Table 1 Pediatric patients with IEIs affected by COVID-19, stratified by type of immune defect and treatment outcome (n = 116 studies), 2020–2022
Type of IEIs | Number of patientsa | ICU admission ratea | Use of MVa | Suffered ARDSa | Case fatality ratea |
|---|---|---|---|---|---|
Predominantly antibody deficiencies | 197 (27.7) | 16 (8.1) | 9 (4.6) | 13 (6.6) | 5 (2.5) |
 CVID | 53 (26.9) | 9 (17) | 5 (9.4) | 7 (13.2) | 3 (5.7) |
 XLA | 45 (22.8) | 2 (4.4) | 2 (4.4) | 4 (8.9) | 2 (4.4) |
 AR or AD agammaglobulinemia/hypogammaglobulinemia | 41 (20.8) | 2 (4.9) | 1 (2.4) | 1 (2.4) | 0 |
 Isolated IgG subclass deficiencies | 28 (14.2) | 0 | 0 | 0 | 0 |
 Selective IgA deficiencies | 12 (6.1) | 0 | 0 | 0 | 0 |
 Specific antibody deficiency with normal Ig and B cells levels | 4 (2) | 1 (25) | 1 (25) | 1 (25) | 0 |
 Selective IgM deficiencies | 3 (1.5) | 0 | 0 | 0 | 0 |
 Unspecified predominantly antibody deficiency | 3 (1.5) | 0 | 0 | 0 | 0 |
 IgG subclass deficiency with IgA and/or IgM deficiency | 2 (1) | 0 | 0 | 0 | 0 |
 IgG, IgA and IgM deficiencies | 2 (1) | 0 | 0 | 0 | 0 |
 Partial IgA deficiency | 1 (0.5) | 0 | 0 | 0 | 0 |
 Low IgM level | 1 (0.5) | 0 | 0 | 0 | 0 |
 UNG deficiency | 1 (0.5) | 1 (100) | 0 | 0 | 0 |
 APRIL deficiency | 1 (0.5) | 1 (100) | 0 | 0 | 0 |
Combined immunodeficiencies with associated or syndromic features | 126 (17.7) | 11 (8.7) | 9 (7.1) | 9 (7.1) | 7 (5.5) |
 DiGeorge syndromes | 40 (31.7) | 1 (2.5) | 0 | 0 | 0 |
 Immunodeficiency with ataxia-telangiectasia | 25 (19.8) | 0 | 0 | 0 | 0 |
 Wiskott-Aldrich syndromes | 14 (11.1) | 2 (14.3) | 2 (14.3) | 2 (14.3) | 1 (7.1) |
 Nijmegen breakage syndromes | 9 (7.1) | 0 | 0 | 0 | 0 |
 Unspecified hyper IgM syndromes | 7 (5.5) | 1 (14.3) | 1 (14.3) | 1 (14.3) | 1 (14.3) |
 Immunodeficiencies with centromeric instability and facial anomalies | 6 (4.8) | 2 (33.3) | 2 (33.3) | 2 (33.3) | 1 (16.7) |
 Unspecified hyper IgE syndromes | 5 (4) | 1 (20) | 1 (20) | 1 (20) | 1 (20) |
 ARPC1B deficiency | 3 (2.4) | 0 | 0 | 0 | 0 |
 Hypoparathyroidism-retardation-dysmorphism syndromes | 3 (2.4) | 2 (66.7) | 2 (66.7) | 2 (66.7) | 2 (66.7) |
 STIM1 deficiencies | 2 (1.6) | 1 (50) | 1 (50) | 1 (50) | 1 (50) |
 EDA-ID caused by hypomorphic mutations in encoding the nuclear factor κB essential modulator (NEMO) protein | 2 (1.6) | 0 | 0 | 0 | 0 |
 MCM4 deficiencies | 2 (1.6) | nr | nr | nr | nr |
 Kabuki syndrome | 2 (1.6) | 0 | 0 | 0 | 0 |
 PGM3 deficiency | 2 (1.6) | 0 | 0 | 0 | 0 |
 ORAI-1 deficiency | 1 (0.8) | nr | nr | nr | nr |
 TBX1 deficiency | 1 (0.8) | 1 (100) | 0 | 0 | 0 |
 Bloom syndrome | 1 (0.8) | 0 | 0 | 0 | 0 |
 Schimke immuno-osseous dysplasia | 1 (0.8) | 0 | 0 | 0 | 0 |
