Nat Med
. 2021 Feb 25.
doi: 10.1038/s41591-021-01281-1. Online ahead of print.
A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity
Sirui Zhou # 1 2 , Guillaume Butler-Laporte # 1 2 , Tomoko Nakanishi # 1 3 4 5 , David R Morrison 1 , Jonathan Afilalo 1 2 6 , Marc Afilalo 1 7 , Laetitia Laurent 1 , Maik Pietzner 8 , Nicola Kerrison 8 , Kaiqiong Zhao 1 2 , Elsa Brunet-Ratnasingham 9 10 , Danielle Henry 1 , Nofar Kimchi 1 , Zaman Afrasiabi 1 , Nardin Rezk 1 , Meriem Bouab 1 , Louis Petitjean 1 , Charlotte Guzman 1 , Xiaoqing Xue 1 , Chris Tselios 1 , Branka Vulesevic 1 , Olumide Adeleye 1 , Tala Abdullah 1 , Noor Almamlouk 1 , Yiheng Chen 1 3 , Micha?l Chass? 9 , Madeleine Durand 9 , Clare Paterson 11 , Johan Normark 12 , Robert Frithiof 13 , Mikl?s Lipcsey 13 14 , Michael Hultstr?m 13 15 , Celia M T Greenwood 1 2 16 , Hugo Zeberg 17 , Claudia Langenberg 8 18 , Elin Thysell 19 , Michael Pollak 1 20 , Vincent Mooser 3 , Vincenzo Forgetta 1 , Daniel E Kaufmann 9 21 , J Brent Richards 22 23 24 25
Affiliations
- PMID: 33633408
- DOI: 10.1038/s41591-021-01281-1
Abstract
To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation (odds ratio (OR) = 0.54, P = 7 ? 10-8), hospitalization (OR = 0.61, P = 8 ? 10-8) and susceptibility (OR = 0.78, P = 8 ? 10-6). Measuring OAS1 levels in 504 individuals, we found that higher plasma OAS1 levels in a non-infectious state were associated with reduced COVID-19 susceptibility and severity. Further analyses suggested that a Neanderthal isoform of OAS1 in individuals of European ancestry affords this protection. Thus, evidence from MR and a case-control study support a protective role for OAS1 in COVID-19 adverse outcomes. Available pharmacological agents that increase OAS1 levels could be prioritized for drug development.