Gearing up for a triple threat

Pediatricians might be already seeing more sick children walking through their clinic’s door than normal right now, a trend that may very well continue this winter. Scientists have been warning about the threat of a “triple epidemic” this winter because of the recent rise in respiratory syncytial virus (RSV), COVID-19, and influenza cases flooding the US health care system.¹ 

Tina Q. Tan, MD, FAAP, FIDSA, FPIDS, spoke with ^{Contemporary Pediatrics®} about this potential triple epidemic.In the interview, Tan said that doctors have reported a massive surge in RSV, and that multiple states in the United States are seeing extreme levels of influenza.

Currently, Tan reports that in her area Chicago, RSV is currently surging, but she also expects to see surges in influenza and COVID-19 as well.

According to the Centers for Disease Control and Prevention (CDC), RSV often leads to mild cold-like symptoms, but the virus can be severe for infants.² RSV is also the most common cause of pneumonia and bronchiolitisin USchildren aged less than 1 year. 

Surveillance from the CDC has indicated rising rates in RSV infections and emergency department visits and hospitalizations in the United States. The CDC encouraged health care professionals to remain aware as respiratory viruses, including RSV, increase.

Symptoms of RSV, influenza, and COVID-19 all overlap, and all 3 viruses are circulating through the community.¹ This can make it difficult to pinpoint the cause of symptoms such as fever, irritability, cough, and congestion. Along with the 3 components of the triple epidemic, these symptoms could also be caused by Rhinovirus, enterovirus, para influenza, and Coxsackie viruses.

Tan recommended that practitioners evaluate symptoms for each individual to determine the respiratory illness they have. If RSV is currently circulating at high rates in the area, then it is more likely for a child to have RSV than COVID-19 or influenza. 

Also, Tan suggested distinguishing viruses by onset of symptoms. Rapid onset of symptoms is often a sign of influenza, meaning that parents can predict their children have influenza if symptoms appear over the course of a few hours.

A representative from the CDC discussed how COVID-19 has impacted the spread of other respiratory viruses.³ During the COVID-19 pandemic, the circulation of many respiratory illnesses rapidly slowed, making now a time when many children are being exposed to these illnesses for the first time.

The CDC has observed an increase of RSV rates and influenza rates, with COVID-19 and its variants continuing to circulate. More than 97 million cases of COVID-19 have been reported as of November 2022. 

Tracking systems have let the CDC know that influenza like illness symptoms increase this time of year. The CDC has found that multiple different viruses are contributing to these symptoms. Influenza has accounted for almost 20% of respiratory specimens observed, with young children more likely to be affected and hospitalized by severe influenza.

Symptoms of RSV often appear in children 4 to 6 days after infection, and hospitalization is most likely in children aged 4 years and under. The CDC has tracked RSV using a variety of surveillance systems and has found that the virus is increasing in most regions defined by the United States Department of Health and Human Services.

Vaccines for influenza and COVID-19 have been declared safe by the CDC. The CDC representative recommended staying up to date on these vaccines to protect yourself and your family.

Currently, Pfizer is developing a vaccine against RSV, RSVpreF, which has shown high efficacy in clinical trials for protecting infants when administered during pregnancy.

Positive results were recently announced from a phase 3 trial of the vaccine, showing tolerance in newborns and efficacy in RSV prevention.⁴ The study consisted of about 7,4000 pregnant individuals, who were given either the vaccine or a placebo. Administration occurred during the second of third trimester of pregnancy and led to positive results

The vaccine met 1 of 2 primary endpoints, showing substantial efficacy of 69.4% in infants during the 6-month follow-up period. Statistical success was not met, but 57.1% meaningful efficiency was seen in infants from birth for the first 90 days of life, and 51.3% for infants observed throughout the follow-up period.⁴

Immunogenicity of the vaccine was also tested in maternal patients and their infants to assess safety. Infants were followed for 1 year or more to examine safety and efficiency, with over 50% of infants followed for 2 years. The study took place in 18 countries and began in June 2020, allowing it to span multiple RSV seasons.

With a potential new drug application filing by the end of 2022, this vaccine could open a door to more opportunities to protect infants against RSV in the future. And, if approved, Pfizer’s vaccine could be the first maternal vaccine for protection against RSV in infants up to 6 months.⁴

AstraZeneca and Sanofi are also vying for a spot in the market with their RSV vaccine, the single-dose antibody nirsevimab (Beyfortus).⁵ Most recently, nirsevimabwas approved by the European Medicines Agency for prevention of RSV in infants.⁶

Approval by the US Food and Drug Administration of nirsevimab could make it the first single-dose immunization in infants born both at term and preterm, and those with specific health conditions in the United States. In clinical studies, the vaccine met its primary endpoint of reducing lower respiratory tract infections caused by RSV compared to placebo.

Commercial use of nirsevimabis still in question, as the vaccine did not meet its secondary endpoint of reducing RSV hospitalizations more than placebo.

Reference

1. RSV, influenza, and COVID-19: Gearing up for the threat of a 'triple epidemic'. Contemporary Pediatrics. November 4, 2022. Accessed November 7, 2022. https://www.contemporarypediatrics.com/view/rsv-influenza-and-covid-19-gearing-up-for-the-threat-of-a-triple-epidemic-

2. Respiratory Syncytial Virus Infection (RSV). Centers for Disease Control and Prevention. Accessed November 7, 2022. https://www.cdc.gov/rsv/index.html

3. CDC media telebriefing: update on respiratory disease circulation transcript. Centers for Disease Control and Prevention. November 4, 2022. Accessed November 7, 2022. https://www.cdc.gov/media/releases/2022/t1104-update-respiratory-disease-circulation.html

4. Pfizer announces positive phase 3 data for RSV vaccine. Contemporary Pediatrics. November 2, 2022. Accessed November 7, 2022. https://www.contemporarypediatrics.com/view/pfizer-announces-positive-phase-3-data-for-rsv-vaccine

5. Kansteiner F. Sanofi, AZ's blockbuster hopeful RSV med nears first approval as showdown with Pfizer, GSK looms. September 16, 2022. Accessed November 8, 2022. https://www.fiercepharma.com/pharma/sanofi-and-azs-3b-rsv-contender-nears-approval-europe-showdown-pfizer-gsk-vaccines-looms#:~:text=AstraZeneca%20and%20Sanofi%2C%20meanwhile%2C%20are,season%20with%20a%20single%20dose

6. Beyfortus approved in the EU for the prevention of RSV lower respiratory tract disease in infants. November 4, 2022. Accessed November 8, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/beyfortus-approved-in-the-eu-for-the-prevention-of-rsv-lower-respiratory-tract-disease-in-infants.html