Management and outcome of COVID-19 in CTLA-4 insufficiency.
Blood advances(2023)
Abstract
Despite the high incidence of COVID-19 worldwide, clinical experience with SARS-COV2 in inborn errors of immunity (IEI) remains limited. Recent studies showed patients with defects in type 1 interferon (IFN)-related pathways or those with autoantibodies against type 1 IFNs developed severe COVID-19. We report the clinical course of 22 patients with CTLA-4 insufficiency and COVID-19 and retrospectively examine autoantibodies to type 1 interferons at baseline. Data was obtained from patient interview and chart review. Screening for anti-IFN autoantibodies was carried out using a multiplex particle-based assay. Student's T-test, Mann Whitney, ANOVA, or chi squared tests were used where appropriate. Twenty-two patients, ages 8 months to 54 years old, with genetically confirmed CLTA-4 insufficiency, developed COVID-19 from 2020-2022. Most common symptoms were fever, cough, and nasal congestion, and median duration of illness was 7.5 days. Twenty patients (91%) developed mild COVID-19 and were managed as outpatients. Two patients were hospitalized due to COVID-19 pneumonia but did not require mechanical ventilation. Ten patients (45%) were vaccinated at the time of their first COVID-19 infection. Eleven patients received outpatient treatment with monoclonal antibodies to the SARS-CoV2 spike protein. During the study period, 17 patients were vaccinated against SARS-CoV2, with no severe vaccine-related adverse effects. Although median anti-S titers following vaccination or infection were lower in patients on IVIG (349 IU/dL), compared to those not on IVIG (2594 IU/dL) (p=0.15), 3/9 patients on IVIG developed titers >2000 IU/dL. All patients were negative for autoantibodies to IFN-α, IFN-β and IFN-ω at baseline. Most patients with CTLA-4 insufficiency and COVID-19 had non-severe disease, lacked autoantibodies to type 1 IFNs, and tolerated mRNA vaccines with few adverse effects. Whether our findings can be extrapolated to patients on CTLA-4-targeting checkpoint inhibitors requires further studies.
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