Infectious Diseases

The emergence of multiple inflammatory syndrome in children (MIS-C) in association with COVID-19 may be complicating the investigation and diagnosis of more common viral and bacterial infections, potentially delaying treatment and prolonging hospital stays.

Two recent articles published online in Hospital Pediatrics provide evidence of this phenomenon. The articles outlined case studies of children who underwent extensive investigation for MIS-C when in fact they had less severe and more common infections. MIS-C is a severe but rare syndrome that involves systemic hyperinflammation with fever and multisystem organ dysfunction similar to that of Kawasaki disease (KD).

In one of the articles, Matthew Molloy, MD, MPH, of the division of pediatric hospital medicine at Cincinnati Children’s Hospital Medical Center, and colleagues aptly asked: “What are we missing in our search for MIS-C?”
 

E. coli, not SARS-CoV-2

That question arose from a case involving a 3-year-old boy who had a 6-day history of fever and fatigue. Three days earlier, he had tested negative for strep antigen and COVID-19. He had a persistent, high fever, reduced appetite, and reduced urine output and was taken to the ED. On physical examination, there was no rash, skin peeling, redness of the eye or oral mucosa, congestion, rhinorrhea, cough, shortness of breath, chest pain, abdominal pain, nausea, vomiting, or diarrhea.

Urinalysis results and exam findings were suspicious for pyelonephritis. Other findings from an extensive laboratory workup raised the alarm that the boy was suffering from MIS-C as opposed to incomplete KD. After admission to hospital medicine, the cardiology, rheumatology, and infectious disease teams were called in to consult.

Repeat labs were planned for the following day before initiating therapy. On day 2, the child’s urine culture was positive for gram-negative rods, later identified as Escherichia coli. The boy was started on ceftriaxone. Left renal scarring was apparent on ultrasound. The patient’s condition resolved after 36 hours, and he was discharged home with antibiotics.
 

‘Diagnosis derailed’

Calling this a case of “diagnosis derailed,” the authors noted that, in the pre-COVID era, this child’s signs and symptoms would likely have triggered a more targeted and less costly evaluation for more common infectious and noninfectious causes, including pyelonephritis, absent any physical exam findings consistent with KD.

“However, the patient presented in the midst of the COVID-19 pandemic with growing awareness of a new clinical entity,” Dr. Molloy and colleagues wrote. “Anchored to the patient’s persistent fever, the medical team initiated an extensive, costly, and ultimately unnecessary workup to avoid missing the diagnosis of MIS-C; a not yet well-described diagnosis with potentially severe morbidity.”

Confirmation bias and diagnostic momentum likely contributed to the early focus on MIS-C rather than more common alternatives, the authors acknowledged. The addition of mildly abnormal laboratory data not typically obtained in the evaluation of fever led the team astray. “The diagnosis and definitive treatment may have been made earlier had the focus on concern for MIS-C not been present,” Dr. Molloy said in an interview.
 

Keeping value in care

The authors recognized that their initial approach to evaluating for MIS-C provided low-value care. “In our desire to not ‘miss’ MIS-C, we were performing costly evaluations that at times produced mildly abnormal, nonspecific results,” they wrote. That triggered a cascade of specialty consultations, follow-up testing, and an unwarranted diagnostic preoccupation with MIS-C.

Determining the extra price tag for the child’s workup would be complex and difficult because there is a difference in the cost to the hospital and the cost to the family, Dr. Molloy said. “However, there are potential cost savings that would be related to making a correct diagnosis in a timely manner in terms of preventing downstream effects from delayed diagnoses.”

Even as clinicians struggle with the challenging SARS-CoV-2 learning curve, Dr. Molloy and associates urged them to continue to strive for high-value care, with an unwavering focus on using only necessary resources, a stewardship the pandemic has shown to be critical.

“The COVID-19 pandemic has been an incredibly stressful time for physicians and for families,” Dr. Molloy said. “COVID-19 and related conditions like MIS-C are new, and we are learning more and more about them every week. These diagnoses are understandably on the minds of physicians and families when children present with fever.” Notwithstanding, the boy’s case underscores the need for clinicians to consider alternate diagnoses and the value of the care provided.
 

Impact of bias

Dr. Molloy’s group brings home the cognitive biases practitioners often suffer from, including anchoring and confirmation bias and diagnostic momentum, according to J. Howard Smart, MD, chief of pediatrics at Sharp Mary Birch Hospital for Women and Newborns, San Diego, and an assistant clinical professor of pediatrics at University of California, San Diego.

“But it is one thing to recognize these in retrospect and quite another to consider whether they may be happening to you yourself in real time,” he said in an interview. “It is almost as if we need to have a ‘time out,’ where we stop and ask ourselves whether there is something else that could be explaining our patient’s presentation, something that would be more common and more likely to be occurring.”

According to Dr. Smart, who was not involved in Dr. Molloy’s study, the team’s premature diagnostic focus on MIS-C was almost the inverse of what typically happens with KD. “It is usually the case that Kawasaki disease does not enter the differential diagnosis until late in the course of the fever, typically on day 5 or later, when it may have been better to think of it earlier,” he said.

In the second article, Andrea Dean, MD, of the department of pediatrics at Baylor College of Medicine and Texas Children’s Hospital, both in Houston, and colleagues outlined the cases of five patients aged 8-17 years who were hospitalized in May 2020 for suspected MIS-C. They exhibited inflammatory and other concerning indicators but were eventually discharged with a diagnosis of murine typhus.

This flea-borne infection, most commonly reported in the United States in the southeastern Gulf Coast region, Hawaii, and California, is often associated with a triad of fever, rash, and headache.

Cases have been rising in southern Texas, and Dr. Dean and colleagues postulated that school closures and social distancing may have increased exposure as a result of children spending more time outdoors or with pets. “Alternatively, parental concern for SARS-CoV-2 infection could mean children with symptoms are presenting to care and being referred or admitted to the hospital more frequently due to provider concern for MIS-C,” they wrote.
 

Cardiac involvement

The most concerning of the five cases in terms of possible MIS-C, Dr. Dean said in an interview, was that of a 12-year-old boy who had fever for 6 days in association with headache, eczematous rash, dry lips, and conjunctivitis. Laboratory tests showed a mildly elevated C-reactive protein level, hyponatremia, and thrombocytopenia, as well as sterile pyuria and mildly elevated prothrombin time. He was treated empirically with doxycycline, and his fever resolved over the next 24 hours.

An echocardiogram at initial evaluation, however, revealed mild dilation of the left anterior descending and right coronary arteries, which led to the administration of intravenous immunoglobulin and aspirin for atypical KD, in contrast to MIS-C. The authors postulated that mild cardiac involvement in disorders other than MIS-C and KD may be underrecognized.

The lesson from these cases, Dr. Dean and associates concluded, is that hospitalists must maintain a wide differential diagnosis when assessing a child with prolonged fever and evidence of systemic inflammation. The CDC stipulates that a diagnosis of MIS-C requires the absence of a plausible alternative diagnosis.

In addition to common viral, bacterial, and noninfectious disorders, a range of regional endemic rickettsial and parasitic infections must be considered as alternative diagnoses to MIS-C. “Many of these diseases cannot be reliably differentiated from MIS-C on presentation, and as community exposure to SARS-CoV-2 grows, hospitalists should be prepared to admit febrile children with evidence of systemic inflammation for brief observation periods to evaluate for MIS-C,” Dr. Dean’s group wrote. In this context, however, empiric treatment for common or even uncommon infectious diseases may avoid overdiagnosis and overtreatment of MIS-C as well as improve patient outcomes.

“We do have specific MIS-C guidelines at our institution,” Dr. Dean said, “but like all institutions, we are dealing with the broad definition of MIS-C according to the World Health Organization and the CDC, which is really the takeaway from this paper.”
 

More difficult differentiation

Both groups of authors pointed out that, as SARS-CoV-2 spreads throughout a community, a higher percentage of the population will have positive results on antibody testing, and such results will become less useful for differentiating between MIS-C and other conditions.

Despite these series’ cautionary lessons, other experts point to the critical importance of including MIS-C early on in the interest of efficient diagnosis and therapy. “In the cases cited, other pathologies were evaluated for and treated accordingly,” said Kara Gross Margolis, MD, AGAF, an associate professor of pediatrics in the division of pediatric gastroenterology, hepatology, and nutrition at Morgan Stanley Children’s Hospital,New York. “These papers stress the need for a balance that is important, and all potential diagnoses need to be considered, but MIS-C, due to its potential severe consequences, also needs to be on our differential now.”

In her view, as this new high-morbidity entity becomes more widespread during the pandemic, it will be increasingly important to keep this condition on the diagnostic radar.

Interestingly, in a converse example of diagnostic clouding, Dr. Gross Margolis’s group reported (Gastroenterology. 2020 Oct;159[4]:1571-4.e2) last year on a pediatric case series in which the presence of gastrointestinal symptoms in children with COVID-19–related MIS-C muddied the diagnosis by confusing this potentially severe syndrome with more common and less toxic gastrointestinal infections.

According to Dr. Smart, although the two reports don’t offer evidence for a particular diagnostic practice, they can inform the decision-making process. “It may be that we will have enough evidence shortly to say what the best practice is regarding diagnostic evaluation of possible MIS-C cases,” he said. “Until then, we must remember that common things occur commonly, even during a global pandemic.”

Neither of the two reports received any specific funding. The authors disclosed no relevant financial relationships.

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

The emergence of multiple inflammatory syndrome in children (MIS-C) in association with COVID-19 may be complicating the investigation and diagnosis of more common viral and bacterial infections, potentially delaying treatment and prolonging hospital stays.

Two recent articles published online in Hospital Pediatrics provide evidence of this phenomenon. The articles outlined case studies of children who underwent extensive investigation for MIS-C when in fact they had less severe and more common infections. MIS-C is a severe but rare syndrome that involves systemic hyperinflammation with fever and multisystem organ dysfunction similar to that of Kawasaki disease (KD).

In one of the articles, Matthew Molloy, MD, MPH, of the division of pediatric hospital medicine at Cincinnati Children’s Hospital Medical Center, and colleagues aptly asked: “What are we missing in our search for MIS-C?”
 

E. coli, not SARS-CoV-2

That question arose from a case involving a 3-year-old boy who had a 6-day history of fever and fatigue. Three days earlier, he had tested negative for strep antigen and COVID-19. He had a persistent, high fever, reduced appetite, and reduced urine output and was taken to the ED. On physical examination, there was no rash, skin peeling, redness of the eye or oral mucosa, congestion, rhinorrhea, cough, shortness of breath, chest pain, abdominal pain, nausea, vomiting, or diarrhea.

Urinalysis results and exam findings were suspicious for pyelonephritis. Other findings from an extensive laboratory workup raised the alarm that the boy was suffering from MIS-C as opposed to incomplete KD. After admission to hospital medicine, the cardiology, rheumatology, and infectious disease teams were called in to consult.

Repeat labs were planned for the following day before initiating therapy. On day 2, the child’s urine culture was positive for gram-negative rods, later identified as Escherichia coli. The boy was started on ceftriaxone. Left renal scarring was apparent on ultrasound. The patient’s condition resolved after 36 hours, and he was discharged home with antibiotics.
 

‘Diagnosis derailed’

Calling this a case of “diagnosis derailed,” the authors noted that, in the pre-COVID era, this child’s signs and symptoms would likely have triggered a more targeted and less costly evaluation for more common infectious and noninfectious causes, including pyelonephritis, absent any physical exam findings consistent with KD.

“However, the patient presented in the midst of the COVID-19 pandemic with growing awareness of a new clinical entity,” Dr. Molloy and colleagues wrote. “Anchored to the patient’s persistent fever, the medical team initiated an extensive, costly, and ultimately unnecessary workup to avoid missing the diagnosis of MIS-C; a not yet well-described diagnosis with potentially severe morbidity.”

Confirmation bias and diagnostic momentum likely contributed to the early focus on MIS-C rather than more common alternatives, the authors acknowledged. The addition of mildly abnormal laboratory data not typically obtained in the evaluation of fever led the team astray. “The diagnosis and definitive treatment may have been made earlier had the focus on concern for MIS-C not been present,” Dr. Molloy said in an interview.
 

Keeping value in care

The authors recognized that their initial approach to evaluating for MIS-C provided low-value care. “In our desire to not ‘miss’ MIS-C, we were performing costly evaluations that at times produced mildly abnormal, nonspecific results,” they wrote. That triggered a cascade of specialty consultations, follow-up testing, and an unwarranted diagnostic preoccupation with MIS-C.

Determining the extra price tag for the child’s workup would be complex and difficult because there is a difference in the cost to the hospital and the cost to the family, Dr. Molloy said. “However, there are potential cost savings that would be related to making a correct diagnosis in a timely manner in terms of preventing downstream effects from delayed diagnoses.”

Even as clinicians struggle with the challenging SARS-CoV-2 learning curve, Dr. Molloy and associates urged them to continue to strive for high-value care, with an unwavering focus on using only necessary resources, a stewardship the pandemic has shown to be critical.

“The COVID-19 pandemic has been an incredibly stressful time for physicians and for families,” Dr. Molloy said. “COVID-19 and related conditions like MIS-C are new, and we are learning more and more about them every week. These diagnoses are understandably on the minds of physicians and families when children present with fever.” Notwithstanding, the boy’s case underscores the need for clinicians to consider alternate diagnoses and the value of the care provided.
 

Impact of bias

Dr. Molloy’s group brings home the cognitive biases practitioners often suffer from, including anchoring and confirmation bias and diagnostic momentum, according to J. Howard Smart, MD, chief of pediatrics at Sharp Mary Birch Hospital for Women and Newborns, San Diego, and an assistant clinical professor of pediatrics at University of California, San Diego.

“But it is one thing to recognize these in retrospect and quite another to consider whether they may be happening to you yourself in real time,” he said in an interview. “It is almost as if we need to have a ‘time out,’ where we stop and ask ourselves whether there is something else that could be explaining our patient’s presentation, something that would be more common and more likely to be occurring.”

According to Dr. Smart, who was not involved in Dr. Molloy’s study, the team’s premature diagnostic focus on MIS-C was almost the inverse of what typically happens with KD. “It is usually the case that Kawasaki disease does not enter the differential diagnosis until late in the course of the fever, typically on day 5 or later, when it may have been better to think of it earlier,” he said.

In the second article, Andrea Dean, MD, of the department of pediatrics at Baylor College of Medicine and Texas Children’s Hospital, both in Houston, and colleagues outlined the cases of five patients aged 8-17 years who were hospitalized in May 2020 for suspected MIS-C. They exhibited inflammatory and other concerning indicators but were eventually discharged with a diagnosis of murine typhus.

This flea-borne infection, most commonly reported in the United States in the southeastern Gulf Coast region, Hawaii, and California, is often associated with a triad of fever, rash, and headache.

