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Table 2 An overview of reported outcomes of SARS-CoV-2 infection in patients with known inborn errors of immunity

From: Clinical implications of host genetic variation and susceptibility to severe or critical COVID-19

 

Delavari et al. [63]

Marcus et al. [68]

Hsi-en Ho et al. [64]

Meyts et al. [57]

Shields et al. [69]

Castano-Jaramillo et al. [70]

Esenboga et al. [65]

Millito et al. [71]

Goudouris et al. [72]

Total

Demographics

 Genetic ancestry

Iran

Israel

USA

Europe, UK, Latin America, USA

UK

Mexico

Turkey

Italy

Brazil

 

 Age, mean (IQR)

5.19 (1.04–8.96)

14.3 (15–30)

44.5 (28.0–64.0)

25–34b

42.0 (28.0–57.0)

22.5 (11.5–29.5)

20.5 (9.41–39.0)

35.3

25.1 (10.7–38.6)

 

  <18y, %

78.9

45

12.5

34

7.5

51.6

42.3

25.2

47.1

 

  >18y, %

21.1

55

87.5

66

92.5

48.4

57.7

74.8

52.9

 

 Sex, M:F

63:37

60:40

69:31

65:35

57:43

74:28

54:46

61:39

45:55

 

Distribution of IEI groups

 Total, n

19

20

16

94

67c

31

26

131

121e

525

 Primary antibody deficiency (PAD), n (%)

4 (21.1)

6 (30.0)

14 (87.5)

53 (56.4)

45 (67.2)

20 (64.5)

13 (50.0)

99 (75.6)

53 (43.8)

307 (58.5)

  CVID

1

4

9

29

23

11

5

76

26

184

  Agammaglobulinemia (XL/AR)

1

2

3

6

4

7

4

16

11

54

  Other (hypogammaglobulinemia, specific Ab or Ig subclass deficiency)

2

0

2

18

18

2

4

7

16

69

 Combined immunodeficiency, n (%)

10 (52.6)

9 (45)

1 (6.3)

14 (14.9)

4 (6.0)

3 (9.7)

7d (26.9)

22 (17.0)

17 (14.0)

87 (16.6)

  Syndromal

4

1

0

10

3

1

6

14

5

44

  Non-syndromal (including SCID)a

6

8

1

4

1

2

1

8

12f

31

 Immune dysregulation, n (%)

2 (10.5)

3 (15)

0 (0)

9 (9.6)

4 (3.0)

1 (3.2)

4 (15.4)

2 (1.5)

3 (2.5)

28 (5.3)

  EBV/HLH

2

0

0

1

2

0

1

0

3

9

  Autoimmunity

0

3

0

8

2

1

3

2

0

19

 Auto-inflammatory disorder, n (%)

1 (5.3)

0

0 (0)

7 (7.4)

3 (4.5)

1 (3.2)

0 (0)

1 (0.8)

9 (7.4)

22 (4.2)

  Periodic fever syndrome

0

0

0

3

1

0

0

0

6

10

  Interferonopathy

0

0

0

3

1

0

0

1

0

5

  Other

1

0

0

1

1

1

0

0

3

7

 Phagocyte defect, n (%)

2 (10.5)

2 (10)

0 (0)

6 (6.4)

4 (4.5)

5 (16.1)

1 (3.8)

0 (0)

6 (5.0)

26 (5.0)

  Functional defect (i.e. CGD)

2

2

0

4

4

5

0

0

5

22

  Neutropenia/other

0

0

0

2

0

0

1

0

1

4

 Innate/intrinsic defect, n (%)

0 (0)

0 (0)

1 (6.3)

3 (3.2)

0 (0)

0 (0)

1 (3.8)

4 (3.1)

7 (5.8)

16 (3.0)

  Bacterial/parasitic

0

0

1

2

0

0

1

2

4

10

  MSMD/viral

0

0

0

1

0

0

0

2

3

6

 Complement deficiencies, n (%)

0 (0)

0 (0)

0 (0)

0 (0)

5 (7.5)

0 (0)

0 (0)

0 (0)

25 (20.7)

30 (5.7)

 Bone marrow failure, n (%)

0 (0)

0 (0)

0 (0)

2 (2.1)

0 (0)

0 (0)

0 (0)

0 (0)

0 (0)

2 (0.4)

 Phenocopies, n (%)

0 (0)

0 (0)

0 (0)

0 (0)

0 (0)

1 (3.2)

0 (0)

3 (2.3)

