key: cord-0801931-xyyjk4xi authors: Madhi, Shabir A; Ihekweazu, Chikwe; Rees, Helen; Pollard, Andrew J title: Decoupling of omicron variant infections and severe COVID-19 date: 2022-02-18 journal: Lancet DOI: 10.1016/s0140-6736(22)00109-x sha: 548b2c3daedd3210184da0bb4437c7a87c97e6f5 doc_id: 801931 cord_uid: xyyjk4xi nan Nevertheless, real-world data showed more than 80% effectiveness against severe disease and hospitalisations. 4, 5 Although preliminary evidence suggests booster doses might enhance protection against omicron, 6 studies are underway to fully determine vaccine effectiveness. Given the natural lag between infection and severe outcomes, we await further data on omicron for effectiveness of vaccinations in preventing severe disease-the key intended outcome of vaccination. 7 In the meantime, the South Africa National Institute for Communicable Diseases has shared preliminary data indicating a decoupling of infection rates from hospitalisations and deaths with omicron. These data suggest underlying immune responses following infection and that primary and booster vaccination might attenuate the course of illness. Complementary humoral (antibody) and cellular (T cell) immune responses are activated following natural SARS-CoV-2 infection or vaccination. T-cell responses encompass a broad range of spike-protein-specific T-cell receptors that recognise multiple epitopes both within and outside of mutated regions in variants of concern. 8 Thus, even if spike protein mutations enable neutralising antibody escape, non-neutalising antibodies or T-cell-mediated responses can provide protection. The beta variant has only a few mutations in the spike gene that affect T-cell epitopes, meaning T-cell response is maintained; this is expected to be the case with omicron. 1, 8 At this stage of the pandemic, omicron is spreading in populations where many individuals have been previously infected with SARS-CoV-2 and are now being vaccinated, or where many have received two or three COVID-19 vaccine doses. These populations might be expected to have greater depth of antibody response and a broader and deeper poly-epitopic T-cell response, 9, 10 which should overcome some of the anticipated antibody evasion of omicron. In these scenarios, protection against severe disease is anticipated. Most cases of severe disease and hospitalisation with omicron are among the unvaccinated; we recommend an accelerated and equitable roll-out of COVID-19 vaccines, which have a continued role in enhancing protection against omicron. Contribution of single mutations to selected SARS-CoV-2 emerging variants spike antigenicity Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B.1.351 variant Neutralization of SARS-CoV-2 variants by convalescent and BNT162b2 vaccinated serum Effectiveness of the BNT162b2 Covid-19 vaccine against the B.1.1.7 and B.1.351 variants Effectiveness of mRNA and ChAdOx1 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe outcomes with variants of concern in Ontario Effectiveness of COVID-19 vaccines against the omicron (B.1.1.529) variant of concern COVID-19 vaccine strategies must focus on severe disease and global equity AZD1222/ChAdOx1 nCoV-19 vaccination induces a polyfunctional spike protein-specific TH1 response with a diverse TCR repertoire Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection Does infection with or vaccination against SARS-CoV-2 lead to lasting immunity? 1ยท1.529)-sarscov-2-variant-of-concern For more on preliminary data see