Metabolomic and gut microbiome profiles across the spectrum of community-based COVID and non-COVID disease: A COVID-19 Biobank study

Whilst many with SARS-CoV-2 infection have mild disease, managed in the community, individuals with cardiovascular risk factors experienced often more severe acute disease, requiring hospitalisation. Increasing concern has also developed over long symptom duration in many individuals, including the majority who managed acutely in the community. Risk factors for long symptom duration, including biological variables, are still poorly defined. We examine post-illness metabolomic and gut-microbiome profiles, in community-dwelling participants with SARS-CoV-2, ranging from asymptomatic illness to Post-COVID Syndrome, and participants with prolonged non-COVID-19 illnesses. We also assess a pre-established metabolomic biomarker score for its association with illness duration. We found an atherogenic-dyslipidaemic metabolic profile, and greater biomarker scores, associated with longer illness, both in individuals with and without SARS-CoV-2 infection. We found no association between illness duration and gut microbiome in convalescence. Findings highlight the potential role of cardiometabolic dysfunction to the experience of long illness duration, including after COVID-19. ### Competing Interest Statement TDS is a shareholder and cofounder of ZOE Global Ltd, and has received payment for scientific consultancy services to ZOE Global Ltd. No other authors have competing interests to declare ### Funding Statement The CSS Biobank is supported by the Chronic Disease Research Foundation. We are also supported by the Wellcome EPSRC Centre for Medical Engineering at King's College London (WT 203148/Z/16/Z) and the UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. Investigators also received support from Medical Research Council (MRC), British Heart Foundation (BHF), Alzheimer's Society, European Union, NIHR, COVID-19 Driver Relief Fund (CDRF) and the NIHR-funded BioResource, Clinical Research Facility and Biomedical Research Centre (BRC) based at GSTT NHS Foundation Trust in partnership with KCL. SO was supported by the French government, through the 3IA Cote d'Azur Investments in the Future project managed by the National Research Agency (ANR) with the reference number ANR-19-P3IA-0002. ZOE Limited provided in-kind support for all aspects of building, running and supporting the app and service to all users worldwide. This research was funded in part by the Wellcome Trust [215010/Z/18/Z]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Study participants were volunteers from the COVID Symptom Study Biobank (CSSB, approved by Yorkshire & Humber NHS Research Ethics Committee Ref: 20/YH/0298). Individuals were recruited to the CSSB via the ZOE COVID Study (ZCS) using a smartphone-based app developed by Zoe Ltd, King's College London, the Massachusetts General Hospital, Lund University, and Uppsala University, launched in the UK on 24 March 2020 (approved by the King's College London Ethics Committee LRS-19/20-18210). 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data collected in the ZCS smartphone application are shared with other health researchers through the UK National Health Service-funded Health Data Research UK (HDRUK) and Secure Anonymised Information Linkage consortium, housed in the UK Secure Research Platform (Swansea, UK). Anonymised data are available to be shared with researchers according to their protocols in the public interest (). The code is available in: . Access to data in the CSS Biobank is available to bona fide health researchers on application to the CSS Biobank Management Group. Further details are available online at: including application forms and contact information.