Cellular and molecular features of COVID-19 associated ARDS: therapeutic relevance.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can be asymptomatic or cause a disease (COVID-19) characterized by different levels of severity. The main cause of severe COVID-19 and death is represented by acute (or acute on chronic) respiratory failure and acute respiratory distress syndrome (ARDS), often requiring hospital admission and ventilator support.The molecular pathogenesis of COVID-19-related ARDS (by now termed c-ARDS) is still poorly understood. In this review we will discuss the genetic susceptibility to COVID-19, the pathogenesis and the local and systemic biomarkers correlated with c-ARDS and the therapeutic options that target the cell signalling pathways of c-ARDS.

Sex differences and disparities in cardiovascular outcomes of COVID-19.

AIMS: Previous analyses on sex differences in case fatality rates at population-level data had limited adjustment for key patient clinical characteristics thought to be associated with coronavirus disease 2019 (COVID-19) outcomes. We aimed to estimate the risk of specific organ dysfunctions and mortality in women and men. METHODS AND RESULTS: This retrospective cross-sectional study included 17 hospitals within 5 European countries participating in the International Survey of Acute Coronavirus Syndromes COVID-19 (NCT05188612). Participants were individuals hospitalized with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 2020 to February 2022. Risk-adjusted ratios (RRs) of in-hospital mortality, acute respiratory failure (ARF), acute heart failure (AHF), and acute kidney injury (AKI) were calculated for women vs. men. Estimates were evaluated by inverse probability weighting and logistic regression models. The overall care cohort included 4499 patients with COVID-19-associated hospitalizations. Of these, 1524 (33.9%) were admitted to intensive care unit (ICU), and 1117 (24.8%) died during hospitalization. Compared with men, women were less likely to be admitted to ICU [RR: 0.80; 95% confidence interval (CI): 0.71-0.91]. In general wards (GWs) and ICU cohorts, the adjusted women-to-men RRs for in-hospital mortality were of 1.13 (95% CI: 0.90-1.42) and 0.86 (95% CI: 0.70-1.05; pinteraction = 0.04). Development of AHF, AKI, and ARF was associated with increased mortality risk (odds ratios: 2.27, 95% CI: 1.73-2.98; 3.85, 95% CI: 3.21-4.63; and 3.95, 95% CI: 3.04-5.14, respectively). The adjusted RRs for AKI and ARF were comparable among women and men regardless of intensity of care. In contrast, female sex was associated with higher odds for AHF in GW, but not in ICU (RRs: 1.25; 95% CI: 0.94-1.67 vs. 0.83; 95% CI: 0.59-1.16, pinteraction = 0.04). CONCLUSIONS: Women in GW were at increased risk of AHF and in-hospital mortality for COVID-19 compared with men. For patients receiving ICU care, fatal complications including AHF and mortality appeared to be independent of sex. Equitable access to COVID-19 ICU care is needed to minimize the unfavourable outcome of women presenting with COVID-19-related complications.

Cutting Edge: Hyperinflammatory Monocytes Expressing CD56 Abound in Severe COVID-19 Patients.

Proinflammatory monocytes play a preponderant role in the development of a cytokine storm causing fatal consequences in coronavirus disease 2019 (COVID-19) patients, highlighting the importance of analyzing in more detail monocyte distribution in these patients. In this study, we identified an atypical monocyte subpopulation expressing CD56 molecules that showed a low level of HLA-DR and high level of l-selectin. They released higher amounts of TNF-α and IL-6 and expressed genes associated with an excessive inflammatory process. Remarkably, the frequency of CD56+ monocytes inversely correlated with that of CD16+ monocytes and a high CD56+/CD16+monocyte ratio was associated with both disease severity and mortality, as well as with serum concentration of type I IFN, a factor able to induce the appearance of CD56+ monocytes. In conclusion, severe COVID-19 is characterized by the abundance of hyperinflammatory CD56+ monocytes, which could represent a novel marker with prognostic significance and, possibly, a therapeutic target for controlling the inflammatory process occurring during COVID-19.

One-Year Functional, Cognitive, and Psychological Outcomes Following the Use of Extracorporeal Membrane Oxygenation in Coronavirus Disease 2019: A Prospective Study.

To prospectively describe 1-year outcomes, with a focus on functional outcome, cognitive outcome, and the burden of anxiety, depression, and post-traumatic stress disorder, in coronavirus disease 2019 patients managed with extracorporeal membrane oxygenation. DESIGN: Prospective case series. SETTING: Tertiary extracorporeal membrane oxygenation center in the United States. PATIENTS: Adult coronavirus disease 2019 acute respiratory distress syndrome patients managed with extracorporeal membrane oxygenation March 1, 2020, to July 31, 2020. INTERVENTIONS: Baseline variables, treatment measures, and short-term outcomes were obtained from the medical record. Survivors were interviewed by telephone, a year following the index intensive care admission. Functional outcome was assessed using the modified Rankin Scale and the World Health Organization Disability Assessment Scale 2.0. Cognitive status was assessed with the 5-minute Montreal Cognitive Assessment. The Hospital Anxiety and Depression Scale was used to screen for anxiety and depression. Screening for post-traumatic stress disorder was performed with the Posttraumatic Stress Disorder Checklist 5 instrument. MEASUREMENTS AND MAIN RESULTS: Twenty-three patients were managed with extracorporeal membrane oxygenation, 14 (61%) survived to hospital discharge. Thirteen (57%) were alive at 1 year. One patient was dependent on mechanical ventilation, another intermittently required supplemental oxygen at 1 year. The median modified Rankin Scale score was 2 (interquartile range, 1-2), median World Health Organization Disability Assessment Scale 2.0 impairment score was 21% (interquartile range, 6-42%). Six of 12 previously employed individuals (50%) had returned to work, and 10 of 12 (83%) were entirely independent in activities of daily living. The median Montreal Cognitive Assessment score was 14 (interquartile range, 13-14). Of 10 patients assessed with Hospital Anxiety and Depression Scale, 4 (40%) screened positive for depression and 6 (60%) for anxiety. Four of 10 (40%) screened positive for post-traumatic stress disorder. CONCLUSIONS: Functional impairment was common a year following the use of extracorporeal membrane oxygenation in coronavirus disease 2019, although the majority achieved independence in daily living and about half returned to work. Long-term anxiety, depression, and post-traumatic stress disorder were common, but cognitive impairment was not.