In this study, we report the paucity of respiratory co-pathogens detected in COVID-19 patients presenting with ARI compared with the background rates of respiratory pathogens in non-COVID-19 ARI patients. We observed seasonal changes both in incidence and variety (supplementary Table 3). While in spring 2020 we detected influenza, RSV, HMPV and seasonal coronaviruses, later in the year we saw the disappearance of those viruses with almost exclusive detection of HRV (as implied from supplementary Fig. 2). Our findings are compatible with the 2020–2021 disappearance of influenza and RSV as reported by the Israeli Center for Disease Control (ICDC)[9].
Unlike other reports addressing co-pathogen occurrence in COVID-19 patients[10–13], our study was designed to circumvent several biases: i) we included only ED admitted patients with acute respiratory complaints and age-matched them. ii) the study was annual and longitudinal with similar number of samples per group monthly. This highly selective design overcomes biases of either secondary/nosocomial complications of severe COVID-19 patients or merely a “virome map” from testing asymptomatic COVID-19 patients.
Numerous factors presumably account for the disappearance of major respiratory viruses during COVID-19 pandemic year: social distancing, face masks, gloves and extensive hand and surface disinfection, lockdowns and flight halting. Never the less, SARS-CoV-2 incidence and prevalence were extremely high during disease surges despite these measures and the low activity of other viruses. Thus, did the new player in the "respiratory arena" displace other viral pathogens? Does these phenomena are related to intrinsic viral factors effecting epidemiological patterns of SARS-CoV-2 transmissibility compared to other respiratory viruses? A recent Australian study demonstrated that with the decline of COVID-19 and the lift of restrictions, a rise in RSV activity was detected [14]. Likewise, a reflexive rise in respiratory illness and detected viruses is noted from the ICDC latest reports[15]. However, the relatedness of the resurgence of other respiratory viruses to the actual presence of airways SARS-CoV-2 remains unanswered.
A notable observation of our study is the paucity of respiratory co-pathogens detected in COVID-19 patients. Should this observation prove consistent, it may have a significant impact on the diagnostic flow of ARI patients in high-COVID-19 prevalence zones, questioning the immediate need to search for pathogens other than SARS-CoV-2. This observation may further influence infection control policies in terms of placement of ARI patients within the emergency departments and later, hospitalization units, especially those of vulnerable patients as immunocompromised and pregnant women.
In conclusion, the annual rates of co-pathogens in Israeli COVID-19 patients with ARI were low compared with the background rates of respiratory pathogens in SARS-CoV-2 negative ARI patients. The appearance patterns of the various pathogens diverged from previous years and along the study period, with human rhinovirus being the prominent non-SARS-CoV-2 pathogen. Further studies should address the impact of SARS-CoV-2 presence per-se on the co-occurrence of other respiratory pathogens seasonality and diversity. Such data are of major importance for policy makers with regards to surveillance, acute illness diagnostics and infection control.