Prolonged stay and endothelial dysfunction in hospitalized patients with covid-19

Introduction: COVID-19 is not only a respiratory disease, produces a severe systemic and multi-organ response. This illness generates vascular disorders, leading the patient to endothelial dysfunction. It acutely and chronically affects the patient's evolution, prolonging the patient's stay and worsening life prognosis. Objective(s): To evaluate differences in endothelial dysfunction present in patients hospitalized for COVID-19 who had a hospital stay longer than 18 days compared to those who did not. Method(s): A prospective cohort study was conducted. Hospitalized patients with confirmed SARS-COV 2 andolder than 18 years were included. Subjects in whom endothelial function markers could not be processed wereexcluded. Endothelial dysfunction was evaluated using E-selectin, endothelin-1, glutathione-s-transferase, arginase, and MDAM. A prolonged hospital stay was established >=18 days. Result(s): A total of 165 patients were evaluated, the average age of the population was 57.18 +/- 13.37 years, 73.33% were men. Subjects with prolonged hospital stay were older (59.38 +/- 12.08 vs 51.15 +/- 14.96, p=0.004), a higher number of patients required intubation (87.60 % vs 75, p=0.049) and e-selectin (1 [0.79 - 1.32] vs 0.88 [0.68 -1.14], p=0.0323) compared to subjects without prolonged hospital stay. Conclusion(s): Hospitalized patients over 18 days showed elevated levels of E-selectin reflecting endothelial damage, affecting vascular homeostasis, added to this, a significant number of them were intubated, increasing the risk of mortality, as well as future cardiovascular complications.

Safety of oral Nirmatrelvir plus Ritonavir in Lung transplant recipients

Introduction: Lung transplant recipients (LTR) are at significant risk for severe covid-19 disease. The oral combination therapy Nirmatrelvir plus Ritonavir (Paxlovid) has been shown to reduce the risk for disease progression. Due to drug interactions with calcineurin inhibitors (CNI), significant concern exists in treating LTR with Paxlovid. We describe safety related outcomes of Paxlovid use among our LTR. Method(s): We retrospectively collected data of all LTR with a positive COVID-19 test since Paxlovid was available in Israel from January 2022 - May 2022. During this time, Paxlovid was the drug of choice, unless contraindicated. Data collection included: demographics, hospitalization for covid-19, death of any cause and drug related adverse events. Result(s): A total of 96 LTR tested positive for covid-19 during this period. View inline There was no evidence of posterior reversible encephalopathy (PRES), seizures, kidney failure or ED visits in any of the paxlovid treated patients. Conclusion(s): Despite significant drug related interactions between CNI and Paxlovid, the drug can be administrated safely in LTR. Given the high risk for severe covid-19 disease among LTR and the demonstrated safety of this study, use of paxlovid among this population should be considered.

No Association Between BNT162B2 Vaccine and Graft Rejection Among Lung Transplant Recipients

Safety of the BNT162b2 vaccine has been described among the general population and solid organ transplant recipients (SOTR). Post vaccination development of donor specific antibodies (DSA) and organ rejection is a specific concern among SOTR. Yet data on effects of mRNA vaccine on the development of de novo DSA (ddDSA) and acute cellular rejection (ACR) in lung transplant recipients (LTR) is lacking. The purpose of this study is to describe the effect of the mRNA BNT162b2 vaccine on the development of ddDSA and prevalence of ACR episodes following vaccination. A retrospective study including all LTR who participated in our observational prospective cohort study of immunogenicity following BNT162b2 vaccine. We collected data regarding demographics, documented ACR episodes, FEV1 decline and development of ddDSA between December 2020 and December 2021. Two doses of BNT162b2 mRNA vaccine were administrated to 168 LTR. Of them 139 patients received another booster dose. Median age was 60.5 years (IQR 49.25-67.75) and 33.3% were females. Median time from transplantation was 46.66 months (IQR 20.03-96.96). Among 139 patients who received three vaccine doses ACR episodes were documented in 4 patients (2.8%), similar to ACR rate documented within the six months preceding vaccine administration. DSAs were evaluated among 60 patients following two vaccine doses, none of whom developed ddDSA. Six patients had a positive DSA titer prior to vaccination, with no significant increase in mean fluorescence intensity (MFI) following vaccination. Lung function remained stable among the vast majority of our cohort with 94.6% demonstrating stable FEV1 following BNT162b2 vaccine (figure 1). Despite previous concerns of possible graft targeted immune reactions to mRNA vaccines, the risk of ACR episodes and development of ddDSA after BNT162b2 vaccination among LTR is very low. Transplant centers should recommend appropriate vaccination for this immunosuppressed population. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Impact of endothelial function on the prognosis of COVID19 patients

