Fourth Affiliated Hospital, College of Medicine, Zhejiang University, Jinhua, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Front Cell Infect Microbiol. 2021 Nov 3;11:715143. doi: 10.3389/fcimb.2021.715143. eCollection 2021.
Recently, more patients who recovered from the novel coronavirus disease 2019 (COVID-19) may later test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) again using reverse transcription-polymerase chain reaction (RT-PCR) testing. Even though it is still controversial about the possible explanation for clinical cases of long-term viral shedding, it remains unclear whether the persistent viral shedding means re-infection or recurrence.
Specimens were collected from three COVID-19-confirmed patients, and whole-genome sequencing was performed on these clinical specimens during their first hospital admission with a high viral load of SARS-CoV-2. Laboratory tests were examined and analyzed throughout the whole course of the disease. Phylogenetic analysis was carried out for SARS-CoV-2 haplotypes.
We found haplotypes of SARS-CoV-2 co-infection in two COVID-19 patients (YW01 and YW03) with a long period of hospitalization. However, only one haplotype was observed in the other patient with chronic lymphocytic leukemia (YW02), which was verified as one kind of viral haplotype. Patients YW01 and YW02 were admitted to the hospital after being infected with COVID-19 as members of a family cluster, but they had different haplotype characteristics in the early stage of infection; YW01 and YW03 were from different infection sources; however, similar haplotypes were found together.
These findings show that haplotype diversity of SARS-CoV-2 may result in viral adaptation for persistent shedding in multiple recurrences of COVID-19 patients, who met the discharge requirement. However, the correlation between haplotype diversity of SARS-CoV-2 virus and immune status is not absolute. It showed important implications for the clinical management strategies for COVID-19 patients with long-term hospitalization or cases of recurrence.
最近，越来越多的新型冠状病毒病 2019（COVID-19）康复患者在使用逆转录-聚合酶链反应（RT-PCR）检测时，可能会再次检测出严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）呈阳性。尽管对于临床长期病毒脱落的可能解释仍存在争议，但目前尚不清楚持续性病毒脱落是否意味着再次感染或复发。
从 3 名 COVID-19 确诊患者中采集标本，对这些临床标本进行全基因组测序，这些标本来自 SARS-CoV-2 病毒载量高的首次住院患者。对整个疾病过程中的实验室检测进行了检查和分析。对 SARS-CoV-2 单倍型进行了系统进化分析。
我们发现 2 名住院时间较长的 COVID-19 患者（YW01 和 YW03）存在 SARS-CoV-2 合并感染的单倍型。然而，另一名患有慢性淋巴细胞白血病的患者（YW02）只观察到一种单倍型，该单倍型被证实为一种病毒单倍型。患者 YW01 和 YW02 作为家族聚集性感染 COVID-19 住院，但他们在感染早期具有不同的单倍型特征；YW01 和 YW03 来自不同的感染源，但相似的单倍型同时出现。
这些发现表明，SARS-CoV-2 单倍型多样性可能导致 COVID-19 患者在满足出院要求的多次复发中持续性病毒脱落，从而实现病毒适应。然而，SARS-CoV-2 病毒单倍型多样性与免疫状态之间的相关性并非绝对。这对 COVID-19 患者的临床管理策略具有重要意义，这些患者需要长期住院或出现复发。
