Navigating the Intersection of Multiple Myeloma and Severe Sars-Cov-2: Therapeutic Insights from Exosomal Vesicles

Introduction During the early phase of the pandemic, COVID-19 patients with multiple myeloma (MM) exhibited a 56% hospitalization rate, with 20% requiring critical care, and an 18% increased risk of death. MM patients with symptomatic COVID-19 infections undergoing anticancer therapy showed a 55% higher risk of mortality. Even in the post-pandemic world, MM patients remain at heightened risk for severe SARS-CoV-2 infections due to their immunocompromised status. In this study, we (1) developed a model to explain the pathogenesis and interplay between MM and severe SARS-CoV-2, and (2) explained the efficacy and therapeutic potential of exosomal vesicles (EVs) as a therapeutic intervention against severe SARS-CoV-2 supported by clinical evidence. Methods Severe SARS-CoV-2 infection triggers multi-organ dysfunction through IL-6 mediated inflammation, compounded by malignancies such as MM which contribute to apoptosis via IL-6 induced hypoxia. In the MM microenvironment, IL-6 fuels inflammation, tumorigenesis, and inhibits apoptosis, driving disease progression. This model reveals that severe SARS-CoV-2 infection heightens pro-inflammatory responses in MM patients, stemming from elevated IL-6 production, resulting in increased systemic injury. Results Amidst limited therapeutic options for severe SARS-CoV-2, EVs emerge as a promising avenue. Clinical evidence indicates that EVs effectively neutralize viral entry and modulate immunity. Their capacity to deliver therapeutic agents bolsters immune responses, aiding interventions against SARS-CoV-2 in the immunocompromised. Additionally, EVs offer regenerative and stem cell-derived properties, fostering tissue repair and angiogenesis, enabling comprehensive anti-viral and anti-inflammatory effects. Clinical trials showcase over 90% survival rates among severe SARS-CoV-2 patients within a month of EV treatment, sustained for at least 6 months. Conclusion EVs stand as safe, well-tolerated interventions that bolster survival rates in severe SARS-CoV-2 patients. Their versatility in addressing disease progression, suppressing inflammation, and promoting tissue repair underscores their promise. EVs can work independently or synergistically with other therapies, countering viral heterogeneity and adaptations. With minimal side effects and drug interactions, EVs offer a feasible strategy to combat SARS-CoV-2 without disrupting MM treatment regimens. Consequently, EVs present a promising avenue for managing severe SARS-CoV-2 infections in MM patients.