Viral interference with SARS-CoV-2 during the COVID-19 pandemic: An individual participant data meta-analysis

Viral interference between SARS-CoV-2 and other respiratory virus infections has been implicated, but symptom-based testing in observational studies may bias estimations. We used individual participant data from ten cohort studies conducted during pandemic years 2020-2024 to study virus interference. Respiratory samples were PCR-tested for viruses including SARS-CoV-2. The primary analysis was based on samples collected from cohort participants regardless of respiratory symptoms. A secondary analysis included only symptom-based testing data. We estimated odds ratios for co-occurrence of SARS-CoV-2 with other respiratory viruses. The primary analysis included data from six cohorts ( n = 1 023). In total 205 of 2 465 samples were SARS-CoV-2 positive (8.3%). Co-detections with SARS-CoV-2 occurred less frequently than expected under the assumption of zero interference (OR: 0.72; 95% CI: 0.40-1.25) for samples positive for another virus. The secondary analysis (five cohorts, n = 1 715) included 2 088 samples from symptomatic subjects, with 506 SARS-CoV-2 infections (24.2%). The OR of SARS-CoV-2 detection was 0.16 (95% CI: 0.10-0.25) for samples positive for another virus. Minimizing selection bias, our results still point towards negative viral interference with SARS-CoV-2, but effect-estimates are weaker and non-significant. Apart from selection bias, the stronger effects found in symptomatic individuals could also indicate that symptomatic infection enhances virus interference.