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).

Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS-CoV-2.

PURPOSE: To investigate the clinical and imaging characteristics of computed tomography (CT) in novel coronavirus pneumonia (NCP) caused by SARS-CoV-2. MATERIALS AND METHODS: A retrospective analysis was performed on the imaging findings of patients confirmed with COVID-19 pneumonia who had chest CT scanning and treatment after disease onset. The clinical and imaging data were analyzed. RESULTS: Fifty patients were enrolled, including mild type in nine, common in 28, severe in 10 and critically severe in the rest three. Mild patients (29 years) were significantly (P<0.03) younger than either common (44.5 years) or severe (54.7) and critically severe (65.7 years) patients, and common patients were also significantly (P<0.03) younger than severe and critically severe patients. Mild patients had low to moderate fever (<39.1 °C), 49 (98%) patients had normal or slightly reduced leukocyte count, 14 (28%) had decreased counts of lymphocytes, and 26 (52%) patients had increased C-reactive protein. Nine mild patients were negative in CT imaging. For all the other types of NCP, the lesion was in the right upper lobe in 30 cases, right middle lobe in 22, right lower lobe in 39, left upper lobe in 33 and left lower lobe in 36. The lesion was primarily located in the peripheral area under the pleura with possible extension towards the pulmonary hilum. Symmetrical lesions were seen in 26 cases and asymmetrical in 15. The density of lesion was mostly uneven with ground glass opacity as the primary presentation accompanied by partial consolidation and fibrosis. CONCLUSION: CT imaging presentations of NCP are mostly patchy ground glass opacities in the peripheral areas under the pleura with partial consolidation which will be absorbed with formation of fibrotic stripes if improved. CT scanning provides important bases for early diagnosis and treatment of NCP.