Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study.
Identifieur interne : 000621 ( Main/Exploration ); précédent : 000620; suivant : 000622Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study.
Auteurs : Barnaby E. Young [Singapour] ; Siew-Wai Fong [Singapour] ; Yi-Hao Chan [Singapour] ; Tze-Minn Mak [Singapour] ; Li Wei Ang [Singapour] ; Danielle E. Anderson [Singapour] ; Cheryl Yi-Pin Lee [Singapour] ; Siti Naqiah Amrun [Singapour] ; Bernett Lee [Singapour] ; Yun Shan Goh [Singapour] ; Yvonne C F. Su [Singapour] ; Wycliffe E. Wei [Singapour] ; Shirin Kalimuddin [Singapour] ; Louis Yi Ann Chai [Singapour] ; Surinder Pada [Singapour] ; Seow Yen Tan [Singapour] ; Louisa Sun [Singapour] ; Purnima Parthasarathy [Singapour] ; Yuan Yi Constance Chen [Singapour] ; Timothy Barkham [Singapour] ; Raymond Tzer Pin Lin [Singapour] ; Sebastian Maurer-Stroh [Allemagne] ; Yee-Sin Leo [Singapour] ; Lin-Fa Wang [Singapour] ; Laurent Renia [Singapour] ; Vernon J. Lee [Singapour] ; Gavin J D. Smith [Singapour] ; David Chien Lye [Singapour] ; Lisa F P. Ng [Singapour]Source :
- Lancet (London, England) [ 1474-547X ] ; 2020.
Descripteurs français
- KwdFr :
- Adulte (MeSH), Adulte d'âge moyen (MeSH), Betacoronavirus (MeSH), Cadres ouverts de lecture (MeSH), Délétion de gène (MeSH), Génome viral (génétique), Humains (MeSH), Hypoxie (thérapie), Hypoxie (étiologie), Indice de gravité de la maladie (MeSH), Infections à coronavirus (complications), Infections à coronavirus (virologie), Infections à coronavirus (épidémiologie), Pandémies (MeSH), Pneumopathie virale (complications), Pneumopathie virale (virologie), Pneumopathie virale (épidémiologie), Réplication virale (MeSH), Singapour (épidémiologie), Sujet âgé (MeSH), Thérapie respiratoire (MeSH), Études prospectives (MeSH).
- MESH :
- génétique : Génome viral.
- thérapie : Hypoxie.
- virologie : Infections à coronavirus, Pneumopathie virale.
- épidémiologie : Infections à coronavirus, Pneumopathie virale, Singapour.
- étiologie : Hypoxie.
- Adulte, Adulte d'âge moyen, Betacoronavirus, Cadres ouverts de lecture, Délétion de gène, Humains, Indice de gravité de la maladie, Pandémies, Réplication virale, Sujet âgé, Thérapie respiratoire, Études prospectives.
- Wicri :
- geographic : Singapour.
English descriptors
- KwdEn :
- Adult (MeSH), Aged (MeSH), Betacoronavirus (MeSH), Coronavirus Infections (complications), Coronavirus Infections (epidemiology), Coronavirus Infections (virology), Gene Deletion (MeSH), Genome, Viral (genetics), Humans (MeSH), Hypoxia (etiology), Hypoxia (therapy), Middle Aged (MeSH), Open Reading Frames (MeSH), Pandemics (MeSH), Pneumonia, Viral (complications), Pneumonia, Viral (epidemiology), Pneumonia, Viral (virology), Prospective Studies (MeSH), Respiratory Therapy (MeSH), Severity of Illness Index (MeSH), Singapore (epidemiology), Virus Replication (MeSH).
- MESH :
- geographic , epidemiology : Singapore.
- complications : Coronavirus Infections, Pneumonia, Viral.
- epidemiology : Coronavirus Infections, Pneumonia, Viral.
- etiology : Hypoxia.
- genetics : Genome, Viral.
- therapy : Hypoxia.
- virology : Coronavirus Infections, Pneumonia, Viral.
- Adult, Aged, Betacoronavirus, Gene Deletion, Humans, Middle Aged, Open Reading Frames, Pandemics, Prospective Studies, Respiratory Therapy, Severity of Illness Index, Virus Replication.
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.
