Kevin Kunzmann is the managing editor for 

. Prior to joining parent company MJH Life Sciences in 2017, he worked as a health care and government reporter for The Pocono Record, and as a freelance writer for NJ Advance Media, The Express-Times, The Daily Journal, and more. He graduated from Rowan University with a degree in journalism in 2015. In his spare time, he enjoys reading, cooking, running his dog, and complaining about the Mets. Follow him on Twitter 

Kevin Kunzmann

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The US Food and Drug Administration (FDA) has approved Genentech’s baloxavir marboxil (Xofluza) for the treatment of acute, uncomplicated 

 in healthy children aged 5 to ≤12 years old who have been symptomatic with the flu for ≤48 hours.

The supplemental New Drug Application (sNDA) for the novel antiviral therapy also indicates its use for post-exposure prevention of flu in children from the same age group who have made contact with a person infected with influenza. Baloxavir marboxil is now the first single-dose oral medication approved for treating flu in children of this age group.

This second FDA approval is based on results from the phase 3 miniSTONE-2 and BLOCKSTONE trials—the former showing baloxavir marboxil’s benefit in treating influenza in children aged 5 to ≤12 years old after 48 hours versus oseltamivir, and the latter showing its benefit as a prophylactic treatment for household members living with someone infected with influenza versus placebo.

Investigators observed common adverse events such as vomiting and diarrhea in approximately 5% of the pediatric populations treated with baloxavir marboxil in each study.

MiniSTONE-2 investigator Pedro Piedra, MD, professor of molecular virology, microbiology and pediatrics at Baylor College of Medicine, emphasized the historic and significant role of school-aged children in the community-level transmission of influenza every flu season. Per the Centers for Disease Control and Prevention (CDC), US pediatric flu cases prior to prominent public masking due to COVID-19 were upward of 6 million cases annually.

“The annual influenza vaccine continues to be the most important first step to prevent illness in children, though there can still be breakthrough cases where antiviral treatment is needed,” Piedra said in a 

. “Today’s FDA approval provides children with a single-dose antiviral option, Xofluza, to treat influenza."

Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, praised the added indications for baloxavir marboxil to cover flu treatment and prevention of nearly every at-risk pediatric patient.

“Despite the ongoing COVID-19 pandemic, influenza continues to be a threat to public health, and effective influenza antivirals remain critical to alleviating the burden on healthcare systems,” Garraway said. “Xofluza has proven to be an important tool in fighting and preventing influenza in adults as well as adolescents, and we are pleased to now offer households and younger children our single-dose oral treatment.”

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The FDA has approved Baloxavir Marboxil (Xofluza) for children 5 years and older to treat and prevent influenza.

FDA Approves Baloxavir Marboxil Flu Drug for Children

The US Food and Drug Administration (FDA) has granted an Emergency Use Authorization (EUA) to Novavax for its adjuvanted vaccine against COVID-19 in adults aged ≥18 years old.

The indication concludes 2 years of clinical research and US regulation pursuit for the biotechnology, making the two-dose NVX-CoV2373 the fourth vaccine authorized by the FDA for prevention of the pandemic virus.

The protein-based vaccine is comprised of genetic original SARS-CoV-2 strain sequencing, with antigen derived from the Spike protein and formulated with a proprietary Novavax adjuvant designed to improve immune response and increase neutralizing antibody levels.

Last month, the FDA's Vaccines and Related Biologics Advisory Committee 

 to support the Novavax EUA application, with experts highlighting the benefit of an alternative COVID-19 background to the widely available messenger RNA (mRNA) regimens from Pfizer-BioNTech and Moderna.

Its emergency authorization was based on findings from the phase 3 pivotal PREVENT-19 trial, in which investigators assessed NVX-CoV2373 in approximately 30,000 participants aged ≥18 years old in the US and Mexico. PREVENT-19 data showed a 90.4% vaccine efficacy (95% CI, 83.8 - 94.3; 

Common solicited adverse reactions among vaccinated participants aged 18 - 64 years old included local pain (82.2%), fatigue (62.0%), muscle pain (54.1%) headache (52.9%), joint pain (25.4%), and nausea or vomiting (15.6%).

