europe.

“While we are disappointed with the trend vote, we strongly believe in the strength of our data and that aducanumab has the potential to make a positive and meaningful difference for people and families affected by Alzheimer’s disease [AD],” Priya Singhal, MD, MPH, head of global safety and regulatory sciences and interim head of research and development at Biogen, said in the release.

The EMA committee is expected to adopt a formal opinion on the marketing application at its December meeting (Dec. 13-16, 2021).

“Biogen will continue to engage with the EMA and CHMP as it considers next steps towards the goal of providing access to aducanumab to patients in Europe,” the company said.

At the recent Clinical Trials on Alzheimer’s Disease conference, Biogen announced new phase 3 findings that “provide further evidence of aducanumab’s effect on lowering amyloid beta plaque and downstream tau pathology, the two defining pathologies of Alzheimer’s disease,” the company said.
 

No clinically meaningful effect

In a statement from the nonprofit U.K. Science Media Centre, Prof. Robert Howard, from University College London, said the result of the CHMP vote “is absolutely the decision that we should have expected from the EMA’s expert advisory panel and is consistent with the FDA’s [U.S. Food and Drug Administration’s] Advisory Committee who voted unanimously 12 months ago against approval of aducanumab because of a lack of demonstrable efficacy in the pivotal phase 3 trials ENGAGE and EMERGE.”

“The FDA’s accelerated approval of aducanumab, solely on the grounds that it was reasonable to expect that reduction in amyloid would lead to improvement in the course of Alzheimer’s disease, despite all the evidence indicating no meaningful correlation between amyloid reduction and symptom improvement, has been highly controversial and has called into question the impartiality of the FDA and its staff,” Prof. Howard noted.

He anticipates that when the EMA panel meets in December they will not grant a license to aducanumab.

“Aducanumab is a treatment without convincing efficacy, with serious associated adverse effects and a high financial cost. On the basis of the available evidence and in the best interests of people with Alzheimer’s disease, their families and those who care for them, EMA and MHRA [Medicines and Healthcare products Regulatory Agency] should not approve a license for aducanumab,” Prof. Howard said.

Also weighing in, David Thomas, head of policy at Alzheimer’s Research UK, said the need for new AD treatments is “urgent,” but added that “it’s vital that regulators judge that any new treatment is safe and effective.”

“Results of aducanumab’s phase 3 trials, EMERGE and ENGAGE, have sparked much debate among the research community about how to judge the effectiveness of any new Alzheimer’s treatment,” Mr. Thomas noted.

“The FDA’s approval of aducanumab in the U.S. was based on the drug’s ability to clear the hallmark Alzheimer’s protein amyloid from the brain. As part of this approval the regulator now requires further trials to be carried out to ensure that aducanumab brings long-term improvement to people’s memory, thinking and day-to-day lives,” Mr. Thomas said.

EMA is now undertaking its own review of the data and “it’s important that we wait for the committee’s official recommendation, which is expected next month. In the meantime, we must continue to work at pace to ensure researchers are developing a broad pipeline of potential new treatments for diseases like Alzheimer’s, and that health systems like the NHS [National Health Service] will be ready to deliver them in the years ahead,” he added.
 

‘Reckless’ FDA decision

In related news, the Centers for Medicare and Medicaid Services (CMS) has announced that the Medicare Part B standard premium would rise to $170 per month for all enrollees, a 15% spike over the 2021 premium level.

“All Part B Medicare beneficiaries soon will be forced to bear significant financial burden as a direct result of the FDA’s reckless decision to approve aducanumab, a drug that has not been proven to provide any clinically meaningful benefit to Alzheimer’s patients but nevertheless carries an indefensible annual price tag set by Biogen at $56,000 per year for just the drug alone,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said in a statement.

“To protect the many Medicare beneficiaries who cannot afford the unacceptable 15% jump in Part B premiums, CMS must promptly announce that it will exclude aducanumab from coverage under the Medicare program until there is definitive evidence that the drug provides substantial evidence of cognitive benefit to Alzheimer’s disease patients,” Dr. Carome said.

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

At its November meeting, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) voted against Biogen’s controversial Alzheimer’s drug aducanumab (Aduhelm), making it highly unlikely the drug will be recommended for approval at its December meeting.

In a news release issued Nov. 17, Biogen said the company received a “negative trend vote” on the aducanumab marketing authorization application in Europe.

“While we are disappointed with the trend vote, we strongly believe in the strength of our data and that aducanumab has the potential to make a positive and meaningful difference for people and families affected by Alzheimer’s disease [AD],” Priya Singhal, MD, MPH, head of global safety and regulatory sciences and interim head of research and development at Biogen, said in the release.

The EMA committee is expected to adopt a formal opinion on the marketing application at its December meeting (Dec. 13-16, 2021).

“Biogen will continue to engage with the EMA and CHMP as it considers next steps towards the goal of providing access to aducanumab to patients in Europe,” the company said.

At the recent Clinical Trials on Alzheimer’s Disease conference, Biogen announced new phase 3 findings that “provide further evidence of aducanumab’s effect on lowering amyloid beta plaque and downstream tau pathology, the two defining pathologies of Alzheimer’s disease,” the company said.
 

No clinically meaningful effect

In a statement from the nonprofit U.K. Science Media Centre, Prof. Robert Howard, from University College London, said the result of the CHMP vote “is absolutely the decision that we should have expected from the EMA’s expert advisory panel and is consistent with the FDA’s [U.S. Food and Drug Administration’s] Advisory Committee who voted unanimously 12 months ago against approval of aducanumab because of a lack of demonstrable efficacy in the pivotal phase 3 trials ENGAGE and EMERGE.”

“The FDA’s accelerated approval of aducanumab, solely on the grounds that it was reasonable to expect that reduction in amyloid would lead to improvement in the course of Alzheimer’s disease, despite all the evidence indicating no meaningful correlation between amyloid reduction and symptom improvement, has been highly controversial and has called into question the impartiality of the FDA and its staff,” Prof. Howard noted.

He anticipates that when the EMA panel meets in December they will not grant a license to aducanumab.

“Aducanumab is a treatment without convincing efficacy, with serious associated adverse effects and a high financial cost. On the basis of the available evidence and in the best interests of people with Alzheimer’s disease, their families and those who care for them, EMA and MHRA [Medicines and Healthcare products Regulatory Agency] should not approve a license for aducanumab,” Prof. Howard said.

Also weighing in, David Thomas, head of policy at Alzheimer’s Research UK, said the need for new AD treatments is “urgent,” but added that “it’s vital that regulators judge that any new treatment is safe and effective.”

“Results of aducanumab’s phase 3 trials, EMERGE and ENGAGE, have sparked much debate among the research community about how to judge the effectiveness of any new Alzheimer’s treatment,” Mr. Thomas noted.

“The FDA’s approval of aducanumab in the U.S. was based on the drug’s ability to clear the hallmark Alzheimer’s protein amyloid from the brain. As part of this approval the regulator now requires further trials to be carried out to ensure that aducanumab brings long-term improvement to people’s memory, thinking and day-to-day lives,” Mr. Thomas said.

EMA is now undertaking its own review of the data and “it’s important that we wait for the committee’s official recommendation, which is expected next month. In the meantime, we must continue to work at pace to ensure researchers are developing a broad pipeline of potential new treatments for diseases like Alzheimer’s, and that health systems like the NHS [National Health Service] will be ready to deliver them in the years ahead,” he added.
 

‘Reckless’ FDA decision

In related news, the Centers for Medicare and Medicaid Services (CMS) has announced that the Medicare Part B standard premium would rise to $170 per month for all enrollees, a 15% spike over the 2021 premium level.

