World's First Experience of the Low-Dose Radionuclide Inhalation Therapy in the Treatment of COVID-19-Associated Viral Pneumonia: Phase 1/2 Clinical Trial.

OBJECTIVE: Previously, low-dose radiation therapy was used for pneumonia treatment. We aimed to investigate the safety and effectiveness of carbon nanoparticles labeled with Technetium isotope (99mTc) in a form of ultradispersed aerosol in combination with standard COVID-19 therapy. The study was a randomized phase 1 and phase 2 clinical trial of low-dose radionuclide inhalation therapy for patients with COVID-19 related pneumonia. METHODS: We enrolled 47 patients with confirmed COVID-19 infection and early laboratory signs of cytokine storm and randomized them into the Treatment and Control groups. We analyzed blood parameters reflecting the COVID-19 severity and inflammatory response. RESULTS: Low-dose 99mTc-labeled inhalation showed a minimal accumulation of radionuclide in lungs in healthy volunteers. We observed no significant differences between the groups before treatment in WBC-count, D-dimer, CRP, Ferritin or LDH levels. We found that Ferritin and LDH levels significantly raised after the 7th day follow-up only in the Control group (p < 0.0001 and p = 0.0005, respectively), while mean values of the same indicators did not change in patients in the Treatment group after the radionuclide treatment. D-dimer values also lowered in the radionuclide treated group, however, this effect was not statistically significant. Furthermore, we observed a significant decrease in CD19+ cell counts in patients of the radionuclide-treated group. CONCLUSION: Inhalation low-dose radionuclide therapy of 99mTc aerosol affects the major prognostic indicators of COVID-19- related pneumonia restraining inflammatory response. Overall, we identified no evidence of major adverse events in the group receiving radionuclide.

Prolonged prothrombin time as an early prognostic indicator of severe acute respiratory distress syndrome in patients with COVID-19 related pneumonia.

BACKGROUND: Clinical observations demonstrated that COVID-19 related pneumonia is often accompanied by hematological and coagulation abnormalities including lymphopenia, thrombocytopenia, and prolonged prothrombin time. The evaluation of laboratory findings including coagulation and inflammation parameters may represent a promising approach for early determination of COVID-19 severity. METHODS AND MATERIALS: In the present study, we aimed to identify laboratory parameters present upon admission in patients with COVID-19 related viral pneumonia and associated with an early in-hospital development of refractory respiratory failure or severe acute respiratory distress syndrome requiring treatment in an intensive care unit. We investigated differences in the C-reactive protein (CRP) and fibrinogen levels, prothrombin time (PT) and international normalized ratio (INR) between COVID-19 patients who had been transferred to an ICU within two weeks after admission (n = 82) and COVID-19 patients with stable course of the disease (n = 74). RESULTS: Multiple comparisons showed statistically significantly prolonged PT on admission in ICU-transferred COVID-19 patients (14.15 sec, median, CI 95% 13.4 ÷ 14.9) compared to the stable COVID-19 patients (13.25 sec, median, CI 95% 12.9 ÷ 13.6) (p-value = .0005). CRP levels upon admission were statistically significantly higher in ICU-transferred COVID-19 patients (132 mg/L, median, CI95% 113 ÷ 159) compared to the stable COVID-19 patients (51 mg/L, median, CI95% 33 ÷ 72) (p-value < .0001). On-admission fibrinogen and INR levels did not statistically significantly differ between ICU-transferred COVID-19 patients and stable COVID-19 patients. CONCLUSION: We suggest that CRP and PT levels present on admission in COVID-19 patients may be used as early prognostic markers of severe pneumonia requiring transfer to ICU.