Dow College of Biotechnology, Dow University of Health Sciences - Ojha Campus, Karachi, Pakistan. Sindh Infectious Disease Hospital and Research Center, Karachi, Pakistan. Dow Research Institute of Biotechnology and Biomedical Sciences, Dow University of Health Sciences - Ojha Campus, Karachi, Pakistan. Dow University Hospital, Dow University of Health Sciences - Ojha Campus, Karachi, Pakistan. National Control Laboratory for Biologicals, Islamabad, Pakistan. Department of Research, Dow University of Health Sciences, Karachi, Pakistan. Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan. Dow University of Health Sciences - Ojha Campus, Karachi, Pakistan.
BACKGROUND Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG) is an unexplored therapy amidst the rapidly evolving spectrum of medical therapies for COVID-19 and is expected to counter the three most life-threatening consequences of COVID-19 including lung injury by the virus, cytokine storm and sepsis. METHODS A single center, phase I/II, randomized controlled, single-blinded trial was conducted at Dow University of Health Sciences, Karachi,
Pakistan. Participants were COVID-19 infected individuals, classified as either severely or critically ill with Acute Respiratory Distress Syndrome (ARDS). Participants were randomized through parallel-group design with sequential assignment in a 4:1 allocation to either intervention group with four C-IVIG dosage arms (0.15, 0.20, 0.25, 0.30 g/kg), or control group receiving standard of care only (n = 10). Primary outcomes were 28-day mortality, patient's clinical status on ordinal scale and Horowitz index (HI), and were analysed in all randomized participants that completed the follow-up period (intention-to-treat population). The trial was registered at clinicaltrials.gov (NCT04521309). FINDINGS Fifty participants were enrolled in the study from June 19, 2020 to February 3, 2021 with a mean age of 56.54±13.2 years of which 22 patients (44%) had severe and 28 patients (56%) had critical COVID-19. Mortality occurred in ten of 40 participants (25%) in intervention group compared to six of ten (60%) in control group, with relative risk reduction in intervention arm I (RR, 0.333; 95% CI, 0.087-1.272), arm II (RR, 0.5; 95% CI, 0.171-1.463), arm III (RR, 0.167; 95% CI, 0.024-1.145), and arm IV (RR, 0.667; 95% CI, 0.268-1.660). In intervention group, median HI significantly improved to 359 mmHg [interquartile range (IQR) 127-400, P = 0.009)] by outcome day, while the clinical status of intervention group also improved as compared to control group, with around 15 patients (37.5%) being discharged by 7th day with complete recovery. Additionally, resolution of chest X-rays and restoration of biomarkers to normal levels were also seen in intervention groups. No drug-related adverse events were reported during the study. INTERPRETATION Administration of C-IVIG in severe and critical COVID-19 patients was safe, increased the chance of survival and reduced the risk of disease progression. FUNDING Higher Education Commission (HEC), Pakistan (Ref no. 20-RRG-134/RGM/R&D/HEC/2020).