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) |
AD autosomal dominant, ALPS autoimmune lymphoproliferative syndrome, APS-1 autoimmune polyendocrine syndromes type-1, AR autosomal recessive; ARDS acute respiratory distress syndrome; CGD chronic granulomatous disease; CID combined immunodeficiency; COVID-19 coronavirus disease 2019, CVID common variable immunodeficiency, EDA-ID anhidrotic ectodermodysplasia with immunodeficiency, FHL familial hemophagocytic lymphohistiocytosis, FMF familial Mediterranean fever, ICU intensive care unit, IEIs inborn errors of immunity, IFN interferon, IFNAR interferon alpha/beta receptor subunit, Ig immunoglobulin, IgA immunoglobulin A, IgE immunoglobulin E, IgG immunoglobulin G, IgM immunoglobulin M, IPEX immune-dysregulation polyendocrinopathy X-linked, MV mechanical ventilation, nr not reported, PAPA pyogenic sterile arthritis, pyoderma gangrenosum, acne, SCID severe combined immunodeficiencies, TLR toll-like receptors, TNF tumor necrosis factor, TPP2 tripeptidyl-Peptidase II, WHIM. warts hypogammaglobulinemia, infections, and myelokathexis, XLA X-linked agammaglobulinemia, XLP X-linked lymphoproliferative disease
aData are presented as number (%). Data was calculated on patients for whom the information was available
Percentages do not total 100% owing to missing data