Mild SARS-CoV-2 Infection After Gene Therapy in a Child With Wiskott-Aldrich Syndrome: A Case Report

Abstract

In this work we present the case of SARS-CoV-2 infection in a 1.5-year-old boy affected by severe Wiskott-Aldrich Syndrome with previous history of autoinflammatory disease, occurring 5 months after treatment with gene therapy. Before SARS-CoV-2 infection, the patient had obtained engraftment of gene corrected cells, resulting in WASP expression restoration and early immune reconstitution. The patient produced specific immunoglobulins to SARS-CoV-2 at high titer with neutralizing capacity and experienced a mild course of infection, with limited inflammatory complications, despite pre-gene therapy clinical phenotype.

Impact of SARS-CoV-2 infection and COVID-19 on patients with inborn errors of immunity

“…Over the past 2 years, outcomes of SARS-CoV-2 infection have been reported for ∼1330 individuals with IEI. These studies range from reports of single cases or small numbers of patients 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 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 to cohort studies from Iran, 89 , 90 , 91 Turkey, 92 , 93 , 94 Brazil, 95 , 96 Israel, 97 Italy, 98 , 99 , 100 , 101 Spain, 102 the United Kingdom, 15 , 103 , 104 Mexico, 105 Denmark, 106 , 107 Poland, 108 …”

Mechanisms underlying host defense and disease pathology in response to severe acute respiratory syndrome (SARS)-CoV2 infection: insights from inborn errors of immunity

“…However, the age of affected IEI patients was lower (median 24 yrs vs 48 yrs; Fig. 1A), and the proportion admitted to ICU was higher (14.0% vs 2–5%) than the general population [12,27–63,67,69–75,76 ▪▪ ]. Within the different classifications of IEIs, SARS-CoV2-infected CVID patients were significantly older (mean: 40.4 years) than SARS-CoV2 + patients with agammaglobulinemia (mean: 23.1 years), chronic granulomatous disease (CGD) (mean: 15.4 years), or APECED (mean: 24.4 years) (Fig.…”

“…Examples of this include not only susceptibility to infection by HSV-1 [4], respiratory infections [5,6,8], EBV [7], or attenuated viral vaccines [5,6] in some IEIs, but also the occurrence of enteroviral meningioencephalitis (∼5%) and vaccine-associated poliomyelitis (∼1.5%) in X-linked agammaglobulinemia (XLA) patients [26]. Over the past 12 months, reports of individual cases [27–53] and of individuals with the same type of IEI [54 ▪ ,55–66], as well as local [58,67,68], national [69–75] and international [76 ▪▪ ] cohort studies have assessed the outcomes of SARS-CoV2 infection on such individuals. These studies have provided key findings regarding host defense against SARS-CoV2 infection, and mechanisms of disease pathogenesis.…”

Case Report: A Severe Paediatric Presentation of COVID-19 in APDS2 Immunodeficiency

“…It is still unclear whether immunocompromised children are at higher risk of complications secondary to either of these clinical entities ( 1 – 4 ), although children with co-morbidities involving more than one body system do seem to be at higher risk of severe disease and death ( 1 ). A number of individual case reports describe paediatric patients with primary immunodeficiency (PID) experiencing asymptomatic infection or mild illness followed by SARS-CoV-2 clearance ( 5 , 6 ). Increased morbidity and mortality from COVID-19 have been described in adult PID patients ( 7 ), particularly those with combined immune deficiency and immune dysregulation ( 8 ), as well as protracted disease courses in antibody-deficient patients ( 9 ).…”