RESUMEN
Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and can affect multiple organs, among which is the circulatory system. Inflammation and mortality risk markers were previously detected in COVID-19 plasma and red blood cells (RBCs) metabolic and proteomic profiles. Additionally, biophysical properties, such as deformability, were found to be changed during the infection. Based on such data, we aim to better characterize RBC functions in COVID-19. We evaluate the flow properties of RBCs in severe COVID-19 patients admitted to the intensive care unit by using in vitro microfluidic techniques and automated methods, including artificial neural networks, for an unbiased RBC analysis. We find strong flow and RBC shape impairment in COVID-19 samples and demonstrate that such changes are reversible upon suspension of COVID-19 RBCs in healthy plasma. Vice versa, healthy RBCs immediately resemble COVID-19 RBCs when suspended in COVID-19 plasma. Proteomics and metabolomics analyses allow us to detect the effect of plasma exchanges on both plasma and RBCs and demonstrate a new role of RBCs in maintaining plasma equilibria at the expense of their flow properties. Our findings provide a framework for further investigations of clinical relevance for therapies against COVID-19 and possibly other infectious diseases.
RESUMEN
RationaleCOVID-19 convalescent plasma (CCP) has been considered a treatment option in COVID-19. ObjectivesTo assess the efficacy of neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment. MethodsPatients (n=105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. Primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21. The trial is registered: clinicaltrials.gov #NCT04433910. Measurements and main resultsThe primary outcome occurred in 43.4% of patients in the CCP and 32.7% in the control group (p=0.32). The median time to clinical improvement was 26 days (IQR 15-not reached (n.r.)) in the CCP group and 66 days (IQR 13-n.r.) in the control group (p=0.27). Median time to discharge from hospital was 31 days (IQR 16-n.r.) in the CCP and 51 days (IQR 20-n.r.) in the control group (p=0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies the primary outcome occurred in 56.0% (versus 32.1%), with a shorter interval to clinical improvement, shorter time to hospital discharge and better survival compared to the control group. ConclusionCCP added to standard treatment did not result in a significant difference in the primary and secondary outcomes. A pre-defined subgroup analysis showed a significant benefit for CCP among those who received a larger amount of neutralizing antibodies.
