Convalescent plasma therapy in COVID-19 critically ill patients during advanced phases of clinical trials and their preliminary results

Abstract

The objective of this study was to highlight the global scientific effort to fight the SARS-CoV-2, addressing the preliminary results of passive immunization through convalescent plasma. We performed a search at the major databases of interventional clinical trial protocols about the transfusion of convalescent plasma in patients with COVID-19, as well as, published articles (n≥25), using the following search strategy: [(COVID-19 OR SARS-CoV-2 OR nCoV-2019) AND (Convalescent plasma OR Plasma exchange) AND (Treatment OR Therapy)]. A total of 24 interventional clinical trial protocols (advanced in phases II-III, III, and IV) were included in this review, as well as three studies that had enough outcomes to evaluate the efficacy of convalescent plasma therapy for patients with COVID-19. All interventional clinical trial protocols applied approximately 500mL of convalescent plasma (from single or more donations) in hospitalized patients, mainly in patients with severe disease associated with standard therapy for COVID-19, and compared to placebo or standard therapy plus specific drugs. Most of interventional clinical trial protocols are multicenter, and the phase IV studies are recruiting at intercontinental centers of North America, Oceania, Europe, but most are recruiting center inside their own county. The three studies published reported similar approach of convalescent plasma intervention with decrease in length of stay, mortality, with less than 4% of adverse events, mainly for treating critical cases with life-threatening disease. All advanced clinical trials focused on convalescent plasma therapy in patients with COVID-19 hospitalized in severe conditions, and the preliminary results provide strong evidence for therapy for the COVID-19 patients.

The Rise of SARS-CoV-2 Variants and the Role of Convalescent Plasma Therapy for Management of Infections

“…Limitations of the studies include small sample sizes (maximum of 10 patients) and a lack of control patients (not treated with CPT) [ 88 ]. There is a need to determine the effectiveness of CPT for COVID-19 disease deployed during the pandemic, and clinical trials are ongoing that will provide data to justify (or otherwise) the use of CPT for COVID-19 patients [ 89 , 90 , 91 , 92 ].…”

“…A second challenge is the possibility of the preformed antibodies to inhibit the immune response of the host from responding adequately [ 93 ]. This can occur from antibodies passed on from mother to offspring, which can prevent infants from responding adequately to vaccination and is the reason vaccines administered earliest started at eight weeks postnatal [ 90 , 91 , 92 ].…”

“…Standard operating procedures for using convalescent whole blood and convalescent plasma among people with different diseases do not exist. Although studies to date support the safety and the efficacy of CPT to treat infectious diseases such as COVID-19 [ 92 , 93 , 94 ], uncertainty exists regarding the safety and efficacy of CPT therapy for people with infectious diseases. Although there is a theoretical reason to think that antibodies in the blood or plasma of individuals who have survived viral diseases can reduce the viral levels of severely ill patients, research regarding this is still ongoing [ 17 , 96 ].…”

“…CP transfusion is well tolerated by most patients, and improved clinical outcomes in severe cases of patients with COVID-19 are observed, although some adverse effects are also seen [ 98 ]. CPT has been used successfully for treating and reducing the mortality of people infected with South American hemorrhagic fevers, Ebola, SARS, MERS, Hantavirus infection, and COVID-19 [ 92 , 93 , 97 ].…”

“…IVIg immunomodulatory actions can lead to diminished cytokines, leukocyte adhesion molecules, Fc-gamma receptors (FcγRs), smothering pathogenic cytokine subsets, and killing pathogenic autoantibodies [ 107 , 115 , 116 ]. IVIg influences regulatory T-cells by inducing cyclo-oxygenase-2-dependent prostaglandin E2 production in dendritic cells [ 92 ].…”