Clinical improvement 2 years after starting elexacaftor/tezacaftor/ivacaftor in patients with advanced lung disease

Background: With the introduction of new cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (elexacaftor/tezacaftor/ ivacaftor), peoplewith CF experiencing severe lung disease can experience significant improvements in clinical symptoms. Method(s): This single-center institutional review board-approved retrospective chart review identified patients with advanced lung disease who met criteria for a compassionate use or expanded access program because of high risk of death or transplant need within 2 years. Clinical data collection for all patients began at baseline, 2 to 4 weeks after therapy initiation, and continued every 3 months for 2 years. Datawere collected on demographic characteristics, clinic progress notes, clinical labs, forced expiratory volume in 1 minute (FEV1),weight, body mass index, respiratory colonization, and hospitalizations after drug initiation. Patients also completed sinus and chest computed tomography (CT) to track clinical changes. Result(s): Eighteen people with CF (aged 15-49, 56% male) from a large midwestern CF center who initiated drug therapy between July and September 2019 in an inpatient hospital or clinic setting were identified. Clinical markers (Table 1) indicated that modulator therapy was well tolerated and not discontinued by any participant;safety lab values did not indicate medical concern or discontinuation. There were 90 admissions for the group in the 2 years before therapy and 17 admissions during the 2 years after, although seven of the posttherapy admissions were for nonrespiratory indications. Monitoring results indicated the safety of modulator therapy because there were no adverse clinical occurrences or laboratory events, and all patients presented with universal stabilization. There have been no deaths and no transplants. Unlike lumacaftor/ivacaftor, therewere no problems with chest tightness or any difficulty with troublesome increases in expectoration burden or choking during initiation of therapy. Most had significant reduction in or loss of spontaneous cough and sputum production. The impact on microbial colonization is unclear, because even in this severe group, inability to produce sputum on command led to considerable missing data in follow-up, leaving colonization status at follow-up unclear. Conclusion(s): This study focused on people with CF who qualified for modulator therapy based on advanced lung disease. Initiation of modulator therapy was deemed safe and resulted in objective positive changes in nutrition;cough;FEV1);and subjective reports of clinical status, level of activity, and reduction in burden of treatment. No evidence was found of difficulty managing the increased expectoration during initial therapy. Limitations were noted in missing data during the COVID-19 pandemic, small sample size, and delayed follow-up for drug monitoring.(Table Presented) Clinical indicators before and after modulator therapy *Completed post-drug initiation (earlier than 12 months), **24 months before and after therapy initiationCopyright © 2022, European Cystic Fibrosis Society. All rights reserved

Clinical value of outpatient screening in department of general surgery during the COVID-19 outbreak.

Objective: To investigate the clinical value of outpatient screening in department of general surgery during the Corona Virus Disease 2019 (COVID-19) outbreak. Method(s): The retrospective and descriptive study was conducted. The clinical data of 57 patients who visited surgery clinic and emergency department of Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology between February 1st and 26th in 2020 were collected. There were 30 males and 27 females, aged (53+/-16)years, with a range from 17 to 87 years. All the 57 patients were measured score of outpatient screening in department of general surgery. The score >=3 indicated high risk and the score < 3 indicated low risk. Observation indicators: (1) clinical data of patients;(2) score of outpatient screening for COVID-19 of patients. Measurement data with normal distribution were represented as Mean+/-SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were described as M (IQR), and comparison between groups was analyzed by the rank sum test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Result(s): (1) Clinical data of patients: of the 57 patients, there were 12 males and 14 females of the 26 confirmed or suspected cases, versus 18 males and 13 females of the 31 non-infection cases, showing no significant difference between the two groups (chi2=0.805, P>0.05). The 26 confirmed or suspected cases of COVID-19 had an age of (57+/-16)years, and 31 non-infection cases had an age of (50+/-16) years, with no significant difference between the two groups (t=-1.646, P>0.05). (2) Score of outpatient screening for COVID-19 of patients: the score of outpatient screening for COVID-19 of the 26 confirmed or suspected cases was 3.0(4.0), versus 1.0(1.0) of the 31 non-infection cases, showing a significant difference between the two groups (Z=-3.695, P<0.05). There were 17 and 9 of the 26 confirmed or suspected cases with high risks and low risks, respectively, versus 3 and 28 of the 31 non-infection cases, with a significant difference between the two groups (chi2=19.266, P<0.05). Conclusion(s): During the COVID-19 outbreak, outpatient screening in department of general surgery can effectively screen out high-risk patients.Copyright © 2020 by the Chinese Medical Association.

