Infectious Disease Practitioner

Half of Chinese American parents and their children report having experienced an in-person episode of racial discrimination related to the COVID-19 pandemic, according to results from a survey study.

In the United States, where public officials continue to refer to SARS-CoV-2 as the “China virus” and have often sought to draw attention to its origins in Wuhan, China, “the associations between discrimination triggered by the racialization of this acute public health crisis and mental health are unknown,” Charissa S.L. Cheah, PhD, of the University of Maryland, Baltimore County, and colleagues wrote.

For their research published Oct. 29 in Pediatrics, Dr. Cheah and colleagues recruited a cohort of 543 Chinese American parents of school-age children, and 230 of their children aged 10-18 years, to complete online surveys between mid-March and late May 2020. Parents in the cohort were largely foreign born, with all identifying as ethnically Chinese, while their children were mostly U.S. born.
 

Evidence of discrimination against Chinese Americans

Half of parents and their children (51% of parents and 50% of youth) reported experiencing at least one in-person incident of direct discrimination (assessed using questions derived from a validated scale of racial aggression) related to the pandemic. Dr. Cheah and colleagues also reported a high incidence of direct discrimination online (32% of parents and 46% of youth). Additionally, the researchers measured reports of vicarious or indirect discrimination – such as hearing jokes or disparaging remarks about one’s ethnic group – which they used a different adapted scale to capture. More than three-quarters of the cohort reported such experiences.

The experiences of discrimination likely bore on the mental health of both parents and youth. Using a series of instruments designed to measure overall psychological well-being as well as symptoms of depression, anxiety, and certain emotional and behavioral outcomes, Dr. Cheah and colleagues reported significant negative associations between direct online or in-person discrimination and psychological health. For parents and children alike, anxiety and depressive symptoms were positively associated with all varieties of discrimination experiences measured in the study.

About a fifth of the youth in the study were deemed, based on the symptom scales used in the study, to have an elevated risk of clinically significant mental health problems, higher than the 10%-15% that would be expected for these age groups in the United States.

“This study revealed that a high percentage of Chinese American parents and their children personally experienced or witnessed anti-Chinese or anti–Asian American racial discrimination both online and in person due to the COVID-19 pandemic,” the investigators wrote. “Most respondents reported directly experiencing or witnessing racial discrimination against other Chinese or Asian American individuals due to COVID-19 at least once.”

Dr. Cheah and colleagues noted that their cross-sectional study did not lend itself to causal interpretations and was vulnerable to certain types of reporting bias. Nonetheless, they argued, as the pandemic continues, “pediatricians should be sensitive to the potential mental health needs of Chinese American youth and their parents related to various forms of racism, in addition to other stressors, as the foundations of perceptions of racial-ethnic discrimination and their consequences may be set during this period.”
 

COVID-19 didn’t only bring infection

In an accompanying editorial, Tina L. Cheng, MD, of Johns Hopkins University, Baltimore, and her daughter Alison M. Conca-Cheng, a medical student at Brown University, Providence, R.I., remarked that the study’s findings were consistent with recent research that found “4 in 10 Americans reported that it has become more common since COVID-19 for people to express racist views about Asian Americans,” and also described an increase in complaints of discriminatory experiences by Asian Americans.

In this context, a link to poor mental health “should be no surprise,” Dr. Cheng and Ms. Conca-Cheng argued, and urged pediatricians to consult the American Academy of Pediatrics’ 2019 policy statement on racism and on child and adolescent health. “It calls for us to optimize clinical practice, improve workforce development and professional education, strengthen research, and deploy systems through community engagement, advocacy, and public policy.”

David Rettew, MD, a child and adolescent psychiatrist and associate professor of psychiatry and pediatrics at the University of Vermont, Burlington, called the study’s main points “clear and disturbing.”

“While it is difficult to find much in the way here of a silver lining, these alarming reports have helped people working in health care and mental health to understand racism as another form of trauma and abuse which, like other types, can have real negative effects on health,” Dr. Rettew said in an interview. “The more we as mental health professions ask about racism and offer resources for people who have experienced it, just as we would people who have endured other types of trauma, the more we can help people heal. That said, it would be better just to stop this from happening in the first place.”

Dr. Cheah and colleagues’ study was supported by a National Science Foundation grant. The investigators disclosed no conflicts of interest. Dr. Cheng and Ms. Conca-Cheng disclosed no financial conflicts of interest related to their editorial. Dr. Rettew said he had no relevant financial disclosures.

SOURCE: Cheah CSL et al. Pediatrics. 2020;146(5):e2020021816.

Half of Chinese American parents and their children report having experienced an in-person episode of racial discrimination related to the COVID-19 pandemic, according to results from a survey study.

In the United States, where public officials continue to refer to SARS-CoV-2 as the “China virus” and have often sought to draw attention to its origins in Wuhan, China, “the associations between discrimination triggered by the racialization of this acute public health crisis and mental health are unknown,” Charissa S.L. Cheah, PhD, of the University of Maryland, Baltimore County, and colleagues wrote.

For their research published Oct. 29 in Pediatrics, Dr. Cheah and colleagues recruited a cohort of 543 Chinese American parents of school-age children, and 230 of their children aged 10-18 years, to complete online surveys between mid-March and late May 2020. Parents in the cohort were largely foreign born, with all identifying as ethnically Chinese, while their children were mostly U.S. born.
 

Evidence of discrimination against Chinese Americans

Half of parents and their children (51% of parents and 50% of youth) reported experiencing at least one in-person incident of direct discrimination (assessed using questions derived from a validated scale of racial aggression) related to the pandemic. Dr. Cheah and colleagues also reported a high incidence of direct discrimination online (32% of parents and 46% of youth). Additionally, the researchers measured reports of vicarious or indirect discrimination – such as hearing jokes or disparaging remarks about one’s ethnic group – which they used a different adapted scale to capture. More than three-quarters of the cohort reported such experiences.

The experiences of discrimination likely bore on the mental health of both parents and youth. Using a series of instruments designed to measure overall psychological well-being as well as symptoms of depression, anxiety, and certain emotional and behavioral outcomes, Dr. Cheah and colleagues reported significant negative associations between direct online or in-person discrimination and psychological health. For parents and children alike, anxiety and depressive symptoms were positively associated with all varieties of discrimination experiences measured in the study.

About a fifth of the youth in the study were deemed, based on the symptom scales used in the study, to have an elevated risk of clinically significant mental health problems, higher than the 10%-15% that would be expected for these age groups in the United States.

“This study revealed that a high percentage of Chinese American parents and their children personally experienced or witnessed anti-Chinese or anti–Asian American racial discrimination both online and in person due to the COVID-19 pandemic,” the investigators wrote. “Most respondents reported directly experiencing or witnessing racial discrimination against other Chinese or Asian American individuals due to COVID-19 at least once.”

Dr. Cheah and colleagues noted that their cross-sectional study did not lend itself to causal interpretations and was vulnerable to certain types of reporting bias. Nonetheless, they argued, as the pandemic continues, “pediatricians should be sensitive to the potential mental health needs of Chinese American youth and their parents related to various forms of racism, in addition to other stressors, as the foundations of perceptions of racial-ethnic discrimination and their consequences may be set during this period.”
 

COVID-19 didn’t only bring infection

In an accompanying editorial, Tina L. Cheng, MD, of Johns Hopkins University, Baltimore, and her daughter Alison M. Conca-Cheng, a medical student at Brown University, Providence, R.I., remarked that the study’s findings were consistent with recent research that found “4 in 10 Americans reported that it has become more common since COVID-19 for people to express racist views about Asian Americans,” and also described an increase in complaints of discriminatory experiences by Asian Americans.

In this context, a link to poor mental health “should be no surprise,” Dr. Cheng and Ms. Conca-Cheng argued, and urged pediatricians to consult the American Academy of Pediatrics’ 2019 policy statement on racism and on child and adolescent health. “It calls for us to optimize clinical practice, improve workforce development and professional education, strengthen research, and deploy systems through community engagement, advocacy, and public policy.”

David Rettew, MD, a child and adolescent psychiatrist and associate professor of psychiatry and pediatrics at the University of Vermont, Burlington, called the study’s main points “clear and disturbing.”

“While it is difficult to find much in the way here of a silver lining, these alarming reports have helped people working in health care and mental health to understand racism as another form of trauma and abuse which, like other types, can have real negative effects on health,” Dr. Rettew said in an interview. “The more we as mental health professions ask about racism and offer resources for people who have experienced it, just as we would people who have endured other types of trauma, the more we can help people heal. That said, it would be better just to stop this from happening in the first place.”

Dr. Cheah and colleagues’ study was supported by a National Science Foundation grant. The investigators disclosed no conflicts of interest. Dr. Cheng and Ms. Conca-Cheng disclosed no financial conflicts of interest related to their editorial. Dr. Rettew said he had no relevant financial disclosures.

