Influenza A Virus Exposure May Cause Increased Symptom Severity and Deaths in Coronavirus Disease 2019
The coronavirus disease 2019 (COVID-19) outbreak, caused by the novel coronavirus (2019-nCoV), has become a global public health emergency. The outbreak occurred during the flu season in the northern hemisphere, raising concerns about the potential impact of influenza A virus (IAV) exposure on COVID-19 patients. This study aimed to analyze the effects of IAV exposure on the clinical characteristics and outcomes of COVID-19 patients.
The study was conducted as a retrospective cohort analysis of 70 COVID-19 patients admitted to an isolation ward in Tongji Hospital, Wuhan, China, between January and February 2020. All patients were confirmed to have 2019-nCoV infection through reverse transcription-polymerase chain reaction (RT-PCR) of pharyngeal or nasopharyngeal swabs and chest computed tomography results. Serum tests for respiratory pathogen immunoglobulin M (IgM) antibodies, including IAV, were performed upon admission. Patients were excluded if they tested positive for IgM antibodies against other pathogens such as influenza B, mycoplasma, or respiratory syncytial virus (RSV).
Among the 70 patients, 32 (45.71%) tested positive for anti-IAV IgM, indicating recent exposure to IAV. The baseline characteristics, symptoms, and inflammation biomarkers were compared between the IAV-positive and IAV-negative groups. The IAV-positive group had a significantly higher proportion of female patients (59.38% vs. 34.21%) and patients reporting fatigue (59.38% vs. 34.21%). Fever and cough were the most common symptoms in both groups, with no significant differences in other symptoms. However, the IAV-positive group tended to have more complaints overall.
Inflammation biomarkers, including soluble interleukin 2 receptor (sIL-2R) and tumor necrosis factor alpha (TNFα), were measured upon admission. Surprisingly, the levels of sIL-2R (median 791.00 vs. 1075.50 IU/mL) and TNFα (median 10.75 vs. 11.50 pg/mL) were significantly lower in the IAV-positive group. This finding contrasts with previous reports that both 2019-nCoV and IAV infections elevate these biomarkers, suggesting complex cytokine interactions in co-infected patients.
Disease severity was classified into common, severe, and critical types based on the national COVID-19 treatment protocol. The IAV-positive group had a higher proportion of critical patients (31.25% vs. 15.79%) and a higher fatality rate (21.88% vs. 7.89%), although these differences did not reach statistical significance. Notably, the use of oseltamivir, an antiviral medication for influenza, had a significant impact on outcomes in the IAV-positive group. Among IAV-positive patients, those who received oseltamivir had a fatality rate of 0%, compared to 36.84% in those who did not receive the drug. This suggests that empirical use of oseltamivir may reduce mortality in COVID-19 patients with recent IAV exposure.
The study highlights the importance of considering IAV exposure during the flu season, as it may exacerbate COVID-19 symptoms and increase the risk of severe outcomes. The high prevalence of anti-IAV IgM positivity in this cohort (45.71%) underscores the potential for co-infections or consecutive infections with 2019-nCoV and IAV. However, the retrospective nature of the study and the lack of RT-PCR confirmation for IAV infection limit the ability to distinguish between co-infection and recent exposure.
The findings also have important implications for clinical practice. During the flu season, clinicians should be vigilant for the possibility of IAV exposure in COVID-19 patients and consider the empirical use of oseltamivir in suspected cases. The study suggests that concurrent IAV infection may worsen the prognosis of COVID-19, and early antiviral treatment could mitigate this risk. However, prospective studies with larger sample sizes are needed to confirm these findings and further elucidate the mechanisms underlying the interaction between IAV and 2019-nCoV.
In conclusion, this study provides valuable insights into the impact of IAV exposure on COVID-19 patients. The results indicate that recent IAV exposure may lead to increased symptom severity and higher fatality rates in COVID-19 patients. The empirical use of oseltamivir appears to reduce mortality in IAV-positive patients, highlighting the potential benefits of anti-influenza treatment during the flu season. Future research should focus on larger, prospective studies to confirm these findings and explore the underlying mechanisms of IAV and 2019-nCoV interactions.
doi.org/10.1097/CM9.0000000000000966
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