Umbilical cord mesenchymal stem cells for COVID-19

Abstract Background: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. Methods: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients received intravenous infusions of MSCs at a dose of 4 × 107 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. Results: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] v.s 2.11 [1.96, 2.35], P = 0.008; VCmax, 2.92 [2.55, 3.60] v.s 2.47 [2.18, 2.68], P = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] v.s 2.38 [2.24, 2.63], P = 0.017; VCmax, 3.52 [3.02, 3.80] v.s 2.59 [2.45, 3.15], P = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] v.s 2.30 [2.16, 2.70], P = 0.019; VCmax,3.61 [3.35, 3.97] v.s 2.69 [2.56, 3.23], P = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 (P = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. Conclusions: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000031430.

Acute respiratory distress syndrome (ARDS) is intricately linked with SARS-CoV-2-associated disease severity and mortality, especially in patients with co-morbidities. Lung tissue injury caused as a consequence of ARDS leads to fluid build-up in the alveolar sacs, which in turn affects oxygen supply from the capillaries. ARDS is a result of a hyperinflammatory, non-specific local immune response (cytokine storm), which is aggravated as the virus evades and meddles with protective anti-viral innate immune responses. Treatment and management of ARDS remain a major challenge, first, because the condition develops as the virus keeps replicating and, therefore, immunomodulatory drugs are required to be used with caution. Second, the hyperinflammatory responses observed during ARDS are quite heterogeneous and dependent on the stage of the disease and the clinical history of the patients. In this review, we present different anti-rheumatic drugs, natural compounds, monoclonal antibodies, and RNA therapeutics and discuss their application in the management of ARDS. We also discuss on the suitability of each of these drug classes at different stages of the disease. In the last section, we discuss the potential applications of advanced computational approaches in identifying reliable drug targets and in screening out credible lead compounds against ARDS.