Cases have been rising in southern Texas, and Dr. Dean and colleagues postulated that school closures and social distancing may have increased exposure as a result of children spending more time outdoors or with pets. “Alternatively, parental concern for SARS-CoV-2 infection could mean children with symptoms are presenting to care and being referred or admitted to the hospital more frequently due to provider concern for MIS-C,” they wrote.
 

Cardiac involvement

The most concerning of the five cases in terms of possible MIS-C, Dr. Dean said in an interview, was that of a 12-year-old boy who had fever for 6 days in association with headache, eczematous rash, dry lips, and conjunctivitis. Laboratory tests showed a mildly elevated C-reactive protein level, hyponatremia, and thrombocytopenia, as well as sterile pyuria and mildly elevated prothrombin time. He was treated empirically with doxycycline, and his fever resolved over the next 24 hours.

An echocardiogram at initial evaluation, however, revealed mild dilation of the left anterior descending and right coronary arteries, which led to the administration of intravenous immunoglobulin and aspirin for atypical KD, in contrast to MIS-C. The authors postulated that mild cardiac involvement in disorders other than MIS-C and KD may be underrecognized.

The lesson from these cases, Dr. Dean and associates concluded, is that hospitalists must maintain a wide differential diagnosis when assessing a child with prolonged fever and evidence of systemic inflammation. The CDC stipulates that a diagnosis of MIS-C requires the absence of a plausible alternative diagnosis.

In addition to common viral, bacterial, and noninfectious disorders, a range of regional endemic rickettsial and parasitic infections must be considered as alternative diagnoses to MIS-C. “Many of these diseases cannot be reliably differentiated from MIS-C on presentation, and as community exposure to SARS-CoV-2 grows, hospitalists should be prepared to admit febrile children with evidence of systemic inflammation for brief observation periods to evaluate for MIS-C,” Dr. Dean’s group wrote. In this context, however, empiric treatment for common or even uncommon infectious diseases may avoid overdiagnosis and overtreatment of MIS-C as well as improve patient outcomes.

“We do have specific MIS-C guidelines at our institution,” Dr. Dean said, “but like all institutions, we are dealing with the broad definition of MIS-C according to the World Health Organization and the CDC, which is really the takeaway from this paper.”
 

More difficult differentiation

Both groups of authors pointed out that, as SARS-CoV-2 spreads throughout a community, a higher percentage of the population will have positive results on antibody testing, and such results will become less useful for differentiating between MIS-C and other conditions.

Despite these series’ cautionary lessons, other experts point to the critical importance of including MIS-C early on in the interest of efficient diagnosis and therapy. “In the cases cited, other pathologies were evaluated for and treated accordingly,” said Kara Gross Margolis, MD, AGAF, an associate professor of pediatrics in the division of pediatric gastroenterology, hepatology, and nutrition at Morgan Stanley Children’s Hospital,New York. “These papers stress the need for a balance that is important, and all potential diagnoses need to be considered, but MIS-C, due to its potential severe consequences, also needs to be on our differential now.”

In her view, as this new high-morbidity entity becomes more widespread during the pandemic, it will be increasingly important to keep this condition on the diagnostic radar.

Interestingly, in a converse example of diagnostic clouding, Dr. Gross Margolis’s group reported (Gastroenterology. 2020 Oct;159[4]:1571-4.e2) last year on a pediatric case series in which the presence of gastrointestinal symptoms in children with COVID-19–related MIS-C muddied the diagnosis by confusing this potentially severe syndrome with more common and less toxic gastrointestinal infections.

According to Dr. Smart, although the two reports don’t offer evidence for a particular diagnostic practice, they can inform the decision-making process. “It may be that we will have enough evidence shortly to say what the best practice is regarding diagnostic evaluation of possible MIS-C cases,” he said. “Until then, we must remember that common things occur commonly, even during a global pandemic.”

Neither of the two reports received any specific funding. The authors disclosed no relevant financial relationships.

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

The emergence of multiple inflammatory syndrome in children (MIS-C) in association with COVID-19 may be complicating the investigation and diagnosis of more common viral and bacterial infections, potentially delaying treatment and prolonging hospital stays.

Two recent articles published online in Hospital Pediatrics provide evidence of this phenomenon. The articles outlined case studies of children who underwent extensive investigation for MIS-C when in fact they had less severe and more common infections. MIS-C is a severe but rare syndrome that involves systemic hyperinflammation with fever and multisystem organ dysfunction similar to that of Kawasaki disease (KD).

In one of the articles, Matthew Molloy, MD, MPH, of the division of pediatric hospital medicine at Cincinnati Children’s Hospital Medical Center, and colleagues aptly asked: “What are we missing in our search for MIS-C?”
 

E. coli, not SARS-CoV-2

That question arose from a case involving a 3-year-old boy who had a 6-day history of fever and fatigue. Three days earlier, he had tested negative for strep antigen and COVID-19. He had a persistent, high fever, reduced appetite, and reduced urine output and was taken to the ED. On physical examination, there was no rash, skin peeling, redness of the eye or oral mucosa, congestion, rhinorrhea, cough, shortness of breath, chest pain, abdominal pain, nausea, vomiting, or diarrhea.

Urinalysis results and exam findings were suspicious for pyelonephritis. Other findings from an extensive laboratory workup raised the alarm that the boy was suffering from MIS-C as opposed to incomplete KD. After admission to hospital medicine, the cardiology, rheumatology, and infectious disease teams were called in to consult.

Repeat labs were planned for the following day before initiating therapy. On day 2, the child’s urine culture was positive for gram-negative rods, later identified as Escherichia coli. The boy was started on ceftriaxone. Left renal scarring was apparent on ultrasound. The patient’s condition resolved after 36 hours, and he was discharged home with antibiotics.
 

‘Diagnosis derailed’

Calling this a case of “diagnosis derailed,” the authors noted that, in the pre-COVID era, this child’s signs and symptoms would likely have triggered a more targeted and less costly evaluation for more common infectious and noninfectious causes, including pyelonephritis, absent any physical exam findings consistent with KD.

“However, the patient presented in the midst of the COVID-19 pandemic with growing awareness of a new clinical entity,” Dr. Molloy and colleagues wrote. “Anchored to the patient’s persistent fever, the medical team initiated an extensive, costly, and ultimately unnecessary workup to avoid missing the diagnosis of MIS-C; a not yet well-described diagnosis with potentially severe morbidity.”

Confirmation bias and diagnostic momentum likely contributed to the early focus on MIS-C rather than more common alternatives, the authors acknowledged. The addition of mildly abnormal laboratory data not typically obtained in the evaluation of fever led the team astray. “The diagnosis and definitive treatment may have been made earlier had the focus on concern for MIS-C not been present,” Dr. Molloy said in an interview.
 

Keeping value in care

The authors recognized that their initial approach to evaluating for MIS-C provided low-value care. “In our desire to not ‘miss’ MIS-C, we were performing costly evaluations that at times produced mildly abnormal, nonspecific results,” they wrote. That triggered a cascade of specialty consultations, follow-up testing, and an unwarranted diagnostic preoccupation with MIS-C.

Determining the extra price tag for the child’s workup would be complex and difficult because there is a difference in the cost to the hospital and the cost to the family, Dr. Molloy said. “However, there are potential cost savings that would be related to making a correct diagnosis in a timely manner in terms of preventing downstream effects from delayed diagnoses.”

Even as clinicians struggle with the challenging SARS-CoV-2 learning curve, Dr. Molloy and associates urged them to continue to strive for high-value care, with an unwavering focus on using only necessary resources, a stewardship the pandemic has shown to be critical.

“The COVID-19 pandemic has been an incredibly stressful time for physicians and for families,” Dr. Molloy said. “COVID-19 and related conditions like MIS-C are new, and we are learning more and more about them every week. These diagnoses are understandably on the minds of physicians and families when children present with fever.” Notwithstanding, the boy’s case underscores the need for clinicians to consider alternate diagnoses and the value of the care provided.
 

Impact of bias

Dr. Molloy’s group brings home the cognitive biases practitioners often suffer from, including anchoring and confirmation bias and diagnostic momentum, according to J. Howard Smart, MD, chief of pediatrics at Sharp Mary Birch Hospital for Women and Newborns, San Diego, and an assistant clinical professor of pediatrics at University of California, San Diego.

“But it is one thing to recognize these in retrospect and quite another to consider whether they may be happening to you yourself in real time,” he said in an interview. “It is almost as if we need to have a ‘time out,’ where we stop and ask ourselves whether there is something else that could be explaining our patient’s presentation, something that would be more common and more likely to be occurring.”

According to Dr. Smart, who was not involved in Dr. Molloy’s study, the team’s premature diagnostic focus on MIS-C was almost the inverse of what typically happens with KD. “It is usually the case that Kawasaki disease does not enter the differential diagnosis until late in the course of the fever, typically on day 5 or later, when it may have been better to think of it earlier,” he said.

In the second article, Andrea Dean, MD, of the department of pediatrics at Baylor College of Medicine and Texas Children’s Hospital, both in Houston, and colleagues outlined the cases of five patients aged 8-17 years who were hospitalized in May 2020 for suspected MIS-C. They exhibited inflammatory and other concerning indicators but were eventually discharged with a diagnosis of murine typhus.

This flea-borne infection, most commonly reported in the United States in the southeastern Gulf Coast region, Hawaii, and California, is often associated with a triad of fever, rash, and headache.

Cases have been rising in southern Texas, and Dr. Dean and colleagues postulated that school closures and social distancing may have increased exposure as a result of children spending more time outdoors or with pets. “Alternatively, parental concern for SARS-CoV-2 infection could mean children with symptoms are presenting to care and being referred or admitted to the hospital more frequently due to provider concern for MIS-C,” they wrote.
 

Cardiac involvement

The most concerning of the five cases in terms of possible MIS-C, Dr. Dean said in an interview, was that of a 12-year-old boy who had fever for 6 days in association with headache, eczematous rash, dry lips, and conjunctivitis. Laboratory tests showed a mildly elevated C-reactive protein level, hyponatremia, and thrombocytopenia, as well as sterile pyuria and mildly elevated prothrombin time. He was treated empirically with doxycycline, and his fever resolved over the next 24 hours.

An echocardiogram at initial evaluation, however, revealed mild dilation of the left anterior descending and right coronary arteries, which led to the administration of intravenous immunoglobulin and aspirin for atypical KD, in contrast to MIS-C. The authors postulated that mild cardiac involvement in disorders other than MIS-C and KD may be underrecognized.

The lesson from these cases, Dr. Dean and associates concluded, is that hospitalists must maintain a wide differential diagnosis when assessing a child with prolonged fever and evidence of systemic inflammation. The CDC stipulates that a diagnosis of MIS-C requires the absence of a plausible alternative diagnosis.

In addition to common viral, bacterial, and noninfectious disorders, a range of regional endemic rickettsial and parasitic infections must be considered as alternative diagnoses to MIS-C. “Many of these diseases cannot be reliably differentiated from MIS-C on presentation, and as community exposure to SARS-CoV-2 grows, hospitalists should be prepared to admit febrile children with evidence of systemic inflammation for brief observation periods to evaluate for MIS-C,” Dr. Dean’s group wrote. In this context, however, empiric treatment for common or even uncommon infectious diseases may avoid overdiagnosis and overtreatment of MIS-C as well as improve patient outcomes.

“We do have specific MIS-C guidelines at our institution,” Dr. Dean said, “but like all institutions, we are dealing with the broad definition of MIS-C according to the World Health Organization and the CDC, which is really the takeaway from this paper.”
 

More difficult differentiation

Both groups of authors pointed out that, as SARS-CoV-2 spreads throughout a community, a higher percentage of the population will have positive results on antibody testing, and such results will become less useful for differentiating between MIS-C and other conditions.

Despite these series’ cautionary lessons, other experts point to the critical importance of including MIS-C early on in the interest of efficient diagnosis and therapy. “In the cases cited, other pathologies were evaluated for and treated accordingly,” said Kara Gross Margolis, MD, AGAF, an associate professor of pediatrics in the division of pediatric gastroenterology, hepatology, and nutrition at Morgan Stanley Children’s Hospital,New York. “These papers stress the need for a balance that is important, and all potential diagnoses need to be considered, but MIS-C, due to its potential severe consequences, also needs to be on our differential now.”

In her view, as this new high-morbidity entity becomes more widespread during the pandemic, it will be increasingly important to keep this condition on the diagnostic radar.

Interestingly, in a converse example of diagnostic clouding, Dr. Gross Margolis’s group reported (Gastroenterology. 2020 Oct;159[4]:1571-4.e2) last year on a pediatric case series in which the presence of gastrointestinal symptoms in children with COVID-19–related MIS-C muddied the diagnosis by confusing this potentially severe syndrome with more common and less toxic gastrointestinal infections.

According to Dr. Smart, although the two reports don’t offer evidence for a particular diagnostic practice, they can inform the decision-making process. “It may be that we will have enough evidence shortly to say what the best practice is regarding diagnostic evaluation of possible MIS-C cases,” he said. “Until then, we must remember that common things occur commonly, even during a global pandemic.”

Neither of the two reports received any specific funding. The authors disclosed no relevant financial relationships.

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

Clinical questions: What are the demographics and clinical features of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) syndromes, and which admitting demographics and clinical features are predictive of disease severity?

Background: In children, SARS-CoV-2 causes respiratory disease and multisystem inflammatory syndrome in children (MIS-C) as well as other clinical manifestations. The authors of this study chose to address the gap of identifying characteristics for severe disease caused by SARS-CoV-2, including respiratory disease, MIS-C and other manifestations.

Study design: Retrospective and prospective cohort analysis of hospitalized children

Setting: Participating hospitals in Tri-State Pediatric COVID-19 Consortium, including hospitals in New York, New Jersey, and Connecticut.

Synopsis: The authors identified hospitalized patients 22 years old or younger who had a positive SARS-CoV-2 test or met the U.S. Centers for Disease Control and Preventions’ MIS-C case definition. For comparative analysis, patients were divided into a respiratory disease group (based on the World Health Organization’s criteria for COVID-19), MIS-C group or other group (based on the primary reason for hospitalization).

The authors included 281 patients in the study. 51% of the patients presented with respiratory disease, 25% with MIS-C and 25% with other symptoms, including gastrointestinal, or fever. 51% of all patients were Hispanic and 23% were non-Black Hispanic. The most common pre-existing comorbidities amongst all groups were obesity (34%) and asthma (14%).

Patients with respiratory disease had a median age of 14 years while those with MIS-C had a median age of 7 years. Patients more commonly identified as non-Hispanic Black in the MIS-C group vs the respiratory group (35% vs. 18%). Obesity and medical complexity were more prevalent in the respiratory group relative to the MIS-C group. 75% of patients with MIS-C had gastrointestinal symptoms. 44% of respiratory patients had a chest radiograph with bilateral infiltrates on admission, and 18% or respiratory patients required invasive mechanical ventilation. The most common complications in the respiratory group were acute respiratory distress syndrome (17%) and acute kidney injury (11%), whereas shock (35%) and cardiac dysfunction (25%) were the most common complications in the MIS-C group. The median length of stay for all patients was 4 days (IQR 2-8 days).