SOURCE: Cheah CSL et al. Pediatrics. 2020;146(5):e2020021816.

Half of Chinese American parents and their children report having experienced an in-person episode of racial discrimination related to the COVID-19 pandemic, according to results from a survey study.

In the United States, where public officials continue to refer to SARS-CoV-2 as the “China virus” and have often sought to draw attention to its origins in Wuhan, China, “the associations between discrimination triggered by the racialization of this acute public health crisis and mental health are unknown,” Charissa S.L. Cheah, PhD, of the University of Maryland, Baltimore County, and colleagues wrote.

For their research published Oct. 29 in Pediatrics, Dr. Cheah and colleagues recruited a cohort of 543 Chinese American parents of school-age children, and 230 of their children aged 10-18 years, to complete online surveys between mid-March and late May 2020. Parents in the cohort were largely foreign born, with all identifying as ethnically Chinese, while their children were mostly U.S. born.
 

Evidence of discrimination against Chinese Americans

Half of parents and their children (51% of parents and 50% of youth) reported experiencing at least one in-person incident of direct discrimination (assessed using questions derived from a validated scale of racial aggression) related to the pandemic. Dr. Cheah and colleagues also reported a high incidence of direct discrimination online (32% of parents and 46% of youth). Additionally, the researchers measured reports of vicarious or indirect discrimination – such as hearing jokes or disparaging remarks about one’s ethnic group – which they used a different adapted scale to capture. More than three-quarters of the cohort reported such experiences.

The experiences of discrimination likely bore on the mental health of both parents and youth. Using a series of instruments designed to measure overall psychological well-being as well as symptoms of depression, anxiety, and certain emotional and behavioral outcomes, Dr. Cheah and colleagues reported significant negative associations between direct online or in-person discrimination and psychological health. For parents and children alike, anxiety and depressive symptoms were positively associated with all varieties of discrimination experiences measured in the study.

About a fifth of the youth in the study were deemed, based on the symptom scales used in the study, to have an elevated risk of clinically significant mental health problems, higher than the 10%-15% that would be expected for these age groups in the United States.

“This study revealed that a high percentage of Chinese American parents and their children personally experienced or witnessed anti-Chinese or anti–Asian American racial discrimination both online and in person due to the COVID-19 pandemic,” the investigators wrote. “Most respondents reported directly experiencing or witnessing racial discrimination against other Chinese or Asian American individuals due to COVID-19 at least once.”

Dr. Cheah and colleagues noted that their cross-sectional study did not lend itself to causal interpretations and was vulnerable to certain types of reporting bias. Nonetheless, they argued, as the pandemic continues, “pediatricians should be sensitive to the potential mental health needs of Chinese American youth and their parents related to various forms of racism, in addition to other stressors, as the foundations of perceptions of racial-ethnic discrimination and their consequences may be set during this period.”
 

COVID-19 didn’t only bring infection

In an accompanying editorial, Tina L. Cheng, MD, of Johns Hopkins University, Baltimore, and her daughter Alison M. Conca-Cheng, a medical student at Brown University, Providence, R.I., remarked that the study’s findings were consistent with recent research that found “4 in 10 Americans reported that it has become more common since COVID-19 for people to express racist views about Asian Americans,” and also described an increase in complaints of discriminatory experiences by Asian Americans.

In this context, a link to poor mental health “should be no surprise,” Dr. Cheng and Ms. Conca-Cheng argued, and urged pediatricians to consult the American Academy of Pediatrics’ 2019 policy statement on racism and on child and adolescent health. “It calls for us to optimize clinical practice, improve workforce development and professional education, strengthen research, and deploy systems through community engagement, advocacy, and public policy.”

David Rettew, MD, a child and adolescent psychiatrist and associate professor of psychiatry and pediatrics at the University of Vermont, Burlington, called the study’s main points “clear and disturbing.”

“While it is difficult to find much in the way here of a silver lining, these alarming reports have helped people working in health care and mental health to understand racism as another form of trauma and abuse which, like other types, can have real negative effects on health,” Dr. Rettew said in an interview. “The more we as mental health professions ask about racism and offer resources for people who have experienced it, just as we would people who have endured other types of trauma, the more we can help people heal. That said, it would be better just to stop this from happening in the first place.”

Dr. Cheah and colleagues’ study was supported by a National Science Foundation grant. The investigators disclosed no conflicts of interest. Dr. Cheng and Ms. Conca-Cheng disclosed no financial conflicts of interest related to their editorial. Dr. Rettew said he had no relevant financial disclosures.

SOURCE: Cheah CSL et al. Pediatrics. 2020;146(5):e2020021816.

Two experts at IDWeek 2020 debated the best treatment for patients with the most severe type of Clostridioides difficile infection – fulminant C. diff. The discussion pitted fecal microbiota transplants (FMT) from the stool of healthy donors against traditional antibiotics.

Fulminant C. diff infection (CDI) represents about 8% of all CDI cases and is often fatal. Patients frequently don’t respond to maximum antibiotic therapy.

Should these patients be treated with FMT before surgery is considered?

“Unequivocally, yes,” said Jessica R. Allegretti, MD, MPH, associate director of the Crohn’s and Colitis Center at Brigham and Women’s Hospital in Boston.
 

Patients face full colectomy

Fulminant infection, she says, typically requires a total abdominal colectomy with end ileostomy.

“Patients have a quite high perioperative and intraoperative mortality because this is typically an older population with significant comorbidities,” she said.

Often the patients are poor candidates for surgery, she added.

She pointed to the efficacy of FMT in studies such as one published in Gut Microbes in 2017. The study, by Monika Fischer, MD, of Indiana University, Indianapolis, and colleagues showed a 91% cure rate at 1 month in severe patients with an average of 1.5 fecal transplants, noting that was “quite remarkable” in this very sick population.

Though FMT is not approved by the US Food and Drug Administration for fulminant CDI, Dr. Allegretti said, the FDA does allow treatment under “enforcement discretion,” which means no investigational new drug license is needed specifically if treating CDI patients who haven’t responded to standard therapy, as long as proper consent has been obtained.

“This is a patient population that is likely going to die,” she said. “If you were the one in the ICU with fulminant C. diff and you’ve been on maximum therapy for 3-5 days and you’re not getting better, wouldn’t you want somebody to offer you a fecal transplant and give you the chance to recover and leave the hospital with your colon intact? The data suggest that is possible, with a high likelihood and a good safety profile.”

She said the most recent guidelines have supported FMT, and emerging guidelines coming within months “will support this as well.”
 

Unknowns with FMT

Taking the other side of the debate, Kevin Garey, PharmD, chair of the department of pharmacy practice and translational research at University of Houston College of Pharmacy, warned against trading traditional antibiotics, such as vancomycin and fidaxomicin, for the novelty of FMT.

“With the science of the microbiome and the novelty of fecal microbiota transplantation in expanding use, I think people have somewhat forgotten pharmacotherapy,” he said.

He pointed out safety concerns with FMT reported in June 2019, after which the FDA issued an alert. Two immunocompromised patients who received FMT, both from the same donor, developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli. One died.

The FDA explained that the donated FMT samples the patients received were not tested for ESBL-producing gram-negative organisms before use.

Dr. Allegretti agreed antibiotics play a role in treatment with FMT, but she argued that the safety profile of FMT remains strong and that the safety issues came from isolated incidents at a single center.

Dr. Garey countered that there are just too many unknowns with FMT.

“We will never know what the next superbug that’s going to land in an FMT is until we’ve identified that superbug in somebody – the next Candida auris, the next CRE [carbapenem-resistant Enterobacteriaceae], the next thing that’s going to show up in FMT – until we get rid of the ‘F,’ “ Dr. Garey said.

“[Until] we get microbial therapy that’s generated without the need for healthy donors, I think we’re always going to be in this problem.”

He said although FMT “has an amazing ability to alter a microbiome” it “pales in comparison” to vancomycin’s ability to do so.

Disruption of the microbiome is, without a doubt, a hallmark of C. diff, but we don’t have to run to FMT,” Dr. Garey said. “We can think about prophylaxis strategies, we can think about new drug development that spares the microbiota. The need for FMT might be a consequence of poor pharmacotherapy management, not a part of pharmacotherapy management.”

Moderator Sam Aitken, PharmD, MPH, a clinical pharmacy specialist in infectious disease at MD Anderson Cancer Center in Houston, said in an interview the speakers found some common ground.

“I think there was a general consensus between both Dr. Allegretti and Dr. Garey that both traditional therapeutics and fecal microbiota transplantation have a role to play in these patients, although there is still quite a bit of discussion around where those might be best positioned,” Dr. Aitken said.

He added, “There’s also a general consensus that there is not likely to be one right answer for all patients with multiple recurrent CDI.”

Dr. Allegretti, Dr. Garey, and Dr. Aitken have disclosed no relevant financial relationships.
 