An Early Detection Of NIPAH Infectious Disease Based On Integrated Medical Features For Human Using Ensemble RBM Techniques

Background: The importance of early diagnosis of a hazardous illness cannot be overstated. The transmission rate is extremely high, especially in the current pandemic condition. The ability to predict epidemics will aid public health in reducing mortality and morbidity. Machine Learning (ML) approaches are used in the construction of an effective disease prognosis model. Furthermore, only if the model learns good associated features from the data is it possible to generate a speedy outcome. As a result, selecting features is also necessary before beginning the forecasting process. Objective(s): However, because of the virus's dynamic structure, it's difficult to predict Nipah disease and/or zoonotic infection. Furthermore, there is no clinical treatment for Nipah. The major goal of this research is to develop a prognostic model for early diagnosis of Nipah disease using a combination of several clinical factors such as symptoms, disease incubation information, and routine blood test results confirmed by a lab technician.Proposed System: The healthcare application and data are more complex to handle than other ML applications since various clinical features are assessed throughout disease manifestation. As a result, selecting the most relevant variables is critical when designing a prognosis model for any viral disease. To deal with clinical features from a vast number of features, we proposed a Restricted Boltzmann Machine (RBM) method in this research. Additionally, we employed a hybrid ensemble learning method to predict if the patient was infected with NiV after choosing features using the RBM. Data Collection: The proposed system is being implemented using the NiV infection dataset that erupted in Kozhikode, Kerala in 2018 and 2019. Result(s): The developed stacking-based ensemble Meta classifier was successfully implemented using the python programming language, and its performance was evaluated using a variety of metrics includingaccuracy, precision, recall, f1-score, log loss, AUROC and MCC. Our proposed Stacking Ensemble Meta Classifier (SEMC) model achieved an accuracy rate of 88.3% with a log loss of 0.36. Model precision, recall, f1-score, AUROC, and MCC value were 92.5%, 89.2%, 90.9%, 92.1%, and 0.74 respectively. In addition, we calculated the gravitational pull of each feature using the SHAP approach and discovered that altered sensorium, fever, headache, and cough were the most critical clinical indicators that distinguished NiVD infection from our dataset. Therefore, this classification may assist the pathologist in diagnosing NiVD with symptoms before performing the RT-PCR medical test. Conclusion(s): Using our proposed SEMC technique, we developed a prognostic model for the diagnosis of Nipah in humans. The proposed technique's discriminatory efficiency exhibited good NiVD diagnosis efficacy. We anticipate that this model will aid medics in determining a prognosis more quickly during future epidemics. However, to achieve maximum accuracy, the model requires more unique samples.Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Characteristics of fever in patients with COVID-19 at presentation and after initiation of treatment

Coronavirus-19 (COVID-19) infection presents in a many ways, from asymptomatic or mild symptoms to death or serious illness. Coughing, shortness of breath, and fever are the common symptoms. Other symptoms include weakness, muscle discomfort, lethargy, sore throat, breathing problems, and loss of smell and/or taste. COVID-19 is diagnosed using clinical indicators, CT scans or chest x-rays, serological tests, and molecular diagnostics of the viral genome using reverse transcription polymerase chain reaction. This study analyzes the duration of fever, the most important symptom of the disease, and its association with other patient characteristics. The cross-sectional study was conducted in Iraq's Al-Diwaniyah Province, located in the Mid-Euphrates region. The study included 99 COVID-19 cases, 50 males and 49 females aged 16–81 years. Age, gender, white blood cell (WBC) count, lymphocyte percent, lung involvement assessed by CT scan, duration of fever at the time of presentation, and duration until the fever subsides following initiation of treatment were the main variables studied, in addition to the presence of chronic medical illnesses such as diabetes mellitus, systemic hypertension, asthma, and pulmonary tuberculosis. The mean age of all patients was 50.38 ± 16.27 years, with no significant difference between males and females (P = 0.924). There was also no significant difference in mean WBC count and lymphocyte percent between males and females (P > 0.05). Lung involvement from CT scan ranged from 0 to 80% and the mean was 26.77 ± 21.43%, with no significant difference between males and females (P = 0.770). The mean duration of fever at the time of presentation was 6.61 ± 3.60 days and it ranged from 1 to 21 days. The duration of subsiding fever ranged between 2 and 25 days in all patients with a mean of 5.82 ± 3.53 days, with no significant difference between males and females (P = 0.214). The duration needed for the fever to subside was positively and significantly correlated to the WBC count, the duration of fever at presentation, and the presence of diabetes mellitus (P < 0.05). Longer duration of fever after diagnosis and treatment of COVID-19 can be predicted with a high WBC count. Patients with diabetes having a longer duration of fever are at high risk of developing severe complications and death.

