Mortality Of Severe Coronavirus Disease Research Articles

Immuno-Modulatory Effects of Dexamethasone in Severe COVID-19-A Swedish Cohort Study.

Dexamethasone (Dex) has been shown to decrease mortality in severe coronavirus disease 2019 (COVID-19), but the mechanism is not fully elucidated. We aimed to investigate the physiological and immunological effects associated with Dex administration in patients admitted to intensive care with severe COVID-19. A total of 216 adult COVID-19 patients were included-102 (47%) received Dex, 6 mg/day for 10 days, and 114 (53%) did not. Standard laboratory parameters, plasma expression of cytokines, endothelial markers, immunoglobulin (Ig) IgA, IgM, and IgG against SARS-CoV-2 were analyzed post-admission to intensive care. Patients treated with Dex had higher blood glucose but lower blood lactate, plasma cortisol, IgA, IgM, IgG, D-dimer, cytokines, syndecan-1, and E-selectin and received less organ support than those who did not receive Dex (Without-Dex). There was an association between Dex treatment and IL-17A, macrophage inflammatory protein 1 alpha, syndecan-1 as well as E-selectin in predicting 30-day mortality. Among a subgroup of patients who received Dex early, within 14 days of COVID-19 debut, the adjusted mortality risk was 0.4 (95% CI 0.2-0.8), i.e., 40% compared with Without-Dex. Dex administration in a cohort of critically ill COVID-19 patients resulted in altered immunological and physiologic responses, some of which were associated with mortality.

Biruni Index as a Novel Diagnostic Tool for the Early Prediction of Mortality in Critical Patients With COVID-19: A Cohort Study.

The aim of this study was to find out the potential risk factors associated with mortality in severe coronavirus disease 2019 (COVID-19) patients hospitalized due to viral bronchopneumonia, and to establish a novel COVID-19 mortality index for daily use. The study included 431 quantitative real-time polymerase chain reaction (qRT-PCR)-confirmed COVID-19-positive patients admitted to the intensive care unit in a tertiary care hospital. Patients were divided into training and validation cohorts at random (n= 285 and n= 130, respectively). Biruni Indexwas developed by multivariate logistic regression analysis for predicting COVID-19-related mortality. In univariate logistic regression analysis, age, systolic and diastolic blood pressures,respiratory and pulse rates per minute, D-dimer, pH, urea, ferritin, and lactate dehydrogenaselevels at first admission were statistically significant factors for the prediction of mortality in the training cohort. By using multivariate logistic regression analysis, all of these statistically significant parameters were used to produceBiruni Index. Statistically significant differences in Biruni Index were observed between ex and non-ex groups in both training and validation cohorts (P< 0.001 for both comparisons). Areas under receiver operating characteristic (ROC) curve for Biruni Index were 0.901 (95CI%: 0.864-0.938, P< 0.001) and 0.860 (95CI%: 0.795-0.926, P< 0.001) in training and validation cohorts, respectively. As a pioneering clinical study, Biruni Index may be a useful diagnostic tool for clinicians to predict the mortalityin critically ill patients with COVID-19 hospitalized due to severe viral bronchopneumonia. However, Biruni Index should be validated with larger series of multicenter prospective clinical studies.

Are lipid ratios and triglyceride-glucose index associated with critical care outcomes in COVID-19 patients?

