Recovery from COVID-19 in a Child with Chronic Granulomatous Disease and T Cell Lymphopenia

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first discovered in December 2019, has led to an ongoing, unprecedented global pandemic due to coronavirus disease 2019 (COVID-19). This novel single-stranded RNA virus infects airway epithelial and other cell types expressing surface angiotensin-converting enzyme 2, with clinical manifestations ranging from asymptomatic infection to acute respiratory distress syndrome and severe organ dysfunction [1, 2]. Symptom onset is typically between 4 to 12 days of incubation. Older age and co-morbidities such as cancer, diabetes, and cardiovascular disease increase the risk for more severe disease, and a hyper-inflammatory response to the virus plays a key role in the multi-organ damage that is seen in severe cases [3]. Case reports of patients with inborn errors of immunity (IEI) suggest that the presence of B cells may contribute to immunopathology compared to a milder course in patients lacking B cells [4, 5]. A larger international retrospective cohort reported the clinical course of 94 patients with IEI,

COVID-19-related health outcomes in people with primary immunodeficiency: A systematic review

“…A total of 459 people with PI and COVID-19 are described from 54 of the 68 studies [ 12 , 13 , 16 , [18] , [19] , [20] , [21] , 24 , 26 , 27 , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] ] (Table 2). These cases came from case reports as well as cohort studies with information available for individual patients.…”

“…Supporting this, some patients with PI with autoimmune or inflammatory complications had poorer outcomes [ 19 ], and some studies have found that severe COVID-19 cases are more likely to have a greater IgG response than mild cases [ 41 ]. In contrast, the more severe outcomes seen in people with defects in the T cell and innate pathways point to the importance of these pathways in preventing severe disease [ 11 , 12 , 47 , 86 ]. These findings support the development of vaccines that better target the T cells to better protect both people with PI and the general population.…”

Coronavirus disease 2019 in patients with inborn errors of immunity: lessons learned

“…A total of 15 other patients treated with HSCT or gene therapy were infected with SARS-CoV-2 [ 5 ▪ , 9 ▪ , 10 , 16 , 27 , 43 ]. Of three Wiskott–Aldrich syndrome (WAS) patients who underwent HSCT ( n = 2) or gene therapy ( n = 1), one succumbed to cytomegalovirus (CMV) encephalitis and bacterial pneumonia, while the other two survived [ 5 ▪ , 10 ].…”

“…Two patients who were transplanted to treat X-linked proliferative syndrome due to mutations in the gene encoding X-linked inhibitor of apoptosis protein (XIAP) died after being infected with SARS-CoV-2 post-HSCT: one was infected on day 6 post-HSCT and had a mild disease, but later succumbed to fungal infection in the context of poor engraftment, and the other died of sepsis and HLH in the context of severe graft-versus-host disease (GVHD) [ 5 ▪ , 10 ]. One patient each was transplanted for leukocyte adhesion deficiency III, nuclear factor-kappa B (NF-κB) essential modulator (NEMO) deficiency, cytotoxic T-lymphocyte associated protein 4 (CTLA4) haploinsufficiency, Chediak–Higashi syndrome, or chronic granulomatous disease (CGD), and all survived COVID-19 [ 5 ▪ , 10 , 16 , 27 , 43 ]. Finally, the Italian IEI network reports five additional patients (a sixth with WAS is already included in the report from Meyts et al ) with unspecified IEIs treated with HSCT, gene therapy or thymus transplantation, who all survived COVID-19 [ 9 ▪ ].…”

“…Thirty-four patients with phagocyte defects are reported (5%), among whom 18 have CGD (53%) [ 4 , 5 ▪ , 10 , 12 – 14 , 16 , 43 , 50 , 57 , 66 ]. ICU admission rate and CFR is 6% ( n = 2).…”