A Developing Crisis in Hunger: Food Insecurity within 3 Public Colleges before and during the COVID-19 Pandemic

During the COVID-19 pandemic, food insecurity increased across the United States, with college students being particularly vulnerable. This study surveyed 1989 undergraduates attending three public colleges before and during the first year of the pandemic. At all times, students' food insecurity was related to worse academic performance, greater housing insecurity, poorer psychological and physical health, and less access to healthcare. Compared to pre-pandemic students, during-pandemic students reported greater use of and fewer barriers to food programs, spending more on and and receiving more government aid for food, experiencing more academic difficulties due to food insecurity, having greater housing insecurity, and enduring less access to healthcare. © 2022 Taylor & Francis Group, LLC.

From sepsis to COVID-19: the emerging role of Monocyte Distribution Width (MDW)

Immune activation of the monocyte-macrophage population plays a pivotal role in the systemic hyper-inflammatory response, typically observed during severe dysimmune diseases, such as sepsis and COVID-19. In this commentary, we have reviewed the literature data on the novel cytometric marker of monocyte activation, known as MDW (Monocyte Volume Distribution Width), a monocyte dimensional parameter obtainable by blood count examination, which has recently been approved for clinical use as "Early Sepsis Indicator" (ESId), in patients accessing the Emergency Department. In particular, in this Opinion paper, we highlight the main clinical applications and relevant perspectives of this new test: from its use for (early) diagnosis of sepsis, in different hospital settings, to its emerging prognostic role in patients with COVID-19, as a biomarker of disease severity. In view of the reported evidence, we discuss the clinico-pathological notion that, basically, severe COVID-19 can be considered a new form of viral sepsis. Further clinical studies are needed to better understand the pre-analytical and analytical variables of this parameter, correlate MDW dynamics with those of other humoral and cytometric markers, and validate the new diagnostic and prognostic applications of MDW on large multicenter case series. Copyright © 2022 Biomedia. All rights reserved.

Determining Risk Factors Associated with an Increased Incidence of Pulmonary Embolism: A Multi-Center Study of 3,675 Patients

Background. Coronavirus Disease 2019 (COVID-19) is associated with an increased incidence of pulmonary embolism (PE). Both conditions increase hospital complications and mortality, especially when exhibited concurrently. Unfortunately, both conditions may present similarly, and physicians often have a difficult time finding clinical indicators to suggest pursuing further evaluation of a PE during a COVID-19 infection. Methods. Using a multi-center facility database, we conducted a retrospective analysis of 3,675 COVID-19 patients at Methodist Health System from March 2020 to December 2020. COVID-19 infection was determined via molecular PCR testing and PE was determined by computed tomography (CT) scan with angiography. Patient demographics and laboratory values were determined by a manual review of patient charts. Chi-Square test was used to analyze observed variables. Odds ratios were calculated for variables with a statistically significant difference (p < 0.05). Results. Of the 3,675 patients diagnosed with COVID-19, 150 (4.1%) were diagnosed with PE. Elevated D-dimer level had a statistically significant association with increased rate of PE (OR 0.1988, 95% CI 0.0727 - 0.5438, p < 0.001). Factors such as elevated C-reactive protein (p = 0.61), IL-6 (p = 0.26), smoking history (p = 0.70), age over 65 (p=0.54), BMI over 25 (p = 0.42), and history of chronic kidney disease (p = 0.16) did not show a significant association with PE incidence. Of note, patients with PE during admission were seen to have an increased incidence of intubation (OR 0.40, 95% CI 0.2660 - 0.6029, p < 0.001). Conclusion. Our study suggests that COVID-19 patients with elevated D-dimer have higher odds of having a PE. This study also suggests that COVID-19 patients that develop a PE during hospitalization are more likely to require intubation.

