Outcome of SARS-CoV-2 Infection in 121 Patients With Inborn Errors of Immunity: A Cross-sectional Study

Abstract

Purpose: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and to identify factors influencing the outcome of infection.Methods: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. Results: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n=53). The infection presented mostly as asymptomatic (n=21) and mild (n=66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex related susceptibility and observed a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. Conclusion: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. Patients with complement deficiencies had milder COVID-19. However, the type of IEI was not a determining factor for severity. The severity of SARS-CoV-2 infection seems to be more related to older age, higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).

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

“…We here analyze the published case series and single cases describing the outcome of COVID-19 in patients with IEIs. Removing duplicate patients, to the best of our knowledge, we count a total of 649 reported patients with IEI who were infected with SARS-CoV-2, spanning all subgroups of immune defects as defined by the International Union of Immunological Societies committee for IEI (Table 1 ) [ 1 ▪▪ , 3 , 4 , 5 ▪ , 9 ▪ , 10 – 65 ]. Patients were mostly included based on a positive molecular test, antigenic test, or serology, although some reports also include patients with symptoms and clinical imaging compatible with a diagnosis of COVID-19, with or without a history of exposure to infected individuals [ 10 , 12 , 14 , 15 , 18 ].…”

“…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 ].…”

Antibody responses to the SARS-CoV-2 vaccine in individuals with various inborn errors of immunity

“…Some groups of immunocompromised patients are at increased risk for severe SARS-CoV-2 infection. 1,2 For patients with inborn errors of immunity (IEIs), some studies have reported an infection fatality rate similar to that in the general population, 3,4 but others have documented increased hospitalization and death rates [5][6][7][8] along with younger age at death and prolonged SARS-CoV-2 positivity. 4,5 The nature of the underlying gene defect and associated immunopathology may be important predictors of disease severity and outcome.…”

Outcomes Following SARS-CoV-2 Infection in Patients With Primary and Secondary Immunodeficiency in The United Kingdom

“…National epidemiological studies tend to consider immunocompromised individuals as a homogenous group (e.g., HIV-1 infection, solid organ transplant, immunosuppressive medications) and are unable to inform our understanding of outcome in individuals with rare diseases [1,2]. Instead, retrospective case series have been used to develop our understanding of the risk in patients with PID and SID [3][4][5][6][7][8][9]. While the results of such studies must be interpreted with caution, a consistent pattern has emerged showing that adult patients with PID and SID are at an increased risk of morbidity and mortality from COVID-19 compared to the general population, and that an increased prevalence of chronic co-morbidities, potentially driven by underlying immunode ciency, partially contributes to that risk.…”