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评估 COVID-19 恢复期与免疫状态变化的关联及其在患者和未感染暴露亲属中的临床严重程度。

Assessment of changes in immune status linked to COVID-19 convalescent and its clinical severity in patients and uninfected exposed relatives.

机构信息

National Center of Medical Genetics, 146 Ave No 3102, Havana 11300, Cuba.

National Center of Medical Genetics, 146 Ave No 3102, Havana 11300, Cuba.

出版信息

Immunobiology. 2022 May;227(3):152216. doi: 10.1016/j.imbio.2022.152216. Epub 2022 Apr 12.

Abstract

INTRODUCTION

The immune response during and after SARS-CoV-2 infection can be complex and heterogeneous, and it can be affected by the severity of the disease. It can also contribute to an unfavorable evolution and bring about short and long term effects. The aim of this study was to characterize the lymphocyte composition according to the severity of COVID-19, as well as its degree of relationship to the specific humoral response to SARS-CoV-2 in convalescents up to 106 days after the infection and in their exposed relatives.

METHODS

An applied research was carried out with a cross-section analytical design, from March 11 to June 11, 2020 in Cuba. The sample consisted of 251 convalescents from COVID-19 over 18 years of age and 88 exposed controls who did not become ill. The B and T cell subpopulations, including memory T cells, as well as the relationship with the humoral immune response against SARS-CoV-2, were identified by flow cytometry and enzyme immunoassay.

RESULTS

Convalescent patients, who evolved with severe forms, showed a decrease in frequency and a greater proportion of individuals with values ​​lower than the minimum normal range of B cells, CD3 + CD4 + cells and the CD4 + / CD8 + ratio, as well as a higher frequency and a greater proportion of individuals with values ​​above the normal maximum range of CD3 + CD8 + and NK cells. Convalescent patients with severe forms of COVID-19 that exhibited IgG / RBD titers ≥ 1/200 had a lower frequency of TEMRA CD8 + cells (p = 0.0128) and TEMRA CD4 + (p = 0.0068). IgG / RBD titers were positively correlated with the relative frequency of CD4 + CM T memory cells (r = 0.4352, p = 0.0018).

CONCLUSIONS

The identified alterations of B and T lymphocytes suggest that convalescent patients with the severe disease could be vulnerable to infectious, autoimmune or autotinflammatory processes; therefore, these individuals need medical follow-up after recovering from the acute disease. Furthermore, the role of T cells CD4 + CM in the production of antibodies against SARS-CoV-2 is confirmed, and it is noted that the defect of memory T cells CD8 + TEMRA could contribute to the development of severe forms of COVID-19.

摘要

简介

SARS-CoV-2 感染期间和之后的免疫反应可能复杂且具有异质性,并可能受到疾病严重程度的影响。它也可能导致不利的演变,并带来短期和长期影响。本研究的目的是根据 COVID-19 的严重程度描述淋巴细胞组成,以及其与恢复期患者感染后 106 天内以及其暴露亲属中针对 SARS-CoV-2 的特异性体液反应的关系。

方法

这是一项于 2020 年 3 月 11 日至 6 月 11 日在古巴进行的应用研究,采用了横断面分析设计。样本包括 251 名年龄在 18 岁以上的 COVID-19 康复患者和 88 名未患病的暴露对照者。通过流式细胞术和酶联免疫吸附试验鉴定 B 和 T 细胞亚群,包括记忆 T 细胞,以及与针对 SARS-CoV-2 的体液免疫反应的关系。

结果

病情严重的康复患者表现出 B 细胞频率降低和低于最低正常范围的个体比例增加,CD3+CD4+细胞和 CD4+/CD8+比值降低,以及 CD3+CD8+和 NK 细胞高于正常最高范围的个体频率和比例增加。COVID-19 严重程度表现为 IgG/RBD 滴度≥1/200 的康复患者 TEMRA CD8+细胞频率较低(p=0.0128)和 TEMRA CD4+细胞频率较低(p=0.0068)。IgG/RBD 滴度与 CD4+CMT 记忆细胞的相对频率呈正相关(r=0.4352,p=0.0018)。

结论

鉴定出的 B 和 T 淋巴细胞改变表明,患有严重疾病的康复患者可能容易受到感染、自身免疫或自身炎症过程的影响;因此,这些患者在急性疾病康复后需要进行医疗随访。此外,证实了 CD4+CMT 细胞在产生针对 SARS-CoV-2 的抗体中的作用,并且注意到 TEMRA CD8+记忆 T 细胞的缺陷可能导致 COVID-19 的严重形式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fdb/9004226/6ac4357610b3/gr1_lrg.jpg

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