Influenza A viruses dual and multiple infections with other respiratory viruses and risk of hospitalization and mortality

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Abstract

Introduction: Epidemiological studies have indicated that 5-38% of influenza like illnesses (ILI) develop into severe disease due to, among others, factors such as; underlying chronic diseases, age, pregnancy, and viral mutations. There are suggestions that dual or multiple virus infections may affect disease severity. This study investigated the association between co-infection between influenza A viruses and other respiratory viruses and disease severity. Methodology: Datum for samples from North West England tested between January 2007 and June 2012 was analysed for patterns of co-infection between influenza A viruses and ten respiratory viruses. Risk of hospitalization to a general ward ICU or death in single versus mixed infections was assessed using multiple logistic regression models. Results: One or more viruses were identified in 37.8% (11,715/30,975) of samples, of which 10.4% (1,214) were mixed infections and 89.6% (10,501) were single infections. Among patients with influenza A(H1N1)pdm09, co-infections occurred in 4.7% (137⁄2,879) vs. 6.5% (59⁄902) in those with seasonal influenza A virus infection. In general, patients with mixed respiratory virus infections had a higher risk of admission to a general ward (OR: 1.43, 95% CI: 1.2 – 1.7, p = <0.0001) than those with a single infection. Co-infection between seasonal influenza A viruses and influenza B virus was associated with a significant increase in the risk of admission to ICU/ death (OR: 22.0, 95% CI: 2.21 – 219.8 p = 0.008). RSV/seasonal influenza A viruses co-infection also associated with increased risk but this was not statistically significant. For the pandemic influenza A(H1N1)pdm09 virus, RSV and AdV co-infection increased risk of hospitalization to a general ward, whereas Flu B increased risk of admission to ICU/ death, but none of these were statistically significant. Considering only single infections, RSV and hPIV1-3 increased risk of admission to a general ward (OR: 1.49, 95% CI: 1.28 – 1.73, p = <0.0001 and OR: 1.34, 95% CI: 1.003 – 1.8, p = 0.05) and admission to ICU/ death (OR: 1.5, 95% CI: 1.20 – 2.0, p = <0.0001 and OR: 1.60, 95% CI: 1.02 – 2.40, p = 0.04). Conclusion: Co-infection is a significant predictor of disease outcome; there is insufficient public health data on this subject as not all samples sent for investigation of respiratory virus infection are tested for all respiratory viruses. Integration of testing for respiratory viruses’ co-infections into routine clinical practice and R&D on integrated drugs and vaccines for influenza A&B, RSV, and AdV, and development of multi-target diagnostic tests is encouraged.

Layman's Abstract

Introduction: Studies indicate that up to a third (5-38%) of patients with flu develop serious disease. A number of reasons makes this happen; in some cases, flu is more severe when it attacks individuals who have lifelong illnesses like diabetes, or with other risk factors. Some reports have suggested that being infected with more than one respiratory virus increases the chances of developing more severe flu. This study compared hospitalizations and deaths in patients infected with a single virus, and those who had mixed infections.Methodology: Records of results of laboratory tests that were done to investigate whether one had a flu like virus, between January 2007 and June 2012, at the Manchester Microbiology Partnership Laboratory, and were patients from North West England, were used to make this comparison. Results: One or more viruses were identified in 37.8% (11,715/30,975) of patients, of which 10.4% (1,214) were mixed infections and 89.6% (10,501) were single infections. Four point seven percent (4.7%) of the 2,879 patients with pandemic influenza virus and 6.5% of the 902 patients with seasonal influenza A virus had mixed infections. Generally, having a mixed infection increased ones chances of being admitted to a general ward (GW) by 43%. The odds of being admitted to a general ward or dying were 22-folds if one had a combined infection between seasonal influenza A and influenza B viruses. Having RSV and seasonal influenza A virus mixed infection slightly increased the risk of being admitted to an intensive care unit (ICU) or dying. Similarly, ones risk of being hospitalized to a GW increased if one had a mixed infection between pandemic influenza A(H1N1) virus and RSV or pandemic flu with adenovirus (AdV), or were more likely to be admitted to an ICU if they had pandemic virus and Flu B. However, single infection with RSV or human parainfluenza virus types 1 or 2 or 3 also increased the risk of being hospitalized to a general ward, the ICU or dying. Conclusion: The results show that having a mixed virus infection is one of the reasons that causes more severed flu. This study calls on the development of multi-target tests and highly recommends routine testing of RSV and AdV in patients suspected of suffering from influenza A or B in clinical practice. It also calls for research on drugs and vaccines that target influenza A, Flu B, RSV, and AdV because of their role in causing more severe disease when they co-infect with influenza virus.

Keyword(s)

influenza A virus, Flu A, pandemic influenza A(H1N1)pdm09, respiratory virus infections, influenza B virus, Flu B, respiratory syncytial virus, RSV, rhinovirus, RV, adenovirus, AdV, human metapneumovirus, hMPV, parainfluenza virus types 1 to 3, hPIV1-3, hospitalization, admission to a general ward (GW), admission to an intensive care unit (ICU), death, mortality, severe disease, severity

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