Severe flu management: a point of view Torres, Antoni; Loeches, Ignacio-Martin; Sligl, Wendy ...
Intensive care medicine,
02/2020, Letnik:
46, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Annual flu seasons are typically characterized by changes in types and subtypes of influenza, with variations in terms of severity. Despite remarkable improvements in the prevention and management of ...patients with suspected or laboratory-confirmed diagnosis of influenza, annual seasonal influenza continues to be associated with a high morbidity and mortality. Admission to the intensive care unit is required for patients with severe forms of seasonal influenza infection, with primary pneumonia being present in most of the cases. This review summarizes the most recent knowledge on the diagnosis and treatment strategies in critically ill patients with influenza, focused on diagnostic testing methods, antiviral therapy, use of corticosteroids, antibacterial and antifungal therapy, and supportive measures. The review focuses on diagnostic testing methods, antiviral therapy, use of corticosteroids, antibacterial and antifungal therapy, supportive measures and relevant existing evidence, in order to provide the non-expert clinician a useful overview. An enhanced understanding of current diagnostic and treatment aspects of influenza infection can contribute to improve outcomes and reduce mortality among ICU patients with influenza.
COVID19 coagulopathy in Caucasian patients Fogarty, Helen; Townsend, Liam; Ni Cheallaigh, Cliona ...
British journal of haematology,
June 2020, Letnik:
189, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Summary
Although the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung‐centric coagulopathy may play an important role. Elevated D‐dimer ...levels which correlated inversely with overall survival were recently reported in Chinese cohort studies. Critically however, ethnicity has major effects on thrombotic risk, with a 3–4‐fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African‐Americans. In this study, we investigated COVID19 coagulopathy in Caucasian patients. Our findings confirm that severe COVID19 infection is associated with a significant coagulopathy that correlates with disease severity. Importantly however, Caucasian COVID19 patients on low molecular weight heparin thromboprophylaxis rarely develop overt disseminated intravascular coagulation (DIC). In rare COVID19 cases where DIC does develop, it tends to be restricted to late‐stage disease. Collectively, these data suggest that the diffuse bilateral pulmonary inflammation observed in COVID19 is associated with a novel pulmonary‐specific vasculopathy termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC. Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID19 mortality.
Background
Persistent fatigue, breathlessness, and reduced exercise tolerance have been reported following acute COVID‐19 infection. Although immuno‐thrombosis has been implicated in acute COVID‐19 ...pathogenesis, the biological mechanisms underpinning long COVID remain unknown. We hypothesized that pulmonary microvascular immuno‐thrombosis may be important in this context.
Methods
One hundred fifty COVID‐19 patients were reviewed at St James's Hospital Dublin between May and September 2020 at a median of 80.5 (range 44–155) days after initial diagnosis. These included patients hospitalized during initial illness (n = 69) and others managed entirely as out‐patients (n = 81). Clinical examination, chest x‐ray, and 6‐min walk tests were performed. In addition, a range of coagulation and inflammatory markers were assessed.
Results
Increased D‐dimer levels (>500 ng/ml) were observed in 25.3% patients up to 4 months post‐SARS‐CoV‐2 infection. On univariate analysis, elevated convalescent D‐dimers were more common in COVID‐19 patients who had required hospital admission and in patients aged more than 50 years (p < .001). Interestingly, we observed that 29% (n = 11) of patients with elevated convalescent D‐dimers had been managed exclusively as out‐patients during their illness. In contrast, other coagulation (prothrombin time, activated partial thromboplastin time, fibrinogen, platelet count) and inflammation (C‐reactive protein, interleukin‐6, and sCD25) markers had returned to normal in >90% of convalescent patients.
Conclusions
Elucidating the biological mechanisms responsible for sustained D‐dimer increases may be of relevance in long COVID pathogenesis and has implications for clinical management of these patients.
Background
Persistent symptoms including breathlessness, fatigue, and decreased exercise tolerance have been reported in patients after acute SARS‐CoV‐2 infection. The biological mechanisms ...underlying this “long COVID” syndrome remain unknown. However, autopsy studies have highlighted the key roles played by pulmonary endotheliopathy and microvascular immunothrombosis in acute COVID‐19.
Objectives
To assess whether endothelial cell activation may be sustained in convalescent COVID‐19 patients and contribute to long COVID pathogenesis.
Patients and Methods
Fifty patients were reviewed at a median of 68 days following SARS‐CoV‐2 infection. In addition to clinical workup, acute phase markers, endothelial cell (EC) activation and NETosis parameters and thrombin generation were assessed.
Results
Thrombin generation assays revealed significantly shorter lag times (p < .0001, 95% CI −2.57 to −1.02 min), increased endogenous thrombin potential (p = .04, 95% CI 15–416 nM/min), and peak thrombin (p < .0001, 95% CI 39–93 nM) in convalescent COVID‐19 patients. These prothrombotic changes were independent of ongoing acute phase response or active NETosis. Importantly, EC biomarkers including von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), and factor VIII were significantly elevated in convalescent COVID‐19 compared with controls (p = .004, 95% CI 0.09–0.57 IU/ml; p = .009, 95% CI 0.06–0.5 IU/ml; p = .04, 95% CI 0.03–0.44 IU/ml, respectively). In addition, plasma soluble thrombomodulin levels were significantly elevated in convalescent COVID‐19 (p = .02, 95% CI 0.01–2.7 ng/ml). Sustained endotheliopathy was more frequent in older, comorbid patients, and those requiring hospitalization. Finally, both plasma VWF:Ag and VWFpp levels correlated inversely with 6‐min walk tests.
Conclusions
Collectively, our findings demonstrate that sustained endotheliopathy is common in convalescent COVID‐19 and raise the intriguing possibility that this may contribute to long COVID pathogenesis.