DOI: 10.1016/S0140-6736(20)31757-8
PubMed: 32822564
PubMed Central: PMC7434477
Affiliations:
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Le document en format XML
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Anderson</name><affiliation wicri:level="4"><nlm:affiliation>Duke-NUS Medical School, National University of Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Duke-NUS Medical School, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Lee, Cheryl Yi Pin" sort="Lee, Cheryl Yi Pin" uniqKey="Lee C" first="Cheryl Yi-Pin" last="Lee">Cheryl Yi-Pin Lee</name><affiliation wicri:level="1"><nlm:affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research</wicri:regionArea><wicri:noRegion>and Research</wicri:noRegion></affiliation></author><author><name sortKey="Amrun, Siti Naqiah" sort="Amrun, Siti Naqiah" uniqKey="Amrun S" first="Siti Naqiah" last="Amrun">Siti Naqiah Amrun</name><affiliation wicri:level="1"><nlm:affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research</wicri:regionArea><wicri:noRegion>and Research</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Bernett" sort="Lee, Bernett" uniqKey="Lee B" first="Bernett" last="Lee">Bernett Lee</name><affiliation wicri:level="1"><nlm:affiliation>Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Singapore Immunology Network, Agency for Science, Technology, and Research</wicri:regionArea><wicri:noRegion>and Research</wicri:noRegion></affiliation></author><author><name sortKey="Goh, Yun Shan" sort="Goh, Yun Shan" uniqKey="Goh Y" first="Yun Shan" last="Goh">Yun Shan Goh</name><affiliation wicri:level="1"><nlm:affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research</wicri:regionArea><wicri:noRegion>and Research</wicri:noRegion></affiliation></author><author><name sortKey="Su, Yvonne C F" sort="Su, Yvonne C F" uniqKey="Su Y" first="Yvonne C F" last="Su">Yvonne C F. Su</name><affiliation wicri:level="4"><nlm:affiliation>Duke-NUS Medical School, National University of Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Duke-NUS Medical School, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Wei, Wycliffe E" sort="Wei, Wycliffe E" uniqKey="Wei W" first="Wycliffe E" last="Wei">Wycliffe E. Wei</name><affiliation wicri:level="1"><nlm:affiliation>National Public Health and Epidemiology Unit, National Centre for Infectious Diseases, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>National Public Health and Epidemiology Unit, National Centre for Infectious Diseases</wicri:regionArea><wicri:noRegion>National Centre for Infectious Diseases</wicri:noRegion></affiliation></author><author><name sortKey="Kalimuddin, Shirin" sort="Kalimuddin, Shirin" uniqKey="Kalimuddin S" first="Shirin" last="Kalimuddin">Shirin Kalimuddin</name><affiliation wicri:level="4"><nlm:affiliation>Duke-NUS Medical School, National University of Singapore, Singapore; Department of Infectious Diseases, Singapore General Hospital, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Duke-NUS Medical School, National University of Singapore, Singapore; Department of Infectious Diseases, Singapore General Hospital</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Chai, Louis Yi Ann" sort="Chai, Louis Yi Ann" uniqKey="Chai L" first="Louis Yi Ann" last="Chai">Louis Yi Ann Chai</name><affiliation wicri:level="4"><nlm:affiliation>Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Medicine, National University Health System, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Medicine, National University Health System</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Pada, Surinder" sort="Pada, Surinder" uniqKey="Pada S" first="Surinder" last="Pada">Surinder Pada</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Infectious Diseases Service, Ng Teng Fong General Hospital, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Medicine, Infectious Diseases Service, Ng Teng Fong General Hospital</wicri:regionArea><wicri:noRegion>Ng Teng Fong General Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Tan, Seow Yen" sort="Tan, Seow Yen" uniqKey="Tan S" first="Seow Yen" last="Tan">Seow Yen Tan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Infectious Diseases, Changi General Hospital, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Infectious Diseases, Changi General Hospital</wicri:regionArea><wicri:noRegion>Changi General Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Louisa" sort="Sun, Louisa" uniqKey="Sun L" first="Louisa" last="Sun">Louisa Sun</name><affiliation wicri:level="1"><nlm:affiliation>Alexandra Hospital, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Alexandra Hospital</wicri:regionArea></affiliation></author><author><name sortKey="Parthasarathy, Purnima" sort="Parthasarathy, Purnima" uniqKey="Parthasarathy P" first="Purnima" last="Parthasarathy">Purnima Parthasarathy</name><affiliation wicri:level="1"><nlm:affiliation>Department of General Medicine, Khoo Teck Puat Hospital, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of General Medicine, Khoo Teck Puat Hospital</wicri:regionArea><wicri:noRegion>Khoo Teck Puat Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yuan Yi Constance" sort="Chen, Yuan Yi Constance" uniqKey="Chen Y" first="Yuan Yi Constance" last="Chen">Yuan Yi Constance Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Laboratory Medicine, Tan Tock Seng Hospital</wicri:regionArea><wicri:noRegion>Tan Tock Seng Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Barkham, Timothy" sort="Barkham, Timothy" uniqKey="Barkham T" first="Timothy" last="Barkham">Timothy