Role of Convalescent Plasma Therapy in Patients with Moderate to Severe COVID 19

Significance: Given the lack of evidence of effective treatments and vaccines for Corona virus disease-19(COVID-19), several treatment options are under investigation, including Convalescent Plasma. The FDA granted emergency use authorization (EUA) on August 23, 2020 for use of convalescent plasma in hospitalized patients with COVID-19 but further data from randomized clinical trials are needed. Objective: The objective of the study was to find evidence of efficacy of Convalescent Plasma therapy in patients with moderate to severe COVID-19. Study Design, Setting, and Sample size: Open label, observational study, where participants were allocated using predefined assessment criteria. The study included 42 patients admitted in Fatima Memorial Hospital, Lahore with moderate to severe COVID-19. The study was terminated early after 42 patients of a planned sample size of 50 patients due to no further admissions of COVID-19 in the hospital. Groups: Standard treatment for COVID-19 disease (antibiotics, steroids, Tocilizumab, Remdesivir) according to disease severity was given in 15 patients (control group), while Convalescent plasma was administered in addition to standard treatment in 27 patients (cases). Primary and Secondary Outcomes: Primary outcome was to see clinical improvement in patients with moderate to severe COVID-19, defined as patient recovered and discharged home. Secondary outcomes looked at oxygen requirement in both cases and controls after administration of treatment and any improvement in biochemical markers. Results: 42 patients were observed in the study. 27 patients assigned to the cases group received standard treatment and convalescent plasma therapy for moderate to severe Covid-19 disease whilst 15 patients received standard treatment only, assigned as control group. The median age of patients in the convalescent plasma group was 59.81±10.14 and 54.37 ±12.93 in the control group (p-value = 0.086). There was no statistically significant difference in baseline characteristics between the cases and control group. Primary outcome measured as patient recovered and discharged home was achieved in 64.3% of patients in the cases group and 35.7% in the control group (p value = 1). Secondary outcome compared oxygen requirements in cases (median 20 l/min) and controls (median 8 l/min) after treatment. There was no statistically significant difference in oxygen requirements between cases and controls after treatment (p=0.059). Biochemical markers of inflammatory response such as Total leukocyte count, D-dimer, Lactate dehydrogenase (LDH) did not show any statistically significant difference in the two groups. CRP however decreased markedly in those patients treated with Convalescent plasma in addition to standard treatment when compared with control group (p value= 0.002). Also, serum Ferritin was also found to be much lower in cases as compared to controls (p value = 0.001). No adverse effects were seen in the cases after administration of convalescent plasma. Conclusion: Convalescent Plasma therapy administered in addition to standard treatment did not result in a statically significant improvement in patient survival in patients with moderate to severe COVID-19 when compared with standard treatment alone. There was however, a significant reduction in two inflammatory markers associated with severe disease i.e. C-reactive protein (CRP) and serum Ferritin in the cases group. The study results may have failed to detect a clinically significant difference because of early termination of the study resulting in small sample size.