Globally, pneumonia is a serious public health concern and a major cause of mortality and morbidity. Despite advances in antimicrobial therapies, microbiological diagnostic tests and prevention ...measures, pneumonia remains the main cause of death from infectious disease in the world. An important reason for the increased global mortality is the impact of pneumonia on chronic diseases, along with the increasing age of the population and the virulence factors of the causative microorganism. The increasing number of multidrug-resistant bacteria, difficult-to-treat microorganisms, and the emergence of new pathogens are a major problem for clinicians when deciding antimicrobial therapy. A key factor for managing and effectively guiding appropriate antimicrobial therapy is an understanding of the role of the different causative microorganisms in the etiology of pneumonia, since it has been shown that the adequacy of initial antimicrobial therapy is a key factor for prognosis in pneumonia. Furthermore, broad-spectrum antibiotic therapies are sometimes given until microbiological results are available and de-escalation cannot be performed quickly. This review provides an overview of microbial etiology, resistance patterns, epidemiology and microbial diagnosis of pneumonia.
An increasing number of critically ill patients are immunocompromised. Acute hypoxemic respiratory failure (ARF), chiefly due to pulmonary infection, is the leading reason for ICU admission. ...Identifying the cause of ARF increases the chances of survival, but may be extremely challenging, as the underlying disease, treatments, and infection combine to create complex clinical pictures. In addition, there may be more than one infectious agent, and the pulmonary manifestations may be related to both infectious and non-infectious insults. Clinically or microbiologically documented bacterial pneumonia accounts for one-third of cases of ARF in immunocompromised patients. Early antibiotic therapy is recommended but decreases the chances of identifying the causative organism(s) to about 50%. Viruses are the second most common cause of severe respiratory infections. Positive tests for a virus in respiratory samples do not necessarily indicate a role for the virus in the current acute illness. Invasive fungal infections (
Aspergillus
,
Mucorales
, and
Pneumocystis jirovecii
) account for about 15% of severe respiratory infections, whereas parasites rarely cause severe acute infections in immunocompromised patients. This review focuses on the diagnosis of severe respiratory infections in immunocompromised patients. Special attention is given to newly validated diagnostic tests designed to be used on non-invasive samples or bronchoalveolar lavage fluid and capable of increasing the likelihood of an early etiological diagnosis.
Prolonged recovery is common after acute SARS-CoV-2 infection; however, the pathophysiological mechanisms underpinning Long COVID syndrome remain unknown. VWF/ADAMTS-13 imbalance, dysregulated ...angiogenesis, and immunothrombosis are hallmarks of acute COVID-19. We hypothesized that VWF/ADAMTS-13 imbalance persists in convalescence together with endothelial cell (EC) activation and angiogenic disturbance. Additionally, we postulate that ongoing immune cell dysfunction may be linked to sustained EC and coagulation activation.
Fifty patients were reviewed at a minimum of 6 weeks following acute COVID-19. ADAMTS-13, Weibel Palade Body (WPB) proteins, and angiogenesis-related proteins were assessed and clinical evaluation and immunophenotyping performed. Comparisons were made with healthy controls (n = 20) and acute COVID-19 patients (n = 36).
ADAMTS-13 levels were reduced (p = 0.009) and the VWF-ADAMTS-13 ratio was increased in convalescence (p = 0.0004). Levels of platelet factor 4 (PF4), a putative protector of VWF, were also elevated (p = 0.0001). A non-significant increase in WPB proteins Angiopoietin-2 (Ang-2) and Osteoprotegerin (OPG) was observed in convalescent patients and WPB markers correlated with EC parameters. Enhanced expression of 21 angiogenesis-related proteins was observed in convalescent COVID-19. Finally, immunophenotyping revealed significantly elevated intermediate monocytes and activated CD4+ and CD8+ T cells in convalescence, which correlated with thrombin generation and endotheliopathy markers, respectively.
Our data provide insights into sustained EC activation, dysregulated angiogenesis, and VWF/ADAMTS-13 axis imbalance in convalescent COVID-19. In keeping with the pivotal role of immunothrombosis in acute COVID-19, our findings support the hypothesis that abnormal T cell and monocyte populations may be important in the context of persistent EC activation and hemostatic dysfunction during convalescence.
In accordance with the recommendations of, amongst others, the Surviving Sepsis Campaign and the recently published European treatment guidelines for hospital-acquired pneumonia (HAP) and ...ventilator-associated pneumonia (VAP), in the event of a patient with such infections, empirical antibiotic treatment must be appropriate and administered as early as possible. The aim of this manuscript is to update treatment protocols by reviewing recently published studies on the treatment of nosocomial pneumonia in the critically ill patients that require invasive respiratory support and patients with HAP from hospital wards that require invasive mechanical ventilation. An interdisciplinary group of experts, comprising specialists in anaesthesia and resuscitation and in intensive care medicine, updated the epidemiology and antimicrobial resistance and established clinical management priorities based on patients' risk factors. Implementation of rapid diagnostic microbiological techniques available and the new antibiotics recently added to the therapeutic arsenal has been reviewed and updated. After analysis of the categories outlined, some recommendations were suggested, and an algorithm to update empirical and targeted treatment in critically ill patients has also been designed. These aspects are key to improve VAP outcomes because of the severity of patients and possible acquisition of multidrug-resistant organisms (MDROs).
In 2023, the new European guidelines on severe community-acquired pneumonia, providing clinical practice recommendations for the management of this life-threatening infection, characterized by a high ...burden of mortality, morbidity, and costs for the society. This review article aims to summarize the principal evidence related to eight different questions covered in the guidelines, by also highlighting the future perspectives for research activity.
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