Lipid ratios and the triglyceride and glucose index (TyG) could be a simple biochemical marker of insulin resistance (IR). The current study was carried out to examine the correlation between triglyceride to high-density lipoprotein-cholesterol (TG/HDL-C), total cholesterol to HDL-C (TC/HDL-C), low-density lipoprotein-cholesterol to HDL-C ratio (LDL-C/HDL-C), as well as TyG index with the severity and mortality of severe coronavirus disease 2019 (COVID-19). A total of 1228 confirmed COVID-19 patients were included in the current research. Regression models were performed to evaluate the correlation between the lipid index and severity and mortality of COVID-19. The TyG index and TG/HDL-C levels were significantly higher in the severe patients (P<0.05). TG/HDL-C, LDL-C/HDL-C, TC/HDL-C ratios, and TyG index were significantly lower in survivor cases (P<0.05). Multivariate logistic regression analysis demonstrated that predictors of the severity adjusted for age, sex and BMI were TyG index, TG/HDL-C ratio (OR = 1.42 CI:1.10–1.82, OR = 1.06 CI: 1.02–1.11, respectively). This analysis showed that TG/HDL-C, TC/HDL-C, LDL-C/HDL-C ratios, and TyG index statistically are correlated with COVID-19 mortality (OR = 1.12 CI:1.06–1.18, OR = 1.24 CI:1.05–1.48, OR = 1.47 CI:1.19–1.80, OR = 1.52 CI:1.01–2.31, respectively). In summary, the TyG index and lipid ratios such as TC/HDL-C, TG/HDL-C, LDL-C/HDL-C could be used as an early indicator of COVID-19 mortality. Furthermore, the study revealed that TyG index and TG/HDL-C indices are biochemical markers of COVID-19 severe prognosis.

Adjunctive Recombinant Human Plasma Gelsolin for Severe Coronavirus Disease 2019 Pneumonia.

BackgroundExcessive inflammation contributes to the morbidity and mortality of severe coronavirus disease 2019 (COVID-19) pneumonia. Recombinant human plasma gelsolin (rhu-pGSN) improves disease outcomes in diverse experimental models of infectious and noninfectious inflammation.MethodsIn a blinded, randomized study, 61 subjects with documented COVID-19 pneumonia having a World Health Organization (WHO) Severity Score of 4 to 6 and evidence of a hyperinflammatory state were treated with standard care and either adjunctive rhu-pGSN 12 mg/kg or an equal volume of saline placebo given intravenously at entry, 12 hours, and 36 hours. The prespecified coprimary outcomes were survival without major respiratory, hemodynamic, or renal support on Day 14 and the incidence of serious adverse events (SAEs) during the 90-day study period.ResultsAll subjects receiving ≥1 dose of study drug were analyzed. Fifty-four of 61 subjects (88.5%) were WHO severity level 4 at entry. The proportions of subjects alive without support on Day 14 were 25 of 30 rhu-pGSN recipients (83.3%) and 27 of 31 placebo recipients (87.1%). Over the duration of the study, WHO Severity Scores improved similarly in both treatment groups. No statistically significant differences were observed between treatment groups at any time point examined. Two subjects died in each group. Numerically fewer subjects in the rhu-pGSN group had SAEs (5 subjects; 16.7%) or ≥ Grade 3 adverse events (5 subjects; 16.7%) than in the placebo group (8 subjects [25.8%] and 9 subjects [29.0%], respectively), mostly involving the lungs. Three rhu-pGSN recipients (10.0%) were intubated compared to 6 placebo recipients (19.4%).ConclusionsOverall, subjects in this study did well irrespective of treatment arm. When added to dexamethasone and remdesivir, no definitive benefit was demonstrated for rhu-pGSN relative to placebo. Safety signals were not identified after the administration of 3 doses of 12 mg/kg rhu-pGSN over 36 hours. The frequencies of SAEs and intubation were numerically fewer in the rhu-pGSN group compared with placebo.

Cardiovascular drugs and analysis of potential risk factors associated with mortality in severe coronavirus disease 2019 patients.

