Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden.
Front Immunol. 2021 Nov 2;12:750448. doi: 10.3389/fimmu.2021.750448. eCollection 2021.
The risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined.
314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for COVID-19 patients. IgG antibodies were measured using two commercial assays (Abbot Architect nucleocapsid (N)-assay and YHLO iFlash-1800 N and spike (S)-assays) at five time-points, from March 2020 to January 2021, covering two pandemic waves. Seroprevalence was assessed in matched blood donors at three time-points. More extensive analyses were performed in 190 HCWs in September/October 2020, including two additional IgG-assays (DiaSorin LiaisonXL S1/S2 and Abbot Architect receptor-binding domain (RBD)-assays), neutralizing antibodies (NAbs), and CD4 T-cell reactivity using an in-house developed whole-blood assay based on flow cytometric detection of activated cells after stimulation with Spike S1-subunit or Spike, Membrane and Nucleocapsid (SMN) overlapping peptide pools.
Seroprevalence was higher among HCWs compared to sex and age-matched blood donors at all time-points. Seropositivity increased from 6.4% to 16.3% among HCWs between May 2020 and January 2021, compared to 3.6% to 11.9% among blood donors. We found significant correlations and high levels of agreement between NAbs and all four commercial IgG-assays. At 200-300 days post PCR-verified infection, there was a wide variation in sensitivity between the commercial IgG-assays, ranging from <30% in the N-assay to >90% in the RBD-assay. There was only moderate agreement between NAbs and CD4 T-cell reactivity to S1 or SMN. Pre-existing CD4 T-cell reactivity was present in similar proportions among HCW who subsequently became infected and those that did not.
HCWs in COVID-19 patient care in Sweden have been infected with SARS-CoV-2 at a higher rate compared to blood donors. We demonstrate substantial variation between different IgG-assays and propose that multiple serological targets should be used to verify past infection. Our data suggest that CD4 T-cell reactivity is not a suitable measure of past infection and does not reliably indicate protection from infection in naive individuals.
医护人员（HCWs）感染 SARS-CoV-2 的风险令人担忧，但能够明确确定 HCWs 是否感染人数过高的研究仍然有限。此外，用于确认既往感染的方法各不相同，并且 COVID-19 轻症后的免疫反应仍未得到很好的定义。
从一家瑞典传染病诊所招募了 314 名照顾 COVID-19 患者的 HCWs。使用两种商业检测方法（Abbot Architect 核衣壳（N）检测和 YHLO iFlash-1800 N 和刺突（S）检测），于 2020 年 3 月至 2021 年 1 月，共五个时间点检测 IgG 抗体，涵盖了两个大流行波次。在三个时间点评估了匹配的献血者的血清阳性率。2020 年 9 月/10 月，对 190 名 HCWs 进行了更广泛的分析，包括另外两种 IgG 检测（DiaSorin LiaisonXL S1/S2 和 Abbot Architect 受体结合域（RBD）检测）、中和抗体（NAbs）和使用基于全血的免疫细胞反应检测，该检测方法是在刺激后通过流式细胞术检测 Spike S1 亚单位或 Spike、膜和核衣壳（SMN）重叠肽池后，检测激活细胞。
与同期性别和年龄匹配的献血者相比，所有时间点的 HCWs 血清阳性率均更高。与献血者的 3.6%至 11.9%相比，2020 年 5 月至 2021 年 1 月期间，HCWs 的血清阳性率从 6.4%上升至 16.3%。我们发现 NAbs 与所有四种商业 IgG 检测之间存在显著相关性和高度一致性。在 PCR 确认感染后 200-300 天，商业 IgG 检测之间的灵敏度差异很大，从 N 检测的<30%到 RBD 检测的>90%。NAbs 与针对 S1 或 SMN 的 CD4 T 细胞反应之间的一致性仅为中等。在随后感染和未感染的 HCW 中，存在相似比例的预先存在的 CD4 T 细胞反应。
在瑞典照顾 COVID-19 患者的 HCWs 感染 SARS-CoV-2 的比率高于献血者。我们证明了不同 IgG 检测之间存在很大差异，并建议使用多种血清学指标来验证既往感染。我们的数据表明，CD4 T 细胞反应不是既往感染的合适指标，并且不能可靠地表明对未感染个体的感染保护。
