Estimating the impact of influenza on the epidemiological dynamics of SARS-CoV-2

As in past pandemics, co-circulating pathogens may play a role in the epidemiology of coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In particular, experimental evidence indicates that influenza infection can up-regulate the expression of ACE2-the receptor of SARS-CoV-2 in human cells-and facilitate SARS-CoV-2 infection. Here we hypothesized that influenza impacted the epidemiology of SARS-CoV-2 during the early 2020 epidemic of COVID-19 in Europe. To test this hypothesis, we developed a population-based model of SARS-CoV-2 transmission and of COVID-19 mortality, which simul-taneously incorporated the impact of non-pharmaceutical control measures and of influenza on the epidemiological dynamics of SARS-CoV-2. Using statistical inference methods based on iterated filtering, we confronted this model with mortality incidence data in four European countries (Belgium, Italy, Norway, and Spain) to systematically testa range of assumptions about the impact of influenza. We found consistent evidence for a 1.8-3.4-fold (uncertainty range across countries: 1.1 to 5.0) average population-level increase in SARS-CoV-2 transmission associated with influenza during the period of co-circulation. These estimates remained robust to a variety of alternative assumptions regarding the epidemiological traits of SARS-CoV-2 and the modeled impact of control measures. Although further confirmatory evidence is required, our results suggest that influenza could facilitate the spread and hamper effective control of SARS-CoV-2. More generally, they highlight the possible role of co-circulating pathogens in the epidemiology of COVID-19.