BackgroundOn 26 November 2021, the World Health Organization designated the B.1.1.529 lineage of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as the fifth variant of concern, Omicron. Infections have quickly spread worldwide, but understanding of the viral dynamics and the cytokine and cellular immunological response during infection remain limited.MethodsDetailed patient-level data from 174 age-matched patients with sequence confirmed Omicron or Delta infection admitted to the National Centre for Infectious Diseases, Singapore were analyzed in an observational cohort study. Peripheral blood samples for measurement of SARS-CoV-2 immunological parameters were obtained from a subset. Respiratory samples were collected for viral cultures and correlated to corresponding PCR cycle threshold (Ct) values. ResultsOmicron and Delta variant infections in this hospitalized cohort were mild with only 3 (3%) and 14 (16%) developing pneumonia respectively. Omicron infections were more likely to present with sore throat (46.0 vs x23.0%, p=0.005). Neutrophil counts and C-reactive protein (CRP) were significantly lower among the Omicron cohort (Median neutrophil 2.95 [IQR 2.16 – 3.96] vs 4.60 [IQR 3.76 – 6.10] x 109/L , p<0.001; Median CRP 5.7 [IQR 2.0 – 10.0] vs 12.0 [IQR 6.1 – 22.0] mg/L, p<0.001). Trough polymerase chain reaction (PCR) cycle threshold (Ct) values were significantly higher with Omicron infection (17.6 [IQR 16.3 – 19.3] vs 14.9 [IQR 13.9 – 19.0], p=0.001). The pattern and rate of rise in Ct values was similar between Omicron and Delta. At the time of infection, Omicron infected patients had lower levels of pro-inflammatory cytokines Vaccine breakthrough infections with the Omicron variant had a low concentration of proinflammatory cytokines, chemokines, and growth factors at the acute phase of infection, but a more robust IFN-γ response. Less dysregulated immune cell profiles were also observed, including a lower immature neutrophil cell count in Omicron breakthrough casesConclusionsOmicron infections resulted in mild vaccine breakthrough illness in the majority of patients. Compared with Delta, Omicron infections were more frequently associated with upper respiratory tract infections, had lower viral loads, lower levels of pro-inflammatory cytokines and less dysregulated immune cell profiles.
Early treatment of high‐risk COVID‐19 patients may prevent disease progression. However, there are limited data to support treatment of hospitalized or fully vaccinated patients with mild‐to‐moderate disease. In this retrospective cohort study, we studied the effect of early use of sotrovimab and remdesivir in high‐risk hospitalized COVID‐19 patients. We included PCR‐confirmed COVID‐19 patients admitted to the National Centre for Infectious Diseases who presented within the first 5 days of illness, and who were not requiring oxygen or ICU care at presentation. Sotrovimab‐ and remdesivir‐treated groups were compared with control (no early treatment). A multiple propensity‐score adjusted multivariable regression analysis was conducted with a composite primary endpoint of in‐hospital deterioration (oxygen requirement, ICU admission, or mortality). Of 1118 patients, 841 were in the control group, 106 in the sotrovimab group and 169 in the remdesivir group. The median age was 63 years (IQR 46–74 years) and 505 (45.2%) were female. In unvaccinated patients, both remdesivir and sotrovimab treatment were protective (adjusted odds ratio [aOR] 0.19, 95% CI 0.064–0.60 and 0.18 [95% CI 0.066–0.47]), respectively. Contrarily, among the vaccinated patients there was no significant treatment effect with early remdesivir treatment (aOR 2.51, 95% CI 0.83–7.57, p = 0.10). Remdesivir and sotrovimab treatment, given early in the disease course to unvaccinated high‐risk patients, was effective in reducing the risk of in‐hospital deterioration and severe disease. This effect was not seen in fully vaccinated patients, which may be due to a small sample size or residual confounding.
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