Symptom propagation in respiratory pathogens of public health concern: a review of the evidence

Symptom propagation occurs when the symptom set an individual experiences is correlated with the symptom set of the individual who infected them. Symptom propagation may dramatically affect epidemiological outcomes, potentially causing clusters of severe disease. Conversely, it could result in chains of mild infection, generating widespread immunity with minimal cost to public health. Despite accumulating evidence that symptom propagation occurs for many respiratory pathogens, the underlying mechanisms are not well understood. Here we conducted a scoping literature review for 14 respiratory pathogens to ascertain the extent of evidence for symptom propagation by two mechanisms: dose-severity relationships and route-severity relationships. We identify considerable heterogeneity between pathogens in the relative importance of the two mechanisms, highlighting the importance of pathogen-specific investigations. For almost all pathogens, including influenza and SARS-CoV-2, we found support for at least one of the two mechanisms. For some pathogens, including influenza, we found convincing evidence that both mechanisms contribute to symptom propagation. Furthermore, infectious disease models traditionally do not include symptom propagation. We summarise the present state of modelling advancements to address the methodological gap. We then investigate a simplified disease outbreak scenario, finding that under strong symptom propagation, quarantining mildly infected individuals can have negative epidemiological implications. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement PA and MJK were supported by the Engineering and Physical Sciences Research Council through the MathSys CDT [grant number EP/S022244/1]. MJK was also supported by the Medical Research Council through the JUNIPER partnership award [grant number MR/X018598/1]. MJK and EMH are linked with the JUNIPER partnership (MRC grant no MR/X018598/1) and would like to acknowledge their help and support. RM was supported by The Leckie Fellowship, the Medical Research Council [grant number MC UU 00022/4] and the Chief Scientist Office [grant number SPHSU19]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. For the purpose of open access, the authors have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced are available online at https://github.com/pasplin/symptom-propagation-case-study