加拿大麦吉尔大学J. Brent Richards小组发现，一个起源于尼安德特人的OAS1亚型可提高欧洲人种对COVID-19的保护。2021年2月25日，《自然—医学》杂志在线发表了这项成果。

为了确定影响COVID-19易感性和严重性的循环蛋白，研究人员进行了两次样本孟德尔随机（MR）研究来快速筛选数百种循环蛋白，同时减少了因反向因果关系和混杂而引起的偏倚。在多达14,134个病例和120万个对照中，研究人员发现OAS1水平升高与COVID-19死亡或人工通气（比值比（OR）= 0.54，P=7×10^-8）、住院（OR=0.61，P=8×10^-8）和易感性（OR=0.78，P=8×10^-6）的减少相关。

通过测量504个人的OAS1水平，研究人员发现在非感染状态下较高的血浆OAS1水平与降低的COVID-19敏感性和严重程度有关。进一步的分析表明，在欧洲血统的个体中，OAS1的一种尼安德特人亚型提供了这种保护。

因此，MR和病例对照研究的证据支持OAS1在COVID-19不良预后中的保护作用。能够提高OAS1水平的现有药物可被优先用于药物开发。 

附：英文原文

Title: A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity

Author: Sirui Zhou, Guillaume Butler-Laporte, Tomoko Nakanishi, David R. Morrison, Jonathan Afilalo, Marc Afilalo, Laetitia Laurent, Maik Pietzner, Nicola Kerrison, Kaiqiong Zhao, Elsa Brunet-Ratnasingham, Danielle Henry, Nofar Kimchi, Zaman Afrasiabi, Nardin Rezk, Meriem Bouab, Louis Petitjean, Charlotte Guzman, Xiaoqing Xue, Chris Tselios, Branka Vulesevic, Olumide Adeleye, Tala Abdullah, Noor Almamlouk, Yiheng Chen, Michal Chass, Madeleine Durand, Clare Paterson, Johan Normark, Robert Frithiof, Mikls Lipcsey, Michael Hultstrm, Celia M. T. Greenwood, Hugo Zeberg, Claudia Langenberg, Elin Thysell, Michael Pollak, Vincent Mooser, Vincenzo Forgetta, Daniel E. Kaufmann, J. Brent Richards

Issue&Volume: 2021-02-25

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 1.2million 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=7×108), hospitalization (OR=0.61, P=8×108) and susceptibility (OR=0.78, P=8×106). 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.

DOI: 10.1038/s41591-021-01281-1

Source: https://www.nature.com/articles/s41591-021-01281-1