ABSTRACT
Patients with antibody deficiency disorders, such as common variable immunodeficiency (CVID), or secondary immunodeficiency (SIDs) to B-cell lymphoproliferative disorder (B-CLPD), are two vulnerable groups of developing severe or chronic form of coronavirus disease caused by SARS-CoV-2 (COVID-19). Data on adaptive immune responses against SARS-CoV-2 is well described in healthy donors, but still limited in patients with antibody deficiency of different cause. Herein, we analyzed Spike-specific IFN-γ and anti-Spike IgG antibody responses at 3 and 6 months after exposure to SARS-CoV-2 derived from vaccination and infection in two cohorts of immunodeficient patients (CVID vs. SID) compared to healthy controls (HC). Baseline cellular responses before vaccine administration were measured in 10 CVID patients. Adequate specific cellular responses was observed in 18 out of 20 (90%) CVID patients, in 14 out of 20 (70%) out of 20 SID patients and in 74 out of 81 (96%) HC. Specific IFN-γ response was significantly higher in HC respect to CVID (1,908.5 mUI/ml versus 1,694.1 mUI/ml; p = 0.005). Pre-vaccine anti-SARS-CoV-2 cellular responses were detectable in 4 out of 10 CVID patients, who had COVID-19 prior to vaccination, noticing an increase in cellular responses after vaccination (p < 0.001). Whereas all SID and HC mounted a specific humoral immune response, only 80% of CVID patients showed positive anti-SARS-CoV-2 IgG. The titer of anti-SARS-CoV-2 IgG was significantly lower in SID compared with HC (p = 0.040), without significant differences between CVID and HC (p = 0.123) and between CVID and SID (p = 0.683). High proportions of CVID and SID patients showed adequate specific cellular responses to S1 neoantigen, with divergence between cellular and humoral immune responses in CVID and SID patients. Our data might support the relevance of these immunological studies to determine the correlate of protection to severe disease and for deciding the need of additional boosters. Follow-up studies are required to evaluate the duration and variability of the immune response to COVID-19 vaccination or infection.
Subject(s)
COVID-19ABSTRACT
BackgroundCorticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. No benefit in patients not requiring respiratory support at randomization was observed. However, we believe that the use of corticosteroids in patients with COVID-19 pneumonia might not be subject to a decision based solely on oxygen needs. Evidence has shown that 30% of COVID-19 patients with mild symptoms at presentation will progress to acute respiratory distress syndrome (ARDS), particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that dexamethasone treatment in hospitalized patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease might lead to a decrease in the development of ARDS, and thereby reduce death.Methods/designThis is a multicenter, randomized, controlled, parallel, open-label trial testing dexamethasone in 252 adult patients with COVID-19 pneumonia who do not require supplementary oxygen on admission, but are at risk factors for development ARDS. Risk for development ARDS is defined as levels of lactate dehydrogenase >245 U/L, C-reactive protein >100 mg/L, and lymphocyte count of <0.80 × 109/L. Eligible patients will be randomly assigned to receive either dexamethasone or standard of care. Patients in the dexamethasone group will receive an intravenous dose of 6 mg once daily from day 1 to day 3, followed by an oral dose of 6 mg once daily from day 4 to day 7. The primary outcome is a composite of development of moderate ARDS and all-cause mortality during the 30-day period following enrollment.DiscussionIf our hypothesis is correct, the results of this study will provide additional insights about the management and progression of this specific subpopulation of patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease.Trial registrationClinicalTrials.gov NCT04836780. Registered on 8 April 2021 as EARLY-DEX COVID-19.
Subject(s)
COVID-19ABSTRACT
Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention with plitidepsin in hospitalized COVID-19 adult patients where three doses were assessed (1.5, 2 and 2.5 mg/day for 3 days, as a 90-minute intravenous infusion) in 45 patients (15 per dose-cohort). Treatment was well tolerated, with only two Grade 3 treatment-related adverse events observed (hypersensitivity and diarrhea). The discharge rates by Days 8 and 15 were 56.8% and 81.8%, respectively, with data sustaining dose-effect. A mean 4.2 log10 viral load reduction was attained by Day 15. Improvement in inflammation markers was also noted in a seemingly dose-dependent manner. These results suggest that plitidepsin impacts the outcome of patients with COVID-19.