SARS-CoV-2-specific T cells associate with inflammation and reduced lung function in pulmonary post-acute sequalae of SARS-CoV-2.
SARS-CoV-2-specific T cells associate with inflammation and reduced lung function in pulmonary post-acute sequalae of SARS-CoV-2.
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DOI：
10.1371/journal.ppat.1010359
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发表时间：
2022-05
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
截至 2022 年 1 月，估计至少有 6000 万人在感染严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 后出现 SARS-CoV-2 (PASC) 急性后遗症。虽然在非特异性 PASC 中观察到 SARS-CoV-2 特异性 T 细胞水平升高，但人们对其对肺功能的影响知之甚少，而肺功能在大多数个体中均受到损害。本研究比较了患有肺部 PASC 并已治愈的 COVID-19 (RC) 参与者的 SARS-CoV-2 特异性 T 细胞和炎症标志物的频率与肺功能。与 RC 相比，患有呼吸道 PASC 的参与者外周血中产生 IFN-γ 和 TNF-α 的 SARS-CoV-2 特异性 CD4+ 和 CD8+ T 细胞的频率高出 6 至 105 倍，并且血浆 CRP 和 IL-6 水平升高。重要的是，在 PASC 参与者中，产生 TNF-α 的 SARS-CoV-2 特异性 CD4+ 和 CD8+ T 细胞的频率与血浆 IL-6 呈正相关，与血浆 IL-6 呈正相关，与肺功能指标（包括一秒用力呼气量 (FEV1)）呈负相关，而产生 IFN-γ 的 SARS-CoV-2 特异性 T 细胞的频率增加与长时间呼吸困难相关。按年龄、合并症数量和住院状况分层的统计分析表明，这些因素均不会影响 PASC 和 RC 队列之间测量的 SARS-CoV-2 T 细胞频率和血浆 IL-6 水平的差异。总而言之，这些研究结果表明，肺部 PASC 患者中 SARS-CoV-2 特异性 T 细胞频率升高与全身炎症增加和肺功能下降相关，这表明 SARS-CoV-2 特异性 T 细胞导致持续的肺部症状。这些发现还提供了对 PASC 病理生理学的机制见解，可以为开发潜在的治疗方法以减轻症状负担提供信息。长期 COVID-19 或 SARS-CoV-2 急性后遗症 (PASC) 影响 20-30% 的 SARS-CoV-2 感染者，其特征是 COVID-19 症状从症状出现起超过 4 周。虽然 PASC 患者会出现各种持续症状，包括呼吸急促、咳嗽、胸痛、心律不齐、脑雾、疲劳和间歇性发烧，但与肺部相关的症状是最常见的。尽管 SARS-CoV-2 感染显然是 PASC 的诱发因素，但造成长期肺功能障碍的机制尚不清楚，目前的治疗方法无法有效解决肺部症状。广义 PASC 与 SARS-CoV-2 特异性 T 细胞（适应性免疫的一个组成部分）相关，表明残留病毒可能持续存在。在这里，我们研究了肺 PASC 患者血液中病毒特异性 T 细胞的频率和功能，并将它们的存在与全身炎症和肺功能相关联。我们的研究结果表明，肺 PASC 患者血液中 SARS-CoV-2 特异性 T 细胞升高，并与 IL-6 升高（一种与 COVID-19 严重程度密切相关的细胞因子）和肺功能下降相关。这些发现为开发新疗法以改善受影响者的生活质量所需的肺 PASC 病理生理学提供了机制上的见解。
As of January 2022, at least 60 million individuals are estimated to develop post-acute sequelae of SARS-CoV-2 (PASC) after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While elevated levels of SARS-CoV-2-specific T cells have been observed in non-specific PASC, little is known about their impact on pulmonary function which is compromised in the majority of these individuals. This study compares frequencies of SARS-CoV-2-specific T cells and inflammatory markers with lung function in participants with pulmonary PASC and resolved COVID-19 (RC). Compared to RC, participants with respiratory PASC had between 6- and 105-fold higher frequencies of IFN-γ- and TNF-α-producing SARS-CoV-2-specific CD4+ and CD8+ T cells in peripheral blood, and elevated levels of plasma CRP and IL-6. Importantly, in PASC participants the frequency of TNF-α-producing SARS-CoV-2-specific CD4+ and CD8+ T cells, which exhibited the highest levels of Ki67 indicating they were activity dividing, correlated positively with plasma IL-6 and negatively with measures of lung function, including forced expiratory volume in one second (FEV1), while increased frequencies of IFN-γ-producing SARS-CoV-2-specific T cells associated