Objectives: Evaluation of the presence and effect of SARS-CoV-2 co-infections on disease severity. Methods: We collected both symptom data and nose- and throat samples from symptomatic people during the 2022/2023 respiratory season in a large participatory surveillance study in the Netherlands, and tested these for 18 respiratory viruses including SARS-CoV-2. We compared reported health status, symptoms and odds of having a mono respiratory viral infection or co-infection with SARS-CoV-2 and another respiratory virus. Results: In total 4,655 samples were included with 22% (n=1,017) testing SARS-CoV-2 positive. Of these 11% (n=116) also tested positive for a second respiratory virus. The most frequently occurring co-infections in SARS-CoV-2 positive participants were with rhinovirus (59%; n=69), seasonal coronaviruses (15%; n=17) and adenovirus (7%; n=8). Participants with a co-infection with one of these three viruses did not report more severe disease compared to those with a SARS-CoV-2 mono-infection. The odds of experiencing SARS-CoV-2 co-infection with seasonal coronavirus or rhinovirus were lower compared to the odds of the respective non-SARS-CoV-2 mono-infection (OR: 0.16, CI 95%: 0.10 - 0.24; OR: 0.21 CI 95%: 0.17 - 0.26; respectively). Conclusions: SARS-CoV-2 co-infections with rhinovirus, seasonal coronavirus and adenovirus are frequently observed in the general population, but are not associated with more severe disease compared to SARS-CoV-2 mono-infections. Furthermore, we found indications for inter-virus interaction with rhinovirus and seasonal coronavirus, possibly decreasing risk of co-infection.

The authors have declared no competing interest.

This work was supported by the ministry of Health, Welfare and Sports (VWS), the Netherlands. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The samples were collected as part of Infectieradar. The protocol for Infectieradar was approved by the Medical Ethics Review Committee Utrecht (reference number: WAG/avd/20/008757; protocol 20-131) was obtained given the nature of data collection. All participants provided informed consent upon registration, which included agreement to the privacy statement and described the processing of personal data and research results, website security measures taken, and how to file a complaint. Participants were eligible to withdraw from the study at any time. Individuals had to be 16 years or over to be able to participate.

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The processed data required to reproduce the findings of this study are available from the corresponding author upon reasonable request. Due to confidentiality concerns, access to the raw data may be restricted.