Placenta-Derived Cell Therapy to Treat Patients With Respiratory Failure Due to Coronavirus Disease 2019.

OBJECTIVES: To determine whether placental cell therapy PLacental eXpanded (PLX)-PAD (Pluristem Therapeutics, Haifa, Israel) may be beneficial to treating critically ill patients suffering from acute respiratory distress syndrome due to coronavirus disease 2019. DESIGN: Retrospective case report of critically ill coronavirus disease 2019 patients treated with PLacental eXpanded (PLX)-PAD from March 26, 2020, to April 4, 2020, with follow-up through May 2, 2020. SETTING: Four hospitals in Israel (Rambam Health Care Campus, Bnai Zion Medical Center, and Samson Assuta Ashdod University Hospital), and Holy Name Medical Center in New Jersey. PATIENTS: Eight critically ill patients on invasive mechanical ventilation, suffering from acute respiratory distress syndrome due to coronavirus disease 2019. INTERVENTIONS: Intramuscular injection of PLacental eXpanded (PLX)-PAD (300 × 106 cells) given as one to two treatments. MEASUREMENTS AND MAIN RESULTS: Mortality, time to discharge, and changes in blood and respiratory variables were monitored during hospitalization to day 17 posttreatment. Of the eight patients treated (median age 55 yr, seven males and one female), five were discharged, two remained hospitalized, and one died. By day 3 postinjection, mean C-reactive protein fell 45% (240.3-131.3 mg/L; p = 0.0019) and fell to 77% by day 5 (56.0 mg/L; p < 0.0001). Pao2/Fio2 improved in 5:8 patients after 24-hour posttreatment, with similar effects 48-hour posttreatment. A decrease in positive end-expiratory pressure and increase in pH were statistically significant between days 0 and 14 (p = 0.0032 and p = 0.00072, respectively). A decrease in hemoglobin was statistically significant for days 0-5 and 0-14 (p = 0.015 and p = 0.0028, respectively), whereas for creatinine, it was statistically significant between days 0 and 14 (p = 0.032). CONCLUSIONS: Improvement in several variables such as C-reactive protein, positive end-expiratory pressure, and Pao2/Fio2 was observed following PLacental eXpanded (PLX)-PAD treatment, suggesting possible therapeutic effect. However, interpretation of the data is limited due to the small sample size, use of concomitant investigational therapies, and the uncontrolled study design. The efficacy of PLacental eXpanded (PLX)-PAD in coronavirus disease 2019 should be further evaluated in a controlled clinical trial.

Immature platelets in patients with Covid-19: association with disease severity.

Coronavirus disease 2019 (Covid-19) is associated with a high incidence of venous and arterial thromboembolic events. Currently, there are no clinical or laboratory markers that predict thrombotic risk. Circulating immature platelets are hyper-reactive platelets, which are associated with arterial thrombotic events. The aim of this study was to assess whether the proportion of circulating immature platelets is associated with disease severity in Covid-19 patients. Patients admitted with Covid-19 disease were prospectively assessed. Immature platelet count (IPC) and immature platelet fraction (IPF) were measured at admission and at additional time points during the hospital course using the Sysmex XN-3000 auto-analyzer. A total of 136 consecutive patients with Covid-19 were recruited [mean age 60 ± 19 years, 49% woman, 56 (41%) had mild-moderate disease and 80 (59%) had severe disease at presentation]. The median IPF% was higher in patients with severe compared to mild-moderate disease [5.8 (3.9-8.7) vs. 4.2 (2.73-6.45), respectively, p = 0.01]. The maximal IPC value was also higher in patients with severe disease [15 (10.03-21.56), vs 10.9 (IQR 6.79-15.62), respectively, p = 0.001]. Increased IPC was associated with increased length of hospital stay. Patients with severe Covid-19 have higher levels of IPF than patients with mild-moderate disease. IPF may serve as a prognostic marker for disease severity in Covid-19 patients.

Immature platelets in patients hospitalized with Covid-19.

Coronavirus disease 2019 (Covid-19) is associated with high incidence of venous and arterial thromboembolic events. Currently, there are no markers to guide antithrombotic therapy in Covid-19. Immature platelets represent a population of hyper-reactive platelets associated with arterial events. This prospective study compared consecutive Covid-19 patients (n = 47, median age = 56 years) to patients with acute myocardial infarction (AMI, n = 100, median age = 59 years) and a group of stable patients with cardiovascular risk factors (n = 64, median age = 68 years). Immature platelet fraction (IPF) and immature platelet count (IPC) were determined by the Sysmex XN-3000 auto-analyzer on admission and at subsequent time-points. IPF% on admission was higher in Covid-19 than the stable group and similar to the AMI group (4.8% [IQR 3.4-6.9], 3.5% [2.7-5.1], 4.55% [3.0-6.75], respectively, p = 0.0053). IPC on admission was also higher in Covid-19 than the stable group and similar to the AMI group (10.8 × 109/L [8.3-18.1], 7.35 × 109/L [5.3-10.5], 10.7 × 109/L [7.7-16.8], respectively, P < 0.0001). The maximal IPF% among the Covid-19 group was higher than the stable group and similar to the AMI group. The maximal IPC in Covid-19 was higher than the maximal IPC in both the stable and AMI groups (COVID-19: 14.4 × 109/L [9.4-20.9], AMI: 10.9 × 109/L [7.6-15.2], P = 0.0035, Stable: 7.55 × 109/L [5.55-10.5], P < 0.0001). Patients with Covid-19 have increased immature platelets indices compared to stable patients with cardiovascular risk factors, and as the disease progresses also compared to AMI patients. The enhanced platelet turnover and reactivity may have a role in the development of thrombotic events in Covid-19 patients.