Pathogenic antibodies induced by spike proteins of COVID-19 and SARS-CoV viruses

Abstract

This study, using a virus-free mouse model, explores the pathogenic roles of certain antibodies specific to the spike proteins of highly pathogenic coronaviruses such as the COVID-19 and the SARS-CoV viruses. Our data showed that these pathogenic antibodies, through a mechanism of Antibody Dependent Auto-Attack (ADAA), target and bind to host vulnerable cells or tissues such as damaged lung epithelium cells, initiate a self-attack immune response, and lead to serious conditions including ARDS, cytokine release, and death. Moreover, the pathogenic antibodies also induced inflammation and hemorrhage of the kidneys, brain, and heart. Furthermore, the pathogenic antibodies can bind to unmatured fetal tissues and cause abortions, postpartum labors, still births, and neonatal deaths of pregnant mice. Novel clinical interventions, through disrupting the host-binding of these pathogenic antibodies, can be developed to fight the COVID-19 pandemic. In addition, the new concept of ADAA explored by this study may be applicable to other infectious diseases, such as the highly pathogenic influenza infections. It should be noted that the majority of anti-spike antibodies are non-pathogenic, as only 2 of 7 monoclonal antibodies tested showed significant pathogenic effects.

A drug candidate for treating adverse reactions caused by pathogenic antibodies inducible by COVID-19 virus and vaccines

“…In addition, a recent study reported that some pregnant females with mRNA COVID-19 vaccinations suffered from miscarriages (Shimabukuro et al, 2021). This observation is consistent with our recent results that certain anti-spike antibodies derived from COVID-19 infected patients induced abortion, still birth, and neonatal death of pregnant mice (Wang et al, 2021). Therefore, a treatment capable of blocking the binding of pathogenic antibodies to host cells will be effective for the ADAA-based diseases, including adverse reactions of vaccines.…”

“…During an infection of a virus with RDE, the terminal sialic acids on cell surfaces can be removed, and the cellular structures become "non-self" (Schauer and Kamerling, 2018) (Figure 4A). Our recent study has shown that damaged lung epithelium cells with missing sialic acid are particularly vulnerable to pathogenic antibodies of the COVID-19 virus (Wang et al, 2021 autoimmune reactions (ADAA) caused by pathogenic antibodies. These autoimmune reactions are not minor side effects of the infection, but rather can be the main contributors to the severity of an infection and can lead to serious clinical conditions including ARDS, cytokine storms, and even death.…”

“…Treatment for the adverse reactions of vaccines will be helpful in eliminating the concerns about the COVID-19 vaccines' safety and will help promote the increased vaccination globally. Our recent study reported a newly discovered pathogenic mechanism of COVID-19 infection, one that is induced by certain anti-spike antibodies of the COVID-19 virus (Wang et al, 2021). These antibodies are pathogenic in of themselves, and can target and bind to host vulnerable cells or tissues, initiate a self-attack immune response, and lead to serious clinical conditions including acute respiratory distress A drug candidate for treating adverse reactions caused by pathogenic antibodies inducible by COVID-19 virus and vaccines syndrome (ARDS), cytokine storms, and death (Wang et al, 2021).…”

“…We have termed this novel mechanism "Antibody Dependent Auto-Attack" (ADAA) in a recent article. Since anti-viral antibodies continue to exist for a period of time in recovered COVID-19 patients, certain pathogenic antibodies among them can induce the symptoms of long haulers (Wang et al, 2021). Given the similarities of antibodies inducible by COVID-19 vaccines, the pathogenic anti-spike antibodies, despite only being minority of the antibodies induced, provided a possible cause for the adverse reactions of COVID-19 vaccines.…”

“…After the loss of sialic acids the cellular structures become "non-self" (Schauer and Kamerling, 2018), which can activate immune responses. In a recent report, we have shown that damaged lung epithelium cells with missing sialic acid and human inflammatory tissues are particularly vulnerable to pathogenic anti-spike antibodies (Wang et al, 2021). During the COVID-19 infection, the sialic acid on lung epithelium cells can be removed by the receptor-destroying enzyme (RDE) of SARS-CoV-2 virus (Huang et al, 2015), that makes the damaged cells vulnerable to pathogenic antibodies.…”