78 Chapter 4 Introduction Co-infection with SARS-CoV-2 and additional endemic respiratory viruses has been reported in people with Coronavirus disease 2019 (COVID-19), potentially associated with increased disease severity1,2. However, current knowledge on these co-infections is limited: most studies are small (median 116 patients investigated for co-infection, interquartile range 70-840; Supplementary Table 1 and 2), restricted to specific patient cohorts (ICU or high risk patients)2–4, and do not report outcomes1,4–9.The incidence of respiratory virus co-infection also differs widely between studies, from 0 to 63% of patients1–6,8–11. Comparing results between studies is difficult given the use of different virologic diagnostic approaches. Furthermore, most studies were conducted over a short time1,3–5,8,9,11 and/or out with the typical influenza season1. Social distancing, self-isolation and the wearing of face coverings have reduced transmission of SARS-CoV-2. These non-pharmaceutical countermeasures have also reduced the transmission and associated disease burden of other endemic respiratory viruses, such as influenza and respiratory syncytial virus (RSV)5,12– 14. However, as these countermeasures are less stringently implemented and we enter the influenza season14, it is plausible we will see an increase in infections with SARS-CoV-2 and other respiratory viruses6,12. If co-infections lead to more severe disease, this could increase morbidity and mortality and use scarce hospital capacity, especially during traditional respiratory virus seasons. Influenza has been the predominant cause of severe seasonal respiratory viral disease for decades13. Risk factors for severe viral pneumonia are similar in SARSCoV-2 and influenza2,15. Seasonal influenza virus can cause severe disease leading to ICU admission, the need for invasive mechanical ventilation (IMV) and death16. Both influenza virus and SARS-CoV-2 damage the epithelial cells and cause inflammation17,18. Whilst RSV mainly causes bronchiolitis in children, it can cause severe viral pneumonia in the elderly and immunocompromised14. Adenovirus can also cause severe viral pneumonia, especially in immunocompromised people or those with many comorbidities19. Many that are discharged after severe infection suffer increased frailty20. Overall, understanding the clinical consequences of co-infection with SARS-CoV-2 and endemic respiratory viruses is of importance for anticipating clinical demand during the respiratory virus season. We aimed to investigate clinical characteristics and outcomes of respiratory virus co-infections in hospitalised people with COVID-19 in the ISARIC/WHO CCP-UK multicentre prospective cohort study.
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