with prolonged dyspnea. Statistical analyses stratified by age, number of comorbidities and hospitalization status demonstrated that none of these factors affect differences in the frequency of SARS-CoV-2 T cells and plasma IL-6 levels measured between PASC and RC cohorts. Taken together, these findings demonstrate elevated frequencies of SARS-CoV-2-specific T cells in individuals with pulmonary PASC are associated with increased systemic inflammation and decreased lung function, suggesting that SARS-CoV-2-specific T cells contribute to lingering pulmonary symptoms. These findings also provide mechanistic insight on the pathophysiology of PASC that can inform development of potential treatments to reduce symptom burden. Long COVID-19 or post-acute sequelae of SARS-CoV-2 (PASC) impacts 20–30% of those infected with SARS-CoV-2 and is characterized by COVID-19 symptoms exceeding 4 weeks from symptom onset. While those with PASC experience a wide variety of persistent symptoms including shortness of breath, cough, chest pain, irregular heartbeat, brain fog, fatigue and intermittent fever, lung-related conditions are the most common. Although, infection with SARS-CoV-2 is clearly the inciting factor for PASC, the mechanisms responsible for long-term lung dysfunction are unclear and current treatments are ineffective at resolving pulmonary symptoms. Generalized PASC has been associated with SARS-CoV-2-specific T cells, a component of adaptive immunity, suggesting that residual virus may persist. Here, we investigated the frequency and function of virus-specific T cells in the blood of individuals with pulmonary PASC and correlated their presence with systemic inflammation and lung function. Our findings demonstrated that T cells specific for SARS-CoV-2 are elevated in the blood of those with pulmonary PASC and are associated with increased IL-6, a cytokine strongly associated with COVID-19 severity, and decreased lung function. These findings provide mechanistic insight into the pathophysiology of pulmonary PASC needed for the development of new treatments to improve quality of life for those affected.
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影响因子：
3.7
作者：
Gong J;Dong H;Xia QS;Huang ZY;Wang DK;Zhao Y;Liu WH;Tu SH;Zhang MM;Wang Q;Lu FE
通讯作者：
Lu FE
影响因子：
8.6
作者：
Kassu, Afework;D'Souza, Michelle;Palmer, Brent E.
通讯作者：
Palmer, Brent E.
人类肾脏是新型严重急性呼吸综合征冠状病毒2感染的目标
影响因子：
16.6
作者：
Diao B;Wang C;Wang R;Feng Z;Zhang J;Yang H;Tan Y;Wang H;Wang C;Liu L;Liu Y;Liu Y;Wang G;Yuan Z;Hou X;Ren L;Wu Y;Chen Y
通讯作者：
Chen Y
DOI：
10.1186/ar557
发表时间：
2002
期刊：
Arthritis research
影响因子：
--
作者：
Cope AP
通讯作者：
Cope AP
影响因子：
24.8
作者：
Cheon IS;Li C;Son YM;Goplen NP;Wu Y;Cassmann T;Wang Z;Wei X;Tang J;Li Y;Marlow H;Hughes S;Hammel L;Cox TM;Goddery E;Ayasoufi K;Weiskopf D;Boonyaratanakornkit J;Dong H;Li H;Chakraborty R;Johnson AJ;Edell E;Taylor JJ;Kaplan MH;Sette A;Bartholmai BJ;Kern R;Vassallo R;Sun J
通讯作者：
Sun J