Circulating miRNAs and Cytokines Uncover Novel Physiopathological Mechanisms of COVID-19 (preprint)

Coronavirus Disease 2019 (COVID-19) pneumonia is a life-threatening infectious disease, especially for elderly patients with multiple comorbidities. Despite enormous efforts to understand its underlying etiopathogenic mechanisms, most of them remain elusive. In this study, we compared differential plasma miRNAs and cytokines profiles between COVID-19 and other community-acquired pneumonias (CAP). A first screening and subsequent validation assays in an independent cohort of patients revealed a signature of 15 dysregulated miRNAs between COVID-19 and CAP patients. Additionally, multivariate analysis displayed a combination of 4 miRNAs (miR-106b-5p, miR-221-3p, miR-25-3p and miR-30a-5p) that significantly discriminated between both pathologies. Search for targets of these miRNAs, combined with plasma protein measurements, identified a differential cytokine signature between COVID-19 and CAP that included EGFR, CXCL12 and IL-10. Significant differences were also detected in plasma levels of CXCL12, IL-17, TIMP-2 and IL-21R between mild and severe COVID-19 patients. These findings provide new insights into the etiopathological mechanisms underlying COVID-19.

Long-Term Survival of Mechanically Ventilated Patients with Severe COVID-19: An Observational Cohort Study (preprint)

Background: Information is lacking regarding long-term survival and predictive factors for mortality in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) and undergoing invasive mechanical ventilation. We aimed to estimate 90-day and 180-day survival of patients with COVID-19 requiring invasive ventilation and to develop a predictive model for intensive care unit mortality.Methods: Retrospective, multicentre, national cohort study between March 8 and April 30, 2020 in 16 intensive care units (ICU) in Spain. Participants were consecutive adults who received invasive mechanical ventilation for COVID–19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected in positive testing of a nasopharyngeal sample and confirmed by real time reverse-transcriptase polymerase chain reaction (rt-PCR). The primary outcomes were 90-day and 180-day survival after hospital admission. Secondary outcomes were length of ICU and hospital stay, and ICU and in-hospital mortality. A predictive model and a nomogram were developed to estimate the probability of ICU mortality. Results: 868 patients were included (median age, 64 years [interquartile range [IQR], 56-71 years]; 72% male). Severity at ICU admission, estimated by SAPS3, was 56 points [IQR 50-63]. Prior to intubation, 26% received some type of noninvasive respiratory support. The 90-day and 180-day survival rates were 69% (95% confidence interval [CI] 66%-72%) and 59% (95% CI 56%-62%) respectively. The predictive factors associated with ICU mortality were: age (odds ratio [OR] 1.049 [95% CI 1.032-1.066] per 1-year increase), SAPS3 (OR 1.025 [95% CI 1.008-1.041] per 1-point increase), neutrophil to lymphocyte ratio (OR 1.009 [95% CI 1.002-1.016]), a failed attempt of noninvasive positive pressure ventilation previous to orotracheal intubation(OR 2.131 [95% CI 1.279-3.550]), and use of selective digestive decontamination (OR 0.587 [95% CI 0.358-0.963]).Conclusion: The long-term survival of mechanically ventilated patients with severe COVID-19 reaches more than 50% and may help to provide individualized risk stratification and potential treatments.Trial registration: ClinicalTrials.gov Identifier: NCT04379258. Registered 10 April 2020 (retrospectively registered).