Introduction: The pathophysiological mechanisms related to the severity of the clinical picture of Sars-Cov-2 infection remain questions that the medical community seeks to resolve and whose knowledge will allow the design of therapeutic strategies. Purpose(s): To evaluate the association between endothelial function and mortality in patients with COVID-19. Material(s) and Method(s): Prospective cohort study. Patients with confirmed diagnosis of COVID-19, who required hospitalization, oxygen saturation <60% and laboratory data of endothelial function markers were included;all those with incomplete data were excluded. Result(s): The age of the population was 57.06 +/- 13.405, 69% were intubated, those who died had poorer ventilatory parameters;peak pressure (30.06 +/- 6.13 vs 24.82 +/- 6.06, p<0.001), Fi02 (57.5 [40 - 80] vs 45 [40 -80], p <0.001) and PaO2/FiO2 calculation (127.84 +/- 50.08 vs 163.36 +/- 45.47, p<0.001). In addition, they had greater laboratory alterations: procalcitonin (0.49 [0.16 - 4] vs. 18 [0.07 - 0.52], p=0.03) and CRP (13.34[7.67 - 19.03] vs 6.69 [2.4 - 15 89], p=0.05), higher levels of clotting times, PT(14.8 [14 - 16.6] vs 14.4 [13.7 -15.6], p=0.5) and INR (1.04 [0.98 - 1.17] vs 1.01 [.95 - 1.1], p=0.05). In blood biometry, higher numbers of leukocytes of (11.3 [8.65 - 14.4] vs. 9.9 [6.7 - 13], p=0.041), neutrophils (8.8 [7.4 - 12.5] vs. 8.1 [4.74 - 11.1], p=0.01) and lower numbers of lymphocytes (. 7 [.40 - 1.1] vs 1.1 [.7 - 1.5], p<0.001) and with significant statistical trend, hemoglobin(11.26 +/- 2.55 vs 12.42 +/- 2.4, p=0.07) compared to surviving subjects. Conclusion(s): Hematological and liver alterations are markers of higher mortality in patients with COVID-19 as an expression of multiorgan disease.

Effect of physical conditioning evaluated in the 6-minute walk in subjects recovered from COVID-19

Introduction: Physical conditioning develops conditional and coordinative capacities to improve physical performance through exercise. The 6-minute walk test (PC6M) assesses in an integrated manner the response of the respiratory, cardiovascular, metabolic, musculoskeletal, and neurosensory systems to the stress imposed by exercise. Functional integration is analyzed by the maximum distance an individual can cover during six minutes of walking as fast as possible. Objective(s): To evaluate the effect of physical conditioning on the physical capacity of subjects recovered from COVID 19. Method(s): Clinical trial in subjects recovered from COVID-19 who required hospitalization during the acute phase, > 18 years were included. Subjects with musculoskeletal lesions were excluded. Physical capacity was assessed by PC6M. The intervention had a duration of 20 sessions of physical conditioning on cycle ergometer for arms and legs, treadmill and elliptical trainer. Result(s): Forty-two patients were evaluated, 56.41% of whom were men, with a mean age of 53.48 +/- 14.3 years. After 20 physical conditioning sessions, increase the physical capacity (434.58 +/- 89.10 vs. 546.63 +/- 101.34;p < 0.001), assessing dyspnea, fatigue, and saturation where no significant differences were found observed. Conclusion(s): An improvement in functional capacity was observed after 20 sessions.

Collection of the Main Anti-Virus Detection and Bypass Techniques

A large amount a new threats, technologies and business models have emerged in the cybersecurity area through the COVID-19 pandemic. The remote work involved unplanned cloud migrations and swift procurement of IT products and services the remote landscape. In this context, the role of anti-viruses is crucial for the private life and work. In this paper, we study the workings of anti-viruses as to understand how to avoid them. We created a collection of the main bypass techniques whilst analyzing their respective advantages and drawbacks. We show that it is possible to avoid both static and emulation analyses, while enunciating the techniques and approaches being used. © 2021, Springer Nature Switzerland AG.

