Outcome of SARS-CoV-2 Infection in 121 Patients with Inborn Errors of Immunity: A Cross-Sectional Study.

PURPOSE: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many unresolved questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and identify factors influencing the 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 was mostly asymptomatic (n = 21) and mild (n = 66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex-related susceptibility, and there was 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. However, the type of IEI was not a determining factor for severity, except for complement deficiencies linked to milder COVID-19. The severity of SARS-CoV-2 infection seems to be more related to older age, a higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).

Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19.

Coagulation activation is a prominent feature of severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We therefore sought to assess activation of the contact system and intrinsic pathway in individuals with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by enzyme-linked immunosorbent assay, and extrinsic pathway activation was assessed by microvesicle tissue factor-mediated factor Xa (FXa; MVTF) generation. Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and 30 age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased plasma levels of FXIIa:C1 esterase inhibitor (C1), kallikrein:C1, FXIa:C1, FXIa:α1-antitrypsin, and FIXa:antithrombin (AT). MVTF levels were also increased in patients with COVID-19. Because FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically total length of hospitalization, length of intensive care unit stay, and extent of lung computed tomography changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes.

Hipogamaglobulinemia e rituximabe: relato de casos / Hypogammaglobulinemia and rituximab: case reports

Secondary immunodeficiency can result from neoplasms, infections, or immunosuppressive therapy. Rituximab (RTX) is an anti-CD20 antibody that depletes B lymphocytes and can induce symptomatic hypogammaglobulinemia. We report 3 cases of symptomatic hypogammaglobulinemia associated with the use of RTX. In patient 1 with rheumatoid arthritis, RTX induced low levels of immunoglobulins and recurrent airway infections. RTX discontinuation led to a normalization of the humoral immune response. Patients 2 and 3, treated with RTX for non-Hodgkin lymphoma and systemic lupus erythematosus, respectively, developed persistent secondary hypogammaglobulinemia requiring immunoglobulin replacement therapy for years. After RTX discontinuation, patients may experience rapid recovery of humoral function or remain with low serum immunoglobulin levels for extended periods. With the increasing use of therapies targeting components of the immune system, a high degree of clinical suspicion for the development of secondary immunodeficiency may minimize the morbidity and mortality associated with these therapies.

As imunodeficiências secundárias podem ser uma consequência de neoplasias, infecções ou tratamentos imunossupressores. O rituximabe (RTX) é um anticorpo anti-CD20 que depleta os linfócitos B e pode induzir uma hipogamaglobulinemia sintomática. Aqui, relatamos três casos de hipogamaglobulinemia sintomática associada ao uso de RTX. Na primeira paciente com artrite reumatoide, o RTX induziu a baixos níveis de imunoglobulinas associadas a infecções de vias aéreas de repetição. Após a suspensão do RTX, houve normalização da resposta imune humoral. Os outros dois casos, com o uso de RTX para tratamento de linfoma não-Hodgkin e lúpus eritematoso sistêmico, respectivamente, as pacientes evoluíram com hipogamaglobulinemia secundária persistente, com necessidade de reposição de imunoglobulina por vários anos. Pacientes tratados com RTX podem apresentar, após a sua suspensão, uma recuperação rápida da função humoral ou permanecerem com baixos níveis séricos de imunoglobulinas por longos períodos. Com o crescente uso dos tratamentos direcionados para componentes do sistema imunológico, um alto grau de suspeição clínica para o aparecimento de imunodeficiências secundárias pode minimizar a morbimortalidade associada a estes tratamentos.