Recent findings on the Coronavirus disease 2019 (COVID-19); immunopathogenesis and immunotherapeutics

Abstract

Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) is responsible for recent ongoing public health emergency in the world. Sharing structural and behavioral similarities with its ancestors [SARS and Middle East Respiratory Syndrome (MERS)], SARS-CoV-2 has lower fatality but faster transmission. We have gone through a long path to recognize SARS and MERS, therefore our knowledge regarding SARS-CoV-2 is not raw. Various responses of the immune system account for the wide spectrum of clinical manifestations in Coronavirus disease-2019 (COVID-19). Given the innate immune response as the front line of defense, it is immediately activated after the virus entry. Consequently, adaptive immune response is activated to eradicate the virus. However, this does not occur in every case and immune response is the main culprit causing the pathological manifestations of COVID-19. Lethal forms of the disease are correlated with inefficient and/or insufficient immune responses associated with cytokine storm. Current therapeutic approach for COVID-19 is in favor of suppressing extreme inflammatory responses, while maintaining the immune system alert and responsive against the virus. This could be contributing along with administration of antiviral drugs in such patients. Furthermore, supplementation with different compounds, such as vitamin D, has been tested to modulate the immune system responses. A thorough understanding of chronological events in COVID-19 contributing to the development of a highly efficient treatment has not figured out yet. This review focuses on the virus-immune system interaction as well as currently available and potential therapeutic approaches targeting immune system in the treatment of COVID-19 patients.

Keywords: Coronavirus disease-2019; Immune system; Immunotherapeutics; Severe acute respiratory syndrome Coronavirus-2; Treatment.

Fig. 1

Immunopathology of COVID-19. Numerous cells and molecules are involved in viral response during the infection by SARS-CoV-2. Neutrophils and macrophages are the first cellular members to start responses. Alveolar damage is caused primarily by crowded cell trafficking and hyaline membrane formation, leading to hypoxia. As the figure depicts briefly, clotting dysregulation has been detected in severe COVID-19 patients. Several mechanisms may contribute to immunothrombosis (e.g. elevated levels of pro-inflammatory cytokines). An interconnected and complex network of cells is activated during the acute phase. The most significant cytokines released by these members are illustrated. During the acute phase in alveoli, histological changes occur. Increase in the collagen synthesis and fibrin deposition is associated with hypoxic environments and makes tissues vulnerable to further injuries.

Fig. 2

Currently proposed methods to prevent or cure COVID-19. The first stage of a viral infection is the entry phase. SARS-CoV-2 infects the ACE2 and TMPRSS2 expressing cells. ACE2 and TMPRSS2 have been demonstrated to play a major role in opening the gates for this virus. The figure illustrates the proposed strategies in restricting virus entry. Blocking spike proteins by the means of monoclonal antibodies, employing soluble ACE2 as a competitive agent for normally expressed ACE2 on cells, hindering ACE2 itself or suppressing the TMPRSS2 from activating the spike protein are theoretically efficient strategies. Promoting immune response in the protective phase and downregulating it in the acute phase are established as the most effective approaches to minimize the complications caused by divergent immune responses. In addition, vaccination can boost the cytotoxic activity exerted by CD8+ T cells, which in turn prevents the body from manifesting advanced symptoms. Occluding the viral replication cycle in several phases is the basis for developing many anti-viral drugs. The normal process of vesicle formation, RNA polymerization, proteolysis, and assembly of viral compartments are crucial stages that have been targeted by anti-viral drugs.