Background SARS-CoV-2 variant Omicron rapidly evolved over 2022, causing three waves of infection due to sub-variants BA.1, BA.2 and BA.4/5. We sought to characterise symptoms and viral loads over the course of COVID-19 infection with these sub-variants in otherwise-healthy, vaccinated, non-hospitalised adults, and compared data to infections with the preceding Delta variant of concern (VOC).Methods In a prospective, observational cohort study, healthy vaccinated UK adults who reported a positive PCR or lateral flow test, self-swabbed on alternate days until day 10. We compared symptoms and viral load trajectories between infections caused by VOCs Delta and Omicron (sub-variants BA.1, BA.2 and BA.4/5), and tested for relationships between vaccine dose, symptoms and PCR Ct value as a proxy for viral load.Results 555 infection episodes were reported among 483 participants. Across VOCs, symptom burden and duration were similar, however symptom profiles differed among infections caused by Delta compared to Omicron sub-variants; symptoms of all Omicron sub-variants BA.1, BA.2 and BA.4/5 were very similar. Anosmia was reported in 7-13% of participants with Omicron sub-variants, compared to 25/60 (42%) with Delta infection (P= 1.31e-08 or 1.03e-05 or 5.63e-05; χ2 test d2+Delta vs. Omicron BA.1 or vs. BA.2, or BA.5, respectively), fever was more common with Omicron BA.5 (30/55, 55%) than Delta (20/60, 33%) (p 0.03). Amongst infections with all Omicron sub-variants, symptoms of coryza, fatigue, cough and myalgia predominated. Viral load trajectories and peaks did not differ between Delta, and Omicron, irrespective of symptom severity (including asymptomatic participants), VOC or vaccination status. Ct values were negatively associated with time since vaccination in participants infected with BA.1; however, this trend was not observed in BA.2/BA.4/5 infections.Conclusion Our study emphasises both the changing symptom profile of COVID-19 infections in the Omicron era, and ongoing transmission risk of Omicron sub-variants in vaccinated adults.Trial registration NCT04750356### Competing Interest StatementCSw reports interests unrelated to this Correspondence: grants from BMS, Ono-Pharmaceuticals, Boehringer-Ingelheim, Roche-Ventana, Pfizer and Archer Dx, unrelated to this Correspondence; personal fees from Genentech, Sarah Canon Research Institute, Medicxi, Bicycle Therapeutics, GRAIL, Amgen, AstraZeneca, BMS, Illumina, GlaxoSmithKline, MSD, and Roche-Ventana, unrelated to this Correspondence; and stock options from Apogen Biotech, Epic Biosciences, GRAIL, and Achilles Therapeutics, unrelated to this Correspondence. DLVB reports grants from AstraZeneca unrelated to this Correspondence. All other authors declare no competing interests.### Funding StatementThis work was supported by UCLH/UCL who received a proportion of funding from the National Institute for Health Research (NIHR) University College London Hospitals Department of Health NIHR Biomedical Research Centre (BRC). EW VL and BW are supported by the Centre funding scheme. This work was supported jointly by the BRC and core funding from the Francis Crick Institute which receives its funding from Cancer Research UK the UK Medical Research Council and the Wellcome Trust. This research was funded in whole or in part by the Wellcome Trust. For the purpose of Open Access the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. DLVB is additionally supported by the Genotype to Phenotype National Virology Consortium via UK Research and Innovation and the UK Medical Research Council and TWR and AJK are additionally supported by the Wellcome Trust. ### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Legacy study was approved by London Camden and Kings Cross Health Research Authority Research and Ethics committee (IRAS number 286469)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.YesI 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).YesI 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.YesAll data produced in the present work are contained in the manuscript and will be made openly available online after peer reviewAll data produced in the present work are contained in the manuscript and will be made openly available online after peer review
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