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Table 1 Articles included as eligible for data abstraction, ordered by year of publication and first author. For each study, main features, genes/loci examined and summary of the main findings are reported

From: Genetic variants of the human host influencing the coronavirus-associated phenotypes (SARS, MERS and COVID-19): rapid systematic review and field synopsis

Author, year

Population description

Country

Disease

Primary outcome

Other outcomes

Sample N

Cases N

Controls N

Notes on cohorts

Gene/locus

Conclusions

Ref.

Lin M, 2003

SARS cases admitted to Taipei Hospital, Taiwan

Taiwan

SARS

Manifest disease

Severity

134

33

101

 

HLA-A, HLA-B, HLA-DRB1

HLA-B*4601 nominally associated with severity (vs larger control group), not with infection after P correction

[28]

Chiu RWK, 2004

SARS patients admitted at Hong Kong Chinese University Hospital

Hong Kong

SARS

Manifest disease

Severity

496

168

328

 

ACE2

Negative results

[29]

Itoyama S, 2004

Vietnamese patients with SARS

Vietnam

SARS

Manifest disease

Hypoxemia

147

44

103

#

ACE

ACE nominally associated with severity

[30]

Ng MHL, 2004

SARS patients admitted at Hong Kong Chinese University Hospital

Hong Kong

SARS

Manifest disease

Severity

18864

90

18774

 

HLA-A, HLA-B, HLA-DR, HLA-DQ

HLA-B*0703 and -B*0301 nominally associated with the disease; no association with severity

[31]

Chan KC, 2005

SARS patients previously admitted at Hong Kong Hospitals

Hong Kong

SARS

Manifest disease

Severity

466

140

326

 

ACE

Negative results

[32]

Hamano E, 2005

SARS patients

Vietnam

SARS

Manifest disease

Severity (oxygen therapy)

147

44

103

 

OAS-1, MxA, PKR

Nominal association of OAS-1 with disease but not severity; nominal association of MxA with severity only

[33]

Ip WK, 2005

SARS patients previously admitted at 5 Hong Kong Hospitals

Hong Kong

SARS

Manifest disease

Serum MBL level; severity (death)

1757

569

1188

 

MBL

Association of -221 Y allele with disease and MBL level; no association with mortality

[34]

Itoyama S, 2005

Vietnamese patients with SARS

Vietnam

SARS

Manifest disease

 

147

44

103

#

ACE2

Negative results

[35]

Yuan FF, 2005

SARS patients admitted at Prince of Wales Hospital, Hong Kong

Hong Kong

SARS

Manifest disease

Severity (ICU or death)

380

180

200

§

FcγRIIA, MBL

No association with MBL; FcγRIIA nominally associated with severity

[36]

Zhang H, 2005

SARS patients from Bejing, China

China

SARS

Manifest disease

Serum MBL level

744

352

392

 

MBL

Association of nt 54 B allele with disease and MBL level

[37]

Chan VS, 2006

SARS patients admitted at four hospitals in Hong Kong

Hong Kong

SARS

Manifest disease

 

1127

285

842

$

CLEC4M (L-SIGN)

CLEC4M nominally associated with homozigosity (protective).

Functional analysis consistent with genetic risk.

[38]

Chong WP, 2006

SARS cases retrospecivelly selected in Hong Kong and Bejing, China

Hong Kong

SARS

Manifest disease

Severity (death)

925

476

449

 

IFN-γ, IL-10, TNF-α

No association with IL-10 and TNFalfa; IFNγ nominally associated with disease, not associated with severity

[39]

He J, 2006

SARS patients from Bejing, China

China

SARS

Manifest disease

 

66

66

64

Cohort assessed for risk factors

OAS-1, MxA

Nominal association of OAS-1 and MxA with disease.

For both variants association found in dominant model only.

[40]

Chen WJ, 2006

SARS cases retrospecivelly selected from the National Taiwan database

Taiwan

SARS

Positive NPS

Manifest disease

188

94

94

 

ACE2, ACP5, ADAR, AIP, ANPEP, B2M, CAT, CCL5/RANTES, CD209, CIITA, CXCL9, CXCL10, CYP17A1, EIF2AK3, EIF2S1, EIF4G1, ESR1, FGL2, FN1, G6PD, GNB3, GPX1, GSS, HMOX1, IFNAR1, IFNAR2, IFNG, IFNGR1, IFNGR2, IL1A, IL1B, IL1RN, IL4, IL6, IL10, IL10RB, IL12A, IL15, IL18, IRF1, IRF3, IRF7, MBL2, MX1, NFRKB, OAS1, PRDX2, PRKRA, PTGS2, RelB, RFX5, RNASEL, SERPINB3, SH2DIA, SLAMF1, SOCS1, SOCS3, SOD1, TBF, TFRC, TGFB1, TLR3, TLR4, TRAF6, WSX1

Nominal association of detectable NPS with 4 genes (IL1A, IL18, FGL2, RelB) in the patients’ cohort; no association with infection in the case-control study

[41]

Chen YM, 2006

Employees of the Municipal Hoping Hospital, Taipei

Taiwan

SARS

Seropositivity

 

100

20

80

 

HLA-A, HLA-B, HLA-Cw, HLA-DQB1, HLA-DRB1

HLA-Cw0801 nominally associated with SARS infection

[42]

Chan KYK, 2007

SARS patients previously admitted at 6 Hong Kong Hospitals

Hong Kong

SARS

Manifest disease

LDH level, WBC

1723

817

906

$

ICAM3, FCER2, CD209 (DC-SIGN), CLEC4M (L-SIGN)

ICAM3 possibly associated with severity, via LDH level as a proxy

[43]

