Table 1.
Summary of published studies on pediatric immunocompromised patients and COVID-19
| Country and Study Period | Study Design | Testing Strategy (%) and Detection (% Positive) | Patients Characteristics (%) | Clinical Course (%) | Treatment (%) | Outcomes (%) |
|---|---|---|---|---|---|---|
| Cancer and hematopoietic stem cell transplant | ||||||
| Czech Republic105 Up to 3/16/20 |
Care provider survey; 32 centers | >200 tested patients; 8 positive cases | 8 patients: 7 ST, 1 ALL | All patients asymptomatic or had mild symptoms | 2 HCQ, 2 AZI, 1 LPV/r | No deaths or ICU admissions |
| US (NY)106 3/10/20–4/6/20 |
Retrospective cohort; 2 centers | Asymptomatic (before admission, before procedure, before chemotherapy, contact, transfer), symptomatic (84); NP PCR; positive cases (11) | 19 patients: Leukemia/lymphoma (32), ST (42), nonmalignant hematology (16), HSCT (11) | Asymptomatic (16), MV (2), ICU (26) | HCQ + AZI (16); Cancer-directed therapy delayed in oncology patients (64) | No deaths in oncology patients; 1 sickle cell patient died |
| Spain107 Up to 4/15/20 |
Retrospective cohort in Madrid | NP PCR | 15 patients: ALL (53), AML/MDS (13), lymphoma (7), NBL (7), ST (20) | Asymptomatic (13), mild/moderate (87) | HCQ (73); chemotherapy delayed (40) | No deaths or ICU admission at time of report |
| Italy60 2/20/20–4/15/20 |
Retrospective cohort in Lombardia; 6 centers | Asymptomatic (74): screening (65) or close contact (9); positive cases (7) | 21 patients: leukemia (48), lymphoma (10), CNS (5), ST (38) | Severe (10) | Cancer treatment modified (48) | No deaths |
| France108 Up to 4/16/20 |
Physician survey; 30 centers | NP PCR or CT; 33 cases identified and only reporting 5 severe cases | 5 patients: 3 ALL, 1 allo-HSCT, 1 CNS | All 5 patients admitted to ICU | N/A | No deaths at time of reporting |
| Italy35 2/23/20–4/24/20 |
Registry study; 13 centers | Asymptomatic (before chemotherapy or procedure) or symptomatic; NP PCR or bronchoalveolar lavage | 29 patients: ALL (48), AML (7), lymphoma (10), CNS (3), ST (28), histiocytosis (3); 3 patients also had HSCT (10) | Asymptomatic (62), mild (24), moderate (14), severe/critical (0) | HCQ (31), AZI (31), LPV/r (10), GC (3); treatment suspended (55) or reduced/delayed (7) | No deaths or ICU admissions; 1 lymphoma patient had progression after chemotherapy withdrawal due to COVID |
| United States (NY, NJ)12 1/15/20–4/27/20 |
Retrospective cohort; 13 centers | Asymptomatic (before procedure, treatment) and symptomatic; NP PCR; 578 tested, 98 positive cases (17) | 98 patients: ALL (53), AML (9), lymphoma (3), CNS (9), NBL (5), ST (16), auto-HSCT (5), allo-HSCT (3); obese (22) | Asymptomatic (25), mild (45), moderate (11), severe (17), ICU (23), MV (8) | HCQ (15), AZI (15), TCZ (5), RDV (4), CVP (2), ANR + GC (1); interruptions to chemotherapy (67) | Died (4) – none solely due to COVID |
| France52 Up to 5/28/20 |
Retrospective and prospective cohort; multicenter | NP PCR (92), serology (5), clinical + radiological diagnosis (3) | 37 patients; ALL (27), AML (3), CML (3), NHL (3), CNS (19), ST (30), NBL (3); HSCT (11); 1 patient each for aplastic anemia, sickle cell, EBV-MAS, familial septic granulomatosis | Asymptomatic (24), ICU (15), MV (5) | HCQ (5), RDV (3), TCZ (5); treatment delayed in oncology patients (48) for a mean of 14 d | 1 Patient with ALL died (3) from severe macrophage activation syndrome with COVID |
| Turkey51 3/11/20–5/31/20 |
Physician survey; 66 centers | Asymptomatic (contact history, before HSCT, before surgery) and symptomatic; NP PCR or symptomatic + chest CT findings/contact history | 51 patients: leukemia (51), lymphomas, and LCH/HLH (10), CNS (10), NBL (8), ST (22); 6 had undergone HSCT (12) | Asymptomatic/mild (49), moderate/severe (33), critical (18), ICU (18), MV (6) | No treatment (20), AZI (20), HCQ (8), HCQ + AZI (27), AZI + antivirals (2), HCQ + AZI + antivirals (6), CVP (2); interruption/delay in chemotherapy (63) | 1 HSCT patient died (2) from COVID and also had concurrent recurrent leukemia and fungal infection |