COVID-19 Pandemic and Its Impact on CKD Patient Care and Clinical Parameters

Background: In CKD management, periodic visit of nephrologist and multiple professions are known to be important. However, with the COVID-19 pandemic from the end of 2019, due to the tightening of medical care resources and intermittent lockdowns, these patients seem to be could not receive the full of nephrology care. We assessed changes of CKD patients care during the COVID-19 Pandemic and evaluated its impact on clinical parameters. Method(s): Patients with CKD over stage 4 and who had regularly attended CKD out-patients clinic in St. Luke's International Hospital, Tokyo, Japan, were included. We definite the pre post pandemic periods as: pre-pandemic: Pre-C, from January 2018 to December 2019, and post-pandemic;Post-C, January 2020 to December 2021. The following data was compared between the 2 periods: 1. number of nephrology visits per patient;2. rate of using telemedicine;3. rate of receiving multidisciplinary educational support;4. rate of drop-out patients;5. Decline rate of GFR and 6. number of initiating renal replacement therapy, newly. Result(s): 289 individual patients were eligible for the analysis. The baseline data were as follows: mean age 67.9+/-14 years, 63.5% male, mean eGFR 22.2+/-5.9 ml/min and 40.2% comorbid DM. The number of nephrology visits and receiving multidisciplinary support was decreased in Post-C periods: Nephrology visits;Pre-C: 9.8+/-5.1 visits/year, Post-C 7.7+/-5.2 visits/year, P<0.01, Multidisciplinary support;Pre-C: 78%, Post-C 32%, P<0.01. Multiprofessional educational support was provided mainly for CKD stage 5 patients during the Post-C. More, the rate of using telemedicine and dropout increased in Post-C. Especially, the dropout rate of elderly patients over 70 years old was significant: 8% in Pre-C and 17% in Post-C, P<0.05. On the other hand, clinical indicators such as delta GFR and RRT initiation rate remained unchanged. Conclusion(s): Although the frequency of nephrology visits and multidisciplinary educational care has been decreased with COVID-19, there was no difference in the shortterm prognosis of CKD patients, from our study. This may be an effect of a kind of triage function, which focused on the more severely ill patients with CKD. On the other hand, the drop out rate in the elderly was increased, the prognosis of these patients needs to be followed up and verified.

The Efficacy of Methylprednisolone in Clinical Manifestations, Inflammatory Biomarkers, and Antioxidant Changes in the COVID-19 Patients

Background: The application of methylprednisolone in ARDS patients has led to a sustained reduction in inflammatory plasma cytokines and chemokines and has recently been used in the treatment of patients with SARS-CoV-2 infection. Objectives: In this study, the effect of methylprednisolone on clinical symptoms and antioxidant changes of patients with COVID-19 has been investigated. Methods: In the present study, patients with moderate to severe COVID-19 who required hospitalization were entered into the study phase. Then, in addition to standard treatment, patients received methylprednisolone at a dose of 250 mg intravenously over three days. Necessary evaluations include analysis of arterial blood gases, pulse oximetry, monitoring of patient clinical signs, examination of inflammatory biomarkers, and also receiving 10 cc of peripheral blood samples to check for antioxidant changes, at the beginning of the study, after 24 hours, and 72 hours after receiving methylprednisolone was on the agenda. Results: Changes in fever, superoxide dismutase (SOD, Glutathione-S-Transferase (GST, the ferric reducing ability of plasma (FRAP, malondialdehyde (MDA, Nitric oxide, Ferritin, and TNF-α before treatment and 72 hours after treatment were significantly different between the two stages (P < 0.05). Conclusions: The use of methylprednisolone improves the balance of antioxidants and immunological factors in patients with COVID-19 and thus improves some clinical indicators in these patients.

