Influenza viral infection is a risk factor for severe illness in COVID-19 patients: a nationwide population-based cohort study

Abstract

In order to prepare for the twindemic of influenza and SARS-CoV-2 infection, we investigated the association between influenza infection and subsequent severity of SARS-CoV-2 infection. A population-based nationwide cohort study was performed using data from the National Health Insurance Service (NHIS) in the Republic of Korea. This study included 274,126 individuals who underwent SARS-CoV-2 PCR testing between 20 January 2020 and 1 October 2020. Among these patients, 28,338 tested positive for SARS-CoV-2, and 4,003 of these individuals had a history of influenza. The control group was selected through 1:1 propensity score matching. In the group of 4,003 COVID-19-positive individuals with no history of influenza, 192 (4.8%) experienced severe illness from COVID-19 infection. In the group of 4,003 COVID-19-positive individuals with a history of influenza, 260 (6.5%) had severe illness from COVID-19, and the overall adjusted odds ratio (aOR) was 1.29 (95% confidence interval 1.04-1.59). Among the 4,003 COVID-19-positive individuals with a history of influenza, severe COVID-19 infection was experienced by 143 of 1,760 (8.1%) with an influenza history within 1 year before the onset of COVID-19, 48 of 1,129 (4.3%) between 1 and 2 years, and 69 of 1,114 (6.2%) between 2 and 3 years before COVID-19 onset, and the aORs were 1.54 (1.20-1.98), 1.19 (0.84-1.70), and 1.00 (0.73-1.37), respectively. In conclusion, individuals who had an influenza infection less than 1 year before COVID-19 infection were at an increased risk of experiencing severe illness from the SARS-CoV-2 infection. To control the public health burden, it is essential that effective public health control measures, which include influenza vaccination, hand washing, cough etiquette, and mask use are in place.

Keywords: COVID 19; Influenza; SARS-CoV-2; mortality; severity; twindemic.

Figure 1.

The influenza-positive group was classified into five subgroups according to history of influenza infection within 1 year, 1–2 years, 2–3 years before the onset of the COVID-19 pandemic.

Figure 2.

Distribution and flow chart of influenza and SARS-CoV-2 patients in a nationwide Korean cohort.

Figure 3.

Propensity score-matched association between influenza and severe clinical outcomes of COVID-19 in patients who tested positive for SARS-CoV-2. Sensitivity analysis was performed according to 1) matching ratio, 2) matching variables (minimally: age + sex + demography, 3 underlying diseases: minimally + HTN + DM + CKD matching, 4 underlying diseases: minimally + HTN + DM + CKD + lung diseases matching, 5 underlying diseases: minimally + HTN + DM + CKD + lung diseases + liver diseases matching, fully matching: minimally + HTN + DM + CKD + lung diseases + liver diseases + cardiac diseases (CHF + angina + MI) matching). (Abbreviations: HTN, hypertension; DM, diabetes mellitus; CKD, chronic kidney disease; CHF, congestive heart failure; MI, myocardial infarction).

Figure 4.

Sensitivity analysis was performed according to 1) matching ratio, 2) matching variables (minimally: age + sex + demography, 3 underlying diseases: minimally + HTN + DM + CKD matching, 4 underlying diseases: minimally + HTN + DM + CKD + lung diseases matching, 5 underlying diseases: minimally + HTN + DM + CKD + lung diseases + liver diseases matching, fully matching: minimally + HTN + DM + CKD + lung diseases + liver diseases + cardiac diseases (CHF + angina + MI) matching). (Abbreviations: HTN, hypertension; DM, diabetes mellitus; CKD, chronic kidney disease; CHF, congestive heart failure; MI, myocardial infarction)