Muhammad Hasan, Mohammad Usman Shaikh, Muhammad Jehangir Malik, Bushra Jamil, Nosheen Nasir, Kiren Habib, Adil Aziz, Iffat Khanum, Aisha Ilyas, Ramla Ghafoor, Saeed Hamid, Anila Anjum, Natasha Ali*, Faisal Mahmood
Introduction: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred initially in December 2019 in the city of Wuhan, Hubei province, China where patients mainly presented with respiratory symptoms. In Pakistan the first case was identified on February 26, 2020 and since then Aga Khan University Karachi is at the forefront of the fight against COVID-19. After receiving all required approvals, this trial was undertaken to determine safety and efficacy of transfusing Convalescent Plasma (CP) in patients admitted with COVID-19.
Methods: This was a non-randomized, open label, phase II clinical trial with 110 cases and 34 controls recruited during April 2020 till July 2020. Convalescent plasma donors and patients who received it were recruited using donor eligibility criteria issued by U.S. Department of Health and Human Services Food and Drug Administration. All donors were screened for transfusion transmitted diseases and tested for SARS-CoV-2 infection by rRT-PCR. Documentation of IgG antibody in donors was done through Novel Coronavirus COVID-19 IgG ELISA Kits. Patients in the intervention group received 500 ml of CP along with concomitant therapies. Patients in the control group received concomitant therapies only. Outcome measures included assessment of safety, decreased length of stay and decrease in values of inflammatory makers (CRP, D-Dimer, procalcitonin, serum ferritin).
Results: We recruited 96 males and 48 females during the study period. The median age was 60.2 years. Age was found to be a significant prognostic marker in both groups as patients less than 60 years had increased overall survival (hazard ratio: 0.33, p-value: 0.001). Presence of two or more co-morbidities provided disadvantage to the overall outcome. Survival was increased by 10 days in patients who received plasma as compared to controls. However, it was not significant. The overall survival in cases was 68% while in controls it was 62%. There was an improvement seen in all inflammatory markers after transfusion of convalescent plasma in cases. Use of concomitant therapies e.g. tocilizumab (hazard ratio: 1.09, 95% CI: 0.54-2.23) and methylprednisolone (hazard ratio: 1.3, 95% CI: 0.6-2.88) did not affect overall survival. There was no serious adverse event reported after transfusion of convalescent plasma.
Conclusion: Transfusion of CP was found to be safe as no adverse event was reported. There was a significant decrease in the inflammatory marker levels in cases. There was no significant difference in length of stay and overall survival in both groups.