SIMILAR, YET SO DIFFERENT: A TALE OF TWO DISEASES

SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Pneumocystis Pneumonia (PCP) is an opportunistic infection caused by a yeast-like fungus pneumocystis jirovecii. It is characterized by hypoxemia and increased inflammatory markers with elevated lactate dehydrogenase (LDH) often used as a clinical indicator of possible infection. COVID-19 is a viral infection caused by severe acute respiratory syndrome coronavirus and presents with a variety of symptoms, pneumonia being the most frequent and serious manifestation. Common laboratory markers include lymphopenia, elevated LDH and inflammatory markers. CASE PRESENTATION: Our patient is a 54 yo African American male with an unremarkable history who presented to our facility from an outside hospital (OH) for worsening respiratory failure in the setting of a large left pulmonary artery thrombosis. He was infected with COVID-19, four months prior and had experienced worsening weakness, SOB and anorexia two months before admission. Work up at OH revealed the large pulmonary emboli as well as extensive multifocal opacities consistent with prior COVID infection and described as post- COVID fibrosis. His sputum also tested positive for pseudomonas aeruginosa and mycoplasma pneumoniae for which he was treated. Unfortunately his hypoxemia worsened and he required intubation;prompting transfer to our facility for hopes of thrombectomy. He continued with hypoxemic, hypercarbic respiratory failure and underwent a bronchoscopy which was grossly normal. As serology indicated lymphopenia and paraprotein gap > 4, we decided to order HIV RNA PCR, which came back positive (CD4 count 11cells/ mm3). One week later, pneumocystis jirovecii was identified from an immunohistochemical stain from bronchial alveolar lavage (BAL). DISCUSSION: PCP is a common opportunistic infection in patients with human immunodeficiency virus, generally presenting when CD4 counts decrease below 200 cells/ mm3. Along with similar symptoms and elevated inflammatory markers, COVID-19 and PCP share common radiographic findings of ground glass opacities. In addition to his compromised lung (from COVID-19) and prolonged hospitalization, the positive cultures of m. pneumoniae and p.aeruginosa were originally misleading. Although cases of co-infection of PJP and COVID-19 exist, our case demonstrates that having a broad differential after recovery from COVID-19 continues to be necessary. CONCLUSIONS: PCP and COVID-19 pneumonia share similarities in radiographic and laboratory findings proving difficult to differentiate from each other. This case highlights the importance of assessing the immunological status of patients with unknown HIV history especially in a time where considering different etiologies of pneumonia have taken the backseat in the height of the COVID-19 pandemic Reference #1: Anggraeni AT, Soedarsono S, Soeprijanto B. Concurrent COVID-19 and Pneumocystis jirovecii pneumonia: The importance of radiological diagnostic and HIV testing. Radiol Case Rep. 2021;16(12):3685-3689. Published 2021 Oct 2. doi:10.1016/j.radcr.2021.09.002 Reference #2: Analysis of underlying diseases and prognosis factors associated with Pneumocystis carinii pneumonia in immunocompromised HIV-negative patients. Roblot F, Godet C, Le Moal G, Garo B, Faouzi Souala M, Dary M, De Gentile L, Gandji JA, Guimard Y, Lacroix C, Roblot P, Becq-Giraudon B. Eur J Clin Microbiol Infect Dis. 2002;21(7):523. DISCLOSURES: No relevant relationships by Cynthia Espinosa No relevant relationships by Jason Kovacevic No relevant relationships by Laura Mendez Morente No relevant relationships by Zuleikha Muzaffarr

Major risk factors associated with severe COVID-19 outcomes in patients with multiple myeloma: Report from the National COVID-19 Cohort Collaborative (N3C)

Background: Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems due to multiple factors that may increase the risk of severe COVID-19. The NCATS' National COVID Cohort Collaborative (N3C) is a centralized data resource representing the largest multi-center cohort of ∼12M COVID-19 cases and controls nationwide. In this study, we aim to analyze risk factors associated with COVID-19 severity and death in MM patients using the N3C database. Methods: Our cohort included MM patients within the N3C registry diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter, and clinical indicators of severity (hospitalization/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation/ECMO). Results: As of 09/10/2021, the N3C registry included 690371 cancer patients, out of which 17791 were MM patients (4707 were COVID-19+). The mean age at diagnosis was 65.9yrs, 57.6% were >65yo, 46.4% were females, and 21.8% were Blacks. 25.6% had a Charlson Comorbidity Index (CCI) score of ≥2. 55.6% required an inpatient or ED visit, and 3.65% required invasive ventilation. 11.4% developed acute kidney injury during hospitalization. Multivariate logistic regression analysis showed histories of pulmonary disease (OR 2.2;95%CI: 1.7-2.8), renal disease (OR 1.8;95%CI: 1.4-2.4), and black race (p<0.001) were associated with higher risk of severity. Interestingly, smoking status was significantly associated with a lower risk of severity (OR 0.7;95%CI: 0.5-0.9). Further, protective association was also observed between COVID-19 severity and blood or marrow transplant (BMT) (OR 0.52;95%CI: 0.4-0.7), daratumumab therapy (OR 0.64;95%CI: 0.42- 0.99) and COVID-19 vaccination (OR 0.28;95%CI: 0.18-0.44). IMiDs were associated increase in the risk of COVID-19 severity (OR 2.1;95%CI: 1.6-2.7). 2.3% of N3C-myeloma COVID-19+ patients died within the first 10 days, while 4.95% died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.5% across the course of the study. Multivariate cox proportional hazard model showed that CCI score ≥2 (HR 4.4;95%CI: 2.2-8.8), hypertension (HR 1.6;95%CI: 1.02- 2.4), IMiD (HR 2.6;95%CI: 1.8-3.8) and proteasome inhibitor (HR 1.6;95%CI: 1.1-2.5) therapy were associated with worse survival. COVID-19 vaccination (HR 0.195;95%CI: 0.09-0.45) and BMT (HR 0.65;95%CI: 0.4-0.995) were associated with lower risk of death. Conclusions: We have identified previously unpublished potential risk factors for COVID-19 severity and death in MM as well as validated some published ones. To the best of our knowledge, this is the largest nationwide study on multiple myeloma patients with COVID-19.

