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Introduction: Patients with COVID-19-related acute respiratory distress syndrome (ARDS) require respiratory support with invasive mechanical ventilation and show varying responses to recruitment manoeuvres. In patients with ARDS not related to COVID-19, two pulmonary subphenotypes that differed in recruitability were identified using latent class analysis (LCA) of imaging and clinical respiratory parameters [1]. We aimed to validate these phenotypes and evaluate if similar subphenotypes are present in patients with COVID-19-related ARDS. Method(s): This is the retrospective analysis of mechanically ventilated patients with COVID-19-related ARDS who underwent CT scans at positive end-expiratory pressure of 10 cmH2O and after a recruitment manoeuvre at 20 cmH2O. LCA was applied to quantitative CT-derived parameters, clinical respiratory parameters, blood gas analysis and routine laboratory values before recruitment to identify subphenotypes. Result(s): 99 patients were included. Using 12 variables, a two-class LCA model was identified as best fitting. Subphenotype 2 (recruitable) was characterized by a lower PaO2/ FiO2, lower normally aerated lung volume and lower compliance as opposed to a higher nonaerated lung mass and higher mechanical power when compared to subphenotype 1 (non-recruitable) (Fig. 1). Patients with subphenotype 2 had more decrease in non-aerated lung mass in response to a standardized recruitment manoeuvre (p = 0.024) and were mechanically ventilated longer until successful extubation (adjusted SHR 0.46, 95% CI 0.23-0.91, p = 0.026), while no difference in survival was found (p = 0.814). Conclusion(s): A recruitable and non-recruitable subphenotype were identified in patients with COVID-19-related ARDS. The subphenotypes are similar to non-COVID-19-related ARDS and are promising for identification of recruitable patients in future practice as they can be classified with only few clinically available parameters before the recruitment manoeuvre.
ABSTRACT
Introduction: Since 2020 COVID-19 pandemic has spread throughout the world and became an ongoing global health crisis due to SARS-CoV-2 virus. Elderly and pre-existing disorders including hypertension, heart problems, diabetes, cancer, autoimmune diseases and IBD are found associated with an increased risk of COVID-19. Although COVID-19 leads to mild flu-like symptoms in the majority of patients, the disease may cause severe complications and death. To date, a few clinical studies suggested that IBD and/or immunomodulation may reduce the susceptibility to COVID-19;however, the mechanisms through which this is happening is largely unknown. Aims & Methods: Aim of this study is to investigate the effects of IBD and different therapies on the risk of SARS-CoV-2 infection and COVID-19 severity through serum proteomics and metabolomics. Between April 2020 and April 2022, 238 IBD patients (N=145 Crohn disease, N=93 Ulcerative colitis) and 45 healthy controls (HC) of the North Italy area were enrolled and serum samples were collected. To evaluate the exposure to SARSCoV- 2, both clinical data were collected and seroprevalence of anti-SARSCoV- 2 Ab were analyzed by means of multiplex technology, the BioPlex 2200 Sars-Cov-2 IgG Panel (biorad, Italy). Serum samples underwent untargeted metabolomics analysis and the frequency of a serum metabolomics signature associated with protection were evaluated in IBD compared to HC and also between anti-TNF and Vedolizumab biological therapies for IBD patients. Result(s): The seroprevalence of anti-SARS-CoV-2 Ab in IBD cohort (22/238) indicates an overall lower incidence of COVID-19 in comparison with the general population of Lombardy. Our data indicated that IBD patients in treated with biologic drugs as anti-TNF (10,5%) and Vedolizumab (7,5%) have a lower incidence than IBD patients treated with conventional therapies (28,0%). Accordingly, we observed that serum metabolomics signature associated with protection was more frequent in IBD patients treated with anti-TNF (N=50, 70%), and with Vedolizumab (N=57, 85%) than healthy controls (N=45, 50%). The metabolomic protective profile is characterized by the presence of fat-soluble Tocopherols family members and Cholecalciferol and also of omega-3 and omega-6 polyunsaturated fatty acid. Conclusion(s): Our study indicates that IBD population treated with biologics has an overall lower risk to contract SARS-CoV-2 infection and a serum proteomic/metabolomic protection profile. The increased presence in IBD patients of radical scavengers such as tocopherols which are incorporated into cell membranes and protect against oxidative damage and anti-inflammatory and immunomodulating fatty acids suggest a better response to SARS-CoV-2 infection. Also increased levels of omega;-3 interfere with the entry of the virus by modulating the Lipid Rafts where ACE2 and TMPRSS2 are mainly expressed and PUFAs inhibit the attachment of SARS-CoV-2 virions to the human ACE2 receptor by interacting directly with the RBD sequence. Mechanistically understanding how this protection profile exerts its effects on COVID-19 severity might shed light on potential targets to increase resistance in higher risk subgroups of patients.
