Antibody-Dependent Enhancement and the Critical Pattern of COVID-19: Possibilities and Considerations

Abstract

Coronavirus disease 2019 (COVID-19), a pandemic infection with profound effects on human society, has been emerged recently and rigorously challenged our ability to control viral infections. Although at the beginning of the COVID-19 outbreak, the epidemic seems controllable in Southern Iran, the disease presents a critical pattern as of May 2020. After a few months of COVID-19 emergence, in a twisted turn of events, the severity and mortality of COVID-19 increased dramatically. It has been proposed that the antibodies obtained from previous exposure to local circulating human coronaviruses or possibly SARS-CoV-2 might contribute to the development of more severe and lethal presentations of COVID-19 possibly by triggering antibody-dependent enhancement. The binding of virions complexed with antibodies to Fcγ receptors on the target cells initiates receptor-mediated signaling events leading to enhanced expression of inflammatory cytokines and suppression of intracellular antiviral responses at the transcriptomic level, followed by endocytosis of the virus and subsequent activation of immune cells. The activated immune cells might accumulate in the lung and promote cytokine storm and lymphopenia. Furthermore, the formation of immune complexes can promote complement activation and subsequent tissue damage. Although there are currently no clinical data to support this hypothesis, a better understanding of these immunopathologic phenomena and their relation to disease course and severity might give insight into the development of the most efficient prophylactic and therapeutic approaches. This review demonstrates the critical pattern of COVID-19 in Southern Iran and highlights the possible interplaying factors leading to this condition.

Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants

“…One of the oldest polyclonal approaches dating back to the late nineteenth century, known as hyperimmune equine serum therapy, has also been used in efforts to treat COVID-19. For this approach, IgG from horses immunized with SARS-CoV-2 spike protein were collected, proteolytically cleaved to F(Ab′) 2 fragments to reduce immunogenicity as well as to minimize potential adverse effects (such as antibody dependent enhancement, or ADE [ 196 ] (see also Sect. 4.3.2 ), and used to treat COVID-19 patients [ 5 – 7 ].…”

“…Both antibodies possess the “TM” triple mutations L234F/L235E/P331S described by Oganesyan et al [ 420 ] to decrease their binding to human FcγRI, FcγRIIa, FcγRIIIa, and C1q, resulting in reduced ADCC, ADCP, and complement-dependent cytotoxicity (CDC). These mutations also reduce the theoretical risk of ADE [ 196 ]. Additionally, both antibodies have the M252Y/S254T/T256E “YTE” modification [ 421 ] in their Fc to extend their half-life in circulation (called “LAAB, long-acting antibody”).…”

COVID-19 in Dental Practice Is Prevented by Eugenol Responsible for the Ambient Odor Specific to Dental Offices: Possibility and Speculation

“…When SARS-CoV-2 enters human cells, its spike protein plays a critical role by binding to angiotensin-converting enzyme 2 (ACE2) on host cells [ 43 ]. The SARS-CoV-2 spike protein is composed of two subunits S1 and S2; S1 contains a receptor-binding domain, which recognizes and binds to ACE2 [ 44 ]. Molecular docking analysis indicated that eugenol interacts with the SARS-CoV-2 spike protein as a possible ligand [ 45 ].…”

From Detection to Protection: Antibodies and Their Crucial Role in Diagnosing and Combatting SARS-CoV-2

“…However, the emergence of highly contagious variants continues to diminish the efficacy and utility of the available vaccines and antibody-based treatments against these new variants. Additionally, the phenomenon of antibody-dependent enhancement (ADE), defined by the possible post-infection or post-vaccination entry of immune complexes into cells with Fc receptors, as observed previously during pre-clinical studies of SARS-CoV and MERS-CoV vaccine development, has been a significant concern for the advancement of COVID-19 vaccines [31,32]. Since the onset of the pandemic, the approaches to diagnosing, treating, and vaccinating against COVID-19 have continually evolved, driven by the emergence of novel virus variants worldwide, and antibodies targeting SARS-CoV-2 have been instrumental in shaping these strategies.…”