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Background and Objective: The risk of thrombotic complications in critical patients with COVID-19 remains extremely high, and multicenter trials failed to prove a survival benefit of escalated doses of low-molecular-weight heparins (nadroparin calcium) in this group. The aim of this study was to develop a pharmacokinetic model of nadroparin according to different stages of COVID-19 severity., Methods: Blood samples were obtained from 43 patients with COVID-19 who received nadroparin and were treated with conventional oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation. We recorded clinical, biochemical, and hemodynamic variables during 72 h of treatment. The analyzed data comprised 782 serum nadroparin concentrations and 219 anti-Xa levels. We conducted population nonlinear mixed-effects modeling (NONMEM) and performed Monte Carlo simulations of the probability of target attainment for reaching 0.2-0.5 IU/mL anti-Xa levels in study groups., Results: We successfully developed a one-compartment model to describe the population pharmacokinetics of nadroparin in different stages of COVID-19. The absorption rate constant of nadroparin was 3.8 and 3.2 times lower, concentration clearance was 2.22 and 2.93 times higher, and anti-Xa clearance was 0.87 and 1.1 times higher in mechanically ventilated patients and the extracorporeal membrane oxygenation group compared with patients treated with conventional oxygen, respectively. The newly developed model indicated that 5.900 IU of nadroparin given subcutaneously twice daily in the mechanically ventilated patients led to a similar probability of target attainment of 90% as 5.900 IU of subcutaneous nadroparin given once daily in the group supplemented with conventional oxygen., Conclusions: Different nadroparin dosing is required for patients undergoing mechanical ventilation and extracorporeal membrane oxygenation to achieve the same targets as those for non-critically ill patients., Clinical Trial Registration: ClinicalTrials.gov identifier no. NCT05621915., (© 2023. The Author(s).)

Background: Available data identify pregnancy as a strong determinant of a severe course of COVID-19 with increased mortality. Extracorporeal membrane oxygenation (ECMO) remains the last resort treatment in the critical course of COVID-19 yet may increase the risk of excessive bleeding, especially in the immediate post-cesarean section period. One in five patients receiving ECMO during the COVID-19 pandemic were women who were pregnant or postpartum. While the risk of critical respiratory failure in the peripartum period is high, in an early survey only 52% of pregnant patients intended to receive the COVID-19 vaccine., Methods: Our study aimed to evaluate clinical characteristics and treatment modalities in a series of five pregnant and peripartum women supported with ECMO and anticoagulated with anti-Xa-guided nadroparin therapy in our center. We reviewed the full treatment courses; inflammatory, hemodynamic, and coagulation variables; and maternal and neonatal outcomes. We identified adverse events during the therapy., Results: All five patients developed acute respiratory distress syndrome due to COVID-19 in the third trimester of pregnancy. Termination of pregnancy occurred between 28 and 36 gestational weeks. While four of five newborns survived to hospital discharge, only two of the five mothers survived to leave hospital., Conclusions: ECMO is feasible in the third trimester but not devoid of complications. The severity of respiratory failure during COVID-19 and extracorporeal support may not adversely impact neonatal outcomes., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Bacterial superinfections are common in severely ill COVID-19 patients and could be associated with a significant increase in morbidity and mortality., Material and Methods: We assessed 29 critically ill patients treated in a university hospital's intensive care unit (ICU). Each patient required mechanical ventilation due to COVID-19-induced acute respiratory distress syndrome (ARDS). Fifteen patients who required venovenous extracorporeal membrane oxygenation (VV-ECMO) support (ECMO group) were compared to a control group (CON group) of 14 individuals without ECMO. This study aimed to assess the prevalence of superinfection in both studied groups. Moreover, we evaluated mortality, length of stay in the ICU, positive culture results, antibiotics used during treatment, and the impact of immunomodulatory drugs on secondary infections., Results: We did not find a difference in the number of superinfections between the ECMO and CON groups (11 vs. 10, P = 1.0). The mortality rate was 67% in the ECMO group and 64% in the CON group ( P = 1.0). The patients in both groups had similar numbers of positive culture results and days in the ICU prior to the detection of a positive culture. Antibiotics were administered to ten patients in the ECMO and eight patients in the CON group. The mortality rate was 81% in patients with superinfection versus 25% in those without co-infection ( P = 0.009). We found a negative impact of urea concentration on mortality in our cohort, with an odds ratio of 0.942 (0.891-0.996, P = 0.034)., Conclusions: Our results suggest that bacterial superinfection in COVID-19 patients negatively impacted survival in the ICU. VV-ECMO support in COVID-19 patients does not seem to improve the outcomes of patients with severe ARDS.

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout Europe. However, there is a lack of data on the full clinical course of patients infected with SARS-CoV-2 in Europe, especially in the population that developed acute respiratory failure (ARF)., Objectives: To identify risk factors associated with developing ARF during SARS-CoV-2 infection., Material and Methods: This was an observational study of 60 adult patients with laboratory-confirmed SARS-CoV-2 infection. Data were collected from March 26, 2020 to May 26, 2020 in a tertiary academic hospital in Poland. All patients reached final outcome (discharge from the hospital or death). We divided patients into 2 groups based on whether they developed ARF, compared their clinical data, and performed multivariate logistic regression., Results: Twenty-two patients (36%) from the observed cohort developed ARF. Logistic regression identified that a high sequential organ failure assessment score at admission (odds ratio (OR) = 6.97 (1.57-30.90, p = 0.011)), and a long time from admission until pneumonia (OR = 1.41 (1.06-1.87, p = 0.016)), correlated with ARF development. D-dimer, lactate dehydrogenase, neutrophil to lymphocyte ratio, C-reactive protein (CRP), and interleukin 6 (IL-6) differed both statistically and clinically between ARF and non-ARF groups. The mortality rate in the observed cohort of patients was 13.3%, and it was 32% in the group that developed ARF., Conclusions: Routine vigilant examination of the above markers may identify patients at the highest risk of ARF early on during COVID-19 infection.