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.

Feasibility of telemedicine in the management strategy of patients with lymphoma amid the COVID-19 pandemic in Spain, a prospective study.

BACKGROUND: In March 14, 2020, the state of alarm and was declared in Spain due to the spread of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Beyond this date, the coronavirus disease 2019 (COVID-19) in the country changed the practice of oncologic care. OBJECTIVE: Since recurrent hospital visits were potential risk factors for contagion, the aims of this prospective observational study was to analyze the consequences of COVID-19 pandemic in the health care of patients with lymphoma. METHODS: All data were obtained from the electronic medical record (EMR). Variables such as age, sex, matter of the visit, use of patient's portal, changes in management, impact in clinical trials and suffering from COVID-19 contagion were recorded. RESULTS: 290 patients were attended in the lymphoma clinic accomplishing 437 appointments. The median age was 66 years (range 18-94) and 157 (54.13%) were male. Of them, 214 patients (73.79%) had only 1 visit to the clinic. Only 23 patients (7.93%) didn't have access to patient's portal. Amid the COVID-19 pandemic, 78 patients (26.89%) remained in active treatment, 35 patients (12.06%) suffered from delayed in their treatments and 6 patients (2.06%) suffered from treatment discontinuation. During the follow-up, only 8 patients (2.75%) suffered from COVID-19 (7 cases with confirmed PCR test and 1 case with clinical suspicion). Despite the implementation of telemedicine strategies to avoid visit to hospital, 66 patients (22.75%) had in-person visits to the lymphoma clinic. Patients who attended in-person consultation were younger than those who preferred telemedicine consultation (62 vs 66 years) and had less use of patient's portal (7.58% vs 9%), although these differences didn't reach statistical significance. Patients who atttended in-person visits used to have only 1 visit to hospital (43.93% vs 82.58%, P<.0001). Regarding the matter of in-person consultation, more patients were on active treatment in comparison with those using telemedicine resources (56.06% vs 18.30%, P<.0001). Patients with preference for telemedicine strategies had more surveillance visits (65.62% vs 36.36%, P<.0001). With regards of treatment modifications, more treatment delays (12.94% vs 9.09%) and more definite treatment discontinuations (2.67% vs 0%) were seen in patients using telemedicine resources when compared to patients attending in-person visits, although these differences didn't reach statistical significance. Regarding the type of therapy, patients attending in-person visits were more likely to receive an intravenous treatment rather than those on telemedicine (62.16% vs 40.47%, P<.0001). CONCLUSIONS: Telemedicine such as patient's portal are feasible strategies in the management of patients with lymphoma during the COVID-19 pandemic, with a reduction of in-person visits to hospital and a very low contagion rate.

The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex-vivo.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already caused 6 million deaths worldwide. While asymptomatic individuals are responsible of many potential transmissions, the difficulty to identify and isolate them at the high peak of infection constitutes still a real challenge. Moreover, SARS-CoV-2 provokes severe vascular damage and thromboembolic events in critical COVID-19 patients, deriving in many related deaths and long-hauler symptoms. Understanding how these processes are triggered as well as the potential long-term sequelae, even in asymptomatic individuals, becomes essential. METHODS: We have evaluated, by application of a proteomics-based quantitative approach, the effect of serum from COVID-19 asymptomatic individuals over circulating angiogenic cells (CACs). Healthy CACs were incubated ex-vivo with the serum of either COVID-19 negative (PCR -/IgG -, n:8) or COVID-19 positive asymptomatic donors, at different infective stages: PCR +/IgG - (n:8) and PCR -/IgG + (n:8). Also, a label free quantitative approach was applied to identify and quantify protein differences between these serums. Finally, machine learning algorithms were applied to validate the differential protein patterns in CACs. RESULTS: Our results confirmed that SARS-CoV-2 promotes changes at the protein level in the serum of infected asymptomatic individuals, mainly correlated with altered coagulation and inflammatory processes (Fibrinogen, Von Willebrand Factor, Thrombospondin-1). At the cellular level, proteins like ICAM-1, TLR2 or Ezrin/Radixin were only up-regulated in CACs treated with the serum of asymptomatic patients at the highest peak of infection (PCR + /IgG -), but not with the serum of PCR -/IgG + individuals. Several proteins stood out as significantly discriminating markers in CACs in response to PCR or IgG + serums. Many of these proteins particiArticle title: Kindly check and confirm the edit made in the article title.pate in the initial endothelial response against the virus. CONCLUSIONS: The ex vivo incubation of CACs with the serum of asymptomatic COVID-19 donors at different stages of infection promoted protein changes representative of the endothelial dysfunction and inflammatory response after viral infection, together with activation of the coagulation process. The current approach constitutes an optimal model to study the response of vascular cells to SARS-CoV-2 infection, and an alternative platform to test potential inhibitors targeting either the virus entry pathway or the immune responses following SARS-CoV-2 infection.

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.

Increased vulnerability of clinical research units during the COVID-19 crisis and their protection.

LAY SUMMARY: Currently, the complexity of clinical trial development in oncology is being further complicated by the coronavirus disease 2019 (COVID-19) pandemic, which is reducing the resources needed to comply with protocol-specific procedures while putting patients in units, who are already vulnerable, at increased general risk not only for COVID-19 infection but also with respect to their baseline disease. Individualizing the management of patients while ensuring their safety and adherence to the study protocol, establishing specific staff contingency plans, and maintaining sponsor and contract research organization (CRO) alignment are some of the key issues for maintaining the continuity of cancer patients' investigational treatment and minimizing their infection risk as well as the risk to staff members of the unit, sponsors, and CROs while maintaining the integrity of data quality and compliance with good clinical practice.