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

Two experts at IDWeek 2020 debated the best treatment for patients with the most severe type of Clostridioides difficile infection – fulminant C. diff. The discussion pitted fecal microbiota transplants (FMT) from the stool of healthy donors against traditional antibiotics.

Fulminant C. diff infection (CDI) represents about 8% of all CDI cases and is often fatal. Patients frequently don’t respond to maximum antibiotic therapy.

Should these patients be treated with FMT before surgery is considered?

“Unequivocally, yes,” said Jessica R. Allegretti, MD, MPH, associate director of the Crohn’s and Colitis Center at Brigham and Women’s Hospital in Boston.
 

Patients face full colectomy

Fulminant infection, she says, typically requires a total abdominal colectomy with end ileostomy.

“Patients have a quite high perioperative and intraoperative mortality because this is typically an older population with significant comorbidities,” she said.

Often the patients are poor candidates for surgery, she added.

She pointed to the efficacy of FMT in studies such as one published in Gut Microbes in 2017. The study, by Monika Fischer, MD, of Indiana University, Indianapolis, and colleagues showed a 91% cure rate at 1 month in severe patients with an average of 1.5 fecal transplants, noting that was “quite remarkable” in this very sick population.

Though FMT is not approved by the US Food and Drug Administration for fulminant CDI, Dr. Allegretti said, the FDA does allow treatment under “enforcement discretion,” which means no investigational new drug license is needed specifically if treating CDI patients who haven’t responded to standard therapy, as long as proper consent has been obtained.

“This is a patient population that is likely going to die,” she said. “If you were the one in the ICU with fulminant C. diff and you’ve been on maximum therapy for 3-5 days and you’re not getting better, wouldn’t you want somebody to offer you a fecal transplant and give you the chance to recover and leave the hospital with your colon intact? The data suggest that is possible, with a high likelihood and a good safety profile.”

She said the most recent guidelines have supported FMT, and emerging guidelines coming within months “will support this as well.”
 

Unknowns with FMT

Taking the other side of the debate, Kevin Garey, PharmD, chair of the department of pharmacy practice and translational research at University of Houston College of Pharmacy, warned against trading traditional antibiotics, such as vancomycin and fidaxomicin, for the novelty of FMT.

“With the science of the microbiome and the novelty of fecal microbiota transplantation in expanding use, I think people have somewhat forgotten pharmacotherapy,” he said.

He pointed out safety concerns with FMT reported in June 2019, after which the FDA issued an alert. Two immunocompromised patients who received FMT, both from the same donor, developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli. One died.

The FDA explained that the donated FMT samples the patients received were not tested for ESBL-producing gram-negative organisms before use.

Dr. Allegretti agreed antibiotics play a role in treatment with FMT, but she argued that the safety profile of FMT remains strong and that the safety issues came from isolated incidents at a single center.

Dr. Garey countered that there are just too many unknowns with FMT.

“We will never know what the next superbug that’s going to land in an FMT is until we’ve identified that superbug in somebody – the next Candida auris, the next CRE [carbapenem-resistant Enterobacteriaceae], the next thing that’s going to show up in FMT – until we get rid of the ‘F,’ “ Dr. Garey said.

“[Until] we get microbial therapy that’s generated without the need for healthy donors, I think we’re always going to be in this problem.”

He said although FMT “has an amazing ability to alter a microbiome” it “pales in comparison” to vancomycin’s ability to do so.

Disruption of the microbiome is, without a doubt, a hallmark of C. diff, but we don’t have to run to FMT,” Dr. Garey said. “We can think about prophylaxis strategies, we can think about new drug development that spares the microbiota. The need for FMT might be a consequence of poor pharmacotherapy management, not a part of pharmacotherapy management.”

Moderator Sam Aitken, PharmD, MPH, a clinical pharmacy specialist in infectious disease at MD Anderson Cancer Center in Houston, said in an interview the speakers found some common ground.

“I think there was a general consensus between both Dr. Allegretti and Dr. Garey that both traditional therapeutics and fecal microbiota transplantation have a role to play in these patients, although there is still quite a bit of discussion around where those might be best positioned,” Dr. Aitken said.

He added, “There’s also a general consensus that there is not likely to be one right answer for all patients with multiple recurrent CDI.”

Dr. Allegretti, Dr. Garey, and Dr. Aitken have disclosed no relevant financial relationships.
 

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

Two experts at IDWeek 2020 debated the best treatment for patients with the most severe type of Clostridioides difficile infection – fulminant C. diff. The discussion pitted fecal microbiota transplants (FMT) from the stool of healthy donors against traditional antibiotics.

Fulminant C. diff infection (CDI) represents about 8% of all CDI cases and is often fatal. Patients frequently don’t respond to maximum antibiotic therapy.

Should these patients be treated with FMT before surgery is considered?

“Unequivocally, yes,” said Jessica R. Allegretti, MD, MPH, associate director of the Crohn’s and Colitis Center at Brigham and Women’s Hospital in Boston.
 

Patients face full colectomy

Fulminant infection, she says, typically requires a total abdominal colectomy with end ileostomy.

“Patients have a quite high perioperative and intraoperative mortality because this is typically an older population with significant comorbidities,” she said.

Often the patients are poor candidates for surgery, she added.

She pointed to the efficacy of FMT in studies such as one published in Gut Microbes in 2017. The study, by Monika Fischer, MD, of Indiana University, Indianapolis, and colleagues showed a 91% cure rate at 1 month in severe patients with an average of 1.5 fecal transplants, noting that was “quite remarkable” in this very sick population.

Though FMT is not approved by the US Food and Drug Administration for fulminant CDI, Dr. Allegretti said, the FDA does allow treatment under “enforcement discretion,” which means no investigational new drug license is needed specifically if treating CDI patients who haven’t responded to standard therapy, as long as proper consent has been obtained.

“This is a patient population that is likely going to die,” she said. “If you were the one in the ICU with fulminant C. diff and you’ve been on maximum therapy for 3-5 days and you’re not getting better, wouldn’t you want somebody to offer you a fecal transplant and give you the chance to recover and leave the hospital with your colon intact? The data suggest that is possible, with a high likelihood and a good safety profile.”

She said the most recent guidelines have supported FMT, and emerging guidelines coming within months “will support this as well.”
 

Unknowns with FMT

Taking the other side of the debate, Kevin Garey, PharmD, chair of the department of pharmacy practice and translational research at University of Houston College of Pharmacy, warned against trading traditional antibiotics, such as vancomycin and fidaxomicin, for the novelty of FMT.

“With the science of the microbiome and the novelty of fecal microbiota transplantation in expanding use, I think people have somewhat forgotten pharmacotherapy,” he said.

He pointed out safety concerns with FMT reported in June 2019, after which the FDA issued an alert. Two immunocompromised patients who received FMT, both from the same donor, developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli. One died.

The FDA explained that the donated FMT samples the patients received were not tested for ESBL-producing gram-negative organisms before use.

Dr. Allegretti agreed antibiotics play a role in treatment with FMT, but she argued that the safety profile of FMT remains strong and that the safety issues came from isolated incidents at a single center.

Dr. Garey countered that there are just too many unknowns with FMT.

“We will never know what the next superbug that’s going to land in an FMT is until we’ve identified that superbug in somebody – the next Candida auris, the next CRE [carbapenem-resistant Enterobacteriaceae], the next thing that’s going to show up in FMT – until we get rid of the ‘F,’ “ Dr. Garey said.

“[Until] we get microbial therapy that’s generated without the need for healthy donors, I think we’re always going to be in this problem.”

He said although FMT “has an amazing ability to alter a microbiome” it “pales in comparison” to vancomycin’s ability to do so.

Disruption of the microbiome is, without a doubt, a hallmark of C. diff, but we don’t have to run to FMT,” Dr. Garey said. “We can think about prophylaxis strategies, we can think about new drug development that spares the microbiota. The need for FMT might be a consequence of poor pharmacotherapy management, not a part of pharmacotherapy management.”

Moderator Sam Aitken, PharmD, MPH, a clinical pharmacy specialist in infectious disease at MD Anderson Cancer Center in Houston, said in an interview the speakers found some common ground.

“I think there was a general consensus between both Dr. Allegretti and Dr. Garey that both traditional therapeutics and fecal microbiota transplantation have a role to play in these patients, although there is still quite a bit of discussion around where those might be best positioned,” Dr. Aitken said.

He added, “There’s also a general consensus that there is not likely to be one right answer for all patients with multiple recurrent CDI.”

Dr. Allegretti, Dr. Garey, and Dr. Aitken have disclosed no relevant financial relationships.
 

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

A new formulation of an existing antibacterial agent and a potential therapeutic approach to a challenging clinical problem were the focus of a session on potentially practice-changing clinical trials in antimicrobial therapy presented during IDWeek 2020, an annual scientific meeting on infectious diseases.

