Kevin Kunzmann

 following vaccination with either available messenger RNA (mRNA) vaccine for 

 is significantly low, but altogether higher than expected in persons aged 24 years and younger, according to a new national study.

A team of investigators from the Centers for Disease Control and Prevention (CDC) reported findings from the Vaccine Adverse Event Reporting System (VAERS) showing that cases of the inflammatory heart event occurred 1626 times after an mRNA vaccine dose in US individuals from December 2020 to August 2021.

Contrasted against the 354,100,845 total doses of mRNA vaccine doses administered in that time frame, the prevalence of myocarditis is significantly low (.0000046%), three-fourths of the observed cases occurred in vaccinated persons younger than 30 years old, and one-third in those younger than 21 years old.

The research team, led by Matthew E. Oster, MD, MPH, of the CDC and the Emory University School of Medicine, additionally found differing rates of myocarditis risk in mRNA-vaccinated individuals dependent on gender and total doses received. They hope the findings can contribute to continued benefit-risk discussion for young adults and adolescents eligible for COVID-19 vaccination.

Oster and colleagues sought to describe the reports and confirmed cases of myocarditis available in the national passive surveillance VAERS database among individuals vaccinated with either Pfizer-BioNTech’s BNT162b2 or Moderna’s mRNA-1273, to provide estimated risks of myocarditis after vaccination based on age, sex and vaccine type.

The concept of vaccination serving as a trigger for myocarditis—a condition most commonly observed in infancy, adolescence or young adulthood—is mostly hypothesis, investigators wrote; only the smallpox vaccine has been causally linked to the cardiovascular event based on clinical reports. But the widespread and unprecedentedly expedited COVID-19 vaccination rollout implemented in December 2020 following the US Food and Drug Administration (FDA) Emergency Use Authorization (EUA) of BNT162b2—the first ever regulated mRNA vaccine in the US—warranted monitoring of special-interest adverse events via VAERS.

“As the reports of myocarditis after COVID-19 vaccination were reported to VAERS, the Clinical Immunization Safety Assessment Project, a collaboration between the CDC and medical research centers, which includes physicians treating infectious diseases and other specialists (eg, cardiologists), consulted on several of the cases,” investigators wrote. “In addition, reports from several countries raised concerns that mRNA-based COVID-19 vaccines may be associated with acute myocarditis.”

Investigator adjudicated and summarized reports of myocarditis to VAERS for all age groups through the observed time. Rates of myocarditis were calculated and stratified by age and sex of patient. They additionally calculated rates of myocarditis by age and sex for 2017-2019 through claims data. Clinical presentation, diagnostic test results, treatment and early outcomes of patients aged ≤30 years old were conducted.

Their assessment included 192,405,448 individuals who received 354,100,845 doses of either mRNA COVID-19 vaccine. Of the 1991 reports of myocarditis in COVID-19 mRNA vaccine recipients from the observed time, 1626 met the case definition of the condition.

Median patient age for myocarditis patients was 21 years old (IQR, 16 – 31) and median time to symptom onset was 2 days (IQR, 1 -3) post-vaccine dose. Among eligible reports that included patient sex, men comprised 82% of all observed myocarditis cases.

Investigators noted that the crude reporting rates for cases of myocarditis within 7 days of COVID-19 mRNA vaccination exceeded expectation across multiple strata of age and sex. Approximately 71 per 1 million doses of BNT162b2 resulted in myocarditis among adolescent males aged 12 – 15 years old; the rate was even greater in males aged 16 – 17 years old (105.9 per 1 million). The rate remained significant for men aged 18 – 24 years old for both vaccines (BNT162b2, 52.4 per 1 million; mRNA-1273,56.3 per 1 million).

Of the 826 cases observed among adults ≤30 years old, a majority (98%) were shown to include elevated troponin levels, as well as abnormal electrocardiogram results (72%) and abnormal cardiac magnetic resonance imaging (MRI) results (72%). Nonsteroidal anti-inflammatory drugs were the most common therapy prescribed to patients (87%). “Cardiac MRI was often used for diagnostic purposes and also for possible prognostic purposes,” Oster and colleagues noted. “Supportive care was a mainstay of treatment, with specific cardiac or intensive care therapies as indicated by the patient’s clinical status.”

The cases of myocarditis reported after COVID-19 mRNA vaccination were generally diagnosed within days of patients’ vaccination—contrasted to typical viral myocarditis cases, which can often have “indolent courses with symptoms sometimes present for weeks to months after a trigger if the cause is ever identified.”

