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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
Authors: Young, Barnaby E
Fong, Siew-Wai
Chan, Yi-Hao
Mak, Tze-Minn
Ang, Li Wei
Anderson, Danielle E 
Lee, Cheryl Yi-Pin
Amrun, Siti Naqiah 
Lee, Bernett
Goh, Yun Shan
Su, Yvonne CF
Wei, Wycliffe E
Kalimuddin, Shirin 
Chai, Louis Yi Ann 
Pada, Surinder 
Tan, Seow Yen
Sun, Louisa
Parthasarathy, Purnima
Chen, Yuan Yi Constance
Barkham, Timothy
Lin, Raymond Tzer Pin 
Maurer-Stroh, Sebastian
Leo, Yee-Sin 
Wang, Lin-Fa
Renia, Laurent 
Lee, Vernon J 
Smith, Gavin JD 
Lye, David Chien 
Ng, Lisa FP
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
Issue Date: 29-Aug-2020
Citation: Young, Barnaby E, Fong, Siew-Wai, Chan, Yi-Hao, Mak, Tze-Minn, Ang, Li Wei, Anderson, Danielle E, Lee, Cheryl Yi-Pin, Amrun, Siti Naqiah, Lee, Bernett, Goh, Yun Shan, Su, Yvonne CF, Wei, Wycliffe E, Kalimuddin, Shirin, Chai, Louis Yi Ann, Pada, Surinder, Tan, Seow Yen, Sun, Louisa, Parthasarathy, Purnima, Chen, Yuan Yi Constance, Barkham, Timothy, Lin, Raymond Tzer Pin, Maurer-Stroh, Sebastian, Leo, Yee-Sin, Wang, Lin-Fa, Renia, Laurent, Lee, Vernon J, Smith, Gavin JD, Lye, David Chien, Ng, Lisa FP (2020-08-29). Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study. LANCET 396 (10251) : 603-611. ScholarBank@NUS Repository.
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. Funding: National Medical Research Council Singapore.
Source Title: LANCET
ISSN: 01406736
DOI: 10.1016/S0140-6736(20)31757-8
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