ABSTRACT
BACKGROUND: Treatment options for patients with COVID-19-related acute respiratory distress syndrome (ARDS) are desperately needed. Allogeneic human umbilical cord derived mesenchymal stromal cells (hCT-MSCs) have potential therapeutic benefits in these critically ill patients, but feasibility and safety data are lacking. MATERIALS AND METHODS: In this phase I multisite study, 10 patients with COVID-19-related ARDS were treated with 3 daily intravenous infusions of hCT-MSCs (1 million cells/kg, maximum dose 100 million cells). The primary endpoint assessed safety. RESULTS: Ten patients (7 females, 3 males; median age 62 years (range 39-79)) were enrolled at 2 sites and received a total of 30 doses of study product. The average cell dose was 0.93 cells/kg (range 0.56-1.45 cells/kg and total dose range 55-117 million cells) with 5/30 (17%) of doses lower than intended dose. Average cell viability was 85% (range 63%-99%) with all but one meeting the >70% release criteria. There were no infusion-related reactions or study-related adverse events, 28 non-serious adverse events in 3 unique patients, and 2 serious adverse events in 2 unique patients, which were expected and unrelated to the study product. Five patients died: 3 by day 28 and 5 by day 90 of the study (median 27 days, range 7-76 days). All deaths were determined to be unrelated to the hCT-MSCs. CONCLUSION: We were able to collect relevant safety outcomes for the use of hCT-MSCs in patients with COVID-19-related ARDS. Future studies to explore their safety and efficacy are warranted.
Subject(s)
COVID-19 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Male , Female , Humans , Adult , Middle Aged , Aged , COVID-19/therapy , COVID-19/etiology , Feasibility Studies , Mesenchymal Stem Cell Transplantation/adverse effects , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapyABSTRACT
BACKGROUND: Inflammatory responses from benign conditions can cause non-cancer-related elevations in tumor markers. The severe acute respiratory coronavirus 2 (SARS-CoV-2) induces a distinct viral inflammatory response, resulting in coronavirus disease 2019 (COVID-19). Clinical data suggest carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and cancer antigen 125 (CA 125) levels might rise in patients with COVID-19. However, available data excludes cancer patients, so little is known about the effect of COVID-19 on tumor markers among cancer patients. METHODS: We conducted a case series and identified patients with a positive SARS-CoV-2 PCR test, diagnosis of a solid tumor malignancy, and a CEA, CA 19-9, CA 125, or CA 27-29 laboratory test. Cancer patients with documented COVID-19 infection and at least one pre- and two post-infection tumor marker measurements were included. We abstracted the electronic health record for demographics, cancer diagnosis, treatment, evidence of cancer progression, date and severity of COVID-19 infection, and tumor marker values. RESULTS: Seven patients were identified with a temporary elevation of tumor marker values during the post-COVID-19 period. Elevation in tumor marker occurred within 56 days of COVID-19 infection for all patients. Tumor markers subsequently decreased at the second time point in the post-infectious period among all patients. CONCLUSION: We report temporary elevations of cancer tumor markers in the period surrounding COVID-19 infection. To our knowledge this is the first report of this phenomenon in cancer patients and has implications for clinical management and future research.