“I know it has been a big year for viral disease of course, with COVID, but there has been some really good work that has gone on in the bacterial space, and of course as those of you who are on service know, you may have your fair share of COVID patients, but these are infections that we still deal with on a daily basis,” said Michael Satlin, MD, an infectious disease specialist at Weill Cornell Medicine in New York.

He combed through studies published during the previous 12 months in leading medical journals, including the New England Journal of Medicine, JAMA network publications, Lancet Infectious Diseases, Lancet Respiratory Medicine, Clinical Infectious Diseases, and Clinical Microbiology and Infection, looking for randomized trials of interventions to treat bacterial infections, and selecting those most likely to change practice of U.S. infectious diseases practitioners.

He excluded meta-analyses, post hoc analyses, evaluations of diagnostic tests, stewardship, or any studies presented previously at IDWeek.

Two of the trials he highlighted are described here.
 

Fosfomycin for injection

In the United States, fosfomycin, the only antibiotic in its class, is currently available only in an oral sachet formulation (Monurol), “and typically we’ve only given this for patients with cystitis because we know that we don’t achieve significant levels [of drug] in the kidney or in the bloodstream for other types of infections,” Dr. Satlin said.

In Europe, however fosfomycin for injection (ZTI-01) has been available for several years.

“There’s been a lot of interest in fosfomycin because it has a different mechanism of action from other agents. It’s an epoxide antibiotic that inhibits early peptidoglycan synthesis by binding to MurA,” he explained.

The phase 2/3 randomized ZEUS trial compared ZTI-01 with piperacillin/tazobactam (pip/taz) for treatment of complicated urinary tract infection (UTI) including acute pyelonephritis.

A total of 465 hospitalized adults with suspected or microbiologically confirmed complicated UTI or acute pyelonephritis were randomized to 6 g of ZTI-01 every 8 hours or 4.5 g of intravenous pip/taz every 8 hours for a fixed 7-day course with no oral switch; patients with concomitant bacteremia (about 9% of the study population) could receive the assigned therapy for up to 14 days.

The primary endpoint of noninferiority of ZTI-01 was met and clinical cure rates were high and similar between the treatments, at approximately 91% each. Treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mostly mild and transient.

The hypokalemia seen in the trial may be attributable to the high salt load of fosfomycin relative to pip/taz, Dr. Satlin said.

“How might this change your practice? Well, if IV fosfomycin is ever FDA [Food and Drug Administration] approved – and my understanding is that the delays have been more related to manufacturing than scientific quality of data – it could potentially be an alternative to beta-lactams and fluoroquinolones” and has activity against most extend spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae, he said.

Fosfomycin susceptibility testing is challenging, however, with no Clinical & Laboratory Standards Institute (CLSI) or FDA breakpoints for Enterobacterales other than Escherichia coli, and there are questions about the step-down therapy.

“Do you just give a 3-gram sachet chaser when they walk out the door? Do you switch to another agent? I think that needs to be worked out,” he said.
 

Inhaled amikacin

“We know that some IV antibiotics, particularly for resistant organisms, may not achieve sufficient concentrations in the lung to treat pneumonia. We know that inhaled antibiotics can give a lot of concentration of that drug right at the at the site of infection, but we don’t really have [randomized controlled trial] data to see whether it really helps,” Dr. Satlin said.

The INHALE trial was a double-blind, placebo-controlled superiority trial to see whether adding inhaled amikacin to IV standard-of-care antibiotics could improve outcomes for mechanically ventilated patients with gram-negative pneumonia.

The investigators enrolled 725 adults who were receiving mechanical ventilation for pneumonia, 45% of who had ventilator-associated pneumonia (VAP). Of the total cohort, 508 patients analyzed for efficacy had gram-negative pathogens, including 32% with Pseudomonas aeurginosa, 29% with Acinetobacter baumannii, 30% with E. coli, and the remainder with Klebsiella pneumoniae.

Patients were randomized to standard-of-care intravenous antibiotics plus either inhaled amikacin 400 mg twice daily for 10 days or inhaled saline placebo.

“Of note, the median standard-of-care antibiotics in this study was 18 days, which is certainly longer than what our guidelines recommend.”

There was no significant difference between study arms in the primary endpoint of survival at days 28-32 for all patients who had received at least one dose of study drug, were infected with a gram-negative pathogen, and an Acute Physiology and Chronic Health Evaluation (APACHE) II score of at 10 or higher at diagnosis. The respective survival rates for the inhaled amikacin and placebo groups were 75% and 77%. The incidence of treatment-emergent adverse events or serious treatment-emergent adverse events were similar between the two treatment arms.

“No matter how you sliced and diced it – days of mechanical ventilation, duration of ICU stay – essentially they looked the same. Even for [extensively drug resistant] pathogens where you might expect that you’d see the benefit of inhaled amikacin, they didn’t really see a mortality benefit in this study,” Dr. Satlin said.

The study is practice changing, he said “because I think inhaled aminoglycosides should not be routinely added to the standard of care IV antibiotics for pneumonia in ventilated patients,” he said.

It’s still unclear whether inhaled aminoglycosides might play a role in the treatment of select patients infected with organisms resistant to all beta-lactams and fluoroquinolones, he added.
 

Tempting strategy

“Adding inhaled antibiotics is a tempting strategy for treatment of ventilated pneumonia, which often has poor outcomes,” commented Thomas Holland, MD, a hospitalist and infectious disease specialist at Duke University Hospital in Durham, N.C. “This is valuable and practical information as clinicians choose antibiotics regimens for this difficult-to-treat syndrome,” he said in an interview.

Dr. Holland comoderated the session in which Dr. Satlin presented the study findings and opinions.

No funding source for the presentation was reported. Dr. Satlin reported consulting for Shionogi and Achaogen and research grants from Allergan, Merck, and BioFire Diagnostics. Dr. Holland disclosed consulting fees and other material support from Basilea Pharmaceutica, Genetech, Karius and Theravance.

A new formulation of an existing antibacterial agent and a potential therapeutic approach to a challenging clinical problem were the focus of a session on potentially practice-changing clinical trials in antimicrobial therapy presented during IDWeek 2020, an annual scientific meeting on infectious diseases.

“I know it has been a big year for viral disease of course, with COVID, but there has been some really good work that has gone on in the bacterial space, and of course as those of you who are on service know, you may have your fair share of COVID patients, but these are infections that we still deal with on a daily basis,” said Michael Satlin, MD, an infectious disease specialist at Weill Cornell Medicine in New York.

He combed through studies published during the previous 12 months in leading medical journals, including the New England Journal of Medicine, JAMA network publications, Lancet Infectious Diseases, Lancet Respiratory Medicine, Clinical Infectious Diseases, and Clinical Microbiology and Infection, looking for randomized trials of interventions to treat bacterial infections, and selecting those most likely to change practice of U.S. infectious diseases practitioners.

He excluded meta-analyses, post hoc analyses, evaluations of diagnostic tests, stewardship, or any studies presented previously at IDWeek.

Two of the trials he highlighted are described here.
 

Fosfomycin for injection

In the United States, fosfomycin, the only antibiotic in its class, is currently available only in an oral sachet formulation (Monurol), “and typically we’ve only given this for patients with cystitis because we know that we don’t achieve significant levels [of drug] in the kidney or in the bloodstream for other types of infections,” Dr. Satlin said.

In Europe, however fosfomycin for injection (ZTI-01) has been available for several years.

“There’s been a lot of interest in fosfomycin because it has a different mechanism of action from other agents. It’s an epoxide antibiotic that inhibits early peptidoglycan synthesis by binding to MurA,” he explained.

The phase 2/3 randomized ZEUS trial compared ZTI-01 with piperacillin/tazobactam (pip/taz) for treatment of complicated urinary tract infection (UTI) including acute pyelonephritis.

A total of 465 hospitalized adults with suspected or microbiologically confirmed complicated UTI or acute pyelonephritis were randomized to 6 g of ZTI-01 every 8 hours or 4.5 g of intravenous pip/taz every 8 hours for a fixed 7-day course with no oral switch; patients with concomitant bacteremia (about 9% of the study population) could receive the assigned therapy for up to 14 days.

The primary endpoint of noninferiority of ZTI-01 was met and clinical cure rates were high and similar between the treatments, at approximately 91% each. Treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mostly mild and transient.

The hypokalemia seen in the trial may be attributable to the high salt load of fosfomycin relative to pip/taz, Dr. Satlin said.

“How might this change your practice? Well, if IV fosfomycin is ever FDA [Food and Drug Administration] approved – and my understanding is that the delays have been more related to manufacturing than scientific quality of data – it could potentially be an alternative to beta-lactams and fluoroquinolones” and has activity against most extend spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae, he said.

Fosfomycin susceptibility testing is challenging, however, with no Clinical & Laboratory Standards Institute (CLSI) or FDA breakpoints for Enterobacterales other than Escherichia coli, and there are questions about the step-down therapy.