“All Part B Medicare beneficiaries soon will be forced to bear significant financial burden as a direct result of the FDA’s reckless decision to approve aducanumab, a drug that has not been proven to provide any clinically meaningful benefit to Alzheimer’s patients but nevertheless carries an indefensible annual price tag set by Biogen at $56,000 per year for just the drug alone,” Michael Carome, MD, director of Public Citizen’s Health Research Group, said in a statement.

“To protect the many Medicare beneficiaries who cannot afford the unacceptable 15% jump in Part B premiums, CMS must promptly announce that it will exclude aducanumab from coverage under the Medicare program until there is definitive evidence that the drug provides substantial evidence of cognitive benefit to Alzheimer’s disease patients,” Dr. Carome said.

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

The Centers for Disease Control and Prevention reported that an estimated 100,306 Americans died from drug overdoses during the period from April 2020 to April 2021, a 28.5% increase from the previous year.

Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.

The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.

The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.

“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.

“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.

Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”

Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”

Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support. 

Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.

In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.

“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
 

Fake pills, fentanyl a huge issue

Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.

“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.

Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.

The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.

“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.

National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.

Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”

Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.

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

The Centers for Disease Control and Prevention reported that an estimated 100,306 Americans died from drug overdoses during the period from April 2020 to April 2021, a 28.5% increase from the previous year.

Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.

The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.

The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.

“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.

“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.

Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”

Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”

Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support. 

Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.

In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.

“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
 

Fake pills, fentanyl a huge issue

Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.

“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.

Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.

The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.

“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.

National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.

Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”

Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.

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

The Centers for Disease Control and Prevention reported that an estimated 100,306 Americans died from drug overdoses during the period from April 2020 to April 2021, a 28.5% increase from the previous year.

Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.

The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.

The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.

“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.

“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.

Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”

Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”

Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support. 

Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.

In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.

“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
 

Fake pills, fentanyl a huge issue

Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.

“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.

Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.

The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.

“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.

National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.

Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”

Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.

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

Background: Prior studies have failed to show a benefit to earlier endoscopic intervention in acute GI bleeding. However, those studies were performed in all-comers without attention to the varying risk within the patient population.

Dr. Lee is a hospitalist at Northwestern Memorial Hospital and Lurie Children’s Hospital and assistant professor of medicine, Feinberg School of Medicine, all in Chicago.

Background: Prior studies have failed to show a benefit to earlier endoscopic intervention in acute GI bleeding. However, those studies were performed in all-comers without attention to the varying risk within the patient population.

Dr. Lee is a hospitalist at Northwestern Memorial Hospital and Lurie Children’s Hospital and assistant professor of medicine, Feinberg School of Medicine, all in Chicago.

Background: Prior studies have failed to show a benefit to earlier endoscopic intervention in acute GI bleeding. However, those studies were performed in all-comers without attention to the varying risk within the patient population.

Dr. Lee is a hospitalist at Northwestern Memorial Hospital and Lurie Children’s Hospital and assistant professor of medicine, Feinberg School of Medicine, all in Chicago.

To the Editor:

There is emerging evidence of skin findings in patients with COVID-19, including perniolike changes of the toes as well as urticarial and vesicular eruptions.¹ Magro et al² reported 3 cases of livedoid and purpuric skin eruptions in critically ill COVID-19 patients with evidence of thrombotic vasculopathy on skin biopsy, including a 32-year-old man with striking buttocks retiform purpura. Histopathologic analysis revealed thrombotic vasculopathy and pressure-induced ischemic necrosis. Since that patient was first evaluated (March 2020), we identified 6 more cases of critically ill COVID-19 patients from a single academic hospital in New York City with essentially identical clinical findings. Herein, we report those 6 cases of critically ill and intubated patients with COVID-19 who developed retiform purpura on the buttocks only, approximately 11 to 21 days after onset of COVID-19 symptoms.

We provided consultation for 5 men and 1 woman (age range, 42–78 years) who were critically ill with COVID-19 and developed retiform purpura on the buttocks (Figures 1 and 2). All had an elevated D-dimer concentration: 2 patients, >700 ng/mL; 2 patients, >2000 ng/mL; 2 patients, >6000 ng/mL (reference, 229 ng/mL). Three patients experienced a peak D-dimer concentration on the day retiform purpura was reported.

Further evidence of coagulopathy in these patients included 1 patient with a newly diagnosed left popliteal deep vein thrombosis and 1 patient with a known history of protein C deficiency and deep vein thromboses. Five patients were receiving anticoagulation on the day the skin changes were documented; anticoagulation was contraindicated in the sixth patient because of oropharyngeal bleeding. Anticoagulation was continued at the treatment dosage (enoxaparin 80 mg twice daily) in 3 patients, and in 2 patients receiving a prophylactic dose (enoxaparin 40 mg daily), anticoagulation was escalated to treatment dose due to rising D-dimer levels and newly diagnosed retiform purpura. Skin biopsy was deferred for all patients due to positional and ventilatory restrictions. At that point in their care, 3 patients remained admitted on medicine floors, 2 were in the intensive care unit, and 1 had died.

Although the differential diagnosis for retiform purpura is broad and should be fully considered in any patient with this finding, based on the elevated D-dimer concentration, critical illness secondary to COVID-19, and striking similarity to earlier reported case of buttocks retiform purpura with thrombotic vasculopathy and pressure injury noted histopathologically,² we suspect the buttocks retiform purpura in our 6 cases also represent a combination of cutaneous thrombosis and pressure injury. In addition to acral livedoid eruptions (also reported by Magro and colleagues²), we suspect that this cutaneous manifestation might be associated with a hypercoagulable state in some patients, especially in the setting of a rising D-dimer concentration. One study found that 31% of 184 patients with severe COVID-19 had thrombotic complications,³ a clinical picture that portends a poor prognosis.⁴

COVID-19 patients presenting with retiform purpura should be fully evaluated based on the broad differential for this morphology. We present 6 cases of buttocks retiform purpura in critically ill COVID-19 patients—all with strikingly similar morphologic findings, an elevated D-dimer concentration, and critical illness due to COVID-19—to alert clinicians to this constellation of findings and propose that this cutaneous manifestation could indicate an associated hypercoaguable state and should prompt a hematology consultation. Additionally, biopsy of this skin finding should be considered, especially if biopsy results might serve to guide management; however, obtaining a biopsy specimen can be technically difficult because of ventilatory requirements.

Given the magnitude of the COVID-19 pandemic and the propensity of these patients to experience thrombotic events, recognition of this skin finding in COVID-19 is important and might allow timely intervention.

To the Editor:

There is emerging evidence of skin findings in patients with COVID-19, including perniolike changes of the toes as well as urticarial and vesicular eruptions.¹ Magro et al² reported 3 cases of livedoid and purpuric skin eruptions in critically ill COVID-19 patients with evidence of thrombotic vasculopathy on skin biopsy, including a 32-year-old man with striking buttocks retiform purpura. Histopathologic analysis revealed thrombotic vasculopathy and pressure-induced ischemic necrosis. Since that patient was first evaluated (March 2020), we identified 6 more cases of critically ill COVID-19 patients from a single academic hospital in New York City with essentially identical clinical findings. Herein, we report those 6 cases of critically ill and intubated patients with COVID-19 who developed retiform purpura on the buttocks only, approximately 11 to 21 days after onset of COVID-19 symptoms.

We provided consultation for 5 men and 1 woman (age range, 42–78 years) who were critically ill with COVID-19 and developed retiform purpura on the buttocks (Figures 1 and 2). All had an elevated D-dimer concentration: 2 patients, >700 ng/mL; 2 patients, >2000 ng/mL; 2 patients, >6000 ng/mL (reference, 229 ng/mL). Three patients experienced a peak D-dimer concentration on the day retiform purpura was reported.