THEMES AND CHALLENGES OF END OF LIFE CARE FOR COVID-19 PATIENTS REQUIRING NON-INVASIVE RESPIRATORY SUPPORT

Introduction The COVID-19 pandemic created new challenges due to the high numbers and the high symptom burden of end-of-life patients on respiratory support. Methods We conducted an audit of end-of-life patients on the respiratory HDU wards at Whipps Cross Hospital between 17/09/2020-30/01/2021. Results 84 patients receiving respiratory support (in the form of CPAP and HFNT) died during that time at a mean age of 77 (95% CI 67-87) and median of 79 years. All but one death, which followed a cardiac arrest, were expected. The most common clinical indicator for a patient approaching end-of-life was hypoxia on respiratory support, which was documented in 36 (43%) patients, followed by terminal agitation in 27 (32%) patients. Objections to the medical assessment of terminal illness were raised by 3 families and in 1 case the patient had conflicting wishes. The average time between recognition of a terminal deterioration and death was 1.4 days with a median of 2 days. 29 (35%) patients did not have a specialist palliative care review primarily due to the rapid patient deterioration. 25 (30%) patients were not visited by a relative due to the infection risk. 72 (86%) patients were weaned off respiratory support and those who continued did so due to a medical or patient decision. Despite most patients (82%) receiving continuous subcutaneous infusions with an opiate and benzodiazepine most patients had persistent terminal symptoms: 51 (74%) on infusions had agitation and 38 (55%) were persistently breathlessness. Discussion This data highlights some of the major difficulties faced in caring for patients with COVID on respiratory support and approaching end of life. With the inevitably persisting nature of this pandemic and the possibility of future pandemics still present, it is vital to be able to offer guidance and multidisciplinary input to ensure comfort and dignity for these patients.

Comparison of SARS-CoV-2 Variants of Concern Alpha (B.1.1.7) vs. Beta (B.1.351) in Critically Ill Patients: A Multicenter Cohort Study.

Objectives: The clinical outcomes of the Beta (B.1.351) variant of concern (VOC) of the SARS-CoV-2 virus remain poorly understood. In early 2021, northeastern France experienced an outbreak of Beta that was not observed elsewhere. This outbreak slightly preceded and then overlapped with a second outbreak of the better understood VOC Alpha (B.1.1.7) in the region. This situation allowed us to contemporaneously compare Alpha and Beta in terms of the characteristics, management, and outcomes of critically ill patients. Methods: A multicenter prospective cohort study was conducted on all consecutive adult patients who had laboratory confirmed SARS CoV-2 infection, underwent variant screening, and were admitted to one of four intensive care units (ICU) for acute respiratory failure between January 9th and May 15th, 2021. Primary outcome was 60-day mortality. Differences between Alpha and Beta in terms of other outcomes, patient variables, management, and vaccination characteristics were also explored by univariate analysis. The factors that associated with 60-day death in Alpha- and Beta-infected patients were examined with logistic regression analysis. Results: In total, 333 patients (median age, 63 years; 68% male) were enrolled. Of these, 174 and 159 had Alpha and Beta, respectively. The two groups did not differ significantly in terms of 60-day mortality (19 vs. 23%), 28-day mortality (17 vs. 20%), need for mechanical ventilation (60 vs. 61%), mechanical ventilation duration (14 vs. 15 days), other management variables, patient demographic variables, comorbidities, or clinical variables on ICU admission. The vast majority of patients were unvaccinated (94%). The remaining 18 patients had received a partial vaccine course and 2 were fully vaccinated. The vaccinated patients were equally likely to have Alpha and Beta. Conclusions: Beta did not differ from Alpha in terms of patient characteristics, management, or outcomes in critically ill patients. Trial Registration: ClinicalTrials.gov, identifier: NCT04906850.

Sars-Cov-2 Induced Endotheliopathy and the Impact on Clinical Outcomes in Critically Ill Pediatric Patients