“Do you just give a 3-gram sachet chaser when they walk out the door? Do you switch to another agent? I think that needs to be worked out,” he said.
 

Inhaled amikacin

“We know that some IV antibiotics, particularly for resistant organisms, may not achieve sufficient concentrations in the lung to treat pneumonia. We know that inhaled antibiotics can give a lot of concentration of that drug right at the at the site of infection, but we don’t really have [randomized controlled trial] data to see whether it really helps,” Dr. Satlin said.

The INHALE trial was a double-blind, placebo-controlled superiority trial to see whether adding inhaled amikacin to IV standard-of-care antibiotics could improve outcomes for mechanically ventilated patients with gram-negative pneumonia.

The investigators enrolled 725 adults who were receiving mechanical ventilation for pneumonia, 45% of who had ventilator-associated pneumonia (VAP). Of the total cohort, 508 patients analyzed for efficacy had gram-negative pathogens, including 32% with Pseudomonas aeurginosa, 29% with Acinetobacter baumannii, 30% with E. coli, and the remainder with Klebsiella pneumoniae.

Patients were randomized to standard-of-care intravenous antibiotics plus either inhaled amikacin 400 mg twice daily for 10 days or inhaled saline placebo.

“Of note, the median standard-of-care antibiotics in this study was 18 days, which is certainly longer than what our guidelines recommend.”

There was no significant difference between study arms in the primary endpoint of survival at days 28-32 for all patients who had received at least one dose of study drug, were infected with a gram-negative pathogen, and an Acute Physiology and Chronic Health Evaluation (APACHE) II score of at 10 or higher at diagnosis. The respective survival rates for the inhaled amikacin and placebo groups were 75% and 77%. The incidence of treatment-emergent adverse events or serious treatment-emergent adverse events were similar between the two treatment arms.

“No matter how you sliced and diced it – days of mechanical ventilation, duration of ICU stay – essentially they looked the same. Even for [extensively drug resistant] pathogens where you might expect that you’d see the benefit of inhaled amikacin, they didn’t really see a mortality benefit in this study,” Dr. Satlin said.

The study is practice changing, he said “because I think inhaled aminoglycosides should not be routinely added to the standard of care IV antibiotics for pneumonia in ventilated patients,” he said.

It’s still unclear whether inhaled aminoglycosides might play a role in the treatment of select patients infected with organisms resistant to all beta-lactams and fluoroquinolones, he added.
 

Tempting strategy

“Adding inhaled antibiotics is a tempting strategy for treatment of ventilated pneumonia, which often has poor outcomes,” commented Thomas Holland, MD, a hospitalist and infectious disease specialist at Duke University Hospital in Durham, N.C. “This is valuable and practical information as clinicians choose antibiotics regimens for this difficult-to-treat syndrome,” he said in an interview.

Dr. Holland comoderated the session in which Dr. Satlin presented the study findings and opinions.

No funding source for the presentation was reported. Dr. Satlin reported consulting for Shionogi and Achaogen and research grants from Allergan, Merck, and BioFire Diagnostics. Dr. Holland disclosed consulting fees and other material support from Basilea Pharmaceutica, Genetech, Karius and Theravance.

A new formulation of an existing antibacterial agent and a potential therapeutic approach to a challenging clinical problem were the focus of a session on potentially practice-changing clinical trials in antimicrobial therapy presented during IDWeek 2020, an annual scientific meeting on infectious diseases.

“I know it has been a big year for viral disease of course, with COVID, but there has been some really good work that has gone on in the bacterial space, and of course as those of you who are on service know, you may have your fair share of COVID patients, but these are infections that we still deal with on a daily basis,” said Michael Satlin, MD, an infectious disease specialist at Weill Cornell Medicine in New York.

He combed through studies published during the previous 12 months in leading medical journals, including the New England Journal of Medicine, JAMA network publications, Lancet Infectious Diseases, Lancet Respiratory Medicine, Clinical Infectious Diseases, and Clinical Microbiology and Infection, looking for randomized trials of interventions to treat bacterial infections, and selecting those most likely to change practice of U.S. infectious diseases practitioners.

He excluded meta-analyses, post hoc analyses, evaluations of diagnostic tests, stewardship, or any studies presented previously at IDWeek.

Two of the trials he highlighted are described here.
 

Fosfomycin for injection

In the United States, fosfomycin, the only antibiotic in its class, is currently available only in an oral sachet formulation (Monurol), “and typically we’ve only given this for patients with cystitis because we know that we don’t achieve significant levels [of drug] in the kidney or in the bloodstream for other types of infections,” Dr. Satlin said.

In Europe, however fosfomycin for injection (ZTI-01) has been available for several years.

“There’s been a lot of interest in fosfomycin because it has a different mechanism of action from other agents. It’s an epoxide antibiotic that inhibits early peptidoglycan synthesis by binding to MurA,” he explained.

The phase 2/3 randomized ZEUS trial compared ZTI-01 with piperacillin/tazobactam (pip/taz) for treatment of complicated urinary tract infection (UTI) including acute pyelonephritis.

A total of 465 hospitalized adults with suspected or microbiologically confirmed complicated UTI or acute pyelonephritis were randomized to 6 g of ZTI-01 every 8 hours or 4.5 g of intravenous pip/taz every 8 hours for a fixed 7-day course with no oral switch; patients with concomitant bacteremia (about 9% of the study population) could receive the assigned therapy for up to 14 days.

The primary endpoint of noninferiority of ZTI-01 was met and clinical cure rates were high and similar between the treatments, at approximately 91% each. Treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mostly mild and transient.

The hypokalemia seen in the trial may be attributable to the high salt load of fosfomycin relative to pip/taz, Dr. Satlin said.

“How might this change your practice? Well, if IV fosfomycin is ever FDA [Food and Drug Administration] approved – and my understanding is that the delays have been more related to manufacturing than scientific quality of data – it could potentially be an alternative to beta-lactams and fluoroquinolones” and has activity against most extend spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae, he said.

Fosfomycin susceptibility testing is challenging, however, with no Clinical & Laboratory Standards Institute (CLSI) or FDA breakpoints for Enterobacterales other than Escherichia coli, and there are questions about the step-down therapy.

“Do you just give a 3-gram sachet chaser when they walk out the door? Do you switch to another agent? I think that needs to be worked out,” he said.
 

Inhaled amikacin

“We know that some IV antibiotics, particularly for resistant organisms, may not achieve sufficient concentrations in the lung to treat pneumonia. We know that inhaled antibiotics can give a lot of concentration of that drug right at the at the site of infection, but we don’t really have [randomized controlled trial] data to see whether it really helps,” Dr. Satlin said.

The INHALE trial was a double-blind, placebo-controlled superiority trial to see whether adding inhaled amikacin to IV standard-of-care antibiotics could improve outcomes for mechanically ventilated patients with gram-negative pneumonia.

The investigators enrolled 725 adults who were receiving mechanical ventilation for pneumonia, 45% of who had ventilator-associated pneumonia (VAP). Of the total cohort, 508 patients analyzed for efficacy had gram-negative pathogens, including 32% with Pseudomonas aeurginosa, 29% with Acinetobacter baumannii, 30% with E. coli, and the remainder with Klebsiella pneumoniae.

Patients were randomized to standard-of-care intravenous antibiotics plus either inhaled amikacin 400 mg twice daily for 10 days or inhaled saline placebo.

“Of note, the median standard-of-care antibiotics in this study was 18 days, which is certainly longer than what our guidelines recommend.”

There was no significant difference between study arms in the primary endpoint of survival at days 28-32 for all patients who had received at least one dose of study drug, were infected with a gram-negative pathogen, and an Acute Physiology and Chronic Health Evaluation (APACHE) II score of at 10 or higher at diagnosis. The respective survival rates for the inhaled amikacin and placebo groups were 75% and 77%. The incidence of treatment-emergent adverse events or serious treatment-emergent adverse events were similar between the two treatment arms.

“No matter how you sliced and diced it – days of mechanical ventilation, duration of ICU stay – essentially they looked the same. Even for [extensively drug resistant] pathogens where you might expect that you’d see the benefit of inhaled amikacin, they didn’t really see a mortality benefit in this study,” Dr. Satlin said.

The study is practice changing, he said “because I think inhaled aminoglycosides should not be routinely added to the standard of care IV antibiotics for pneumonia in ventilated patients,” he said.

It’s still unclear whether inhaled aminoglycosides might play a role in the treatment of select patients infected with organisms resistant to all beta-lactams and fluoroquinolones, he added.
 

Tempting strategy

“Adding inhaled antibiotics is a tempting strategy for treatment of ventilated pneumonia, which often has poor outcomes,” commented Thomas Holland, MD, a hospitalist and infectious disease specialist at Duke University Hospital in Durham, N.C. “This is valuable and practical information as clinicians choose antibiotics regimens for this difficult-to-treat syndrome,” he said in an interview.