Further evidence of coagulopathy in these patients included 1 patient with a newly diagnosed left popliteal deep vein thrombosis and 1 patient with a known history of protein C deficiency and deep vein thromboses. Five patients were receiving anticoagulation on the day the skin changes were documented; anticoagulation was contraindicated in the sixth patient because of oropharyngeal bleeding. Anticoagulation was continued at the treatment dosage (enoxaparin 80 mg twice daily) in 3 patients, and in 2 patients receiving a prophylactic dose (enoxaparin 40 mg daily), anticoagulation was escalated to treatment dose due to rising D-dimer levels and newly diagnosed retiform purpura. Skin biopsy was deferred for all patients due to positional and ventilatory restrictions. At that point in their care, 3 patients remained admitted on medicine floors, 2 were in the intensive care unit, and 1 had died.

Although the differential diagnosis for retiform purpura is broad and should be fully considered in any patient with this finding, based on the elevated D-dimer concentration, critical illness secondary to COVID-19, and striking similarity to earlier reported case of buttocks retiform purpura with thrombotic vasculopathy and pressure injury noted histopathologically,² we suspect the buttocks retiform purpura in our 6 cases also represent a combination of cutaneous thrombosis and pressure injury. In addition to acral livedoid eruptions (also reported by Magro and colleagues²), we suspect that this cutaneous manifestation might be associated with a hypercoagulable state in some patients, especially in the setting of a rising D-dimer concentration. One study found that 31% of 184 patients with severe COVID-19 had thrombotic complications,³ a clinical picture that portends a poor prognosis.⁴

COVID-19 patients presenting with retiform purpura should be fully evaluated based on the broad differential for this morphology. We present 6 cases of buttocks retiform purpura in critically ill COVID-19 patients—all with strikingly similar morphologic findings, an elevated D-dimer concentration, and critical illness due to COVID-19—to alert clinicians to this constellation of findings and propose that this cutaneous manifestation could indicate an associated hypercoaguable state and should prompt a hematology consultation. Additionally, biopsy of this skin finding should be considered, especially if biopsy results might serve to guide management; however, obtaining a biopsy specimen can be technically difficult because of ventilatory requirements.

Given the magnitude of the COVID-19 pandemic and the propensity of these patients to experience thrombotic events, recognition of this skin finding in COVID-19 is important and might allow timely intervention.

To the Editor:

There is emerging evidence of skin findings in patients with COVID-19, including perniolike changes of the toes as well as urticarial and vesicular eruptions.¹ Magro et al² reported 3 cases of livedoid and purpuric skin eruptions in critically ill COVID-19 patients with evidence of thrombotic vasculopathy on skin biopsy, including a 32-year-old man with striking buttocks retiform purpura. Histopathologic analysis revealed thrombotic vasculopathy and pressure-induced ischemic necrosis. Since that patient was first evaluated (March 2020), we identified 6 more cases of critically ill COVID-19 patients from a single academic hospital in New York City with essentially identical clinical findings. Herein, we report those 6 cases of critically ill and intubated patients with COVID-19 who developed retiform purpura on the buttocks only, approximately 11 to 21 days after onset of COVID-19 symptoms.

We provided consultation for 5 men and 1 woman (age range, 42–78 years) who were critically ill with COVID-19 and developed retiform purpura on the buttocks (Figures 1 and 2). All had an elevated D-dimer concentration: 2 patients, >700 ng/mL; 2 patients, >2000 ng/mL; 2 patients, >6000 ng/mL (reference, 229 ng/mL). Three patients experienced a peak D-dimer concentration on the day retiform purpura was reported.

Further evidence of coagulopathy in these patients included 1 patient with a newly diagnosed left popliteal deep vein thrombosis and 1 patient with a known history of protein C deficiency and deep vein thromboses. Five patients were receiving anticoagulation on the day the skin changes were documented; anticoagulation was contraindicated in the sixth patient because of oropharyngeal bleeding. Anticoagulation was continued at the treatment dosage (enoxaparin 80 mg twice daily) in 3 patients, and in 2 patients receiving a prophylactic dose (enoxaparin 40 mg daily), anticoagulation was escalated to treatment dose due to rising D-dimer levels and newly diagnosed retiform purpura. Skin biopsy was deferred for all patients due to positional and ventilatory restrictions. At that point in their care, 3 patients remained admitted on medicine floors, 2 were in the intensive care unit, and 1 had died.

Although the differential diagnosis for retiform purpura is broad and should be fully considered in any patient with this finding, based on the elevated D-dimer concentration, critical illness secondary to COVID-19, and striking similarity to earlier reported case of buttocks retiform purpura with thrombotic vasculopathy and pressure injury noted histopathologically,² we suspect the buttocks retiform purpura in our 6 cases also represent a combination of cutaneous thrombosis and pressure injury. In addition to acral livedoid eruptions (also reported by Magro and colleagues²), we suspect that this cutaneous manifestation might be associated with a hypercoagulable state in some patients, especially in the setting of a rising D-dimer concentration. One study found that 31% of 184 patients with severe COVID-19 had thrombotic complications,³ a clinical picture that portends a poor prognosis.⁴

COVID-19 patients presenting with retiform purpura should be fully evaluated based on the broad differential for this morphology. We present 6 cases of buttocks retiform purpura in critically ill COVID-19 patients—all with strikingly similar morphologic findings, an elevated D-dimer concentration, and critical illness due to COVID-19—to alert clinicians to this constellation of findings and propose that this cutaneous manifestation could indicate an associated hypercoaguable state and should prompt a hematology consultation. Additionally, biopsy of this skin finding should be considered, especially if biopsy results might serve to guide management; however, obtaining a biopsy specimen can be technically difficult because of ventilatory requirements.

Given the magnitude of the COVID-19 pandemic and the propensity of these patients to experience thrombotic events, recognition of this skin finding in COVID-19 is important and might allow timely intervention.

To the Editor:

A 56-year-old man with a history of opioid abuse and splenectomy decades prior due to a motor vehicle accident was brought to an outside emergency department with confusion, slurred speech, and difficulty breathing. Over the next few days, he became febrile and hypotensive, requiring vasopressors. Clinical laboratory testing revealed a urine drug screen positive for opioids and a low platelet count in the setting of a rapidly evolving retiform purpuric rash.

The patient was transferred to our institution 6 days after initial presentation with primary diagnoses of septic shock with multiorgan failure and disseminated intravascular coagulation (DIC). Blood cultures were positive for gram-negative rods. After several days of broad-spectrum antibiotics and supportive care, cultures were reported as positive for Capnocytophaga canimorsus. Upon further questioning, the patient’s wife reported that the couple had a new puppy and that the patient often allowed the dog to bite him playfully and lick abrasions on his hands and legs. He had not received medical treatment for any of the dog’s bites.

On initial examination at the time of transfer, the patient’s skin was remarkable for diffuse areas of stellate and retiform purpura with dusky centers and necrosis of the nasal tip and earlobes. Both hands were purpuric, with necrosis of the fingertips (Figure 1A). The flank was marked by large areas of full-thickness sloughing of the skin (Figure 1B). The lower extremities were edematous, with some areas of stellate purpura and numerous large bullae that drained straw-colored fluid (Figure 1C). Lower extremity pulses were found with Doppler ultrasonography.

Given the presence of rapidly developing retiform purpura in the clinical context of severe sepsis, purpura fulminans (PF) was the primary consideration in the differential diagnosis. Levamisole-induced necrosis syndrome also was considered because of necrosis of the ears and nose as well as the history of substance use; however, the patient was not known to have a history of cocaine abuse, and a test of antineutrophil cytoplasmic antibody was negative.

A punch biopsy of the abdomen revealed intravascular thrombi with epidermal and sweat gland necrosis, consistent with PF (Figure 2). Gram, Giemsa, and Gomori methenamine-silver stains were negative for organisms. Tissue culture remained negative. Repeat blood cultures demonstrated Candida parapsilosis fungemia. Respiratory culture was positive for budding yeast.

