Perspectives of Immune Therapy in Coronavirus Disease 2019

Abstract

The global fight against coronavirus disease 2019 (COVID-19) is largely based on strategies to boost immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent its severe course and complications. The human defence may include antibodies which interact with SARS-CoV-2 and neutralize its aggressive actions on multiple organ systems. Protective cross-reactivity of antibodies against measles and other known viral infections has been postulated, primarily as a result of the initial observations of asymptomatic and mild COVID-19 in children. Uncontrolled case series have demonstrated virus-neutralizing effect of convalescent plasma, supporting its efficiency at early stages of contracting SARS-CoV-2. Given the variability of the virus structure, the utility of convalescent plasma is limited to the geographic area of its preparation, and for a short period of time. Intravenous immunoglobulin may also be protective in view of its nonspecific antiviral and immunomodulatory effects. Finally, human monoclonal antibodies may interact with some SARS-CoV-2 proteins, inhibiting the virus-receptor interaction and prevent tissue injury. The improved understanding of the host antiviral responses may help develop safe and effective immunotherapeutic strategies against COVID-19 in the foreseeable future.

Keywords: Antibodies; COVID-19; Comorbidities; Convalescent Serum; Immunotherapy; Vaccination.

Fig. 1. Structure of SARS-CoV-2 and potential antibody targets.

SARS-CoV-2 has four major targets: the N protein covering the viral ribonucleic acid (RNA), the E protein encompassing the viral envelope, the M protein protruding from the cell membrane and the S protein that engages with the angiotensin-converting enzyme 2 receptor on host cells. Specific neutralizing IgG antibodies to N and S proteins, which are less prone to mutate, may provide successful host immunity; these are also potential targets for future vaccination strategies (A). Antibodies to E and M proteins, which often mutate, may not be protective against SARS-CoV-2. Cross-reactive antibodies which are generated in response to measles and other known viral vaccines may offer a degree of anti-SARS-CoV-2 protection (B). Intravenous immunoglobulin and neutralizing antibodies in convalescent serum may block the virus entry to host cells (C) and dampen hyperinflammation (D). SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2, N = nucleocapsid, E = envelope, M = membrane, S = spike.