Human placenta-derived mesenchymal stem cells transplantation in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 (phase I clinical trial): safety profile assessment.

BACKGROUND: High morbidity and mortality rates of the COVID-19 pandemic have made it a global health priority. Acute respiratory distress syndrome (ARDS) is one of the most important causes of death in COVID-19 patients. Mesenchymal stem cells have been the subject of many clinical trials for the treatment of ARDS because of their immunomodulatory, anti-inflammatory, and regenerative potentials. The aim of this phase I clinical trial was the safety assessment of allogeneic placenta-derived mesenchymal stem cells (PL-MSCs) intravenous injection in patients with ARDS induced by COVID-19. METHODS: We enrolled 20 patients suffering from ARDS caused by COVID-19 who had been admitted to the intensive care unit. PL-MSCs were isolated and propagated using a xeno-free/GMP compliant protocol. Each patient in the treatment group (N = 10) received standard treatment and a single dose of 1 × 106 cells/kg PL-MSCs intravenously. The control groups (N = 10) only received the standard treatment. Clinical signs and laboratory tests were evaluated in all participants at the baseline and during 28 days follow-ups. RESULTS: No adverse events were observed in the PL-MSC group. Mean length of hospitalization, serum oxygen saturation, and other clinical and laboratory parameters were not significantly different in the two groups (p > 0.05). CONCLUSION: Our results demonstrated that intravenous administration of PL-MSCs in patients with COVID-19 related ARDS is safe and feasible. Further studies whit higher cell doses and repeated injections are needed to evaluate the efficacy of this treatment modality. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); IRCT20200621047859N4. Registered 1 March 2021, https://en.irct.ir/trial/52947 .

Concurrent atypical diffused tuberculosis and macrorhabdosis in a canary (Serinus canaria).

A dead canary from a mixed species zoological garden was presented for diagnostic necropsy. Cachexia with prominent atrophy of pectoral muscles, yellowish brown discoloration of the liver and kidney, dark brown to black intestinal contents and moderate proventricular dilatation with some degree of catarrhal gastritis were the significant macroscopic findings. Parenchymatous organs like the liver, the spleen, the lung and the kidneys were extremely affected by massive diffuse necrosis and heavy infiltration of mononuclear inflammatory cells, histopathologically. Many giant bacilli resembling Macrorrhabdus ornithogaster were seen microscopically in the wet smear of the isthmus mucosa. Ghost-like unstained bacilli were revealed in the Giemsa stained contact smears of the liver and spleen. No typical mycobacterial granulomatous lesion was found in different tissues, but in Ziehl-Neelsen stained thin layer histologic sections from the liver, spleen, lung and kidney, numerous acid fast organisms were diffusely distributed. The case was diagnosed an atypical avian tuberculosis with concurrent macrorhabdosis. Mycobacterium sp. are capable of giving rise to a progressive disease in humans, especially in immunocompromised individuals. Cases of avian tuberculosis might be overlooked for lack of pathognomonic lesions suggestive of mycobacteriosis.