The patient was treated with antimicrobials, intravenous argatroban, and subcutaneous heparin. Purpura and bullae on the trunk slowly resolved with systemic therapy and wound care with petrolatum and nonadherent dressings. However, lesions on the nasal tip, all fingers of both hands, and several toes evolved into dry gangrene. The hospital course was complicated by renal failure requiring continuous renal replacement therapy; respiratory failure requiring ventilator support; and elevated levels of liver enzymes, consistent with involvement of the hepatic microvasculature.

The patient was in the medical intensive care unit at our institution for 2 weeks and was transferred to a burn center for specialized wound care. At transfer, he was still on a ventilator and receiving continuous renal replacement therapy. Subsequently, the patient required a left above-the-knee amputation, right below-the-knee amputation, and amputation of several digits of the upper extremities. In the months after the amputations, he required multiple stump revisions and experienced surgical site infections that complicated healing.

Purpura fulminans is an uncommon syndrome characterized by intravascular thrombosis and hemorrhagic infarction of the skin. The condition commonly is associated with septic shock, causing vascular collapse and DIC. It often develops rapidly.

Because of associated high mortality, it is important to differentiate PF from other causes of cutaneous retiform purpura, including other causes of thrombosis and large vessel vasculitis. Leading causes of PF include infection and hereditary or acquired deficiency of protein C, protein S, or antithrombin III. Regardless of cause, biopsy results demonstrate vascular thrombosis out of proportion to vasculitis. The mortality rate is 42% to 50%. The incidence of postinfectious sepsis sequelae in PF is higher than in survivors of sepsis only, especially amputation.^1-3 Most patients do not die from complications of sepsis but from sequelae of the hypercoagulable and prothrombotic state associated with PF.⁴ Hemorrhagic infarction can affect the kidneys, brain, lungs, heart, eyes, and adrenal glands (ie, necrosis, namely Waterhouse-Friderichsen syndrome).⁵

The most common infectious cause of PF is sepsis secondary to Neisseria meningitidis, with as many as 25% of infected patients developing PF.⁶Streptococcus pneumoniae is another common cause. Other important causative organisms include Streptococcus pyogenes; Staphylococcus aureus (in the setting of intravenous substance use); Klebsiella oxytoca; Klebsiella aerogenes; rickettsial organisms; and viruses, including cytomegalovirus and varicella-zoster virus.^2,7-13 Two earlier cases associated with Capnocytophaga were characterized by concomitant renal failure, metabolic acidosis, hemolytic anemia, and DIC.¹⁴

It is estimated that Capnocytophaga causes 11% to 46% of all cases of sepsis¹⁵; sepsis resulting from Capnocytophaga has extremely poor outcomes, with mortality reaching as high as 60%. The organism is part of the normal oral flora of cats and dogs, and a bite (less often, a scratch) is the cause of most Capnocytophaga infections. The clinical spectrum of C canimorsus infection associated with dog saliva exposure more commonly includes cellulitis at or around the site of inoculation, meningitis, and endocarditis.¹⁶

Although patients affected by PF can be young and healthy, several risk factors for PF have been identified^2,6,16: asplenia, an immunocompromised state, systemic corticosteroid use, cirrhosis, and alcoholism. Asplenic patients have been shown to be particularly susceptible to systemic Capnocytophaga infection; when bitten by a dog, they should be treated with prophylactic antibiotics to cover Capnocytophaga.¹⁷ Immunocompetent patients rarely develop severe infection with Capnocytophaga.^16,18,19 The complement system in particular is critically important in defending against C canimorsus.²⁰

The underlying pathophysiology of acute infectious PF is multifactorial, encompassing increased expression of procoagulant tissue factor by monocytes and endothelial cells in the presence of bacterial pathogens. Dysfunction of protein C, an anticoagulant component of the coagulation cascade, often is cited as a crucial derangement leading to the development of a prothrombotic state in acute infectious PF.²¹ Serum protein S and antithrombin deficiency also can play a role.²² Specific in vitro examination of C canimorsus has revealed a protease that catalyzes N-terminal cleavage of procoagulant factor X, resulting in loss of function.¹⁵

Retiform purpura is a hallmark feature of PF, often beginning as nonblanching erythema with localized edema and petechiae before evolving into the characteristic stellate lesions with hemorrhagic bullae and subsequent necrosis.²³ Pathologic examination reveals microthrombi involving arterioles and smaller vessels.²⁴ There typically is laboratory evidence of DIC in PF, including elevated prothrombin time and partial thromboplastin time, thrombocytopenia, elevated D-dimer, and a decreased fibrinogen level.^6,23

Capnocytophaga bacteria are challenging to grow on standard culture media. Optimal media for growth include 5% sheep’s blood and chocolate agar.¹⁶ Polymerase chain reaction can identify Capnocytophaga; in cases in which blood culture does not produce growth, 16S ribosomal RNA gene sequencing of tissue from skin biopsy has identified the pathogen.²⁵

Some Capnocytophaga isolates have been shown to produce beta-lactamase; individual strains can be resistant to penicillins, cephalosporins, and imipenem.²⁶ Factors associated with an increased risk for death include decreased leukocyte and platelet counts and an increased level of arterial lactate.²⁷

Empiric antibiotic therapy for Capnocytophaga sepsis should include a beta-lactam and beta-lactamase inhibitor, such as piperacillin-tazobactam. Management of DIC can include therapeutic heparin or low-molecular-weight heparin and prophylactic platelet transfusion to maintain a pre-established value.^28-30 Debridement should be conservative; it is important to wait for definite delineation between viable and necrotic tissue,³¹ which might take several months.³² Human skin allografts, in addition to artificial skin, are utilized as supplemental therapy for more rapid wound closure after removal of necrotic tissue.^33,34 Hyperoxygenated fatty acids have been noted to aid in more rapid wound healing in infants with PF.³⁵

Fresh frozen plasma is one method to replace missing factors, but it contains little protein C.³⁶ Outcomes with recombinant human activated protein C (drotrecogin alfa) are mixed, and studies have shown no benefit in reducing the risk for death.^37,38 Protein C concentrate has shown therapeutic benefit in some case reports and small retrospective studies.⁴ In one case report, protein C concentrate and heparin were utilized in combination with antithrombin III.²¹

Hyperbaric O₂ might be of benefit when initiated within 5 days after onset of PF. However, hyperbaric O₂ does carry risk; O₂ toxicity, barotrauma, and barriers to timely resuscitation when the patient is inside the pressurized chamber can occur.²

There is a single report of successful use of the vasodilator iloprost for meningococcal PF without need for surgical intervention; the team also utilized topical nitroglycerin patches on the fingers to avoid digital amputation.³⁹ Epoprostenol, tissue plasminogen activator, and antithrombin have been utilized in cases of extensive PF. Fibrinolytic therapy might have some utility, but only in a setting of malignancy-associated DIC.⁴⁰

Treatment of acute infectious PF lacks a high level of evidence. Options include replacement of anticoagulant factors, anticoagulant therapy, hyperbaric O₂, topical and systemic vasodilators, and, in the setting of underlying cancer, fibrinolytics. Even with therapy, prognosis is guarded.

To the Editor:

A 56-year-old man with a history of opioid abuse and splenectomy decades prior due to a motor vehicle accident was brought to an outside emergency department with confusion, slurred speech, and difficulty breathing. Over the next few days, he became febrile and hypotensive, requiring vasopressors. Clinical laboratory testing revealed a urine drug screen positive for opioids and a low platelet count in the setting of a rapidly evolving retiform purpuric rash.