Anxiety and depression among individuals in mandatory institutional quarantine in Tunisia

Background The COVID-19 pandemic is a challenging public health issue that have impacted people's health and livelihoods worldwide. Restrictive measures, such as quarantine, have been implemented in many countries in order to limit the spread of the virus. We aimed in this study to assess the impact of institutional mandatory quarantine on mental health in Tunisia and to determine factors associated with the occurrence of anxiety and or depression. Methods A cross sectional phone survey was conducted in Tunisia from April to November 2020 among people who were placed in mandatory institutional quarantine. Generalized anxiety disorder and depression were assessed using the Generalized anxiety disorder scale (GAD-7) and the Centre for Epidemiological Studies Depression Scale (CES-D-10). Bivariate and multivariate analyses were used to determine factors associated with the occurrence of depression and or anxiety symptoms. Results In the present study, 506 participants were enrolled with an age ranging from 18 to 83 years and a sex ratio equal to 1.9. More than third of participants (38.3%) had experienced anxiety and/or depressive symptoms. Being a woman, younger age, being a student, spending longer time on COVID-19 news, fear of infection in the quarantine facility, having experienced stigma, financial struggle due to the COVID-19 pandemic and dissatisfaction by the accommodations conditions of the quarantine facility were independently associated with occurrence of depression and or anxiety symptoms. Conclusions A high percentage of participants have experienced anxiety or depressive symptoms during the quarantine period. Providing mental health support and updated and relevant information to quarantined individuals is necessary. Improving the accommodation conditions in the quarantine facilities is also needed. Key messages More than third of participants had experienced anxiety and/or depressive symptoms. Good quality communication and mental health support are necessary in quarantine facilities.

Impact of mandatory institutional quarantine on sleep quality: A cross sectional Tunisian study

Background Given the COVID-19 pandemic, Tunisian authorities have imposed quarantine in dedicated centers mainly for travelers coming from countries with highest coronavirus infection rates. Such restrictive measures may have a detrimental impact on people's mental health and can thus affect sleep. We aimed in this study to assess the impact of mandatory institutional quarantine on sleep quality in Tunisia and to determine factors associated with clinical insomnia. Methods Data were collected through a cross sectional study conducted from April to November 2020 among individuals who were in quarantine for 14 days including at least a week in a Tunisian quarantine center. Sleep quality was assessed using the Insomnia Severity Index. Factors associated with clinical insomnia were assessed using bivariate and multivariate analysis. Results In the present study, 506 participants were included with a mean age of 37.6±13.6 years. Majority (66.4%) were men. Nearly one fifth (19.2%) of surveyed individuals had symptoms of clinical insomnia. In multivariate analysis, we found that being a woman, spending longer time on covid-19 news per day, having experienced stigma during the quarantine period, financial difficulties due to the coronavirus pandemic and dissatisfaction by the accommodation conditions of the quarantine facility were independently associated with clinical insomnia. Conclusions Nearly one fifth of participants had clinical insomnia during the quarantine period. Providing a good sleep environment, educating sleep healthy behavior and giving adequate psychological support to quarantined individuals in quarantine centers is necessary. Key messages Among surveyed participants, 19.2% had symptoms of clinical insomnia. Providing a good sleep environment in quarantine centers and providing mental health support to quarantined individuals is essential.

POS-112 HEMODIALYSIS EMERGENCIES : A MONOCLONAL EXPERIENCE

Introduction: Hemodialysis emergencies in nephrology are frequent. Prompt diagnosis and management are needed to save life and enhance prognosis. The aim of this work was to determine the hemodialysis’ prevalence in emergency situations, its indications, the clinical, paraclinical and evolutionary profiles and to describe the parameters of the session as well as the per-dialytic incidents and their impacts on patient mortality. Methods: It is a retrospective monocentric descriptive study during 3 months (July, August, and September 2020) carried out in the nephrology department of the University teaching hospital of Sousse. We collect patients who underwent at least one session of HD. Results: We included 61 patients who underwent emergency hemodialysis. The average age of our patients was 58±17 years (17- 95) and the sex ratio was 1,5. Our patients have hypertension and diabetes in respectively 56,1% and 34,4% of cases. 42,6% of patients were admitted from the emergency department, 27,9% of patients from the surgical and urology department, 18% of patients from nephrology departments and 11,5% of patients from other departments. Our population consists in chronic HD patients in 34,5%. Chronic renal failure was noted in 43,6% with diabetic nephropathy as the most primary cause (44,1%). Acute renal failure was found in 18.2% with Obstructive nephropathy (66,1%) as the main etiology.two patients were transplanted (3,3%). HD indications were hyperkalemia in 30%, acute pulmonary edema in 25% and metabolic acidosis in 23,3% of cases. Conventional HD was performed with mean session duration of 3,4 hours. Ultrafiltration was required in 73,8% with an average of 1800ml (range: 500-4000).The most frequently used approach was the femoral route in 54,1% followed by arterioveinous fistula in 24,6%. Transfusion was required in 26,2% of cases. Perdialytic complications were observed in 29,5% of cases. Hypotension was the most common complication present in 13,1% of case;which leads to the interruption of the session in 4.9% of cases;followed by agitation in 4,9% of case. The renal evolution of our population was hemodialysis dependence in 35,6%, back to basic level in13,3%chronic kidney disease in4,4% and recovery in 2,2%. Death occurred in 5 cases including 3 patients outside dialysis and 2 patients on dialysis. Infection by SARS covid 19 was the cause of death in 1 patient. Conclusions: Extra-renal purification (REE) is sometimes essential in an emergency situation in the management of severe ARI or terminal CKD. Early diagnosis and relevant treatment will enhance the prognosis of patients in the short and medium term. No conflict of interest

