Distinguishing COVID-19 from seasonal influenza in patients under age 65 years—a retrospective observational cohort study comparing the 2009 influenza A (H1N1) and 2022 SARS-CoV-2 pandemics

INTRODUCTION: This study explored the differences in clinical characteristics between the 2009 pandemic influenza A (H1N1) and SARS-CoV-2 BA.2 variant (Omicron) infections in patients younger than age 65 years, to improve identification of these diseases and better respond to the current epidemic. METHODS: Data from 127 patients with the 2009 pandemic influenza A (H1N1) diagnosed between May and July of 2009 and 3,265 patients with Omicron diagnosed between March and May of 2022 were collected. Using a 1:2 match based on age (difference <2 years), sex, and underlying diseases, data from 115 patients with the 2009 pandemic influenza A (H1N1) infection (H1N1 group) and 230 patients with SARS-CoV-2 Omicron BA.2 infection (Omicron group) were analyzed. The clinical manifestations were compared between the groups, logistic regression was performed to identify possible independent risk factors for each group, and multiple linear regression was used to analyze the factors predicting time for nucleic acid negativization (NAN). RESULTS: The median [interquartile range] age of the two groups was 21 [11, 26] years. Compared with the H1N1 group, the Omicron group had: lower white blood cell counts and C-reactive protein levels; less fever, nasal congestion, sore throat, cough, sputum, and headache; and more olfactory loss, muscle soreness, and lactate dehydrogenase (LDH) abnormalities. Patients in the Omicron group used fewer antibiotics and antiviral drugs, and the time for NAN was longer (17 [14,20] VS 4 [3,5] days, P<0.001). Logistic regression showed that fever, cough, headache, and increased white blood cell count were more strongly correlated with the H1N1 group, while muscle soreness and LDH abnormalities were more strongly correlated with the Omicron group. Fever (B 1.529, 95% confidence interval [0.149,2.909], P=0.030) significantly predicted a longer time for NAN in patients with Omicron. DISCUSSION: There are significant differences in clinical characteristics between SARS-CoV-2 Omicron infection and the 2009 pandemic influenza A (H1N1) infection. Recognition of these differences has important implications for clinical practice.