Gastrointestinal Manifestations of Coronavirus Disease 2019 Across the United States: A Multicenter Cohort Study.

Background and Aims: Gastrointestinal (GI) symptoms occur among patients diagnosed with coronavirus disease 2019 (COVID-19), and there is clear evidence that SARS-CoV-2, the causative pathogen, infects the GI tract. In this large, multicenter cohort study, we evaluated variations in gastrointestinal and hepatic manifestations of COVID-19 throughout the United States (US). Methods: Patients hospitalized with a positive COVID-19 test prior to October 2020 were identified at 7 US academic centers. Demographics, presenting symptoms, laboratory data, and hospitalization outcomes were abstracted. Descriptive and regression analyses were used to evaluate GI manifestations and their potential predictors. Results: Among 2031 hospitalized patients with COVID-19, GI symptoms were present in 18.9%; diarrhea was the most common (15.2%), followed by nausea and/or vomiting (12.6%) and abdominal pain (6.0%). GI symptoms were less common in the Western cohort (16.0%) than the Northeastern (25.6%) and Midwestern (26.7%) cohorts. Compared to nonintensive care unit (ICU) patients, ICU patients had a higher prevalence of abnormal aspartate aminotransferase (58.1% vs 37.3%; P < .01), alanine aminotransferase (37.5% vs 29.3%; P = .01), and total bilirubin (12.7% vs 9.0%; P < .01). ICU patients also had a higher mortality rate (22.7% vs 4.7%; P < .01). Chronic liver disease was associated with the development of GI symptoms. Abnormal aspartate aminotransferase or alanine aminotransferase was associated with an increased risk of ICU admission. Conclusion: We present the largest multicenter cohort of patients with COVID-19 across the United States. GI manifestations were common among patients hospitalized with COVID-19, although there was significant variability in prevalence and predictors across the United States.

Effect of a diet based on Iranian traditional medicine on inflammatory markers and clinical outcomes in COVID-19 patients: A double-blind, randomized, controlled trial.

Introduction: SARS-CoV-2 causes severe acute respiratory syndrome prompting worldwide demand for new antiviral treatments and supportive care for organ failure caused by this life-threatening virus. This study aimed to help develop a new Traditional Persian Medicine (TPM) -based drug and assess its efficacy and safety in COVID-19 patients with major symptoms. Methods: In February 2022, a randomized clinical trial was conducted among 160 patients with a confirmed diagnosis of COVID-19 admitted to Emam Reza (AJA) Hospital in Tehran, Iran. During their hospitalization, the intervention group received a treatment protocol approved by Iran's Ministry of Health and Medical Education (MOHME), consisting of an Iranian regimen, Ficus carica; Vitis vinifera, Safflower, Cicer arietinum, Descurainiasophia seeds, Ziziphus jujuba, chicken soup, barley soup, rose water, saffron, and cinnamon spices. All patients were compared in terms of demographics, clinical, and laboratory variables. Results: One hundred and sixty COVID-19 patients were divided into two groups: intervention and control. In baseline characteristics, there was no significant difference between the intervention and control groups (p>0.05). Using SPSS software version 22, statistical analysis revealed a significant difference in four symptoms: myalgia, weakness, headache, and cough (p<0.05). During the 5-day treatment period, the control group had significantly lower C-reactive protein (p<0.05). Conclusion: While more research with a larger sample size is needed, the proposed combination appears to be effective in the treatment of symptoms as well as inflammatory biomarkers such as C-reactive protein in COVID-19 patients.Iranian registry of clinical trials (IRCT) IRCT20220227054140N1.

Epidemiological characteristics, clinical course, and laboratory investigation of pediatric COVID-19 patients in a tertiary care center in Saudi Arabia.

Background: Since the initial emergence of the novel SARS-CoV-2 coronavirus responsible for the 2019 coronavirus disease (COVID-19) pandemic, many studies have been exploring the nature and characteristics of this virus and its associated clinical manifestations. The present study aimed to describe the clinical presentation and outcomes of COVID-19 infections in pediatric patients. Methods: A retrospective review of findings associated with 143 pediatric patients (age <14 years) with a confirmed COVID-19 diagnosis who had undergone inpatient or outpatient treatment at King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia, between March 2020 and October 2020, was conducted. The analyzed data included patient demographic information, pre-existing medical conditions, symptoms, interventions, and outcomes. Results: The median age of this patient population was 7 years. Of these 143 patients, 67 (46.8%) had known pre-existing medical conditions including bronchial asthma (12.8%), chronic lung disease (CLD) (3%), congenital heart disease (CHD) (17%), primary immunodeficiencies (1.5%), malignancies (9.8%), and 7.5% were post-transplant patients. Thirty-seven patients (26%) were overweight or obese. Sixty-three of these patients (51%) were symptomatic, with the most common symptom being fever (55%). Ultimately, 45 patients (31%) required admission to the hospital, with a median duration of hospitalization of 9.6 days for admitted patients. There were no documented cases of infection-related mortality among this pediatric cohort, although 11 patients experienced post-infectious complications that primarily manifested as a loss of taste and smell. Conclusion: These findings suggest that pediatric COVID-19 patients tend to experience mild forms of the disease, without any significant differences in disease severity as a function of patient gender or immune status.

