Results of phase 2 randomized multi-center study to evaluate the safety and efficacy of infusion of memory T cells as adoptive therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and/or lymphopenia (RELEASE NCT04578210).

BACKGROUND AIMS: There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA- memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment. METHODS: Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 106/kg CD45RA- memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA- memory T cells and the most frequent human leukocyte antigen typing in the Spanish population. RESULTS: We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events. CONCLUSIONS: Adoptive cell therapy with off-the-shelf CD45RA- memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia. TRIAL REGISTRATION: NCT04578210.

Effect of EARLY administration of DEXamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome (EARLY-DEX COVID-19): study protocol for a randomized controlled trial.

BACKGROUND: Corticosteroids 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. 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/DESIGN: This 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 the development of ARDS. Risk for the development of 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 a dose of 6 mg once daily during 7 days. The primary outcome is a composite of the development of moderate or more severe ARDS and all-cause mortality during the 30-day period following enrolment. DISCUSSION: If our hypothesis is correct, the results of this study will provide additional insights into 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 REGISTRATION: ClinicalTrials.gov NCT04836780. Registered on 8 April 2021 as EARLY-DEX COVID-19.

Clinical course and prognostic factors of COVID-19 infection in an elderly hospitalized population.

INTRODUCTION: Older subjects have a higher risk of COVID-19 infection and a greater mortality. However, there is a lack of studies evaluating the characteristics of this infection at advanced age. PATIENTS AND METHODS: We studied 404 patients ≥ 75 years (mean age 85.2 ±â€¯5.3 years, 55 % males), with PCR-confirmed COVID-19 infection, attended in two hospitals in Madrid (Spain). Patients were followed-up until they were discharged from the hospital or until death. RESULTS: Symptoms started 2-7 days before admission, and consisted of fever (64 %), cough (59 %), and dyspnea (57 %). A total of 145 patients (35.9 %) died a median of 9 days after hospitalization. In logistic regression analysis, predictive factors of death were age (OR 1.086; 1.015-1.161 per year, p = 0.016), heart rate (1.040; 1.018-1.061 per beat, p < 0.0001), a decline in renal function during hospitalization (OR 7.270; 2.586-20.441, p < 0.0001) and worsening dyspnea during hospitalization (OR 73.616; 30.642-176.857, p < 0.0001). Factors predicting survival were a female sex (OR 0.271; 0.128-0.575, p = 0.001), previous treatment with RAAS inhibitors (OR 0.459; 0.222-0.949, p = 0.036), a higher oxygen saturation at admission (OR 0.901; 0.842-0.963 per percentage point increase, p = 0.002), and a greater platelet count (OR 0.995; 0.991-0.999 per 106/L, p = 0.025). CONCLUSION: Elderly patients with COVID-19 infection have a similar clinical course to younger individuals. Previous treatment with RAAS inhibitors, and demographic, clinical and laboratory data influence prognosis.