Barkham</name><affiliation wicri:level="4"><nlm:affiliation>Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Lin, Raymond Tzer Pin" sort="Lin, Raymond Tzer Pin" uniqKey="Lin R" first="Raymond Tzer Pin" last="Lin">Raymond Tzer Pin Lin</name><affiliation wicri:level="1"><nlm:affiliation>National Public Health Laboratory, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>National Public Health Laboratory</wicri:regionArea></affiliation></author><author><name sortKey="Maurer Stroh, Sebastian" sort="Maurer Stroh, Sebastian" uniqKey="Maurer Stroh S" first="Sebastian" last="Maurer-Stroh">Sebastian Maurer-Stroh</name><affiliation wicri:level="4"><nlm:affiliation>National Centre for Infectious Diseases, Singapore; Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore; Department of Biological Sciences, National University of Singapore, Singapore; Global Initiative on Sharing All Influenza Data, Munich, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>National Centre for Infectious Diseases, Singapore; Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore; Department of Biological Sciences, National University of Singapore, Singapore; Global Initiative on Sharing All Influenza Data, Munich</wicri:regionArea><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Leo, Yee Sin" sort="Leo, Yee Sin" uniqKey="Leo Y" first="Yee-Sin" last="Leo">Yee-Sin Leo</name><affiliation wicri:level="4"><nlm:affiliation>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; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>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; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Wang, Lin Fa" sort="Wang, Lin Fa" uniqKey="Wang L" first="Lin-Fa" last="Wang">Lin-Fa Wang</name><affiliation wicri:level="4"><nlm:affiliation>Duke-NUS Medical School, National University of Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Duke-NUS Medical School, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Renia, Laurent" sort="Renia, Laurent" uniqKey="Renia L" first="Laurent" last="Renia">Laurent Renia</name><affiliation wicri:level="1"><nlm:affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research</wicri:regionArea><wicri:noRegion>and Research</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Vernon J" sort="Lee, Vernon J" uniqKey="Lee V" first="Vernon J" last="Lee">Vernon J. Lee</name><affiliation wicri:level="4"><nlm:affiliation>Saw Swee Hock School of Public Health, National University of Singapore, Singapore; Ministry of Health, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Saw Swee Hock School of Public Health, National University of Singapore, Singapore; Ministry of Health</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Smith, Gavin J D" sort="Smith, Gavin J D" uniqKey="Smith G" first="Gavin J D" last="Smith">Gavin J D. Smith</name><affiliation wicri:level="4"><nlm:affiliation>Duke-NUS Medical School, National University of Singapore, Singapore. Electronic address: gavin.smith@duke-nus.edu.sg.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Duke-NUS Medical School, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Lye, David Chien" sort="Lye, David Chien" uniqKey="Lye D" first="David Chien" last="Lye">David Chien Lye</name><affiliation wicri:level="4"><nlm:affiliation>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; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>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; Yong Loo Lin School of Medicine, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Ng, Lisa F P" sort="Ng, Lisa F P" uniqKey="Ng L" first="Lisa F P" last="Ng">Lisa F P. Ng</name><affiliation wicri:level="1"><nlm:affiliation>Infectious 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.sg.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research</wicri:regionArea><wicri:noRegion>and Research</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32822564</idno><idno type="pmid">32822564</idno><idno type="doi">10.1016/S0140-6736(20)31757-8</idno><idno type="pmc">PMC7434477</idno><idno type="wicri:Area/Main/Corpus">000537</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000537</idno><idno type="wicri:Area/Main/Curation">000537</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000537</idno><idno type="wicri:Area/Main/Exploration">000537</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study.</title><author><name sortKey="Young, Barnaby E" sort="Young, Barnaby E" uniqKey="Young B" first="Barnaby E" last="Young">Barnaby E. Young</name><affiliation wicri:level="1"><nlm:affiliation>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.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>National Centre for Infectious Diseases, Singapore; Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University</wicri:regionArea><wicri:noRegion>Nanyang Technological University</wicri:noRegion></affiliation></author><author><name sortKey="Fong, Siew Wai" sort="Fong, Siew Wai" uniqKey="Fong S" first="Siew-Wai" last="Fong">Siew-Wai Fong</name><affiliation wicri:level="4"><nlm:affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore; Department of Biological Sciences, National University of Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore; Department of Biological Sciences, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Chan, Yi Hao" sort="Chan, Yi Hao" uniqKey="Chan Y" first="Yi-Hao" last="Chan">Yi-Hao Chan</name><affiliation wicri:level="1"><nlm:affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research</wicri:regionArea><wicri:noRegion>and