Journal Article

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

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

2020

Overview

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. 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. 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. 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. National Medical Research Council Singapore.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adult / Aged / Betacoronavirus / Binding sites / Clinical outcomes / Cohort analysis / Coronavirus Infections - complications / Coronavirus Infections - epidemiology / Coronavirus Infections - virology / Coronaviruses / COVID-19 / Cytokines / Disease transmission / Electronic health records / Electronic medical records / Epidemics / Gene Deletion / Genome, Viral - genetics / Genomes / Glycoproteins / Hospitals / Humans / Hypoxia / Hypoxia - etiology / Hypoxia - therapy / Identification methods / Infections / Infectious diseases / Inflammation / Inflammatory response / Medical research / Middle Aged / Nucleotides / Observational studies / Open Reading Frames / Oxygen / Pandemics / Patients / Pneumonia, Viral - complications / Pneumonia, Viral - epidemiology / Pneumonia, Viral - virology / Prospective Studies / Proteins / Respiratory diseases / Respiratory Therapy / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / Severity of Illness Index / Singapore - epidemiology / Vaccines / Viral diseases / Virus Replication / Viruses