Anti-IgE monoclonal antibodies as potential treatment in COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) is associated with irreversible effects on vital organs, especially the respiratory and cardiac systems. While the immune system plays a key role in the survival of patients to viral infections, in COVID-19, there is a hyperinflammatory immune response evoked by all the immune cells, such as neutrophils, monocytes, and includes release of various cytokines, resulting in an exaggerated immune response, named cytokine storm. This severe, dysregulated immune response causes multi-organ damage, which eventually leads to high mortality. One of the most important components of hypersensitivity is immunoglobulin E (IgE), which plays a major role in susceptibility to respiratory infections and can lead to the activation of mast cells. There is also a negative association between IgE and IFN-α, which can reduce Toll-like receptor (TLR) nine receptor expression and TLR-7 signaling to disrupt IFN production. Moreover, anti-IgE drugs such as omalizumab reduces the severity and duration of COVID-19. In addition to its anti-IgE effect, omalizumab inhibits inflammatory cells such as neutrophils. Hence, blockade of IgE may have clinical utility as an immunotherapy for COVID-19.

Impact of Anti-Type 2 Inflammation Biologic Therapy on COVID-19 Clinical Course and Outcome

“…During respiratory viral infections, the production of specific IgE against different viruses has been reported, and IgE may contribute in the immune response to these infections at later stages, maybe by activating mast cells and basophils and/or by modulating the production of pro-inflammatory cytokines, such as TNF-α and IL-6. 53 , 55 , 56 Anti-IgE therapy may be effective in this regard, considering the effect on mast cells and basophils production and activation. 57 , 58 Actually, eosinophils may also have a direct role in COVID-19-related inflammation.…”

Therapeutic antibodies for COVID-19: is a new age of IgM, IgA and bispecific antibodies coming?

“… 112 Lanadelumab Human IgG1κ - Plasma kallikrein - Phase 1/2/3 (NCT04422509, etc.) 113 Omalizumab Humanized IgG1κ Mouse IgE - Phase 2 (NCT04720612) 114 ADE, antibody-dependent enhancement; CCR5, C-C chemokine receptor type 5; EU, European Union; EUA, Emergency Use Authorization; FcγR, Fc receptor γ chain; huIg, humanized immunoglobulin; mAb, monoclonal antibody; NTD, N-terminal domain; pt(s), patient(s); RBD, SARS-CoV-2 receptor-binding domain; S. Korea, South Korea; Ref., reference(s); Tc, transchromosomic; UK, United Kingdom. a EUA, emergency use authorization.…”

Effectiveness and durability of the mRNA vaccine-induced SARS-CoV-2-specific humoral and cellular immunity in severe asthma patients on biological therapy

“…IgE antibodies are also important for cross-talk between innate and adaptive immunity and play a role in susceptibility to respiratory infections ( 42 ) and antiviral responses ( 43 ). As such, anti-IgE monoclonal antibodies were suggested as a potential treatment in COVID-19 to enhance the antiviral responses to the virus ( 44 ). Mepolizumab and reslizumab (anti-IL5 therapy) bind to IL-5 and therefore stop IL-5 from binding to its receptor on the surface of eosinophils.…”