Patients with MIS-C were more likely to be admitted to the intensive care unit (ICU) but all deaths (7 patients) occurred in the respiratory group. 40% of patients with respiratory disease, 56% of patients with MIS-C, and 6% of other patients met the authors’ definition of severe disease (ICU admission > 48 hours). For the respiratory group, younger age, obesity, increasing white blood cell count, hypoxia, and bilateral infiltrates on chest radiograph were independent predictors of severe disease based on multivariate analyses. For the MIS-C group, lower absolute lymphocyte count and increasing CRP at admission were independent predictors of severity.

Bottom line: Mortality in pediatric patients is low. Ethnicity and race were not predictive of disease severity in this model, even though 51% of the patients studied were Hispanic and 23% were non-Hispanic Black. Severity of illness for patients with respiratory disease was found to be associated with younger age, obesity, increasing white blood cell count, hypoxia, and bilateral infiltrates on chest radiograph. Severity of illness in patients with MIS-C was associated with lower absolute lymphocyte count and increasing CRP.

Citation: Fernandes DM, et al. Severe acute respiratory syndrome coronavirus 2 clinical syndromes and predictors of disease severity in hospitalized children and youth. J Pediatr. 2020 Nov 14;S0022-3476(20):31393-7. DOI: 10.1016/j.jpeds.2020.11.016.

Dr. Kumar is an assistant professor of pediatrics at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and a pediatric hospitalist at Cleveland Clinic Children’s. She is the pediatric editor of The Hospitalist.

Clinical questions: What are the demographics and clinical features of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) syndromes, and which admitting demographics and clinical features are predictive of disease severity?

Background: In children, SARS-CoV-2 causes respiratory disease and multisystem inflammatory syndrome in children (MIS-C) as well as other clinical manifestations. The authors of this study chose to address the gap of identifying characteristics for severe disease caused by SARS-CoV-2, including respiratory disease, MIS-C and other manifestations.

Study design: Retrospective and prospective cohort analysis of hospitalized children

Setting: Participating hospitals in Tri-State Pediatric COVID-19 Consortium, including hospitals in New York, New Jersey, and Connecticut.

Synopsis: The authors identified hospitalized patients 22 years old or younger who had a positive SARS-CoV-2 test or met the U.S. Centers for Disease Control and Preventions’ MIS-C case definition. For comparative analysis, patients were divided into a respiratory disease group (based on the World Health Organization’s criteria for COVID-19), MIS-C group or other group (based on the primary reason for hospitalization).

The authors included 281 patients in the study. 51% of the patients presented with respiratory disease, 25% with MIS-C and 25% with other symptoms, including gastrointestinal, or fever. 51% of all patients were Hispanic and 23% were non-Black Hispanic. The most common pre-existing comorbidities amongst all groups were obesity (34%) and asthma (14%).

Patients with respiratory disease had a median age of 14 years while those with MIS-C had a median age of 7 years. Patients more commonly identified as non-Hispanic Black in the MIS-C group vs the respiratory group (35% vs. 18%). Obesity and medical complexity were more prevalent in the respiratory group relative to the MIS-C group. 75% of patients with MIS-C had gastrointestinal symptoms. 44% of respiratory patients had a chest radiograph with bilateral infiltrates on admission, and 18% or respiratory patients required invasive mechanical ventilation. The most common complications in the respiratory group were acute respiratory distress syndrome (17%) and acute kidney injury (11%), whereas shock (35%) and cardiac dysfunction (25%) were the most common complications in the MIS-C group. The median length of stay for all patients was 4 days (IQR 2-8 days).

Patients with MIS-C were more likely to be admitted to the intensive care unit (ICU) but all deaths (7 patients) occurred in the respiratory group. 40% of patients with respiratory disease, 56% of patients with MIS-C, and 6% of other patients met the authors’ definition of severe disease (ICU admission > 48 hours). For the respiratory group, younger age, obesity, increasing white blood cell count, hypoxia, and bilateral infiltrates on chest radiograph were independent predictors of severe disease based on multivariate analyses. For the MIS-C group, lower absolute lymphocyte count and increasing CRP at admission were independent predictors of severity.

Bottom line: Mortality in pediatric patients is low. Ethnicity and race were not predictive of disease severity in this model, even though 51% of the patients studied were Hispanic and 23% were non-Hispanic Black. Severity of illness for patients with respiratory disease was found to be associated with younger age, obesity, increasing white blood cell count, hypoxia, and bilateral infiltrates on chest radiograph. Severity of illness in patients with MIS-C was associated with lower absolute lymphocyte count and increasing CRP.

Citation: Fernandes DM, et al. Severe acute respiratory syndrome coronavirus 2 clinical syndromes and predictors of disease severity in hospitalized children and youth. J Pediatr. 2020 Nov 14;S0022-3476(20):31393-7. DOI: 10.1016/j.jpeds.2020.11.016.

Dr. Kumar is an assistant professor of pediatrics at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and a pediatric hospitalist at Cleveland Clinic Children’s. She is the pediatric editor of The Hospitalist.

Clinical questions: What are the demographics and clinical features of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) syndromes, and which admitting demographics and clinical features are predictive of disease severity?

Background: In children, SARS-CoV-2 causes respiratory disease and multisystem inflammatory syndrome in children (MIS-C) as well as other clinical manifestations. The authors of this study chose to address the gap of identifying characteristics for severe disease caused by SARS-CoV-2, including respiratory disease, MIS-C and other manifestations.

Study design: Retrospective and prospective cohort analysis of hospitalized children

Setting: Participating hospitals in Tri-State Pediatric COVID-19 Consortium, including hospitals in New York, New Jersey, and Connecticut.

Synopsis: The authors identified hospitalized patients 22 years old or younger who had a positive SARS-CoV-2 test or met the U.S. Centers for Disease Control and Preventions’ MIS-C case definition. For comparative analysis, patients were divided into a respiratory disease group (based on the World Health Organization’s criteria for COVID-19), MIS-C group or other group (based on the primary reason for hospitalization).

The authors included 281 patients in the study. 51% of the patients presented with respiratory disease, 25% with MIS-C and 25% with other symptoms, including gastrointestinal, or fever. 51% of all patients were Hispanic and 23% were non-Black Hispanic. The most common pre-existing comorbidities amongst all groups were obesity (34%) and asthma (14%).

Patients with respiratory disease had a median age of 14 years while those with MIS-C had a median age of 7 years. Patients more commonly identified as non-Hispanic Black in the MIS-C group vs the respiratory group (35% vs. 18%). Obesity and medical complexity were more prevalent in the respiratory group relative to the MIS-C group. 75% of patients with MIS-C had gastrointestinal symptoms. 44% of respiratory patients had a chest radiograph with bilateral infiltrates on admission, and 18% or respiratory patients required invasive mechanical ventilation. The most common complications in the respiratory group were acute respiratory distress syndrome (17%) and acute kidney injury (11%), whereas shock (35%) and cardiac dysfunction (25%) were the most common complications in the MIS-C group. The median length of stay for all patients was 4 days (IQR 2-8 days).

Patients with MIS-C were more likely to be admitted to the intensive care unit (ICU) but all deaths (7 patients) occurred in the respiratory group. 40% of patients with respiratory disease, 56% of patients with MIS-C, and 6% of other patients met the authors’ definition of severe disease (ICU admission > 48 hours). For the respiratory group, younger age, obesity, increasing white blood cell count, hypoxia, and bilateral infiltrates on chest radiograph were independent predictors of severe disease based on multivariate analyses. For the MIS-C group, lower absolute lymphocyte count and increasing CRP at admission were independent predictors of severity.

Bottom line: Mortality in pediatric patients is low. Ethnicity and race were not predictive of disease severity in this model, even though 51% of the patients studied were Hispanic and 23% were non-Hispanic Black. Severity of illness for patients with respiratory disease was found to be associated with younger age, obesity, increasing white blood cell count, hypoxia, and bilateral infiltrates on chest radiograph. Severity of illness in patients with MIS-C was associated with lower absolute lymphocyte count and increasing CRP.

Citation: Fernandes DM, et al. Severe acute respiratory syndrome coronavirus 2 clinical syndromes and predictors of disease severity in hospitalized children and youth. J Pediatr. 2020 Nov 14;S0022-3476(20):31393-7. DOI: 10.1016/j.jpeds.2020.11.016.

Dr. Kumar is an assistant professor of pediatrics at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and a pediatric hospitalist at Cleveland Clinic Children’s. She is the pediatric editor of The Hospitalist.

Immunogenicity of the high-dose influenza vaccine (HD IIV3) in patients with chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis (MBL, the precursor state to CLL) was found lower than reported in healthy adults according to a report in Vaccine.

In addition, immunogenicity to influenza B was found to be greater in those patients with MBL, compared with those with CLL.

“Acute and chronic leukemia patients hospitalized with influenza infection document a case fatality rate of 25%-37%,” according to Jennifer A. Whitaker, MD, of the Mayo Clinic, Rochester, Minn., and colleagues in pointing out the importance of their study.

The prospective pilot study assessed the humoral immune responses of patients to the 2013-2014 and 2014-2015 HD IIV3 (Fluzone High-Dose; Sanofi Pasteur), which was administered as part of routine clinical care in 30 patients (17 with previously untreated CLL and 13 with MBL). The median patient age was 69.5 years.

The primary outcomes were seroconversion and seroprotection, as measured by hemagglutination inhibition assay (HAI).
 

Lower response rate

At day 28 post vaccination, the seroprotection rates for the overall cohort were 19/30 (63.3%) for A/H1N1, 21/23 (91.3%) for A/H3N2, and 13/30 (43.3%) for influenza B. Patients with MBL achieved significantly higher day 28 HAI geometric mean titers (GMT), compared with CLL patients (54.1 vs. 12.1]; P = .01), In addition, MBL patients achieved higher day 28 seroprotection rates against the influenza B vaccine strain virus than did those with CLL (76.9% vs. 17.6%; P = .002). Seroconversion rates for the overall cohort were 3/30 (10%) for A/H1N1; 5/23 (21.7%) for A/H3N2; and 3/30 (10%) for influenza B. No individual with CLL demonstrated seroconversion for influenza B, according to the researchers.

“Our studies reinforce rigorous adherence to vaccination strategies in patients with hematologic malignancy, including those with CLL, given the increased risk of serious complications among those experiencing influenza infection,” the authors stated.

“Even suboptimal responses to influenza vaccination can provide partial protection, reduce hospitalization rates, and/or prevent serious disease complications. Given the recent major issue with novel and aggressive viruses such COVID-19, we absolutely must continue with larger prospective studies to confirm these findings and evaluate vaccine effectiveness in preventing influenza or other novel viruses in these populations,” the researchers concluded.

This study was funded by the National Institutes of Health. Dr. Whitaker reported having no disclosures. Several of the coauthors reported financial relationships with a variety of pharmaceutical and biotechnology companies.

mlesney@mdedge.com

Immunogenicity of the high-dose influenza vaccine (HD IIV3) in patients with chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis (MBL, the precursor state to CLL) was found lower than reported in healthy adults according to a report in Vaccine.

In addition, immunogenicity to influenza B was found to be greater in those patients with MBL, compared with those with CLL.

“Acute and chronic leukemia patients hospitalized with influenza infection document a case fatality rate of 25%-37%,” according to Jennifer A. Whitaker, MD, of the Mayo Clinic, Rochester, Minn., and colleagues in pointing out the importance of their study.

The prospective pilot study assessed the humoral immune responses of patients to the 2013-2014 and 2014-2015 HD IIV3 (Fluzone High-Dose; Sanofi Pasteur), which was administered as part of routine clinical care in 30 patients (17 with previously untreated CLL and 13 with MBL). The median patient age was 69.5 years.

The primary outcomes were seroconversion and seroprotection, as measured by hemagglutination inhibition assay (HAI).
 

Lower response rate

At day 28 post vaccination, the seroprotection rates for the overall cohort were 19/30 (63.3%) for A/H1N1, 21/23 (91.3%) for A/H3N2, and 13/30 (43.3%) for influenza B. Patients with MBL achieved significantly higher day 28 HAI geometric mean titers (GMT), compared with CLL patients (54.1 vs. 12.1]; P = .01), In addition, MBL patients achieved higher day 28 seroprotection rates against the influenza B vaccine strain virus than did those with CLL (76.9% vs. 17.6%; P = .002). Seroconversion rates for the overall cohort were 3/30 (10%) for A/H1N1; 5/23 (21.7%) for A/H3N2; and 3/30 (10%) for influenza B. No individual with CLL demonstrated seroconversion for influenza B, according to the researchers.

“Our studies reinforce rigorous adherence to vaccination strategies in patients with hematologic malignancy, including those with CLL, given the increased risk of serious complications among those experiencing influenza infection,” the authors stated.

“Even suboptimal responses to influenza vaccination can provide partial protection, reduce hospitalization rates, and/or prevent serious disease complications. Given the recent major issue with novel and aggressive viruses such COVID-19, we absolutely must continue with larger prospective studies to confirm these findings and evaluate vaccine effectiveness in preventing influenza or other novel viruses in these populations,” the researchers concluded.

This study was funded by the National Institutes of Health. Dr. Whitaker reported having no disclosures. Several of the coauthors reported financial relationships with a variety of pharmaceutical and biotechnology companies.

mlesney@mdedge.com

Immunogenicity of the high-dose influenza vaccine (HD IIV3) in patients with chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis (MBL, the precursor state to CLL) was found lower than reported in healthy adults according to a report in Vaccine.

In addition, immunogenicity to influenza B was found to be greater in those patients with MBL, compared with those with CLL.

“Acute and chronic leukemia patients hospitalized with influenza infection document a case fatality rate of 25%-37%,” according to Jennifer A. Whitaker, MD, of the Mayo Clinic, Rochester, Minn., and colleagues in pointing out the importance of their study.

The prospective pilot study assessed the humoral immune responses of patients to the 2013-2014 and 2014-2015 HD IIV3 (Fluzone High-Dose; Sanofi Pasteur), which was administered as part of routine clinical care in 30 patients (17 with previously untreated CLL and 13 with MBL). The median patient age was 69.5 years.

The primary outcomes were seroconversion and seroprotection, as measured by hemagglutination inhibition assay (HAI).
 

Lower response rate

At day 28 post vaccination, the seroprotection rates for the overall cohort were 19/30 (63.3%) for A/H1N1, 21/23 (91.3%) for A/H3N2, and 13/30 (43.3%) for influenza B. Patients with MBL achieved significantly higher day 28 HAI geometric mean titers (GMT), compared with CLL patients (54.1 vs. 12.1]; P = .01), In addition, MBL patients achieved higher day 28 seroprotection rates against the influenza B vaccine strain virus than did those with CLL (76.9% vs. 17.6%; P = .002). Seroconversion rates for the overall cohort were 3/30 (10%) for A/H1N1; 5/23 (21.7%) for A/H3N2; and 3/30 (10%) for influenza B. No individual with CLL demonstrated seroconversion for influenza B, according to the researchers.