Background: Coronavirus disease-19 (COVID-19) is an acute respiratory illness caused by the SARS-COV-2 virus. Patients with COVID-19 infection can present with thrombosis in the setting of inflammation (thromboinflammation), presumably from endothelial dysfunction, or “endotheliopathy”. Yu et al demonstrated in vitro that the spike protein subunit of SARS-COV2 acts as a potent activator of the alternative complement pathway (AP), one of three complement pathways within the innate immune system. Satyam et alreported the deposition of complement components on lung tissue of patients who succumbed to COVID-19, consistent with activation of classical and alternate pathways. These studies suggest complement dysregulation potentially causing endotheliopathy in COVID-19 patients. Thrombomodulin (TM) is an endothelial glycoprotein that plays two crucial roles in maintaining a healthy endothelium - as a natural anticoagulant and a negative regulator of complement. TM shed into the circulation due to endothelial injury can be measured in the plasma as soluble TM (sTM). Goshua et al showed elevated sTM in an adult cohort of patients with COVID-19. However, it is yet to be demonstrated if there is any correlation between endothelial injury and AP activation in COVID-19, or if either play a role in clinical outcome in the pediatric population. Objective: To 1) assess endothelial injury and AP activation in a cohort of critically ill pediatric patients with COVID-19 by measuring sTM and Ba (an AP activation product);2) determine the correlation between endothelial injury and AP activation;and 3) analyze the utility of sTM and Ba in predicting pediatric clinical outcomes. Methods: We collected plasma samples of patients admitted to the Pediatric Intensive Care Unit and found to be positive for SARS-CoV-2 between Dec 2, 2020 and Jan 22, 2021 at Texas Children's Hospital. For controls, we collected plasma samples from pediatric patients undergoing preoperative clearance, all at their baseline state of health. sTM levels and Ba levels were measured in plasma samples using commercially available TM and Ba ELISA kits. sTM greater than 7.6 ng/ml (based on the assay range in adults) and Ba greater than 1080 ng/ml (based on data from adult healthy controls) were considered elevated. Data regarding demographics, length of ICU stay, clinical indicators of end organ damage- mechanical ventilation, dialysis, use of vasopressors, ECMO, mortality were obtained retrospectively via chart review. Inclusion criteria included all patients with a positive SARS-COV2 PCR admitted to the ICU. Exclusion criteria was age greater than 21 years, pregnant female, patients with known inflammatory or complement-mediated disorders. Statistical analysis: For sTM and Ba levels between control and COVID-19 patients, mean +/- standard deviation was calculated and significance determined with an unpaired t-test. Fischer exact test, Wilcoxon rank sum and Pearson product-moment correlation tests were used for statistical analysis of clinical outcomes as appropriate. A p-value <0.05 was considered statistically significant. Results: A total of 38 control patients and 33 COVID-19 patients were enrolled. Ba and sTM levels were both significantly higher in the COVID-19 pediatric patients compared to the controls (Fig. 1). Within the COVID-19 patient cohort, 61% (n=20) had elevated sTM and 42% (n=14) had elevated Ba levels. There was a moderately positive correlation between sTM and plasma Ba levels in the COVID-19 cohort (Fig. 2). Within the COVID-19 patients' cohort, though higher Ba levels were not associated with an increased rate of intubation, they were associated with an increased duration of mechanical ventilation (p=.039) for those intubated (Table 1). Elevated sTM was associated with increased vasopressor use (p=.011). Although other clinical outcome variables did not reach statistical significance likely owing to small numbers, overall trend indicated worse outcomes in patients with elevated sTM. Conclusions: Our findings are consistent with the hypothesi that SARS-COV-2 activates AP and causes endothelial injury in children. The positive correlation between sTM and Ba suggest interplay between inflammation, coagulation and endotheliopathy supporting thromboinflammation in COVID-19. Higher sTM and Ba levels indicated worse clinical outcomes in children, but larger studies are needed to confirm our findings. [Formula presented] Disclosures: Sartain: Alexon Pharamaceuticals: Membership on an entity's Board of Directors or advisory committees.

Derivation of a Cost-Sensitive COVID-19 Mortality Risk Indicator Using a Multistart Framework

The overall global death rate for COVID-19 patients has escalated to 2.13% after more than a year of worldwide spread. Despite strong research on the infection pathogenesis, the molecular mechanisms involved in a fatal course are still poorly understood. Machine learning constitutes a perfect tool to develop algorithms for predicting a patient's hospitalization outcome at triage. This paper presents a probabilistic model, referred to as a mortality risk indicator, able to assess the risk of a fatal outcome for new patients. The derivation of the model was done over a database of 2,547 patients from the first COVID-19 wave in Spain. Model learning was tackled through a five multistart configuration that guaranteed good generalization power and low variance error estimators. The training algorithm made use of a class weighting correction to account for the mortality class imbalance and two regularization learners, logistic and lasso regressors. Outcome probabilities were adjusted to obtain cost-sensitive predictions by minimizing the type II error. Our mortality indicator returns both a binary outcome and a three-stage mortality risk level. The estimated AUC across multistarts reaches an average of 0.907. At the optimal cutoff for the binary outcome, the model attains an average sensitivity of 0.898, with a 0.745 specificity. An independent set of 121 patients later released from the same consortium attained perfect sensitivity (1), with a 0.759 specificity when predicted by our model. Best performance for the indicator is achieved when the prediction's time horizon is within two weeks since admission to hospital. In addition to a strong predictive performance, the set of selected features highlights the relevance of several underrated molecules in COVID-19 research, such as blood eosinophils, bilirubin, and urea levels. © 2021 IEEE.

