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
Authors: Townsley Hermaleigh , Gahir Joshua , Russell Timothy W. , Greenwood David , Carr Edward J. , Dyke Matala , Adams Lorin , Miah Murad , Clayton Bobbi , Smith Callie , Miranda Mauro , Mears Harriet V. , Bailey Chris , Black James R. M. , Fowler Ashley S. , Crawford Margaret , Wilkinson Katalin , Hutchinson Matthew , Harvey Ruth , O’Reilly Nicola , Kelly Gavin , Goldstone Robert , Beale Rupert , Papineni Padmasayee , Corrah Tumena , Gilson Richard , Caidan Simon , Nicod Jerome , Gamblin Steve , Kassiotis George , Libri Vincenzo , Williams Bryan , Gandhi Sonia , Kucharski Adam J. , Swanton Charles , Bauer David L. V. , Wall Emma C. 
Published: March 2024

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.