Dr. Holland comoderated the session in which Dr. Satlin presented the study findings and opinions.

No funding source for the presentation was reported. Dr. Satlin reported consulting for Shionogi and Achaogen and research grants from Allergan, Merck, and BioFire Diagnostics. Dr. Holland disclosed consulting fees and other material support from Basilea Pharmaceutica, Genetech, Karius and Theravance.

Tocilizumab (Actemra/RoActemra) was not found to have any clear role as a treatment for COVID-19 in four new studies.

Three randomized controlled trials showed that the drug either had no benefit or only a modest one, contradicting a large retrospective study that had hinted at a more robust effect.

“This is not a blockbuster,” said David Cennimo, MD, an infectious disease expert at Rutgers New Jersey Medical School, Newark, New Jersey. “This is not something that’s going to revolutionize our treatment of COVID-19.”

But some researchers still regard these studies as showing evidence that the drug benefits certain patients with severe inflammation.

The immune response to SARS-CoV-2 includes elevated levels of the cytokine interleukin-6 (IL-6). In some patients, this response becomes a nonspecific inflammation, a “cytokine storm,” involving edema and inflammatory cell infiltration in the lungs. These cases are among the most severe.

Dexamethasone has proved effective in controlling this inflammation in some patients. Researchers have theorized that a more targeted suppression of IL-6 could be even more effective or work in cases that don’t respond to dexamethasone.

A recombinant monoclonal antibody, tocilizumab blocks IL-6 receptors. It is approved by the US Food and Drug Administration for use in patients with rheumatologic disorders and cytokine release syndrome induced by chimeric antigen receptor T-cell therapy.

Current National Institutes of Health (NIH) guidelines recommend against the use of tocilizumab as a treatment for COVID-19, despite earlier observational studies that suggested the drug might help patients with moderate to severe disease. Controlled trials were lacking until now.

The most hopeful results in this batch came from the CORIMUNO-19 platform of open-label, randomized controlled trials of immune modulatory treatments for moderate or severe COVID-19 in France.

Published in JAMA Internal Medicine , the trial recruited patients from nine French hospitals. Patients were eligible if they required at least 3 L/min of oxygen without ventilation or admission to the intensive care unit.

The investigators randomly assigned 64 patients to receive tocilizumab 8 mg/kg body weight intravenously plus usual care and 67 patients to usual care alone. Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants.

After 4 days, the investigators scored patients on the World Health Organization 10-point Clinical Progression Scale. Twelve of the patients who received tocilizumab scored higher than 5 vs 19 of the patients in the usual care group, with higher scores indicating clinical deterioration.

After 14 days, 24% of the patients taking tocilizumab required either noninvasive ventilation or mechanical ventilation or had died, vs 36% in the usual care group (median posterior hazard ratio [HR], 0.58; 90% credible interval, 0.33 – 1.00).

“We reduced the risk of dying or requiring mechanical ventilation, so for me, the study was positive,” said Olivier Hermine, MD, PhD, a professor of hematology at Paris Descartes University in Paris, France.

However, there was no difference in mortality at 28 days. Hermine hopes to have longer-term outcomes soon, he told Medscape Medical News.

A second randomized controlled trial, also published in JAMA Internal Medicine , provided less hope. In this RCT-TCZ-COVID-19 Study Group trial, conducted at 24 Italian centers, patients were enrolled if their partial pressure of arterial oxygen to fraction of inspired oxygen (PaO₂/FiO₂) ratios were between 200 and 300 mm Hg and if their inflammatory phenotypes were defined by fever and elevated C-reactive protein level.

The investigators randomly assigned 60 patients to receive tocilizumab 8 mg/kg up to a maximum of 800 mg within 8 hours of randomization, followed by a second dose after 12 hours. They assigned 66 patients to a control group that received supportive care until clinical worsening, at which point patients could receive tocilizumab as a rescue therapy.

Of the patients who received tocilizumab, 28.3% showed clinical worsening within 14 days, compared to 27.0% in the control group (rate ratio, 1.05; 95% CI, 0.59 – 1.86). There was no significant difference between the groups in terms of the proportion admitted to intensive care. The researchers stopped the trial prematurely because tocilizumab did not seem to be making a difference.

The BACC Bay Tocilizumab Trial was conducted at seven Boston hospitals. The results, which were published in The New England Journal of Medicine, were also discouraging.

In that trial, enrolled patients met two sets of parameters. First, the patients had at least one of the following signs: C-reactive protein level higher than 50 mg/L, ferritin level higher than 500 ng/mL, D-dimer level higher than 1000 ng/mL, or a lactate dehydrogenase level higher than 250 U/L. Second, the patients had to have at least two of the following signs: body temperature >38° C, pulmonary infiltrates, or the need for supplemental oxygen to maintain an oxygen saturation greater than 92%.

The investigators randomly assigned 161 patients to receive intravenous tocilizumab 8 mg/kg up to 800 mg and 81 to receive a placebo.

They didn’t find a statistically significant difference between the groups. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% CI, 0.38 – 1.81; P = .64). The hazard ratio for disease worsening was 1.11 (95% CI, 0.59 – 2.10; P = .73). At 14 days, the conditions of 18.0% of the patients who received tocilizumab and 14.9% of the patients who received the placebo worsened.

In contrast to these randomized trials, STOP-COVID, a retrospective analysis of 3924 patients, also published in JAMA Internal Medicine, found that the risk for death was lower for patients treated with tocilizumab compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56 – 0.92) over a median follow-up period of 27 days.

Also on the bright side, none of the new studies showed significant adverse reactions to tocilizumab.

More randomized clinical trials are underway. In press releases announcing topline data, Roche reported mostly negative results in its phase 3 COVACTA trial but noted a 44% reduction in the risk for progression to death or ventilation in its phase 3 IMPACTA trial. Roche did not comment on the ethnicity of its COVACTA patients; it said IMPACTA enrolled a majority of Hispanic patients and included large representations of Native American and Black patients.
 

Results don’t support routine use

Commenting on the new studies, editorialists in both JAMA Internal Medicine and The New England Journal of Medicine concluded that the tocilizumab results were not strong enough to support routine use.

“My take-home point from looking at all of these together is that, even if it does help, it’s most likely in a small subset of the population and/or a small effect,” Cennimo told Medscape Medical News.

But the NIH recommendation against tocilizumab goes too far, argued Cristina Mussini, MD, a professor of infectious diseases at the University of Modena and Reggio Emilia in Italy, who is a coauthor of a cohort study of tocilizumab and served on the CORIMUNO-19 Data Safety and Monitoring Board.

“I really think it’s too early to recommend against it because at least two clinical trials showed protection against mechanical ventilation and death,” she said.

She prescribes tocilizumab for patients who have not been helped by dexamethasone. “It’s just a rescue drug,” she told Medscape Medical News. “It’s not something you use for everybody, but it’s the only weapon we have now when the patient is really going to the intensive care unit.”

The BACC Bay Tocilizumab Trial was funded by Genentech/Roche. Genentech/Roche provided the drug for the CORIMUNO and RCT-TCZ-COVID-19 trials. The STOP-COVID study was supported by grants from the NIH and by the Frankel Cardiovascular Center COVID-19: Impact Research Ignitor. Cennimo, Hermine, and Mussini have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Tocilizumab (Actemra/RoActemra) was not found to have any clear role as a treatment for COVID-19 in four new studies.

Three randomized controlled trials showed that the drug either had no benefit or only a modest one, contradicting a large retrospective study that had hinted at a more robust effect.

“This is not a blockbuster,” said David Cennimo, MD, an infectious disease expert at Rutgers New Jersey Medical School, Newark, New Jersey. “This is not something that’s going to revolutionize our treatment of COVID-19.”

But some researchers still regard these studies as showing evidence that the drug benefits certain patients with severe inflammation.

The immune response to SARS-CoV-2 includes elevated levels of the cytokine interleukin-6 (IL-6). In some patients, this response becomes a nonspecific inflammation, a “cytokine storm,” involving edema and inflammatory cell infiltration in the lungs. These cases are among the most severe.

Dexamethasone has proved effective in controlling this inflammation in some patients. Researchers have theorized that a more targeted suppression of IL-6 could be even more effective or work in cases that don’t respond to dexamethasone.

A recombinant monoclonal antibody, tocilizumab blocks IL-6 receptors. It is approved by the US Food and Drug Administration for use in patients with rheumatologic disorders and cytokine release syndrome induced by chimeric antigen receptor T-cell therapy.

Current National Institutes of Health (NIH) guidelines recommend against the use of tocilizumab as a treatment for COVID-19, despite earlier observational studies that suggested the drug might help patients with moderate to severe disease. Controlled trials were lacking until now.

The most hopeful results in this batch came from the CORIMUNO-19 platform of open-label, randomized controlled trials of immune modulatory treatments for moderate or severe COVID-19 in France.