Among adults ≥65 administered the vaccine regimen, each of the common solicited adverse events were observed at lesser rates.

The federal government secured an initial 3.2 million doses of the Novavax vaccine earlier this week, with plans to make them available for free to the public, as administered by health care professionals.

Donald Alcendor, PhD, assistant professor of cancer biology at Meharry Medical College and adjunct associate professor of pathology, microbiology and immunology at Vanderbilt University School of Medicine, explained the distinct benefit of NVX-CoV2373 among currently marketed vaccines in an interview with 

“When you look at the 5 major vaccines...what you see is that Novavax is unique among all of them," he said. "What makes Novavax new and different is it gets rid of trying to teach your body how to make that protein; Novavax gives you the actual protein."

 accompanying the EUA announcement, PREVENT-19 co-lead Karen Kotloff, MD, professor of pediatrics at University of Maryland School of Medicine and associate director of clinical studies at the Center for Vaccine Development and Global Health, emphasized the significance of introducing a protein-based COVID-19 vaccine to the US population.

“Offering more vaccine technologies and options in our vaccination portfolio, including those built upon technologies that have been successfully used for years, will hopefully help to increase our country's vaccination rate,” Kotloff said.

Novavax president and chief executive officer Stanley Erck echoed a similar sentiment, stating the EUA underscores “the critical need to offer another vaccine option for the US population while the pandemic continues."

Approximately 222,000,000 (67.5%) of the US population has been reported as fully vaccinated against COVID-19 as of Monday, according to Our World in Data. The 7-day average for new COVID-19 cases surpassed 130,000 as of Tuesday.

The federal agency says it is indicated as a two-dose primary series for active immunization to prevent the virus in individuals 18 years of age and over.

Novavax Gets Nod for FDA EUA for its COVID-19 Vaccine

People previously infected with SARS-CoV-2 are at a significantly reduced risk of reinfection—especially those who received a dose of the Pfizer-BioNTech 

 afterward, according to new findings from a retrospective cohort study.

In new data presented by a team of investigators in Israel, SARS-CoV-2 reinfection appeared to be “relatively rare” among previously diagnosed patients; the risk was even less among those received a dose of vaccine BNT162b2 (Comirnaty) ≥3 months after their infection.

The findings from what investigators called the largest real-world observational assessment of natural versus vaccinated immunity against SARS-CoV-2 is limited by the glaring fact that it was conducted prior to the spread of the highly transmissible Omicron variant. Nonetheless, they may help to inform policies and practices for vaccinating convalescent populations against the pandemic virus going forward.

Investigators led by Sivan Gazit, MD, MA, of the Kahn Sagol Maccabi Research & Innovation Center and Maccabitech Institute for Research and Innovation conducted the retrospective cohort analysis to compare incident rates of SARS-CoV-2 reinfection (per hazard ratios [HRs]) in previously infected unvaccinated persons to those who did receive a single dose of the mRNA vaccine after infection.

As they noted, current evidence supporting the combined effect of naturally-acquired and vaccine-induced immunity against SARS-CoV-2 is insufficient—especially in defining the magnitude and durability of such immunity.

“Both short-term effectiveness of the BNT162b2 mRNA COVID-19 vaccine and waning of vaccine-induced immunity have been shown, although the latter has been mild against severe disease,” investigators wrote. “Unlike the large volume of published population-based research investigating the long-term effectiveness of COVID-19 vaccines, there is a relative paucity of large studies examining long-term protection against reinfection in previously infected persons although evidence suggesting long-term immunity has been published.”

While previous trials have shown the effect of “hybrid immunity” against SARS-CoV-2, Gazit and colleagues noted they include small cohorts and focus on biological outcomes including antibody and memory B cell counts instead of real-world data showing population-based outcomes.

“Given still unclear correlates of protection, and the global need for vaccine resource allocation, evidence of a substantial boosting effect for vaccination after recovery from COVID-19 is needed,” they wrote.

