A prospective study evaluating depression in COVID- 19 long haulers syndrome treated with allogeneic marrow stromal cells. Accruing evidence suggests cognitive and affective dysfunction, depression, and fatigue occur after COVID-19 infection. These impairments, likely arise from multiple factors that may include cell/organ damage due to direct viral infection or inflammatory process. The current proposal hypothesizes that the inflammatory response is a critical mechanism underlying these neuropsychiatric conditions.~After recovery from COVID-19, the hyperimmune activity secondary to tissue damages and endothelial activation may leave post-acute COVID-19 patients vulnerable to the neural consequences of proinflammatory cytokines Heightened inflammation can alert the central nervous system to induce sickness behaviors and elevated risk of depression.~We hypothesize that allogeneic marrow stromal cells (MSCs) will attenuate post-covid inflammation and reduce the resulting neuropsychiatric symptoms.~Aim 1: Evaluate the feasibility and acceptability of recruiting, providing MSC/sham infusions, and following participants to collect biomarker and clinical outcomes.~• MSC's infusions, baseline and follow-up measurements will be feasible and acceptable to participants.~Aim 2: Estimate the probability of demonstrating improvement in depression (i.e. > 30% reduction on the MADRS) among adult patients experiencing post-COVID depression randomized to MSC Infusion versus Sham Infusion. To determine (obtain, evaluate, verify, etc.) …~• MSC Infusion will out-perform Sham Infusion on the proportion of MADRS responders.~Aim 3: Relative to usual care, estimate the differential improvement of MSC-treated participants on cognitive measures and PROMIS (Health-Related Quality of Life; HRQOL) scales (e.g. Fatigue, Pain, Anger, Anxiety, etc.).~• MSC Infusion will out-perform Sham Infusion +on improvements in cognitive function and HRQOL measures.~Aim 4: Estimate the change attributable to MSC treatment on a panel of inflammatory biomarkers relative to usual care.~• Relative to Sham Infusion, MSC Infusion will down-regulate pro-inflammatory processes while upregulating anti-inflammatory processes, and this modulation will be related to improvement in depression, cognitive and PROMIS measures. Relative to Sham Infusion, MSC Infusion will down-regulate pro-inflammatory processes while upregulating anti-inflammatory processes, and this modulation will be related to improvement in depression, cognitive, and PROMIS measures.
Single site, double blind, placebo-controlled, longitudinal study of depression in Subjects with COVID- 19 long haulers syndrome using a 1:1 ratio randomization for a single IV infusion of 6 million cells/kg allogeneic marrow stromal cells (MSCs).