Ng MW, 2007

SARS cases retrospectively selected in Hong Kong and Bejing, China

Hong Kong

SARS

Manifest disease

Severity (ICU or death)

1073

495

578

 

CCL5/RANTES, IP-10, Mig

No association with IL-10 and Mig; CCL5/RANTES -28C > G is associated with disease (discovery cohort only) and severity (both discovery and validation cohorts). Association between CCL5/RANTES and severity was validated in an independent cohort of Chinese patients

[44]

Yuan FF, 2007

SARS patients admitted at Prince of Wales Hospital, Hong Kong

Hong Kong

SARS

Manifest disease

Severity (ICU)

350

152

198

§

TLR2, TLR4, CD14

No informative variant in TLR2 and TLR4; CD14 nominally associated with severity

[45]

Li H, 2008

SARS patients retrospectively collected

Hong Kong

SARS

Manifest disease

Severity (ICU or death)

353

181

172

 

FCER2, CLEC4G, CD209, CLEC4M (L-SIGN)

Negative results (4 genes in the C-type lectin genes cluster, chr. 19).

[46]

Wang S, 2008

SARS patients admitted at Tianjin Hospital, China

China

SARS

Manifest disease

Interstitial lung fibrosis; femoral head necrosis

208

75

133

 

TNF-α

No association with infection and interstitial lung fibrosis; nominal association with femoral head necrosis

[47]

Xiong P, 2008

SARS patients from Guangdong province, China

China

SARS

Manifest disease

Severity

498

95

403

 

HLA-A, HLA-B, HLA-DRB1

Negative results

[48]

Keicho N, 2009

Vietnamese patients with SARS

Vietnam

SARS

Manifest disease

Seropositivity

145

44

101

#

HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1

HLA-DRB1*12 possibly associated with disease

[49]

Wang Y, 2009

SARS patients from Bejing and Guangzhou, China

China

SARS

Manifest disease

 

899

376

523

 

MASP2

Negative results (MASP is a downstream protein of MBL).

[50]

Chan KYK, 2010

SARS patients previously admitted at Hong Kong Hospitals

Hong Kong

SARS

LDH level

 

681

681

n/a

$

CD209 (DC-SIGN); combined CD209 and ICAM3

CD209 and CD209 + ICAM3 possibly associated with severity, via LDH level as proxy

[51]

Ching JCY, 2010

SARS patients previously admitted at 6 Hong Kong Hospitals

Hong Kong

SARS

Manifest disease

Severity (assisted ventilation and other not reported measures)

1210

792

418

$

MxA

Nominal association of MxA with disease, not with severity; OAS-1 + MxA dyplotype also analysed

[52]

Ng MH, 2010

SARS patients recruited from the Hong Kong Department of Health database

Hong Kong

SARS

Manifest disease

 

210

102

108

Controls were contact of patients; families also enrolled

HLA-A, HLA-B, HLA-Cw, HLA-DQ, HLA-DR

Negative results: nominal association with disease (increase in DRB4*01010101 frequency, decrease in HLA-B*1502 and HLA-DRB3*030101 frequency in patients) not surviving to correction.

Replication of previous study failed. Analysis of family data was done.

[53]

Wang SF, 2011

Affected health care workers followed-up at the Dept. of Health, Taipei

Taiwan

SARS

Manifest disease

Prolonged neutralising antibody expression

97

56

41

 

HLA-B, HLA-Cw, HLA-DR

HLA-Cw1502 and DR0301 possibly associated with resistance to SARS infection

[54]

Yuan FF, 2014

SARS patients admitted at Hong Kong Chinese University Hospital

Hong Kong

SARS

Manifest disease

Severity

18950

176

18774

48 cases classified as severe

HLA-A, HLA-B, HLA-DR

Negative results

[55]

Hajeer AH, 2016

Patients with laboratory-confirmed MERS-CoV infection admitted at King Abdulaziz Medical City, Riyadh

Saudi Arabia

MERS

Manifest disease

Severity

184

23

161

 

HLA-DRB1, HLA-DQB1

HLA-DRB1*11:01 nominally associated with severe MERS

[56]

Kuo CL, 2020

COVID-19 patients from the UN Biobank

 

COVID-19

COVID-19 positivity status

 

323570

622

322948

General population as control

APOE

APOE ε4 homozygous genotype associated, independent of preexisting dementia

[57]

Wang W, 2020

Donors of convalescent plasma who recovered from COVID-19 in Zhejiang, China

China

COVID-19

Manifest disease

 

3630

82

3548

No severe case; 242 controls for HLA-DP1 locus

HLA-A, HLA-B, HLA-C, HLA-DQ, HLA-DR, HLA-DP

HLA haplotype C*07:29 and B*15:27 nominally associated with SARS-CoV-2 infection

[58]

Zhang Y, 2020

Patients with COVID-19 admitted to Beijing Youan Hospital, China

China

COVID-19

Disease severity

 

80

80

 

24 severe cases vs 56 mild

IFITM3

Association with severity

[59]

  1. Notes and legend: gene and polymorphism names were reported as described in articles; the dbSNP nomenclature was added in brackets; statistics was reported if the significant association was found, not significant was annotated otherwise.
  2. ICU intensive care unit, LDH lactate dehydrogenase, WBC white blood counts, LR logistic regression, ns not significant, n/r not reported, n/a not applicable, #: Same cohort used by Itoyama S 2004, 2005, Keicho N 2009; § Same cohort used by Yuan FF 2005, 2007; $: Same cohort used by Chan VS 2006, Chan KYK 2007, 2010, Ching JCY 2010.