Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized, double-blind, placebo-controlled clinical trial (NCT04288102). METHODS: A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4 × 107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. Outcomes measured included: 6-min walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire (SF-36), COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, tumor markers, and MSC-related adverse events (AEs). FINDINGS: Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). At month 18, the general health score from the SF-36 was higher in the MSC group than in the placebo group (50.00 vs. 35.00, 95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.018). Total severity score of lung imaging and the titer of neutralizing antibodies were similar between the two groups at months 18 and 24. There was no difference in AEs or tumor markers at the 2-year follow-up between the two groups. INTERPRETATION: Long-term safety was observed for the COVID-19 patients who received MSC treatment. However, efficacy of MSC treatment was not significantly sustained through the end of the 2-year follow-up period. FUNDING: The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900, 2022YFC2304401), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRC-ID202105,413FZT6).

COVID-19 and Diabetes: A Comprehensive Review of Angiotensin Converting Enzyme 2, Mutual Effects and Pharmacotherapy.

The potential relationship between diabetes and COVID-19 has been evaluated. However, new knowledge is rapidly emerging. In this study, we systematically reviewed the relationship between viral cell surface receptors (ACE2, AXL, CD147, DC-SIGN, L-SIGN and DPP4) and SARS-CoV-2 infection risk, and emphasized the implications of ACE2 on SARS-CoV-2 infection and COVID-19 pathogenesis. Besides, we updated on the two-way interactions between diabetes and COVID-19, as well as the treatment options for COVID-19 comorbid patients from the perspective of ACE2. The efficacies of various clinical chemotherapeutic options, including anti-diabetic drugs, renin-angiotensin-aldosterone system inhibitors, lipid-lowering drugs, anticoagulants, and glucocorticoids for COVID-19 positive diabetic patients were discussed. Moreover, we reviewed the significance of two different forms of ACE2 (mACE2 and sACE2) and gender on COVID-19 susceptibility and severity. This review summarizes COVID-19 pathophysiology and the best strategies for clinical management of diabetes patients with COVID-19.