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BackgroundSARS-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).MethodsIn 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.Results555 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; χ2test 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.ConclusionOur 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 registrationNCT04750356

Mycobacterium tuberculosis is associated with the activation of cytokine circuits both at sites of active tuberculosis in vivo and in cultures of mononuclear cells stimulated by M. tuberculosis or its components in vitro. Interactive stimulatory and/or inhibitory pathways are established between cytokines, which may result in potentiation or attenuation of the effects of each molecule on T-cell responses. Here we examined the interaction of transforming growth factor β1 (TGF-β1) and interleukin-10 (IL-10) in purified protein derivative (PPD)-stimulated human mononuclear cell cultures in vitro. TGF-β1 induced monocyte IL-10 (but not tumor necrosis factor alpha) production (by 70-fold, P < 0.02) and mRNA expression in the absence but not in the presence of PPD. Both exogenous recombinant (r) IL-10 and rTGF-β1 independently suppressed the production of PPD-induced gamma interferon (IFN-γ) in mononuclear cells from PPD skin test-positive individuals. Synergistic suppression of IFN-γ in cultures containing both rTGF-β1 and rIL-10 was only seen when the responder cell population were peripheral blood mononuclear cells (PBMC) and not monocyte-depleted mononuclear cells and when PBMC were pretreated with rTGF-β1 but not with rIL-10. Suppression of PPD-induced IFN-γ in PBMC containing both rTGF-β1 (1 ng/ml) and rIL-10 (100 pg/ml) was 1.5-fold higher ( P < 0.05) than cultures containing TGF-β1 alone and 5.7-fold higher ( P < 0.004) than cultures containing IL-10 alone. Also, neutralization of endogenous TGF-β1 and IL-10 together enhanced PPD-induced IFN-γ in PBMC in a synergistic manner. Thus, TGF-β1 and IL-10 together potentiate the downmodulatory effect on M. tuberculosis -induced T-cell production of IFN-γ, and TGF-β1 alone enhances IL-10 production. At sites of active M. tuberculosis infection, these interactions may be conducive to the suppression of mononuclear cell functions.