“Our studies reinforce rigorous adherence to vaccination strategies in patients with hematologic malignancy, including those with CLL, given the increased risk of serious complications among those experiencing influenza infection,” the authors stated.

“Even suboptimal responses to influenza vaccination can provide partial protection, reduce hospitalization rates, and/or prevent serious disease complications. Given the recent major issue with novel and aggressive viruses such COVID-19, we absolutely must continue with larger prospective studies to confirm these findings and evaluate vaccine effectiveness in preventing influenza or other novel viruses in these populations,” the researchers concluded.

This study was funded by the National Institutes of Health. Dr. Whitaker reported having no disclosures. Several of the coauthors reported financial relationships with a variety of pharmaceutical and biotechnology companies.

mlesney@mdedge.com

Background: Early antibiotic administration reduces mortality in patients with severe sepsis. Administering antibiotics before blood cultures could potentially decrease time to treatment and improve outcomes, but the diagnostic yield of blood cultures drawn shortly after antibiotics is unknown.

There were several study limitations including: lack of sequential recruitment, lower than expected proportion of bacteremic patients, and variation in blood culture collection. Despite this, the magnitude of the findings are convincing and support current practice.

Bottom line: Continue to obtain blood cultures before antibiotics.

Citation: Cheng MP et al. Blood culture results before and after antimicrobial administration in patients with severe manifestations of sepsis. Ann Intern Med. 2019 Oct 15;171(8):547-54.

Dr. Waner is clinical instructor of medicine, hospital medicine, at the Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, Colo.

Background: Early antibiotic administration reduces mortality in patients with severe sepsis. Administering antibiotics before blood cultures could potentially decrease time to treatment and improve outcomes, but the diagnostic yield of blood cultures drawn shortly after antibiotics is unknown.

There were several study limitations including: lack of sequential recruitment, lower than expected proportion of bacteremic patients, and variation in blood culture collection. Despite this, the magnitude of the findings are convincing and support current practice.

Bottom line: Continue to obtain blood cultures before antibiotics.

Citation: Cheng MP et al. Blood culture results before and after antimicrobial administration in patients with severe manifestations of sepsis. Ann Intern Med. 2019 Oct 15;171(8):547-54.

Dr. Waner is clinical instructor of medicine, hospital medicine, at the Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, Colo.

Background: Early antibiotic administration reduces mortality in patients with severe sepsis. Administering antibiotics before blood cultures could potentially decrease time to treatment and improve outcomes, but the diagnostic yield of blood cultures drawn shortly after antibiotics is unknown.

There were several study limitations including: lack of sequential recruitment, lower than expected proportion of bacteremic patients, and variation in blood culture collection. Despite this, the magnitude of the findings are convincing and support current practice.

Bottom line: Continue to obtain blood cultures before antibiotics.

Citation: Cheng MP et al. Blood culture results before and after antimicrobial administration in patients with severe manifestations of sepsis. Ann Intern Med. 2019 Oct 15;171(8):547-54.

Dr. Waner is clinical instructor of medicine, hospital medicine, at the Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, Colo.

People with rheumatic and musculoskeletal diseases (RMDs) who contract the SARS-CoV-2 virus appear more likely to die from COVID-19 if their rheumatologic condition is not being well controlled at the time of their infection.

New data from the COVID-19 Global Rheumatology Alliance (GRA) physician registry reported in Annals of the Rheumatic Diseases have found that the odds of dying from COVID-19 were 87% higher in individuals recorded as having moderate to high disease activity versus those reported to be in remission or having low disease activity.

“I think this really highlights the importance of continuing to appropriately, and actively, treat our patients, and the importance of controlling their disease,” Pedro Machado, MD, PhD, said in an interview. Dr. Machado, an associate professor in rheumatology and muscle diseases at University College London and a consultant rheumatologist at several U.K. hospitals, has been involved in the GRA physician registry from the start, and sits on the GRA steering committee.

Alongside higher disease activity, several other important factors were found to be associated with increased odds of dying from COVID-19 – older age, male gender, and the presence of one or more comorbidities, such as hypertension combined with cardiovascular disease or chronic lung disease.

These demographic and disease-based factors have been linked to an increased risk for COVID-19–related hospitalization before, both in people with RMDs and in the general population, but the latest GRA physician registry data now take that a step further, and link them also to an increased risk for death, together with several other factors more specific to RMDs.
 

Logging COVID-19 rheumatologic cases

Since the start of the global pandemic, the potential effects that SARS-CoV-2 infection might have on people with RMDs in particular has concerned the rheumatology community. The main worries being that, either because of the underlying RMD itself or to its treatment, there may be immunoregulatory deficits or other risk factors that would make individuals more susceptible to not only infection but also to developing more severe COVID-19 than the general population.

These concerns led to the rapid formation of the GRA and the COVID-19 GRA physician registry in March 2020 to collect and analyze data on adults with rheumatic disease and confirmed or presumptive COVID-19. Entries into the registry are made by or under the direction of rheumatologists, and this is a voluntary process.

“This population cannot ever be entirely representative of the population of patients with rheumatic diseases,” Dr. Machado acknowledged. There will be selection and other biases that affect the reported data. That said, it’s the largest database of reported COVID-19 cases in adult rheumatology patients across the world, with more than 9,000 cases so far included from multiple registries, including those based in Europe and North and South America. Data from one of these – the French RMD cohort – have also recently been published in Annals of the Rheumatic Diseases, showing much the same findings but on a national level.

Hospitalization was the focus of a previous report because “you need large sample sizes” to look at endpoints that occur less frequently. When the first analysis was done, there were around 600 cases from 40 countries in the registry with sufficient data that could be used. Now, with a greater number of recorded cases, factors influencing the risk for death could be examined.

Death rate and risk factors found

Data on 3,729 COVID-19 cases in people with RMDs were included in the current analysis, all recorded in the first few months of the registry being open and up until July 1, 2020. In all, 390 (10.5%) of people died. While this is “clearly higher” than reported in the general population in most countries, the analysis was not designed to calculate a precise estimate.

“It should not be taken as an estimate of the overall death rate among patients with rheumatic diseases and COVID-19,” Dr. Machado and coauthors have been keen to point out.

“Age is always the biggest risk factor,” Dr. Machado explained. “There’s always a gradient: the older the patient, the worse the outcome.”

Indeed, there was a threefold increased risk for death among those aged 66-75 years versus those who were 65 years or younger (odds ratio, 3.00), and a sixfold increased risk for patients older than 75, compared with the younger age group (OR, 6.18).

Having both hypertension and cardiovascular disease was associated with an OR of 1.89, and coexisting chronic lung disease also significantly increased the chances of dying from COVID-19 (OR, 1.68).

Being of male sex was associated with a 46% increased risk for death from COVID-19 versus being of female sex.

The risk for COVID-19 death also rose with the use of corticosteroids. Compared with no steroid use, there was a 69% increased risk for with death at doses of 10 mg or more prednisolone equivalent per day.

“The finding about moderate to high doses of steroids being associated with a worse outcome is consistent with the first report; it was the same for hospitalization,” Dr. Machado observed.

The general consensus on steroid use in the COVID-19 setting is that they should be continued as needed, but at the lowest possible dose, as outlined in provisional recommendations set out by the recently renamed European Alliance of Associations for Rheumatology.

The GRA physician registry findings provide further support for this, suggesting that disease control should be optimized with disease-modifying antirheumatic drugs, ideally without increasing the dose of steroids.

Surprise over sulfasalazine risk

“Taking all medications into account – such as methotrexate, leflunomide, hydroxychloroquine, [tumor necrosis factor] blockers, interleukin-6 blockers, and [Janus kinase] inhibitors – it is quite reassuring because we did not see an association with worse outcome with those drugs overall,” Dr. Machado said.

However, treatment with rituximab (OR, 4.0), sulfasalazine (OR, 3.6), and immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine, mycophenolate, or tacrolimus (OR, 2.2), were associated with higher odds of dying from COVID-19 when compared with treatment with methotrexate alone.

The findings for rituximab and immunosuppressant use were perhaps not unexpected, but the possible association between sulfasalazine and COVID-19 death was “a bit intriguing,” Dr. Machado observed. “Sulfasalazine is believed to have low immunosuppressive effect.”

This warrants further investigation, but there are likely a range of confounding factors at play. One could be that people considered to be at higher risk may have been more often prescribed sulfasalazine because it was thought to be less immunosuppressive. Another might be because people taking sulfasalazine were more likely to be smokers, and they were also not advised to protect themselves from exposure to the virus (shielding) during the first wave of the pandemic, at least not in the United Kingdom.
 

Rituximab caution and vaccination

“Rituximab is a concern,” Dr. Machado acknowledged. “It is a concern that rheumatologists are now aware of and they are addressing, but then it’s a concern for a very specific subgroup of patients.”

While rheumatologists are, and will continue to prescribe it, there will be even more careful consideration over when, in whom, and how to use it during, and possibly even after, the pandemic.

“COVID is here to stay, it will become endemic, and it’s going to be part of our lives like the flu virus is,” Dr. Machado predicted.

Then there is the issue on vaccinating people against COVID-19, should those on rituximab still receive it? The answer is a yes, but, as with other vaccinations it’s all about the timing of when the vaccination is given.

Societies such as the British Society for Rheumatology have already begun to include guidance on this, recommending one of the available COVID-19 vaccines is given at least a month before the next or first dose of rituximab is due. As rituximab is given every few months, with doses sometimes spaced as much as 9 months or even a year apart, this should not be too much of a problem, but it is “better to have the vaccine first,” Dr. Machado said.
 

Has COVID-19 care improved in RMDs?

In separate research published in The Lancet Rheumatology, April Jorge, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and associates found that the risks of severe COVID-19 outcomes have improved over time, although they still “remain substantial.”

Dr. Jorge and colleagues looked at temporal trends in COVID-19 outcomes in patients with RMDs over the course of the first 6 months of the pandemic in 2020, using data from a large, multicenter, electronic health record network (TriNetX).

They formed two patient cohorts – a late (diagnosed from April 20 to July 20) and an early (diagnosed from January 20 to April 20) cohort – to see if outcomes had improved and discovered lower relative risks among patients in the late cohort for hospitalization (0.67), admission to the ICU (0.56), mechanical ventilation (0.39), acute kidney injury (0.66), renal replacement (0.53), and death (0.39).

“These results are encouraging,” but it’s difficult to match these different populations of patients, Dr. Machado said. “There are always factors that you cannot match for” and were not included in the U.S. analysis.

While there are important caveats in how the analysis was performed and thus in interpreting these data, they do “suggest that one of the reasons why outcomes have improved is because we have become better at treating these patients,” Dr. Machado added.

“Our treatment has improved, and our capacity to treat the complications has improved. We understand better how the disease behaves – we know that they can have thromboembolic complications that we can manage, and we are now able to manage ventilation issues better.”

Moreover, Dr. Machado said that, not only were clinicians more aware of what they should or should not do, there were treatments that were being used routinely or in some cases based on recent clinical trial results. “I think we are indeed treating these patients better.”

The COVID-19 GRA physician registry is financially supported by the American College of Rheumatology and EULAR. Dr. Machado had no relevant conflicts of interest.

People with rheumatic and musculoskeletal diseases (RMDs) who contract the SARS-CoV-2 virus appear more likely to die from COVID-19 if their rheumatologic condition is not being well controlled at the time of their infection.

New data from the COVID-19 Global Rheumatology Alliance (GRA) physician registry reported in Annals of the Rheumatic Diseases have found that the odds of dying from COVID-19 were 87% higher in individuals recorded as having moderate to high disease activity versus those reported to be in remission or having low disease activity.

“I think this really highlights the importance of continuing to appropriately, and actively, treat our patients, and the importance of controlling their disease,” Pedro Machado, MD, PhD, said in an interview. Dr. Machado, an associate professor in rheumatology and muscle diseases at University College London and a consultant rheumatologist at several U.K. hospitals, has been involved in the GRA physician registry from the start, and sits on the GRA steering committee.

Alongside higher disease activity, several other important factors were found to be associated with increased odds of dying from COVID-19 – older age, male gender, and the presence of one or more comorbidities, such as hypertension combined with cardiovascular disease or chronic lung disease.

These demographic and disease-based factors have been linked to an increased risk for COVID-19–related hospitalization before, both in people with RMDs and in the general population, but the latest GRA physician registry data now take that a step further, and link them also to an increased risk for death, together with several other factors more specific to RMDs.
 

Logging COVID-19 rheumatologic cases

Since the start of the global pandemic, the potential effects that SARS-CoV-2 infection might have on people with RMDs in particular has concerned the rheumatology community. The main worries being that, either because of the underlying RMD itself or to its treatment, there may be immunoregulatory deficits or other risk factors that would make individuals more susceptible to not only infection but also to developing more severe COVID-19 than the general population.

These concerns led to the rapid formation of the GRA and the COVID-19 GRA physician registry in March 2020 to collect and analyze data on adults with rheumatic disease and confirmed or presumptive COVID-19. Entries into the registry are made by or under the direction of rheumatologists, and this is a voluntary process.

“This population cannot ever be entirely representative of the population of patients with rheumatic diseases,” Dr. Machado acknowledged. There will be selection and other biases that affect the reported data. That said, it’s the largest database of reported COVID-19 cases in adult rheumatology patients across the world, with more than 9,000 cases so far included from multiple registries, including those based in Europe and North and South America. Data from one of these – the French RMD cohort – have also recently been published in Annals of the Rheumatic Diseases, showing much the same findings but on a national level.

Hospitalization was the focus of a previous report because “you need large sample sizes” to look at endpoints that occur less frequently. When the first analysis was done, there were around 600 cases from 40 countries in the registry with sufficient data that could be used. Now, with a greater number of recorded cases, factors influencing the risk for death could be examined.

Death rate and risk factors found

Data on 3,729 COVID-19 cases in people with RMDs were included in the current analysis, all recorded in the first few months of the registry being open and up until July 1, 2020. In all, 390 (10.5%) of people died. While this is “clearly higher” than reported in the general population in most countries, the analysis was not designed to calculate a precise estimate.

“It should not be taken as an estimate of the overall death rate among patients with rheumatic diseases and COVID-19,” Dr. Machado and coauthors have been keen to point out.

“Age is always the biggest risk factor,” Dr. Machado explained. “There’s always a gradient: the older the patient, the worse the outcome.”

Indeed, there was a threefold increased risk for death among those aged 66-75 years versus those who were 65 years or younger (odds ratio, 3.00), and a sixfold increased risk for patients older than 75, compared with the younger age group (OR, 6.18).

Having both hypertension and cardiovascular disease was associated with an OR of 1.89, and coexisting chronic lung disease also significantly increased the chances of dying from COVID-19 (OR, 1.68).

