Influenza A virus exposure may cause increased symptom severity and deaths in coronavirus disease 2019

Abstract

Background: The coronavirus disease 2019 (COVID-19) outbreak occurred during the flu season around the world. This study aimed to analyze the impact of influenza A virus (IAV) exposure on COVID-19.

Methods: Seventy COVID-19 patients admitted to the hospital during January and February 2020 in Wuhan, China were included in this retrospective study. Serum tests including respiratory pathogen immunoglobulin M (IgM) and inflammation biomarkers were performed upon admission. Patients were divided into common, severe, and critical types according to disease severity. Symptoms, inflammation indices, disease severity, and fatality rate were compared between anti-IAV IgM-positive and anti-IAV IgM-negative groups. The effects of the empirical use of oseltamivir were also analyzed in both groups. For comparison between groups, t tests and the Mann-Whitney U test were used according to data distribution. The Chi-squared test was used to compare disease severity and fatality between groups.

Results: Thirty-two (45.71%) of the 70 patients had positive anti-IAV IgM. Compared with the IAV-negative group, the positive group showed significantly higher proportions of female patients (59.38% vs. 34.21%, χ = 4.43, P = 0.035) and patients with fatigue (59.38% vs. 34.21%, χ = 4.43, P = 0.035). The levels of soluble interleukin 2 receptor (median 791.00 vs. 1075.50 IU/mL, Z = -2.70, P = 0.007) and tumor necrosis factor α (median 10.75 vs. 11.50 pg/mL, Z = -2.18, P = 0.029) were significantly lower in the IAV-positive group. Furthermore, this group tended to have a higher proportion of critical patients (31.25% vs. 15.79%, P = 0.066) and a higher fatality rate (21.88% vs. 7.89%, P = 0.169). Notably, in the IAV-positive group, patients who received oseltamivir had a significantly lower fatality rate (0 vs. 36.84%, P = 0.025) compared with those not receiving oseltamivir.

Conclusions: The study suggests that during the flu season, close attention should be paid to the probability of IAV exposure in COVID-19 patients. Prospective studies with larger sample sizes are needed to clarify whether IAV increases the fatality rate of COVID-19 and to elucidate any benefits of empirical usage of oseltamivir.

Figure 1

Distribution of disease severity in IAV-negative and IAV-positive groups. The Fisher Exact test was used to compare the severity between IAV-negative and IAV-positive groups. In the IAV-positive group, the proportion of critical type patients tended to be higher, but with no statistical significance (31.25% vs. 15.79%, P = 0.066). Common type: Patients with pneumonia but with no signs of severe type or critical type. Severe type: Patients with respiratory frequency ≥30/min, blood oxygen saturation ≤93% at room air, and/or partial pressure of arterial oxygen to fraction of inspired oxygen ratio ≤300 mmHg. Critical type: Patients with respiratory failure that required mechanical ventilation, septic shock, and/or multiple organ dysfunction or failure that demanded the intensive care unit treatment. IAV: Influenza A virus; COVID-19: Coronavirus disease 2019.

Figure 2

Distribution of disease severity in oseltamivir and non-oseltamivir group stratified by anti-IAV IgM positivity. The Fisher Exact test was used to compare the severity and fatality rate between oseltamivir and non-oseltamivir group, stratified by anti-IAV IgM. Common type: COVID-19 patients with pneumonia but with no signs of severe type or critical type. Severe type: Patients with respiratory frequency ≥30/min, blood oxygen saturation ≤93% at room air, and/or partial pressure of arterial oxygen to fraction of inspired oxygen ratio ≤300 mmHg. Critical type: Patients with respiratory failure that required mechanical ventilation, septic shock, and/or multiple organ dysfunction or failure that demanded the intensive care unit treatment. IAV: Influenza A virus; IgM: immunoglobulin M; COVID-19: Coronavirus disease 2019.