| Egypt47 mid-April to mid-June 2020 |
Prospective, nonintervention | NP PCR conducted on all admitted pediatric oncology patients | 15 patients: ALL (67), AML (7), lymphoma (13), SOT (13) | Asymptomatic (33), mild (67) | HCQ, AZI, ceftriaxone, enoxaparin used per hospital guidelines; chemotherapy revised on individual basis | Died (13) – not related to COVID; 1 new oncology diagnosis patient died from treatment delay related to COVID |
| Mexico11 3/20/20–6/20/20 |
Retrospective cohort; 1 center | Only symptomatic tested; PCR; positive cases (58) | 14 patients: leukemia (63), lymphoma (7), ST (21), CNS (7) | Oxygen required (80), no ICU or MV | Cancer treatment delayed until negative PCR | 1 patient died with pulmonary metastases and pulmonary hemorrhage |
| Peru109 3/6/20–7/7/20 |
Retrospective cohort; 9 centers | PCR (49), serology (33), not reported (18) | 69 patients: ALL (52), AML (4), lymphoma (7), CNS (5), ST (14), other (17) | Asymptomatic (54), ICU (4), but 2 patients who died did not have ICU beds available | AZI/IVM/GC (13); chemotherapy stopped (100) | Died due to COVID (4), died not related to COVID (6) |
| United Kingdom110 3/12/20–7/31/20 |
Retrospective + prospective registry study; 20 centers | Asymptomatic (before admission) and symptomatic; NP PCR | 54 patients: ALL (44), AML (7), lymphoma (4), CNS (9), NBL (11), ST (19), other (6) | Asymptomatic (28), mild (63), moderate (2), severe (2), critical (6) | N/A | Died (2) – not related to COVID |
| Mexico111 3/12/20–9/25/20 |
Retrospective cohort; 1 center | Asymptomatic (before procedure, before admission); NP PCR | 38 patients: ALL (55), AML (8), histiocytosis (8), CNS (5), ST (21), NBL (3) | Asymptomatic (18), mild (71), ICU (5), MV (5) | Treatment delay (68) | Deaths (8) – not related to COVID |
| United States Pediatric Oncology COVID-19 Case Report53 As of 1/21/21 |
Registry study; 93 centers | Asymptomatic and symptomatic | 657 patients: HM (64), ST (36); in addition, a proportion of patients had an allo-HSCT (6) or auto-HSCT (3) | Asymptomatic: HM (33), ST (41); intubation: HM (4), ST (4); ICU: HM (13), ST (8); MIS-C: HM (2), ST (2) | Change in oncology therapy: HM (47), ST (37) | Died (2) |
| Global Global Registry of COVID-19 in Childhood Cancer54 As of 2/10/21 |
Registry study; 48 countries | Asymptomatic and symptomatic; testing included NP (80.5), nasal (18.0), oropharyngeal swab (8.4), and blood serology (5.2) | 1557 patients: ALL (49.1), ST (24.5), CNS (8.1), other HM (17.9), after HSCT for nonmalignant disorders (0.39); in addition, a proportion of cancer patients had an HSCT (5.16) | Asymptomatic (34.9), mild (36.1), moderate (9.3), severe (12.1), critical (17.6); ICU (9.1), MV (4.4) | No treatment (70.3), AZI (20.2), GC (14.7), RDV (4.8), IVIG (4.4), HCQ (4.0), LPV/r (2.0), CP (0.7), TZM (0.4), FPV (0.1); chemotherapy reduced (5.9) or withheld (37.6) | Died from COVID-19 (3.44), died from other causes (2.19) |
| Solid organ transplant | ||||||
| United States (TX, CA, FL, CO)50 4/1/20–7/20/20 |
Retrospective cohort; 5 centers | NP PCR | 26 SOT patients: liver (38), kidney (31), heart (23), lung (8); median time to COVID-19 from transplant 1246 d (range 12–6574 d) | Asymptomatic (23), hospitalized (20) for COVID-19 for median of 3 d, none required supplemental oxygen | No change in IST (92); 1 patient developed acute cellular rejection (kidney) 7 d after IST reduction for COVID | No deaths or ICU admissions |
| Europe62 | Care provider survey; 18 centers | N/A | 5 SOT patients: 2 kidney, 3 liver; 3 HSCT patients | All SOT had mild symptoms; HSCT: 1 mild, 2 moderate/severe | No change in IST for all patients | No deaths or ICU admissions |
