Efficacy and safety of convalescent plasma and intravenous immunoglobulin in critically ill COVID-19 patients. A controlled clinical trial
Background The proportion of critically ill COVID-19 patients has collapsed hospital care worldwide. The need for alternative therapies for this group of patients is imperative. This study aims to compare the safety and efficacy of convalescent plasma (CP) compared with human immunoglobulin (IVIg) in patients requiring the administration of high oxygen levels or mechanical ventilation.
Methods This is a controlled, randomized, open clinical trial of patients with pneumonia secondary to SARS-CoV-2 infection, that fulfilled criteria for severe or critical disease. They were randomized in a 1:2 ratio; group 1 was administered IVIg at a dose of 0.3 grams per kilogram of ideal weight, in an 8-hour infusion every 24 hours, for 5 days. Group 2 was administered 200 ml of CP infused in 2 hours, for 2 days. The primary outcomes were duration of hospitalization and mortality at 28 days.
Results: One hundred and ninety (190) patients were randomized; 130 to the CP group, and 60 to the IVIg group. Their average age was 58 years (IQR 47 -72), and most were male (n= 119, 62.6 %). On inclusion, 85.2 % of patients (n=162) were on invasive mechanical ventilation therapy. Overall mortality in all included patients was 53 % (n= 102), with a median follow-up of 14 days (IQI 8 -26). Mortality at 28 days was 45.2 % (n=86). In the intention-to-treat analysis, there was no difference between groups neither in mortality on follow-up (53.8 vs. 53.3, p =1.0) nor at 28 days (46.2 vs 43 %, p=0.75, Log Rank p = 0.83). Per-protocol analysis between treatment groups revealed no difference in mortality throughout hospitalization (51.5 vs 51.4 %, p=1.0) nor after 28 days (42.1 vs 42.87 %, p=0.92 Log Rank p = 0.54). Only 23 patients in the CP group received plasma with detectable anti-SARS-CoV-2 antibodies.
Conclusions: In critically ill patients or on invasive mechanical ventilation for treatment of Covid-19, the use of CP is not superior to IVIg in terms of hospitalization duration or mortality. The use of CP is based on complex logistics and requires an assured level of antibodies if used therapeutically. IVIg does not appear to be useful in this group of patients. clinicaltrials.gov identifier: NCT04381858.
Agarwal, Mukherjee, Kumar, Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomized controlled trial (PLACID Trial), BMJ
Arabi, Hajeer, Luke, Feasibility of using convalescent plasma immunotherapy for MERS-CoV infection, Saudi Arabia, Emerg Infect Dis
Barrett, Moore, Yaffe, ISTH interim guidance on recognition and management of coagulopathy in COVID-19: A comment, J Thromb Haemost
Beigel, Tomashek, Dodd, Remdesivir for the treatment of Covid-19 -final report, N Engl J Med
Cantini, Niccoli, Nannini, Beneficial impact of Baricitinib in COVID-19 moderate pneumonia; multicentre study, J Infect
Gharebaghi, Nejadrahim, Mousavi, The use of intravenous immunoglobulin gamma for the treatment of severe coronavirus disease 2019: a randomized placebo-controlled doubleblind clinical trial, BMC Infect Dis
Horby, Lim, Dexamethasone in Hospitalized Patients with Covid-19 -Preliminary Report, N Engl J Med, doi:10.1056/NEJMoa2021436
Hung, To, Lee, Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection, Clin Infect Dis
Kalil, Patterson, Mehta, Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19, N Engl J Med
Kruse, Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China
Li, Zhang, Hu, Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: A Randomized Clinical Trial, JAMA
Libster, Marc, Wappner, Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults, N Engl J Med, doi:10.1056/NEJMoa2033700
Mair-Jenkins, Saavedra-Campos, Baillie, The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis, J Infect Dis
Metlay, Waterer, Long, Diagnosis and Treatment of Adults with Communityacquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America, Am J Respir Crit Care Med
Simonovich, Pratx, Scibona, A randomized trial of convalescent plasma in Covid-19 severe pneumonia, N Engl J Med, doi:10.1056/NEJMoa2031304
Tabarsi, Barati, Jamaati, Evaluating the effects of Intravenous Immunoglobulin (IVIg) on the management of severe COVID-19 cases: A randomized controlled trial, Int Immunopharmacol
Van Griensven, Edwards, De Lamballerie, Evaluation of convalescent plasma for Ebola virus disease in Guinea, N Engl J Med
Wiersinga, Rhodes, Cheng, Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review, JAMA
Woolf, Chapman, Lee, COVID-19 as the leading cause of death in the United States, JAMA
Xie, Cao, Dong, Effect of regular intravenous immunoglobulin therapy on prognosis of severe pneumonia in patients with COVID-19, J Infect
Zhai, Li, Chen, Prevention and Treatment of Venous Thromboembolism Associated with Coronavirus Disease 2019 Infection: A Consensus Statement before Guidelines, Thromb Haemost