Research</wicri:noRegion></affiliation></author><author><name sortKey="Mak, Tze Minn" sort="Mak, Tze Minn" uniqKey="Mak T" first="Tze-Minn" last="Mak">Tze-Minn Mak</name><affiliation wicri:level="1"><nlm:affiliation>National Public Health Laboratory, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>National Public Health Laboratory</wicri:regionArea></affiliation></author><author><name sortKey="Ang, Li Wei" sort="Ang, Li Wei" uniqKey="Ang L" first="Li Wei" last="Ang">Li Wei Ang</name><affiliation wicri:level="1"><nlm:affiliation>National Public Health and Epidemiology Unit, National Centre for Infectious Diseases, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>National Public Health and Epidemiology Unit, National Centre for Infectious Diseases</wicri:regionArea><wicri:noRegion>National Centre for Infectious Diseases</wicri:noRegion></affiliation></author><author><name sortKey="Anderson, Danielle E" sort="Anderson, Danielle E" uniqKey="Anderson D" first="Danielle E" last="Anderson">Danielle E. Anderson</name><affiliation wicri:level="4"><nlm:affiliation>Duke-NUS Medical School, National University of Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Duke-NUS Medical School, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Lee, Cheryl Yi Pin" sort="Lee, Cheryl Yi Pin" uniqKey="Lee C" first="Cheryl Yi-Pin" last="Lee">Cheryl Yi-Pin Lee</name><affiliation wicri:level="1"><nlm:affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research</wicri:regionArea><wicri:noRegion>and Research</wicri:noRegion></affiliation></author><author><name sortKey="Amrun, Siti Naqiah" sort="Amrun, Siti Naqiah" uniqKey="Amrun S" first="Siti Naqiah" last="Amrun">Siti Naqiah Amrun</name><affiliation wicri:level="1"><nlm:affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research</wicri:regionArea><wicri:noRegion>and Research</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Bernett" sort="Lee, Bernett" uniqKey="Lee B" first="Bernett" last="Lee">Bernett Lee</name><affiliation wicri:level="1"><nlm:affiliation>Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Singapore Immunology Network, Agency for Science, Technology, and Research</wicri:regionArea><wicri:noRegion>and Research</wicri:noRegion></affiliation></author><author><name sortKey="Goh, Yun Shan" sort="Goh, Yun Shan" uniqKey="Goh Y" first="Yun Shan" last="Goh">Yun Shan Goh</name><affiliation wicri:level="1"><nlm:affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research</wicri:regionArea><wicri:noRegion>and Research</wicri:noRegion></affiliation></author><author><name sortKey="Su, Yvonne C F" sort="Su, Yvonne C F" uniqKey="Su Y" first="Yvonne C F" last="Su">Yvonne C F. Su</name><affiliation wicri:level="4"><nlm:affiliation>Duke-NUS Medical School, National University of Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Duke-NUS Medical School, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Wei, Wycliffe E" sort="Wei, Wycliffe E" uniqKey="Wei W" first="Wycliffe E" last="Wei">Wycliffe E. Wei</name><affiliation wicri:level="1"><nlm:affiliation>National Public Health and Epidemiology Unit, National Centre for Infectious Diseases, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>National Public Health and Epidemiology Unit, National Centre for Infectious Diseases</wicri:regionArea><wicri:noRegion>National Centre for Infectious Diseases</wicri:noRegion></affiliation></author><author><name sortKey="Kalimuddin, Shirin" sort="Kalimuddin, Shirin" uniqKey="Kalimuddin S" first="Shirin" last="Kalimuddin">Shirin Kalimuddin</name><affiliation wicri:level="4"><nlm:affiliation>Duke-NUS Medical School, National University of Singapore, Singapore; Department of Infectious Diseases, Singapore General Hospital, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Duke-NUS Medical School, National University of Singapore, Singapore; Department of Infectious Diseases, Singapore General Hospital</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Chai, Louis Yi Ann" sort="Chai, Louis Yi Ann" uniqKey="Chai L" first="Louis Yi Ann" last="Chai">Louis Yi Ann Chai</name><affiliation wicri:level="4"><nlm:affiliation>Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Medicine, National University Health System, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Medicine, National University Health System</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Pada, Surinder" sort="Pada, Surinder" uniqKey="Pada S" first="Surinder" last="Pada">Surinder Pada</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Infectious Diseases Service, Ng Teng Fong General Hospital, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Medicine, Infectious Diseases Service, Ng Teng Fong General Hospital</wicri:regionArea><wicri:noRegion>Ng Teng Fong General Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Tan, Seow Yen" sort="Tan, Seow Yen" uniqKey="Tan S" first="Seow Yen" last="Tan">Seow Yen Tan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Infectious Diseases, Changi General Hospital, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Infectious Diseases, Changi General Hospital</wicri:regionArea><wicri:noRegion>Changi General Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Louisa" sort="Sun, Louisa" uniqKey="Sun L" first="Louisa" last="Sun">Louisa Sun</name><affiliation wicri:level="1"><nlm:affiliation>Alexandra Hospital, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Alexandra Hospital</wicri:regionArea></affiliation></author><author><name sortKey="Parthasarathy, Purnima" sort="Parthasarathy, Purnima" uniqKey="Parthasarathy