ABSTRACT

Omicron variant is circulating in the presence of a globally acquired immunity unlike the ancestral SARS-CoV-2 isolate. Herein, we investigated the normalized viral load dynamics and viral culture status in 44 fully vaccinated healthcare workers (HCWs) infected with the Omicron BA.1 variant. Viral load dynamics of 38 unvaccinated HCWs infected with the 20A variant during the first pandemic wave was also studied. We then explored the impact of Omicron infection on pre-existing immunity assessing anti-RBD IgG levels, neutralizing antibody titres against 19A, Delta and Omicron isolates, as well as IFN-γ release following cell stimulation with SARS-CoV-2 peptides. We reported that two weeks after diagnosis a greater proportion of HCWs infected with 20A (78.9%, 15/19) than with Omicron BA.1 (44.7%, 17/38; p = 0.02) were still positive by RT-qPCR. We found that Omicron breakthrough infections led to an overall enhancement of vaccine-induced humoral and cellular immunity as soon as a median [interquartile range] of 8 [7–9] days post symptom onset. Among samples with similar high viral loads, non-culturable samples exhibited higher neutralizing antibody titres and anti-RBD IgG levels than culturable samples. Additionally, Omicron infection led to an enhancement of antibodies neutralization capacity against other SARS-CoV-2 isolates. Taken together, the results suggest that Omicron BA.1 vaccine breakthrough infection is associated with a faster viral clearance than that of the ancestral SARS-CoV-2, in addition this new variant leads to a rapid enhancement of the humoral response against multiple SARS-CoV-2 variants, and of the cellular response.

摘要

与祖先的 SARS-CoV-2 分离株不同，Omicron 变体在具有全球获得性免疫力的情况下传播。在此，我们调查了感染 Omicron BA.1 变体的 44 名完全接种疫苗的医护人员 (HCW) 的标准化病毒载量动态和病毒培养状态。还研究了第一次大流行期间感染 20A 变体的 38 名未接种疫苗的医护人员的病毒载量动态。然后，我们探讨了 Omicron 感染对预先存在的免疫力的影响，评估抗 RBD IgG 水平、针对 19A、Delta 和 Omicron 分离株的中和抗体滴度，以及用 SARS-CoV-2 肽刺激细胞后的 IFN-γ 释放。我们报告说，在诊断后两周，与 Omicron BA.1（44.7%，17/38；p = 0.02）相比，感染 20A（78.9%，15/19）的医护人员中，RT-qPCR 仍然呈阳性的比例更高。我们发现，Omicron 突破性感染导致疫苗诱导的体液免疫和细胞免疫的整体增强，只要中位值 [四分位数范围] 为症状发作后 8 [7–9] 天。在具有相似高病毒载量的样品中，不可培养样品表现出比可培养样品更高的中和抗体滴度和抗 RBD IgG 水平。此外，Omicron 感染导致针对其他 SARS-CoV-2 分离株的抗体中和能力增强。综上所述，结果表明，Omicron BA.1 疫苗突破性感染与比祖先 SARS-CoV-2 更快的病毒清除相关，此外，这种新变体导致对多种 SARS- CoV-2 变体和细胞反应。