Preparing for the "tripledemic": RSV, influenza, and COVID-19

Kenny Lin, MD, MPH
Posted on October 30, 2022

During the first two winters of the pandemic, social distancing and mask wearing protected many persons - particularly infants and older adults - from SARS-CoV-2 and other potentially serious viral respiratory infections. With most people having returned to pre-pandemic social interactions, the viruses are making a comeback. Children's hospitals in several states are filled to capacity with patients infected with respiratory syncytial virus (RSV); high levels of influenza-like illness are being reported across most of the South; and with waning immunity and low uptake of bivalent vaccine booster shots, many scientists predict another COVID-19 winter surge. Health officials are concerned that the combination of RSV, influenza, and SARS-CoV-2 variants may produce a "tripledemic" that could overwhelm outpatient practices and hospitals.

Prior to 2020, 2 to 3 percent of U.S. infants younger than 12 months were hospitalized for RSV bronchiolitis, and RSV was estimated to cause 177,000 hospitalizations and 14,000 deaths annually in adults aged 65 years and older. For the family physician evaluating a child with bronchiolitis, accurate risk stratification remains a key skill. Unfortunately, aside from oxygen supplementation, no other therapies offer significant benefit: bronchodilators do not improve oxygen saturation, hospitalization rate or duration; and the American Academy of Pediatrics practice guideline recommends against using systemic corticosteroids, antibiotics, nebulized hypertonic saline (unless the child is hospitalized), or chest physiotherapy. RSV prophylaxis in the first year of life with the monoclonal antibody palivizumab (Synagis) is recommended only for infants born before 29 weeks of gestation or infants with chronic lung or heart disease, neuromuscular disease, or profound immunocompromise. No vaccines have been approved by the U.S. Food and Drug Administration (FDA) to prevent RSV infections in infants or older adults.

Although not in time for this RSV season, new prevention tools are around the corner. Earlier this year, a placebo-controlled trial of 1490 late-preterm (>35 weeks gestation) and term infants reported that the monoclonal antibody nirsevimab provided reduced medically attended RSV bronchiolitis by 75 percent and hospitalization by 62 percent, with no difference in adverse events. The FDA and the European Medicines Agency are both considering approval. Several companies are also in the late stages of developing a vaccine against RSV for older adults, with two reporting positive outcomes in unpublished Phase 3 trials.

In the meantime, nonpharmacologic interventions (handwashing, avoiding sick persons, and mask wearing) remain the mainstay of preventing respiratory virus infections. Finally, to increase lagging COVID-19 and influenza vaccine uptake, the American Academy of Family Physicians has assembled an Immunizations & Vaccines web page with up-to-date clinical and patient education resources.