Cardiovascular-related proteomic changes in ECFCs exposed to the serum of COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection significantly affects the cardiovascular system, causing vascular damage and thromboembolic events in critical patients. Endothelial dysfunction represents one of the first steps in response to COVID-19 that might lead to cardiovascular complications and long-term sequelae. However, despite the enormous efforts in the last two years, the molecular mechanisms involved in such processes remain poorly understood. Herein, we analyzed the protein changes taking place in endothelial colony forming cells (ECFCs) after the incubation with the serum from individuals infected with COVID-19, whether asymptomatic or critical patients, by application of a label free-quantitative proteomics approach. Specifically, ECFCs from healthy individuals were incubated ex-vivo with the serum of either COVID-19 negative donors (PCR-/IgG-, n:8), COVID-19 asymptomatic donors at different infective stages (PCR+/ IgG-, n:8and PCR-/IgG+, n:8), or hospitalized critical COVID-19 patients (n:8), followed by proteomics analysis. In total, 590 proteins were differentially expressed in ECFCs in response to all infected serums. Predictive analysis highlighted several proteins like CAPN5, SURF4, LAMP2 or MT-ND1, as highly discriminating features between the groups compared. Protein changes correlated with viral infection, RNA metabolism or autophagy, among others. Remarkably, the angiogenic potential of ECFCs in response to the infected serums was impaired, and many of the protein alterations in response to the serum of critical patients were associated with cardiovascular-related pathologies.

Serum microRNAs targeting ACE2 and RAB14 genes distinguish asymptomatic from critical COVID-19 patients.

Despite the extraordinary advances achieved to beat COVID-19 disease, many questions remain unsolved, including the mechanisms of action of SARS-CoV-2 and which factors determine why individuals respond so differently to the viral infection. Herein, we performed an in silico analysis to identify host microRNA targeting ACE2, TMPRSS2, and/or RAB14, all genes known to participate in viral entry and replication. Next, the levels of six microRNA candidates previously linked to viral and respiratory-related pathologies were measured in the serum of COVID-19-negative controls (n = 16), IgG-positive COVID-19 asymptomatic individuals (n = 16), and critical COVID-19 patients (n = 17). Four of the peripheral microRNAs analyzed (hsa-miR-32-5p, hsa-miR-98-3p, hsa-miR-423-3p, and hsa-miR-1246) were upregulated in COVID-19 critical patients compared with COVID-19-negative controls. Moreover, hsa-miR-32-5p and hsa-miR-1246 levels were also altered in critical versus asymptomatic individuals. Furthermore, these microRNA target genes were related to viral infection, inflammatory response, and coagulation-related processes. In conclusion, SARS-CoV-2 promotes the alteration of microRNAs targeting the expression of key proteins for viral entry and replication, and these changes are associated with disease severity. The microRNAs identified could be taken as potential biomarkers of COVID-19 progression as well as candidates for future therapeutic approaches against this disease.

Association Between Drug Burden Index and Functional and Cognitive Function in Patients with Multimorbidity.

BACKGROUND: Anticholinergic and sedative drugs are associated with adverse events such as cognitive and functional impairment in elderly. The Drug Burden Index (DBI) is a measure of an individual's total exposure to anticholinergic and sedative drugs. Objetive: The study aimed to evaluate the association between the total DBI and cognitive and functional impairment in patients with multimorbidity. SETTING: Patients with multimorbidity enrolled in the IMPACTO project. METHODS: Cross-sectional observational study. MAIN OUTCOME MEASURE: The anticholinergic and sedative exposure was calculated using DBI. The Pfeiffer Test (PT) was used for cognitive status and the Barthel Index (BI) for functional status. RESULTS: 336 patients were included (mean age 77.6 ± 8.7 years, 54.2% men and a mean of 11.5 ± 3.7 prescribed drugs). 180 patients (53.6%) exposed to anticholinergic and/or sedative drugs were identified. The median score obtained in PT was slightly higher in exposed patients (1 (IQR 0-2) and 2 (IQR 0-4), p = 0.082 in "non-exposed" and "exposed", respectively). The bivariate analysis showed an association [0.544 (95% CI 0.044-1.063, p = 0.03)]. The median obtained in the BI analysis was 85.0 (IQR 30.0) and 75.5 (IQR 42.5) p = 0.002, in "nonexposed" and "exposed", respectively. After the adjusted analysis, a relationship was obtained between both the variables [-9,558 (95% CI-15,794; -3,321, p = 0.03)]. CONCLUSION: Higher DBI is associated with the impairment of functional status and, slightly to the deterioration of cognitive function in patients with multimorbidity. DBI should be considered in patients with multimorbidity to optimize the pharmacological treatment of a group of special interest due to its vulnerability.