The patient was transferred to our institution 6 days after initial presentation with primary diagnoses of septic shock with multiorgan failure and disseminated intravascular coagulation (DIC). Blood cultures were positive for gram-negative rods. After several days of broad-spectrum antibiotics and supportive care, cultures were reported as positive for Capnocytophaga canimorsus. Upon further questioning, the patient’s wife reported that the couple had a new puppy and that the patient often allowed the dog to bite him playfully and lick abrasions on his hands and legs. He had not received medical treatment for any of the dog’s bites.

On initial examination at the time of transfer, the patient’s skin was remarkable for diffuse areas of stellate and retiform purpura with dusky centers and necrosis of the nasal tip and earlobes. Both hands were purpuric, with necrosis of the fingertips (Figure 1A). The flank was marked by large areas of full-thickness sloughing of the skin (Figure 1B). The lower extremities were edematous, with some areas of stellate purpura and numerous large bullae that drained straw-colored fluid (Figure 1C). Lower extremity pulses were found with Doppler ultrasonography.

Given the presence of rapidly developing retiform purpura in the clinical context of severe sepsis, purpura fulminans (PF) was the primary consideration in the differential diagnosis. Levamisole-induced necrosis syndrome also was considered because of necrosis of the ears and nose as well as the history of substance use; however, the patient was not known to have a history of cocaine abuse, and a test of antineutrophil cytoplasmic antibody was negative.

A punch biopsy of the abdomen revealed intravascular thrombi with epidermal and sweat gland necrosis, consistent with PF (Figure 2). Gram, Giemsa, and Gomori methenamine-silver stains were negative for organisms. Tissue culture remained negative. Repeat blood cultures demonstrated Candida parapsilosis fungemia. Respiratory culture was positive for budding yeast.

The patient was treated with antimicrobials, intravenous argatroban, and subcutaneous heparin. Purpura and bullae on the trunk slowly resolved with systemic therapy and wound care with petrolatum and nonadherent dressings. However, lesions on the nasal tip, all fingers of both hands, and several toes evolved into dry gangrene. The hospital course was complicated by renal failure requiring continuous renal replacement therapy; respiratory failure requiring ventilator support; and elevated levels of liver enzymes, consistent with involvement of the hepatic microvasculature.

The patient was in the medical intensive care unit at our institution for 2 weeks and was transferred to a burn center for specialized wound care. At transfer, he was still on a ventilator and receiving continuous renal replacement therapy. Subsequently, the patient required a left above-the-knee amputation, right below-the-knee amputation, and amputation of several digits of the upper extremities. In the months after the amputations, he required multiple stump revisions and experienced surgical site infections that complicated healing.

Purpura fulminans is an uncommon syndrome characterized by intravascular thrombosis and hemorrhagic infarction of the skin. The condition commonly is associated with septic shock, causing vascular collapse and DIC. It often develops rapidly.

Because of associated high mortality, it is important to differentiate PF from other causes of cutaneous retiform purpura, including other causes of thrombosis and large vessel vasculitis. Leading causes of PF include infection and hereditary or acquired deficiency of protein C, protein S, or antithrombin III. Regardless of cause, biopsy results demonstrate vascular thrombosis out of proportion to vasculitis. The mortality rate is 42% to 50%. The incidence of postinfectious sepsis sequelae in PF is higher than in survivors of sepsis only, especially amputation.^1-3 Most patients do not die from complications of sepsis but from sequelae of the hypercoagulable and prothrombotic state associated with PF.⁴ Hemorrhagic infarction can affect the kidneys, brain, lungs, heart, eyes, and adrenal glands (ie, necrosis, namely Waterhouse-Friderichsen syndrome).⁵

The most common infectious cause of PF is sepsis secondary to Neisseria meningitidis, with as many as 25% of infected patients developing PF.⁶Streptococcus pneumoniae is another common cause. Other important causative organisms include Streptococcus pyogenes; Staphylococcus aureus (in the setting of intravenous substance use); Klebsiella oxytoca; Klebsiella aerogenes; rickettsial organisms; and viruses, including cytomegalovirus and varicella-zoster virus.^2,7-13 Two earlier cases associated with Capnocytophaga were characterized by concomitant renal failure, metabolic acidosis, hemolytic anemia, and DIC.¹⁴

It is estimated that Capnocytophaga causes 11% to 46% of all cases of sepsis¹⁵; sepsis resulting from Capnocytophaga has extremely poor outcomes, with mortality reaching as high as 60%. The organism is part of the normal oral flora of cats and dogs, and a bite (less often, a scratch) is the cause of most Capnocytophaga infections. The clinical spectrum of C canimorsus infection associated with dog saliva exposure more commonly includes cellulitis at or around the site of inoculation, meningitis, and endocarditis.¹⁶

Although patients affected by PF can be young and healthy, several risk factors for PF have been identified^2,6,16: asplenia, an immunocompromised state, systemic corticosteroid use, cirrhosis, and alcoholism. Asplenic patients have been shown to be particularly susceptible to systemic Capnocytophaga infection; when bitten by a dog, they should be treated with prophylactic antibiotics to cover Capnocytophaga.¹⁷ Immunocompetent patients rarely develop severe infection with Capnocytophaga.^16,18,19 The complement system in particular is critically important in defending against C canimorsus.²⁰

The underlying pathophysiology of acute infectious PF is multifactorial, encompassing increased expression of procoagulant tissue factor by monocytes and endothelial cells in the presence of bacterial pathogens. Dysfunction of protein C, an anticoagulant component of the coagulation cascade, often is cited as a crucial derangement leading to the development of a prothrombotic state in acute infectious PF.²¹ Serum protein S and antithrombin deficiency also can play a role.²² Specific in vitro examination of C canimorsus has revealed a protease that catalyzes N-terminal cleavage of procoagulant factor X, resulting in loss of function.¹⁵

Retiform purpura is a hallmark feature of PF, often beginning as nonblanching erythema with localized edema and petechiae before evolving into the characteristic stellate lesions with hemorrhagic bullae and subsequent necrosis.²³ Pathologic examination reveals microthrombi involving arterioles and smaller vessels.²⁴ There typically is laboratory evidence of DIC in PF, including elevated prothrombin time and partial thromboplastin time, thrombocytopenia, elevated D-dimer, and a decreased fibrinogen level.^6,23

Capnocytophaga bacteria are challenging to grow on standard culture media. Optimal media for growth include 5% sheep’s blood and chocolate agar.¹⁶ Polymerase chain reaction can identify Capnocytophaga; in cases in which blood culture does not produce growth, 16S ribosomal RNA gene sequencing of tissue from skin biopsy has identified the pathogen.²⁵

Some Capnocytophaga isolates have been shown to produce beta-lactamase; individual strains can be resistant to penicillins, cephalosporins, and imipenem.²⁶ Factors associated with an increased risk for death include decreased leukocyte and platelet counts and an increased level of arterial lactate.²⁷

Empiric antibiotic therapy for Capnocytophaga sepsis should include a beta-lactam and beta-lactamase inhibitor, such as piperacillin-tazobactam. Management of DIC can include therapeutic heparin or low-molecular-weight heparin and prophylactic platelet transfusion to maintain a pre-established value.^28-30 Debridement should be conservative; it is important to wait for definite delineation between viable and necrotic tissue,³¹ which might take several months.³² Human skin allografts, in addition to artificial skin, are utilized as supplemental therapy for more rapid wound closure after removal of necrotic tissue.^33,34 Hyperoxygenated fatty acids have been noted to aid in more rapid wound healing in infants with PF.³⁵

Fresh frozen plasma is one method to replace missing factors, but it contains little protein C.³⁶ Outcomes with recombinant human activated protein C (drotrecogin alfa) are mixed, and studies have shown no benefit in reducing the risk for death.^37,38 Protein C concentrate has shown therapeutic benefit in some case reports and small retrospective studies.⁴ In one case report, protein C concentrate and heparin were utilized in combination with antithrombin III.²¹

Hyperbaric O₂ might be of benefit when initiated within 5 days after onset of PF. However, hyperbaric O₂ does carry risk; O₂ toxicity, barotrauma, and barriers to timely resuscitation when the patient is inside the pressurized chamber can occur.²

There is a single report of successful use of the vasodilator iloprost for meningococcal PF without need for surgical intervention; the team also utilized topical nitroglycerin patches on the fingers to avoid digital amputation.³⁹ Epoprostenol, tissue plasminogen activator, and antithrombin have been utilized in cases of extensive PF. Fibrinolytic therapy might have some utility, but only in a setting of malignancy-associated DIC.⁴⁰

Treatment of acute infectious PF lacks a high level of evidence. Options include replacement of anticoagulant factors, anticoagulant therapy, hyperbaric O₂, topical and systemic vasodilators, and, in the setting of underlying cancer, fibrinolytics. Even with therapy, prognosis is guarded.