Cardiovascular diseases are also considered to increase the risk of death in COVID-19 patients. However, real-world data concerning the risk factors for death in patients with severe COVID-19 still remain vague. This study aimed to identify the potential risk factors associated with mortality in severe COVID-19 patients. All consecutive patients admitted to the intensive care unit (ICU) of our institute for COVID-19 for severe COVID-19 pneumonia from April 1, 2020 to July 20, 2020 were included in the analysis. Patient characteristics, including complete medical history and comorbid diseases, blood test results during admission and on day 7, and clinical characteristics were compared between survivors and nonsurvivors. There was no significant difference between survivors and nonsurvivors regarding age, gender, and preexisting cardiovascular diseases. Moreover, the rate of the medications including angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blockers did not differ between survivors and nonsurvivors. The peak C-reactive protein (CRP), procalcitonin, fibrinogen, and d-dimer levels and the rate for chronic renal failure were significantly higher in nonsurvivors compared with survivors. Intubated patients had a higher risk of death than the others had. This study failed to demonstrate a significant difference in preexisting cardiovascular diseases and cardiovascular medications between survivors and nonsurvivors who were admitted to ICU for severe COVID-19. Our findings indicate that the presence of chronic renal failure, a high peak ferritin concentration, and the need for invasive mechanical ventilation appear predictive for mortality. We propose that these risk factors should be taken into account in defining the risk status of severe COVID-19 patients admitted to the ICU.

Clinical profile of bloodstream infections in COVID-19 patients: a retrospective cohort study

BackgroundBloodstream infections (BSIs) are an emerging cause of significant morbidity and mortality in severe Coronavirus disease 2019 (COVID-19). We aimed to assess the prevalence, clinical profile and outcome of BSIs in critically ill COVID-19 patients.MethodsThis was a single-centre retrospective study conducted at a tertiary care hospital in Western India. All patients (age > 18 years) with reverse-transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 admitted in the intensive care unit (ICU) were included. Hospital electronic records were searched for demographic data, time of bloodstream infection since admission, clinical profile, antimicrobial resistance pattern and clinical outcome of all patients who developed BSIs.ResultsOut of 750 patients admitted in COVID ICU, 8.5% developed secondary BSIs. All severe COVID-19 patients who developed BSIs succumbed to illness. A significant proportion of BSIs were Gram-negative pathogens (53/64, 82.8%). Acinetobacter baumannii was the commonest isolate, followed by Klebsiella pneumoniae (32.8% and 21.9%, respectively). Multidrug-resistance organisms (MDRO) were found in 57.8% of the cases. The majority of MDRO belonged to K. pneumoniae and Enterococcus groups. The proportion of Gram-negative bacteria resistant to carbapenems was 47.2% (25/53). On multivariate analysis, raised total leukocyte counts, mechanical ventilation and presence of comorbidities were significantly associated with the incidence of BSIs.ConclusionWe found a significant prevalence of Acinetobacter baumannii in COVID-19 associated BSIs. The presence of comorbidities raised leukocyte counts and mechanical ventilation should alarm clinicians for possible BSIs. The timely initiation of empirical antibiotics and rapid de-escalation is vital to improve the outcome. At the same time, strict compliance of infection control practices should be accomplished to reduce the occurrence of MDRO.

Acute Kidney Injury in Patients Hospitalized With COVID-19 in New York City: Temporal Trends From March 2020 to April 2021

Acute Kidney Injury in Patients Hospitalized With COVID-19 in New York City: Temporal Trends From March 2020 to April 2021

Vascular mechanisms and manifestations of COVID-19

Vascular mechanisms and manifestations of COVID-19

Respiratory and Psychophysical Sequelae Among Patients With COVID-19 Four Months After Hospital Discharge

