Long-term outcomes of mesenchymal stem cell therapy in severe COVID-19 patients: 3-year follow-up of a [RCT], 2025, Yuan et al

Long-term outcomes of mesenchymal stem cell therapy in severe COVID-19 patients: 3-year follow-up of a randomized, double-blind, placebo-controlled trial

Meng-Qi Yuan, Le Song, Ze-Rui Wang, Zi-Ying Zhang, Ming Shi, Junli He, Qiong Mo, Ning Zheng, Wei-Qi Yao, Yu Zhang, Tengyun Dong, Yuanyuan Li, Chao Zhang, Jinwen Song, Lei Huang, Zhe Xu, Xin Yuan, Jun-Liang Fu, Cheng Zhen, Jianming Cai, Jinghui Dong, Jianzeng Zhang, Wei-Fen Xie, Yonggang Li, Bo Zhang, Lei Shi & Fu-Sheng Wang

Background
The long-term effects and outcomes of human mesenchymal stem cell (MSC) therapy in patients with severe coronavirus disease 2019 (COVID-19) remain poorly understood. This study aimed to evaluate the extended safety and efficacy of MSC treatment in severe patients with COVID-19 who participated in our earlier randomized, double-blind, placebo-controlled clinical trial, with follow-up conducted over 3 years.

Methods
One hundred patients with severe COVID-19 were randomized to receive either an MSC infusion (n = 65, 4 × 107 cells/dose, on days 0, 3, and 6) or a placebo, with both groups receiving the standard of care. At 36 months post-MSC therapy, patients were followed up to long-term safety and efficacy, particularly the effects of MSC therapy on persistent COVID-19 symptoms. Evaluated outcomes included lung imaging results, 6-min walking distance (6-MWD), pulmonary function test results, quality of life scores based on the Short Form-36 (SF-36) health survey, Long COVID symptoms, new-onset comorbidities, tumor marker levels, and rates of COVID-19 reinfection.

Results
Three years post-treatment, 46.94% (23/49) of patients in the MSC group and 34.48% (10/29) in the placebo group showed normal findings on computed tomography (CT) images (odds ratio [OR] = 1.68, 95% confidence interval [CI]: 0.65–4.34). The general health (GH) score from the SF-36 was higher in the MSC group (67.0) compared to the placebo group (50.0), with a difference of 12.86 (95% CI: 1.44–24.28). Both groups showed similar results for total lung severity scores (TSS), 6-MWD, pulmonary function tests, and Long COVID symptoms. No significant differences between groups were observed in new-onset complications (including tumorigenesis) or tumor marker levels. After adjusting for China’s dynamic zero-COVID-19 strategy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection rates were 53.06% (26/49) in the MSC group and 67.86% (19/28) in the placebo group (OR = 0.54, 95% CI: 0.20–1.41).

Conclusions
These findings support the long-term safety of MSC therapy in patients with severe COVID-19 over 3 years. MSC treatment may offer potential benefits for lung recovery and improved quality of life in patients experiencing Long COVID symptoms.

Link | PDF (Stem Cell Research and Therapy) [Open Access]

 

From the original study, line breaks added.

Inclusion and exclusion criteria
Hospitalized patients with severe COVID-19 with laboratory-confirmed SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR) were screened.

Patients were eligible if they met any of the following criteria: (1) severe COVID-19 diagnosed after onset of disease; (2) chest computed tomography (CT) imaging confirmed pneumonia combined with lung damage. The illness severity of COVID-19 was evaluated in accordance with Guidelines issued by the National Health Commission of China (version 7.0).33

In brief, patients with any of the following conditions but without invasive ventilation, shock or other organ failure (need organ support therapy) were considered as severe cases: (1) dyspnea (respiratory rate ≥ 30 times/min); (2) oxygen saturation of 93% or lower on room air; (3) arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen ≤ 300 mmHg; (4) pulmonary imaging showing that the foci progressed by > 50% in 24–48 h.

The exclusion criteria included patients with shock or COVID-19 combined with any one of other organ failures, those who received invasive ventilation, or patients with any malignant tumor, pregnancy or breastfeeding, or co-infection of other pathogens.

https://www.nature.com/articles/s41392-021-00488-5

 

It looks as if maybe lung CT was the one thing that seemed different.
They don't say in the abstract if reading was blinded.

I have no idea why stem cells should be of help in Long Covid. The abstract does not even say whether this is autologous, where from or whatever.

Ummmm...

 

Looks like umbilical cord cells, as a follow-up from their phase 2 study —

Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial (2021)

Spoiler: Authors

Shi, Lei; Huang, Hai; Lu, Xuechun; Yan, Xiaoyan; Jiang, Xiaojing; Xu, Ruonan; Wang, Siyu; Zhang, Chao; Yuan, Xin; Xu, Zhe; Huang, Lei; Fu, Jun-Liang; Li, Yuanyuan; Zhang, Yu; Yao, Wei-Qi; Liu, Tianyi; Song, Jinwen; Sun, Liangliang; Yang, Fan; Zhang, Xin; Zhang, Bo; Shi, Ming; Meng, Fanping; Song, Yanning; Yu, Yongpei; Wen, Jiqiu; Li, Qi; Mao, Qing; Maeurer, Markus; Zumla, Alimuddin; Yao, Chen; Xie, Wei-Fen; Wang, Fu-Sheng

Spoiler: Abstract

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data.

In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35).

UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was −13.31%, 95% CI −29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: −15.45%; 95% CI −30.82%, −0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups.

These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.

Link | PDF (Nature Signal Transduction and Targeted Therapy) [Open Access]

 

Which one would expect to be destroyed by rejection within days if not hours.