Coronavirus disease 2019 in patients with inborn errors of immunity: An international study

Abstract

Background: There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense. Objective: We sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2. Methods: An invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI. Results: We gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died.

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

“…primarily adults, with approximately 30% of patients having asymptomatic or mild infection, and major risk factors for disease severity including co-morbidities also present in the general population, with a fatality rate of~10% [6]. This cohort included 4 patients with chronic granulomatous disease (CGD), 3 of whom did well, while one patient with concomitant Burkholderia infection died.…”

Zoonotic coronavirus epidemics

“…All adult patients who died from SARS-CoV-2 had pre-existing comorbidities. 175 The innate immune system is the first line of defense against pathogens, CoV are recognized by pattern recognition receptors -such as toll-like receptors (TLRs), particularly TLR 3, TLR 4, and TLR7, and retinoic acid inducible gene 1 (RIG-1)-like receptors (RLRs) -that induce proinflammatory cytokines that help propagate anti-viral responses. 176 There have been few specific reports of COVID-19 in patients with known innate system immune deficiencies.…”

“…From J o u r n a l P r e -p r o o f the larger international study, innate system immune deficiencies were described in 3 young children younger than 2 years of age that ranged from an asymptomatic child with STAT1 GOF to a one-year-old male with IFNGR2 deficiency who required ICU admission. 175,177 In NY, the one-year-old male with IFNGR2 deficiency with COVID-19 and a miliary Mycobacterium avium coinfection was treated with steroids in the ICU but recovered. 175,177 There was also a report of a young child in Italy who became infected with SARS-CoV-2 and developed mild myocarditis and recovered.…”

“…Predominantly antibody deficiencies represent the most common group of primary immunodeficiency diagnoses and reports have shown a wide range of clinical presentations of COVID-19 in these patients but suggest that the adaptive immune system may not be as critical of a defense against SARS-CoV-2 as other aspects of the immune system. 175,177,[182][183][184][185][186][187] Cases of COVID-19 in children with PID are limited. From the international study of patients with PID, 32 of the 94 patients reported were younger than 18 years of age.…”

“…In the few reports describing COVID-19 in adult patients with CVID, X-linked agammaglobulinemia (XLA) and autosomal-recessive agammaglobulinemia (ARA), patients with more severe B cell defects appeared to experience a milder clinical course. 175,177,[182][183][184][187][188][189] Out of the patients described in these reports, there were 10 patients who were asymptomatic (one with ARA, one with XLA, and one with hypogammaglobuinemia). 175,177,[182][183][184][187][188][189] In the international study with 94 PID patients, 26% had mild disease and were treated outpatient and the most commonly reported PID in that group was predominantly antibody deficiency with 14 patients.…”