Treatment of chronic or relapsing COVID-19 in immunodeficiency

Abstract

Background: Patients with some types of immunodeficiency can experience chronic or relapsing infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This leads to morbidity and mortality, infection control challenges, and the risk of evolution of novel viral variants. The optimal treatment for chronic coronavirus disease 2019 (COVID-19) is unknown. Objective: Our aim was to characterize a cohort of patients with chronic or relapsing COVID-19 disease and record treatment response. Methods: We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features, and treatment response of immunodeficient patients with chronic (lasting > _21 days) or relapsing (> _2 episodes) of COVID-19. Results: We identified 31 patients (median age 49 years). Their underlying immunodeficiency was most commonly characterized by antibody deficiency with absent or profoundly reduced peripheral B-cell levels; prior anti-CD20 therapy, and X-linked agammaglobulinemia. Their clinical features of COVID-19 were similar to those of the general population, but their median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to 5 episodes of illness. Remdesivir monotherapy (including when given for prolonged courses of < _20 days) was associated with sustained viral clearance in 7 of 23 clinical episodes (30.4%), whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 mAbs resulted in viral clearance in 13 of 14 episodes (92.8%). Patients receiving no therapy did not clear SARS-CoV-2. Conclusions: COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise. (J Allergy Clin Immunol 2021;nnn:nnn-nnn.)

The Impact of SARS-CoV-2 Infection in Patients with Inborn Errors of Immunity: the Experience of the Italian Primary Immunodeficiencies Network (IPINet)

“…Among the patients with prolonged infection, all but one patient with SIgAD were under IgRT, and patients with profound humoral immunodeficiency also showed a longer viral shedding compared to other IEI. This confirms what reported in previous studies from the literature showing that persistent infection or relapsing–remitting infection is associated with profound humoral immunodeficiency and the failure to make de novo humoral responses to SARS-CoV-2 [ 27 ]. In one patient with XLA from our cohort, readmission was required for the development of worsening dyspnea after a complete resolution of acute COVID-19 phase and negativization of the PRC on the nasopharyngeal swab.…”

Impact of Hypogammaglobulinemia on the Course of COVID-19 in a Non-Intensive Care Setting: A Single-Center Retrospective Cohort Study

“…As already reported for PAD patients ( 11 ), our patients with hypogammaglobulinemia also presented longer disease duration and hospitalization. These might in part be due to an impairment in viral clearance and to the increased rate of superinfection ( 10 ). As a consequence, hypogammaglobulinemia was also associated to a more severe COVID-19 course, with higher need for non-invasive and invasive ventilation, higher score of disease severity and more frequent admission to s-ICU/ICU, despite all enrolled patients presenting a seven-category score ≤4 at admission.…”

“…It is indeed broadly recognized that a profound interplay exists between the host immune response and the COVID-19 course both in terms of susceptibility and clinical outcome ( 9 ). As a result, different published cohorts of patients with inborn errors of immunity (IEIs) reported mixed results depending on the underlying immunological defect ( 10 ). A multicenter retrospective study investigated the impact of SARS-CoV-2 infection on 94 patients with a spectrum of IEIs, mainly antibody deficiencies, reporting that disease severity and mortality were globally similar to those in the general population ( 11 ).…”

Ex vivo and in vivo suppression of SARS-CoV-2 with combinatorial AAV/RNAi expression vectors

“…In the context of persistent viral infection, we also note reports of chronic or recurrent infection with SARS-CoV-2 in immunocompromised or immunodeficient individuals. [61][62][63] Although these may be amenable to treatment with convalescent plasma 63 or antiviral agents such as remdesivir, 64 they should also benefit from therapeutic application of AAV-SAVIOR, as supported by the robust viral clearance we observed here in chronically infected Caco-2 cells. It may be beneficial to include a genetic circuit in future vector generations that senses the presence of active or chronic viral replication or expression and temporally restricts vector activity.…”