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Introduction: The current pandemia is due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that was originally identified in China in 2019, when numerous cases of atypical pneumonia were reported. Elderly and pre-existing disorders including hypertension, heart problems, diabetes, cancer, autoimmune diseases and IBD are found associated with an increased risk of COVID-19. A few clinical studies suggested that IBD and immunomodulation may reduce the susceptibility to COVID-19;however, the molecular mechanisms are not fully revealed. Aims & Methods: In this study, we attempted to identify a transcriptomic signature as candidate of the effects of IBD and different therapies on the risk of SARS-CoV-2 infection and COVID-19 severity through colonic tissue gene expression. In 2020-2022, 192 IBD patients, 115 Crohn disease (CD), 77 Ulcerative colitis (UC) and 36 Healthy Controls (HC) of the North Italy area were enrolled. Colon biopsies from inflamed and non-inflamed mucosa were collected from IBD patients and healthy mucosa samples were collected from HC. To evaluate the exposure to SARS-CoV-2, clinical data were collected and seroprevalence of anti-SARS-CoV-2 Ab were analyzed by means of multiplex technology with BioPlex 2200 Sars-Cov-2 IgG Panel (biorad, Italy). Gene expression analysis of ACE2, TMPRSS2, TMPRSS4, ADAM17 were performed by qPCR in biopsies of the three experimental groups. Result(s): In IBD patients cohort the seroprevalence of anti-SARS-CoV-2 antibodies indicates an overall lower incidence of COVID-19 in comparison with the general population of Lombardy, and also a lower incidence in IBD patients in biological therapies vs. conventional ones. Gene expression analysis of the proteins involved in SARS-CoV-2 entry indicated that IBD patients treated with anti-TNF (N=72) had a lower mucosal level of SARS-CoV-2 receptor ACE2 and its sheddase ADAM17 than non-IBD subjects along with higher expression of the proteases TMPRSS2 and TMPRSS4. Moreover, vedolizumab-treated patients (N=40) showed a significant lower expression of ACE2, TMPRSS2 and TMPRSS4 than controls, whereas ADAM17 levels were similar. Conclusion(s): Data presented in our study suggest that the biologic-treated IBD population has an overall lower risk of contracting SARS-CoV-2 infection. Colonic expression of proteins involved in SARS-CoV-2 virus entry suggested an additional protective mechanism. Understanding the association of this protection profile with COVID-19 severity and the mechanisms of virus entry into the colon could reveal resistance pathways in higher-risk patient subgroups.
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SARS-CoV-2 virus caused millions of admissions to the hospital and deaths due to ARDS;it was immediately clear that ARDS in COVID was different to classical ARDS. Despite invasive mechanical ventilation should be the key of ARDS treatment it’s not unusual to use noninvasive ventilation (NIV). Today, although there are several promising studies about mortality and safety, there are no guidelines or strong evidences about the use of the NIV in COVID-19 ARDS, therefore careful monitoring it’s important during the use of the NIV not to delay intubation and protective ventilation especially in patients with severe respiratory exchange deficit (PaO2/FiO2 < 200).
Subject(s)
COVID-19 , Respiratory Insufficiency , Hospitalization , Humans , Intensive Care Units , SARS-CoV-2ABSTRACT
AIM: To determine whether the duration of respiratory distress symptoms in severe COVID-19 pneumonia affects the need for invasive mechanical ventilation and clinical outcomes. MATERIALS AND METHODS: An observational multicentre cohort study of patients hospitalised in five COVID-19-designated ICUs of the University Hospitals of Emilia-Romagna Region. Patients included were adults with pneumonia due to SARS-CoV-2 with PaO2/FiO2 ratio <300 mmHg, respiratory distress symptoms, and need for mechanical ventilation (invasive or non-invasive). Exclusion criteria were an uncertain time of respiratory distress, end-of-life decision, and mechanical respiratory support before hospital admission. MEASUREMENTS AND MAIN RESULTS: We analysed 171 patients stratified into tertiles according to respiratory distress duration (distress time, DT) before application of mechanical ventilation support. The rate of patients requiring invasive mechanical ventilation was significantly different (p < 0.001) among the tertiles: 17/57 patients in the shortest duration, 29/57 in the intermediate duration, and 40/57 in the longest duration. The respiratory distress time significantly increased the risk of invasive ventilation in the univariate analysis (OR 5.5 [CI 2.48-12.35], p = 0.003). Multivariable regression analysis confirmed this association (OR 10.7 [CI 2.89-39.41], p < 0.001). Clinical outcomes (mortality and hospital stay) did not show significant differences between DT tertiles. DISCUSSION: Albeit preliminary and retrospective, our data raised the hypothesis that the duration of respiratory distress symptoms may play a role in COVID-19 patients' need for invasive mechanical ventilation. Furthermore, our observations suggested that specific strategies may be directed towards identifying and managing early symptoms of respiratory distress, regardless of the levels of hypoxemia and the severity of the dyspnoea itself.
