The role of respiratory co-infection with influenza or respiratory syncytial virus in the clinical severity of COVID-19 patients: A systematic review and meta-analysis

Abstract

Background: With the easing of COVID-19 non-pharmaceutical interventions, the resurgence of both influenza and respiratory syncytial virus (RSV) was observed in several countries globally after remaining low in activity for over a year. However, whether co-infection with influenza or RSV influences disease severity in COVID-19 patients has not yet been determined clearly. We aimed to understand the impact of influenza/RSV co-infection on clinical disease severity among COVID-19 patients.

Methods: We conducted a systematic literature review of publications comparing the clinical severity between the co-infection group (ie, influenza/RSV with SARS-CoV-2) and mono-infection group (ie, SARS-CoV-2), using the following four outcomes: need or use of supplemental oxygen, intensive care unit (ICU) admission, mechanical ventilation, and deaths. We summarized the results by clinical outcome and conducted random-effect meta-analyses where applicable.

Results: Twelve studies reporting a total of 7862 COVID-19 patients were included in the review. Influenza and SARS-CoV-2 co-infection were found to be associated with a higher risk of ICU admission (five studies, odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.64-2.68) and mechanical ventilation (five studies, OR = 2.31, 95% CI = 1.10-4.85). No significant association was found between influenza co-infection and need/use of supplemental oxygen or deaths among COVID-19 patients (four studies, OR = 1.04, 95% CI = 0.37-2.95; 11 studies, OR = 1.41, 95% CI = 0.65-3.08, respectively). For RSV co-infection, data were only sufficient to allow for analyses for the outcome of deaths, and no significant association was found between RSV co-infection and deaths among COVID-19 patients (three studies, OR = 5.27, 95% CI = 0.58-47.87).

Conclusions: Existing evidence suggests that co-infection with influenza might be associated with a 2-fold increase in the risk for ICU admission and for mechanical ventilation among COVID-19 patients whereas evidence is limited on the role of RSV co-infection. Co-infection with influenza does not increase the risk of death in COVID-19 patients.

Registration: PROSEPRO CRD42021283045.

Figure 1

PRISMA diagram for selection of studies.

Figure 2

Comparison of risk for need or use of supplemental oxygen between SARS-CoV-2 mono-infection and A) SARS-CoV-2 co-infection with influenza, B) SARS-CoV-2 co-infection with influenza A virus. Panel A – SARS-CoV-2 co-infection with influenza. Panel B – SARS-CoV-2 co-infection with influenza A virus. N – the total number of SARS-CoV-2 coinfected and mono-infected patients, QA – the score of quality assessment.

Figure 3

Comparison of risk for mechanical ventilation between SARS-CoV-2 mono-infection and A) SARS-CoV-2 co-infection with influenza, B) SARS-CoV-2 co-infection with influenza A virus. Panel A – SARS-CoV-2 co-infection with influenza. Panel B – SARS-CoV-2 co-infection with influenza A virus. N – the total number of SARS-CoV-2 coinfected and mono-infected patients, QA – the score of quality assessment.

Figure 4

Comparison of risk for ICU admission between SARS-CoV-2 mono-infection and A) SARS-CoV-2 co-infection with influenza, B) SARS-CoV-2 co-infection with influenza A virus. Panel A – SARS-CoV-2 co-infection with influenza. Panel B – SARS-CoV-2 co-infection with influenza A virus. N – the total number of SARS-CoV-2 coinfected and mono-infected patients, QA – the score of quality assessment.

Figure 5

Comparison of risk for death between SARS-CoV-2 mono-infection and A) SARS-CoV-2 co-infection with influenza, B) SARS-CoV-2 co-infection with influenza A virus, C) SARS-CoV-2 co-infection with influenza B virus, D) SARS-CoV-2 co-infection with RSV. Panel A – SARS-CoV-2 co-infection with influenza. Panel B – SARS-CoV-2 co-infection with influenza A virus. Panel C – SARS-CoV-2 co-infection with influenza B virus. Panel D – SARS-CoV-2 co-infection with RSV. N – the total number of SARS-CoV-2 coinfected and mono-infected patients, QA – the score of quality assessment.