SARS-CoV-2 and influenza co-infection throughout the COVID-19 pandemic: An assessment of co-infection rates and cohort characterization
Authors: Pawlowski Colin , Silvert Eli , O’Horo John C. , Lenehan Patrick J. , Challener Doug , Gnass Esteban , Murugadoss Karthik , Ross Jason , Speicher Leigh , Geyer Holly , Venkatakrishnan AJ , Badley Andrew , Soundararajan Venky 
Published: February 2022

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.