Clin Exp Pediatr.  2020 Jul;63(7):239-250. 10.3345/cep.2020.00759.

Immunopathogenesis of COVID-19 and early immunomodulators

• Lee KY
• Rhim JW
• Kang JH

• KMID: 2504489
• DOI: http://doi.org/10.3345/cep.2020.00759

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 protein-homeostasis-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.

Keyword

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