P" first="Purnima" last="Parthasarathy">Purnima Parthasarathy</name><affiliation wicri:level="1"><nlm:affiliation>Department of General Medicine, Khoo Teck Puat Hospital, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of General Medicine, Khoo Teck Puat Hospital</wicri:regionArea><wicri:noRegion>Khoo Teck Puat Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yuan Yi Constance" sort="Chen, Yuan Yi Constance" uniqKey="Chen Y" first="Yuan Yi Constance" last="Chen">Yuan Yi Constance Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Laboratory Medicine, Tan Tock Seng Hospital</wicri:regionArea><wicri:noRegion>Tan Tock Seng Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Barkham, Timothy" sort="Barkham, Timothy" uniqKey="Barkham T" first="Timothy" last="Barkham">Timothy Barkham</name><affiliation wicri:level="4"><nlm:affiliation>Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Lin, Raymond Tzer Pin" sort="Lin, Raymond Tzer Pin" uniqKey="Lin R" first="Raymond Tzer Pin" last="Lin">Raymond Tzer Pin Lin</name><affiliation wicri:level="1"><nlm:affiliation>National Public Health Laboratory, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>National Public Health Laboratory</wicri:regionArea></affiliation></author><author><name sortKey="Maurer Stroh, Sebastian" sort="Maurer Stroh, Sebastian" uniqKey="Maurer Stroh S" first="Sebastian" last="Maurer-Stroh">Sebastian Maurer-Stroh</name><affiliation wicri:level="4"><nlm:affiliation>National Centre for Infectious Diseases, Singapore; Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore; Department of Biological Sciences, National University of Singapore, Singapore; Global Initiative on Sharing All Influenza Data, Munich, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>National Centre for Infectious Diseases, Singapore; Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore; Department of Biological Sciences, National University of Singapore, Singapore; Global Initiative on Sharing All Influenza Data, Munich</wicri:regionArea><placeName><region type="land" nuts="1">Bavière</region><region type="district" nuts="2">District de Haute-Bavière</region><settlement type="city">Munich</settlement></placeName><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Leo, Yee Sin" sort="Leo, Yee Sin" uniqKey="Leo Y" first="Yee-Sin" last="Leo">Yee-Sin Leo</name><affiliation wicri:level="4"><nlm:affiliation>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; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>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; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Wang, Lin Fa" sort="Wang, Lin Fa" uniqKey="Wang L" first="Lin-Fa" last="Wang">Lin-Fa Wang</name><affiliation wicri:level="4"><nlm:affiliation>Duke-NUS Medical School, National University of Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Duke-NUS Medical School, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Renia, Laurent" sort="Renia, Laurent" uniqKey="Renia L" first="Laurent" last="Renia">Laurent Renia</name><affiliation wicri:level="1"><nlm:affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research</wicri:regionArea><wicri:noRegion>and Research</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Vernon J" sort="Lee, Vernon J" uniqKey="Lee V" first="Vernon J" last="Lee">Vernon J. Lee</name><affiliation wicri:level="4"><nlm:affiliation>Saw Swee Hock School of Public Health, National University of Singapore, Singapore; Ministry of Health, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Saw Swee Hock School of Public Health, National University of Singapore, Singapore; Ministry of Health</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Smith, Gavin J D" sort="Smith, Gavin J D" uniqKey="Smith G" first="Gavin J D" last="Smith">Gavin J D. Smith</name><affiliation wicri:level="4"><nlm:affiliation>Duke-NUS Medical School, National University of Singapore, Singapore. Electronic address: gavin.smith@duke-nus.edu.sg.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Duke-NUS Medical School, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Lye, David Chien" sort="Lye, David Chien" uniqKey="Lye D" first="David Chien" last="Lye">David Chien Lye</name><affiliation wicri:level="4"><nlm:affiliation>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; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>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; Yong Loo Lin School of Medicine, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Ng, Lisa F P" sort="Ng, Lisa F P" uniqKey="Ng L" first="Lisa F P" last="Ng">Lisa F P. Ng</name><affiliation wicri:level="1"><nlm:affiliation>Infectious 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.sg.