Effectiveness of early use of low doses of tocilisumab in the treatment of COVID-19 associated pneumonia

Background: The SARS Cov-2 virus can cause cytokine storm, a key cause of severe course, complications and mortality. Hyperproduction of IL-6 correlates with a poor prognosis in COVID-19 with IL-6 increase preceding the negative effects and occurring at a stage earlier than the development of the worst symptoms. This study assesses the ability to reduce or prevent the risk of invasive artificial lung ventilation and death by early administration of low doses of tocilizumab in severe pneumonia with COVID-19. Method: 92 adult (38-81 years) patients with severe pneumonia COVID-19 with progressive course and growing markers of inflammation were studied. All patients received standard treatment but patients in the study group (42 people) also received soluble IL-6 receptor inhibitor tocilizumab (Actemra) 162 mg as two doses simultaneously, one in each thigh. Results: In the tocilizumab group 85.7% of patients showed a positive effect on clinical manifestations with normalization of body temperature and increased oxygen saturation within 5-7 days after the start of tocilizumab treatment relative to 63% in the control group with standard treatment (p < 0.05). There was decreasing risk for need of oxygen supplementation 7 days after treatment (1.42 fold, p < 0.05), deterioration of patients (1.68 fold, p < 0.05), and the need for artificial lung ventilation and death (1.96 fold, p < 0.05) in tocilizumab group compared to control. Blood clinical indicators including C reactive protein, ferritin and D-dimer were also lowered faster in tocilizumab group. Conclusion: Early use of the soluble IL-6 receptor inhibitor tocilizumab in patients with COVID-19 associated severe pneumonia reduces the risk of respiratory dysfunction and death.

Effects of remote monitoring of patients with heart failure based on smartphone application in the context of the COVID-19 pandemic in the Kyrgyz Republic

Background: Patients with CHF were the most vulnerable during the COVID-19 pandemic. Given to reduce hospitalizations and outpatient appointments, remote monitoring of CHF patients using a mobile application in response to the COVID-19 pandemic has proven particularly relevant, providing continuous specialized medical care and ensuring social distancing. Purpose: To study the clinical effectiveness of the implementation of a mobile application for remote monitoring of patients with CHF compared with standard practice during the COVID-19 pandemic in a mountainous country. Methods: ERICA-HF is a randomized, controlled, open-label study. Were included patients with verified CHF III FC (NYHA) with randomization to the main group of remote monitoring of patients using a mobile application + standard treatment (n=200) or to the control group on standard outpatient follow-up at the place of residence (n=100), for 12 months. The assessment of the clinical course of CHF is carried out on the basis of clinical indicators that allow assessing the current state of patients, depending on the quantitative assessment of deviations above or below the threshold values, consisting of seven points: shortness of breath, position in bed, heartbeating, edema, weight, blood pressure, heart rate, which the patient fills twice a week, with the possibility of automatically notifying the doctor and the patient. The application is equipped with two-way feedback in the form of structured telephone support and online chat. Quality of life assessment according to the Minnesota Living With Heart Failure Questionnaire, the ability to self-control according to the scale EHFScBS-9. The primary outcome is the percentage of unplanned rehospitalizations for HF decompensation, quality of life, mortality from CHF. The main secondary outcomes are cost-effectiveness and adherence to treatment. Results: During the COVID-19 pandemic, 209 patients on remote monitoring with CHF from all regions (63% men, age 65±11 years) were observed by coordinating cardiologists, 24 of them got sick with COVID-19, 7 received hospital treatment due to the development of HF decompensation, pneumonia and respiratory failure, 3 died of pneumonia. 9 participants dropped out of the study due to Internet traffic interruptions. 95% of patients noted high compliance, confidence, gave a positive assessment and use of the mobile application. Conclusion: Remote monitoring using a mobile application was an effective means of managing patients with CHF in socially isolation. This suggests that remote monitoring using a smart phone can be a good alternative to outpatient practice, which we have demonstrated in the context of the COVID-19 pandemic. Also, the relatively low cost can greatly facilitate the implementation of remote monitoring programs using a mobile application.