| Rheumatologic disorders | ||||||
| Turkey112 3/11/20–4/15/20 |
Parent survey | 23 patients with suspicion for COVID-19 tested with NP PCR (30% positive) | 7 patients: 7 FMF (all on colchicine), 1 PFAPA | 2 asymptomatic, 4 outpatient therapy, 1 hospitalized for 5 d | 5 HCQ, 3 AZI, 4 OTV, 2 none | No deaths or ICU admissions |
| Spain113 Up to 6/30/20 |
Registry study; 49 hospitals | N/A | 8 patients: 3 JIA, 1 JDM, 1 cytoplasmic-ANCA vasculitis, 1 PFAPA, 1 polyarteritis nodosa, 1 phospholipid antibody syndrome | 3 required oxygen, 1 with central line associated thrombosis, 1 with venous thrombosis and adrenal hemorrhage | 5 HCQ, 1 RDV, 1 LPV/r, 1 TCZ, 1 enoxaparin; 1 reduction in IST | 1 death in JDM from rapidly progressive interstitial lung disease before COVID |
| Chronic kidney disease on immunosuppressive therapy | ||||||
| Spain114 3/1/20–4/15/20 |
Physician survey; 43 hospitals | PCR | 16 patients: NS (31), renal dysplasia (31), uropathy (13), IgA nephropathy (6), vasculitis (6), scarring nephropathy (6), cortical necrosis (6); 9 patients (56) on IST and 3 patients had a kidney transplant (19) | Asymptomatic (19), no patients required oxygen | HCQ (38), LPLV/r (6); azathioprine stopped in vasculitis patient; MMF decreased in 2 of 3 and tacrolimus decreased in 1 of 3 transplant patients | No deaths or ICU admissions |
| Global115 3/15/20-End of April 2020 |
Retrospective survey; 16 centers | N/A | 18 patients: kidney transplant (61), NS (17), ANCA-vasculitis (11), aHUS (6), ESKD with IBD (6) | Outpatient (39), oxygen support (17) | N/A | No deaths or ICU admissions |
| Global116 3/15/20–7/5/20 |
Registry study; 30 countries | 113 cases (104 by PCR or antibody testing, 9 clinically suspected) | 113 patients: kidney transplant (47), NS (27), SLE (10), glomerulonephritis/vasculitis (6), other (11); all on IST | Asymptomatic (21), admitted but no respiratory support (38), admitted with respiratory support (17), MV (4) | N/A | Died (4) |
| Inflammatory bowel disease | ||||||
| Global78 Before 3/26/20 |
Registry study; 102 sites | 6 by NP PCR or 2 with symptoms + positive first degree relative | 8 patients: 5 Crohn’s disease, 2 Ulcerative colitis, 1 unclassified | All 8 with mild disease and no admissions | No suspension of IBD-related medications | No deaths or ICU admissions |
| Global45 Before May 2020 |
Registry study; 33 countries | NP PCR | 29 patients | Hospitalized (10) | N/A | No deaths or ICU admissions |
| Italy65 3/9/20–5/4/20 |
Retrospective cohort; 21 centers | 6 COVID-19 cases identified out of 2291 patients (0.2%) by NP test | 6 patients: 4 Crohn’s disease, 2 ulcerative colitis | 1 asymptomatic, 4 mild, 1 hospitalized for 7 d | No suspension of IBD-related medications | No deaths |
| Global16 Before 10/1/20 |
Registry study; 23 countries | N/A | 209 patients: Crohn’s disease (66), ulcerative colitis (29), unclassified (5) | Hospitalized (7), MV (1); of the 2 patients on MV, 1 patient had MIS and 1 patient had secondary infection | N/A | No deaths |
| Inborn errors of immunity | ||||||
| Global41 3/16/20–6/30/20 | Physician survey | Asymptomatic, symptomatic; PCR or serology | 32 pediatric patients: CID (28), CVID or antibody deficiency (13), CGD (9), AGS (9), ALPS (9), WAS (6), XLA (3), CTLA4 deficiency (3), CMC with recurrent sepsis (3), MSMD (3), STAT1 GOF (3), GATA2 haploinsufficiency (3), XIAP deficiency (3), BMF (3); 2 had received HSCT, 1 gene therapy | Asymptomatic (25), ICU admission (28), MIS-C in patient with MSMD (IFNGR2) | Antibiotics (31), GC (16), immunoglobulin (16), RDV (9), LPV/r (3), CP (6), TCZ (3), chloroquine (3), aspirin (3), enoxaparin (3) | Deaths (6): 1 child with CGD and Burkholderia sepsis and HLH; 1 child following HSCT for XIAP deficiency, severe gut GVHD, septic shock, HLH |
| Israel40 Mid-February to Mid-September 2020 |