</nlm:affiliation><country xml:lang="fr">Singapour</country><wicri:regionArea>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research</wicri:regionArea><wicri:noRegion>and Research</wicri:noRegion></affiliation></author></analytic><series><title level="j">Lancet (London, England)</title><idno type="eISSN">1474-547X</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult (MeSH)</term><term>Aged (MeSH)</term><term>Betacoronavirus (MeSH)</term><term>Coronavirus Infections (complications)</term><term>Coronavirus Infections (epidemiology)</term><term>Coronavirus Infections (virology)</term><term>Gene Deletion (MeSH)</term><term>Genome, Viral (genetics)</term><term>Humans (MeSH)</term><term>Hypoxia (etiology)</term><term>Hypoxia (therapy)</term><term>Middle Aged (MeSH)</term><term>Open Reading Frames (MeSH)</term><term>Pandemics (MeSH)</term><term>Pneumonia, Viral (complications)</term><term>Pneumonia, Viral (epidemiology)</term><term>Pneumonia, Viral (virology)</term><term>Prospective Studies (MeSH)</term><term>Respiratory Therapy (MeSH)</term><term>Severity of Illness Index (MeSH)</term><term>Singapore (epidemiology)</term><term>Virus Replication (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte (MeSH)</term><term>Adulte d'âge moyen (MeSH)</term><term>Betacoronavirus (MeSH)</term><term>Cadres ouverts de lecture (MeSH)</term><term>Délétion de gène (MeSH)</term><term>Génome viral (génétique)</term><term>Humains (MeSH)</term><term>Hypoxie (thérapie)</term><term>Hypoxie (étiologie)</term><term>Indice de gravité de la maladie (MeSH)</term><term>Infections à coronavirus (complications)</term><term>Infections à coronavirus (virologie)</term><term>Infections à coronavirus (épidémiologie)</term><term>Pandémies (MeSH)</term><term>Pneumopathie virale (complications)</term><term>Pneumopathie virale (virologie)</term><term>Pneumopathie virale (épidémiologie)</term><term>Réplication virale (MeSH)</term><term>Singapour (épidémiologie)</term><term>Sujet âgé (MeSH)</term><term>Thérapie respiratoire (MeSH)</term><term>Études prospectives (MeSH)</term></keywords><keywords scheme="MESH" type="geographic" qualifier="epidemiology" xml:lang="en"><term>Singapore</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Hypoxia</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genome, Viral</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Génome viral</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Hypoxia</term></keywords><keywords scheme="MESH" qualifier="thérapie" xml:lang="fr"><term>Hypoxie</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term><term>Pneumopathie virale</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr"><term>Infections à coronavirus</term><term>Pneumopathie virale</term><term>Singapour</term></keywords><keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Hypoxie</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Betacoronavirus</term><term>Gene Deletion</term><term>Humans</term><term>Middle Aged</term><term>Open Reading Frames</term><term>Pandemics</term><term>Prospective Studies</term><term>Respiratory Therapy</term><term>Severity of Illness Index</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Betacoronavirus</term><term>Cadres ouverts de lecture</term><term>Délétion de gène</term><term>Humains</term><term>Indice de gravité de la maladie</term><term>Pandémies</term><term>Réplication virale</term><term>Sujet âgé</term><term>Thérapie respiratoire</term><term>Études prospectives</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Singapour</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>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.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>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.</p></div><div type="abstract" xml:lang="en"><p><b>FINDINGS</b></p><p>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.</p></div><div type="abstract" xml:lang="en"><p><b>INTERPRETATION</b></p><p>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.</p></div><div type="abstract" xml:lang="en"><p><b>FUNDING</b></p><p>National Medical Research Council Singapore.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32822564</PMID><DateCompleted><Year>2020</Year><Month>09</Month><Day>08</Day></DateCompleted><DateRevised><Year>2020</Year><Month>09</Month><Day>08</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1474-547X</ISSN><JournalIssue CitedMedium="Internet"><Volume>396</Volume><Issue>10251</Issue><PubDate><Year>2020</Year><Month>08</Month><Day>29</Day></PubDate></JournalIssue><Title>Lancet (London, England)</Title><ISOAbbreviation>Lancet</ISOAbbreviation></Journal><ArticleTitle>Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study.</ArticleTitle><Pagination><MedlinePgn>603-611</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0140-6736(20)31757-8</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/S0140-6736(20)31757-8</ELocationID><Abstract><AbstractText Label="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.</AbstractText><AbstractText Label="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.</AbstractText><AbstractText Label="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.</AbstractText><AbstractText Label="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.</AbstractText><AbstractText Label="FUNDING">National Medical Research Council Singapore.</AbstractText><CopyrightInformation>Copyright © 2020 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Young</LastName><ForeName>Barnaby E</ForeName><Initials>BE</Initials><AffiliationInfo><Affiliation>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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fong</LastName><ForeName>Siew-Wai</ForeName><Initials>SW</Initials><AffiliationInfo><Affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore; Department of Biological Sciences, National University of Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chan</LastName><ForeName>Yi-Hao</ForeName><Initials>YH</Initials><AffiliationInfo><Affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mak</LastName><ForeName>Tze-Minn</ForeName><Initials>TM</Initials><AffiliationInfo><Affiliation>National Public Health Laboratory, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ang</LastName><ForeName>Li Wei</ForeName><Initials>LW</Initials><AffiliationInfo><Affiliation>National Public