RESUMO
On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.
RESUMO
Little is known about T-cell responses during acute coronavirus disease-2019 (COVID-19). We measured T-cell interferon gamma (IFN-{gamma}) responses to spike 1 (S1), spike 2 (S2), nucleocapsid (N) and membrane (M) SARS-CoV-2 antigens using the T-SPOT(R) Discovery SARS-CoV-2 assay, a proven EliSPOT technology, in 114 hospitalised adult COVID-19 patients and assessed their association with clinical disease phenotype. T-SPOT(R) Discovery SARS-CoV-2 responses were detectable within 2 days of a positive PCR and did not correlate with vaccination status or symptom duration. Higher responses to S1 protein associated with a higher symptom burden, and serum IL-6 levels. Despite treatment with dexamethasone this subgroup was also at greater risk of requiring continuous positive airway pressure (CPAP) in the days following sampling. Higher T-cell responses measured using T-SPOT(R) Discovery SARS-CoV-2 associate with progressive disease in acute COVID-19 disease and may have utility as a prognostic biomarker that should be evaluated in larger cohorts.
