As many parts of the world continue to fight the innumerable waves of COVID-19 infection, SARS-CoV-2 continues to sculpt its antigenic determinants to enhance its virulence and evolvability. Several vaccines were developed and used around the world, and oral antiviral medications are being developed against SARS-CoV-2. However, studies showed that the virus is mutating in line with the antibody’s neutralization escape; thus, new therapeutic alternatives are solicited. We hereby review the key role that miRNAs can play as epigenetic mediators of the cross-talk between SARS-CoV-2 and the host cells. The limitations resulting from the “virus intelligence” to escape and antagonize the host miRNAs as well as the possible mechanisms that could be used in the viral evasion strategies are discussed. Lastly, we suggest new therapeutic approaches based on viral miRNAs.

A large variety of therapeutic products have been developed as vaccines or treatments of COVID-19 infection. Meanwhile SARS-CoV-2 continues to mutate and spread. The severe COVID-19 patients have limited treatment options. Therefore, mesenchymal stem cells (MSCs) are proposed as another therapeutic target. They are known for their regenerative and immunomodulatory properties. They showed potent efficacy and safety abilities for the treatment of critical COVID-19 patients and intriguing benefits in reducing lungs damage, mortality, and cytokine storm in several clinical studies. Another promising treatment option is the use of dental pulp stem cells (DPSCs) to combat SARS-CoV-2, despite the fact that detailed therapeutic strategies and mechanisms are still lacking. In this review we shed light on the immune response against COVID-19 infection and the relevant knowledge considering the role of MSCs in innate and adaptive immune responses to better understand the immunophysiological mechanisms of MSCs treatment. Lastly, we summarize the latest progress in clinical and research studies suggesting potential MSCs/DPSCs as therapeutic targets in battling COVID-19.