Convalescent donor plasma to treat patients with severe SARS-CoV-2 infection (COVID-19)

Abstract

The pandemia caused by the virus SARS-CoV-2 is spreading rapidly around the world, and now reached Brazil. However, its magnitude and consequences are still unknown in this country. In this study, the authors intend to evaluate the impact of convalescent plasma transfusion on patients with severe COVID-19. The clinical picture of this disease is heterogenous, with most patients with mild disease, even asymptomatic, however, a minority of patients present severe clinical picture, with shortness of breath, which causes most of the deaths. There is no established specific treatment for COVID-19. A promising alternative is the transfusion of pre-formed antibodies against the virus, obtained from individuals' convalescent of COVID-19. This therapy provides immediate immunity, which could allow the organism the necessary time to mount an immune response against the aggressor (adaptive immunity). The first reports of this treatment modality were published almost a century ago in which the objective was to control illnesses as poliomyelitis, measles, mumps, and influenza. More recently, in 2009 and 2010, convalescent plasma was used to treat patients with severe H1N1 influenza, in which it was shown that the group of transfused (n= 20) presented lower mortality rate than that in non-transfused group (n= 73) (20.0% vs 54.8%; P = 0,01). The group of transfused patients had reduced viral load and inflammatory cytokines (IL-6, TNF±) on days 3, 5 and 7, inferior to that observed in the group of non-transfused patients (P < 0,05). The first outbreak of coronavirus SARS-CoV-2, which also originated in China, in 2002/2003, provided information regarding the feasibility of using convalescent plasma, in which it was identified neutralizing antibodies against the virus. The second coronavirus outbreak took place in Middle East in 2012 and afterwards in South Korea. In both outbreaks mortality rates were extremely high, which stimulated researchers from the affected countries to evaluate the efficacy of convalescent plasma. In one study, 80 patients with severe acute respiratory syndrome (SARS) caused by coronavirus were treated with plasma, with a more favorable outcome in transfused patients. Plasma from convalescent donor was harvested on the seventh day of recovery, a period sufficient to allow the production of high titres of antibodies. A recent meta-analysis suggested that transfusion of convalescent reduced mortality in patients with SARS caused by coronavirus influenza. The authors identified 32 publications, most of them of low methodological quality and high risk of bias. The hypothesis is that transfusion of convalescent plasma of COVID-19 could improve clinical outcomes and increase survival rate in patients with severe disease. Forty patients will be treated with convalescent plasma, whose outcomes will be compared with those from a control group of 80 non-transfused patients with the same disease. Each patient is scheduled to receive a dose of 10 mL/kg/day of plasma (600 mL/day), for 3 consecutive days. The primary outcome is to compare survival rates on day 60 of randomizations between the two groups of patients with COVID-19, transfused and non-transfused. The most important secondary objectives were to evaluate of viral load in both groups, the influence of age on outcomes and the type and frequency of adverse reaction to plasma transfusion. (AU)