Remdesivir plus dexamethasone is associated to improve the clinical outcome of COVID-19 hospitalized patients regardless of their vaccination status Remdesivir más dexametasona se asocian a una reducción de los eventos clínicos en los pacientes hospitalizados por COVID-19, independientemente de su estado de vacunación

Introduction Remdesivir seems to reduce the risk of hospitalization and improve clinical outcome in hospitalized patients with COVID-19. Objectives To compare the clinical outcome of COVID-19 hospitalized patients treated with remdesivir plus dexamethasone versus dexamethasone alone, according to their vaccination status. Material and methods A retrospective observational study was carried out in 165 patients hospitalized for COVID-19 from October 2021 to January 2022. Multivariate logistic regression, Kaplan–Meier and the log-rank tests were used to evaluate the event (need for ventilation or death). Results Patients treated with remdesivir plus dexamethasone (n = 87) compared with dexamethasone alone (n = 78) showed similar age (60 ± 16, 47–70 vs. 62 ± 37, 51–74 years) and number of comorbidities: 1 (0–2) versus 1.5 (1–3). Among 73 fully vaccinated patients, 42 (47.1%) were in remdesivir plus dexamethasone and 31 (41%) in dexamethasone alone. Patients treated with remdesivir plus dexamethasone needed intensive care less frequently (17.2% vs. 31%;p = 0.002), high-flow oxygen (25.3% vs. 50.0%;p = 0.002) and non-invasive mechanical ventilation (16.1% vs. 47.4%;p < 0.001). Furthermore, they had less complications during hospitalization (31.0% vs. 52.6%;p = 0.008), need of antibiotics (32.2% vs. 59%;p = 0.001) and radiologic worsening (21.8% vs. 44.9%;p = 0.005). Treatment with remdesivir plus dexamethasone (aHR, 0.26;95% CI: 0.14–0.48;p < 0.001) and vaccination (aHR 0.39;95% CI: 0.21–0.74) were independent factors associated with lower progression to mechanical ventilation or death. Conclusions Remdesivir in combination with dexamethasone and vaccination independently and synergistically protects hospitalized COVID-19 patients requiring oxygen therapy from progression to severe disease or dead.

Remdesivir plus dexamethasone is associated to improve the clinical outcome of COVID-19 hospitalized patients regardless of their vaccination status.

INTRODUCTION: Remdesivir seems to reduce the risk of hospitalization and improve clinical outcome in hospitalized patients with COVID-19. OBJECTIVES: To compare the clinical outcome of COVID-19 hospitalized patients treated with remdesivir plus dexamethasone versus dexamethasone alone, according to their vaccination status. MATERIAL AND METHODS: A retrospective observational study was carried out in 165 patients hospitalized for COVID-19 from October 2021 to January 2022. Multivariate logistic regression, Kaplan-Meier and the log-rank tests were used to evaluate the event (need for ventilation or death). RESULTS: Patients treated with remdesivir plus dexamethasone (n=87) compared with dexamethasone alone (n=78) showed similar age (60±16, 47-70 vs. 62±37, 51-74 years) and number of comorbidities: 1 (0-2) versus 1.5 (1-3). Among 73 fully vaccinated patients, 42 (47.1%) were in remdesivir plus dexamethasone and 31 (41%) in dexamethasone alone. Patients treated with remdesivir plus dexamethasone needed intensive care less frequently (17.2% vs. 31%; p=0.002), high-flow oxygen (25.3% vs. 50.0%; p=0.002) and non-invasive mechanical ventilation (16.1% vs. 47.4%; p<0.001). Furthermore, they had less complications during hospitalization (31.0% vs. 52.6%; p=0.008), need of antibiotics (32.2% vs. 59%; p=0.001) and radiologic worsening (21.8% vs. 44.9%; p=0.005). Treatment with remdesivir plus dexamethasone (aHR, 0.26; 95% CI: 0.14-0.48; p<0.001) and vaccination (aHR 0.39; 95% CI: 0.21-0.74) were independent factors associated with lower progression to mechanical ventilation or death. CONCLUSIONS: Remdesivir in combination with dexamethasone and vaccination independently and synergistically protects hospitalized COVID-19 patients requiring oxygen therapy from progression to severe disease or dead.

Activating Killer-Cell Immunoglobulin-Like Receptors Are Associated With the Severity of Coronavirus Disease 2019.

BACKGROUND: Etiopathogenesis of the clinical variability of the coronavirus disease 2019 (COVID-19) remains mostly unknown. In this study, we investigate the role of killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen class-I (HLA-I) interactions in the susceptibility and severity of COVID-19. METHODS: We performed KIR and HLA-I genotyping and natural killer cell (NKc) receptors immunophenotyping in 201 symptomatic patients and 210 noninfected controls. RESULTS: The NKcs with a distinctive immunophenotype, suggestive of recent activation (KIR2DS4low CD16low CD226low CD56high TIGIThigh NKG2Ahigh), expanded in patients with severe COVID-19. This was associated with a higher frequency of the functional A-telomeric activating KIR2DS4 in severe versus mild and/or moderate patients and controls (83.7%, 55.7% and 36.2%, P < 7.7 × 10-9). In patients with mild and/or moderate infection, HLA-B*15:01 was associated with higher frequencies of activating B-telomeric KIR3DS1 compared with patients with other HLA-B*15 subtypes and noninfected controls (90.9%, 42.9%, and 47.3%; P < .002; Pc = 0.022). This strongly suggests that HLA-B*15:01 specifically presenting severe acute respiratory syndrome coronavirus 2 peptides could form a neoligand interacting with KIR3DS1. Likewise, a putative neoligand for KIR2DS4 could arise from other HLA-I molecules presenting severe acute respiratory syndrome coronavirus 2 peptides expressed on infected an/or activated lung antigen-presenting cells. CONCLUSIONS: Our results support a crucial role of NKcs in the clinical variability of COVID-19 with specific KIR/ligand interactions associated with disease severity.