Cellular and humoral immunodeficiencies | 102 (14.4) | 27 (26.5) | 23 (22.5) | 23 (22.5) | 19 (18.6) |
 CID | 60 (58.8) | 15 (25) | 12 (20) | 12 (20) | 9 (15) |
 SCID | 42 (41.2) | 12 (28.6) | 11 (26.2) | 11 (26.2) | 10 (23.8) |
Immune dysregulatory diseases | 95 (13.4) | 34 (35.8) | 25 (26.3) | 27 (28.4) | 17 (17.9) |
 FHL syndromes | 25 (26.3) | 10 (40) | 7 (28) | 6 (24) | 5 (20) |
 APS-1 | 19 (20) | 8 (42.1) | 6 (31.6) | 9 (47.4) | 1 (5.3) |
 ALPS | 9 (9.5) | 0 | 0 | 0 | 0 |
 LRBA deficiency | 6 (6.3) | 2 (33.3) | 2 (33.3) | 2 (33.3) | 1 (16.7) |
 TPP2 deficiency | 5 (5.3) | 0 | 0 | 0 | 0 |
 Unspecified immune dysregulatory disease | 5 (5.3) | 1 (20) | 1 (20) | 1 (20) | 1 (20) |
 XLP1 | 4 (4.2) | 3 (75) | 3 (75) | 3 (75) | 3 (75) |
 XLP2 | 4 (4.2) | 2 (50) | 2 (50) | 2 (50) | 2 (50) |
 SOCS1 deficiency | 2 (2.1) | 0 | 0 | 0 | 0 |
 CTLA4 deficiency | 2 (2.1) | 0 | 0 | 0 | 0 |
 Interleukin-10Ra deficiency | 2 (2.1) | 0 | 0 | 0 | 0 |
 BACH2 deficiency | 2 (2.1) | 2 (100) | 0 | 0 | 0 |
 RLTPR deficiency | 2 (2.1) | 1 (50) | 1 (50) | 1 (50) | 1 (50) |
 NOTCH1 mutation | 1 (1) | 1 (100) | 0 | 0 | 0 |
 ALPS-Caspase10 | 1 (1) | 1 (100) | 0 | 0 | 0 |
 CD137 deficiency | 1 (1) | 1 (100) | 1 (100) | 1 (100) | 1 (100) |
 Interleukin-37 deficiency | 1 (1) | 1 (100) | 1 (100) | 1 (100) | 1 (100) |
 IPEX syndrome | 1 (1) | 1 (100) | 1 (100) | 1 (100) | 1 (100) |
 Prolidase deficiency | 1 (1) | nr | nr | nr | nr |
 PRKCD deficiency | 1 (1) | 0 | 0 | 0 | 0 |
 MAGT1 deficiency | 1 (1) | 0 | 0 | 0 | 0 |
Autoinflammatory diseases | 67 (9.4) | 3 (4.5) | 2 (3) | 2 (3) | 2 (3) |
 FMF | 36 (53.7) | 0 | 0 | 0 | 0 |
 Blau syndrome | 4 (6) | nr | nr | nr | nr |
 Aicardi-Goutières syndrome | 3 (4.5) | 0 | 0 | 0 | 0 |
 Familial cold autoinflammatory syndromes 1 | 3 (4.5) | 0 | 0 | 0 | 0 |
 ADA2 deficiency | 2 (3) | 0 | 0 | 0 | 0 |
 NLRP1 deficiency | 2 (3) | 1 (50) | 0 | 0 | 0 |
 TNF receptor-associated periodic syndrome | 2 (3) | 0 | 0 | 0 | 0 |
 Hyperpigmentation hypertrichosis, histiocytosis-lymphadenopathy plus syndrome SLC29A3 mutation | 2 (3) | 0 | 0 | 0 | 0 |
 RNASEH2B deficiency | 2 (3) | 0 | 0 | 0 | 0 |
 Unspecified autoinflammatory diseases | 2 (3) | 1 (50) | 1 (50) | 1 (50) | 1 (50) |
 Familial cold autoinflammatory syndrome 4 | 1 (1.5) | 0 | 0 | 0 | 0 |
 Deficiency of the interleukin 1 receptor antagonist | 1 (1.5) | 1 (100) | 1 (100) | 1 (100) | 1 (100) |
 PAPA syndrome, hyperzincemia and hypercalprotectinemia | 1 (1.5) | nr | nr | nr | nr |
 Mevalonate kinase deficiency | 1 (1.5) | 0 | 0 | 0 | 0 |
 SAMHD1 deficiency | 1 (1.5) | 0 | 0 | 0 | 0 |
 A20 deficiency | 1 (1.5) | 0 | 0 | 0 | 0 |
 Majeed syndrome | 1 (1.5) | nr | nr | nr | nr |
 STING-like disease | 1 (1.5) | nr | nr | nr | nr |
 CARD14 mediated psoriasis | 1 (1.5) | nr | nr | nr | nr |