To the Editor:

A 56-year-old man with a history of opioid abuse and splenectomy decades prior due to a motor vehicle accident was brought to an outside emergency department with confusion, slurred speech, and difficulty breathing. Over the next few days, he became febrile and hypotensive, requiring vasopressors. Clinical laboratory testing revealed a urine drug screen positive for opioids and a low platelet count in the setting of a rapidly evolving retiform purpuric rash.

The patient was transferred to our institution 6 days after initial presentation with primary diagnoses of septic shock with multiorgan failure and disseminated intravascular coagulation (DIC). Blood cultures were positive for gram-negative rods. After several days of broad-spectrum antibiotics and supportive care, cultures were reported as positive for Capnocytophaga canimorsus. Upon further questioning, the patient’s wife reported that the couple had a new puppy and that the patient often allowed the dog to bite him playfully and lick abrasions on his hands and legs. He had not received medical treatment for any of the dog’s bites.

On initial examination at the time of transfer, the patient’s skin was remarkable for diffuse areas of stellate and retiform purpura with dusky centers and necrosis of the nasal tip and earlobes. Both hands were purpuric, with necrosis of the fingertips (Figure 1A). The flank was marked by large areas of full-thickness sloughing of the skin (Figure 1B). The lower extremities were edematous, with some areas of stellate purpura and numerous large bullae that drained straw-colored fluid (Figure 1C). Lower extremity pulses were found with Doppler ultrasonography.

Given the presence of rapidly developing retiform purpura in the clinical context of severe sepsis, purpura fulminans (PF) was the primary consideration in the differential diagnosis. Levamisole-induced necrosis syndrome also was considered because of necrosis of the ears and nose as well as the history of substance use; however, the patient was not known to have a history of cocaine abuse, and a test of antineutrophil cytoplasmic antibody was negative.

A punch biopsy of the abdomen revealed intravascular thrombi with epidermal and sweat gland necrosis, consistent with PF (Figure 2). Gram, Giemsa, and Gomori methenamine-silver stains were negative for organisms. Tissue culture remained negative. Repeat blood cultures demonstrated Candida parapsilosis fungemia. Respiratory culture was positive for budding yeast.

The patient was treated with antimicrobials, intravenous argatroban, and subcutaneous heparin. Purpura and bullae on the trunk slowly resolved with systemic therapy and wound care with petrolatum and nonadherent dressings. However, lesions on the nasal tip, all fingers of both hands, and several toes evolved into dry gangrene. The hospital course was complicated by renal failure requiring continuous renal replacement therapy; respiratory failure requiring ventilator support; and elevated levels of liver enzymes, consistent with involvement of the hepatic microvasculature.

The patient was in the medical intensive care unit at our institution for 2 weeks and was transferred to a burn center for specialized wound care. At transfer, he was still on a ventilator and receiving continuous renal replacement therapy. Subsequently, the patient required a left above-the-knee amputation, right below-the-knee amputation, and amputation of several digits of the upper extremities. In the months after the amputations, he required multiple stump revisions and experienced surgical site infections that complicated healing.

Purpura fulminans is an uncommon syndrome characterized by intravascular thrombosis and hemorrhagic infarction of the skin. The condition commonly is associated with septic shock, causing vascular collapse and DIC. It often develops rapidly.

Because of associated high mortality, it is important to differentiate PF from other causes of cutaneous retiform purpura, including other causes of thrombosis and large vessel vasculitis. Leading causes of PF include infection and hereditary or acquired deficiency of protein C, protein S, or antithrombin III. Regardless of cause, biopsy results demonstrate vascular thrombosis out of proportion to vasculitis. The mortality rate is 42% to 50%. The incidence of postinfectious sepsis sequelae in PF is higher than in survivors of sepsis only, especially amputation.^1-3 Most patients do not die from complications of sepsis but from sequelae of the hypercoagulable and prothrombotic state associated with PF.⁴ Hemorrhagic infarction can affect the kidneys, brain, lungs, heart, eyes, and adrenal glands (ie, necrosis, namely Waterhouse-Friderichsen syndrome).⁵

The most common infectious cause of PF is sepsis secondary to Neisseria meningitidis, with as many as 25% of infected patients developing PF.⁶Streptococcus pneumoniae is another common cause. Other important causative organisms include Streptococcus pyogenes; Staphylococcus aureus (in the setting of intravenous substance use); Klebsiella oxytoca; Klebsiella aerogenes; rickettsial organisms; and viruses, including cytomegalovirus and varicella-zoster virus.^2,7-13 Two earlier cases associated with Capnocytophaga were characterized by concomitant renal failure, metabolic acidosis, hemolytic anemia, and DIC.¹⁴

It is estimated that Capnocytophaga causes 11% to 46% of all cases of sepsis¹⁵; sepsis resulting from Capnocytophaga has extremely poor outcomes, with mortality reaching as high as 60%. The organism is part of the normal oral flora of cats and dogs, and a bite (less often, a scratch) is the cause of most Capnocytophaga infections. The clinical spectrum of C canimorsus infection associated with dog saliva exposure more commonly includes cellulitis at or around the site of inoculation, meningitis, and endocarditis.¹⁶

Although patients affected by PF can be young and healthy, several risk factors for PF have been identified^2,6,16: asplenia, an immunocompromised state, systemic corticosteroid use, cirrhosis, and alcoholism. Asplenic patients have been shown to be particularly susceptible to systemic Capnocytophaga infection; when bitten by a dog, they should be treated with prophylactic antibiotics to cover Capnocytophaga.¹⁷ Immunocompetent patients rarely develop severe infection with Capnocytophaga.^16,18,19 The complement system in particular is critically important in defending against C canimorsus.²⁰

The underlying pathophysiology of acute infectious PF is multifactorial, encompassing increased expression of procoagulant tissue factor by monocytes and endothelial cells in the presence of bacterial pathogens. Dysfunction of protein C, an anticoagulant component of the coagulation cascade, often is cited as a crucial derangement leading to the development of a prothrombotic state in acute infectious PF.²¹ Serum protein S and antithrombin deficiency also can play a role.²² Specific in vitro examination of C canimorsus has revealed a protease that catalyzes N-terminal cleavage of procoagulant factor X, resulting in loss of function.¹⁵

Retiform purpura is a hallmark feature of PF, often beginning as nonblanching erythema with localized edema and petechiae before evolving into the characteristic stellate lesions with hemorrhagic bullae and subsequent necrosis.²³ Pathologic examination reveals microthrombi involving arterioles and smaller vessels.²⁴ There typically is laboratory evidence of DIC in PF, including elevated prothrombin time and partial thromboplastin time, thrombocytopenia, elevated D-dimer, and a decreased fibrinogen level.^6,23

