Immunopathogenesis of COVID-19 and early immunomodulators

Abstract

The novel coronavirus disease 2019 (COVID-19) is spreading globally. Although its etiologic agent is discovered as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), there are many unsolved issues in COVID-19 and other infectious diseases. The causes of different clinical phenotypes and incubation periods among individuals, species specificity, and cytokine storm with lymphopenia as well as the mechanism of damage to organ cells are unknown. It has been suggested that in viral pneumonia, virus itself is not a direct cause of acute lung injury; rather, aberrant immune reactions of the host to the insults from viral infection are responsible. According to its epidemiological and clinical characteristics, SARS-CoV-2 may be a virus with low virulence in nature that has adapted to the human species. Current immunological concepts have limited ability to explain such unsolved issues, and a presumed immunopathogenesis of COVID-19 is presented under the proteinhomeostasis-system hypothesis. Every disease, including COVID-19, has etiological substances controlled by the host immune system according to size and biochemical properties. Patients with severe pneumonia caused by SARS-CoV-2 show more severe hypercytokinemia with corresponding lymphocytopenia than patients with mild pneumonia; thus, early immunomodulator treatment, including corticosteroids, has been considered. However, current guidelines recommend their use only for patients with advanced pneumonia or acute respiratory distress syndrome. Since the immunopathogenesis of pneumonia may be the same for all patients regardless of age or severity and the critical immune-mediated lung injury may begin in the early stage of the disease, early immunomodulator treatment, including corticosteroids and intravenous immunoglobulin, can help reduce morbidity and possibly mortality rates of older patients with underlying conditions.

Keywords: COVID-19; Corticosteroids; Intravenous immunoglobulin; Pathogenesis; Protein-homeostasis-system hypothesis.

Fig. 1.

A presumed pathogenesis of acute lung injury in the novel coronavirus disease 2019 (COVID-19). During the incubation period, the severe acute respiratory syndrome coronavirus-2 virus replicates within certain host cells and numerous substances are produced, including replicated virions, pathogen-origin substances such as pathogen-associated molecular patterns and by-products, and host cell-origin substances such as damage (danger)-associated molecular patterns, immune proteins, pathogenic proteins, and pathogenic peptides. These substances spread via the local or systemic circulation when infected cells are destroyed (A). Among these substances, pathogenic peptides or other substances bind to the receptors on target lung cells, which can be directly toxic to the target cells or signal to immune cells via other proteins produced by the target cells (B). First, activation of nonspecific T cells and other immune cells and/or an aberrant cytokine imbalance induces target-cell injury. Then, substances from injured lung cells and the subsequent bacterial invasion induce further inflammation with corresponding activation of immune cells and immune proteins (C). Once specific T-cell and B-cell clones (specific antibodies) appear to control pathogenic proteins and peptides, the tissue injury ceases. The specific immune cell responses to cellular injury may be delayed or absent in some patients with COVID-19, leading to chronic lung diseases, other organ diseases, or even death. NK, natural killer.