Published in JAMA Internal Medicine , the trial recruited patients from nine French hospitals. Patients were eligible if they required at least 3 L/min of oxygen without ventilation or admission to the intensive care unit.

The investigators randomly assigned 64 patients to receive tocilizumab 8 mg/kg body weight intravenously plus usual care and 67 patients to usual care alone. Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants.

After 4 days, the investigators scored patients on the World Health Organization 10-point Clinical Progression Scale. Twelve of the patients who received tocilizumab scored higher than 5 vs 19 of the patients in the usual care group, with higher scores indicating clinical deterioration.

After 14 days, 24% of the patients taking tocilizumab required either noninvasive ventilation or mechanical ventilation or had died, vs 36% in the usual care group (median posterior hazard ratio [HR], 0.58; 90% credible interval, 0.33 – 1.00).

“We reduced the risk of dying or requiring mechanical ventilation, so for me, the study was positive,” said Olivier Hermine, MD, PhD, a professor of hematology at Paris Descartes University in Paris, France.

However, there was no difference in mortality at 28 days. Hermine hopes to have longer-term outcomes soon, he told Medscape Medical News.

A second randomized controlled trial, also published in JAMA Internal Medicine , provided less hope. In this RCT-TCZ-COVID-19 Study Group trial, conducted at 24 Italian centers, patients were enrolled if their partial pressure of arterial oxygen to fraction of inspired oxygen (PaO₂/FiO₂) ratios were between 200 and 300 mm Hg and if their inflammatory phenotypes were defined by fever and elevated C-reactive protein level.

The investigators randomly assigned 60 patients to receive tocilizumab 8 mg/kg up to a maximum of 800 mg within 8 hours of randomization, followed by a second dose after 12 hours. They assigned 66 patients to a control group that received supportive care until clinical worsening, at which point patients could receive tocilizumab as a rescue therapy.

Of the patients who received tocilizumab, 28.3% showed clinical worsening within 14 days, compared to 27.0% in the control group (rate ratio, 1.05; 95% CI, 0.59 – 1.86). There was no significant difference between the groups in terms of the proportion admitted to intensive care. The researchers stopped the trial prematurely because tocilizumab did not seem to be making a difference.

The BACC Bay Tocilizumab Trial was conducted at seven Boston hospitals. The results, which were published in The New England Journal of Medicine, were also discouraging.

In that trial, enrolled patients met two sets of parameters. First, the patients had at least one of the following signs: C-reactive protein level higher than 50 mg/L, ferritin level higher than 500 ng/mL, D-dimer level higher than 1000 ng/mL, or a lactate dehydrogenase level higher than 250 U/L. Second, the patients had to have at least two of the following signs: body temperature >38° C, pulmonary infiltrates, or the need for supplemental oxygen to maintain an oxygen saturation greater than 92%.

The investigators randomly assigned 161 patients to receive intravenous tocilizumab 8 mg/kg up to 800 mg and 81 to receive a placebo.

They didn’t find a statistically significant difference between the groups. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% CI, 0.38 – 1.81; P = .64). The hazard ratio for disease worsening was 1.11 (95% CI, 0.59 – 2.10; P = .73). At 14 days, the conditions of 18.0% of the patients who received tocilizumab and 14.9% of the patients who received the placebo worsened.

In contrast to these randomized trials, STOP-COVID, a retrospective analysis of 3924 patients, also published in JAMA Internal Medicine, found that the risk for death was lower for patients treated with tocilizumab compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56 – 0.92) over a median follow-up period of 27 days.

Also on the bright side, none of the new studies showed significant adverse reactions to tocilizumab.

More randomized clinical trials are underway. In press releases announcing topline data, Roche reported mostly negative results in its phase 3 COVACTA trial but noted a 44% reduction in the risk for progression to death or ventilation in its phase 3 IMPACTA trial. Roche did not comment on the ethnicity of its COVACTA patients; it said IMPACTA enrolled a majority of Hispanic patients and included large representations of Native American and Black patients.
 

Results don’t support routine use

Commenting on the new studies, editorialists in both JAMA Internal Medicine and The New England Journal of Medicine concluded that the tocilizumab results were not strong enough to support routine use.

“My take-home point from looking at all of these together is that, even if it does help, it’s most likely in a small subset of the population and/or a small effect,” Cennimo told Medscape Medical News.

But the NIH recommendation against tocilizumab goes too far, argued Cristina Mussini, MD, a professor of infectious diseases at the University of Modena and Reggio Emilia in Italy, who is a coauthor of a cohort study of tocilizumab and served on the CORIMUNO-19 Data Safety and Monitoring Board.

“I really think it’s too early to recommend against it because at least two clinical trials showed protection against mechanical ventilation and death,” she said.

She prescribes tocilizumab for patients who have not been helped by dexamethasone. “It’s just a rescue drug,” she told Medscape Medical News. “It’s not something you use for everybody, but it’s the only weapon we have now when the patient is really going to the intensive care unit.”

The BACC Bay Tocilizumab Trial was funded by Genentech/Roche. Genentech/Roche provided the drug for the CORIMUNO and RCT-TCZ-COVID-19 trials. The STOP-COVID study was supported by grants from the NIH and by the Frankel Cardiovascular Center COVID-19: Impact Research Ignitor. Cennimo, Hermine, and Mussini have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Tocilizumab (Actemra/RoActemra) was not found to have any clear role as a treatment for COVID-19 in four new studies.

Three randomized controlled trials showed that the drug either had no benefit or only a modest one, contradicting a large retrospective study that had hinted at a more robust effect.

“This is not a blockbuster,” said David Cennimo, MD, an infectious disease expert at Rutgers New Jersey Medical School, Newark, New Jersey. “This is not something that’s going to revolutionize our treatment of COVID-19.”

But some researchers still regard these studies as showing evidence that the drug benefits certain patients with severe inflammation.

The immune response to SARS-CoV-2 includes elevated levels of the cytokine interleukin-6 (IL-6). In some patients, this response becomes a nonspecific inflammation, a “cytokine storm,” involving edema and inflammatory cell infiltration in the lungs. These cases are among the most severe.

Dexamethasone has proved effective in controlling this inflammation in some patients. Researchers have theorized that a more targeted suppression of IL-6 could be even more effective or work in cases that don’t respond to dexamethasone.

A recombinant monoclonal antibody, tocilizumab blocks IL-6 receptors. It is approved by the US Food and Drug Administration for use in patients with rheumatologic disorders and cytokine release syndrome induced by chimeric antigen receptor T-cell therapy.

Current National Institutes of Health (NIH) guidelines recommend against the use of tocilizumab as a treatment for COVID-19, despite earlier observational studies that suggested the drug might help patients with moderate to severe disease. Controlled trials were lacking until now.

The most hopeful results in this batch came from the CORIMUNO-19 platform of open-label, randomized controlled trials of immune modulatory treatments for moderate or severe COVID-19 in France.

Published in JAMA Internal Medicine , the trial recruited patients from nine French hospitals. Patients were eligible if they required at least 3 L/min of oxygen without ventilation or admission to the intensive care unit.

The investigators randomly assigned 64 patients to receive tocilizumab 8 mg/kg body weight intravenously plus usual care and 67 patients to usual care alone. Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants.

After 4 days, the investigators scored patients on the World Health Organization 10-point Clinical Progression Scale. Twelve of the patients who received tocilizumab scored higher than 5 vs 19 of the patients in the usual care group, with higher scores indicating clinical deterioration.

After 14 days, 24% of the patients taking tocilizumab required either noninvasive ventilation or mechanical ventilation or had died, vs 36% in the usual care group (median posterior hazard ratio [HR], 0.58; 90% credible interval, 0.33 – 1.00).

“We reduced the risk of dying or requiring mechanical ventilation, so for me, the study was positive,” said Olivier Hermine, MD, PhD, a professor of hematology at Paris Descartes University in Paris, France.

However, there was no difference in mortality at 28 days. Hermine hopes to have longer-term outcomes soon, he told Medscape Medical News.

A second randomized controlled trial, also published in JAMA Internal Medicine , provided less hope. In this RCT-TCZ-COVID-19 Study Group trial, conducted at 24 Italian centers, patients were enrolled if their partial pressure of arterial oxygen to fraction of inspired oxygen (PaO₂/FiO₂) ratios were between 200 and 300 mm Hg and if their inflammatory phenotypes were defined by fever and elevated C-reactive protein level.

The investigators randomly assigned 60 patients to receive tocilizumab 8 mg/kg up to a maximum of 800 mg within 8 hours of randomization, followed by a second dose after 12 hours. They assigned 66 patients to a control group that received supportive care until clinical worsening, at which point patients could receive tocilizumab as a rescue therapy.

