Risk Factors for Severe COVID-19 and Hospital Admission in Patients With Inborn Errors of Immunity - Results From a Multicenter Nationwide Study

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.

COVID-19 in unvaccinated patients with inborn errors of immunity—polish experience

“…The other less characteristic symptoms of COVID-19 were also more common in adults than in children. Similar results were obtained in other studies, although the typical comparative analyses of clinical picture pediatric population and in adults were not found in the available literature (7,12,21).…”

“…In this group, the asymptomatic course concerned almost the same percentage of patients as in presented analysis (21% vs. 20%), but the risk of seriously severe COVID-19 was 2.3 times higher than in the general population. However, taking into account the fact that the mean age of the population was >42 years while in our study-19 years), it can be assumed that the vast majority of the analysis concerned elderly adults, which is itself a risk factor (21).…”

“…Only single reports described the efficacy of convalescent plasma or specific monoclonal antibody cocktails against the viral spike protein in combination with antiviral drugs (remdesivir) at an early stage of SARS-CoV-2 infection. However, most often, patients with IEI and COVID-19 were treated in line with local guidelines (12,21,24). The treatment used in hospitalized patients is often the subject of analysis in the available literature, but there are usually no data on home therapy (6,7,12,21).…”

Targeting thromboinflammation in COVID-19 – A narrative review of the potential of C1 inhibitor to prevent disease progression

“…Based on the depletion of ACE2 and the activation of the CS, KKS and CAS during SARS-CoV-2 infection, it was hypothesized that HAE patients may be at increased risk to develop severe COVID-19 and that SARS-CoV-2 infection may trigger HAE attacks ( Xu et al, 2020 ). However, no individual developed severe disease in 13 and 16 HAE patients infected with SARS-CoV-2 ( Grumach et al, 2021 , Milota et al, 2022 ), and COVID-19 outcome was described as similar compared with the general population in another study of 56 HAE patients and in a survey of more than 800 HAE patients ( Olivares et al, 2022 , Veronez et al, 2021 ). Interestingly, HAE patients on subcutaneous prophylactic (but not intravenous) C1-INH reported a reduced SARS-CoV-2 infection rate compared to household controls and HAE patients not on any HAE medication ( Veronez et al, 2021 ).…”

Real-life data on monoclonal antibodies and antiviral drugs in Italian inborn errors of immunity patients during COVID-19 pandemic

“…Age, sex, high BMI, diabetes, renal and liver impairment, hemoglobinopathies, neurodegenerative diseases, cardiovascular and pulmonary co-morbidities, as well as immunocompromission, have been associated with hospitalization and severe course of COVID-19 both in adolescents and adult patients, thus leading to prioritization for specific early treatment ( 41 – 43 ). In real-world studies, early treatment (within 5 days of symptom onset) with monoclonal antibodies or antivirals was associated with significant reduction in hospital admission, severe disease and hospitalization ( 11 – 13 , 15 , 28 – 31 ).…”