SARS-CoV-2 and influenza co-infection throughout the COVID-19 pandemic: An assessment of co-infection rates and cohort characterization

Background: Case reports of patients infected with COVID-19 and influenza virus ("flurona") have raised questions around the prevalence and clinical significance of these reports. Methods: Epidemiological data from the HHS Protect Public Data Hub was analyzed to show trends in SARS-CoV-2 and influenza co-infection-related hospitalizations in the United States in relation to SARS-CoV-2 and influenza strain data from NCBI Virus and FluView. In addition, we retrospectively analyzed all cases of PCR-confirmed SARS-CoV-2 across the Mayo Clinic Enterprise from January 2020 to January 2022 and identified cases of influenza co-infections within two weeks of PCR-positive diagnosis date. Using a cohort from the Mayo Clinic with joint PCR testing data, we estimated the expected number of co-infection cases given the background prevalences of COVID-19 and influenza during the Wuhan (Original), Alpha, Delta, and Omicron waves of the pandemic. Findings: Considering data from all states of the United States using HHS Protect Public Data Hub, hospitalizations due to influenza co-infection with SARS-CoV-2 were seen to be highest in January 2022 compared to all previous months during the COVID-19 pandemic. Among 171,639 SARS-CoV-2-positive cases analyzed at Mayo Clinic between January 2020 and January 2022, only 73 cases of influenza co-infection were observed. Identified coinfected patients were relatively young (mean age: 28.4 years), predominantly male, and had few comorbidities. During the Delta era (June 16, 2021 to December 13, 2021), there were 9 lab-confirmed co-infection cases observed compared to 13.9 expected cases (95% CI: [12.7, 15.2]), and during the Omicron era (December 14, 2021 to January 17, 2022), there were 54 lab-confirmed co-infection cases compared to 80.9 expected cases (95% CI: [76.6, 85.1]). Conclusions: Reported co-infections of SARS-CoV-2 and influenza are rare. These co-infections have occurred throughout the COVID-19 pandemic and their prevalence can be explained by background rates of COVID-19 and influenza infection. Preliminary assessment of longitudinal EHR data suggests that most co-infections so far have been observed among relatively young and healthy patients. Further analysis is needed to assess the outcomes of "flurona" among subpopulations with risk factors for severe COVID-19 such as older age, obesity, and immunocompromised status. Significance Statement: Reports of COVID-19 and influenza co-infections ("flurona") have raised concern in recent months as both COVID-19 and influenza cases have increased to significant levels in the US. Here, we analyze trends in co-infection cases over the course of the pandemic to show that these co-infection cases are expected given the background prevalences of COVID-19 and influenza independently. In addition, from an initial analysis of these co-infection cases which have been observed at the Mayo Clinic, we find that these co-infection cases are extremely rare and have mostly been observed in relatively young, healthy patients.