MSC therapy delivers long-term benefit in severe COVID-19

A recent study suggests patients with severe COVID-19 may benefit from human mesenchymal stem cell (MSC) therapy.

“This study aimed to evaluate the extended safety and efficacy of MSC treatment in severe COVID-19 patients who participated in our earlier randomized, double-blind, placebo-controlled clinical trial, with follow-up conducted over 3 years,” said the researchers.

“[The current] findings suggest that MSC therapy holds promise as a potential treatment for individuals with severe COVID-19, aiding in recovery from lung damage and enhancing the quality of life (QoL) of patients with long COVID,” they said.

In the prior study, 100 participants were randomized 2:1 to receive three IV infusions of MSC (4×10⁷ cells/dose on days 0, 3, and 6) or placebo, along with standard treatment. The current follow-up evaluated 78 patients (49 [MSC] and 29 [placebo]). Median follow-up was 1,106 days. [Stem Cell Res Ther 2025;doi:10.1186/s13287-025-04148-1]

At month 36, nearly half (46.94 percent) of MSC recipients had normal CT images; only a third (34.48 percent) of placebo recipients achieved this endpoint. A comparison between arms yielded an odds ratio (OR) of 1.68 (p=0.2819). According to the investigators, this finding suggests that MSC transfusion factored in lung damage recovery.

Of note, lung CT normalization occurred earlier with MSC vs placebo (3 vs 18 months).

The 6-minute walking distance (6MWD) results were similar between the MSC and placebo arms (median 430 vs 420 m). Despite the numerical improvement with MSC, the between-arm difference was not statistically significant.

The superior lung CT normalization rate and time, and the numerically improved 6MWD highlight the potential of MSC therapy to expedite exercise capacity rehabilitation and induce physiological improvements in severe COVID-19 patients, the researchers said.

The median general health (GH) score from the Short Form-36 health survey was markedly higher with MSC vs placebo in the overall cohort (67 vs 50; difference, 12.86; p=0.0278) and in the subgroup of patients aged ≥65 years (70 vs 42.5; difference, 25.47; p=0.0031). The higher GH scores with MSC underline its potential in improving QoL and mitigating long COVID symptoms.

There were no significant differences between the MSC and placebo arms regarding new-onset complications, including tumorigenesis (n=22 vs 21) or tumour marker levels. “Most tumour markers remained within normal ranges, and no significant differences were observed between arms,” they said.

Reinfection rate

Compared with the placebo arm, the MSC arm had a lower SARS-CoV-2 reinfection rate (53.06 percent vs 67.86 percent; OR, 0.54), but a higher hospitalization rate (11.54 percent vs 5.26 percent). Most participants received basic symptomatic and supportive treatment. None received antiviral therapy, and there were no severe, critical, or fatal cases reported.

The researchers noted that the reinfections were milder than those observed with the initial infections. “This could be attributed to the humoral and cellular immunity induced by prior infections and vaccinations.”

New treatment modalities warranted

Individuals with critical or severe COVID-19 continue to experience high mortality rates and poor prognoses. [Lancet Respir Med 2020;8:475-481; JAMA 2020;324:782-793] A significant fraction of COVID-19 patients also experience long COVID. [Lancet 2024;404:707-724] “Thus, there is a need to explore new treatment modalities for these persistent effects,” said the researchers.

Known for their self-renewal, multidirectional differentiation, and immunomodulatory properties, MSCs can reduce inflammatory cytokines and accelerate lung recovery in COVID-19 patients, with a good short-term safety profile. [Signal Transduct Target Ther 2022;7:272; Signal Transduct Target Ther 2021;6:339]

“[Our] previous follow-ups [suggest that] MSC therapy has the potential to improve lung damage, enhance activity endurance, and improve QoL, all with good tolerance in severe COVID-19 patients,” said the researchers.

The current findings build on the previous results, showing accelerated recovery of lung damage, a higher GH score, and a lower reinfection rate with MSC over 3 years.

“Collectively, these findings suggest that MSC therapy offers long-term safety and potential therapeutic benefits … These results establish the foundation for continued clinical trials exploring MSC therapy as an intervention for both acute SARS-CoV-2 infection and long COVID,” the researchers concluded.