Huang Lei, Zhang Xiuwen, Zhang Lingli, Xu Jingjing, Wei Zhijian, Xu Yuanhong, Zhang Chengyuan, Xu Aman
Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Front Med (Lausanne). 2021 Aug 17;8:685544. doi: 10.3389/fmed.2021.685544. eCollection 2021.
While some contacts of COVID-19 cases become symptomatic and radiographically abnormal, their SARS-CoV-2 RNA tests remain negative throughout the disease course. This prospective population-based cohort study aimed to explore their characteristics and significances. From January 22, 2020, when the first COVID-19 case was identified in Hefei, China, until July 3, a total of 14,839 people in Feidong, Hefei, with a population of ~1,081,000 underwent SARS-CoV-2 RNA testing, where 36 cases (0.2%) with confirmed COVID-19 infection (Group 1) and 27 close contacts (0.2%) testing negative for SARS-CoV-2 RNA but having both positive COVID-19 exposure histories and CT findings (Group 2) from eight clusters were prospectively identified. Another 62 non-COVID-19 pneumonia cases without any exposure history (Group 3) were enrolled, and characteristics of the three groups were described and compared. We further described a cluster with an unusual transmission pattern. Fever was more common in Group 2 than Groups 1 and 3. Frequency of diarrhea in Group 1 was higher than in Groups 2 and 3. Median leucocyte, neutrophil, monocyte, and eosinophil counts were all lower in Groups 1 and 2 than in Group 3. Median D-dimer level was lower in Group 1 than in Groups 2 and 3. Total protein and albumin levels were higher in Groups 1 and 2 than in Group 3. C-reactive protein level was lower and erythrocyte sedimentation rate slower in Groups 1 and 2 than in Group 3. Combination antibacterial therapy and levofloxacin were more often used in Group 3 than in Groups 1 and 2. Lopinavir/ritonavir was more often administered in Groups 1 and 2 than in Group 3. Group 1 received more often corticosteroids than Groups 2 and 3. Group 2 received less often oxygen therapy than Groups 1 and 3. Median duration from illness onset to discharge was longer in Group 1 (27 d) than Groups 2 and 3 (both 17 d). Among contacts of a confirmed COVID-19 patient, only one had a positive virus RNA test but remained asymptomatic and had negative CT findings, and three had negative virus RNA tests but had symptoms and positive CT findings, one of whom transmitted COVID-19 to another asymptomatic laboratory-confirmed patient who had no other exposures. Among close contacts of confirmed COVID-19 cases, some present with positive symptoms and CT findings but test negative for SARS-CoV-2 RNA using common respiratory (throat swab and sputum) specimens; they have features more similar to confirmed COVID-19 cases than non-COVID-19 pneumonia cases and might have transmitted SARS-CoV-2 to others. Such cases might add to the complexity and difficulty of COVID-19 control. Our hypothesis-generating study might suggest that SARS-CoV-2 RNA testing by rRT-PCR assays of common respiratory (throat swab and sputum) specimens alone, the widely accepted "golden standard" for diagnosing COVID-19, might be sometimes insufficient, and that further studies with some further procedures (e.g., testing via bronchoalveolar lavage or specific antibodies) would be warranted for Group 2-like patients, namely, the SARS-CoV-2 RNA-negative (tested using common respiratory specimens), radiographically positive, symptomatic contacts of COVID-19 cases, to further reveal their nature.
虽然一些新冠病毒病例的密切接触者出现了症状且影像学检查异常，但他们的新冠病毒核糖核酸检测在整个病程中均呈阴性。这项基于人群的前瞻性队列研究旨在探索他们的特征及意义。自2020年1月22日中国合肥发现首例新冠病毒病例起，至7月3日，合肥肥东地区约108.1万人口中的14839人接受了新冠病毒核糖核酸检测，前瞻性地确定了36例确诊感染新冠病毒的病例（第1组）以及来自8个聚集性疫情的27名密切接触者（第2组），这些密切接触者新冠病毒核糖核酸检测呈阴性，但有新冠病毒暴露史且CT检查结果呈阳性。另外纳入了62例无任何暴露史的非新冠病毒肺炎病例（第3组），并对三组的特征进行了描述和比较。我们进一步描述了一个具有不寻常传播模式的聚集性疫情。第2组发热情况比第1组和第3组更常见。第1组腹泻发生率高于第2组和第3组。第1组和第2组白细胞、中性粒细胞、单核细胞和嗜酸性粒细胞计数中位数均低于第3组。第1组D-二聚体水平中位数低于第2组和第3组。第1组和第2组总蛋白和白蛋白水平高于第3组。第1组和第2组C反应蛋白水平较低，红细胞沉降率较慢。第3组比第1组和第2组更常使用联合抗菌治疗和左氧氟沙星。第1组和第2组比第3组更常使用洛匹那韦/利托那韦。第1组比第2组和第3组更常使用糖皮质激素。第2组比第1组和第3组更少接受氧疗。第1组从发病到出院的中位病程（27天）长于第2组和第3组（均为17天）。在一名确诊新冠病毒患者的密切接触者中，只有1人病毒核糖核酸检测呈阳性，但无症状且CT检查结果为阴性，3人病毒核糖核酸检测呈阴性，但有症状且CT检查结果为阳性，其中1人将新冠病毒传播给了另一名无其他暴露史的无症状实验室确诊患者。在确诊新冠病毒病例的密切接触者中，一些人有阳性症状和CT检查结果，但使用普通呼吸道（咽拭子和痰液）标本进行新冠病毒核糖核酸检测呈阴性；他们的特征与确诊新冠病毒病例比非新冠病毒肺炎病例更相似，可能已将新冠病毒传播给他人。此类病例可能会增加新冠疫情防控的复杂性和难度。我们这项产生假设的研究可能表明，仅通过普通呼吸道（咽拭子和痰液）标本的逆转录聚合酶链反应检测新冠病毒核糖核酸，这一广泛认可的诊断新冠病毒的“金标准”，有时可能并不充分，对于第2组这类患者，即新冠病毒核糖核酸阴性（使用普通呼吸道标本检测）、影像学检查呈阳性、有症状的新冠病毒病例密切接触者，有必要进行一些进一步的检查（如通过支气管肺泡灌洗或特异性抗体检测），以进一步揭示其本质。
