Table 1.

Genetic risk factors for severe COVID-19

SARS-CoV-2 susceptibility gene variant or haplotype	Risk estimated [OR]	Frequency [MAF]	References
TLR3, UNC93B1, TICAM1, TBK1, IRF3, IRF7, IFNAR1, IFNAR2 (autosomal-dominant model)	9	< 0.001	Zhang et al. [20]
IRF7, IFNAR1 (autosomal-recessive model)	> 50	< 0.001	Zhang et al. [20]
rs769208985—missense variant of FURIN	N.A	< 0.001	Latini et al. [71]
rs150892504—missense variant of ERAP2	N.A	0.002	Hu et al. [60]
rs138763430—missense variant of BRF2	N.A	0.002	Hu et al. [60]
rs147149459—missense variant of ALOXE3	N.A	0.002	Hu et al. [60]
rs117665206—missense variant of TMEM181	N.A	0.006	Hu et al. [60]
rs114363287—missense variant of TMPRSS2	N.A	0.006	Latini et al. [71]
rs61756766—missense variant of TNFRSF13C	12.3	0.008	Russo et al. [61]
rs7626962—missense variant of SCN5A	8.7	0.008	SeyedAlinaghi et al. [62]
rs1805128—missense variant of KCNE1	9.0	0.009	SeyedAlinaghi et al. [62]
HLA-DRB*27:07	N.A	0.02	Novelli et al. [51]
rs72711165—intronic variant of TMEM65	1.2	0.02	COVID-19 H.G.I. [66]
rs115492982—intronic variant of MRPS21	2.5	0.02	Dite et al. [63]
rs74956615—3'UTR variant of TYK2	1.6	0.03	Pairo-Castineira et al. [11]
rs2034831—intronic variant of ITGA4	1.2	0.05	Dite et al. [63]
rs76374459—intronic variant of LZTFL1	1.2	0.05	Dite et al. [63]
rs35652899—intronic variant of LZTFL1	1.2	0.05	Dite et al. [63]
rs10490770—intronic variant of LZTFL1	2.0	0.06	COVID-19 H.G.I. [66]
rs333—CCR5-Δ32	0.7	0.07	Cuesta-Llavona et al. [76]
rs73064425—intronic variant of LZTFL1	2.1	0.08	Pairo-Castineira et al. [11], Ellinghaus et al. [23]
rs11385942—intronic variant of LZTFL1	1.8	0.07	Ellinghaus et al. [23]
rs1886814—intronic variant of FOXP4	1.3	0.07	COVID-19 H.G.I. [66]
rs76488148—intronic variant of GYG1	1.3	0.07	Dite et al. [63]
rs2271616—5'UTR variant of SLC6A20	1.1	0.08	COVID-19 H.G.I. [66]
HLA-DQB1*06:02	N.A	0.08	Novelli et al. [51]
rs143334143—intronic variant of CCHCR1	1.9	0.09	Pairo-Castineira et al. [11]
HLA-DRB1*15:01	N.A	0.10	Novelli et al. [51]
rs12252:G allele of IFITM3	2.2	0.13	Alghamdi et al. [52]
rs4801778—intronic variant of PLEKHA4	1.0	0.16	COVID-19 H.G.I. [66]
rs6598045—5'UTR variant of IFITM3	N.A	0.19	Kim et al. [53]
rs429358—missense variant of APOE	2.3–2.4	0.20	Kuo et al. [65]
rs12610495—intronic variant of DPP9	N.A	0.25	Moon et al. [41]
rs12329760—intronic variant of TMPRSS2/MX1	0.9	0.25	Andolfo et al. [72]
rs2298661—missense variant of TMPRSS2/MX1	0.9	0.25	Andolfo et al. [72]
rs3787946—intronic variant of TMPRSS2/MX1	0.9	0.28	Andolfo et al. [72]
rs9983330—intronic variant of TMPRSS2/MX1	0.9	0.28	Andolfo et al. [72]
rs9380142—3'UTR variant of HLA-G	13	0.29	Pairo-Castineira et al. [11]