Poor Outcomes of COVID-19 in Lung Transplant Recipients. Cohort Study in a Single Center

Purpose The world SARS-CoV-2 pandemic has affected global health, including the health of lung transplant recipients. There is very little data reported on the outcomes of SARS-CoV-2 on this gruop of patients Methods Retrospective cohort study approved of all LTx recipients with symptoms consistent with COVID-19 investigated with naso-pharyngeal swabs and reverse PCR for SARS-COV-2. Postive test for SARS-COV-2 Inserted to our cohort and investigated their files. We also conducted pooled analysis of published cases of covid 19 cases of lung transplant recipients Results We identified eleven cases of COVID-19 among a cohort of 348 LTx recipients. All but two patients were hospitalized. Seven patients required intensive care and six died (55% mortality). Non-survivors had lower baseline FEV1 than survivors and worse and/or deteriorating chest radiographic scores during admission. No effect of medical therapy including steroids and remdesivir could be determined. This mortality rate compared poorly general hospitalized COVID-19 patients at our institution (13%) and national mortality rate of 0.3% in the general population. Incidence of COVID-19 was similar to the general population (0.3%). In a pooled analysis of published cases, we determined mortality of 28% across different reports of lung transplant patients with COVID-19. Conclusion COVID-19 disease is very severe in lung transplant recipients. In the absence of effective therapy and vaccination, transplant physicians should concentrate their efforts on prevention of disease and encourage meticulous preventative behavior by recipients under their care.

Innate immunity during SARS-CoV-2: evasion strategies and activation trigger hypoxia and vascular damage.

Innate immune sensing of viral molecular patterns is essential for development of antiviral responses. Like many viruses, SARS-CoV-2 has evolved strategies to circumvent innate immune detection, including low cytosine-phosphate-guanosine (CpG) levels in the genome, glycosylation to shield essential elements including the receptor-binding domain, RNA shielding and generation of viral proteins that actively impede anti-viral interferon responses. Together these strategies allow widespread infection and increased viral load. Despite the efforts of immune subversion, SARS-CoV-2 infection activates innate immune pathways inducing a robust type I/III interferon response, production of proinflammatory cytokines and recruitment of neutrophils and myeloid cells. This may induce hyperinflammation or, alternatively, effectively recruit adaptive immune responses that help clear the infection and prevent reinfection. The dysregulation of the renin-angiotensin system due to down-regulation of angiotensin-converting enzyme 2, the receptor for SARS-CoV-2, together with the activation of type I/III interferon response, and inflammasome response converge to promote free radical production and oxidative stress. This exacerbates tissue damage in the respiratory system, but also leads to widespread activation of coagulation pathways leading to thrombosis. Here, we review the current knowledge of the role of the innate immune response following SARS-CoV-2 infection, much of which is based on the knowledge from SARS-CoV and other coronaviruses. Understanding how the virus subverts the initial immune response and how an aberrant innate immune response contributes to the respiratory and vascular damage in COVID-19 may help to explain factors that contribute to the variety of clinical manifestations and outcome of SARS-CoV-2 infection.

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases.

Although most autoimmune diseases are considered to be CD4 T cell- or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab, oblinutuzumab and ofatumumab that are used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities and ocrelizumab in multiple sclerosis. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of autoimmunity and COVID-19, it was hypothesised that while B cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B cell subset inhibition, that controls at least some autoimmunities, would not influence innate and CD8 T cell responses, which are central to SARS-CoV-2 elimination, nor the hypercoagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority of SARS-CoV-2-infected, CD20-depleted people with autoimmunity have recovered. However, protective neutralizing antibody and vaccination responses are predicted to be blunted until naive B cells repopulate, based on B cell repopulation kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose interruption to maintain inflammatory disease control, while allowing effective vaccination against SARS-CoV-29, if and when an effective vaccine is available.