Phagocytic diseases | 54 (7.6) | 4 (7.4) | 3 (5.5) | 5 (9.2) | 3 (5.5) |
 CGD | 26 (48.1) | 3 (11.5) | 2 (7.7) | 4 (15.4) | 2 (7.7) |
 Shwachman-Diamond syndromes | 8 (14.8%) | 0 | 0 | 0 | 0 |
 HAX1 deficiencies | 6 (11.1%) | 0 | 0 | 0 | 0 |
 Unspecified phagocytic diseases | 4 (7.4) | 0 | 0 | 0 | 0 |
 Glycogen storage diseases type 1b | 2 (3.7) | nr | nr | nr | nr |
 Elastase deficiency | 2 (3.7) | 0 | 0 | 0 | 0 |
 JAGN1 deficiency | 1 (1.8) | 0 | 0 | 0 | 0 |
 Poikiloderma with neutropenia | 1 (1.8) | 0 | 0 | 0 | 0 |
 Cystic fibrosis | 1 (1.8) | 1 (100) | 1 (100) | 1 (100) | 1 (100) |
 Leukocyte adhesion deficiency type 3 | 1 (1.8) | 0 | 0 | 0 | 0 |
 GATA2 deficiency | 1 (1.8) | 0 | 0 | 0 | 0 |
 Undefined leukopenia | 1 (1.8) | 0 | 0 | 0 | 0 |
Innate immunodeficiencies | 50 (7) | 19 (38) | 14 (28) | 17 (34) | 5 (10) |
 TLR7 deficiency | 8 (16) | 6 (75) | 5 (62.5) | 5 (62.5) | 0 |
 MyD88 deficiency | 7 (14) | 3 (42.8) | 2 (28.6) | 2 (28.6) | 0 |
 STAT1 deficiency | 7 (14) | 0 | 0 | 0 | 0 |
 Unspecified innate immunodeficiencies | 5 (10) | 0 | 0 | 0 | 0 |
 IFNAR1 deficiency | 3 (6) | 3 (100) | 2 (66.7) | 3 (100) | 2 (66.7) |
 IFNAR2 deficiency | 3 (6) | 3 (100) | 3 (100) | 3 (100) | 2 (66.7) |
 TYK2 deficiency | 3 (6) | 2 (66.7) | 0 | 2 (66.7) | 0 |
 TBK1 deficiency | 2 (4) | 1 (50) | 1 (50) | 1 (50) | 1 (50) |
 Isolated congenital asplenia | 2 (4) | 0 | 0 | 0 | 0 |
 IFN-g receptor 2 deficiency | 2 (4) | 1 (50) | 1 (50) | 1 (50) | 0 |
 MDA5 deficiency | 2 (4) | nr | nr | nr | nr |
 TRIF deficiency | 1 (2) | 0 | 0 | 0 | 0 |
 WHIM syndrome | 1 (2) | 0 | 0 | 0 | 0 |
 IRAK4 deficiency | 1 (2) | 0 | 0 | 0 | 0 |
 IRF9 deficiency | 1 (2) | 0 | 0 | 0 | 0 |
 STAT2 deficiency | 1 (2) | 0 | 0 | 0 | 0 |
 Interleukin-12 and interleukin-23 receptor b1 chain deficiency | 1 (2) | 0 | 0 | 0 | 0 |
Complement deficiencies | 11 (1.5) | 3 (27.3) | 1 (9.1) | 1 (9.1) | 1 (9.1) |
 Factor H deficiency | 3 (27.3) | 2 (66.7) | 1 (33.3) | 1 (33.3) | 1 (33.3) |
 C1 inhibitor deficiency | 3 (27.3) | 0 | 0 | 0 | 0 |
 Ficolin 3 deficiency | 2 (18.2) | nr | nr | nr | nr |
 Factor H –related protein deficiency | 1 (9.1) | 1 (100) | 0 | 0 | 0 |
 Factor I deficiency | 1 (9.1) | nr | nr | nr | nr |
 C3 deficiency | 1 (9.1) | 0 | 0 | 0 | 0 |
Bone marrow failure | 7 (1) | 2 (28.6) | 1 (14.3) | 1 (14.3) | 1 (14.3) |
 Fanconi anaemia | 5 (71.4) | 1 (20) | 1 (20) | 1 (20) | 1 (20) |
 SAMD9 deficiency | 1 (14.3) | 0 | 0 | 0 | 0 |
 DKCA1 deficiency | 1 (14.3) | 1 (100) | 0 | 0 | 0 |
Phenocopies of primary immunodeficiencies | 1 (0.1) | 0 | 0 | 0 | 0 |
 RAS-associated autoimmune leukoproliferative disease | 1 (100) | 0 | 0 | 0 | 0 |
Total | 710 | 119 (16.8) | 87 (12.2) | 98 (13.8) | 60 (8.4) |