Combined Use of Tocilizumab and Mesenchymal Stromal Cells in the Treatment of Severe Covid-19: Case Report

Abstract

The coronavirus pandemic is one of the most significant public health events in recent history. Currently, no specific treatment is available. Some drugs and cell-based therapy have been tested as alternatives to decrease the disease’s symptoms, length of hospital stay, and mortality. We reported the case of a patient with a severe manifestation of COVID-19 in critical condition who did not respond to the standard procedures used, including six liters of O2 supplementation under a nasal catheter and treatment with dexamethasone and enoxaparin in prophylactic dose. The patient was treated with tocilizumab and an advanced therapy product based on umbilical cord-derived mesenchymal stromal cells (UC-MSC). The combination of tocilizumab and UC-MSC proved to be safe, with no adverse effects, and the results of this case report prove to be a promising alternative in the treatment of patients with severe acute respiratory syndrome due to SARS-CoV-2.

Specific Interleukin-1 Inhibitors, Specific Interleukin-6 Inhibitors, and GM-CSF Blockades for COVID-19 (at the Edge of Sepsis): A Systematic Review

“…Following the elimination of duplicates and screening of titles and abstracts, we evaluated 244 articles in full text. Among these, we found 43 eligible articles (5 RCTs, 16 cohort studies, 2 case-control studies, and 20 case reports) (Figure 1) (Salvarani et al, 2021;REMAP-CAP Investigators et al, 2021;Canziani et al, 2020;Menzella et al, 2020;Fisher et al, 2021;Campochiaro et al, 2020;Vazquez Guillamet et al, 2021;Rajendram et al, 2021;Huang et al, 2021;Galván-Román et al, 2021;Saffo et al, 2021;Somers et al, 2021;Brosnahan et al, 2021;Corominas et al, 2021;Cavalli et al, 2021;Abe et al, 2021;Patel et al, 2020;Mady et al, 2020;Bernardo et al, 2020;Morillas et al, 2020;Cascella et al, 2020;Al-Kaf et al, 2021;Eroglu et al, 2021;Kataoka et al, 2021;Kishaba et al, 2021;Leelayuwatanakul et al, 2021;McKenzie et al, 2021;Nourié et al, 2021;Ladna et al, 2021;Senegaglia et al, 2021;Thammathiwat et al, 2021;Lescure et al, 2021;Della-Torre et al, 2020;Gremese et al, 2020;Kyriazopoulou et al, 2021a;Bozzi et al, 2021;Franzetti et al, 2021;…”

Mesenchymal Stromal Cells: Potential Option for COVID-19 Treatment

“…The reviewed case reports differed in MSC concentration, regimes of MSC dosing and their origin. MSC therapy was well tolerated and the clinical effect was positive across the case reports, apart from in a report by Tao and colleagues, who noted that their patient required lung transplantation and died due to complications of transplant rejection [ 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ]. The majority of research groups used human umbilical cord-mesenchymal stem cells (UC-MSCs) (seven case reports), while two groups used human menstrual blood-derived MSCs and two used bone marrow-derived MSCs.…”

“…Across all studies, MSC therapy was applied intravenously and was deemed safe with a positive effect on clinical outcome based on the immunomodulatory effect of MSC therapy (Table 2). [84] menstrual blood 10 6 /kg in 3 doses iv Liang et al [85] umbilical cord 5 × 10 7 /kg in 3 doses iv Peng et al [86] umbilical cord 10 6 /kg in 3 doses iv Tao et al [87] umbilical cord 1.5 × 10 6 /kg in 5 doses iv Zengin et al [88] umbilical cord 0.7 × 10 6 /kg in 2 doses iv iv 0.3 × 10 6 /kg in 2 doses it it Zhu et al [89] umbilical cord 10 6 /kg single dose iv Rich et al [90] bone marrow 10 6 /kg single dose iv Lu et al [91] menstrual blood 3000, 2000, 3000 units per dose iv Senegaglia et al [92] umbilical cord 5 × 10 5 /kg in 3 doses iv Primorac et al [93] bone marrow 10 6 /kg in 3 doses iv Iv-intravenous; it-intratracheal. Shi et al conducted a phase 2 trial using UC-MSC to treat severe COVID-19 patients with lung damage.…”

A Retrospective Look at Recent COVID-19 Articles Published in Cell Transplantation: Research Leading to Further Understanding

“…MSC have been beneficial in animal models of ARDS and were used to treat patients suffering from influenza A (H7N9 infections) 9 , 12 , 14 . In critically ill COVID-19 patients who have failed to respond to all other treatments, MSC have been used almost as a last-ditch effort 7 , 11 , 12 . Fortunately, MSC infusions had a relatively quick and lasting effect, by decreasing pro-inflammatory cytokines (TNFα) and inflammatory markers (i.e., CRP), and increasing anti-inflammatory cytokines (IL10) and growth factors (KGF).…”

“…The Senegaglia et al . 11 case report told the story of an intubated COVID-19 patient that was extubated six days after the first of three MSC infusions, discharged from the ICU 4 days later, and left the hospital shortly after that.…”