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接种疫苗后住院的 SARS-CoV-2 突破性感染的临床和免疫学特征。

Clinical and Immunological Features of SARS-CoV-2 Breakthrough Infections in Vaccinated Individuals Requiring Hospitalization.

机构信息

Department of Experimental and Clinical Medicine, University of Florence, Viale Pieraccini, 6, 50134, Florence, Italy.

Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy.

出版信息

J Clin Immunol. 2022 Oct;42(7):1379-1391. doi: 10.1007/s10875-022-01325-2. Epub 2022 Jul 9.

DOI:10.1007/s10875-022-01325-2
PMID:35809212
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9674730/
Abstract

BACKGROUND AND PURPOSE

Waning immunity and the surge of SARS-CoV-2 variants are responsible for breakthrough infections, i.e., infections in fully vaccinated individuals. Although the majority of vaccinated infected subjects report mild or no symptoms, some others require hospitalization. The clinical and immunological features of vaccinated hospitalized COVID-19 patients are currently unknown.

METHODS

Twenty-nine unvaccinated and 36 vaccinated hospitalized COVID-19 patients were prospectively enrolled and clinical and laboratory data were gathered. Immunophenotyping of leukocytes' subsets, T and B cell SARS-CoV-2-specific responses were evaluated via flow cytometry. Anti-IFN-α autoantibodies were measured via ELISA.

RESULTS

Despite vaccinated patients were older and with more comorbidities, unvaccinated subjects showed higher levels of pro-inflammatory markers, more severe disease, and increased mortality rate. Accordingly, they presented significant alterations in the circulating leukocyte composition, typical of severe COVID-19. Vaccinated patients displayed higher levels of anti-Spike IgGs and Spike-specific B cells. Of all participants, survivors showed higher levels of anti-Spike IgGs and Spike-specific CD4+ T cells than non-survivors. At hospital admission, 6 out of 65 patients (9.2%) displayed high serum concentrations of autoantibodies targeting IFN-α. Remarkably, 3 were unvaccinated and eventually died, while the other 3 were vaccinated and survived.

CONCLUSION

Despite more severe pre-existing clinical conditions, vaccinated patients have good outcome. A rapid activation of anti-SARS-CoV-2-specific immunity is fundamental for the resolution of the infection. Therefore, prior immunization through vaccination provides a significant contribution to prevention of disease worsening and can even overcome the presence of high-risk factors (i.e., older age, comorbidities, anti-IFN-α autoantibodies).

摘要

背景与目的

免疫功能下降和 SARS-CoV-2 变异株的出现导致了突破性感染,即完全接种疫苗的个体感染。尽管大多数接种疫苗的感染者报告症状轻微或无症状,但也有一些需要住院治疗。目前尚不清楚接种疫苗的住院 COVID-19 患者的临床和免疫学特征。

方法

前瞻性纳入 29 例未接种疫苗和 36 例接种疫苗的住院 COVID-19 患者,并收集临床和实验室数据。通过流式细胞术评估白细胞亚群的免疫表型、T 和 B 细胞 SARS-CoV-2 特异性反应。通过 ELISA 测量抗 IFN-α 自身抗体。

结果

尽管接种疫苗的患者年龄较大且合并症较多,但未接种疫苗的患者炎症标志物水平更高、疾病更严重且死亡率更高。因此,他们表现出循环白细胞组成的显著改变,这是 COVID-19 严重程度的典型特征。接种疫苗的患者表现出更高水平的抗刺突 IgG 和刺突特异性 B 细胞。在所有参与者中,幸存者的抗刺突 IgG 和刺突特异性 CD4+T 细胞水平高于非幸存者。在入院时,65 例患者中有 6 例(9.2%)表现出针对 IFN-α 的高血清浓度自身抗体。值得注意的是,3 例未接种疫苗且最终死亡,而另外 3 例接种疫苗且存活。

结论

尽管存在更严重的先前临床状况,但接种疫苗的患者有良好的结局。快速激活针对 SARS-CoV-2 的特异性免疫对于感染的缓解至关重要。因此,通过接种疫苗进行预先免疫为预防疾病恶化提供了重要贡献,甚至可以克服高风险因素(即年龄较大、合并症、抗 IFN-α 自身抗体)的存在。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/9676881/2b720013113f/10875_2022_1325_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/9676881/a2619f409cc2/10875_2022_1325_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/9676881/41a8536e9708/10875_2022_1325_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/9676881/52e39f252cfe/10875_2022_1325_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/9676881/22086f3b79cc/10875_2022_1325_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/9676881/2b720013113f/10875_2022_1325_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/9676881/a2619f409cc2/10875_2022_1325_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/9676881/54599a7b65de/10875_2022_1325_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/9676881/41a8536e9708/10875_2022_1325_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/9676881/52e39f252cfe/10875_2022_1325_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/9676881/22086f3b79cc/10875_2022_1325_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4987/9676881/2b720013113f/10875_2022_1325_Fig6_HTML.jpg

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