Convalescent Plasma for COVID-19: A multicenter, randomized clinical trial

BackgroundPassive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. MethodsWe conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. ResultsThe trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. ConclusionsConvalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523).

Preparation of ex vivo-based biomaterials using convective flow decellularization.

With advantageous biomechanical properties, materials derived from ex vivo tissues are being actively investigated as scaffolds for tissue engineering applications. However, decellularization treatments are required before implantation to reduce the materials immune impact. The aim of these investigations was to assess a convective flow model as an enhanced methodology to decellularize ex vivo tissue. Isolated human umbilical veins were decellularized using two methods: rotary agitation at 100rpm on orbital shaker plates, and convective flow run at 5, 50, and 150mmHg within perfusion bioreactors. Extracted phospholipids and total soluble protein were assessed over time. Histology, SEM, and uniaxial tensile testing analysis were carried out to evaluate variation in the tissues. After 72h, samples exposed to traditional rotary agitation showed retention of whole cells and cellular components, whereas pressure-based systems showed no visual sign of cells. The convective flow method was significantly more effective at removing phospholipid and total protein than the agitation model. High transmembrane pressure (150mmHg) resulted in higher phospholipids extraction. However, a more efficient protein extraction occurred at 50mmHg. Variation in extraction rates was dependent on tissue permeability, which varied as pressure increased. Collectively, these findings show significant improvements in decellularization efficiency that may lead to more immune compliant ex vivo-derived biomaterials.