Health and Epidemiology Unit, National Centre for Infectious Diseases, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Anderson</LastName><ForeName>Danielle E</ForeName><Initials>DE</Initials><AffiliationInfo><Affiliation>Duke-NUS Medical School, National University of Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Cheryl Yi-Pin</ForeName><Initials>CY</Initials><AffiliationInfo><Affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Amrun</LastName><ForeName>Siti Naqiah</ForeName><Initials>SN</Initials><AffiliationInfo><Affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Bernett</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goh</LastName><ForeName>Yun Shan</ForeName><Initials>YS</Initials><AffiliationInfo><Affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Su</LastName><ForeName>Yvonne C F</ForeName><Initials>YCF</Initials><AffiliationInfo><Affiliation>Duke-NUS Medical School, National University of Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wei</LastName><ForeName>Wycliffe E</ForeName><Initials>WE</Initials><AffiliationInfo><Affiliation>National Public Health and Epidemiology Unit, National Centre for Infectious Diseases, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kalimuddin</LastName><ForeName>Shirin</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Duke-NUS Medical School, National University of Singapore, Singapore; Department of Infectious Diseases, Singapore General Hospital, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chai</LastName><ForeName>Louis Yi Ann</ForeName><Initials>LYA</Initials><AffiliationInfo><Affiliation>Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Medicine, National University Health System, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pada</LastName><ForeName>Surinder</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Medicine, Infectious Diseases Service, Ng Teng Fong General Hospital, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Seow Yen</ForeName><Initials>SY</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, Changi General Hospital, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>Louisa</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Alexandra Hospital, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Parthasarathy</LastName><ForeName>Purnima</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of General Medicine, Khoo Teck Puat Hospital, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Yuan Yi Constance</ForeName><Initials>YYC</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Barkham</LastName><ForeName>Timothy</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Raymond Tzer Pin</ForeName><Initials>RTP</Initials><AffiliationInfo><Affiliation>National Public Health Laboratory, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maurer-Stroh</LastName><ForeName>Sebastian</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>National Centre for Infectious Diseases, Singapore; Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore; Department of Biological Sciences, National University of Singapore, Singapore; Global Initiative on Sharing All Influenza Data, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Leo</LastName><ForeName>Yee-Sin</ForeName><Initials>YS</Initials><AffiliationInfo><Affiliation>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; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Lin-Fa</ForeName><Initials>LF</Initials><AffiliationInfo><Affiliation>Duke-NUS Medical School, National University of Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Renia</LastName><ForeName>Laurent</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Infectious Diseases Horizontal Technology Centre, Agency for Science, Technology, and Research, Singapore; Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Vernon J</ForeName><Initials>VJ</Initials><AffiliationInfo><Affiliation>Saw Swee Hock School of Public Health, National University of Singapore, Singapore; Ministry of Health, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smith</LastName><ForeName>Gavin J D</ForeName><Initials>GJD</Initials><AffiliationInfo><Affiliation>Duke-NUS Medical School, National University of Singapore, Singapore. Electronic address: gavin.smith@duke-nus.edu.sg.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lye</LastName><ForeName>David Chien</ForeName><Initials>DC</Initials><AffiliationInfo><Affiliation>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; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ng</LastName><ForeName>Lisa F P</ForeName><Initials>LFP</Initials><AffiliationInfo><Affiliation>Infectious 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.sg.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>HHSN272201400006C</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D064888">Observational Study</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>08</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Lancet</MedlineTA><NlmUniqueID>2985213R</NlmUniqueID><ISSNLinking>0140-6736</ISSNLinking></MedlineJournalInfo><SupplMeshList><SupplMeshName Type="Disease" UI="C000657245">COVID-19</SupplMeshName><SupplMeshName Type="Organism" UI="C000656484">severe acute respiratory syndrome coronavirus 2</SupplMeshName></SupplMeshList><CitationSubset>AIM</CitationSubset><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName><QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017353" MajorTopicYN="Y">Gene