TITLE:
COVID-19 Infection: The Virus and Its Origin, the Variants, the Immune Defense, the Multiorgan Autoimmune Reactions, and the Targeted Treatments
AUTHORS:
Vu Thuong Nguyen, Lawrence S. Chan
KEYWORDS:
COVID-19, Pathogenesis, Autoimmune, Mortality, ARDS, SARS-CoV-2, Origin, Delta Variant, Omicron Variant, Neutrophil, IgA, Neutrophil Adherence, Cytokine Storm, Dapsone, Methylprednisolone, Antithombotic, Treatment, Therapeutic Mechanism
JOURNAL NAME:
Advances in Infectious Diseases,
Vol.12 No.3,
September
30,
2022
ABSTRACT: Background: SARS-CoV-2, the virus responsible for the current COVID-19 infection pandemic, has caused substantial damage and negative impacts in the world, including physical sickness, mental illness, death, society lock down, work interruption, and productivity reduction. From the onset in early 2020, the pandemic has not yet totally subsided as of July 2022. Although great efforts have been made to understand the nature of this pandemic by the medical and scientific communities, a comprehensive review of this pandemic has not been reported. Purpose: We aimed to perform a thorough review of the subject in order to come to a better understanding of the origin of the virus, its mutations and their corresponding health effects, its pathophysiology, and its responses to therapeutic intervention. A more comprehensive set of data on these subject matters, if available, would give healthcare providers a valuable tool in formulating the best methods to respond to the current disease and prevent the disease from spreading in the future. Method: An extensive literature search on the subjects of COVID-19 was conducted regarding the possible origin of the viral pathogen, its evolutionary changes and health impacts, the world’s responses to COVID-19 and outcomes of their responses, and healthcare professional’s actions to understand and manage the disease and the results of their actions. To gather these data, websites of PubMed and Google Scholar were utilized for the search with the following keywords: Pandemic, COVID-19, coronavirus, SARS, SARS-CoV, SARS-CoV-2, origin, pathogenesis, and treatment. Results: Our review revealed data that points to an interesting autoimmune phenomenon where most seriously sick patients affected by COVID-19 were documented by an IgA-dominant immune response to the pathogen, along with a neutrophil-directed infiltration to the vital organ in the lung aveola, resulting in critical lung injury, leading to respiratory failure, multi-organ failure, and death. Surprisingly, this IgA-mediated and neutrophil-directed disease pattern is nearly identical to a group of IgA-mediated autoimmune skin diseases, such as dermatitis herpetiformis, IgA bullous dermatosis, and IgA pemphigus, which respond well to treatment by dapsone, a sulfone class of antibiotic/anti-inflammatory drug. Moreover, the usefulness of dapsone was supported by a small clinical study. In addition, systemic corticosteroid, a trusted anti-inflammatory medication, has been used in this pandemic with variable degrees of success. Conclusion: The data collected from our review of the subject, together with our prior search knowledge, compel us to conclude that the underlying pathophysiology that causes serious respiratory distress and multi-organ failure is most likely to be autoimmune in nature and that strategies to counter these multifacet autoimmune disorders would be the most valuable in life-saving. Specifically, we identified clinical and laboratory evidence pointing to IgA autoimmune reaction as a key factor that causes significant mortality in many patients. Accordingly, we proposed the utilization of a combination of dapsone, corticosteroid, and anti-thrombotic drugs in severely ill patients at the earliest point of the disease process. The autoimmune multi-organ syndrome may explain the pathogenesis of COVID-19 as well as Post-COVID conditions and may guide healthcare professionals in a better direction to manage the disease. The possible origin of the viral pathogen may shed light on a better understanding of the pathogenesis of the disease.