Abstract
Despite the progress in the understanding how COVID-19 infection may impact immunocompromised patients, the data on inborn errors of immunity (IEI) remain limited and ambiguous. Therefore, we examined the risk of severe infection course and hospital admission in a large cohort of patients with IEI. In this multicenter nationwide retrospective survey-based trial, the demographic, clinical, and laboratory data were collected by investigating physicians from 8 national referral centers for the diagnosis and treatment of IEI using a COVID-19-IEI clinical questionnaire. In total, 81 patients with IEI (including 16 with hereditary angioedema, HAE) and confirmed SARS-CoV-2 infection were enrolled, and were found to have a 2.3-times increased (95%CI: 1.44–3.53) risk ratio for hospital admission and a higher mortality ratio (2.4% vs. 1.7% in the general population). COVID-19 severity was associated with the presence of clinically relevant comorbidities, lymphopenia, and hypogammaglobulinemia, but not with age or BMI. No individuals with HAE developed severe disease, despite a hypothesized increased risk due to perturbed bradykinin metabolism. We also demonstrated a high seroconversion rate in antibody-deficient patients and the safety of anti-spike SARS CoV-2 monoclonal antibodies and convalescent plasma. Thus, IEI except for HAE, represent significant risk factors for a severe COVID-19. Therefore, apart from general risk factors, immune system dysregulation may also be involved in the poor outcomes of COVID-19. Despite the study limitations, our results support the findings from previously published trials.
Highlights
Inborn errors of immunity (IEI) are a heterogeneous group of rare disorders characterized by impaired immune system function, manifesting as increased susceptibility to infections and a broad spectrum of non-infectious complications including autoimmunity, autoinflammatory diseases, allergy, and/or malignancy [1, 2]
COVID-19 infection was diagnosed in 81 patients with IEI (47 females, 34 males) including 16 cases of HAE in a multicenter cohort of 805 patients with IEI followed up at 8 national referral centers in the Czech Republic, FIGURE 1 | Study design - participating centers, enrollment process, study period and extent of collected data are shown (IEI, inborn errors of immunity; HAE, hereditary angioedema; Ig, immunoglobulin)
Other IEI were represented by only one patient, including late-onset combined immunodeficiency (LOCID), hyper IgE syndrome (HIES), Kabuki syndrome (KS), STAT-1 gain-of function chronic mucocutaneous candidosis (CMC), WiskottAldrich syndrome (WAS), X-linked agammaglobulinemia (XLA), X-linked lymphoproliferative syndrome type 1 and type 2 (XLP-1, 2), and X-linked hyper IgM syndrome (Figure 2)
Summary
Inborn errors of immunity (IEI) are a heterogeneous group of rare disorders characterized by impaired immune system function, manifesting as increased susceptibility to infections and a broad spectrum of non-infectious complications including autoimmunity, autoinflammatory diseases, allergy, and/or malignancy [1, 2]. The novel coronavirus SARS-CoV-2 raised new concerns in patients with IEI patients This single stranded mRNA virus was originally described in a patient with acute respiratory failure in the Chinese city of Wuhan; the disease was later named COVID-19 [4]. Complicated COVID-19 infection with increased hospital admission and mortality rates compared to the general population was described in immunocompromised patients such as those with cancer or solid organ transplants. Many of these patients had other risk factors (higher age, significant comorbidities) associated with worse outcomes. The study included patients with hereditary angioedema (HAE) due to C1 inhibitor deficiency, as the bradykinin overproduction in the kallikrein-kinin cascade was proposed as a possible mediator involved in the respiratory complications of COVID-19 infection and, as such, a risk factor for severe COVID-19
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