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Background: The current novel coronavirus (SARS-CoV-2) pandemic is an ongoing global health crisis, which represents an important challenge for the whole society and mankind. Patients with inflammatory bowel disease (IBD) are treated with immunosuppressive drugs that are usually associated with more severe viral infections. However, the effects of the different therapies on the risk of SARS-CoV-2 infection and Covid-19 severity in IBD patients are still under investigation. Methods: Between April 2020 and April 2021, 238 IBD patients (N=145 with Crohn disease and N=93 with Ulcerative colitis) of the North Italy area have been enrolled. Both serum samples (N=238 IBD patients and N=45 healthy donors) and colon biopsies from inflamed and non-inflamed mucosa (N=88 IBD patients N=20 non-IBD control) have been collected. To evaluate the exposure to SARS-CoV-2, both clinical data and seroprevalence of anti-SARS-CoV-2 Ab have been analyzed. Serum samples were analyzed by untargeted metabolomics analysis and the frequency of a serum metabolomics signature associated with protection were evaluated in IBD versus healthy donors. Moreover, gene expression analysis of key proteins for virus entry (ACE2, TMPRSS2, TMPRSS4, ADAM17) were analyzed by qPCR in the gut mucosa biopsies of IBD patients. Results: The seroprevalence of anti-SARS-CoV-2 Ab in our cohort of IBD patients (10/238) indicates an overall lower incidence of COVID-19 in comparison with the general population of Lombardy. Accordingly, we observed that the serum metabolomics signature associated with protection was more frequent in IBD patients treated with anti-TNF (N=50, 70%), than healthy controls (N=45, 50%). Gene expression analysis of the proteins involved in SARS-CoV-2 entry also indicated that IBD patients treated with anti-TNF (N=14) had a lower mucosal level of SARS-CoV-2 receptor ACE2 and its sheddase ADAM17 than non-IBD subjects along with higher expression of the proteases TMPRSS2 and TMPRSS4. Moreover, vedolizumab-treated patients (N=7) showed a significant lower expression of ACE2, TMPRSS2 and TMPRSS4 than controls, whereas ADAM17 levels were similar. Conclusion: Our study indicates that IBD population treated with biologics has an overall lower risk to contract SARS-CoV-2 infection. Future studies to gather the mechanisms underpinning the effects of biologics on the expression of the proteins involved in SARS-CoV-2 viral entry in association with the specific metabolomics signature of viral susceptibility might shed light on potential targets to increase resistance in higher risk subgroups of patients.
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WATERLIT Abstract: Management of patients with severe or critical COVID-19 is mainly modeled after care of patients with severe pneumonia or acute respiratory distress syndrome from other causes. These models are based on evidence that primarily originates from investigations in high-income countries, but it may be impractical to apply these recommendations to resource-restricted settings in low- and middle-income countries (LMICs). We report on a set of pragmatic recommendations for microbiology and laboratory testing, imaging, and the use of diagnostic and prognostic models in patients with severe COVID-19 in LMICs. For diagnostic testing, where reverse transcription–PCR (RT-PCR) testing is available and affordable, we recommend using RT-PCR of the upper or lower respiratory specimens and suggest using lower respiratory samples for patients suspected of having COVID-19 but have negative RT-PCR results for upper respiratory tract samples. We recommend that a positive RT-PCR from any anatomical source be considered confirmatory for SARS-CoV-2 infection, but, because false-negative testing can occur, recommend that a negative RT-PCR does not definitively rule out active infection if the patient has high suspicion for COVID-19. We suggest against using serologic assays for the detection of active or past SARS-CoV-2 infection, until there is better evidence for its usefulness. Where available, we recommend the use of point-of-care antigen-detecting rapid diagnostic testing for SARS-CoV-2 infection as an alternative to RT-PCR, only if strict quality control measures are guaranteed. For laboratory testing, we recommend a baseline white blood cell differential platelet count and hemoglobin, creatinine, and liver function tests and suggest a baseline C-reactive protein, lactate dehydrogenase, troponin, prothrombin time (or other coagulation test), and D-dimer, where such testing capabilities are available. For imaging, where availability of standard thoracic imaging is limited, we suggest using lung ultrasound to identify patients with possible COVID-19, but recommend against its use to exclude COVID-19. We suggest using lung ultrasound in combination with clinical parameters to monitor progress of the disease and responses to therapy in COVID-19 patients. We currently suggest against using diagnostic and prognostic models as these models require extensive laboratory testing and imaging, which often are limited in LMICs
ABSTRACT
The coronavirus disease 2019 (COVID-19) constitutes the greatest health and economic challenge of the last century. Since the beginning of 2020, world medical personnel have faced this emergency in the absence of treatments supported by reliable evidence. World Health Organization published an interim guidance in which it took sides against the use of cor-ticosteroids in the treatment of COVID-19. To date, however, we have more data available from clinical studies indicating that administration of systemic corticosteroids is associated with lower 28-day all-cause mortality. This review aims to briefly summarize the pathophysiological bases, the evidence currently available drawing some concepts applicable in daily clinical practice on the use of corticosteroids for the treatment of COVID-19.