Investigators also noted that the major presenting symptoms of myocarditis in vaccinated patients seemed to resolve faster than typical viral cases: “Even though almost all individuals with cases of myocarditis were hospitalized and clinically monitored, they typically experienced symptomatic recovery after receiving only pain management.”

Though long-term effects and recovery of myocarditis cases in COVID-19 vaccinated persons is still under assessment, investigators did observe in these acute cases that 96% of patients were hospitalized and 87% had resolution of presenting symptoms by their discharge. No deaths were observed among hospitalized patients.

The CDC previously began follow-up surveillance in vaccinated adolescents and young adults in order to better interpret health and functional status, including cardiac outcomes, 3-6 months following probably and confirmed cases of myocarditis. Oster and colleagues emphasized the American Heart Association (AHA) and American College of Cardiology (ACC) guidelines advising that such patients should refrain from competitive sports for 3-6 months and that documentation of normal electrocardiogram result, ambulatory rhythm monitoring, and an exercise test should be completed prior to their resumption.

Further doses of mRNA-based COVID-19 vaccines should be deferred, but may be considered in select circumstances,” they wrote.

The study, “Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021,” was published online in 

Articles

New findings from CDC data show three-fourths of all myocarditis cases observed in the first 8 months of COVID-19 vaccination occurred in persons 30 years and younger.

Young Men, Adolescents at Raised Risk for COVID-19 mRNA Vaccine Myocarditis

The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding the New Drug Application for gefapixant, an investigative receptor antagonist therapy from Merck seeking approval for the treatment of refractory or unexplained chronic cough.

The selective P2X3 receptor antagonist was supported by findings from the phase 3 COUGH-1 and COUGH-2 trials, a pair of multinational randomized studies showing 45 mg gefapixant reduced 24-hour cough frequency in patients by 18.45% (95% CI, -32.92 to -0.86; 

 = .041) and 14.64% (95% CI, -26.07 to -1.43; 

 = .031), respectively, by 24 weeks versus placebo.

The FDA’s letter to Merck regarding the application included a request for additional information “related to measurement of efficacy,” the company stated in a 

“The CRL was not related to the safety of gefapixant,” the statement read. “Merck is reviewing the letter and will meet with the agency to discuss next steps.”

Merck leadership expressed their commitment to advancing the regulatory status of gefapixant, which would be the first newly approved drug for chronic cough in 6 decades.

Stuart Green, MD, Vice President of Late Stage Development at Merck, previously 

 the difficulty within the market to identify and progress a new viable drug for chronic cough has been in actually understanding the mediating pathways associated with the condition.

“What we find is that there’s many different pathways, but some of these appear to more important in disease states than others,” he explained. “It’s because of advances in developing not only the understanding of the science, but drugs than can selectively target those pathways, that we’ve now been able to do the kind of studies that allow us to hopefully demonstrate benefit for people with this condition.”

The selective inhibitor therapy is being investigated for the treatment of 2 forms of chronic cough—an indication that's been unmet in 60 years.

Merck Receives FDA Complete Response Letter for Chronic Cough Drug Candidate Gefapixant

 PDE-4 inhibitors and antibiotics for COPD


 Best use of lung volume reduction surgery


 The ALA Airways Clinical Research Center


 Pulmonary vasculature and supplemental oxygen


chronic obstructive pulmonary disease (COPD)

—among the leading causes of death in the US—continue to rise nationally and discriminately affect the midwest region, it’s vital to understand the landscape of research and clinical guidance set by leading institutions.

The first Lungcast episode of 2022 provides as good a resource on COPD as is currently available, from the mind of a leading COPD investigator.

Gerard Criner, MD, Chair and Professor of Thoracic Medicine and Surgery at the Lewis Katz School of Medicine at Temple University and Director of the Temple Lung Center, joins Lungcast host Al Rizzo, MD, Chief Medical Officer of the American Lung Association (ALA) for a comprehensive discussion on the state of COPD care and research.

Lungcast is a monthly respiratory health podcast series from the ALA produced by 

Through the conversation, Rizzo and Criner touch on leading guidance from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and American Thoracic Society (ATS) institutions, the evolving priority and strategy of lung transplant, and the effect of COVID-19 on pulmonary care strategies—both acute and chronic.

Subscribe or listen to Lungcast on your favorite platforms:

https://open.spotify.com/show/1F3u1hKrwxi9snSQ0q3nti

https://podcasts.apple.com/us/podcast/lungcast/id1524712350

Podcasts

The Temple-based investigator and expert joins Lungcast to review recent clinical trials, recommendations and non-surgical techniques for patients who have advanced COPD.

