Impact of Coinfection With SARS-CoV-2 and Influenza on Disease Severity: A Systematic Review and Meta-Analysis

Abstract

Background: Although coinfection with influenza in COVID-19 patients has drawn considerable attention, it is still not completely understood whether simultaneously infected with these two viruses influences disease severity. We therefore aimed to estimate the impact of coinfected with SARS-CoV-2 and influenza on the disease outcomes compared with the single infection of SARS-CoV-2.Materials and Methods: We searched the PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure Database (CNKI) to identify relevant articles up to July 9, 2021. Studies that assessed the effect of SARS-CoV-2 and influenza coinfection on disease outcomes or those with sufficient data to calculate risk factors were included. Risk effects were pooled using fixed or random effects model.Results: We ultimately identified 12 studies with 9,498 patients to evaluate the risk effects of SARS-CoV-2 and influenza coinfection on disease severity. Results indicated that coinfection was not significantly associated with mortality (OR = 0.85, 95%CI: 0.51, 1.43; p = 0.55, I2 = 76.00%). However, mortality was found significantly decreased in the studies from China (OR = 0.51, 95%CI: 0.39, 0.68; I2 = 26.50%), while significantly increased outside China (OR = 1.56, 95%CI: 1.12, 2.19; I2 = 1.00%). Moreover, a lower risk for critical outcomes was detected among coinfection patients (OR = 0.64, 95%CI: 0.43, 0.97; p = 0.04, I2 = 0.00%). Additionally, coinfection patients presented different laboratory indexes compared with the single SARS-CoV-2 infection, including lymphocyte counts and APTT.Conclusion: Our study revealed that coinfection with SARS-CoV-2 and influenza had no effect on overall mortality. However, risk for critical outcomes was lower in coinfection patients and different associations were detected in the studies from different regions and specific laboratory indexes. Further studies on influenza strains and the order of infection were warranted. Systematic testing for influenza coinfection in COVID-19 patients and influenza vaccination should be recommended.

Epidemiological Consequences of Viral Interference: A Mathematical Modeling Study of Two Interacting Viruses

“…Some studies have found that coinfections decrease disease severity (Martin et al, 2011 , 2013 ) or are at least no more severe than mono-infections (Brand et al, 2012 ; Martin et al, 2013 ; Asner et al, 2014 ; Rotzen-Ostlund et al, 2014 ; Mexico Emerging Infect Dis, 2019 ; Xiang et al, 2021 ), although others have found that coinfections can be more severe than mono-infections (Waner, 1994 ; Goka et al, 2015 ; Alosaimi et al, 2021 ; Musuuza et al, 2021 ). In the case of SARS-CoV-2 coinfections, studies are equally mixed about the severity of clinical disease, with some studies indicating a protective effect (Chekuri et al, 2021 ; Goldberg et al, 2021 ), others showing a worsening of clinical outcomes (Alosaimi et al, 2021 ; Stowe et al, 2021 ), and still others showing no significant difference between SARS-CoV-2 coinfections and mono-infections (Cheng et al, 2021 ; Guan et al, 2021 ). A meta-analysis of SARS-CoV-2 coinfections with influenza indicated no overall increase in mortality associated with coinfections, but found that SARS-CoV-2/influenza coinfections had decreased mortality in China and increased mortality in other regions (Guan et al, 2021 ), suggesting that other factors besides the characteristics of the two pathogens might be involved in determining severity.…”

“…In the case of SARS-CoV-2 coinfections, studies are equally mixed about the severity of clinical disease, with some studies indicating a protective effect (Chekuri et al, 2021 ; Goldberg et al, 2021 ), others showing a worsening of clinical outcomes (Alosaimi et al, 2021 ; Stowe et al, 2021 ), and still others showing no significant difference between SARS-CoV-2 coinfections and mono-infections (Cheng et al, 2021 ; Guan et al, 2021 ). A meta-analysis of SARS-CoV-2 coinfections with influenza indicated no overall increase in mortality associated with coinfections, but found that SARS-CoV-2/influenza coinfections had decreased mortality in China and increased mortality in other regions (Guan et al, 2021 ), suggesting that other factors besides the characteristics of the two pathogens might be involved in determining severity.…”

COVID-19 Vaccine Effectiveness at a Referral Hospital in Northern Peru: A Retrospective Cohort Study

“…It has been observed that those vaccinated against influenza and pneumococcus had indirect benefits with respect to the risk of COVID-19 [ 25 ]. In addition, co-infection with SARS-CoV-2 and influenza has been shown to have no effect on mortality [ 26 ]. This suggests that vaccination against different respiratory pathogens may confer an additional immune protection against COVID-19.…”

SARS-CoV-2 and other airborne respiratory viruses in outdoor aerosols in three Swiss cities before and during the first wave of the COVID-19 pandemic

“…8–9), the rare cases of SARS-CoV-2 coinfected with HCoV-229E have been reported ( Boschiero et al, 2022 , Lau et al, 2021 ), suggesting similar rare coinfections between SARS-CoV-2 and other viruses should not be overlooked. After all, the possibility of the emergence of a more virulent and contagious variant of either SARS-CoV-2 or other virus through this way should not be neglected, in addition to the concern that the coinfections with other viruses such as adenovirus and influenza may enhance SARS-CoV-2 infectivity, aggravate the symptoms and even increase mortality( Bai et al, 2021 , Guan et al, 2021 , Swets et al, 2022 ). Clearly, monitoring these viruses in air may give us an early warning.…”