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一例新冠病毒长期排毒病例中双重新冠病毒谱系合并感染的动态变化:对临床严重程度和疾病持续时间的见解

Dynamics of a Dual SARS-CoV-2 Lineage Co-Infection on a Prolonged Viral Shedding COVID-19 Case: Insights into Clinical Severity and Disease Duration.

作者信息

Pedro Nicole, Silva Cláudio N, Magalhães Ana C, Cavadas Bruno, Rocha Ana M, Moreira Ana C, Gomes Maria Salomé, Silva Diogo, Sobrinho-Simões Joana, Ramos Angélica, Cardoso Maria J, Filipe Rita, Palma Pedro, Ceia Filipa, Silva Susana, Guimarães João T, Sarmento António, Fernandes Verónica, Pereira Luisa, Tavares Margarida

机构信息

i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.

Ipatimup-Instituto de Patologia e Imunologia Molecular, Universidade do Porto, 4200-135 Porto, Portugal.

出版信息

Microorganisms. 2021 Feb 2;9(2):300. doi: 10.3390/microorganisms9020300.

Abstract

A few molecularly proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases of symptomatic reinfection are currently known worldwide, with a resolved first infection followed by a second infection after a 48 to 142-day intervening period. We report a multiple-component study of a clinically severe and prolonged viral shedding coronavirus disease 2019 (COVID-19) case in a 17-year-old Portuguese female. She had two hospitalizations, a total of 19 RT-PCR tests, mostly positive, and criteria for releasing from home isolation at the end of 97 days. The viral genome was sequenced in seven serial samples and in the diagnostic sample from her infected mother. A human genome-wide array (>900 K) was screened on the seven samples, and in vitro culture was conducted on isolates from three late samples. The patient had co-infection by two SARS-CoV-2 lineages, which were affiliated in distinct clades and diverging by six variants. The 20A lineage was absolute at the diagnosis (shared with the patient's mother), but nine days later, the 20B lineage had 3% frequency, and two months later, the 20B lineage had 100% frequency. The 900 K profiles confirmed the identity of the patient in the serial samples, and they allowed us to infer that she had polygenic risk scores for hospitalization and severe respiratory disease within the normal distributions for a Portuguese population cohort. The early-on dynamic co-infection may have contributed to the severity of COVID-19 in this otherwise healthy young patient, and to her prolonged SARS-CoV-2 shedding profile.

摘要

目前,全球已知有几例经分子检测证实的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)有症状再感染病例,首次感染康复后,在48至142天的间隔期后出现第二次感染。我们报告了一项针对一名17岁葡萄牙女性的多方面研究,该患者患有临床症状严重且病毒持续排放时间长的2019冠状病毒病(COVID-19)。她住院两次,共进行了19次逆转录聚合酶链反应(RT-PCR)检测,大部分结果呈阳性,在97天结束时达到居家隔离解除标准。对七个连续样本以及其感染母亲的诊断样本进行了病毒基因组测序。对这七个样本进行了人类全基因组阵列(>90万个位点)筛查,并对三个后期样本的分离株进行了体外培养。该患者感染了两种SARS-CoV-2谱系,它们属于不同的进化枝,有六个变异位点差异。诊断时20A谱系占绝对优势(与患者母亲相同),但九天后,20B谱系频率为3%,两个月后,20B谱系频率达到100%。90万个位点的图谱证实了连续样本中患者的身份,并使我们能够推断,她在葡萄牙人群队列的正常分布范围内,具有住院和严重呼吸道疾病的多基因风险评分。早期的动态共同感染可能导致了这名原本健康的年轻患者的COVID-19病情严重,以及她的SARS-CoV-2长时间排放情况。

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