The Impact of SARS-CoV-2 Infection in Patients with Inborn Errors of Immunity: the Experience of the Italian Primary Immunodeficiencies Network (IPINet)

Abstract

COVID-19 manifestations range from asymptomatic to life-threatening infections. The outcome in different inborn errors of immunity (IEI) is still a matter of debate. In this retrospective study, we describe the experience of the of the Italian Primary Immunodeficiencies Network (IPINet). Sixteen reference centers for adult or pediatric IEI were involved. One hundred fourteen patients were enrolled including 35 pediatric and 79 adult patients. Median age was 32 years, and male-to-female ratio was 1.5:1. The most common IEI were 22q11.2 deletion syndrome in children (26%) and common variable immunodeficiency (CVID) in adults (65%). Ninety-one patients did not require hospital admission, and among these, 33 were asymptomatic. Hospitalization rate was 20.17%. Older age (p 0.004) and chronic lung disease (p 0.0008) represented risk factors for hospitalization. Hospitalized patients mainly included adults suffering from humoral immunodeficiencies requiring immunoglobulin replacement therapy and as expected had lower B cell counts compared to non-hospitalized patients. Infection fatality rate in the whole cohort was 3.5%. Seroconversion was observed is 86.6% of the patients evaluated and in 83.3% of CVID patients. 16.85% of the patients reported long-lasting COVID symptoms. All but one patient with prolonged symptoms were under IgRT. The fatality rate observed in IEI was slightly similar to the general population. The age of the patients who did not survive was lower compared to the general population, and the age stratified mortality in the 50–60 age range considerable exceeded the mortality from 50 to 60 age group of the Italian population (14.3 vs 0.6%; p < 0.0001). We hypothesize that this is due to the fact that comorbidities in IEI patients are very common and usually appear early in life.

COVID-19 and Inborn Errors of Immunity

“…The majority of patients with IEI infected with SARS-CoV-2 reported in the literature were affected with primary antibody deficiency (PAD; n = 446) ( 3 – 9 , 26 , 28 , 30 , 32 , 33 , 35 , 37 , 38 , 43 – 68 ), including 290 with common variable immunodeficiency (CVID; 65% of all PAD), 71 with X-linked agammaglobulinemia (XLA; 16%), and 9 with autosomal recessive agammaglobulinemia (2%). The remaining 76 patients had other B-cell defects, including activated PI3Kdelta syndrome (APDS1: n = 6; APDS2: n = 1), nuclear factor-kappa B subunit 1 (NFKB1) deficiency ( n = 2), nuclear factor-kappa B subunit 2 (NFKB2) deficiency ( n = 4), TRNT1 (CCA-adding transfer RNA nucleotidyl transferase) enzyme deficiency ( n = 1), specific polysaccharide antibody deficiency (SPAD; n = 13), isolated IgA deficiency ( n = 17), IgG subclasses deficiency ( n = 3), or unspecified antibody deficiency ( n = 29).…”

Outcome of SARS-CoV-2 infection among patients with common variable immunodeficiency and a matched control group: A Danish nationwide cohort study

“…However, other studies have reported more severe courses of infection among CVID patients. An Italian study reported a 22% hospitalization rate among CVID patients (16). The study included individuals with various IEI and both children and adults, with patients with CVID being the largest patient group (16).…”

“…An Italian study reported a 22% hospitalization rate among CVID patients (16). The study included individuals with various IEI and both children and adults, with patients with CVID being the largest patient group (16). Though the overall mortality rate was similar to that of the background population, the age at death was significantly lower (all deaths were among adult patients) (16).…”

“…The study included individuals with various IEI and both children and adults, with patients with CVID being the largest patient group (16). Though the overall mortality rate was similar to that of the background population, the age at death was significantly lower (all deaths were among adult patients) (16). In the study by Shields et al (8), overall high rates of both hospitalizations and deaths were reported for patients with both primary (PID) and secondary immunodeficiencies (SID), with the latter faring worse than the PID patients.…”

“…In contrast, genetic variants (as well as auto-antibodies) affecting parts of the innate immune system have been associated with increased risk of fulminant SARS-CoV-2 infection (10-12). Given the enormous heterogeneity among patients with IEI, the variation in target populations in the studies (children vs. adults vs. both groups), and the substantial differences in constellation of IEIs in different populations (3,6,7,9,(13)(14)(15)(16)(17), it is perhaps not surprising that the messages have been mixed.…”