The temporal changes of hemostatic activity in hospitalized patients with COVID-19: a prospective observational study.

INTRODUCTION: Hemostatic abnormalities play an important role in the pathogenesis of COVID-19 and are considered to be determinants of patients` outcomes. Less is known about the dynamics of these abnormalities in a short-term observation. PATIENTS AND METHODS: This was a prospective observational study enrolling adult patients hospitalized due to COVID-19 in a tertiary centre in Poland from January to May 2021. Blood samples were drawn upon admission and 28 days after admission to measure markers of coagulation, fibrinolysis and endothelial dysfunction and to evaluate whether there are significant differences between these two time points. All analyses were performed in the entire cohort and after stratification into three groups depending on the degree of respiratory support. RESULTS: We recruited 245 patients at the median age of 63 years (IQR 52; 69), among whom 158 (64.5%) were males. Analysis of hemostatic markers on admission revealed hypercoagulability, hypofibrinolysis and endothelial dysfunction are related to degree of respiratory support. We found significant differences between the admission and 28-day follow-up in all markers except for plasminogen activity (123.75 vs. 121.60, p=0.938). Interestingly, markers of endothelial dysfunction remained the highest in the advanced respiratory support group after 28 days, while differences in other markers subsided. CONCLUSION: Hemostatic abnormalities are significantly attenuated within a month after hospital admission due to COVID-19. Initially observed association between severity of disease and hemostatic derangements persists only for markers of endotheliopathy.

Decreased protein C activity, lower ADAMTS13 antigen and free protein S levels accompanied by unchanged thrombin generation potential in hospitalized COVID-19 patients.

INTRODUCTION: COVID-19 is associated with an increased thromboembolic risk. However, the mechanisms triggering clot formation in those patients remain unknown. PATIENTS AND METHODS: In 118 adult Caucasian severe but non-critically ill COVID-19 patients (median age 58 years; 73 % men) and 46 controls, we analyzed in vitro plasma thrombin generation profile (calibrated automated thrombogram [CAT assay]) and investigated thrombophilia-related factors, such as protein C and antithrombin activity, free protein S level, presence of antiphospholipid antibodies and factor V Leiden R506Q and prothrombin G20210A mutations. We also measured circulating von Willebrand factor (vWF) antigen and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) antigen and activity. In patients, blood samples were collected on admission to the hospital before starting any therapy, including heparin. Finally, we examined the relationship between observed alterations and disease follow-up, such as thromboembolic complications. RESULTS: COVID-19 patients showed 17 % lower protein C activity, 22 % decreased free protein S levels, and a higher prevalence of positive results for IgM anticardiolipin antibodies. They also had 151 % increased vWF, and 27 % decreased ADAMTS13 antigens compared with controls (p < 0.001, all). On the contrary, thrombin generation potential was similar to controls. In the follow-up, pulmonary embolism (PE) occurred in thirteen (11 %) patients. They were characterized by a 55 % elevated D-dimer (p = 0.04) and 2.7-fold higher troponin I (p = 0.002) during hospitalization and 29 % shorter time to thrombin peak in CAT assay (p = 0.009) compared to patients without PE. CONCLUSIONS: In COVID-19, we documented prothrombotic abnormalities of peripheral blood. PE was characterized by more dynamic thrombin generation growth in CAT assay performed on admittance to the hospital.

High-flow nasal oxygen therapy in the treatment of acute respiratory failure in severe COVID-19 pneumonia: a prospective observational study.

INTRODUCTION: A significant proportion of patients with COVID­19 present with a rapidly progressing severe acute respiratory failure. OBJECTIVES: We aimed to assess the efficacy of high­flow nasal oxygen (HFNO) therapy in severe acute respiratory failure in the course of COVID­19 in a noncritical care setting as well as to identify predictors of HFNO failure. PATIENTS AND METHODS: This prospective observational study was conducted between March and December 2020. We enrolled all consecutive patients hospitalized with confirmed SARS­CoV­2 infection in whom HFNO therapy was used. The primary outcome was death or endotracheal intubation within 30 days from admission. RESULTS: Of the 380 patients with COVID­19 hospitalized at our tertiary center, 116 individuals (30.5%) requiring HFNO due to severe pneumonia were analyzed. The primary outcome occurred in 54 patients (46.6%). The overall 30­day mortality rates were 30.2% (35 out of 116 patients) in the entire cohort and 64.7% (34 out of 51 patients) among individuals requiring endotracheal intubation. A multivariable analysis revealed that the ROX index (the ratio of oxygen saturation / fraction of inspired oxygen to respiratory rate) below 3.85 measured within the first 12 hours of therapy was related to increased mortality (hazard ratio, 5.86; 95% CI, 3.03-11.35) compared with the ROX index of 4.88 or higher. CONCLUSIONS: The results of our study suggest that nearly half of patients treated with HFNO due to severe COVID­19 pneumonia will require mechanical ventilation. The ROX index is a useful tool for predicting HFNO failure in this population.

A clinical profile and factors associated with severity of the disease among Polish patients hospitalized due to COVID-19 - an observational study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) is one of the greatest clinical challenges of the last decades. Clinical factors associated with severity of the disease remain unclear. The aim of the study was to characterize Polish patients hospitalized due to COVID-19 and to evaluate potential prognostic factors of severe course of the disease. MATERIAL AND METHODS: An observational study was conducted from March to July 2020 in the Pulmonology and Allergology Department of the University Hospital in Kraków, Poland. Consecutive patients with confirmed SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection were enrolled, and data about past medical history, signs and symptoms, laboratory results, imaging studies results, in-hospital management and outcomes was prospectively gathered. RESULTS: The study sample comprised 100 patients at the mean age of 59.2 (SD 16.1) years among whom 63 (63.0%) were male. Among them 10 (10.0%) died, 47 (47%) presented respiratory failure, 15 (15.0%) were transferred to the intensive care unit, 17 (17.0%) developed acute kidney injury, 7 (7.0%) had sepsis and 10 (10.0%) were diagnosed with pulmonary embolism. Multivariable analysis revealed age (OR 1.1; 95% CI 1.01-1.15), body mass index (BMI; OR 1.24; 95% CI 1.01-1.53), modified early warning score (MEWS; OR 3.95; 95% CI 1.48-12), the highest d-dimer value (OR 1.73; 95% CI 1.03-2.9) and lactate dehydrogenase (LDH; OR 1.16; 95% CI 1.03-1.3) to be associated with severe course of COVID-19. CONCLUSION: This observational study showed that almost half of hospitalized patients with COVID-19 developed respiratory failure in the course of the disease. Increasing age, BMI, MEWS, d-dimer value and LDH concentration were associated with the severity of COVID-19.