[Evaluation of the effects of immunotherapy and mesenchymal stem cells transplantation in the treatment of critically ill coronavirus disease 2019 patients].

ABSTRACT

OBJECTIVE: To analyze the immunotherapy and clinical characteristics of coronavirus disease 2019 (COVID-19) patients, and focus on exploring the effects of immunotherapy and mesenchymal stem cells (MSC) transplantation in the critically ill patients' treatment. METHODS: Fity-five COVID-19 patients were admitted to the Fifth People's Hospital of Wuxi from January 23rd to March 31st, 2020 as the research object. The demographic characteristics of the cases and the methods of immunotherapy were analyzed, focusing on the immunized indicators, positivity of pathogens and clinical indicators of critically ill COVID-19 patient, and the effects of immunotherapy and stem cell transplantation were evaluated. RESULTS: Aged, male and people with comorbidities were the main risk factors in the development of severe and critical COVID-19. All of confirmed COVID-19 cases (n = 55) had been treated with interferon-α (IFN-α), of which 81.8% (n = 45, mild and ordinary) of the patients were recovered, 14.6% (n = 8) of the patients were converted to severe, 3.6% (n = 2) of the patients were converted to critical, and some severe patients were treated with gamma globulin and albumin as adjuvant treatment. Critically ill patients were not only treated with IFN-α, gamma globulin and albumin, but also treated with convalescent plasma and MSC transplantation. Due to pulmonary hemorrhage and persistently low blood oxygen saturation, terminal lung transplantation therapy was implemented. The total number of lymphocytes, CD4+, CD8+ T lymphocytes, natural killer (NK) cells and B cells in peripheral blood of the two critical COVID-19 patients were significantly reduced, and the functions of lung, liver, and kidney were severely damaged on admission, manifested as significant increase of the levels of blood C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN), etc. and decrease of blood oxygen saturation, and type I respiratory failure, and the noninvasive assisted ventilation was needed to improve. After adjuvant immunotherapy such as gamma globulin, the nucleic acid of 2019 novel coronavirus (2019-nCoV) turned into negative. The CRP of one critically ill patient was significantly lower than the value at admission (minimum of 21 mg/L). But the lung inflammation progressed rapidly, and the pathological results of the lung tissue from the lung transplantation showed hemorrhage and irreversible fibrosis. The ability to secrete immunoglobulin A (IgA) was significantly reduced. Liver function had been significantly improved and stabilized after treatment with convalescent plasma during the recovery period. MSC transplantation treatment reduced the BUN level by > 50% compared with the previous period, and the total number of lymphocytes in the patient increased by more than 2 times (rose from 0.23×109/L to 0.57×109/L), but the total amount of lymphocytes was still lower than the normal reference value (< 1.1×109/L). The lung inflammation lesions were obviously absorbed, and the vital signs were stable. CONCLUSIONS: In addition to IFN, gamma globulin, antiserum and MSC transplantation therapy can help clear the virus and reduce inflammation. Although MSC transplantation fail to completely change the immunecompromised state of critically ill patients, it controlled the progression of inflammation in the liver and kidneys.