Although plenty of data exist regarding clinical manifestations, course, case fatality rate, and risk factors associated with mortality in severe coronavirus disease 2019 (COVID-19), long-term respiratory and functional sequelae in survivors of COVID-19 are unknown. To evaluate the prevalence of lung function anomalies, exercise function impairment, and psychological sequelae among patients hospitalized for COVID-19, 4 months after discharge. This prospective cohort study at an academic hospital in Northern Italy was conducted among a consecutive series of patients aged 18 years and older (or their caregivers) who had received a confirmed diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection severe enough to require hospital admission from March 1 to June 29, 2020. SARS-CoV-2 infection was confirmed via reverse transcription-polymerase chain reaction testing, bronchial swab, serological testing, or suggestive computed tomography results. Severe COVID-19 requiring hospitalization. The primary outcome of the study was to describe the proportion of patients with a diffusing lung capacity for carbon monoxide (Dlco) less than 80% of expected value. Secondary outcomes included proportion of patients with severe lung function impairment (defined as Dlco <60% expected value); proportion of patients with posttraumatic stress symptoms (measured using the Impact of Event Scale-Revised total score); proportion of patients with functional impairment (assessed using the Short Physical Performance Battery [SPPB] score and 2-minute walking test); and identification of factors associated with Dlco reduction and psychological or functional sequelae. Among 767 patients hospitalized for severe COVID-19, 494 (64.4%) refused to participate, and 35 (4.6%) died during follow-up. A total of 238 patients (31.0%) (median [interquartile range] age, 61 [50-71] years; 142 [59.7%] men; median [interquartile range] comorbidities, 2 [1-3]) consented to participate to the study. Of these, 219 patients were able to complete both pulmonary function tests and Dlco measurement. Dlco was reduced to less than 80% of the estimated value in 113 patients (51.6%) and less than 60% in 34 patients (15.5%). The SPPB score was suggested limited mobility (score <11) in 53 patients (22.3%). Patients with SPPB scores within reference range underwent a 2-minute walk test, which was outside reference ranges of expected performance for age and sex in 75 patients (40.5%); thus, a total of 128 patients (53.8%) had functional impairment. Posttraumatic stress symptoms were reported in a total of 41 patients (17.2%). These findings suggest that at 4 months after discharge, respiratory, physical, and psychological sequelae were common among patients who had been hospitalized for COVID-19.

Коагулопатия при инфекции COVID-19.

Введение. Известно о коагулопатиях при инфекциях коронавирусами SARS и MERS. Цель исследования: изучить накопленную информацию о коагулопатии при инфекции COVID-19. Материалы и методы. В библиотеке PubMed провели поиск по ключевым словам «COVID-19», «coagulopathy». Обнаружили 15 публикаций, содержащих результаты оригинальных исследований. Результаты. При тяжелом течении заболевания наблюдают цитокиновый шторм, более высокие уровни Д-димера и продуктов деградации фибрина (ПДФ), более длительное протромбиновое время и активированное частичное тромбопластиновое время. Данные о частоте развития синдрома диссеминированного внутрисосудистого свертывания противоречивы. Заключение. У пациентов с COVID-19 с острой дыхательной недостаточностью наблюдается выраженная гиперкоагуляция. Всем госпитализированным пациентам с COVID-19 рекомендована фармакологическая тромбопрофилактика низкомолекулярными гепаринами или фондапаринуксом. Донорскую плазму для пассивной иммунотерапии нужно переливать только в рамках клинических исследований. Background. Coagulopathies are known for infections with SARS and MERS coronaviruses. Objectives: the reviewing the early accumulated information on coagulopathy in COVID-19. Patients / Methods. In PubMed Library with the keywords «COVID-19», «coagulopathy» we selected 15 publications containing the results of original studies. Results. In severe cases of the disease, a cytokine storm is observed, higher levels of D-dimer and fibrin degradation products (FDP), longer prothrombin time and activated partial thromboplastin time. Data about incidence of disseminated intravascular coagulation are contradictory. Conclusions. Patients with COVID-19 with acute respiratory failure exhibit severe hypercoagulation. Pharmacological thromboprophylaxis with low molecular weight heparins or fondaparinux is recommended for all hospitalized patients with COVID-19. Donor plasma for passive immunotherapy should be transfused only as part of clinical trials.

