The clinical and immunological characteristics of COVID‐19 patients with delayed SARS‐CoV‐2 virus clearance

Abstract Background The outbreak of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has posed a great threat to human health. Some severe COVID‐19 patients still carried detectable levels of SARS‐CoV‐2 even after prolonged intensive care uni...

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Main Authors: Jinsong Wang, Debao Li, Bo Tang, Xuemin Sun, Wenjiong Shi, Hao Li, Zhenhua Zhang, Yuzhang Wu, Yi Zhang, Qinghua Qiao
Format: Article
Language:English
Published: Wiley 2023-09-01
Series:Immunity, Inflammation and Disease
Subjects:
Online Access:https://doi.org/10.1002/iid3.999
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author Jinsong Wang
Debao Li
Bo Tang
Xuemin Sun
Wenjiong Shi
Hao Li
Zhenhua Zhang
Yuzhang Wu
Yi Zhang
Qinghua Qiao
author_facet Jinsong Wang
Debao Li
Bo Tang
Xuemin Sun
Wenjiong Shi
Hao Li
Zhenhua Zhang
Yuzhang Wu
Yi Zhang
Qinghua Qiao
author_sort Jinsong Wang
collection DOAJ
description Abstract Background The outbreak of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has posed a great threat to human health. Some severe COVID‐19 patients still carried detectable levels of SARS‐CoV‐2 even after prolonged intensive care unit treatment. However, the immunological features of these COVID‐19 patients with delayed virus clearance (CDVC) are still unclear. Methods We retrospectively reviewed the clinical and immunological data of 13 CDVC cases, who were admitted into one hospital in Wuhan from February to April 2020. These data were also compared to those of perished (n = 9) and recovered (n = 52) cases. The expression of the exhaustion marker PD‐1 on circulating T cells of these patients was measured by flow cytometry. Results High levels of serum interleukin‐6 (IL‐6), IL‐1β, IL‐8, as well as other inflammatory mediators, were seen in CDVC cases. Severe lymphopenia was observed in CDVC patients with the counts of total lymphocytes (0.9 × 109/L), CD4+ T cells (0.35 × 109/L), and CD8+ T cells (0.28 × 109/L) below their corresponding lower limits of normal range. Similar to the perished group, CDVC cases have higher percentages of CD25+Foxp3+ regulatory T cells (Treg) in circulation. Moreover, enhanced expression of the exhaustion marker PD‐1 on CCR7−CD45RA+ effector, CCR7+CD45RA− central memory, and CCR7−CD45RA− effector memory CD4+ and CD8+ T cells were also observed in CDVC cases. Conclusion CDVC patients still have SARS‐CoV‐2 and these cases manifest with severe clinical symptoms due to persistent inflammation. Augmentation of the frequency of circulating Treg, severe lymphopenia, and functional exhaustion of T cells might lead to inefficient clearance of SARS‐CoV‐2. Therefore, enhancing lymphocyte counts and reversing T‐cell exhaustion might be key methods to boost immune responses and eliminate SARS‐CoV‐2 in CDVC patients.
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spelling doaj.art-6852511798404a6dbd5e9908b4263e022023-09-29T16:08:31ZengWileyImmunity, Inflammation and Disease2050-45272023-09-01119n/an/a10.1002/iid3.999The clinical and immunological characteristics of COVID‐19 patients with delayed SARS‐CoV‐2 virus clearanceJinsong Wang0Debao Li1Bo Tang2Xuemin Sun3Wenjiong Shi4Hao Li5Zhenhua Zhang6Yuzhang Wu7Yi Zhang8Qinghua Qiao9Institute of Immunology, PLA Army Medical University Chongqing ChinaDepartment of Immunology Medical College of Qingdao University Qingdao Shandong ChinaChongqing International Institute for Immunology Chongqing ChinaInstitute of Immunology, PLA Army Medical University Chongqing ChinaChongqing International Institute for Immunology Chongqing ChinaPingdingshan Medical District the 989th Hospital of the PLA Joint Logistic Support Force Pingdingshan Henan ChinaDepartment of Radiology the 989th Hospital of the PLA Joint Logistic Support Force Luoyang Henan ChinaInstitute of Immunology, PLA Army Medical University Chongqing ChinaChongqing International Institute for Immunology Chongqing ChinaPingdingshan Medical District the 989th Hospital of the PLA Joint Logistic Support Force Pingdingshan Henan ChinaAbstract Background The outbreak of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has posed a great threat to human health. Some severe COVID‐19 patients still carried detectable levels of SARS‐CoV‐2 even after prolonged intensive care unit treatment. However, the immunological features of these COVID‐19 patients with delayed virus clearance (CDVC) are still unclear. Methods We retrospectively reviewed the clinical and immunological data of 13 CDVC cases, who were admitted into one hospital in Wuhan from February to April 2020. These data were also compared to those of perished (n = 9) and recovered (n = 52) cases. The expression of the exhaustion marker PD‐1 on circulating T cells of these patients was measured by flow cytometry. Results High levels of serum interleukin‐6 (IL‐6), IL‐1β, IL‐8, as well as other inflammatory mediators, were seen in CDVC cases. Severe lymphopenia was observed in CDVC patients with the counts of total lymphocytes (0.9 × 109/L), CD4+ T cells (0.35 × 109/L), and CD8+ T cells (0.28 × 109/L) below their corresponding lower limits of normal range. Similar to the perished group, CDVC cases have higher percentages of CD25+Foxp3+ regulatory T cells (Treg) in circulation. Moreover, enhanced expression of the exhaustion marker PD‐1 on CCR7−CD45RA+ effector, CCR7+CD45RA− central memory, and CCR7−CD45RA− effector memory CD4+ and CD8+ T cells were also observed in CDVC cases. Conclusion CDVC patients still have SARS‐CoV‐2 and these cases manifest with severe clinical symptoms due to persistent inflammation. Augmentation of the frequency of circulating Treg, severe lymphopenia, and functional exhaustion of T cells might lead to inefficient clearance of SARS‐CoV‐2. Therefore, enhancing lymphocyte counts and reversing T‐cell exhaustion might be key methods to boost immune responses and eliminate SARS‐CoV‐2 in CDVC patients.https://doi.org/10.1002/iid3.999COVID‐19delayed clearanceimmunological featuresPD‐1SARS‐CoV‐2
spellingShingle Jinsong Wang
Debao Li
Bo Tang
Xuemin Sun
Wenjiong Shi
Hao Li
Zhenhua Zhang
Yuzhang Wu
Yi Zhang
Qinghua Qiao
The clinical and immunological characteristics of COVID‐19 patients with delayed SARS‐CoV‐2 virus clearance
Immunity, Inflammation and Disease
COVID‐19
delayed clearance
immunological features
PD‐1
SARS‐CoV‐2
title The clinical and immunological characteristics of COVID‐19 patients with delayed SARS‐CoV‐2 virus clearance
title_full The clinical and immunological characteristics of COVID‐19 patients with delayed SARS‐CoV‐2 virus clearance
title_fullStr The clinical and immunological characteristics of COVID‐19 patients with delayed SARS‐CoV‐2 virus clearance
title_full_unstemmed The clinical and immunological characteristics of COVID‐19 patients with delayed SARS‐CoV‐2 virus clearance
title_short The clinical and immunological characteristics of COVID‐19 patients with delayed SARS‐CoV‐2 virus clearance
title_sort clinical and immunological characteristics of covid 19 patients with delayed sars cov 2 virus clearance
topic COVID‐19
delayed clearance
immunological features
PD‐1
SARS‐CoV‐2
url https://doi.org/10.1002/iid3.999
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