Being of male sex was associated with a 46% increased risk for death from COVID-19 versus being of female sex.

The risk for COVID-19 death also rose with the use of corticosteroids. Compared with no steroid use, there was a 69% increased risk for with death at doses of 10 mg or more prednisolone equivalent per day.

“The finding about moderate to high doses of steroids being associated with a worse outcome is consistent with the first report; it was the same for hospitalization,” Dr. Machado observed.

The general consensus on steroid use in the COVID-19 setting is that they should be continued as needed, but at the lowest possible dose, as outlined in provisional recommendations set out by the recently renamed European Alliance of Associations for Rheumatology.

The GRA physician registry findings provide further support for this, suggesting that disease control should be optimized with disease-modifying antirheumatic drugs, ideally without increasing the dose of steroids.

Surprise over sulfasalazine risk

“Taking all medications into account – such as methotrexate, leflunomide, hydroxychloroquine, [tumor necrosis factor] blockers, interleukin-6 blockers, and [Janus kinase] inhibitors – it is quite reassuring because we did not see an association with worse outcome with those drugs overall,” Dr. Machado said.

However, treatment with rituximab (OR, 4.0), sulfasalazine (OR, 3.6), and immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine, mycophenolate, or tacrolimus (OR, 2.2), were associated with higher odds of dying from COVID-19 when compared with treatment with methotrexate alone.

The findings for rituximab and immunosuppressant use were perhaps not unexpected, but the possible association between sulfasalazine and COVID-19 death was “a bit intriguing,” Dr. Machado observed. “Sulfasalazine is believed to have low immunosuppressive effect.”

This warrants further investigation, but there are likely a range of confounding factors at play. One could be that people considered to be at higher risk may have been more often prescribed sulfasalazine because it was thought to be less immunosuppressive. Another might be because people taking sulfasalazine were more likely to be smokers, and they were also not advised to protect themselves from exposure to the virus (shielding) during the first wave of the pandemic, at least not in the United Kingdom.
 

Rituximab caution and vaccination

“Rituximab is a concern,” Dr. Machado acknowledged. “It is a concern that rheumatologists are now aware of and they are addressing, but then it’s a concern for a very specific subgroup of patients.”

While rheumatologists are, and will continue to prescribe it, there will be even more careful consideration over when, in whom, and how to use it during, and possibly even after, the pandemic.

“COVID is here to stay, it will become endemic, and it’s going to be part of our lives like the flu virus is,” Dr. Machado predicted.

Then there is the issue on vaccinating people against COVID-19, should those on rituximab still receive it? The answer is a yes, but, as with other vaccinations it’s all about the timing of when the vaccination is given.

Societies such as the British Society for Rheumatology have already begun to include guidance on this, recommending one of the available COVID-19 vaccines is given at least a month before the next or first dose of rituximab is due. As rituximab is given every few months, with doses sometimes spaced as much as 9 months or even a year apart, this should not be too much of a problem, but it is “better to have the vaccine first,” Dr. Machado said.
 

Has COVID-19 care improved in RMDs?

In separate research published in The Lancet Rheumatology, April Jorge, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and associates found that the risks of severe COVID-19 outcomes have improved over time, although they still “remain substantial.”

Dr. Jorge and colleagues looked at temporal trends in COVID-19 outcomes in patients with RMDs over the course of the first 6 months of the pandemic in 2020, using data from a large, multicenter, electronic health record network (TriNetX).

They formed two patient cohorts – a late (diagnosed from April 20 to July 20) and an early (diagnosed from January 20 to April 20) cohort – to see if outcomes had improved and discovered lower relative risks among patients in the late cohort for hospitalization (0.67), admission to the ICU (0.56), mechanical ventilation (0.39), acute kidney injury (0.66), renal replacement (0.53), and death (0.39).

“These results are encouraging,” but it’s difficult to match these different populations of patients, Dr. Machado said. “There are always factors that you cannot match for” and were not included in the U.S. analysis.

While there are important caveats in how the analysis was performed and thus in interpreting these data, they do “suggest that one of the reasons why outcomes have improved is because we have become better at treating these patients,” Dr. Machado added.

“Our treatment has improved, and our capacity to treat the complications has improved. We understand better how the disease behaves – we know that they can have thromboembolic complications that we can manage, and we are now able to manage ventilation issues better.”

Moreover, Dr. Machado said that, not only were clinicians more aware of what they should or should not do, there were treatments that were being used routinely or in some cases based on recent clinical trial results. “I think we are indeed treating these patients better.”

The COVID-19 GRA physician registry is financially supported by the American College of Rheumatology and EULAR. Dr. Machado had no relevant conflicts of interest.

People with rheumatic and musculoskeletal diseases (RMDs) who contract the SARS-CoV-2 virus appear more likely to die from COVID-19 if their rheumatologic condition is not being well controlled at the time of their infection.

New data from the COVID-19 Global Rheumatology Alliance (GRA) physician registry reported in Annals of the Rheumatic Diseases have found that the odds of dying from COVID-19 were 87% higher in individuals recorded as having moderate to high disease activity versus those reported to be in remission or having low disease activity.

“I think this really highlights the importance of continuing to appropriately, and actively, treat our patients, and the importance of controlling their disease,” Pedro Machado, MD, PhD, said in an interview. Dr. Machado, an associate professor in rheumatology and muscle diseases at University College London and a consultant rheumatologist at several U.K. hospitals, has been involved in the GRA physician registry from the start, and sits on the GRA steering committee.

Alongside higher disease activity, several other important factors were found to be associated with increased odds of dying from COVID-19 – older age, male gender, and the presence of one or more comorbidities, such as hypertension combined with cardiovascular disease or chronic lung disease.

These demographic and disease-based factors have been linked to an increased risk for COVID-19–related hospitalization before, both in people with RMDs and in the general population, but the latest GRA physician registry data now take that a step further, and link them also to an increased risk for death, together with several other factors more specific to RMDs.
 

Logging COVID-19 rheumatologic cases

Since the start of the global pandemic, the potential effects that SARS-CoV-2 infection might have on people with RMDs in particular has concerned the rheumatology community. The main worries being that, either because of the underlying RMD itself or to its treatment, there may be immunoregulatory deficits or other risk factors that would make individuals more susceptible to not only infection but also to developing more severe COVID-19 than the general population.

These concerns led to the rapid formation of the GRA and the COVID-19 GRA physician registry in March 2020 to collect and analyze data on adults with rheumatic disease and confirmed or presumptive COVID-19. Entries into the registry are made by or under the direction of rheumatologists, and this is a voluntary process.

“This population cannot ever be entirely representative of the population of patients with rheumatic diseases,” Dr. Machado acknowledged. There will be selection and other biases that affect the reported data. That said, it’s the largest database of reported COVID-19 cases in adult rheumatology patients across the world, with more than 9,000 cases so far included from multiple registries, including those based in Europe and North and South America. Data from one of these – the French RMD cohort – have also recently been published in Annals of the Rheumatic Diseases, showing much the same findings but on a national level.

Hospitalization was the focus of a previous report because “you need large sample sizes” to look at endpoints that occur less frequently. When the first analysis was done, there were around 600 cases from 40 countries in the registry with sufficient data that could be used. Now, with a greater number of recorded cases, factors influencing the risk for death could be examined.

Death rate and risk factors found

Data on 3,729 COVID-19 cases in people with RMDs were included in the current analysis, all recorded in the first few months of the registry being open and up until July 1, 2020. In all, 390 (10.5%) of people died. While this is “clearly higher” than reported in the general population in most countries, the analysis was not designed to calculate a precise estimate.

“It should not be taken as an estimate of the overall death rate among patients with rheumatic diseases and COVID-19,” Dr. Machado and coauthors have been keen to point out.

“Age is always the biggest risk factor,” Dr. Machado explained. “There’s always a gradient: the older the patient, the worse the outcome.”

Indeed, there was a threefold increased risk for death among those aged 66-75 years versus those who were 65 years or younger (odds ratio, 3.00), and a sixfold increased risk for patients older than 75, compared with the younger age group (OR, 6.18).

Having both hypertension and cardiovascular disease was associated with an OR of 1.89, and coexisting chronic lung disease also significantly increased the chances of dying from COVID-19 (OR, 1.68).

Being of male sex was associated with a 46% increased risk for death from COVID-19 versus being of female sex.

The risk for COVID-19 death also rose with the use of corticosteroids. Compared with no steroid use, there was a 69% increased risk for with death at doses of 10 mg or more prednisolone equivalent per day.

“The finding about moderate to high doses of steroids being associated with a worse outcome is consistent with the first report; it was the same for hospitalization,” Dr. Machado observed.

The general consensus on steroid use in the COVID-19 setting is that they should be continued as needed, but at the lowest possible dose, as outlined in provisional recommendations set out by the recently renamed European Alliance of Associations for Rheumatology.

The GRA physician registry findings provide further support for this, suggesting that disease control should be optimized with disease-modifying antirheumatic drugs, ideally without increasing the dose of steroids.

Surprise over sulfasalazine risk

“Taking all medications into account – such as methotrexate, leflunomide, hydroxychloroquine, [tumor necrosis factor] blockers, interleukin-6 blockers, and [Janus kinase] inhibitors – it is quite reassuring because we did not see an association with worse outcome with those drugs overall,” Dr. Machado said.

However, treatment with rituximab (OR, 4.0), sulfasalazine (OR, 3.6), and immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine, mycophenolate, or tacrolimus (OR, 2.2), were associated with higher odds of dying from COVID-19 when compared with treatment with methotrexate alone.

The findings for rituximab and immunosuppressant use were perhaps not unexpected, but the possible association between sulfasalazine and COVID-19 death was “a bit intriguing,” Dr. Machado observed. “Sulfasalazine is believed to have low immunosuppressive effect.”

This warrants further investigation, but there are likely a range of confounding factors at play. One could be that people considered to be at higher risk may have been more often prescribed sulfasalazine because it was thought to be less immunosuppressive. Another might be because people taking sulfasalazine were more likely to be smokers, and they were also not advised to protect themselves from exposure to the virus (shielding) during the first wave of the pandemic, at least not in the United Kingdom.
 

Rituximab caution and vaccination

“Rituximab is a concern,” Dr. Machado acknowledged. “It is a concern that rheumatologists are now aware of and they are addressing, but then it’s a concern for a very specific subgroup of patients.”

While rheumatologists are, and will continue to prescribe it, there will be even more careful consideration over when, in whom, and how to use it during, and possibly even after, the pandemic.

“COVID is here to stay, it will become endemic, and it’s going to be part of our lives like the flu virus is,” Dr. Machado predicted.

Then there is the issue on vaccinating people against COVID-19, should those on rituximab still receive it? The answer is a yes, but, as with other vaccinations it’s all about the timing of when the vaccination is given.

Societies such as the British Society for Rheumatology have already begun to include guidance on this, recommending one of the available COVID-19 vaccines is given at least a month before the next or first dose of rituximab is due. As rituximab is given every few months, with doses sometimes spaced as much as 9 months or even a year apart, this should not be too much of a problem, but it is “better to have the vaccine first,” Dr. Machado said.
 

Has COVID-19 care improved in RMDs?

In separate research published in The Lancet Rheumatology, April Jorge, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and associates found that the risks of severe COVID-19 outcomes have improved over time, although they still “remain substantial.”

Dr. Jorge and colleagues looked at temporal trends in COVID-19 outcomes in patients with RMDs over the course of the first 6 months of the pandemic in 2020, using data from a large, multicenter, electronic health record network (TriNetX).

They formed two patient cohorts – a late (diagnosed from April 20 to July 20) and an early (diagnosed from January 20 to April 20) cohort – to see if outcomes had improved and discovered lower relative risks among patients in the late cohort for hospitalization (0.67), admission to the ICU (0.56), mechanical ventilation (0.39), acute kidney injury (0.66), renal replacement (0.53), and death (0.39).

“These results are encouraging,” but it’s difficult to match these different populations of patients, Dr. Machado said. “There are always factors that you cannot match for” and were not included in the U.S. analysis.

While there are important caveats in how the analysis was performed and thus in interpreting these data, they do “suggest that one of the reasons why outcomes have improved is because we have become better at treating these patients,” Dr. Machado added.

“Our treatment has improved, and our capacity to treat the complications has improved. We understand better how the disease behaves – we know that they can have thromboembolic complications that we can manage, and we are now able to manage ventilation issues better.”

Moreover, Dr. Machado said that, not only were clinicians more aware of what they should or should not do, there were treatments that were being used routinely or in some cases based on recent clinical trial results. “I think we are indeed treating these patients better.”

The COVID-19 GRA physician registry is financially supported by the American College of Rheumatology and EULAR. Dr. Machado had no relevant conflicts of interest.

Invasive group A Streptococcus (iGAS) disease has been on the rise among indigenous populations around the world. Researchers from University of Alberta, Alberta Ministry of Health, both in Edmonton, and Alberta First Nations Information Governance Center in Alberta conducted a study to find out more. Between 2003 and 2017, they investigated iGAS cases among First Nations, Inuit, and Métis members in Alberta.

During that time, 669 cases of iGAS were reported. The incidence increased from 10 cases per 100,000 in 2003 to 52 cases per 100,000 in 2017—an incidence rate > 6 times that of non–First Nations populations. The researchers say the disproportionately high rates are seen in other Native American groups compared with the rates in the general population: One study, for instance, found the incidence rate for Alaska Natives was 13.7 cases per 100,000 compared with 3.9 cases per 100,000 for non–Alaska Natives.

What’s driving the higher rates isn’t completely clear, the researchers say. They note that risk factor data in their study “frequently” indicated nonsurgical wounds, addiction abuse, and homelessness. They also cite research that has found skin infections and skin breakdown are common among iGAS patients who were injection drug users or homeless. Diabetes mellitus—rampant among Native Americans—was another risk factor.

The researchers found a “striking difference” in that the First Nations members had more skin and soft tissue infections and, unexpectedly, fewer streptococcal toxic shock syndrome cases than did the non–First Nations groups.

Moreover, skin-to-skin transmission may be more common than respiratory transmission: When they grouped emm types (the bacteria are typed according to a protein encoded by the emm gene) by cluster, they found the bulk of disease among the First Nations population was associated with skin-related infections, not throat-related clusters. This may be a consequence of overcrowded households or inadequate housing, both issues for Native American communities. The researchers say emm59, the most prevalent emm type in the First Nations population in the study, displays a tropism for skin infections. Since 2006, they add, when a large outbreak of emm59 was reported, it has become common throughout western Canada and the US, where it had previously been relatively rare.

Of note, the researchers conclude, substantial emm differences could have potential implications for future vaccine.

Source: Tyrrell GJ, Bell B, Bill L, Fathima S. Increasing incidence of invasive group A Streptococcus Disease in First Nations population, Alberta, Canada, 2003-2017. Emerg Infect Dis. 2021;27(2):443-451. doi:doi:10.3201/eid2702.20194

Invasive group A Streptococcus (iGAS) disease has been on the rise among indigenous populations around the world. Researchers from University of Alberta, Alberta Ministry of Health, both in Edmonton, and Alberta First Nations Information Governance Center in Alberta conducted a study to find out more. Between 2003 and 2017, they investigated iGAS cases among First Nations, Inuit, and Métis members in Alberta.