Stroke and Thromboprophylaxis in the Era of COVID-19

Stroke and Thromboprophylaxis in the Era of COVID-19

MASSIVE STROKE IN A CRITICALLY ILL COVID-19 POSITIVE PATIENT DESPITE DUAL ANTI-PLATELET THERAPY AND VTE PROPHYLAXIS

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Current evidence suggests that COVID-19 infection leads to increased incidence of thrombotic events in critically ill patients [1]. Studies regarding the benefits of anticoagulation in COVID-19 patients have yielded mixed results[2,3]. The literature is unclear as to an effective strategy for VTE prevention in COVID-19 patients. In this case we will present a COVID-19 positive critically ill patient who suffered a large ischemic cerebrovascular accident despite receiving daily VTE prophylaxis and dual anti-platelet therapy. CASE PRESENTATION: Our patient is a 66-year-old female with a past medical history of uterine cancer receiving chemotherapy at the time of admission. Patient presented with hypoxemic respiratory failure secondary to COVID-19 pneumonia. Initial head CT scan demonstrated no definite acute intracranial findings. Patient was intubated without complications and admitted to the ICU. She was continued on her home doses of Plavix 75mg daily and Aspirin 81mg daily and started on subcutaneous Enoxaparin 40mg once daily for VTE prophylaxis. On hospital day #15 patient’s sedation was discontinued in preparation for spontaneous breathing trial, yet she did not return to baseline mental status. On hospital day #18 head CT scan was performed which revealed interval development of large late subacute/chronic left anterior and middle cerebral artery territory infarction (Image 1). At this time our patient is still receiving treatment for complications of COVID-19 pneumonia and has had no change in her mental status. DISCUSSION: In this case report our patient with COVID-19 pneumonia suffered an ischemic stroke despite dual anti-platelet therapy and VTE prophylaxis. Thrombotic complications are common in critically ill COVID-19 patients with an incidence reported to be as high as 31% [1]. One study found decreased mortality in critically ill COVID-19 patients receiving therapeutic anticoagulation [2]. However, another found a significant incidence of thrombotic events despite anticoagulation [3]. The role of dual anti-platelet therapy in conjunction with standard VTE prophylaxis has not been studied. Currently no cases of a COVID-19 patient suffering a thrombotic event while on dual anti-platelet therapy and VTE prophylaxis have been reported. A limitation of this case is that our patient was actively being treated for cancer, a known pro-thrombotic state, which may have contributed to her thrombotic event. CONCLUSIONS: This case report demonstrates that despite dual anti-platelet therapy and VTE prophylaxis our COVID-19 patient suffered a thrombotic event. These findings suggest that COVID-19 VTE prevention requires enhanced anticoagulation strategies compared to usual VTE prevention regimens. Further studies examining the role of dual anti-platelet therapy as well as various doses of anticoagulation are needed to elucidate effective strategies for VTE prevention in COVID-19 patients. Reference #1: Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19 [published online ahead of print, 2020 Apr 10]. Thromb Res. 2020;S0049-3848(20)30120-1. doi:10.1016/j.thromres.2020.04.013 Reference #2: Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18(5):1094-1099. doi:10.1111/jth.14817 Reference #3: Llitjos JF, Leclerc M, Chochois C, et al. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients [published online ahead of print, 2020 Apr 22]. J Thromb Haemost. 2020;10.1111/jth.14869. doi:10.1111/jth.14869 DISCLOSURES: No relevant relationships by Mark Guirguis, source=Web Response No relevant relationships by Michael Nicholson, source=Web Response No relevant relationships by Yuriy Takhalov, source=Web Response

Hypercoagulability in ICU Patients With Coronavirus Disease 2019 With Respiratory Failure Results in Increased Prevalence of Venous Thromboembolic Disease

Hypercoagulability in ICU Patients With Coronavirus Disease 2019 With Respiratory Failure Results in Increased Prevalence of Venous Thromboembolic Disease

Metformin: one of the possible options to reduce the mortality of severe coronavirus disease 2019?

