Move Over COVID, Influenza Is Coming to Town

Seasonal influenza sweeps around the world year after year infecting millions of people across the Northern and Southern hemispheres. In a typical year, influenza causes 30-40 million cases in the United States with an average of 37,000 deaths per year from 2010-2019. However, because of the COVID-19 precautions (masks, social distancing, lockdowns, and cancellation of group events), the 2020-21 flu season was minimal in the United States with only about 700 reported fatalities, a 50-fold reduction in deaths from a normal year. Similar reductions in flu incidence were observed all around the world. Such a global suppression of seasonal flu has never before occurred, and now there is concern that the low caseload in 2020-21 combined with the loosening of COVID-19 precautions could lead to a problematic flu season for 2021-22.

Influenza virus has an RNA genome that must be replicated every time the virus reproduces. The enzyme that performs this replication has low accuracy, resulting in a rapid accumulation of mutations in the viral genome, a process known as genetic drift. A major barrier to influenza control is that genetic drift can cause changes in proteins on the surface of the virus. Immunity to influenza, either from natural infection or vaccination, is primarily due to antibodies that bind the virus surface proteins and prevent the virus from infecting our cells. Changes in these surface proteins can result in new viral strains each year that are not recognized by our previously acquired antibodies, thus making us susceptible to infection again. Consequently, acquired immunity to the virus is relatively short-lived, and each year many individuals in the population are susceptible to infection and disease. Adequate protection against this fast-paced viral evolution requires annual vaccination to induce immunity against the new strains prevalent that year, yet only about 50% of Americans get vaccinated for influenza in a typical year. The low infection rate in 2020-21 means that there was very little immunity induced by natural infection in the unvaccinated portion of the American population. Additionally, the low infection rates provided many fewer viral samples to examine for new strains, so predicting the 2021-22 strains to put in the vaccine has been more challenging. With a higher percentage of the population than usual with minimal immunity to influenza and less certainty that this year’s vaccine will be highly effective, the potential for a bad flu season is heightened. A severe flu season, coupled with continued high levels of SARS-CoV-2 spread, could place additional critical stress on already overburdened hospitals in some regions of the country.

Two recent studies (not yet peer-reviewed) from the University of Pittsburg used mathematical modeling to make predictions about the upcoming flu season. The first study predicts an influenza surge with around 100,000 more hospitalizations for flu than in a typical year. Importantly, their model suggests that this surge could be avoided if we increased influenza vaccination from 50% of the population to 75%. The second study used a different modeling scheme and also predicts an influenza upswing with roughly 20% more cases than in an average year. They point out that this year could be particularly hard on infants and young children who completely lack immunity to influenza because they have had neither an infection nor a vaccination. As in the first study, the second report also found that increasing the vaccination coverage in the U.S. would mostly ameliorate the increased cases and make 2021-22 a more standard influenza year. For the vaccine-hesitant, it should be noted that the injected flu shot consists of inactivated virus so it cannot cause influenza in the vaccinated person. The CDC recommends the influenza vaccine for everyone over the age of 6 months, and also states that the flu vaccine and the COVID-19 vaccine can be given at the same time. Here’s hoping that the American public will embrace the recommendations this year so that we reduce influenza-related preventable hospitalizations and deaths and not overwhelm the healthcare system that is still struggling with COVID-19.

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