Deletion</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016679" MajorTopicYN="N">Genome, Viral</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000860" MajorTopicYN="N">Hypoxia</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016366" MajorTopicYN="N">Open Reading Frames</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058873" MajorTopicYN="N">Pandemics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName><QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011446" MajorTopicYN="N">Prospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012138" MajorTopicYN="N">Respiratory Therapy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012720" MajorTopicYN="N">Severity of Illness Index</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012846" MajorTopicYN="N" Type="Geographic">Singapore</DescriptorName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014779" MajorTopicYN="N">Virus Replication</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>06</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>07</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>07</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>8</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>9</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>8</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32822564</ArticleId><ArticleId IdType="pii">S0140-6736(20)31757-8</ArticleId><ArticleId IdType="doi">10.1016/S0140-6736(20)31757-8</ArticleId><ArticleId IdType="pmc">PMC7434477</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Allemagne</li><li>Singapour</li></country><region><li>Bavière</li><li>District de Haute-Bavière</li></region><settlement><li>Munich</li></settlement><orgName><li>Université nationale de Singapour</li></orgName></list><tree><country name="Singapour"><noRegion><name sortKey="Young, Barnaby E" sort="Young, Barnaby E" uniqKey="Young B" first="Barnaby E" last="Young">Barnaby E. Young</name></noRegion><name sortKey="Amrun, Siti Naqiah" sort="Amrun, Siti Naqiah" uniqKey="Amrun S" first="Siti Naqiah" last="Amrun">Siti Naqiah Amrun</name><name sortKey="Anderson, Danielle E" sort="Anderson, Danielle E" uniqKey="Anderson D" first="Danielle E" last="Anderson">Danielle E. Anderson</name><name sortKey="Ang, Li Wei" sort="Ang, Li Wei" uniqKey="Ang L" first="Li Wei" last="Ang">Li Wei Ang</name><name sortKey="Barkham, Timothy" sort="Barkham, Timothy" uniqKey="Barkham T" first="Timothy" last="Barkham">Timothy Barkham</name><name sortKey="Chai, Louis Yi Ann" sort="Chai, Louis Yi Ann" uniqKey="Chai L" first="Louis Yi Ann" last="Chai">Louis Yi Ann Chai</name><name sortKey="Chan, Yi Hao" sort="Chan, Yi Hao" uniqKey="Chan Y" first="Yi-Hao" last="Chan">Yi-Hao Chan</name><name sortKey="Chen, Yuan Yi Constance" sort="Chen, Yuan Yi Constance" uniqKey="Chen Y" first="Yuan Yi Constance" last="Chen">Yuan Yi Constance Chen</name><name sortKey="Fong, Siew Wai" sort="Fong, Siew Wai" uniqKey="Fong S" first="Siew-Wai" last="Fong">Siew-Wai Fong</name><name sortKey="Goh, Yun Shan" sort="Goh, Yun Shan" uniqKey="Goh Y" first="Yun Shan" last="Goh">Yun Shan Goh</name><name sortKey="Kalimuddin, Shirin" sort="Kalimuddin, Shirin" uniqKey="Kalimuddin S" first="Shirin" last="Kalimuddin">Shirin Kalimuddin</name><name sortKey="Lee, Bernett" sort="Lee, Bernett" uniqKey="Lee B" first="Bernett" last="Lee">Bernett Lee</name><name sortKey="Lee, Cheryl Yi Pin" sort="Lee, Cheryl Yi Pin" uniqKey="Lee C" first="Cheryl Yi-Pin" last="Lee">Cheryl Yi-Pin Lee</name><name sortKey="Lee, Vernon J" sort="Lee, Vernon J" uniqKey="Lee V" first="Vernon J" last="Lee">Vernon J. Lee</name><name sortKey="Leo, Yee Sin" sort="Leo, Yee Sin" uniqKey="Leo Y" first="Yee-Sin" last="Leo">Yee-Sin Leo</name><name sortKey="Lin, Raymond Tzer Pin" sort="Lin, Raymond Tzer Pin" uniqKey="Lin R" first="Raymond Tzer Pin" last="Lin">Raymond Tzer Pin Lin</name><name sortKey="Lye, David Chien" sort="Lye, David Chien" uniqKey="Lye D" first="David Chien" last="Lye">David Chien Lye</name><name sortKey="Mak, Tze Minn" sort="Mak, Tze Minn" uniqKey="Mak T" first="Tze-Minn" last="Mak">Tze-Minn Mak</name><name sortKey="Ng, Lisa F P" sort="Ng, Lisa F P" uniqKey="Ng L" first="Lisa F P" last="Ng">Lisa F P. Ng</name><name sortKey="Pada, Surinder" sort="Pada, Surinder" uniqKey="Pada S" first="Surinder" last="Pada">Surinder Pada</name><name sortKey="Parthasarathy, Purnima" sort="Parthasarathy, Purnima" uniqKey="Parthasarathy P" first="Purnima" last="Parthasarathy">Purnima Parthasarathy</name><name sortKey="Renia, Laurent" sort="Renia, Laurent" uniqKey="Renia L" first="Laurent" last="Renia">Laurent Renia</name><name sortKey="Smith, Gavin J D" sort="Smith, Gavin J D" uniqKey="Smith G" first="Gavin J D" last="Smith">Gavin J D. Smith</name><name sortKey="Su, Yvonne C F" sort="Su, Yvonne C F" uniqKey="Su Y" first="Yvonne C F" last="Su">Yvonne C F. Su</name><name sortKey="Sun, Louisa" sort="Sun, Louisa" uniqKey="Sun L" first="Louisa" last="Sun">Louisa Sun</name><name sortKey="Tan, Seow Yen" sort="Tan, Seow Yen" uniqKey="Tan S" first="Seow Yen" last="Tan">Seow Yen Tan</name><name sortKey="Wang, Lin Fa" sort="Wang, Lin Fa" uniqKey="Wang L" first="Lin-Fa" last="Wang">Lin-Fa Wang</name><name sortKey="Wei, Wycliffe E" sort="Wei, Wycliffe E" uniqKey="Wei W" first="Wycliffe E" last="Wei">Wycliffe E. Wei</name></country><country name="Allemagne"><region name="Bavière"><name sortKey="Maurer Stroh, Sebastian" sort="Maurer Stroh, Sebastian" uniqKey="Maurer Stroh S" first="Sebastian" last="Maurer-Stroh">Sebastian Maurer-Stroh</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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