During that time, 669 cases of iGAS were reported. The incidence increased from 10 cases per 100,000 in 2003 to 52 cases per 100,000 in 2017—an incidence rate > 6 times that of non–First Nations populations. The researchers say the disproportionately high rates are seen in other Native American groups compared with the rates in the general population: One study, for instance, found the incidence rate for Alaska Natives was 13.7 cases per 100,000 compared with 3.9 cases per 100,000 for non–Alaska Natives.

What’s driving the higher rates isn’t completely clear, the researchers say. They note that risk factor data in their study “frequently” indicated nonsurgical wounds, addiction abuse, and homelessness. They also cite research that has found skin infections and skin breakdown are common among iGAS patients who were injection drug users or homeless. Diabetes mellitus—rampant among Native Americans—was another risk factor.

The researchers found a “striking difference” in that the First Nations members had more skin and soft tissue infections and, unexpectedly, fewer streptococcal toxic shock syndrome cases than did the non–First Nations groups.

Moreover, skin-to-skin transmission may be more common than respiratory transmission: When they grouped emm types (the bacteria are typed according to a protein encoded by the emm gene) by cluster, they found the bulk of disease among the First Nations population was associated with skin-related infections, not throat-related clusters. This may be a consequence of overcrowded households or inadequate housing, both issues for Native American communities. The researchers say emm59, the most prevalent emm type in the First Nations population in the study, displays a tropism for skin infections. Since 2006, they add, when a large outbreak of emm59 was reported, it has become common throughout western Canada and the US, where it had previously been relatively rare.

Of note, the researchers conclude, substantial emm differences could have potential implications for future vaccine.

Source: Tyrrell GJ, Bell B, Bill L, Fathima S. Increasing incidence of invasive group A Streptococcus Disease in First Nations population, Alberta, Canada, 2003-2017. Emerg Infect Dis. 2021;27(2):443-451. doi:doi:10.3201/eid2702.20194

Invasive group A Streptococcus (iGAS) disease has been on the rise among indigenous populations around the world. Researchers from University of Alberta, Alberta Ministry of Health, both in Edmonton, and Alberta First Nations Information Governance Center in Alberta conducted a study to find out more. Between 2003 and 2017, they investigated iGAS cases among First Nations, Inuit, and Métis members in Alberta.

During that time, 669 cases of iGAS were reported. The incidence increased from 10 cases per 100,000 in 2003 to 52 cases per 100,000 in 2017—an incidence rate > 6 times that of non–First Nations populations. The researchers say the disproportionately high rates are seen in other Native American groups compared with the rates in the general population: One study, for instance, found the incidence rate for Alaska Natives was 13.7 cases per 100,000 compared with 3.9 cases per 100,000 for non–Alaska Natives.

What’s driving the higher rates isn’t completely clear, the researchers say. They note that risk factor data in their study “frequently” indicated nonsurgical wounds, addiction abuse, and homelessness. They also cite research that has found skin infections and skin breakdown are common among iGAS patients who were injection drug users or homeless. Diabetes mellitus—rampant among Native Americans—was another risk factor.

The researchers found a “striking difference” in that the First Nations members had more skin and soft tissue infections and, unexpectedly, fewer streptococcal toxic shock syndrome cases than did the non–First Nations groups.

Moreover, skin-to-skin transmission may be more common than respiratory transmission: When they grouped emm types (the bacteria are typed according to a protein encoded by the emm gene) by cluster, they found the bulk of disease among the First Nations population was associated with skin-related infections, not throat-related clusters. This may be a consequence of overcrowded households or inadequate housing, both issues for Native American communities. The researchers say emm59, the most prevalent emm type in the First Nations population in the study, displays a tropism for skin infections. Since 2006, they add, when a large outbreak of emm59 was reported, it has become common throughout western Canada and the US, where it had previously been relatively rare.

Of note, the researchers conclude, substantial emm differences could have potential implications for future vaccine.

Source: Tyrrell GJ, Bell B, Bill L, Fathima S. Increasing incidence of invasive group A Streptococcus Disease in First Nations population, Alberta, Canada, 2003-2017. Emerg Infect Dis. 2021;27(2):443-451. doi:doi:10.3201/eid2702.20194

The gout drug colchicine appears to lower the severity of COVID-19, a small new Brazilian study finds, adding to evidence that the familiar medication holds promise as a treatment for hospitalized patients.

Patients who received colchicine in this randomized, double-blinded, placebo-controlled clinical trial presented better evolution in terms of the need for supplemental oxygen and the length of hospitalisation. ... Colchicine was safe and well tolerated,” the study authors wrote in RMD Open. However, deaths were rare in the trial, they added, and it is impossible to “evaluate the capacity of colchicine to avoid admission to ICU and reduce mortality.”

The oral anti-inflammatory colchicine, widely used as treatment in rheumatic disease, was first approved in the United States 60 years ago. Researchers began to explore its potential as a COVID-19 treatment in the early months of the pandemic.

On Jan. 25, an international team of researchers reported in a press release – but not yet a published paper – that the drug seemed to reduce hospitalizations, mechanical ventilation, and deaths in the ColCORONA trial. Earlier, a much-smaller, randomized, open-label, Greek trial linked the drug to reduced time to clinical deterioration and hospital stay.

The Brazilian authors of the new study, led by Maria Isabel Lopes of the University of São Paulo’s Ribeirão Preto Medical School, randomly assigned 75 hospitalized patients with moderate to severe COVID-19 to colchicine or placebo. A total of 72 subjects completed the April-August 2020 trial: 36 received colchicine (typically 0.5 mg three times for 5 days, then 0.5 mg twice daily for 5 days; doses were adjusted in low-weight patients and those with chronic kidney disease). The other 36 received the placebo.

(In the United States, 0.6-mg tablets of generic colchicine cost as little as $1.90 each with free coupons, according to goodrx.com.)

The median age in the groups was similar (55 years); and the placebo group had more women (61% vs. 47% in the colchicine group, P = .34). All 72 patients received the same COVID-19 treatment at the time of the trial: azithromycin, hydroxychloroquine, and unfractionated heparin. Most patients, about two-thirds in both groups, also received methylprednisolone because they needed higher amounts of supplemental oxygen.

Patients in the colchicine group needed supplemental oxygen for less time: Their median time of need was 4.0 days (interquartile range [IQR], 2.0-6.0) vs. 6.5 days (IQR, 4.0-9.0) for the placebo group (P < .001). The median time for hospitalization was also lower at 7.0 days (IQR, 5.0–9.0) for the colchicine group vs. 9.0 (IQR, 7.0–12.0) for the placebo group (log rank test, 10.6; P = .001).

The researchers also reported the percentage of patients who needed supplemental oxygen at day 2 as 67% with colchicine vs. 86% with placebo, and at day 7 as 9% vs. 42% (log rank test, 10.6; P = .001). Two patients in the placebo group died, both from ventilator-associated pneumonia.

As for side effects, new or worsened diarrhea was reported more often in the colchicine group (17% vs. 6% with placebo), but the difference was not statistically significant (P = .26), and diarrhea was controlled via medication.

The researchers reported that limitations include the exclusion criteria and their inability to link colchicine to rates of ICU admissions and death.

The drug appears to help patients with COVID-19, the study authors wrote, by “inhibiting inflammasome, reducing neutrophil migration and activation, or preventing endothelial damage.”

A “well-conceived and well-designed” study

In an interview, NYU Langone Health rheumatologist Michael H. Pillinger, MD – an investigator with the ColCORONA trial – praised the Brazilian study. It “appears well-conceived and well-designed, and was enrolled at a rate that was greater than the sample size that was estimated to be needed based on power analysis,” he said.

The Brazilian study is small, he noted. (In contrast, the ColCORONA trial had 4,488 outpatient participants.) “This study differs from ColCORONA in several ways – the most important being that it is a study of inpatients with moderate to severe COVID (really mostly moderate),” he added. “ColCORONA is looking at a target audience that is much larger – outpatients with mild to moderate COVID with risk factors for hospitalization. Both questions are really important and certainly not mutually exclusive, since our care remains inadequate in both venues. This study also adds value in that several other studies have been conducted in hospital patients with enrollment criteria relatively similar to this one, and all showed benefit, but those were open-label or retrospective, and this is blinded and placebo-controlled.”
 

Using colchicine in patients with COVID-19

Should physicians turn to colchicine in patients with COVID-19? “I would rather that it still be used in the context of research until formal recommendations can be made by bodies like the NIH and CDC,” Dr. Pillinger said. “But certainly, there may be times when physicians feel compelled to treat patients off label.”

He cautioned, however, that colchicine should never be used with some other drugs. Its interaction with the antibiotic clarithromycin can be fatal, he noted. And, he said, the drug must be monitored in general since it can cause rare, severe problems.

“Overall, colchicine probably works on the overabundant inflammatory response to COVID, and it may be that it can be combined with other drugs that affect viral replication or promote immunity – e.g. vaccines,” Dr. Pillinger said. “So far, it seems as if there is no safety problem with combining colchicine with other approaches, but this has not been studied in a rigorous manner.”

Moving forward, he said, the drug’s very low price outside of the United States “could provide resource-poor countries with a way to help keep patients out of precious hospital beds – or help them go home sooner once admitted.” For now, however, “we need a large-scale inpatient study, and one is currently going on in Great Britain. We also need validation of the outpatient ColCORONA study, and studies to look at whether colchicine can work in conjunction with other strategies.”

The study was funded by grants from the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and CAPES Foundation. No disclosures are reported. Dr. Pillinger reports serving as an investigator for the ColCORONA trial and receiving a unrelated investigator-initiated grant from Hikma, a colchicine manufacturer.

The gout drug colchicine appears to lower the severity of COVID-19, a small new Brazilian study finds, adding to evidence that the familiar medication holds promise as a treatment for hospitalized patients.

Patients who received colchicine in this randomized, double-blinded, placebo-controlled clinical trial presented better evolution in terms of the need for supplemental oxygen and the length of hospitalisation. ... Colchicine was safe and well tolerated,” the study authors wrote in RMD Open. However, deaths were rare in the trial, they added, and it is impossible to “evaluate the capacity of colchicine to avoid admission to ICU and reduce mortality.”

The oral anti-inflammatory colchicine, widely used as treatment in rheumatic disease, was first approved in the United States 60 years ago. Researchers began to explore its potential as a COVID-19 treatment in the early months of the pandemic.

On Jan. 25, an international team of researchers reported in a press release – but not yet a published paper – that the drug seemed to reduce hospitalizations, mechanical ventilation, and deaths in the ColCORONA trial. Earlier, a much-smaller, randomized, open-label, Greek trial linked the drug to reduced time to clinical deterioration and hospital stay.

The Brazilian authors of the new study, led by Maria Isabel Lopes of the University of São Paulo’s Ribeirão Preto Medical School, randomly assigned 75 hospitalized patients with moderate to severe COVID-19 to colchicine or placebo. A total of 72 subjects completed the April-August 2020 trial: 36 received colchicine (typically 0.5 mg three times for 5 days, then 0.5 mg twice daily for 5 days; doses were adjusted in low-weight patients and those with chronic kidney disease). The other 36 received the placebo.

(In the United States, 0.6-mg tablets of generic colchicine cost as little as $1.90 each with free coupons, according to goodrx.com.)

The median age in the groups was similar (55 years); and the placebo group had more women (61% vs. 47% in the colchicine group, P = .34). All 72 patients received the same COVID-19 treatment at the time of the trial: azithromycin, hydroxychloroquine, and unfractionated heparin. Most patients, about two-thirds in both groups, also received methylprednisolone because they needed higher amounts of supplemental oxygen.

Patients in the colchicine group needed supplemental oxygen for less time: Their median time of need was 4.0 days (interquartile range [IQR], 2.0-6.0) vs. 6.5 days (IQR, 4.0-9.0) for the placebo group (P < .001). The median time for hospitalization was also lower at 7.0 days (IQR, 5.0–9.0) for the colchicine group vs. 9.0 (IQR, 7.0–12.0) for the placebo group (log rank test, 10.6; P = .001).

The researchers also reported the percentage of patients who needed supplemental oxygen at day 2 as 67% with colchicine vs. 86% with placebo, and at day 7 as 9% vs. 42% (log rank test, 10.6; P = .001). Two patients in the placebo group died, both from ventilator-associated pneumonia.

As for side effects, new or worsened diarrhea was reported more often in the colchicine group (17% vs. 6% with placebo), but the difference was not statistically significant (P = .26), and diarrhea was controlled via medication.

The researchers reported that limitations include the exclusion criteria and their inability to link colchicine to rates of ICU admissions and death.

The drug appears to help patients with COVID-19, the study authors wrote, by “inhibiting inflammasome, reducing neutrophil migration and activation, or preventing endothelial damage.”

A “well-conceived and well-designed” study

In an interview, NYU Langone Health rheumatologist Michael H. Pillinger, MD – an investigator with the ColCORONA trial – praised the Brazilian study. It “appears well-conceived and well-designed, and was enrolled at a rate that was greater than the sample size that was estimated to be needed based on power analysis,” he said.

The Brazilian study is small, he noted. (In contrast, the ColCORONA trial had 4,488 outpatient participants.) “This study differs from ColCORONA in several ways – the most important being that it is a study of inpatients with moderate to severe COVID (really mostly moderate),” he added. “ColCORONA is looking at a target audience that is much larger – outpatients with mild to moderate COVID with risk factors for hospitalization. Both questions are really important and certainly not mutually exclusive, since our care remains inadequate in both venues. This study also adds value in that several other studies have been conducted in hospital patients with enrollment criteria relatively similar to this one, and all showed benefit, but those were open-label or retrospective, and this is blinded and placebo-controlled.”
 

Using colchicine in patients with COVID-19

Should physicians turn to colchicine in patients with COVID-19? “I would rather that it still be used in the context of research until formal recommendations can be made by bodies like the NIH and CDC,” Dr. Pillinger said. “But certainly, there may be times when physicians feel compelled to treat patients off label.”

He cautioned, however, that colchicine should never be used with some other drugs. Its interaction with the antibiotic clarithromycin can be fatal, he noted. And, he said, the drug must be monitored in general since it can cause rare, severe problems.

“Overall, colchicine probably works on the overabundant inflammatory response to COVID, and it may be that it can be combined with other drugs that affect viral replication or promote immunity – e.g. vaccines,” Dr. Pillinger said. “So far, it seems as if there is no safety problem with combining colchicine with other approaches, but this has not been studied in a rigorous manner.”

