Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
JCI Insight. 2021 Jul 22;6(14):e148476. doi: 10.1172/jci.insight.148476.
BACKGROUNDIndividuals recovering from COVID-19 frequently experience persistent respiratory ailments, which are key elements of postacute sequelae of SARS-CoV-2 infection (PASC); however, little is known about the underlying biological factors that may direct lung recovery and the extent to which these are affected by COVID-19 severity.METHODSWe performed a prospective cohort study of individuals with persistent symptoms after acute COVID-19, collecting clinical data, pulmonary function tests, and plasma samples used for multiplex profiling of inflammatory, metabolic, angiogenic, and fibrotic factors.RESULTSSixty-one participants were enrolled across 2 academic medical centers at a median of 9 weeks (interquartile range, 6-10 weeks) after COVID-19 illness: n = 13 participants (21%) had mild COVID-19 and were not hospitalized, n = 30 participants (49%) were hospitalized but were considered noncritical, and n = 18 participants (30%) were hospitalized and in the intensive care unit (ICU). Fifty-three participants (85%) had lingering symptoms, most commonly dyspnea (69%) and cough (58%). Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and diffusing capacity for carbon monoxide (DLCO) declined as COVID-19 severity increased (P < 0.05) but these values did not correlate with respiratory symptoms. Partial least-squares discriminant analysis of plasma biomarker profiles clustered participants by past COVID-19 severity. Lipocalin-2 (LCN2), MMP-7, and HGF identified by our analysis were significantly higher in the ICU group (P < 0.05), inversely correlated with FVC and DLCO (P < 0.05), and were confirmed in a separate validation cohort (n = 53).CONCLUSIONSubjective respiratory symptoms are common after acute COVID-19 illness but do not correlate with COVID-19 severity or pulmonary function. Host response profiles reflecting neutrophil activation (LCN2), fibrosis signaling (MMP-7), and alveolar repair (HGF) track with lung impairment and may be novel therapeutic or prognostic targets.FundingNational Heart, Lung, and Blood Institute (K08HL130557 and R01HL142818), American Heart Association (Transformational Project Award), the DeLuca Foundation Award, a donation from Jack Levin to the Benign Hematology Program at Yale University, and Duke University.
从 COVID-19 中康复的个体经常会出现持续的呼吸系统疾病，这是 SARS-CoV-2 感染后急性后遗症（PASC）的关键因素；然而，对于可能指导肺部恢复的潜在生物学因素以及这些因素受 COVID-19 严重程度影响的程度知之甚少。
我们对急性 COVID-19 后出现持续症状的个体进行了前瞻性队列研究，收集了临床数据、肺功能测试和用于炎症、代谢、血管生成和纤维化因子的多重分析的血浆样本。
在 COVID-19 疾病后中位数为 9 周（四分位距，6-10 周）时，在 2 家学术医疗中心共纳入了 61 名参与者：n = 13 名参与者（21%）患有轻度 COVID-19 且未住院，n = 30 名参与者（49%）住院但被认为是非重症患者，n = 18 名参与者（30%）住院且在重症监护病房（ICU）。53 名参与者（85%）有挥之不去的症状，最常见的是呼吸困难（69%）和咳嗽（58%）。用力肺活量（FVC）、1 秒用力呼气量（FEV1）和一氧化碳弥散量（DLCO）随着 COVID-19 严重程度的增加而下降（P < 0.05），但这些值与呼吸症状无关。基于血浆生物标志物谱的偏最小二乘判别分析将参与者按既往 COVID-19 严重程度聚类。我们分析确定的脂联素-2（LCN2）、MMP-7 和 HGF 在 ICU 组中显著升高（P < 0.05），与 FVC 和 DLCO 呈负相关（P < 0.05），并在另一个验证队列（n = 53）中得到证实。
急性 COVID-19 后常出现主观呼吸症状，但与 COVID-19 严重程度或肺功能无关。反映中性粒细胞激活（LCN2）、纤维化信号（MMP-7）和肺泡修复（HGF）的宿主反应谱与肺损伤相关，可能是新的治疗或预后靶点。
美国国立心肺血液研究所（K08HL130557 和 R01HL142818）、美国心脏协会（转化项目奖）、DeLuca 基金会奖、杰克·莱文（Jack Levin）捐赠给耶鲁大学良性血液学项目的款项以及杜克大学。
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