Predicting the impact of low influenza activity in 2020 on population immunity and future influenza season in the United States

Backgrounds: The influenza season of 2020-21 was remarkably low, likely due to implementation of public health preventive measures such as social distancing, mask-wearing, and school closure and due to decreased international travel. This leads to a key public health question: what will happen in the 2021-22 influenza season? To answer this, we developed a multi-season influenza model that accounted for residual immunity from prior infection. Method: We built a multi-strain, non-age structured compartmental model that captures immunity over multiple influenza seasons. By the end of the influenza season, we sorted the population based on their experience of natural infection and/or vaccination, which determines the susceptibility to influenza infection in the following season. Because the exact parameters of transmission rates and immunity are unknown, we implemented Bayesian calibration against the observed influenza epidemics (influenza hospitalization rates from 2012 to 2020 in the US) to estimate those parameters. In forward projections, we simulated low influenza activity in 2020-21 season by lowering transmission rate by 20%. Compared to the counterfactual case, in which influenza activity remained at the normal level in 2020-21, we estimated the change in the number of hospitalizations in the following seasons with varying level of vaccine uptake and effectiveness. We measured the change in population immunity over time by varying the number of seasons with low influenza activity. Result: With the low influenza activity in 2020-21, the model estimated 102,000 [95% CI: 57,000-152,000] additional hospitalizations in 2021-22, without change in vaccine uptake and effectiveness. The expected change in hospitalization varied depending on the level of vaccine uptake and effectiveness in the following year. Achieving 50% increase in one of two measures (1.5X vaccine uptake with 1X vaccine efficacy or 1.5X vaccine efficacy with 1X vaccine uptake) was necessary to avert the expected increase in hospitalization in the next influenza season. Otherwise, increases in both measures by 25% averted the expected increase in influenza-hospitalization. If the low influenza activity seasons continue, population immunity would remain low during those seasons, with 48% the population susceptible to influneza infection. Conclusion: We predicted a large compensatory influenza season in 2021-2 due to a light season in 2020-21. However, higher influenza vaccine uptake would reduce this projected increase in influenza.