The Road towards Polyclonal Anti-SARS-CoV-2 Immunoglobulins (Hyperimmune Serum) for Passive Immunization in COVID-19

Abstract

Effective treatments specific for COVID-19 are still lacking. In the setting of passive immunotherapies based on neutralizing antibodies (nAbs), randomized controlled trials of COVID-19 convalescent plasma (CCP) anti-SARS-CoV-2 Spike protein monoclonal antibodies (mAb), which have been granted emergency use authorization, have suggested benefit in early disease course (less than 72 hours from symptoms and seronegative). Meanwhile, polyclonal immunoglobulins (i.e., hyperimmune serum), derived either from CCP donations or from animals immunized with SARS-CoV-2 antigens, are likely to become the next nAb-derived candidate. We here discuss the pros and cons of hyperimmune serum versus CCP and mAb, and summarize the ongoing clinical trials of COVID-19 hyperimmune sera.

Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review

“…New emerging evidence has confirmed the worldwide presence of three main SARS-Cov-2 variants, 501Y.V1 (B.1.1.7), 501Y.V2 (B.1.351) and 501Y.V3 (P.1) respectively identified in The United Kingdom, South Africa and Brazil, which show immune escape thus, raising doubts about their influence on the effectiveness of current vaccines and hyper-immune serum. Hyper-immune serum obtained from the plasma of patients who had COVID-19 or animals, thereby inoculated with SARS-CoV-2 antigens, has been also authorized to successfully treat COVID-19 patients showing benefits in asymptomatic or symptomatic patients within three days [ 104 , 105 ]. Interestingly, the 501Y.V2 (B.1.351) viral variant confers partial to complete resistance to hyper-immune serum and reduces the efficacy of the AZD1222 vaccine [ 92 ] and sera from Pfizer-BioNTech and Moderna subjects displayed considerably decreased effects on 501Y.V2 [ 106 ].…”

Hyperimmune anti-COVID-19 IVIG (C-IVIG) treatment in severe and critical COVID-19 patients: A phase I/II randomized control trial

“…Coronavirus disease 2019 (COVID- 19) was declared as a pandemic by the World Health Organization on March 11, 2020 [1]. It is a systemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).…”

“…Intravenous immunoglobulin (IVIG), has been used as a therapeutic agent against a variety of inflammatory, infectious, autoimmune, and viral diseases including SARS and Middle East respiratory syndrome (MERS) [5,6]. This study explores Hyperimmune anti-COVID- 19 Intravenous Immunoglobulin (C-IVIG), prepared using pooled high titer convalescent plasma (cut-off index >10) obtained from COVID-19 recovered individuals [7]. C-IVIG when infused in COVID-19 patients, is expected to regulate disease progression via multiple mechanisms including SARS-CoV-2 neutralization, immunomodulation to prevent cytokine storm, and prevention of superimposed bacterial infection (sepsis) due to presence of polyclonal antibodies against other endemic pathogens [8,9,10].…”

Potential use of convalescent plasma for SARS-CoV-2 prophylaxis and treatment in immunocompromised and vulnerable populations

“…The level of protection from commercial aspecific IVIg batches manufactured from plasma donations collected after January 2020 remains to be established. In addition, a number of trials are currently exploring the beneficial effect of specific polyclonal anti-SARS-CoV-2 IVIg [8]. It is important to underline, however, that the production of specific immunoglobulins requires significant investments by the manufacturing companies which take years to recover.…”

“…Similarly, monoclonal antibodies (mAb) have been proven effective when administered early in the disease course and in seronegative recipients [7], but their cost and availability remain severe hurdles. Clinical trials with hyperimmune serum, an industrial derivative of CCP or derived from immunized animals, are still ongoing [8], but to date no experience has been reported in immunocompromised patients. The absolute requirement for early treatment in frail immunocompromised patients is still questioned, leaving hopes for benefit also in late usages [9]: accordingly, many case reports and series have documented success of CCP in late COVID19 stages in such patients.…”