rs2109069—intronic variant of DPP9	1.4	0.33	Pairo-Castineira et al. [11], COVID-19 H.G.I. [66]
rs9985159—intronic variant of TMPRSS2/MX1	0.9	0.33	Andolfo et al. [72]
Rs75603675—missense variant of TMPRSS2	N.A	0.36	Latini et al. [71]
rs1405655—intronic variant of NR1H2	1.1	0.37	COVID-19 H.G.I. [66]
rs12329760—missense variant of TMPRSS2	0.9	0.39	Hou et al. [73]
rs657152—intronic variant of ABO	1.3	0.41	Ellinghaus et al. [23]
rs677800—intronic variant of ABO	N.A	0.55	Moon et al. [41]
rs6020298—intronic variant of TMEM189-UBE2V1	1.2	0.58	Wang et al. [74]
rs10735079—intronic variant of OAS1/3	1.3	0.64	Pairo-Castineira et al. [11]
rs8065800—intronic variant of MAPT	1.7	0.65	COVID-19 H.G.I. [66]
rs10774671—intronic, splicing variant of OAS1	1.1	0.67	COVID-19 H.G.I. [66]
rs13050728—intronic variant of IFNAR2	0.9	0.69	COVID-19 H.G.I. [66]
rs2236757—intronic variant of IFNAR2	1.3	0.71	Pairo-Castineira et al. [11]
rs3131294—intronic variant of NOTCH4	1.5	0.90	Pairo-Castineira et al. [11]
HLA-A*11	N.A	N.A	Fricke-Galindo et al. [54]
HLA-A*11:01:01:01	2.3	N.A	Khor et al. [56]
HLA-A*25:01	N.A	N.A	Fricke-Galindo et al. [54]
HLA-B*46:01	2.1	N.A	Lin et al. [53], Fricke-Galindo et al. [54]
HLA-B*51:01	N.A	N.A	Fricke-Galindo et al. [54]
HLA B*54:01	5.4	N.A	Lin et al. [55]
HLA-C*01	N.A	N.A	Fricke-Galindo et al. [54]
HLA-C*01:02	N.A	N.A	Fricke-Galindo et al. [54]
HLA-C*05	N.A	N.A	Fricke-Galindo et al. [54]
HLA-C12:02:02:01-HLA52:01:02:02	2.3	N.A	Khor et al. [56]
HLA-C*14:02	N.A	N.A	Fricke-Galindo et al. [54]
HLA-C*17	N.A	N.A	Bonaccorsi et al. [57]
HLA-DQB1*04	N.A	N.A	Fricke-Galindo et al. [54]
HLA-DQB1*08	N.A	N.A	Fricke-Galindo et al. [54]
HLA-E*0101/0103	2.1–2.7	N.A	Vietzen et al. [58]
KLRC2^del	2.6–7.1	N.A	Vietzen et al. [58]
ACE1 I/D genotype	2.5	N.A	Verma et al. [69]
C9orf72 with HREs > 10 units	2.4	N.A	Zanella et al. [64]
c.2129_2132del, p.Gln710Argfs18—frameshift variant of TLR7*	N.A	N.A	van der Made et al. [42]
c.2383G > T, p.Val795Phe—missense variant of TLR7	N.A	N.A	van der Made et al. [42]
c.644A > G, p.Asn215Ser—missense variant of TLR7	N.A	N.A	Solanich et al. [43]
c.2797 T > C, p.Trp933Arg—missense variant of TLR7	N.A	N.A	Solanich et al. [43]
c.901 T > C, p.Ser301Pro—missense variant of TLR7	N.A	N.A	Fallerini et al. [44]
c.3094G > A, p.Ala1032Thr— missense variant of TLR7	N.A	N.A	Fallerini et al. [44]
c.2759G > A, p.Arg920Lys—missense variant of TLR7	N.A	N.A	Fallerini et al. [44]
c.863C > T, p.Ala288Val—missense variant of TLR7	N.A	N.A	Fallerini et al. [44]
c.1342C > T, p.Ala448Val—missense variant of TLR7	N.A	N.A	Fallerini et al. [44]
c.655G > A, p.Val219Ile—missense variant of TLR7	N.A	N.A	Fallerini et al. [44]
rs140312271—missense variant of ACE2	N.A	N.A	Novelli et al. [75]

MAF Major Allele Frequency; N.A. Not Applicable; OR Odds Ratio