Stem cell-based therapy for COVID-19 and ARDS: a systematic review

Gabriele Zanirati,Lucas Lobraico Libermann,Ashok K Shetty,Daniel Rodrigo Marinowic,Laura Provenzi,Isadora Machado Ghilardi,Jaderson Costa Da Costa,Sabrina Comin Bizotto

doi:10.1038/s41536-021-00181-9

Abstract

Despite global efforts to establish effective interventions for coronavirus disease 2019 (COVID-19) and its major complications, such as acute respiratory distress syndrome (ARDS), the treatment remains mainly supportive. Hence, identifying an effective and safe therapy for severe COVID-19 is critical for saving lives. A significant number of cell-based therapies have been through clinical investigation. In this study, we performed a systematic review of clinical studies investigating different types of stem cells as treatments for COVID-19 and ARDS to evaluate the safety and potential efficacy of cell therapy. The literature search was performed using PubMed, Embase, and Scopus. Among the 29 studies, there were eight case reports, five Phase I clinical trials, four pilot studies, two Phase II clinical trials, one cohort, and one case series. Among the clinical studies, 21 studies used cell therapy to treat COVID-19, while eight studies investigated cell therapy as a treatment for ARDS. Most of these (75%) used mesenchymal stem cells (MSCs) to treat COVID-19 and ARDS. Findings from the analyzed articles indicate a positive impact of stem cell therapy on crucial immunological and inflammatory processes that lead to lung injury in COVID-19 and ARDS patients. Additionally, among the studies, there were no reported deaths causally linked to cell therapy. In addition to standard care treatments concerning COVID-19 management, there has been supportive evidence towards adjuvant therapies to reduce mortality rates and improve recovery of care treatment. Therefore, MSCs treatment could be considered a potential candidate for adjuvant therapy in moderate-to-severe COVID-19 cases and compassionate use.

Highlights

In January 2020, to raise awareness internationally and to prevent further viral spread, the World Health Organization (WHO) declared the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak a public health emergency[1]
The present systematic review evaluated the available results of stem cell therapy for treating patients with COVID-19 and acute respiratory distress syndrome (ARDS)
The vast number of trials under progress shows that cell therapy has been suggested as a beneficial alternative to treating COVID-19 and its complications ARDS

Summary

Introduction

In January 2020, to raise awareness internationally and to prevent further viral spread, the World Health Organization (WHO) declared the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak a public health emergency[1]. Despite global efforts to establish effective interventions for COVID-19, its treatment remains mainly supportive, and one of the major complications of the disease, acute respiratory distress syndrome (ARDS), poses a significant challenge[3]. A significant number of cell-based therapies have been through clinical investigation, involving, most importantly, mesenchymal stem cells (MSCs) and MSC-derived conditioned media or extracellular vesicles. These therapies have multiple therapeutic targets because MSCs can release a variety of soluble mediators, but their safety and potential efficacy are still to be determined[6]

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Results

Conclusion