Care provider survey; 10 centers | Contact tracing (27), symptomatic (73); NP PCR | 11 pediatric patients: 3 Hyper-IgM, 2 X-linked agammaglobulinemia, 3 CID (RELB mutation), 2 CGD, 1 22q11.2 deletion syndrome | None hospitalized, asymptomatic (46), mild (54) | Additional dose of IVIG (9); no change in treatment for immune disorder | No deaths or ICU admissions |
| Iran55 | Prospective study; 38 centers | Symptomatic only; PCR; incidence of 1 in 144 PID patients | 16 pediatric patients: SCID (19), Omenn’s syndrome (6), CID (13), CGD (13), IGF syndrome (13), WAS (6), AT (6), hyper-IgM (6), specific IgA deficiency (6), Griscelli syndrome type 2 (6), DIRA (6) | ICU (50) | AZI (69), IVIG (63), HCQ (50), other antibiotics (44), GC (6) | Death (50): 4 of 4 SCID/Omenn’s syndrome, STK4 deficiency, 1 of 2 IGF syndrome, Griscelli syndrome type 2, DIRA |
| Other immunocompromised cohorts | ||||||
| Spain117 3/1/20–3/31/20 |
Retrospective cohort; 1 center | NP PCR | 8 patients: 5 HO (3 after HSCT), 2 SOT (1 liver, 1 kidney), 1 CKD | 1 required oxygen, 1 HLH-like syndrome | 5 Anti-viral treatment, 1 GC, 1 TCZ, 6 IST decreased or withdrawn | No deaths or ICU admissions |
| United Arab Emirates118 | Retrospective cohort; 1 center | Contact tracing or symptomatic; NP PCR | 5 patients: 1 CVID, 1 ST, 1 after splenectomy, 1 CKD, 1 SLE | 3 asymptomatic, 2 mild | 3 HCQ, 1 RDV, 1 FPV | No deaths or ICU admissions |
Table includes only studies with at least 5 pediatric (age < 21 y) immunocompromised patients.
Abbreviations: AGS, Aicardi-Goutieres syndrome; aHUS, atypical hemolytic uremic syndrome; ALL, acute lymphoblastic leukemia; Allo-HSCT, allogeneic hematopoietic stem cell transplant; AML, acute myelogenous leukemia; ANCA, antineutrophil cytoplasmic antibody; ANR, anakinra; AT, ataxia telangiectasia; Auto-HSCT, autologous hematopoietic stem cell transplant; AZI, azithromycin; BMF, bone marrow failure; CID, combined immunodeficiency; CGD, chronic granulomatous disease; CKD, chronic kidney disease; CMC, chronic mucocutaneous candidiasis; CNS, central nervous tumor; CT, computed tomography; CVP, convalescent plasma; DIRA, deficiency of IL-1 receptor antagonist; EBV-MAS, EBV-induced macrophage activation syndrome; ESKD, End-stage kidney disease; FMF, familial mediterranean fever; FPV, favipiravir; GC, glucocorticosteroids; GOF, gain-of-function; HCQ, hydroxychloroquine; HM, hematology malignancy; HO, Hematologic-oncologic; HSCT, hematopoietic stem cell transplant; IBD, inflammatory bowel disease; ICU, intensive care unit; IGF, immunodeficiency; centromere instability, facial anomalies; IST, immunosuppressive therapy; IVIG, intravenous immunoglobulin; IVM, ivermectin; JDM, juvenile dermatomyositis; JIA, juvenile idiopathic arthritis; LPV/r, Lopinavir-ritonavir; MIS, multisystem inflammatory syndrome; MIS-C, multisystem inflammatory syndrome in children; MSMD, mendelian susceptibility to mycobacterial diseases; MV, mechanical ventilation; N/A, not available; NBL, neuroblastoma; NP, nasopharyngeal; NS, nephrotic syndrome; OTV, oseltamivir; PCR, polymerase chain reaction; PFAPA, periodic fever-aphthous stomatitis-pharyngitis-adenitis; RDV, remdesivir; SCID, severe combined immunodeficiency; SLE, systemic lupus erythematosus; SOT, solid organ transplant; ST, solid tumor; TCZ, tocilizumab; WAS, Wiskott-Aldrich syndrome; XLA, X-linked agammaglobulinemia; MDS, myelodysplastic syndrome; CML, chronic myeloid leukemia; NHL, non-Hodgkin lymphoma; LCH Langerhan cell histiocytosis; HLH, hemophagocytosis lymphohistiocytosis; TZM, temozolamide; CVID, common variable immunodeficiency; ALPS, autoimmune lymphoproliferative syndrome; CTLA4, cytotoxic T-lymphocyte-associated protein 4; STAT1, signal transducer and activator of transcription 1; XIAP, X-linked inhibitor of apoptosis protein; GVHD, graft versus host disease; PID, primary immunodeficiency.