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 |  |