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Introduction: After the rapid surge of a novel coronavirus (SARS-CoV-2) in 2020 anti-SARS-CoV-2 vaccines have been developed to prevent the development of critical forms of COVID-19 leading to Intensive Care Unit (ICU) admission. The possibility of ICU admission after the first-cycle vaccination has been already reported; however, no data have been published regarding vaccinated patients with a "booster" dose. This retrospective study describes the characteristics of critically ill patients after the implementation of the regional "booster" dose vaccination program in a southern region of Italy. Materials and methods: We screened all medical records of critically ill COVID-19 patients in the period between January to April 2022. We collected the demographic characteristics, the presence of comorbidities, the vaccination status, the clinical course (arterial blood gases and type of respiratory support) and outcomes (rate of tracheostomy, ICU length of stay and mortality). Results: A total of 272 patients were admitted to ICUs during the study period. 161 patients were unvaccinated, whereas 111 were vaccinated with the complete first-cycle or "booster" dose. The type of respiratory support was similar between groups. Vaccinated patients were characterized by a better oxygenation throughout the whole ICU length of stay. Fourteen unvaccinated and 3 vaccinated patients required tracheostomy (p = 0.045). ICU length of stay was 12.2 (± 7.3) days in unvaccinated patients and 10.4 (± 6.7) days in vaccinated patients (p = 0.036). ICU mortalities were 38.5 and 24.3% in unvaccinated and vaccinated patients, respectively (p = 0.014). Conclusion: Vaccinated patients have better clinical course and outcomes as compared to the unvaccinated population.
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(1) Background: In COVID-19 patients, the occurrence of thromboembolic complications contributes to disease progression and mortality. In patients at increased risk for thrombotic complications, therapeutic enoxaparin should be considered. However, critically ill COVID-19 patients could develop resistance to enoxaparin. Bivalirudin, a thrombin inhibitor, may be an alternative. This pilot multicenter randomized controlled trial aims to ascertain if bivalirudin may reduce the time spent under invasive mechanical ventilation, as compared to enoxaparin. (2) Methods: Intubated COVID-19 patients at risk for thrombo-embolic complications were randomized to receive therapeutic doses of enoxaparin or bivalirudin. We ascertained the time spent under invasive mechanical ventilation during the first 28 days from Intensive Care Unit (ICU) admission. A standardized weaning protocol was implemented in all centers. In addition, we assessed the occurrence of thromboembolic complications, the number of patients requiring percutaneous tracheostomy, the gas exchange, the reintubation rate, the ICU length of stay, the ICU and 28-days mortalities. (3) Results: We enrolled 58 consecutive patients. Bivalirudin did not reduce the time spent under invasive mechanical ventilation as compared to enoxaparin (12 [8; 13] vs. 13 [10; 15] days, respectively; p = 0.078). Thrombotic (p = 0.056) and embolic (p = 0.423) complications, need for tracheostomy (p = 0.423) or reintubation (p = 0.999), the ICU length of stay (p = 0.076) and mortality (p = 0.777) were also similar between treatments. Patients randomized to bivalirudin showed a higher oxygenation at day 7 and 15 after randomization, when compared to enoxaparin group. (4) Conclusions: In intubated COVID-19 patients at increased risk for thromboembolic complications, bivalirudin did not reduce the time spent under invasive mechanical ventilation, nor improved any other clinical outcomes.
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Since SARS-CoV-2 outbreak in December 2019, world health-system has been severely impacted with increased hospitalization, Intensive-Care-Unit (ICU) access and high mortality rates, mostly due to severe acute respiratory failure and multi-organ failure. Excessive and uncontrolled release of proinflammatory cytokines (cytokine release/storm syndrome, CRS) have been linked to the development of these events. The recent advancements of immunotherapy for the treatment of hematologic and solid tumors shed light on many of the molecular mechanisms underlying this phenomenon, thus rendering desirable a multidisciplinary approach to improve COVID-19 patients' outcome. Indeed, currently available therapeutic-strategies to overcome CRS, should be urgently evaluated for their capability of reducing COVID-19 mortality. Notably, COVID-19 shares different pathogenic aspects with acute graft-versus-host-disease (aGVHD), hemophagocytic-lymphohistiocytosis (HLH), myelofibrosis, and CAR-T-associated CRS. Specifically, similarly to aGVHD, an induced tissue damage (caused by the virus) leads to increased cytokine release (TNFα and IL-6) which in turn leads to exaggerated dendritic cells, macrophages (like in HLH) and lymphocytes (as in CAR-T) activation, immune-cells migration, and tissue-damage (including late-stage fibrosis, similar to myelofibrosis). Janus Kinase (JAK) signaling represents a molecular hub linking all these events, rendering JAK-inhibitors suitable to limit deleterious effects of an overwhelming inflammatory-response. Accordingly, ruxolitinib is the only selective JAK1 and JAK2-inhibitor approved for the treatment of myelofibrosis and aGVHD. Here, we discuss, from a molecular and hematological point of view, the rationale for targeting JAK signaling in the management of COVID-19 patients and report the clinical results of a patient admitted to ICU among the firsts to be treated with ruxolitinib in Italy.
