新加坡免疫学网络Lisa F P Ng联合新加坡国立大学Gavin J D Smith团队分析了SARS-CoV-2基因组缺失对感染严重程度和炎症反应的影响。2020年8月18日，《柳叶刀》杂志发表了这一成果。

在新加坡和其他国家，已检测到基因组开放阅读框8（ORF8）区域中382位核苷酸缺失（Δ382）的SARS-CoV-2变异株。研究组调查了这种缺失对感染临床特征的影响。

研究组在新加坡的7家公立医院进行了一项前瞻性观察队列研究，招募Δ382变异株感染的患者，将感染Δ382变异株参与者与感染野生型SARS-CoV-2参与者的临床、实验室和放射学数据进行比较。

2020年1月22日至3月21日，研究组对278例经PCR确诊的SARS-CoV-2感染患者进行了Δ382缺失筛查，并将131名患者纳入研究，其中92例（70％）感染了野生型病毒，10例（8％）感染了野生型和Δ382变异株的杂合病毒，29例（22％）仅感染Δ382变异株。Δ382变异株组中没有患者因缺氧而需供氧，但单纯野生型组中有26例（28%）。经年龄和合并症校正后，与单纯野生型病毒相比，Δ382变异株感染的患者发生缺氧而需供氧的几率显著降低。

研究结果表明，SARS-CoV-2的?382变异株似乎与轻度感染有关。观察ORF8缺失的临床效果对治疗方法和疫苗开发有一定意义。

附：英文原文

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

Author: Barnaby E Young, Siew-Wai Fong, Yi-Hao Chan, Tze-Minn Mak, Li Wei Ang, Danielle E Anderson, Cheryl Yi-Pin Lee, Siti Naqiah Amrun, Bernett Lee, Yun Shan Goh, Yvonne C F Su, Wycliffe E Wei, Shirin Kalimuddin, Louis Yi Ann Chai, Surinder Pada, Seow Yen Tan, Louisa Sun, Purnima Parthasarathy, Yuan Yi Constance Chen, Timothy Barkham, Raymond Tzer Pin Lin, Sebastian Maurer-Stroh, Yee-Sin Leo, Lin-Fa Wang, Laurent Renia, Vernon J Lee, Gavin J D Smith, David Chien Lye, Lisa F P Ng

Issue&Volume: 2020-08-18

Abstract:

Background

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.

Methods

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.

Findings

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.

Interpretation

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.

DOI: 10.1016/S0140-6736(20)31757-8

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31757-8/fulltext