da Silva Kátia Nunes, Pinheiro Priscila Carvalho Guedes, Gobatto André Luiz Nunes, Passos Rogério da Hora, Paredes Bruno Diaz, França Luciana Souza de Aragão, Nonaka Carolina Kymie Vasques, Barreto-Duarte Beatriz, Araújo-Pereira Mariana, Tibúrcio Rafael, Cruz Fernanda Ferreira, Martins Gabriele Louise Soares, Andrade Bruno B, de Castro-Faria-Neto Hugo Caire, Rocco Patricia Rieken Macêdo, Souza Bruno Solano de Freitas
Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil.
D'Or Institute for Research and Education (IDOR), Salvador, Brazil.
Front Med (Lausanne). 2021 Nov 17;8:767291. doi: 10.3389/fmed.2021.767291. eCollection 2021.
The patients with coronavirus disease 2019 (COVID-19) associated with severe acute respiratory distress syndrome (ARDS) may require prolonged mechanical ventilation which often results in lung fibrosis, thus worsening the prognosis and increasing fatality rates. A mesenchymal stromal cell (MSC) therapy may decrease lung inflammation and accelerate recovery in COVID-19. In this context, some studies have reported the effects of MSC therapy for patients not requiring invasive ventilation or during the first hours of tracheal intubation. However, this is the first case report presenting the reduction of not only lung inflammation but also lung fibrosis in a critically ill long-term mechanically ventilated patient with COVID-19. This is a case report of a 30-year-old male patient with COVID-19 under invasive mechanical ventilation for 14 days in the intensive care unit (ICU), who presented progressive clinical deterioration associated with lung fibrosis. The symptoms onset was 35 days before MSC therapy. The patient was treated with allogenic human umbilical-cord derived MSCs [5 × 10 (2 doses 2 days interval)]. No serious adverse events were observed during and after MSC administration. After MSC therapy, PaO/FiO ratio increased, the need for vasoactive drugs reduced, chest CT scan imaging, which initially showed signs of bilateral and peripheral ground-glass, as well as consolidation and fibrosis, improved, and the systemic mediators associated with inflammation decreased. Modulation of the different cell populations in peripheral blood was also observed, such as a reduction in inflammatory monocytes and an increase in the frequency of patrolling monocytes, CD4+ lymphocytes, and type 2 classical dendritic cells (cDC2). The patient was discharged 13 days after the cell therapy. Mesenchymal stromal cell therapy may be a promising option in critically ill patients with COVID-19 presenting both severe lung inflammation and fibrosis. Further clinical trials could better assess the efficacy of MSC therapy in critically ill patients with COVID-19 with lung fibrosis associated with long-term mechanical ventilation.
患有新型冠状病毒肺炎（COVID-19）且伴有严重急性呼吸窘迫综合征（ARDS）的患者可能需要长时间机械通气，这常常会导致肺纤维化，进而使预后恶化并增加死亡率。间充质基质细胞（MSC）疗法可能会减轻COVID-19患者的肺部炎症并加速康复。在此背景下，一些研究报道了MSC疗法对无需有创通气的患者或气管插管最初数小时内患者的疗效。然而，这是首例关于一名患有COVID-19的危重症长期机械通气患者不仅肺部炎症减轻而且肺纤维化也减轻的病例报告。这是一例30岁男性COVID-19患者的病例报告，该患者在重症监护病房（ICU）接受有创机械通气14天，出现了与肺纤维化相关的进行性临床恶化。症状出现于MSC治疗前35天。患者接受了异体人脐带源间充质基质细胞治疗[5×10（分2剂，间隔2天）]。在间充质基质细胞给药期间及之后未观察到严重不良事件。MSC治疗后，氧合指数（PaO/FiO）升高，对血管活性药物的需求减少，胸部CT扫描影像最初显示双侧及外周磨玻璃影、实变和纤维化迹象，之后有所改善，且与炎症相关的全身介质减少。外周血中不同细胞群也出现了调节变化，如炎症单核细胞减少，巡逻单核细胞、CD4+淋巴细胞和2型经典树突状细胞（cDC2）频率增加。细胞治疗13天后患者出院。间充质基质细胞疗法对于患有严重肺部炎症和纤维化的COVID-19危重症患者可能是一个有前景的选择。进一步的临床试验可以更好地评估MSC疗法对患有与长期机械通气相关的肺纤维化的COVID-19危重症患者的疗效。
