COVID-19 in non-hospitalised adults caused by either SARS-CoV-2 sub-variants Omicron BA.1, BA.2, BA.4/5 or Delta associates with similar illness duration, symptom severity and viral kinetics, irrespective of vaccination history

PLoS One. 2024 Mar 21;19(3):e0294897. doi: 10.1371/journal.pone.0294897. eCollection 2024.

Abstract

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 polymerase chain reaction (PCR) or lateral flow test, self-swabbed on alternate weekdays until day 10. We compared participant-reported symptoms and viral load trajectories between infections caused by VOCs Delta and Omicron (sub-variants BA.1, BA.2 or BA.4/5), and tested for relationships between vaccine dose, symptoms and PCR cycle threshold (Ct) as a proxy for viral load using Chi-squared (χ2) and Wilcoxon tests.

Results: 563 infection episodes were reported among 491 participants. Across infection episodes, there was little variation in symptom burden (4 [IQR 3-5] symptoms) and duration (8 [IQR 6-11] days). Whilst symptom profiles differed among infections caused by Delta compared to Omicron sub-variants, symptom profiles were similar between Omicron sub-variants. Anosmia was reported more frequently in Delta infections after 2 doses compared with Omicron sub-variant infections after 3 doses, for example: 42% (25/60) of participants with Delta infection compared to 9% (6/67) with Omicron BA.4/5 (χ2 P < 0.001; OR 7.3 [95% CI 2.7-19.4]). Fever was less common with Delta (20/60 participants; 33%) than Omicron BA.4/5 (39/67; 58%; χ2 P = 0.008; OR 0.4 [CI 0.2-0.7]). Amongst infections with an 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. PCR Ct values were negatively associated with time since vaccination in participants infected with BA.1 (β = -0.05 (CI -0.10-0.01); P = 0.031); however, this trend was not observed in BA.2 or 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.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • COVID-19* / prevention & control
  • Humans
  • Prospective Studies
  • SARS-CoV-2
  • Vaccination

Supplementary concepts

  • SARS-CoV-2 variants

Associated data

  • ClinicalTrials.gov/NCT04750356

Grants and funding

This 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’s NIHR Biomedical Research Centre (BRC). EW, VL and BW are supported by the Centre’s 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 [FC011104, FC011233, FC001030, FC001159, FC001827, FC001078, FC001099, FC001169, 206250/Z/17/Z]. 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 (G2P-UK) via UK Research and Innovation and the UK Medical Research Council, and TWR and AJK are additionally supported by the Wellcome Trust.