Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity
Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity
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DOI：
10.1093/cid/ciaa1280
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发表时间：
2021-11-01
影响因子：
11.8
通讯作者：
Lye, David Chien
中科院分区：
文献类型：
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作者：
Young, Barnaby E.;Ong, Sean W. X.;Lye, David Chien
背景在严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）感染的病毒动力学和免疫应答的理解方面仍然存在关键的知识差距。我们对100例PCR证实的SARS-CoV-2感染患者（平均年龄46岁; 56%为男性; 38%有合并症）进行了前瞻性观察性队列研究，评估了这些特征，并确定了它们与临床严重程度的相关性。采集呼吸道样本（n = 74）用于病毒培养，采集血清样本用于测量IgM/IgG水平（n = 30），采集血浆样本用于测量炎性细胞因子和趋化因子水平（n = 81）。疾病的严重程度与病毒培养、血清学检测和免疫标记的结果相关。57例（57%）患者发生病毒性肺炎，其中20例（20%）需要补充氧气，包括12例（12%）有创机械通气。74例患者中有19例（26%）呼吸道样本的病毒培养呈阳性。当症状发作后PCR循环阈值（Ct）值>30或>14天时，没有分离到病毒。IgM发生血清转化的中位数（IQR）为12.5（9-18）天，IgG为15.0（12-20）天; 54/62例患者（87.1%）在第14天或之后采样血清转化。严重感染与早期血清转换和较高的IgM和IgG峰值水平有关。IP-10、HGF、IL-6、MCP-1、MIP-1a、IL-12 p70、IL-18、VEGF-A、PDGF-BB和IL-1 RA水平与疾病严重程度显著相关。我们发现，病毒活力与较低的PCR Ct值在早期疾病。较强的抗体反应与疾病严重程度相关。过度活跃的促炎免疫特征为宿主定向免疫治疗提供了靶点，应在随机对照试验中进行评估。
Background. Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.Methods. We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers.Results. Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9-18) days for IgM and 15.0 (12-20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1a, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity.Conclusions. We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.