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To assess these interactions, standard statistical tests of independence suggest that the prevalence ratio\u2014defined as the ratio of co-infection prevalence to the product of single-infection prevalences\u2014should equal unity for non-interacting pathogens. As a result, earlier epidemiological studies aimed to estimate the prevalence ratio from co-detection prevalence data, under the assumption that deviations from unity implied interaction. To examine the validity of this assumption, we designed a simulation study that built on a broadly applicable epidemiological model of co-circulation of two emerging or seasonal respiratory viruses. By focusing on the pair influenza\u2013SARS-CoV-2, we first demonstrate that the prevalence ratio systematically underestimates the strength of interaction, and can even misclassify antagonistic or synergistic interactions that persist after clearance of infection. In a global sensitivity analysis, we further identify properties of viral infection\u2014such as a high reproduction number or a short infectious period\u2014that blur the interaction inferred from the prevalence ratio. Altogether, our results suggest that ecological or epidemiological studies based on co-detection prevalence data provide a poor guide to assess interactions among respiratory viruses.<\/jats:p>","DOI":"10.1098\/rspb.2021.2358","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T09:00:22Z","timestamp":1641978022000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["The pitfalls of inferring virus\u2013virus interactions from co-detection prevalence data: application to influenza and SARS-CoV-2"],"prefix":"10.1098","volume":"289","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9302-4858","authenticated-orcid":true,"given":"Matthieu","family":"Domenech de Cell\u00e8s","sequence":"first","affiliation":[{"name":"Max Planck Institute for Infection Biology, Infectious Disease Epidemiology group, Charit\u00e9platz 1, Campus Charit\u00e9 Mitte, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3354-1730","authenticated-orcid":true,"given":"Elizabeth","family":"Goult","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Infection Biology, Infectious Disease Epidemiology group, Charit\u00e9platz 1, Campus Charit\u00e9 Mitte, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3271-9856","authenticated-orcid":true,"given":"Jean-Sebastien","family":"Casalegno","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie des HCL, IAI, CNR des virus \u00e0 transmission respiratoire (dont la grippe) H\u00f4pital de la Croix-Rousse F-69317, Lyon cedex 04, France"},{"name":"Virpath, Centre International de Recherche en Infectiologie (CIRI), Universit\u00e9 de Lyon Inserm U1111, CNRS UMR 5308, ENS de Lyon, UCBL F-69372, Lyon cedex 08, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6177-2309","authenticated-orcid":true,"given":"Sarah C.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Infection Biology, Infectious Disease Epidemiology group, Charit\u00e9platz 1, Campus Charit\u00e9 Mitte, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2022,1,12]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30310-4"},{"key":"e_1_3_6_3_2","volume-title":"Annual review of diseases prioritized under the research and development blueprint","author":"WHO Research and Development Blueprint","year":"2018","unstructured":"WHO Research and Development Blueprint. 2018 Annual review of diseases prioritized under the research and development blueprint. 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