Immune Dysfunction and Multiple Treatment Modalities for the SARS-CoV-2 Pandemic: Races of Uncontrolled Running Sweat?

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic threat with more than 11.8 million confirmed cases and more than 0.5 million deaths as of 3 July 2020. Given the lack of definitive pharmaceutical interventions against SARS-CoV-2, multiple therapeutic strategies and personal protective applications are being used to reduce the risk of high mortality and community spread of this infection. Currently, more than a hundred vaccines and/or alternative therapeutic regimens are in clinical trials, and some of them have shown promising results in improving the immune cell environment and controlling the infection. In this review, we discussed high-performance multi-directory strategies describing the uncontrolled deregulation of the host immune landscape associated with coronavirus disease (COVID-19) and treatment strategies using an anti-neoplastic regimen. We also followed selected current treatment plans and the most important on-going clinical trials and their respective outcomes for blocking SARS-CoV-2 pathogenesis through regenerative medicine, such as stem cell therapy, chimeric antigen receptors, natural killer (NK) cells, extracellular vesicular-based therapy, and others including immunomodulatory regimens, anti-neoplastic therapy, and current clinical vaccine therapy.

Keywords: COVID-19; adoptive cell-based therapy; anti-neoplastic regimen; cytokine storm; extracellular vesicles; immunomodulatory drugs; mesenchymal stem cells.

Figure 1

Multi-directive therapeutic intervention currently in clinical trials for combating SARS-CoV-2 pathogenesis. (A) Mesenchymal stem cell (MSC) and NK cell-based therapies for the treatment of SARS CoV-2 pathogenesis. Extracellular vesicles (EVs) derived from MSCs or modified exosomes containing antiviral/anti-inflammatory drugs or respective nucleic acid for therapeutic intervention to target cells. These cell-based or cell-derived therapeutic agents could modulate immune cell functions against SARS-CoV-2 infection. (B) Cytokine storm development is a central pandemic delinquent in SARS-CoV-2 infection. Certain immunomodulatory agents with excellent safety profiles or current anti-neoplastic interventions (D) may be considered for use in combination with antiviral drugs for the treatment of severe or critical COVID-19 cases. (C) Importantly, engineered immune cell receptors, including the chimeric antigen receptor (CAR) T-cell, NK cell therapy, offer new therapeutic approaches for SARS-CoV-2 infection. These immune cells collected from recovered patients offer an advantage as the majority of these cells have been primed with a viral antigen before collection and therefore transmit high proliferative efficiency and anti-viral efficacy.