The Francis Crick Institute
journal.pone.0294897.pdf (2.39 MB)

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.

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posted on 2024-03-25, 15:42 authored by Hermaleigh Townsley, Joshua Gahir, Timothy W Russell, David Greenwood, Edward J Carr, Matala Dyke, Lorin Adams, Murad Miah, Bobbi Clayton, Callie Smith, Mauro Miranda, Harriet V Mears, Chris Bailey, James RM Black, Ashley S Fowler, Margaret Crawford, Katalin Wilkinson, Matthew Hutchinson, Ruth Harvey, Nicola O'Reilly, Gavin Kelly, Robert Goldstone, Rupert Beale, Padmasayee Papineni, Tumena Corrah, Richard Gilson, Simon Caidan, Jerome Nicod, Steve Gamblin, George Kassiotis, Vincenzo Libri, Bryan Williams, Sonia Gandhi, Adam J Kucharski, Charles Swanton, David LV Bauer, Emma C Wall
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.


Crick (Grant ID: CC2166, Grant title: Bauer CC2166) Crick (Grant ID: CC2087, Grant title: Beale CC2087) Crick (Grant ID: CC1283, Grant title: Crick legacy study CC1283) Crick (Grant ID: CC2060, Grant title: Gamblin CC2060) Crick (Grant ID: CC2088, Grant title: Kassiotis CC2088) Crick (Grant ID: CC1064, Grant title: STP Advanced Sequencing) Crick (Grant ID: CC1107, Grant title: STP Bioinformatics & Biostatistics) Crick (Grant ID: CC2041, Grant title: Swanton CC2041)