Moving forward, he said, the drug’s very low price outside of the United States “could provide resource-poor countries with a way to help keep patients out of precious hospital beds – or help them go home sooner once admitted.” For now, however, “we need a large-scale inpatient study, and one is currently going on in Great Britain. We also need validation of the outpatient ColCORONA study, and studies to look at whether colchicine can work in conjunction with other strategies.”

The study was funded by grants from the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and CAPES Foundation. No disclosures are reported. Dr. Pillinger reports serving as an investigator for the ColCORONA trial and receiving a unrelated investigator-initiated grant from Hikma, a colchicine manufacturer.

The gout drug colchicine appears to lower the severity of COVID-19, a small new Brazilian study finds, adding to evidence that the familiar medication holds promise as a treatment for hospitalized patients.

Patients who received colchicine in this randomized, double-blinded, placebo-controlled clinical trial presented better evolution in terms of the need for supplemental oxygen and the length of hospitalisation. ... Colchicine was safe and well tolerated,” the study authors wrote in RMD Open. However, deaths were rare in the trial, they added, and it is impossible to “evaluate the capacity of colchicine to avoid admission to ICU and reduce mortality.”

The oral anti-inflammatory colchicine, widely used as treatment in rheumatic disease, was first approved in the United States 60 years ago. Researchers began to explore its potential as a COVID-19 treatment in the early months of the pandemic.

On Jan. 25, an international team of researchers reported in a press release – but not yet a published paper – that the drug seemed to reduce hospitalizations, mechanical ventilation, and deaths in the ColCORONA trial. Earlier, a much-smaller, randomized, open-label, Greek trial linked the drug to reduced time to clinical deterioration and hospital stay.

The Brazilian authors of the new study, led by Maria Isabel Lopes of the University of São Paulo’s Ribeirão Preto Medical School, randomly assigned 75 hospitalized patients with moderate to severe COVID-19 to colchicine or placebo. A total of 72 subjects completed the April-August 2020 trial: 36 received colchicine (typically 0.5 mg three times for 5 days, then 0.5 mg twice daily for 5 days; doses were adjusted in low-weight patients and those with chronic kidney disease). The other 36 received the placebo.

(In the United States, 0.6-mg tablets of generic colchicine cost as little as $1.90 each with free coupons, according to goodrx.com.)

The median age in the groups was similar (55 years); and the placebo group had more women (61% vs. 47% in the colchicine group, P = .34). All 72 patients received the same COVID-19 treatment at the time of the trial: azithromycin, hydroxychloroquine, and unfractionated heparin. Most patients, about two-thirds in both groups, also received methylprednisolone because they needed higher amounts of supplemental oxygen.

Patients in the colchicine group needed supplemental oxygen for less time: Their median time of need was 4.0 days (interquartile range [IQR], 2.0-6.0) vs. 6.5 days (IQR, 4.0-9.0) for the placebo group (P < .001). The median time for hospitalization was also lower at 7.0 days (IQR, 5.0–9.0) for the colchicine group vs. 9.0 (IQR, 7.0–12.0) for the placebo group (log rank test, 10.6; P = .001).

The researchers also reported the percentage of patients who needed supplemental oxygen at day 2 as 67% with colchicine vs. 86% with placebo, and at day 7 as 9% vs. 42% (log rank test, 10.6; P = .001). Two patients in the placebo group died, both from ventilator-associated pneumonia.

As for side effects, new or worsened diarrhea was reported more often in the colchicine group (17% vs. 6% with placebo), but the difference was not statistically significant (P = .26), and diarrhea was controlled via medication.

The researchers reported that limitations include the exclusion criteria and their inability to link colchicine to rates of ICU admissions and death.

The drug appears to help patients with COVID-19, the study authors wrote, by “inhibiting inflammasome, reducing neutrophil migration and activation, or preventing endothelial damage.”

A “well-conceived and well-designed” study

In an interview, NYU Langone Health rheumatologist Michael H. Pillinger, MD – an investigator with the ColCORONA trial – praised the Brazilian study. It “appears well-conceived and well-designed, and was enrolled at a rate that was greater than the sample size that was estimated to be needed based on power analysis,” he said.

The Brazilian study is small, he noted. (In contrast, the ColCORONA trial had 4,488 outpatient participants.) “This study differs from ColCORONA in several ways – the most important being that it is a study of inpatients with moderate to severe COVID (really mostly moderate),” he added. “ColCORONA is looking at a target audience that is much larger – outpatients with mild to moderate COVID with risk factors for hospitalization. Both questions are really important and certainly not mutually exclusive, since our care remains inadequate in both venues. This study also adds value in that several other studies have been conducted in hospital patients with enrollment criteria relatively similar to this one, and all showed benefit, but those were open-label or retrospective, and this is blinded and placebo-controlled.”
 

Using colchicine in patients with COVID-19

Should physicians turn to colchicine in patients with COVID-19? “I would rather that it still be used in the context of research until formal recommendations can be made by bodies like the NIH and CDC,” Dr. Pillinger said. “But certainly, there may be times when physicians feel compelled to treat patients off label.”

He cautioned, however, that colchicine should never be used with some other drugs. Its interaction with the antibiotic clarithromycin can be fatal, he noted. And, he said, the drug must be monitored in general since it can cause rare, severe problems.

“Overall, colchicine probably works on the overabundant inflammatory response to COVID, and it may be that it can be combined with other drugs that affect viral replication or promote immunity – e.g. vaccines,” Dr. Pillinger said. “So far, it seems as if there is no safety problem with combining colchicine with other approaches, but this has not been studied in a rigorous manner.”

Moving forward, he said, the drug’s very low price outside of the United States “could provide resource-poor countries with a way to help keep patients out of precious hospital beds – or help them go home sooner once admitted.” For now, however, “we need a large-scale inpatient study, and one is currently going on in Great Britain. We also need validation of the outpatient ColCORONA study, and studies to look at whether colchicine can work in conjunction with other strategies.”

The study was funded by grants from the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and CAPES Foundation. No disclosures are reported. Dr. Pillinger reports serving as an investigator for the ColCORONA trial and receiving a unrelated investigator-initiated grant from Hikma, a colchicine manufacturer.

Background: While it is recognized that N95 respirator masks are better than regular medical masks at preventing the inhalation of aerosols, the question of whether they are better at preventing the transmission of infectious viral micro-organisms has never been studied in a robust randomized trial. Prior studies have shown mixed results, from noninferiority of medical masks to superiority of N95 masks, but these studies were stopped early or calibrated to detect outcomes of questionable clinical significance.

The study limitations included: most testing for infection occurred for self-reported symptoms with only a minor component of testing occurring at random; the self-reporting of secondary outcomes; and the somewhat high rate of nonadherence to either intervention. Although these are likely necessary trade-offs in a pragmatic trial.

Bottom line: N95 respirator masks are no better than regular medical masks are at preventing the transmission of influenza and other viral respiratory illnesses.

Citation: Radonovich LJ et al. N95 respirators vs. medical masks for preventing influenza among health care personnel: A randomized clinical trial. JAMA. 2019 Sep 3;322(9):824-33.

Dr. Porter is chief quality and safety resident at the Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, Colo.

Background: While it is recognized that N95 respirator masks are better than regular medical masks at preventing the inhalation of aerosols, the question of whether they are better at preventing the transmission of infectious viral micro-organisms has never been studied in a robust randomized trial. Prior studies have shown mixed results, from noninferiority of medical masks to superiority of N95 masks, but these studies were stopped early or calibrated to detect outcomes of questionable clinical significance.

The study limitations included: most testing for infection occurred for self-reported symptoms with only a minor component of testing occurring at random; the self-reporting of secondary outcomes; and the somewhat high rate of nonadherence to either intervention. Although these are likely necessary trade-offs in a pragmatic trial.

Bottom line: N95 respirator masks are no better than regular medical masks are at preventing the transmission of influenza and other viral respiratory illnesses.

Citation: Radonovich LJ et al. N95 respirators vs. medical masks for preventing influenza among health care personnel: A randomized clinical trial. JAMA. 2019 Sep 3;322(9):824-33.

Dr. Porter is chief quality and safety resident at the Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, Colo.

Background: While it is recognized that N95 respirator masks are better than regular medical masks at preventing the inhalation of aerosols, the question of whether they are better at preventing the transmission of infectious viral micro-organisms has never been studied in a robust randomized trial. Prior studies have shown mixed results, from noninferiority of medical masks to superiority of N95 masks, but these studies were stopped early or calibrated to detect outcomes of questionable clinical significance.

The study limitations included: most testing for infection occurred for self-reported symptoms with only a minor component of testing occurring at random; the self-reporting of secondary outcomes; and the somewhat high rate of nonadherence to either intervention. Although these are likely necessary trade-offs in a pragmatic trial.

Bottom line: N95 respirator masks are no better than regular medical masks are at preventing the transmission of influenza and other viral respiratory illnesses.

Citation: Radonovich LJ et al. N95 respirators vs. medical masks for preventing influenza among health care personnel: A randomized clinical trial. JAMA. 2019 Sep 3;322(9):824-33.

Dr. Porter is chief quality and safety resident at the Rocky Mountain Veterans Affairs Regional Medical Center, Aurora, Colo.

Despite a drop in the number of weekly COVID-19 cases, children made up a larger share of cases for the fourth consecutive week, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Just over 140,000 new cases of COVID-19 in children were reported for the week of Jan. 22-28, down from 165,000 the week before and down from the record high of 211,000 2 weeks earlier, the AAP and the CHA said in their weekly COVID-19 report.

Since the beginning of January, however, the proportion of weekly cases occurring in children has risen from 12.9% to 15.1%, based on data collected by the AAP/CHA from the health department websites of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

Since the beginning of the pandemic, 2.81 million children have been infected by the coronavirus, representing 12.8% of the total for all ages, which is almost 22 million. The cumulative rate since the start of the pandemic passed 3,700 cases per 100,000 children after increasing by 5.2% over the previous week, the AAP and CHA said in their report.

Cumulative hospitalizations in children just passed 11,000 in the 24 states (and New York City) that are reporting data for children, which represents 1.8% of COVID-19–related admissions for all ages, a proportion that has not changed since mid-November. Ten more deaths in children were reported during Jan. 22-28, bringing the total to 215 in the 43 states, along with New York City and Guam, that are tracking mortality.

In the 10 states that are reporting data on testing, rates of positive results in children range from 7.1% in Indiana, in which children make up the largest proportion of total tests performed (18.1%) to 28.4% in Iowa, where children make up the smallest proportion of tests (6.0%), the AAP and CHA said.

rfranki@mdedge.com

Despite a drop in the number of weekly COVID-19 cases, children made up a larger share of cases for the fourth consecutive week, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Just over 140,000 new cases of COVID-19 in children were reported for the week of Jan. 22-28, down from 165,000 the week before and down from the record high of 211,000 2 weeks earlier, the AAP and the CHA said in their weekly COVID-19 report.

Since the beginning of January, however, the proportion of weekly cases occurring in children has risen from 12.9% to 15.1%, based on data collected by the AAP/CHA from the health department websites of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

Since the beginning of the pandemic, 2.81 million children have been infected by the coronavirus, representing 12.8% of the total for all ages, which is almost 22 million. The cumulative rate since the start of the pandemic passed 3,700 cases per 100,000 children after increasing by 5.2% over the previous week, the AAP and CHA said in their report.

Cumulative hospitalizations in children just passed 11,000 in the 24 states (and New York City) that are reporting data for children, which represents 1.8% of COVID-19–related admissions for all ages, a proportion that has not changed since mid-November. Ten more deaths in children were reported during Jan. 22-28, bringing the total to 215 in the 43 states, along with New York City and Guam, that are tracking mortality.

In the 10 states that are reporting data on testing, rates of positive results in children range from 7.1% in Indiana, in which children make up the largest proportion of total tests performed (18.1%) to 28.4% in Iowa, where children make up the smallest proportion of tests (6.0%), the AAP and CHA said.

rfranki@mdedge.com

Despite a drop in the number of weekly COVID-19 cases, children made up a larger share of cases for the fourth consecutive week, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Just over 140,000 new cases of COVID-19 in children were reported for the week of Jan. 22-28, down from 165,000 the week before and down from the record high of 211,000 2 weeks earlier, the AAP and the CHA said in their weekly COVID-19 report.

Since the beginning of January, however, the proportion of weekly cases occurring in children has risen from 12.9% to 15.1%, based on data collected by the AAP/CHA from the health department websites of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

Since the beginning of the pandemic, 2.81 million children have been infected by the coronavirus, representing 12.8% of the total for all ages, which is almost 22 million. The cumulative rate since the start of the pandemic passed 3,700 cases per 100,000 children after increasing by 5.2% over the previous week, the AAP and CHA said in their report.

Cumulative hospitalizations in children just passed 11,000 in the 24 states (and New York City) that are reporting data for children, which represents 1.8% of COVID-19–related admissions for all ages, a proportion that has not changed since mid-November. Ten more deaths in children were reported during Jan. 22-28, bringing the total to 215 in the 43 states, along with New York City and Guam, that are tracking mortality.

In the 10 states that are reporting data on testing, rates of positive results in children range from 7.1% in Indiana, in which children make up the largest proportion of total tests performed (18.1%) to 28.4% in Iowa, where children make up the smallest proportion of tests (6.0%), the AAP and CHA said.

rfranki@mdedge.com

Autopsies on patients who died from COVID-19 are providing important clues on how to treat the disease. In an analysis of 40 hearts from COVID-19 patients who died early in the pandemic, myocyte necrosis was seen in 14 hearts, or 35%.

In the majority of these hearts, pathologists found both small areas of focal necrosis and cardiac thrombi, most of which were microthrombi in myocardial capillaries, arterioles, and small muscular cells.

In an interview, senior author Aloke V. Finn, MD, CVPath Institute, Gaithersburg, Md., stressed the importance of understanding what they saw, but also what they didn’t see.

“What we saw in the majority of patients with myocardial injury were these small areas of infarct and microthrombi in small vessels. What we didn’t see was any evidence of myocarditis and or huge infarcts in, like, the LAD artery,” he said.

“What we’re seeing here is not clinically detectable. ... There is no test that will tell you there are microthrombi and no imaging tests that will show these focal areas of necrosis, but that doesn’t mean it’s not there,” he added.

The finding of myocyte necrosis in about one-third of samples is consistent with another study that showed that 30%-40% of patients hospitalized with COVID-19 have elevated troponins, noted Dr. Finn. The investigators were unable to obtain troponin levels on their patients, which could limit the clinical translation of myocardial necrosis detected at autopsy.

Dr. Finn and colleagues, including first author Dario Pellegrini, MD, from Ospedale Papa Giovanni XXIII in Bergamo, Italy, published their findings online in Circulation on Jan. 22, 2020.

The report is a follow-up to another just published by Dr. Finn’s group in the Journal of the American College of Cardiology, which showed that myocarditis is a very rare finding in COVID-19 autopsies.

Only three of 14 individuals (21.4%) with evidence of myocyte necrosis showed evidence of acute MI, which Dr. Finn and colleagues define as an area of necrosis at least 1 cm² in size. The remaining 11 (78.6%) had only discrete areas of myocyte necrosis (>20 necrotic myocytes with an area of ≥0.05 mm², but <1 cm²).

