Table 1.
Identified genetic susceptibility for COVID-19
| ID | The first author (reference) | Type of study | Country | Study population | Risk factors | Important findings |
|---|---|---|---|---|---|---|
| 1 | Abhari and Kawwass [30] | Review | USA | 112 women with normal endometrial pathology | ACE2, TMPRSS2, TMPRSS4, cathepsin B and L (CTSB and CTSL, respectively), FURIN, MX dynamin-like GTPase 1 (MX1), Basigin (BSG) genes | A positive correlation in ACE2 and TMPRSS4 expression has been found during the early secretory phase, beside a weak but positive correlation in ACE2, TMPRSS4, and CTSL expression during the window of implantation. They also reported that the expression of most viral genes including ACE2, TMPRSS4, CTSL, and CTSB at different stages of the menstrual cycle increases with age. Their findings suggest that older women may be more vulnerable to SARS-CoV-2 endometrial infection |
| 2 | Cao et al. [31] | Letter to the editor | China | COVID-19 patients from different populations | ACE2 gene | People living in East Asia have much higher AFs in the eQTL variants associated with higher ACE2 expression in tissues. It may result in a different susceptibility or response to SARS-CoV-2 indifferent populations under similar conditions |
| 3 | Casanova et al. [32] | Original research | USA | COVID-19 patients | IFN-γ, IL-17A/F genes | While known genetic factors are absent in determining human susceptibility to other Coronaviruses, influenza seems to provide the best comparison. Although the threshold levels of type I and/or III IFN for immunity against SARS-CoV-2 might be similar to those for the 1918 influenza virus, it might be higher than those for seasonal influenza |
| 4 | Debnath et al. [33] | Review | India | Covid-19 patients | ACE2, HLA, cytokine storm, TLR genes, complement genes | Numerous studies show the important role of genes coding ACE2, HLA, cytokine, TLR, and complement components in COVID-19. The distribution of many of these genes varies geographically or demographically and therefore causes different susceptibility and/or resistance to different viral diseases |
| 5 | Devaux et al. [34] | Review | France | COVID-19 patients | ACE2 gene | ACE2 protein at the surface of lung alveolar epithelial cells increases the level of vulnerability to SARS-CoV-2 infection. They assumed that the ACE2 levels correlate with susceptibility to SARS-CoV-2 infection. It should be considered that men have a higher ACE2 expression in the lung than women. In addition, Asian people express a higher level of ACE2 than Caucasian and African-American people |
| 6 | Fakhouri et al. [35] | Review | USA | COVID-19 patients | ACE2 gene | ACE levels are genetically controlled. People with ACE gene polymorphisms are more likely to become infected by the severe inflammation induced by COVID-19 |
| 7 | Fujikura et al. [36] | Research | Japan | Data from 5 population—sequencing projects | ACE2 gene, TMPRSS2 gene | SNVs in ACE2 and TMPRSS2 are mostly are, population-specific, and harmful; however, some very rare SNVs might explain different susceptibility to SARS-CoV-2 |
| 8 | Gemmati et al. [37] | Hypothesis | Italy | COVID-19 patients | ACE 2 gene, TMPRSS2 gene | Males are more likely to become infected with SARS-CoV-2 than females. A strong relation found between SARS-CoV-2 and human ACE 2 receptor |
| 9 | Giudicessi et al. [38] | Creative concepts | USA | African-Americans | A potentially pro-arrhythmic common variant, p.Ser1103-Tyr-SCN5A, present in 1 out of 13 individuals of African descent has the potential to increase the risk of drug- and hypoxia-induced ventricular arrhythmias/sudden cardiac death | They showed that the common ion channel variants p.Asp85Asn-KCNE1 and p.Ser1103TyrSCN5A confer an increased risk of DI-LQTS (drug-induced long QT syndrome) and DI-SCD (Drug-induced sudden cardiac death) |
| 10 | Godri et al. [39] | Review | USA | COVID-19 patients | Polymorphisms in ACE2 gene. Polymorphisms of cellular proteases along with furin and TMPRSS2. HLA-B*46:01 gene product (suggesting individuals with this allele may be more vulnerable to COVID-19) | HLA-B*15:03 (patients possessing HLA-B*15:03 genotype may become immune to the infectious COVID-19) |
| 11 | Hou et al. [40] | Correspondence | USA | COVID-19 patients | 1. ACE2 polymorphisms were more likely to be associated with cardiovascular and pulmonary conditions by altering the angiotensinogen-ACE2 interactions, such as p.Arg514-Gly in the African/African-American population | Developmental regulation of TMPRSS2 may make the infants and children immune to COVID-19. Thus, research should investigate the relationship between age and polymorphisms for TMPRSS2 |