Of the patients who received tocilizumab, 28.3% showed clinical worsening within 14 days, compared to 27.0% in the control group (rate ratio, 1.05; 95% CI, 0.59 – 1.86). There was no significant difference between the groups in terms of the proportion admitted to intensive care. The researchers stopped the trial prematurely because tocilizumab did not seem to be making a difference.

The BACC Bay Tocilizumab Trial was conducted at seven Boston hospitals. The results, which were published in The New England Journal of Medicine, were also discouraging.

In that trial, enrolled patients met two sets of parameters. First, the patients had at least one of the following signs: C-reactive protein level higher than 50 mg/L, ferritin level higher than 500 ng/mL, D-dimer level higher than 1000 ng/mL, or a lactate dehydrogenase level higher than 250 U/L. Second, the patients had to have at least two of the following signs: body temperature >38° C, pulmonary infiltrates, or the need for supplemental oxygen to maintain an oxygen saturation greater than 92%.

The investigators randomly assigned 161 patients to receive intravenous tocilizumab 8 mg/kg up to 800 mg and 81 to receive a placebo.

They didn’t find a statistically significant difference between the groups. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% CI, 0.38 – 1.81; P = .64). The hazard ratio for disease worsening was 1.11 (95% CI, 0.59 – 2.10; P = .73). At 14 days, the conditions of 18.0% of the patients who received tocilizumab and 14.9% of the patients who received the placebo worsened.

In contrast to these randomized trials, STOP-COVID, a retrospective analysis of 3924 patients, also published in JAMA Internal Medicine, found that the risk for death was lower for patients treated with tocilizumab compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56 – 0.92) over a median follow-up period of 27 days.

Also on the bright side, none of the new studies showed significant adverse reactions to tocilizumab.

More randomized clinical trials are underway. In press releases announcing topline data, Roche reported mostly negative results in its phase 3 COVACTA trial but noted a 44% reduction in the risk for progression to death or ventilation in its phase 3 IMPACTA trial. Roche did not comment on the ethnicity of its COVACTA patients; it said IMPACTA enrolled a majority of Hispanic patients and included large representations of Native American and Black patients.
 

Results don’t support routine use

Commenting on the new studies, editorialists in both JAMA Internal Medicine and The New England Journal of Medicine concluded that the tocilizumab results were not strong enough to support routine use.

“My take-home point from looking at all of these together is that, even if it does help, it’s most likely in a small subset of the population and/or a small effect,” Cennimo told Medscape Medical News.

But the NIH recommendation against tocilizumab goes too far, argued Cristina Mussini, MD, a professor of infectious diseases at the University of Modena and Reggio Emilia in Italy, who is a coauthor of a cohort study of tocilizumab and served on the CORIMUNO-19 Data Safety and Monitoring Board.

“I really think it’s too early to recommend against it because at least two clinical trials showed protection against mechanical ventilation and death,” she said.

She prescribes tocilizumab for patients who have not been helped by dexamethasone. “It’s just a rescue drug,” she told Medscape Medical News. “It’s not something you use for everybody, but it’s the only weapon we have now when the patient is really going to the intensive care unit.”

The BACC Bay Tocilizumab Trial was funded by Genentech/Roche. Genentech/Roche provided the drug for the CORIMUNO and RCT-TCZ-COVID-19 trials. The STOP-COVID study was supported by grants from the NIH and by the Frankel Cardiovascular Center COVID-19: Impact Research Ignitor. Cennimo, Hermine, and Mussini have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Eli Lilly announced it will halt its ACTIV-3 trial evaluating the antibody bamlanivimab in combination with remdesivir for people hospitalized with COVID-19, after new evidence regarding efficacy emerged.

The new data from the National Institutes of Health suggest that the experimental neutralizing antibody therapy does not offer significant clinical benefit for people with more advanced COVID-19 illness, according to a company statement.

Eli Lilly also announced it plans to continue its other trials evaluating the antibody, including those assessing a potential role in treating people in the earlier stages of COVID-19.

“While there was insufficient evidence that bamlanivimab improved clinical outcomes when added to other treatments in hospitalized patients with COVID-19, we remain confident based on data from Lilly’s BLAZE-1 study that bamlanivimab monotherapy may prevent progression of disease for those earlier in the course of COVID-19,” the statement reads.

The ACTIV-3 trial was paused on October 13 after a data and safety monitoring board cited safety concerns.

The most recent data update that triggered an end to the trial did not reveal any significant differences in safety, though.  
 

This article first appeared on Medscape.com.

Eli Lilly announced it will halt its ACTIV-3 trial evaluating the antibody bamlanivimab in combination with remdesivir for people hospitalized with COVID-19, after new evidence regarding efficacy emerged.

The new data from the National Institutes of Health suggest that the experimental neutralizing antibody therapy does not offer significant clinical benefit for people with more advanced COVID-19 illness, according to a company statement.

Eli Lilly also announced it plans to continue its other trials evaluating the antibody, including those assessing a potential role in treating people in the earlier stages of COVID-19.

“While there was insufficient evidence that bamlanivimab improved clinical outcomes when added to other treatments in hospitalized patients with COVID-19, we remain confident based on data from Lilly’s BLAZE-1 study that bamlanivimab monotherapy may prevent progression of disease for those earlier in the course of COVID-19,” the statement reads.

The ACTIV-3 trial was paused on October 13 after a data and safety monitoring board cited safety concerns.

The most recent data update that triggered an end to the trial did not reveal any significant differences in safety, though.  
 

This article first appeared on Medscape.com.

Eli Lilly announced it will halt its ACTIV-3 trial evaluating the antibody bamlanivimab in combination with remdesivir for people hospitalized with COVID-19, after new evidence regarding efficacy emerged.

The new data from the National Institutes of Health suggest that the experimental neutralizing antibody therapy does not offer significant clinical benefit for people with more advanced COVID-19 illness, according to a company statement.

Eli Lilly also announced it plans to continue its other trials evaluating the antibody, including those assessing a potential role in treating people in the earlier stages of COVID-19.

“While there was insufficient evidence that bamlanivimab improved clinical outcomes when added to other treatments in hospitalized patients with COVID-19, we remain confident based on data from Lilly’s BLAZE-1 study that bamlanivimab monotherapy may prevent progression of disease for those earlier in the course of COVID-19,” the statement reads.

The ACTIV-3 trial was paused on October 13 after a data and safety monitoring board cited safety concerns.

The most recent data update that triggered an end to the trial did not reveal any significant differences in safety, though.  
 

This article first appeared on Medscape.com.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

The United States just passed a dubious COVID-19 milestone: Just over 1% of all children have been infected by the coronavirus this year, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.

There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.

The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.

Other measures largely put small states at the extremes:

• North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
• Vermont has the lowest cumulative rate: 190.5 per 100,000.
• Wyoming has the highest proportion of cases in children: 27.7%.
• New Jersey has the lowest proportion of child cases: 4.6%.

There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.

[email protected]

The United States just passed a dubious COVID-19 milestone: Just over 1% of all children have been infected by the coronavirus this year, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.

There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.

The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.

Other measures largely put small states at the extremes:

• North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
• Vermont has the lowest cumulative rate: 190.5 per 100,000.
• Wyoming has the highest proportion of cases in children: 27.7%.
• New Jersey has the lowest proportion of child cases: 4.6%.

There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.

[email protected]

The United States just passed a dubious COVID-19 milestone: Just over 1% of all children have been infected by the coronavirus this year, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.

There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.

The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.

Other measures largely put small states at the extremes:

• North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
• Vermont has the lowest cumulative rate: 190.5 per 100,000.
• Wyoming has the highest proportion of cases in children: 27.7%.
• New Jersey has the lowest proportion of child cases: 4.6%.

There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.

[email protected]

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

[email protected]

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

[email protected]

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

[email protected]

Fewer than one-third of women hospitalized with influenza receive the recommended flu vaccine, according to a study using data over nine flu seasons.

Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).

Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.

Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.

Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.

She noted that pregnant women are at high risk for influenza-associated hospitalization.

“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview

“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»

FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
 

Vaccine uptake lowest in first two trimesters

Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.

Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).

“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.

Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.

She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.

Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.

Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”

Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”

Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.

“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.

Holstein and Sheffield have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Fewer than one-third of women hospitalized with influenza receive the recommended flu vaccine, according to a study using data over nine flu seasons.

Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).

Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.

Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.

Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.

She noted that pregnant women are at high risk for influenza-associated hospitalization.

“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview

“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»

FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
 

Vaccine uptake lowest in first two trimesters

Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.

Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).

“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.

Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.

She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.

Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.

Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”

Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”

Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.

“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.

Holstein and Sheffield have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Fewer than one-third of women hospitalized with influenza receive the recommended flu vaccine, according to a study using data over nine flu seasons.

Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).

Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.

Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.

Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.

She noted that pregnant women are at high risk for influenza-associated hospitalization.

“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview

“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»

FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
 

Vaccine uptake lowest in first two trimesters

Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.

Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).

“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.

Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.

She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.

Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.

Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”

Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”

Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.

“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.

Holstein and Sheffield have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.