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[Lancet发表论文]:新冠病毒基因组的主要缺失对感染及炎症反应严重程度的影响:观察队列研究
2020年09月26日 时讯速递, 进展交流 暂无评论

ARTICLES| VOLUME 396, ISSUE 10251, P603-611, AUGUST 29, 2020

Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study

Barnaby E Young, Siew-Wai Fong, Yi-Hao Chan, et al

Lancet 2020; 396: 603-611

Summary 摘要

Background 背景

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and other countries. We investigated the effect of this deletion on the clinical features of infection.

新加坡和其他国家已经发现,新冠病毒(SARS-CoV-2)基因组可发生开放阅读框8 (ORF8)中第382位核苷酸缺失(∆382)的变异。我们研究了这一缺失对感染临床特征的影响。

Methods 方法

We retrospectively identified patients who had been screened for the ∆382 variant and recruited to the PROTECT study—a prospective observational cohort study conducted at seven public hospitals in Singapore. We collected clinical, laboratory, and radiological data from patients' electronic medical records and serial blood and respiratory samples taken during hospitalisation and after discharge. Individuals infected with the ∆382 variant were compared with those infected with wild-type SARS-CoV-2. Exact logistic regression was used to examine the association between the infection groups and the development of hypoxia requiring supplemental oxygen (an indicator of severe COVID-19, the primary endpoint). Follow-up for the study's primary endpoint is completed.

我们回顾确定了PROTECT研究入选的接受∆382变异筛查的患者。PROTECT研究是在新加坡7家公立医院进行的一项前瞻观察性队列研究。我们从患者电子病历中收集了临床、实验室和影像学资料,以及在住院期间和出院后留取的血液和呼吸道标本。我们对受到∆382变异病毒感染的患者与野生型新冠病毒感染患者进行了比较。采用精确logistic回归验证感染分组与发生低氧血症且需要氧疗(提示为重度新冠肺炎,主要预后终点)的相关性。完成了研究主要预后终点的随访。

Findings 结果

Between Jan 22 and March 21, 2020, 278 patients with PCR-confirmed SARS-CoV-2 infection were screened for the ∆382 deletion and 131 were enrolled onto the study, of whom 92 (70%) were infected with the wild-type virus, ten (8%) had a mix of wild-type and ∆382-variant viruses, and 29 (22%) had only the ∆382 variant. Development of hypoxia requiring supplemental oxygen was less frequent in the ∆382 variant group (0 [0%] of 29 patients) than in the wild-type only group (26 [28%] of 92; absolute difference 28% [95% CI 14–28]). After adjusting for age and presence of comorbidities, infection with the ∆382 variant only was associated with lower odds of developing hypoxia requiring supplemental oxygen (adjusted odds ratio 0·07 [95% CI 0·00–0·48]) compared with infection with wild-type virus only.

2020年1月22日至3月21日间,我们对278名PCR确诊的新冠病毒感染患者进行了∆382缺失的筛查,131名患者纳入此项研究,其中92名 (70%) 为野生型病毒感染,10名 (8%) 为野生型和∆382变异株混合感染,29名 (22%) 为∆382变异株感染。与野生型组相比,∆382变异株组发生需要氧疗的低氧血症较少(26/92 [28%] vs. 0/29 [0%]; 绝对差异28% [95% CI 14-28])。经过年龄及基础疾病校正后,∆382变异株感染伴随发生需要氧疗的低氧血症风险降低(校正后比数比 0·07 [95% CI 0·00–0·48])。

Interpretation 结论

The ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection. The observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines.

新冠病毒∆382变异株似乎与较轻的感染相关。ORF8缺失的临床影响对于治疗和疫苗研发有意义。

Funding 资助

National Medical Research Council Singapore.

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