The team used the Maccabi Health Services (MHS) database, hosting the second largest health maintenance organization in Israel, to inform its analysis.

Investigators emulated 41 randomized controlled trials including 107,413 MHS patients aged ≥16 years old, seeking SARS-CoV-2 outcomes of infection, symptomatic disease, hospitalization and death between March 2 and December 13, 2021.

Of the patients, 1374 had a positive PCR test result for SARS-CoV-2 reinfection, 874 experienced a symptomatic reinfection, and 10 incurred a COVID-19 related hospitalization on reinfection. Investigators observed no COVID-19 related deaths in their assessment. Another 21,131 patients received a second dose of the mRNA vaccine and were thus excluded from follow-up, and the remaining patients did not experience any documented outcomes related to the virus.

Investigators observed an 82% decreased risk of reinfection among previously infected patients who received a single dose versus those previously infected with SARS-CoV-2 but unvaccinated (HR, 0.18; 95% CI, 0.15 - 0.20). Symptomatic COVID-19 reinfection risk was reduced by 76% among patients with this “hybrid immunity” versus those previously infection and unvaccinated (HR, 0.24; 95% CI, 0.29 - 0.29).

“This finding supports previous small cohort studies pointing to evidence of a boosting effect of neutralizing antibody activity, or an anamnestic response, in previously infected persons receiving a single dose of an mRNA vaccine, as well as SARS-CoV-2–specific T-cell and memory B-cell response and affinity maturation,” investigators wrote.

As Gazit and colleagues noted, the long-term effects of SARS-CoV-2 reinfection remains mostly unknown. Even without contextual data from the period of Omicron variant outbreaks, the new large-scale findings support the vaccine efficacy of single-dose BNT162b2 given ≥3 months after a patient is first infected with the pandemic virus.

The Incidence of SARS-CoV-2 Reinfection in Persons With Naturally Acquired Immunity With and Without Subsequent Receipt of a Single Dose of BNT162b2 Vaccine,

An Israeli study found COVID-19 reinfection was "relatively rare," and previously infected persons who also received at least 1 dose of the Pfizer-BioNTech mRNA vaccine had an 82% reduced risk of reinfection.

Single COVID-19 mRNA Vaccine Dose Significantly Reduces Risk of Reinfection

Adverse events are not confined to only vaccine recipients in 

A new systematic review and meta-analysis showed approximately one-third of all placebo dose recipients in COVID-19 vaccine trials reported a systemic adverse event (AE) such as headache or fatigue.

The significant prevalence of adverse events elicited by placebos, called “nocebo responses,” may perpetuate an expectation of common nonspecific symptoms including headache and fatigue in new vaccine recipients—thereby leading to greater likelihood of nocebo responses versus actual events associated with COVID-19 vaccines.

“Emerging research has shown that informing patients about nocebo responses and providing a positive framing of potential AEs may be associated with reduced AE-related anxiety and nocebo responses,” investigators wrote. “Although nocebo phenomena have been investigated in many contexts involving medication, evidence of their influence in vaccination remains scarce.”

A team of multinational investigators conducted a systematic review and meta-analysis of 2 major clinical trial databases to compare the frequency of adverse events reported by placebo-controlled participants of COVID-19 vaccine trials versus those reported by actual vaccine recipients.

Led by Julia W. Haas, PhD, of the Program in Placebo Studies at Beth Israel Deaconess Medical Center, investigators noted a global survey from January 2021 showing that 47% of respondents were worried about adverse events from a COVID-19 vaccine. Even before the pandemic, the World Health Organization (WHO) defined vaccination hesitancy as a global health threat; it has since been a burden in reducing the spread and effect of COVID-19.

“Counteracting the underlying motivations for vaccination hesitancy is therefore crucial to overcome this worldwide crisis,” they wrote.

Haas and colleagues used relevant published data on COVID-19 vaccine trials up to July 14, 2021. Eligible trials featured randomization, adults aged ≥16 years old, a placebo arm, data for solicited adverse events within 7 days of injection and a report of adverse events for both vaccine and placebo groups separately.