Capnocytophaga bacteria are challenging to grow on standard culture media. Optimal media for growth include 5% sheep’s blood and chocolate agar.¹⁶ Polymerase chain reaction can identify Capnocytophaga; in cases in which blood culture does not produce growth, 16S ribosomal RNA gene sequencing of tissue from skin biopsy has identified the pathogen.²⁵

Some Capnocytophaga isolates have been shown to produce beta-lactamase; individual strains can be resistant to penicillins, cephalosporins, and imipenem.²⁶ Factors associated with an increased risk for death include decreased leukocyte and platelet counts and an increased level of arterial lactate.²⁷

Empiric antibiotic therapy for Capnocytophaga sepsis should include a beta-lactam and beta-lactamase inhibitor, such as piperacillin-tazobactam. Management of DIC can include therapeutic heparin or low-molecular-weight heparin and prophylactic platelet transfusion to maintain a pre-established value.^28-30 Debridement should be conservative; it is important to wait for definite delineation between viable and necrotic tissue,³¹ which might take several months.³² Human skin allografts, in addition to artificial skin, are utilized as supplemental therapy for more rapid wound closure after removal of necrotic tissue.^33,34 Hyperoxygenated fatty acids have been noted to aid in more rapid wound healing in infants with PF.³⁵

Fresh frozen plasma is one method to replace missing factors, but it contains little protein C.³⁶ Outcomes with recombinant human activated protein C (drotrecogin alfa) are mixed, and studies have shown no benefit in reducing the risk for death.^37,38 Protein C concentrate has shown therapeutic benefit in some case reports and small retrospective studies.⁴ In one case report, protein C concentrate and heparin were utilized in combination with antithrombin III.²¹

Hyperbaric O₂ might be of benefit when initiated within 5 days after onset of PF. However, hyperbaric O₂ does carry risk; O₂ toxicity, barotrauma, and barriers to timely resuscitation when the patient is inside the pressurized chamber can occur.²

There is a single report of successful use of the vasodilator iloprost for meningococcal PF without need for surgical intervention; the team also utilized topical nitroglycerin patches on the fingers to avoid digital amputation.³⁹ Epoprostenol, tissue plasminogen activator, and antithrombin have been utilized in cases of extensive PF. Fibrinolytic therapy might have some utility, but only in a setting of malignancy-associated DIC.⁴⁰

Treatment of acute infectious PF lacks a high level of evidence. Options include replacement of anticoagulant factors, anticoagulant therapy, hyperbaric O₂, topical and systemic vasodilators, and, in the setting of underlying cancer, fibrinolytics. Even with therapy, prognosis is guarded.

To the Editor:

Purpura fulminans (PF) is an acute, life-threatening condition characterized by intravascular thrombosis and hemorrhagic necrosis of the skin. It classically presents as retiform purpura with branched or angular purpuric lesions. Purpura fulminans often occurs in the setting of disseminated intravascular coagulation, secondary to sepsis, trauma, malignancy, autoimmune disease, and congenital or acquired protein C or S deficiency, among other abnormalities.¹ Rapid identification and treatment of the underlying cause are mainstays of management. We report a case of PF secondary to Vibrio vulnificus infection and highlight the importance of timely consideration of this etiologic agent due to the high mortality rate and specific treatment required.

A 58-year-old man with liver cirrhosis and hepatitis B virus presented with pain, swelling, and localized erythema affecting both legs as well as a fever. He reported vomiting blood and an episode of bloody diarrhea over the preceding 24 hours. He denied exposure to sick contacts or a history of autoimmune disease. At initial presentation to the emergency department, physical examination revealed few scattered, sharply demarcated, erythematous to violaceous patches that rapidly progressed overnight to hemorrhagic bullae and widespread retiform purpuric patches on both legs (Figure 1). As the patient’s skin condition worsened, he had a blood pressure of 80/50 mm Hg and a pulse rate of 110/min. Serum analysis was notable for mild leukocytosis (10.74×10⁹/L [reference range, 4.8–10.8×10⁹/L), thrombocytopenia (39×10⁹/L [reference range, 150–450×10⁹/L]), and decreased C3 (25 mg/dL [reference range, 81–157 mg/dL]) and C4 (8 mg/dL [reference range, 13–39 mg/dL]). Laboratory findings also were remarkable for prothrombin time (23.3 seconds [reference range, 8.8–12.3 seconds]), partial thromboplastin time (52.5 seconds [reference range, 23.6–35.8 seconds]), and international normalized ratio (2.01 [reference range, 0.8–1.13]). Aspartate transaminase (237 U/L [reference range, 11–39 U/L]) and alanine transaminase (80 U/L [reference range, 11–35 U/L]) were elevated, while antineutrophil cytoplasmic antibodies, serum immunoglobulin, and cryoglobulins were unremarkable. Punch biopsies of the left thigh were performed, and histopathology revealed small vessel thrombosis and ischemic changes consistent with PF (Figure 2). Vancomycin, clindamycin, cefepime injection, and piperacillin-tazobactam were administered intravenously for empiric broad-spectrum sepsis coverage. Within hours, the patient experienced refractory septic shock with disseminated intravascular coagulation and died from pulmonary embolism and subsequent cardiac arrest. Tissue and blood cultures grew V vulnificus.

Vibrio vulnificus is a gram-negative bacillus and a rare cause of primary septicemia following consumption of shellfish, especially oysters. Wounds exposed to saltwater or brackish water contaminated with the microorganism can produce soft-tissue infections. Individuals with chronic liver disease are at greater risk for V vulnificus infection.² The clinical presentation of V vulnificus includes early cellulitislike patches, late purpura with hemorrhagic bullae, and rapidly progressing shock.³

Mortality rates from V vulnificus infection are high.⁴ Therefore, it is recommended to presumptively diagnose V vulnificus septicemia in any individual at risk for infection who presents with the characteristic history in the setting of hypotension, fever, or septic shock. It is crucial for providers to be aware that broad-spectrum antibiotics commonly used for sepsis are inadequate for the treatment of V vulnificus. Immediate treatment with tetracycline (minocycline or doxycycline) and a third-generation cephalosporin (cefotaxime or ceftriaxone injection) or in combination with ciprofloxacin has been proven effective.^4,5

Vibrio vulnificus rarely is described in the literature as inducing PF. In one previously reported case, the patient was otherwise healthy and managed to recover following antibiotic therapy and wound debridement,⁶ whereas in another case the patient had undiagnosed liver cirrhosis and died from the infection.^6,7 In the latter case, the patient presented to the emergency department in a coma. Our patient did not have the clinical signs of sepsis upon initial presentation to the emergency department. It is possible the infection rapidly progressed because of his underlying liver disease. Genotyping analysis of V vulnificus has shown that strains with low pathogenicity can cause primary septicemia in humans.⁷

Our case reinforces the need to quickly recognize V vulnificus as a rare underlying cause of PF and administer the appropriate treatment.

To the Editor:

Purpura fulminans (PF) is an acute, life-threatening condition characterized by intravascular thrombosis and hemorrhagic necrosis of the skin. It classically presents as retiform purpura with branched or angular purpuric lesions. Purpura fulminans often occurs in the setting of disseminated intravascular coagulation, secondary to sepsis, trauma, malignancy, autoimmune disease, and congenital or acquired protein C or S deficiency, among other abnormalities.¹ Rapid identification and treatment of the underlying cause are mainstays of management. We report a case of PF secondary to Vibrio vulnificus infection and highlight the importance of timely consideration of this etiologic agent due to the high mortality rate and specific treatment required.

