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. Keywords: COVID-19, Coronavirus, Genomic biomarker, Human host, Genetic susceptibility, Genetic association, Genotype, Polymorphism © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. * Correspondence: emilio.dimaria@unige.it 1 Department of Health Sciences, University of Genova, Genova, Italy 2 Unit of Medical Genetics, Galliera Hospital, Genova, Italy Full list of author information is available at the end of the article Di Maria et al. Human Genomics (2020) 14:30 https://doi.org/10.1186/s40246-020-00280-6 Introduction Infectious diseases are known to accompany human evolution through a complex interaction between the host and the infection [1]. Infectious diseases, by definition, are caused by a single infectious agent. However, even prior to the current molecular genetics era, heritability studies provided the first line of evidence that part of inter-individual differences is attributable to the host genetics profile [2, 3]. The global impact of tuberculosis and HIV infection, the interest in the understanding of the genetic background of infectious disease, coupled with the emerging molecular technologies, lead to an increase of investigations on the role of the human host genetics profile [4]. Most candidate-gene studies were concentrating on respiratory infections. However, these studies provided conflicting results [5]. Several human-tropic coronaviruses (CoVs) constantly circulate in the human population and usually cause mild respiratory disease. Two of these RNA viruses— SARS-CoV-1 and MERS-CoV—had been discovered in 2002 and 2012, respectively, as the cause of severe acute respiratory syndromes. The former emerged in Guangdong province, China, and its spread in China is known as the SARS epidemic. The latter caused an epidemic that began in Saudi Arabia and was limited in the Middle East (thus named Middle East Respiratory Syndrome, MERS) [6]. In December 2019, a new infectious respiratory disease emerged in Wuhan, Hubei province, China. The disease, termed coronavirus disease 19 (COVID-19), rapidly spread from China as a global devastating pandemic [7– 9]. At the time we were drafting this manuscript, the impact of the outbreak was still growing worldwide. According to the World Health Organisation, confirmed cases had exceeded 14 million and the number of deaths 600,000 (covid19.who.int—last access July 20, 2020). As the knowledge of the COVID-19 risk factors has progressed, age has become recognised as one of the predominant determinants of severe outcomes [10, 11], in association with cardiovascular disease and metabolic disorders as major comorbidity factors [12]. The latest findings of seroprevalence in COVID-19 were allowed to estimate a higher prevalence of infection than previously inferred [13]. This is in line with the hypothesis that the high rate of severe clinical manifestations experienced in the initial spread was attributable to vulnerable individuals. The extent to which the susceptibility to the severe clinical course is due to comorbidity or is determined by constitutional factors needs to be elucidated. Soon after the SARS outbreak in 2003, researchers tried to respond to the question as to whether germline genetic variants influence the occurrence of the clinical syndrome