| 2. We found 6 germline deleterious variants (p.Val160Met, p.Gly181Arg, p.Arg240Cys, p.Gly259Ser, p.Pro335Leu, and p.Gly432Ala) in the TMPRSS2 coding region | ||||||
| 12 | Junejo et al. [41] | Review | Pakistan/Turkey | COVID-19 patients | Loss of ACE2 function is related to acute lung injury because the ACE2 downregulation can result in RAS dysfunction, and endorse the inflammation that causes vascular permeability | |
| 13 | Kachuri et al. [42] | Research study | USA | COVID-19 patients | ACE2 gene | Sars-Cov-2 uses the ACE2 receptor for cell entry |
| 14 | LoPresti et al. [43] | Review | USA | COVID-19 patients | ACE2 gene, TMPRSS2 gene, HLA-B*46:01 | HLA-B*15:03 may be protective |
| 15 | Sanchez-Gonzalez et al. [44] | Report | USA | COVID-19 patients | Telomeres | In addition to people with immune senescence and dysregulation, SARS-CoV-2 can stimulate an HP-like severe immune reaction, especially in genetically vulnerable individuals. Telomeres typically shorten as the person gets older, but different rates of shortening may allow for measuring chronological versus biological aging. Besides, there is a strong connection between SARS-CoV-2 severe cases and the age of patients. There should be some researches on the association between telomere length and SARS-CoV-2, especially in younger patients with severe disease |
| 16 | Sheikh et al. [45] | Report | India | Covid-19 patients | ACE2 | – |
| 17 | Sironi et al. [46] | Review | USA | COVID-19 patients | ACE2 | S1 spike proteins of SARS-CoV and SARS-CoV-2 connect to ACE2 on the surface of the cell, causing the cleavage of the vasoconstrictor angiotensin II and countering the activity of ACE |
| TMPRSS2 | Lopera et al. [47] have reported a relation between a PheWAS of 178 quantitative phenotypes, including cytokine and cardio-metabolic markers which are not specific SARS-CoV-2 infection markers, and ACE2 and TMPRSS2 variation | |||||
| 18 | Strafella et al. [48] | Cohort | Italy | Italian population | ACE2 | They identified five SNVs in the Italian cohort: rs35803318, rs41303171, rs774469453, rs773676270, and rs2285666. Among them, rs35803318 and rs2285666 had a significantly different frequency distribution in the Italian people concerning worldwide population. The eQTLs analysis of ACE2 revealed a high distribution of eQTL variants in different brain tissues. They suggested that there may be a connection between ACE2 genetic variability and the neurological complications in patients with COVID-19 |
| 19 | Torre-Fuentes et al. [49] | Cohort | Spain | 138 individuals: 52 patients with MS and 86 unaffected family members | ACE2 gene, TMPRSS2 gene | Eleven variants were detected, which three of them were missense: rs75603675, rs12329760, and rs200291871, and eight of them were synonymous variants: rs2298659, rs61735792, rs61735789, rs61735794, rs141788162, rs17854725, rs3787950, andrs142750000, and for the remaining TMPRSS2, there weren’t any significant differences between individuals with and without SARS-CoV-2 |
| 20 | Thüsen and Eerden [50] | Review | Netherlands | COVID-19 patients | ACE2 gene, TMPRSS2 gene | Genetics may also play a role through polymorphisms of genes that encode for two types of proteins. First, proteins that are exploited by SARS-CoV-2, such as the highly conserved ACE2, which uses for docking and cellular entry in respiratory cells, as it was also the case for SARS-CoV. Second, proteins that protect against the effects of the virus (such as surfactant proteins, but also ACE2 itself). As an X-linked phenotype, interaction-booster and interaction-inhibitor variants of ACE2 can have a more definite effect in males than females and could play a role in a higher mortality rate in males. This can be the result of up to ∼70% of death caused by SARS-CoV2, SARS-CoV or MERS-CoV, in addition to a likely higher rate of risk factors (e.g., smoking) and a possibly different immune response in males. Other factors may also contribute. For example, transmembrane protease serine 2 (TMPRSS2), and its variants and expression have been linked to differences in COVID-19 severity |
| 21 | Vuitton et al. [51] | Editorial | France | COVID-19 patients | Immune complexes (ICs), ACE2 | In SARS-CoV-2 infection, the virus binds to ACE2, which is an enzymatic inhibitor of angiotensin II, able to modify the local microenvironment of ICs in vessels and alveoli. This mechanism could be a stimulant for IC-related endotheliitis |