• 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, LinRaymond Tzer PinRTPNational Public Health Laboratory, Singapore., Sebastian Maurer-Stroh, Yee-Sin Leo, Lin-Fa Wang, Laurent Renia, Vernon J Lee, SmithGavin J DGJDDuke-NUS Medical School, National University of Singapore, Singapore. Electronic address: gavin.smith@duke-nus.edu.sg., David Chien Lye, and NgLisa F PLFPInfectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore. Electronic address: lisa_ng@immunol.a-star.edu.s.
• National Centre for Infectious Diseases, Singapore; Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
• Lancet. 2020 Aug 29; 396 (10251): 603611603-611.

BackgroundSevere 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.MethodsWe 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.FindingsBetween 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.InterpretationThe ∆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.FundingNational Medical Research Council Singapore.Copyright © 2020 Elsevier Ltd. All rights reserved.

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