“This makes sense when we saw what type of thrombus there was in these cases; it wasn’t thrombus in major epicardial vessels but microthombi in small vessels,” said Dr. Finn.

In those with necrosis, cardiac thrombi were present in 11 of 14 (78.6%) cases, with 2 of 14 (14.2%) having epicardial coronary artery thrombi and 0 of 14 (64.3%) having microthrombi in myocardial capillaries, arterioles, and small muscular arteries.

Further supporting the role of COVID-19–related hypercoagulability as the cause of myocardial injury in many patients, the investigators noted that the incidence of severe coronary artery disease (defined as >75% cross sectional narrowing) did not differ significantly between those with and without necrosis.
 

COVID-19 vs. non–COVID-19 thrombi

Going one step further, Dr. Finn’s team compared cardiac microthrombi from their COVID-19–positive autopsy cases with intramyocardial thromboemboli from COVID-19 cases. They also compared the samples with aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19–infected patients presenting with ST-segment elevation MI (STEMI).

The autopsy-obtained microthrombi had significantly more fibrin and terminal complement C5b-9 immunostaining than intramyocardial thromboemboli from COVID-19–negative subjects and than aspirated thrombi from either COVID-positive or COVID-negative STEMI patients.

“Basically, what we’re seeing in these thrombi is evidence of an immune-mediated reaction,” said Dr. Finn, explaining that complement C5b-9 is an innate immune system protein that circulates in the blood in response to any kind of activation of the immune system. “It is nonspecific but can also lead to coagulation problems,” he said.
 

Anticoagulation, yes, but dose unclear

These findings clearly support the use of anticoagulation in hospitalized COVID patients, said Jeffrey Weitz, MD, director of the Thrombosis & Atherosclerosis Research Institute, McMaster University, Hamilton, Ont. But the details of how much anticoagulation, what kind, and for whom are still a moving target.

“I think what we can say at this point is that these autopsy findings fit with previous studies that have shown microthrombi in the lungs and thrombi in the legs and gut, and support the notion that these patients should receive prophylactic doses of anticoagulants if they’re sick enough to be hospitalized,” said Dr. Weitz.

“But it’s not as simple as to say that this study shows clots form in the heart of COVID patients and therefore more anticoagulation is going to be better than less anticoagulation,” he said in an interview.

Recent top-line findings from three linked clinical trials – REMAP-CAP, ACTIV-4, and ATTACC – show that full-dose anticoagulation was beneficial in moderately ill patients hospitalized for COVID-19 and reduced the need for mechanical ventilation.

Moderately ill patients are those not in intensive care and who did not require organ support, such as mechanical ventilation, at the time of enrollment.

However, the same group reported findings in December that showed that routine use of full-dose anticoagulation when started in the ICU in critically ill patients was not beneficial and possibly harmful.

Dr. Weitz was only a little bit surprised by this finding of potential harm in the sickest patients. “I figured everybody should get prophylaxis but I wasn’t sure that everybody should get intensified anticoagulant. But my assumption was that if anybody is going to benefit from it, it would be the ICU patients.”

It was notable, said Dr. Weitz, that levels of D-dimer, a fibrin degradation product, were not associated with outcomes. “So, it doesn’t seem to be that patients with evidence of more clotting are more likely to benefit, which might indicate that it’s not the anticoagulant effect of the heparin that’s helping, but maybe the anti-inflammatory effect. At this point, we just don’t know.”

All three studies have paused enrollment of the critically ill subgroup, but are continuing to enroll patients with moderate illness and expect to publish results in the coming months, according to previous coverage from this news organization.

The study was funded by CVPath, a nonprofit institute that receives funding from a number of different industry entities. Dr. Finn and Dr. Weitz reported no relevant conflicts of interest.

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

Autopsies on patients who died from COVID-19 are providing important clues on how to treat the disease. In an analysis of 40 hearts from COVID-19 patients who died early in the pandemic, myocyte necrosis was seen in 14 hearts, or 35%.

In the majority of these hearts, pathologists found both small areas of focal necrosis and cardiac thrombi, most of which were microthrombi in myocardial capillaries, arterioles, and small muscular cells.

In an interview, senior author Aloke V. Finn, MD, CVPath Institute, Gaithersburg, Md., stressed the importance of understanding what they saw, but also what they didn’t see.

“What we saw in the majority of patients with myocardial injury were these small areas of infarct and microthrombi in small vessels. What we didn’t see was any evidence of myocarditis and or huge infarcts in, like, the LAD artery,” he said.

“What we’re seeing here is not clinically detectable. ... There is no test that will tell you there are microthrombi and no imaging tests that will show these focal areas of necrosis, but that doesn’t mean it’s not there,” he added.

The finding of myocyte necrosis in about one-third of samples is consistent with another study that showed that 30%-40% of patients hospitalized with COVID-19 have elevated troponins, noted Dr. Finn. The investigators were unable to obtain troponin levels on their patients, which could limit the clinical translation of myocardial necrosis detected at autopsy.

Dr. Finn and colleagues, including first author Dario Pellegrini, MD, from Ospedale Papa Giovanni XXIII in Bergamo, Italy, published their findings online in Circulation on Jan. 22, 2020.

The report is a follow-up to another just published by Dr. Finn’s group in the Journal of the American College of Cardiology, which showed that myocarditis is a very rare finding in COVID-19 autopsies.

Only three of 14 individuals (21.4%) with evidence of myocyte necrosis showed evidence of acute MI, which Dr. Finn and colleagues define as an area of necrosis at least 1 cm² in size. The remaining 11 (78.6%) had only discrete areas of myocyte necrosis (>20 necrotic myocytes with an area of ≥0.05 mm², but <1 cm²).

“This makes sense when we saw what type of thrombus there was in these cases; it wasn’t thrombus in major epicardial vessels but microthombi in small vessels,” said Dr. Finn.

In those with necrosis, cardiac thrombi were present in 11 of 14 (78.6%) cases, with 2 of 14 (14.2%) having epicardial coronary artery thrombi and 0 of 14 (64.3%) having microthrombi in myocardial capillaries, arterioles, and small muscular arteries.

Further supporting the role of COVID-19–related hypercoagulability as the cause of myocardial injury in many patients, the investigators noted that the incidence of severe coronary artery disease (defined as >75% cross sectional narrowing) did not differ significantly between those with and without necrosis.
 

COVID-19 vs. non–COVID-19 thrombi

Going one step further, Dr. Finn’s team compared cardiac microthrombi from their COVID-19–positive autopsy cases with intramyocardial thromboemboli from COVID-19 cases. They also compared the samples with aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19–infected patients presenting with ST-segment elevation MI (STEMI).

The autopsy-obtained microthrombi had significantly more fibrin and terminal complement C5b-9 immunostaining than intramyocardial thromboemboli from COVID-19–negative subjects and than aspirated thrombi from either COVID-positive or COVID-negative STEMI patients.

“Basically, what we’re seeing in these thrombi is evidence of an immune-mediated reaction,” said Dr. Finn, explaining that complement C5b-9 is an innate immune system protein that circulates in the blood in response to any kind of activation of the immune system. “It is nonspecific but can also lead to coagulation problems,” he said.
 

Anticoagulation, yes, but dose unclear

These findings clearly support the use of anticoagulation in hospitalized COVID patients, said Jeffrey Weitz, MD, director of the Thrombosis & Atherosclerosis Research Institute, McMaster University, Hamilton, Ont. But the details of how much anticoagulation, what kind, and for whom are still a moving target.

“I think what we can say at this point is that these autopsy findings fit with previous studies that have shown microthrombi in the lungs and thrombi in the legs and gut, and support the notion that these patients should receive prophylactic doses of anticoagulants if they’re sick enough to be hospitalized,” said Dr. Weitz.

“But it’s not as simple as to say that this study shows clots form in the heart of COVID patients and therefore more anticoagulation is going to be better than less anticoagulation,” he said in an interview.

Recent top-line findings from three linked clinical trials – REMAP-CAP, ACTIV-4, and ATTACC – show that full-dose anticoagulation was beneficial in moderately ill patients hospitalized for COVID-19 and reduced the need for mechanical ventilation.

Moderately ill patients are those not in intensive care and who did not require organ support, such as mechanical ventilation, at the time of enrollment.

However, the same group reported findings in December that showed that routine use of full-dose anticoagulation when started in the ICU in critically ill patients was not beneficial and possibly harmful.

Dr. Weitz was only a little bit surprised by this finding of potential harm in the sickest patients. “I figured everybody should get prophylaxis but I wasn’t sure that everybody should get intensified anticoagulant. But my assumption was that if anybody is going to benefit from it, it would be the ICU patients.”

It was notable, said Dr. Weitz, that levels of D-dimer, a fibrin degradation product, were not associated with outcomes. “So, it doesn’t seem to be that patients with evidence of more clotting are more likely to benefit, which might indicate that it’s not the anticoagulant effect of the heparin that’s helping, but maybe the anti-inflammatory effect. At this point, we just don’t know.”

All three studies have paused enrollment of the critically ill subgroup, but are continuing to enroll patients with moderate illness and expect to publish results in the coming months, according to previous coverage from this news organization.

The study was funded by CVPath, a nonprofit institute that receives funding from a number of different industry entities. Dr. Finn and Dr. Weitz reported no relevant conflicts of interest.

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

Autopsies on patients who died from COVID-19 are providing important clues on how to treat the disease. In an analysis of 40 hearts from COVID-19 patients who died early in the pandemic, myocyte necrosis was seen in 14 hearts, or 35%.

In the majority of these hearts, pathologists found both small areas of focal necrosis and cardiac thrombi, most of which were microthrombi in myocardial capillaries, arterioles, and small muscular cells.

In an interview, senior author Aloke V. Finn, MD, CVPath Institute, Gaithersburg, Md., stressed the importance of understanding what they saw, but also what they didn’t see.

“What we saw in the majority of patients with myocardial injury were these small areas of infarct and microthrombi in small vessels. What we didn’t see was any evidence of myocarditis and or huge infarcts in, like, the LAD artery,” he said.

“What we’re seeing here is not clinically detectable. ... There is no test that will tell you there are microthrombi and no imaging tests that will show these focal areas of necrosis, but that doesn’t mean it’s not there,” he added.

The finding of myocyte necrosis in about one-third of samples is consistent with another study that showed that 30%-40% of patients hospitalized with COVID-19 have elevated troponins, noted Dr. Finn. The investigators were unable to obtain troponin levels on their patients, which could limit the clinical translation of myocardial necrosis detected at autopsy.

Dr. Finn and colleagues, including first author Dario Pellegrini, MD, from Ospedale Papa Giovanni XXIII in Bergamo, Italy, published their findings online in Circulation on Jan. 22, 2020.

The report is a follow-up to another just published by Dr. Finn’s group in the Journal of the American College of Cardiology, which showed that myocarditis is a very rare finding in COVID-19 autopsies.

Only three of 14 individuals (21.4%) with evidence of myocyte necrosis showed evidence of acute MI, which Dr. Finn and colleagues define as an area of necrosis at least 1 cm² in size. The remaining 11 (78.6%) had only discrete areas of myocyte necrosis (>20 necrotic myocytes with an area of ≥0.05 mm², but <1 cm²).

“This makes sense when we saw what type of thrombus there was in these cases; it wasn’t thrombus in major epicardial vessels but microthombi in small vessels,” said Dr. Finn.

In those with necrosis, cardiac thrombi were present in 11 of 14 (78.6%) cases, with 2 of 14 (14.2%) having epicardial coronary artery thrombi and 0 of 14 (64.3%) having microthrombi in myocardial capillaries, arterioles, and small muscular arteries.

Further supporting the role of COVID-19–related hypercoagulability as the cause of myocardial injury in many patients, the investigators noted that the incidence of severe coronary artery disease (defined as >75% cross sectional narrowing) did not differ significantly between those with and without necrosis.
 

COVID-19 vs. non–COVID-19 thrombi

Going one step further, Dr. Finn’s team compared cardiac microthrombi from their COVID-19–positive autopsy cases with intramyocardial thromboemboli from COVID-19 cases. They also compared the samples with aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19–infected patients presenting with ST-segment elevation MI (STEMI).

The autopsy-obtained microthrombi had significantly more fibrin and terminal complement C5b-9 immunostaining than intramyocardial thromboemboli from COVID-19–negative subjects and than aspirated thrombi from either COVID-positive or COVID-negative STEMI patients.

“Basically, what we’re seeing in these thrombi is evidence of an immune-mediated reaction,” said Dr. Finn, explaining that complement C5b-9 is an innate immune system protein that circulates in the blood in response to any kind of activation of the immune system. “It is nonspecific but can also lead to coagulation problems,” he said.
 

Anticoagulation, yes, but dose unclear

These findings clearly support the use of anticoagulation in hospitalized COVID patients, said Jeffrey Weitz, MD, director of the Thrombosis & Atherosclerosis Research Institute, McMaster University, Hamilton, Ont. But the details of how much anticoagulation, what kind, and for whom are still a moving target.

“I think what we can say at this point is that these autopsy findings fit with previous studies that have shown microthrombi in the lungs and thrombi in the legs and gut, and support the notion that these patients should receive prophylactic doses of anticoagulants if they’re sick enough to be hospitalized,” said Dr. Weitz.

“But it’s not as simple as to say that this study shows clots form in the heart of COVID patients and therefore more anticoagulation is going to be better than less anticoagulation,” he said in an interview.

Recent top-line findings from three linked clinical trials – REMAP-CAP, ACTIV-4, and ATTACC – show that full-dose anticoagulation was beneficial in moderately ill patients hospitalized for COVID-19 and reduced the need for mechanical ventilation.

Moderately ill patients are those not in intensive care and who did not require organ support, such as mechanical ventilation, at the time of enrollment.

However, the same group reported findings in December that showed that routine use of full-dose anticoagulation when started in the ICU in critically ill patients was not beneficial and possibly harmful.

Dr. Weitz was only a little bit surprised by this finding of potential harm in the sickest patients. “I figured everybody should get prophylaxis but I wasn’t sure that everybody should get intensified anticoagulant. But my assumption was that if anybody is going to benefit from it, it would be the ICU patients.”

It was notable, said Dr. Weitz, that levels of D-dimer, a fibrin degradation product, were not associated with outcomes. “So, it doesn’t seem to be that patients with evidence of more clotting are more likely to benefit, which might indicate that it’s not the anticoagulant effect of the heparin that’s helping, but maybe the anti-inflammatory effect. At this point, we just don’t know.”

All three studies have paused enrollment of the critically ill subgroup, but are continuing to enroll patients with moderate illness and expect to publish results in the coming months, according to previous coverage from this news organization.

The study was funded by CVPath, a nonprofit institute that receives funding from a number of different industry entities. Dr. Finn and Dr. Weitz reported no relevant conflicts of interest.

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