1 Vol.:(0123456789) Scientific Reports | (2023) 13:12520 | https://doi.org/10.1038/s41598-023-39268-2 www.nature.com/scientificreports Effectiveness and safety of normoxic allogenic umbilical cord mesenchymal stem cells administered as adjunctive treatment in patients with severe COVID‑19 Bintang Soetjahjo 1 , Rusdy Ghazali Malueka 2 , Arief Nurudhin 3 , Purwoko 4 , Sumardi 5 , Rudi Wisaksana 6 , Artrien Adhiputri 7 , Sudadi 8 , Arto Yuwono Soeroto 6 , Brigitte Rina Aninda Sidharta 9 , Jarir At Thobari 10 , Tri Wahyu Murni 11 , Widiastuti Soewondo 12 , Elizabeth Henny Herningtyas 13 , Reza Widianto Sudjud 14 , Ika Trisnawati 5 , Nur Rahmi Ananda 5 & Ahmad Faried 15* Inflammatory response in COVID‑19 contributes greatly to disease severity. Mesenchymal Stem Cells (MSCs) have the potential to alleviate inflammation and reduce mortality and length of stay in COVID‑19 patients. We investigated the safety and effectiveness of normoxic‑allogenic umbilical cord (NA‑UC)‑MSCs as an adjunctive treatment in severe COVID‑19 patients. A double‑blind, multicentric, randomized, placebo‑controlled trial involving severe COVID‑19 patients was performed from January to June 2021 in three major hospitals across Java, Indonesia. Eligible participants (n = 42) were randomly assigned to two groups (1:1), namely the intervention (n = 21) and control (n = 21) groups. UC‑MSCs dose was 1 × 10 6 /kg body weight on day D0, D3, and D6. The primary outcome was the duration of hospitalization. Meanwhile, the secondary outcomes were radiographical progression (Brixia score), respiratory and oxygenation parameters, and inflammatory markers, in addition to the safety profile of NA‑UC‑MSCs. NA‑UC‑MSCs administration did not affect the length of hospital stay of severe COVID‑19 patients, nor did it improve the Brixia score or mMRC dyspnoea scale better than placebo. Nevertheless, NA‑UC‑MSCs led to a better recuperation in oxygenation index OPEN 1 Department of Orthopaedics and Traumatology, Universitas Sebelas Maret-Dr. Moewardi Hospital, Solo, Indonesia. 2 Department of Neurology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada-Dr. Sardjito General Hospital, Yogyakarta, Indonesia. 3 Department of Internal Medicine, Universitas Sebelas Maret-Dr. Moewardi Hospital, Solo, Indonesia. 4 Department of Anesthesiology and Intensive Therapy, Universitas Sebelas Maret-Dr. Moewardi Hospital, Solo, Indonesia. 5 Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada-Dr. Sardjito General Hospital, Yogyakarta, Indonesia. 6 Department of Internal Medicine, Universitas Padjadjaran-Dr. Hasan Sadikin Hospital, Bandung, Indonesia. 7 Department of Pulmonology and Respiratory Medicine, Universitas Sebelas Maret-Dr. Moewardi Hospital, Solo, Indonesia. 8 Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada-Dr. Sardjito General Hospital, Yogyakarta, Indonesia. 9 Department of Clinical Pathology, Universitas Sebelas Maret-Dr. Moewardi Hospital, Solo, Indonesia. 10 Department of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia. 11 Department of Surgery, Universitas Padjadjaran-Dr. Hasan Sadikin Hospital, Bandung, Indonesia. 12 Department of Radiology, Universitas Sebelas Maret-Dr. Moewardi Hospital, Solo, Indonesia. 13 Department of Clinical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada-Dr. Sardjito General Hospital, Yogyakarta, Indonesia. 14 Department of Anesthesiology-Intensive Therapy, Universitas Padjadjaran-Dr. Hasan Sadikin Hospital, Bandung, Indonesia. 15 Department of Neurosurgery, Universitas Padjadjaran - Dr. Hasan Sadikin Hospital, Bandung 40161, Indonesia. * email: ahmad.faried@ unpad.ac.id