Their analysis included 12 articles with adverse event reports for 45,380 participants (22,578 placebo). Investigators observed adverse event reporting outcomes for both first- and second-dose experiences in patients.

After the first dose, 35.2% (95%, 26.7 - 43.7) of placebo recipients reported systemic adverse events; headaches (19.3%; 95% CI, 13.6 - 25.1) and fatigue (16.7%; 95% CI, 9.8 - 23.8) were the most commonly reported events, followed by muscle pain (9.1%; 95% CI, 6.0 - 12.1).

Even after the second dose, 31.8% (95% CI, 28.7 - 35.0) of placebo recipients reported systemic adverse events—again primarily either headache, fatigue or muscle pain.

Though significantly more COVID-19 vaccine recipients in the analyzed trials reported systemic events, investigators noted that given the ratio between placebo and vaccine arms, nocebo responses accounted for more than three-fourths (76%) of systemic adverse events after the first COVID-19 vaccine dose and more than half (51.8%) after the second dose.

Noting that adverse event frequency dropped among placebo recipients on the second dose, investigators hypothesized that participants in the control arm had lesser expectation of adverse events than vaccine recipients.

“Headache, fatigue, malaise, and joint pain were common in both groups and seem to have been particularly associated with nocebo,” Haas and colleagues wrote. “Furthermore, exploratory analyses suggested that nocebo responses may produce adverse events of severity grades similar to those of active vaccines after the first dose.”

The team pointed to various strategies that could help to inform the public about nocebo responses and reduce the likelihood of misperceived adverse events, including information added to informed consent procedure documents. Even highlighting the probability of not experiencing adverse events in a controlled clinical trial may eventually provide the public a more clear understanding of risks and benefits.

“Although more research on these communication strategies is needed, such honest information adds to full disclosure and is unlikely to cause harm,” they concluded. “In addition, informing the public about the potential for nocebo responses may help reduce worries about COVID-19 vaccination, which might decrease vaccination hesitancy.”

Frequency of Adverse Events in the Placebo Arms of COVID-19 Vaccine Trials

The expectation of COVID-19 vaccination side effects may be leading some placebo recipients to report adverse events in vaccine trials.

Placebo Recipients Reporting Side Effects in COVID-19 Vaccine Trials

 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 

Experiencing myocarditis after COVID-19 mRNA vaccination is rare, but more likely among persons under 24 years and male.

Young Men at Increased Risk of Myocarditis After mRNA COVID-19 Vaccination 

 cases on December 27, as spread of the SARS-CoV-2 omicron variant during the holiday weekend resulted in more than 540,000 new cases.

The 7-day average for new daily COVID-19 cases is rapidly approaching 250,000 and will likely surpass the national high of approximately 259,000 reached in the post-holiday outbreak of early January 2021, per data from the US Centers for Disease Control and Prevention.

In regional and national data collected by 

, the daily average of COVID-19 tests and hospitalizations have also steadily increased during the outbreak; approximately 1.8 million tests are being administered daily, and 71,000 people are hospitalized daily.

Sixteen states including Washington, DC have reported a ≥100% increase in average daily new cases in the last 14 days.

Despite these alarming rates, new daily averages for COVID-19 deaths have decreased by 5% in the last 14 days. This may be due to a well-understood lag in progression from new cases to severe disease, but data suggest a correlation between COVID-19 vaccination and significantly decreased risk of death.

CDC data from 29 states earlier this year suggested daily average cases per 100,000 were approximately 5 times greater in unvaccinated persons than vaccinated persons; average daily deaths per 100,000 were actually 13 times greater.

From September 29 to December 27, the total count of Americans fully vaccinated against COVID-19 increased by 9.2%. In that same time, average daily COVID-19 deaths have decreased by 13.7%.

Amid rising new cases, increasing vaccination and decreasing death rates—as well as ongoing research projecting the Omicron variant may be associated with less severe disease risk than previous variants—the CDC altered recommended isolation time for persons who tested positive from 10 days to 5.

The US is on track to reach new records for 7-day average cases, though death rates remain lower.

Kevin Kunzmann

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