Impact of Alteplase on Mortality in Critically Ill Patients with COVID-19 and Pulmonary Embolism.

COVID-19 is an independent risk factor for pulmonary embolism (PE). Little is known about alteplase therapy in this patient group. A retrospective study analyzed 74 patients with PE and acute respiratory distress syndrome (ARDS) due to COVID-19 who were hospitalized in the intensive care unit in 2021. Patients with or without confirmed right heart thrombi (RHT) were treated with unfractionated heparin or alteplase. The mortality rate in patients with RHT treated with heparin was 100% compared to 37.9% and 55.2% in those treated with alteplase without RHT and alteplase with RHT, respectively. The risk of death in the alteplase group increased with delayed thrombolysis (p = 0.009, odds ratio (OR) = 1.73 95% CI (confidence interval) 1.14-2.62), increased D-dimer concentration (p = 0.02, OR = 1.43 95% CI 1.06-1.93), and decreased PaO2/FiO2 ratio (p = 0.001, OR = 0.56 95% CI 0.41-0.78). The receiver operating characteristic method determined that a 1-day delay in thrombolytic treatment, D-dimer concentration >5.844 mg/L, and PaO2/FiO2 <144 mmHg predicted a fatal outcome. The risk of death in patients with severe COVID-19 with ARDS and PE increases with higher D-dimer levels, decreased PaO2/FiO2, and delayed thrombolytic treatment. Thrombolysis seems to be treatment of choice in severe COVID-19 with PE and RHT. It should be carried out as soon as possible after the diagnosis is established.

Efficacy of Sildenafil in Patients with Severe COVID-19 and Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is common in severe coronavirus disease 2019 (COVID-19) and worsens the prognosis. Sildenafil, a phosphodiesterase-5 inhibitor, is approved for PAH treatment but little is known about its efficacy in cases of severe COVID-19 with PAH. This study aimed to investigate the clinical efficacy of sildenafil in patients with severe COVID-19 and PAH. Intensive care unit (ICU) patients were randomly assigned to receive sildenafil or a placebo, with 75 participants in each group. Sildenafil was administered orally at 0.25 mg/kg t.i.d. for one week in a placebo-controlled, double-blind manner as an add-on therapy alongside the patient's routine treatment. The primary endpoint was one-week mortality, and the secondary endpoints were the one-week intubation rate and duration of ICU stay. The mortality rate was 4% vs. 13.3% (p = 0.078), the intubation rate was 8% and 18.7% (p = 0.09), and the length of ICU stay was 15 vs. 19 days (p < 0.001) for the sildenafil and placebo groups, respectively. If adjusted for PAH, sildenafil treatment significantly reduced mortality and intubation risks: OR = 0.21 (95% CI: 0.05-0.89) and OR = 0.26 (95% CI: 0.08-0.86), respectively. Sildenafil demonstrated some clinical efficacy in patients with severe COVID-19 and PAH and should be considered as an add-on therapy in these patients.

Lack of Difference in Tocilizumab Efficacy in the Treatment of Severe COVID-19 Caused by Different SARS-CoV-2 Variants.

Tocilizumab (TOC) is presumed to be an effective and safe treatment for severe COVID-19, but its usefulness has not been yet investigated for different SARS-CoV-2 variants. This study aimed to evaluate the influence of TOC on mortality in patients with severe COVID-19 caused by Delta and non-Delta SARS-CoV-2 variants. In a retrospective analysis, we compared the medical records of 78 and 224 patients with severe COVID-19 due to Delta and non-Delta variants, respectively. A total of 30 patients with Delta and 84 with non-Delta variants were treated with TOC in addition to standard therapy. There were no statistically significant differences in mortality rate when comparing Delta vs. non-Delta patients nor when comparing those treated with TOC vs. not treated with TOC in both variants. Using a logistic regression model, in the examined population as a whole, we found an increased (p < 0.05) risk of death as leukocyte and erythrocyte counts decreased and as procalcitonin increased. Increased procalcitonin was significant for mortality in the Delta group, while decreased IL-6, leukocytes, and platelets and increased fibrinogen and procalcitonin were significant in the non-Delta group. Tocilizumab efficacy in severe COVID-19 does not differ between Delta or non-Delta virus variants. The Delta variant of SARS-CoV-2 does not increase mortality when compared to other virus strains.

Comparison of the Effect of Unfractionated Heparin and Enoxaparin Sodium at Different Doses on the Course of COVID-19-Associated Coagulopathy.

BACKGROUND: COVID-19-associated coagulopathy (CAC) exacerbates the course of coronavirus infection and contributes to increased mortality. Current recommendations for CAC treatment include the use of low-molecular weight heparins (LMWH) at prophylactic or therapeutic doses, as well as the use of unfractionated heparin (UFH). METHODS: A randomised, controlled trial enrolled 126 patients hospitalised in the intensive care unit with severe COVID-19 complicated by CAC. The effects of LMWH at preventive and therapeutic doses and UFH at therapeutic doses on mortality and intubation rates were compared. RESULTS: The number of intubations and deaths showed no significant difference depending on the anticoagulant therapy used. However, multivariate logistic regression models revealed an increased risk of intubation (p = 0.026, odds ratio (OR) = 3.33, 95% confidence interval (CI) 1.15-9.59), and an increased risk of death (p = 0.046, OR = 3.01, 95% CI 1.02-8.90), for patients treated with LMWH at a prophylactic dose but not at a therapeutic dose as compared to patients treated with UFH when controlling for other risk factors. CONCLUSIONS: The use of unfractionated heparin in the treatment of COVID-19-associated coagulopathy seems to be more effective at reducing the risk of intubation and death than enoxaparin at prophylactic doses.

Efficacy of Tocilizumab Therapy in Different Subtypes of COVID-19 Cytokine Storm Syndrome.

BACKGROUND: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis. METHODS: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In the MAS and CRS groups, treatment results were assessed depending on whether or not tocilizumab was used. RESULTS: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/mL, p < 0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients (p = 0.043), RR = 2.1 (95% CI 1.0-4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients (p = 0.013), RR = 0.50 (95% CI 0.25-0.99). CONCLUSIONS: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients, it contributed to reduced mortality.