Current State of COPD with Dr. Gerard Criner

Americans with depressive symptoms are more likely to endorse COVID-19 vaccine misinformation, according to results of a national survey that highlight the need to address susceptibility to false information among persons with depression.

The new findings from the study conducted by a team of US-based investigators also showed correlates between a person more likely being unvaccinated for COVID-19 and resistant to the practice when in endorsement to any 1 of the 4 COVID-19 vaccine misinformation statements presented to them.

Led by Roy H. Perlis, MD, MSc, of the Massachusetts General Hospital, investigators sought to determine the link between depressive symptoms and likelihood of believing COVID-19 vaccine-related misinformation—a public health behavior recognized even prior to the pandemic. During the pandemic, about one-fourth of US adults have consistently reported moderate or more severe depressive symptoms.

“While misinformation is increasingly well studied, most of this work has concentrated on how and why such misinformation spreads,” Perlis and colleagues wrote. “A general bias toward negativity in information selection, processing, and recall may exacerbate misinformation exposure. In the context of political misinformation, both anger and anxiety are associated with promoting beliefs in certain types of false stories.”

The team analyzed responses compiled from 2 waves of a national nonprobability internet survey conducted from May to July 2021. The survey, provided to more than 15,000 adults aged ≥18 years old, characterized association between depressive symptoms and endorsement of misinformation, as well as potential mediators or moderators of such associations.

Investigators measured depressive symptoms from surveyed adults via the Patient Health Questionnaire 9-item (PHQ-9), and conducted population-reweighted multiple logistic regression analysis to examine the link between moderate to severe depressive symptoms and endorsement of ≥1 item of vaccine information. They further adjusted for sociodemographic features in determining associations.

Of the 15,464 survey respondents, 63.6% were women and mean respondent age was 47.9 years. Respondents were predominately White (76.7%), followed by Black (9.7%), Hispanic (6.6%), then Asian (4.7%).

Similar to previous national assessments during COVID-19, one-quarter (26.9%) of respondents identified moderate or greater depressive symptoms on the PHQ-9. About one-fifth (19.2%) endorsed at least 1 vaccine-related statement of misinformation on the survey; such statements included:

“The COVID-19 vaccines will alter people’s DNA”

“The COVID-19 vaccines contain microchips that could track people”

“The COVID-19 vaccines contain the lung tissue of aborted fetuses”

“The COVID-19 vaccines can cause infertility, making it more difficult to get pregnant”

Respondents with presence of depressive symptoms were more than twice likely to endorse COVID-19 vaccine misinformation (odds ratio [OR], 2.33; 95% CI, 2.09 – 2.61). Respondents endorsing ≥1 misinformation item were significantly less likely to be vaccinated (OR, 0.40; 95% CI, 0.36 – 0.45) and significantly more likely to report resistance to vaccination (OR, 2.54; 95% CI, 2.21 – 2.91).

Among the 2800-plus respondents to answer a subsequent survey in July, the presence of depression in the first survey from May was linked to a greater likelihood of endorsing even more information in July compared with the prior survey (OR, 1.98; 95% CI, 1.42 – 2.75).

Each of these correlates remained statistically significant when investigators adjusted for respondent sociodemographic features, as well as self-reported ideology and political party information. Though the findings do not provide conclusion on causation, the assessment of second-wave survey respondents suggested to investigators that misinformation was unlikely to cause depression.

“In general, negative biases are apparent in information processing even in the absence of depression,” they wrote. “Individuals with major depressive symptoms often exhibit a more pronounced negativity bias, a form of attentional bias in which thoughts with negative valence receive greater focus.”

The team did note that individuals with depression may exhibit less willingness to trust institutions tasked with combating misinformation, such as the Centers for Disease Control and Prevention (CDC). “However, we found that incorporating terms for trust in these institutions in regression models did not change the main association with depression, which does not support a mediating association of trust in institutions,” they wrote.

Perlis and colleagues concluded that while their findings were “associative by necessity,” the results showing a link between depression and COVID-19 misinformation endorsement broadly suggest the significance of directly testing causation in future assessments—if only to derive strategies that could reduce the consequences of depression in individual’s perception of information.

“To date, efforts to combat the impact of misinformation on public health predominantly emphasize reduction in supply,” they wrote. “In parallel, it may be possible to develop interventions targeting negativity bias that reduce demand, or at least modulate the capacity of misinformation to impact health decision-making.”

Association of Major Depressive Symptoms With Endorsement of COVID-19 Vaccine Misinformation Among US Adults

Analysis of 2 national surveys suggest a more than two-fold greater likelihood of depressed Americans endorsing a false fact about COVID-19 vaccines than others. 