COVID-19 in the Context of Inborn Errors of Immunity: a Case Series of 31 Patients from Mexico

Abstract

Highlights1. What is already known about this topic? SARS-CoV-2 causes asymptomatic or mild infection in about 80% of humans, while an excessive immune response has killed millions. Differential susceptibility and risk factors became a concern early in the pandemic. Several monogenic defects that involve innate viral sensors or affect interferon response pathways, as well as autoantibodies against type 1 interferons, have been identified in 14% of patients with life-threatening COVID-19. The impact of the novel betacoronavirus infection in patients with known inborn errors of immunity is less clear. Case series and reports from different countries have suggested a minor impact or even a potential protective effect of the IEI for some patients.2. What does this article add to our knowledge? We describe findings and outcomes of COVID-19 in 31 pediatric and adult patients with known IEI from Mexico, 84% of whom survived. Pediatric patients had a higher hospitalization rate. Inpatient mortality was 40%, and ICU mortality was 63%. Six patients died of secondary bacterial infection or uncontrolled systemic inflammation, but not from overwhelming viral infection. One patient with an autoinflammatory disorder under treatment with anakinra had a catastrophic clinical course. Eighty percent of patients received IVIG as part of their treatment for acute SARS-CoV-2 infection.3. How does this study impact current management guidelines? We recommend continued and/or high-dose IVIG in patients with known IEI seeking care for COVID-19. Patients with autoinflammatory disorders, especially those with inflammasome dysregulation, should probably take extreme measures to prevent exposure, while doctors taking care of SARS-CoV-2 infected patients with immune deficiencies must do everything they can to prevent secondary bacterial infections. The high survival of patients with COVID-19 in the context of inborn errors of immunity worldwide (over 80%) might be the result of patientphysician awareness and special care.

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

“…Reflecting the relative frequency of humoral immunodeficiencies among IEIs, the majority of patients who experienced COVID-19 are affected by antibody deficiency ( n = 330, 51%) [ 5 ▪ , 9 ▪ , 10 , 12 – 17 , 19 , 24 , 26 , 28 , 30 , 33 , 34 , 36 , 37 , 42 , 44 , 45 , 48 , 52 , 53 , 55 , 57 – 62 , 64 , 66 – 69 ]. Among them, 200 have common variable immunodeficiency (CVID, 60% of all antibody deficiencies), 59 have X-linked agammaglobulinemia (XLA, 18%) and eight have autosomal recessive agammaglobulinemia (2%).…”

“…CFR is 8% for the whole group ( n = 26), 9% for CVID, 8% for XLA, 8% for SPAD, and 13% for the unspecified antibody deficiencies, while the CFR of patients with IgA deficiency, other B-cell defects or APDS is 0%. The cause of death was reported for 15 patients: 14/15 had one or multiple comorbidities and succumbed to respiratory failure with or without sepsis and multiorgan failure, and one child developed secondary hemophagocytic lymphohistiocytosis (HLH) and pulmonary hemorrhage [ 5 ▪ , 10 , 12 , 42 , 45 , 68 ].…”

“…Ninety-four patients with a diagnosis of combined immunodeficiency (CID) were infected with SARS-CoV-2 (14%) [ 5 ▪ , 9 ▪ , 10 , 12 – 16 , 27 , 37 , 39 , 49 , 51 , 54 , 57 , 62 , 63 , 66 ]. The rate of ICU admission is 20% in this group, with a CFR of 13% ( n = 12).…”

“…This cohort included 17 patients with severe CID (SCID), 10 of whom had previously undergone hematopoietic stem-cell transplantation (HSCT) or gene therapy [ 5 ▪ , 10 , 12 – 14 , 39 , 49 , 51 ]. The CFR among children with SCID who had not been treated with HSCT is strikingly high ( n = 4/7, all affected by preexisting unspecified lower respiratory tract infections, and one with Omenn syndrome also by BCGitis [ 13 ]), while none of the SCID patients after curative treatment required admission to the ICU or died, even in case of progressive graft failure ( n = 1) [ 5 ▪ , 10 , 12 , 14 , 39 , 49 , 51 ]. The cause of death was respiratory failure in all four cases [ 13 ].…”

“…Autoinflammatory disorders were present in 54 patients infected with SARS-CoV-2 (8%), 39 with familial Mediterranean fever (FMF, 72%) [ 5 ▪ , 12 , 13 , 20 ]. The rate of ICU admission was 4% and CFR 6% ( n = 3) for the entire group, while both ICU admission rate and CFR were 3% ( n = 1) for FMF patients.…”