Variant-specific symptoms of COVID-19 among 1,542,510 people in England

Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study has been monitoring the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell and taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and induced changes in daily activities will become increasingly important. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was funded by the Department of Health and Social Care in England. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of this manuscript. PE is Director of the Medical Research Council (MRC) Centre for Environment and Health (MR/L01341X/1, MR/S019669/1). PE acknowledges support from Health Data Research UK (HDR UK); the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre; NIHR Health Protection Research Units in Chemical and Radiation Threats and Hazards, and Environmental Exposures and Health; the British Heart Foundation Centre for Research Excellence at Imperial College London (RE/18/4/34215); and the UK Dementia Research Institute at Imperial College London (MC\_PC\_17114). HW acknowledges support from an NIHR Senior Investigator Award, the Wellcome Trust (205456/Z/16/Z), and the NIHR Applied Research Collaboration (ARC) North West London. JE is an NIHR academic clinical fellow in infectious diseases. GC is supported by an NIHR Professorship. CAD acknowledges support from the MRC Centre for Global Infectious Disease Analysis, the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections and the NIHR-funded Vaccine Efficacy Evaluation for Priority Emerging Diseases (PR-OD-1017-20007). MC-H and BB acknowledge support from Cancer Research UK, Population Research Committee Project grant 'Mechanomics' (grant No 22184 to MC-H). MC-H acknowledges support from the H2020-EXPANSE (Horizon 2020 grant No 874627) and H2020-LongITools (Horizon 2020 grant No 874739). ### 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: We obtained research ethics approval from the South Central-Berkshire B Research Ethics Committee (IRAS ID: 283787). Notification of favorable opinion and brief summary of the protocol are available here: https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/react1-covid-19-uph/ 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 Access to REACT-1 individual-level data is restricted to protect participants' anonymity. Summary statistics, descriptive tables, and code from the current REACT-1 study are available at https://github.com/mrc-ide/reactidd (doi 10.5281/zenodo.6550327). REACT-1 study materials are available for each round at https://www.imperial.ac.uk/medicine/research-and-impact/groups/react-study/react-1-study-materials/ Sequence read data are available without restriction from the European Nucleotide Archive at https://www.ebi.ac.uk/ena/browser/view/PRJEB37886, and consensus genome sequences are available from the Global initiative on sharing all influenza data (GISAID).