1 (0.8)

5 (1.0)

COVID-19 outcomes

 Hospitalization, %

100

0

75

63

50.7

48

38.4

NA

28.9

184/394 (46.7)

 Respiratory insufficiency, %

NA

0

62.5

31

NA

NA

15.3

NA

18.1

68/266 (25.6)

 Mechanical ventilation, %

NA

0

31.3

16

NA

NA

7.7

NA

NA

 

  (N)ICU admission, %

42.1

0

31.3

21.2

NA

26

7.7

NA

NA

 

 Infection fatality rate (%)

8/19 (42.1)

0

4/16 (25)

9/94 (9.6)

12/67 (17.9)

6 (19.4)

2/26 (7.7)

5/131 (3.8)

6/121 (5.0)

52/525 (9.9)

 Underlying diagnoses among fatal cases

STK4, RAB27, DNMT3B and IL1RN deficiency, SCID (n=4)

NA

CVID (n=2), hypogammaglobulinemia, IgA-IgG2 deficiency

X-CGD with HLH, XIAP deficiency with GVHD following HSCT and septic shock/HLH, syndromic IEI with heart failure, pulmonary hypertension and a pneumothorax, and antibody deficiencies (CVID n=4, IgG n=1, IgA/IgG2 n=1)

Primary antibody deficiency (CVID (n=8), unclassified PAD (n=1), polysaccharide antibody deficiency (n-1), unclassified CID (n=1), CTLA4 (n=1))

Four children died (WAS, XLA with secondary HLH, CGD and unspecified auto-inflammatory syndrome both with MIS-C) and two adults (good syndrome and XLA with both bacterial superinfection)

LRBA deficiency, EBV-related NHL receiving chemotherapy

NA

XLA (n=2), CVID, hyper IgM syndrome/CD40L deficiency, good syndrome and XIAP deficiency

 

  (IEI-associated) comorbidities among fatal cases

Pre-existing IEI-associated autoimmune/inflammatory complications in 3/8 patients, lymphoproliferation in 5/8

NA

Pre-existing IEI-associated autoimmune/inflammatory complications in 3/4 fatal cases, chronic lung disease in 2 and a previous kidney transplant in 1 patient

All had pre-existing comorbidities (cardiomyopathy, kidney transplant recipient with several malignancies, chronic lung and heart disease, diabetes, older age)

Patients were older and had more chronic comorbidities (chronic lung disease, chronic kidney disease, diabetes mellitus)

The WAS patient was post-HSCT and had a CMV infection and chronic lung disease, two patients had bronchiectasis, one had previous autoimmune disease, one had a chronic osteomyelitis

The patient with LRBA deficiency had pre-existing IEI-associated autoimmune disease and bronchiectasis

Patients were older and had pre-existing comorbidities in 2 of 5 patients (hypertension, obesity)

Disease severity correlated with age, immunoglobulin use and the number and type of comorbidities (bronchiectasis, cardiopathy) and inversely correlated with use of immunomodulatory treatment. There was no clear correlation between IEI group and severity of infection

 
  1. Abbreviations: Ab antibody, Ig immunoglobulin, CGD chronic granulomatous disease, CMV cytomegalovirus, CVID common variable immunodeficiency, EBV Epstein-Barr virus, GVHD graft versus host disease, HLH haemophagocytic lymphohistiocytosis, HSCT haematopoietic stem cell transplantation, IQR interquartile range, MSMD Mendelian susceptibility to mycobacterial disease, NHL non-Hodgkin lymphoma, SCID severe combined immunodeficiency, XLA X-linked agammaglobulinemia, WAS Wiskott-Aldrich syndrome
  2. aThe non-syndromal combined immunodeficiencies comprise the severe combined immunodeficiencies and the less profound combined immunodeficiencies
  3. bThe study cohort was stratified in distinct age groups; therefore, no exact mean can be calculated
  4. cThe complete cohort additionally included 33 patients with a secondary immunodeficiency
  5. dThe authors classify STAT1 GoF as CID, but in the most recent IUIS classification, this is classified as a defect in intrinsic and innate immunity
  6. eFour patients (two with familial Mediterranean fever and two with CVID) were already reported in the study of Meyts et al. [57]
  7. fTen patients with SCID (n = 7), LAD (leukocyte adhesion deficiency) type III (n = 1), WAS (n = 1) and XIAP mutation (n = 1) had SARS-CoV-2 infection after haematopoietic stem cell transplant (HSCT)