The COVID-19 pandemic has strengthened the interest in the biological mechanisms underlying the complex interplay between infectious agents and the human host. The spectrum of phenotypes associated with the SARS-CoV-2 infection, ranging from the absence of symptoms to severe systemic complications, raised the question as to what extent the variable response to coronaviruses (CoVs) is influenced by the variability of the hosts’ genetic background. To explore the current knowledge about this question, we designed a systematic review encompassing the scientific literature published from Jan. 2003 to June 2020, to include studies on the contemporary outbreaks caused by SARS-CoV-1, MERS-CoV and SARS-CoV-2 (namely SARS, MERS and COVID-19 diseases). Studies were eligible if human genetic variants were tested as predictors of clinical phenotypes. An ad hoc protocol for the rapid review process was designed according to the PRISMA paradigm and registered at the PROSPERO database (ID: CRD42020180860). The systematic workflow provided 32 articles eligible for data abstraction (28 on SARS, 1 on MERS, 3 on COVID-19) reporting data on 26 discovery cohorts. Most studies considered the definite clinical diagnosis as the primary outcome, variably coupled with other outcomes (severity was the most frequently analysed). Ten studies analysed HLA haplotypes (1 in patients with COVID-19) and did not provide consistent signals of association with disease-associated phenotypes. Out of 22 eligible articles that investigated candidate genes (2 as associated with COVID-19), the top-ranked genes in the number of studies were ACE2, CLEC4M (L-SIGN), MBL, MxA (n = 3), ACE, CD209, FCER2, OAS-1, TLR4, TNF-α (n = 2). Only variants in MBL and MxA were found as possibly implicated in CoV-associated phenotypes in at least two studies. The number of studies for each predictor was insufficient to conduct meta-analyses. Studies collecting large cohorts from different ancestries are needed to further elucidate the role of host genetic variants in determining the response to CoVs infection. Rigorous design and robust statistical methods are warranted.

中文翻译：

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人类宿主的遗传变异影响冠状病毒相关表型（SARS、MERS 和 COVID-19）：快速系统评价和现场概要。

COVID-19 大流行增强了人们对传染源与人类宿主之间复杂相互作用的生物机制的兴趣。与 SARS-CoV-2 感染相关的一系列表型，从无症状到严重的全身并发症，提出了一个问题：宿主遗传变异性在多大程度上影响了对冠状病毒 (CoV) 的可变反应？背景。为了探索目前关于这个问题的知识，我们设计了一份系统综述，涵盖 2003 年 1 月至 2020 年 6 月发表的科学文献，其中包括对 SARS-CoV-1、MERS-CoV 和 SARS-CoV 引起的当代疫情的研究。 2（即 SARS、MERS 和 COVID-19 疾病）。如果人类遗传变异被测试为临床表型的预测因子，那么研究是合格的。根据 PRISMA 范式设计了快速审查过程的临时协议，并在 PROSPERO 数据库中注册（ID：CRD42020180860）。系统工作流程提供了 32 篇符合数据提取条件的文章（28 篇关于 SARS、1 篇关于 MERS、3 篇关于 COVID-19），报告了 26 个发现队列的数据。大多数研究将明确的临床诊断视为主要结局，并不同程度地与其他结局相结合（最常分析的是严重程度）。十项研究分析了 HLA 单倍型（其中 1 项研究针对 COVID-19 患者），但没有提供与疾病相关表型相关的一致信号。在调查候选基因的 22 篇合格文章中（2 篇与 COVID-19 相关），研究数量中排名靠前的基因是 ACE2、CLEC4M (L-SIGN)、MBL、MxA (n = 3)、ACE、 CD209、FCER2、OAS-1、TLR4、TNF-α (n = 2)。在至少两项研究中，仅发现 MBL 和 MxA 的变异可能与 CoV 相关表型有关。每个预测因子的研究数量不足以进行荟萃分析。需要收集来自不同血统的大量群体的研究，以进一步阐明宿主遗传变异在确定对冠状病毒感染的反应中的作用。严格的设计和稳健的统计方法是必要的。