P1629: ADMINISTRATION OF CONVALESCENT PLASMA FOR THE TREATMENT OF SEVERE COVID-19: RESULTS OF A MULTICENTER PHASE II TRIAL

Background: COVID-19 is an ongoing pandemic with high morbidity and mortality. Despite meticulous research, optimal management of patients with severe COVID-19 remains a subject of vigorous debate. On this ground, several studies have assessed the efficacy and safety of convalescent plasma (CP) administration for the management of COVID-19; however, their results have been conflicting. A recent well-designed meta-analysis has highlighted the effectiveness of CP1, albeit other meta-analyses have demonstrated no survival benefit. Nonetheless, a large retrospective study of more than 3000 patients have shown that higher-titer CP administration provides a survival benefit for patients with COVID-192. Aims: The aim of this multicenter phase II study (NCT04408209), conducted at five tertiary hospital of Athens, Greece, was to evaluate the safety and efficacy of CP transfusion in patients with severe COVID-19. Methods: Patients with severe COVID-19 (WHO grade ≥4), confirmed by RT-PCR on nasopharyngeal swabs, were enrolled in the study and received three doses of single-donor CP on days 1, 3 and 5. Donors were eligible if they tested positive for anti-SARS-Cov-2 antibodies determined by the Euroimmun Assay and were symptom free and PCR negative for the virus. All participants were followed for at least 28 days. Clinical and laboratory parameters as well as antibody titers against S1 domain of SARS-CoV-2 were determined in the recipients on days 1–7 and on days 14, 21 and 28. Primary endpoint of the study was survival on day 28. Secondary endpoints included duration of hospital stay, duration of mechanical ventilation and oxygen support, time to PCR negativity and safety. Results: As of the end of March 2021, 106 patients with severe COVID-19 were enrolled and received CP at a median of 7 days from symptoms onset. Notably, 79.2% of patients received high-titer CP (anti-S1 IgG ≥3.5). The median age of patients was 61 years and 56.6% of them were male. Median SOFA score of patients was 4. At baseline, 82.3% of patients needed oxygen support ranging from nasal cannula to mechanical ventilation in 4.8% of patients. During a median follow-up of 25 days, 23 patients needed mechanical ventilation and 16 patients were discharged from Intensive Care Unit (ICU) at a median of 12 days. Median duration of oxygen support and total hospital stay for the entire cohort was 6 and 10 days respectively. 67.7% of participants achieved negative PCR result at a median of 14 days. Mortality at day 28 and end of follow-up was 3.3% and 6.6% respectively. Serious adverse events emerged only in one patient as hypoxemia after first CP infusion that although easily alleviated by conventional measures perturbated further CP administration. No association between anti-SARS CoV-2 anti-S1 antibody titer and survival or clinical status at any time-point or duration of hospital stay was noted; however, administration of CP with anti-S1 IgG above the 80th percentile was predictive of shorter duration of mechanical ventilation (HR: 3.36, 95%CI: 1.07-10.5, p: 0.04). The corresponding Kaplan-Meier curve is provided in Figure 1. The finding remained significant in a multivariate Cox regression analysis including age, sex, baseline SOFA score, and baseline percentage of pulmonary infiltrates in CT imaging. Image:Summary/Conclusion: CP can be administered safely to patients with severe COVID-19 without severe adverse events. Early administration of high-titer CP might be associated with an increased probability of earlier weaning from mechanical ventilation of intubated patients with COVID-19. Validation of this finding in larger cohorts is needed.