Mesenchymal Stem Cells as a Promising Cellular Anti-COVID-19 Therapy for Diffuse Large B Cell Lymphoma Patients affected by Severe SARS-CoV-2

Introduction

Cancer patients are at an 17.9% increased risk for severe SARS-CoV-2 due to their immunocompromised status. While patients with active cancer had worse outcomes, those in remission had an increased risk for severe disease compared to COVID-19 patients without malignancy. Given that the intricate relationship between cancer and severe COVID-19 remains elusive, we developed a model to explain the pathogenesis and interplay between the two conditions and explain the efficacy of a promising cell therapy against severe SARS-CoV-2 with clinical support.

Methods

Severe SARS-CoV-2 causes multi-organ injury and dysfunction through IL-6-mediated inflammation and hypoxic-induced metabolic changes leading to increased IL-6 production and apoptosis. This mechanism exacerbates the severity of Diffuse Large B Cell Lymphomas (DLBCL) by capitalizing on IL-6’s dual role as a growth factor and negative prognostic marker, intensifying disease progression via STAT3 signaling.

Results

In this model, co-occurence with severe SARS-CoV-2 and DLBCL induces a pro-inflammatory state with enhanced IL-6 secretion. This synergy increases cytokine production fostering greater systemic injury as compared to either alone.

Currently, there are limited effective therapeutic interventions against severe SARS-CoV-2 especially in the immunocompromised. Given the virus’s complex nature, single agents therapies have had limited efficacy in controlling viral replication and systemic inflammation. However, mesenchymal stem cells (MSCs), which possess regenerative, antiviral, and immunomodulatory properties, have demonstrated efficacy in clinical trials with a 91% overall survival and 100% survival in patients younger than 85 years old for over 6 months.

Conclusion

MSCs were found to be safe and well tolerated in patients with severe SARS-CoV-2, while demonstrating clinical efficacy and improved survival. Targeting disease pathogenesis at multiple steps within the pathway, while inhibiting viral replication and inflammation, MSCs are a promising therapy to thwart the virus’s heterogeneity and mutational adaptations. Given their limited drug interactions and side-effects, MSCs are a viable approach in those with malignancy to contain SARS-CoV-2 with limited interruptions to their treatment regimens.