According to the world epidemic report, the mortality of patients with severe coronavirus disease 2019 (COVID-19) is high. Diabetic patients are more susceptible to COVID-19. Since the mortality of COVID-19 patients with diabetes is on the top of list, hyperglycemia is considered an independent risk factor for severe COVID-19. Up to now, there is few effective treatment for severe patients infected with 2019 novel coronavirus (2019-nCoV). Clinical studies observed that cytokine storms existed in patients with severe COVID-19. Sustained high levels of cytokines cause diffuse damage to pulmonary capillary endothelial cells and alveolar epithelial cells, resulting in acute respiratory distress syndrome (ARDS). ARDS is the main cause of death in COVID-19 patients. Host-directed therapy (HDT) is an emerging therapeutic method in the field of anti-infection, which can activate the self-protective immune response, suppress excessive inflammatory response, and be used to assist the treatment of traditional drugs to shorten the course of disease. Metformin has been shown to be effective in HDT and can assist in the treatment of the viral and bacterial infectious disease. This paper discusses the rationality and potential therapeutic mechanism of metformin in the treatment of severe COVID-19. It was speculated that the use of metformin for controlling blood glucose in severe COVID-19 patients with diabetes may prevent or inhibit the occurrence of ARDS, thereby reducing the mortality of COVID-19 patients. The possible mechanism is that metformin could inhibit cytokine storm via suppressing interleukin-6 (IL-6) signaling, prevent the process of lung fibrosis, suppress endocytosis, thereby elevating angiotensin converting enzyme 2 (ACE2) expression.

Mortality in COVID-19 is not merely a question of resource availability

Mortality in COVID-19 is not merely a question of resource availability

VTE in ICU Patients With COVID-19

VTE in ICU Patients With COVID-19

Thromboinflammation and the hypercoagulability of COVID‐19

Thromboinflammation and the hypercoagulability of COVID‐19

Anticoagulation, immortality, and observations of COVID‐19

Anticoagulation, immortality, and observations of COVID‐19

COVID-19 and Cushing's syndrome: recommendations for a special population with endogenous glucocorticoid excess

COVID-19 and Cushing's syndrome: recommendations for a special population with endogenous glucocorticoid excess

Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells.

BackgroundWe previously reported that lymphocytopenia and T cell exhaustion is notable in acute COVID19 patients, especially in aged and severe cases. Thymosin alpha 1 (Tα1) had been used in the treatment of viral infections as an immune response modifier for many years. However, clinical benefits and mechanism of Tα1 supplement to COVID-19 are still unclear.MethodsWe retrospectively reviewed the clinical outcomes of 76 severe cases with COVID-19 admitted into two hospitals in Wuhan from December 2019 to March 2020. The thymus output in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients was measured by T cell receptor excision circles (TREC). The levels of T cell exhaustion markers PD-1 and Tim-3 on CD8+ T cells were detected by flow cytometry.ResultsCompared with untreated group, Tα1 treatment significantly reduces mortality of severe COVID-19 patients (11.11% vs. 30.00%, p=0.044). Tα1 timely enhances blood T cell numbers in COVID-19 patients with severe lymphocytopenia (the counts of CD8+ T cells or CD4+ T cells in circulation lower than 400/μL or 650/μL, respectively). Under such conditions, Tα1 also successfully restores CD8+ and CD4+ T cell numbers in aged patients. Meanwhile, Tα1 reduces PD-1 and Tim-3 expression on CD8+ T cells from severe COVID-19 patients in comparison with untreated cases. It is of note that restoration of lymphocytopenia and acute exhaustion of T cells are roughly parallel to the rise of TRECs.ConclusionsTα1 supplement significantly reduce mortality of severe COVID-19 patients. COVID-19 patients with the counts of CD8+ T cells or CD4+ T cells in circulation lower than 400/μL or 650/μL, respectively, gain more benefits from Tα1. Tα1 reverses T cell exhaustion and recovers immune reconstitution through promoting thymus output during SARS-CoV-2 infection.