Respiratory viral co‐infections in patients with COVID‐19 and associated outcomes: A systematic review and meta‐analysis

Abstract

The aim of this systematic review and meta‐analysis was to critically assess the published literature related to community‐acquired viral co‐infections and COVID‐19 and to evaluate the prevalence, most identified co‐pathogens, and relevant risk factors. Furthermore, we aimed to examine the clinical features and outcomes of co‐infected compared to mono‐infected COVID‐19 patients. We systematically searched PubMed, Web of Science, Embase, Scopus, and The Cochrane Library for studies published from 1 November 2019 to 13 August 2021. We included patients of all ages and any COVID‐19 severity who were screened for respiratory viral co‐infection within 48 h of COVID‐19 diagnosis. The main outcome was the proportion of patients with a respiratory viral co‐infection. The systematic review was registered to PROSPERO (CRD42021272235). Out of 6053 initially retrieved studies, 59 studies with a total of 16,643 SARS‐CoV‐2 positive patients were included. The global pooled prevalence was 5.01% (95% CI 3.34%–7.27%; I 2 = 95%) based on a random‐effects model, with Influenza Viruses (1.54%) and Enteroviruses (1.32%) being the most prevalent pathogens. Subgroup analyses showed that co‐infection was significantly higher in paediatric (9.39%) than adult (3.51%) patients ( p ‐value = 0.02). Furthermore, co‐infected patients were more likely to be dyspnoeic and the odds of fatality (OR = 1.66) were increased. Although a relatively low proportion of COVID‐19 patients have a respiratory viral co‐infection, our findings show that multiplex viral panel testing may be advisable in patients with compatible symptoms. Indeed, respiratory virus co‐infections may be associated with adverse clinical outcomes and therefore have therapeutic and prognostic implications.

Influenza and COVID-19 Co-infection

“…Likewise, from a public health standpoint, SARS-CoV-2 and influenza virus co-infection combined with variable clinical prognosis poses a greater challenge. A systematic review by Krumbein et al revealed that a higher case-fatality rate was associated with COVID-19 and other viruses' co-infection (13). This is consistent with other studies showing a positive relation between co-infection and increased mortality risk and severity of the disease in these patients (11,14).…”

Omicron-induced interferon signalling prevents influenza A virus infection

“…Further research will have to show the relevance of our findings in the context of SARS-CoV-2/ influenza virus co-infection. Data on the severity of SARS-CoV-2/ influenza A virus co-infections are inconsistent in cell culture and animal models [Andrés et al, 2022; Kim EH et al, 2022; Kim HK et al, 2022; Oishi et al, 2022] and in humans [Cuadrado-Payán et al, 2020; Yue et al, 2020; Alosaimi et al, 2021; Stowe et al, 2021; Xiang et al, 2021; Krumbein et al, 2022; Swets et al, 2022]. This may not be a surprise, given the differences in interferon signalling between different SARS-CoV-2 variants that we present here and that were described in previous studies [Alfi et al, 2022; Bojkova et al, 2022; Bojkova et al, 2022a; Guo et al, 2022; Thorne et al, 2022].…”

Polymicrobial Infections in the Immunocompromised Host: The COVID-19 Realm and Beyond

“…The phenomenon of co-infection or superinfection with other viruses, bacteria or fungi is being increasingly reported during the COVID-19 pandemic, though the rate remains relatively low with one study demonstrating 8% rate of bacterial and fungal community-acquired co-infections [ 16 ], and another study citing a rate of 2.1% for bacterial and 0.6% for viral co-infections [ 17 ] during the early stages of the pandemic. A metanalysis demonstrated a pooled prevalence of viral co-infections of 5% with influenza and rhinovirus being the most common, followed by adenovirus and human coronaviruses [ 18 ]. Studies have demonstrated increased severity of COVID-19, more frequent ICU admissions and higher risk of death in co-infected patients [ 17 , 18 , 19 , 20 , 21 ].…”

“…A metanalysis demonstrated a pooled prevalence of viral co-infections of 5% with influenza and rhinovirus being the most common, followed by adenovirus and human coronaviruses [ 18 ]. Studies have demonstrated increased severity of COVID-19, more frequent ICU admissions and higher risk of death in co-infected patients [ 17 , 18 , 19 , 20 , 21 ]. Incidence of non-SARS-CoV-2 respiratory viruses was significantly impacted by social distancing measures at the start of the pandemic.…”