A 58-year-old man with liver cirrhosis and hepatitis B virus presented with pain, swelling, and localized erythema affecting both legs as well as a fever. He reported vomiting blood and an episode of bloody diarrhea over the preceding 24 hours. He denied exposure to sick contacts or a history of autoimmune disease. At initial presentation to the emergency department, physical examination revealed few scattered, sharply demarcated, erythematous to violaceous patches that rapidly progressed overnight to hemorrhagic bullae and widespread retiform purpuric patches on both legs (Figure 1). As the patient’s skin condition worsened, he had a blood pressure of 80/50 mm Hg and a pulse rate of 110/min. Serum analysis was notable for mild leukocytosis (10.74×10⁹/L [reference range, 4.8–10.8×10⁹/L), thrombocytopenia (39×10⁹/L [reference range, 150–450×10⁹/L]), and decreased C3 (25 mg/dL [reference range, 81–157 mg/dL]) and C4 (8 mg/dL [reference range, 13–39 mg/dL]). Laboratory findings also were remarkable for prothrombin time (23.3 seconds [reference range, 8.8–12.3 seconds]), partial thromboplastin time (52.5 seconds [reference range, 23.6–35.8 seconds]), and international normalized ratio (2.01 [reference range, 0.8–1.13]). Aspartate transaminase (237 U/L [reference range, 11–39 U/L]) and alanine transaminase (80 U/L [reference range, 11–35 U/L]) were elevated, while antineutrophil cytoplasmic antibodies, serum immunoglobulin, and cryoglobulins were unremarkable. Punch biopsies of the left thigh were performed, and histopathology revealed small vessel thrombosis and ischemic changes consistent with PF (Figure 2). Vancomycin, clindamycin, cefepime injection, and piperacillin-tazobactam were administered intravenously for empiric broad-spectrum sepsis coverage. Within hours, the patient experienced refractory septic shock with disseminated intravascular coagulation and died from pulmonary embolism and subsequent cardiac arrest. Tissue and blood cultures grew V vulnificus.

Vibrio vulnificus is a gram-negative bacillus and a rare cause of primary septicemia following consumption of shellfish, especially oysters. Wounds exposed to saltwater or brackish water contaminated with the microorganism can produce soft-tissue infections. Individuals with chronic liver disease are at greater risk for V vulnificus infection.² The clinical presentation of V vulnificus includes early cellulitislike patches, late purpura with hemorrhagic bullae, and rapidly progressing shock.³

Mortality rates from V vulnificus infection are high.⁴ Therefore, it is recommended to presumptively diagnose V vulnificus septicemia in any individual at risk for infection who presents with the characteristic history in the setting of hypotension, fever, or septic shock. It is crucial for providers to be aware that broad-spectrum antibiotics commonly used for sepsis are inadequate for the treatment of V vulnificus. Immediate treatment with tetracycline (minocycline or doxycycline) and a third-generation cephalosporin (cefotaxime or ceftriaxone injection) or in combination with ciprofloxacin has been proven effective.^4,5

Vibrio vulnificus rarely is described in the literature as inducing PF. In one previously reported case, the patient was otherwise healthy and managed to recover following antibiotic therapy and wound debridement,⁶ whereas in another case the patient had undiagnosed liver cirrhosis and died from the infection.^6,7 In the latter case, the patient presented to the emergency department in a coma. Our patient did not have the clinical signs of sepsis upon initial presentation to the emergency department. It is possible the infection rapidly progressed because of his underlying liver disease. Genotyping analysis of V vulnificus has shown that strains with low pathogenicity can cause primary septicemia in humans.⁷

Our case reinforces the need to quickly recognize V vulnificus as a rare underlying cause of PF and administer the appropriate treatment.

To the Editor:

Purpura fulminans (PF) is an acute, life-threatening condition characterized by intravascular thrombosis and hemorrhagic necrosis of the skin. It classically presents as retiform purpura with branched or angular purpuric lesions. Purpura fulminans often occurs in the setting of disseminated intravascular coagulation, secondary to sepsis, trauma, malignancy, autoimmune disease, and congenital or acquired protein C or S deficiency, among other abnormalities.¹ Rapid identification and treatment of the underlying cause are mainstays of management. We report a case of PF secondary to Vibrio vulnificus infection and highlight the importance of timely consideration of this etiologic agent due to the high mortality rate and specific treatment required.

A 58-year-old man with liver cirrhosis and hepatitis B virus presented with pain, swelling, and localized erythema affecting both legs as well as a fever. He reported vomiting blood and an episode of bloody diarrhea over the preceding 24 hours. He denied exposure to sick contacts or a history of autoimmune disease. At initial presentation to the emergency department, physical examination revealed few scattered, sharply demarcated, erythematous to violaceous patches that rapidly progressed overnight to hemorrhagic bullae and widespread retiform purpuric patches on both legs (Figure 1). As the patient’s skin condition worsened, he had a blood pressure of 80/50 mm Hg and a pulse rate of 110/min. Serum analysis was notable for mild leukocytosis (10.74×10⁹/L [reference range, 4.8–10.8×10⁹/L), thrombocytopenia (39×10⁹/L [reference range, 150–450×10⁹/L]), and decreased C3 (25 mg/dL [reference range, 81–157 mg/dL]) and C4 (8 mg/dL [reference range, 13–39 mg/dL]). Laboratory findings also were remarkable for prothrombin time (23.3 seconds [reference range, 8.8–12.3 seconds]), partial thromboplastin time (52.5 seconds [reference range, 23.6–35.8 seconds]), and international normalized ratio (2.01 [reference range, 0.8–1.13]). Aspartate transaminase (237 U/L [reference range, 11–39 U/L]) and alanine transaminase (80 U/L [reference range, 11–35 U/L]) were elevated, while antineutrophil cytoplasmic antibodies, serum immunoglobulin, and cryoglobulins were unremarkable. Punch biopsies of the left thigh were performed, and histopathology revealed small vessel thrombosis and ischemic changes consistent with PF (Figure 2). Vancomycin, clindamycin, cefepime injection, and piperacillin-tazobactam were administered intravenously for empiric broad-spectrum sepsis coverage. Within hours, the patient experienced refractory septic shock with disseminated intravascular coagulation and died from pulmonary embolism and subsequent cardiac arrest. Tissue and blood cultures grew V vulnificus.

Vibrio vulnificus is a gram-negative bacillus and a rare cause of primary septicemia following consumption of shellfish, especially oysters. Wounds exposed to saltwater or brackish water contaminated with the microorganism can produce soft-tissue infections. Individuals with chronic liver disease are at greater risk for V vulnificus infection.² The clinical presentation of V vulnificus includes early cellulitislike patches, late purpura with hemorrhagic bullae, and rapidly progressing shock.³

Mortality rates from V vulnificus infection are high.⁴ Therefore, it is recommended to presumptively diagnose V vulnificus septicemia in any individual at risk for infection who presents with the characteristic history in the setting of hypotension, fever, or septic shock. It is crucial for providers to be aware that broad-spectrum antibiotics commonly used for sepsis are inadequate for the treatment of V vulnificus. Immediate treatment with tetracycline (minocycline or doxycycline) and a third-generation cephalosporin (cefotaxime or ceftriaxone injection) or in combination with ciprofloxacin has been proven effective.^4,5

Vibrio vulnificus rarely is described in the literature as inducing PF. In one previously reported case, the patient was otherwise healthy and managed to recover following antibiotic therapy and wound debridement,⁶ whereas in another case the patient had undiagnosed liver cirrhosis and died from the infection.^6,7 In the latter case, the patient presented to the emergency department in a coma. Our patient did not have the clinical signs of sepsis upon initial presentation to the emergency department. It is possible the infection rapidly progressed because of his underlying liver disease. Genotyping analysis of V vulnificus has shown that strains with low pathogenicity can cause primary septicemia in humans.⁷

Our case reinforces the need to quickly recognize V vulnificus as a rare underlying cause of PF and administer the appropriate treatment.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a 2-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a 2-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a 2-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.