Comparison of the clinical features, viral shedding and immune response in vaccine breakthrough infection by the Omicron and Delta variants

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.