Kombucha - An ancient fermented beverage with desired bioactivities: A narrowed review.

Kombucha, originated in China 2000  years ago, is a sour and sweet-tasted drink, prepared traditionally through fermentation of black tea. During the fermentation of kombucha, consisting of mainly acidic compounds, microorganisms, and a tiny amount of alcohol, a biofilm called SCOBY forms. The bacteria in kombucha has been generally identified as Acetobacteraceae. Kombucha is a noteworthy source of B complex vitamins, polyphenols, and organic acids (mainly acetic acid). Nowadays, kombucha is tended to be prepared with some other plant species, which, therefore, lead to variations in its composition. Pre-clinical studies conducted on kombucha revealed that it has desired bioactivities such as antimicrobial, antioxidant, hepatoprotective, anti-hypercholestorelomic, anticancer, anti-inflammatory, etc. Only a few clinical studies have been also reported. In the current review, we aimed to overhaul pre-clinical bioactivities reported on kombucha as well as its brief compositional chemistry. The literature data indicate that kombucha has valuable biological effects on human health.

In-hospital mortality and severe outcomes after hospital discharge due to COVID-19: A prospective multicenter study from Brazil.

Background: We evaluated in-hospital mortality and outcomes incidence after hospital discharge due to COVID-19 in a Brazilian multicenter cohort. Methods: This prospective multicenter study (RECOVER-SUS, NCT04807699) included COVID-19 patients hospitalized in public tertiary hospitals in Brazil from June 2020 to March 2021. Clinical assessment and blood samples were performed at hospital admission, with post-hospital discharge remote visits. Hospitalized participants were followed-up until March 31, 2021. The outcomes were in-hospital mortality and incidence of rehospitalization or death after hospital discharge. Kaplan-Meier curves and Cox proportional-hazard models were performed. Findings: 1589 participants [54.5% male, age=62 (IQR 50-70) years; BMI=28.4 (IQR,24.9-32.9) Kg/m² and 51.9% with diabetes] were included. A total of 429 individuals [27.0% (95%CI,24.8-29.2)] died during hospitalization (median time 14 (IQR,9-24) days). Older age [vs<40 years; age=60-69 years-aHR=1.89 (95%CI,1.08-3.32); age=70-79 years-aHR=2.52 (95%CI,1.42-4.45); age≥80-aHR=2.90 (95%CI 1.54-5.47)]; noninvasive or mechanical ventilation at admission [vs facial-mask or none; aHR=1.69 (95%CI 1.30-2.19)]; SAPS-III score≥57 [vs<57; aHR=1.47 (95%CI 1.13-1.92)] and SOFA score≥10 [vs <10; aHR=1.51 (95%CI 1.08-2.10)] were independently associated with in-hospital mortality. A total of 65 individuals [6.7% (95%CI 5.3-8.4)] had a rehospitalization or death [rate=323 (95%CI 250-417) per 1000 person-years] in a median time of 52 (range 1-280) days post-hospital discharge. Age ≥ 60 years [vs <60, aHR=2.13 (95%CI 1.15-3.94)] and SAPS-III ≥57 at admission [vs <57, aHR=2.37 (95%CI 1.22-4.59)] were independently associated with rehospitalization or death after hospital discharge. Interpretation: High in-hospital mortality rates due to COVID-19 were observed and elderly people remained at high risk of rehospitalization and death after hospital discharge. Funding: Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Programa INOVA-FIOCRUZ.

Evaluation of Liver Histopathological Findings of Coronavirus Disease 2019 by Minimally Invasive Autopsies.

AIM: The severe acute respiratory syndrome coronavirus 2 outbreak resulted in severe health impact with the loss of many lives across the world. Pulmonary parenchyma suffers the most from the brunt of the infection. However, evidence suggested a systemic involvement during the course of illness. Information on morphological changes of the liver is sparse in the literature. We aimed to evaluate the pathological findings in the liver by minimally invasive autopsies. METHODS: Postmortem core biopsies of the liver obtained from patients who succumbed to coronavirus disease 2019 disease were studied. Demographic findings, comorbidities, and relevant laboratory tests were collected. Detailed histopathological changes were assessed. RESULTS: Liver function tests were available in 40 cases, and it was deranged in 80% cases. A spectrum of histological changes was observed. Macrovesicular steatosis and nonspecific portal inflammation of mild degree were the common morphological changes. Features suggestive of vascular alteration were noted in more than half of the cases. These included increased portal vein branches, irregular luminal dilation, and herniation of portal veins into the periportal hepatocytes. In addition, we observed morphological changes attributed to terminal shock-related changes. CONCLUSION: The present study results highlight that liver parenchyma changes may be related to multiple pathogenic mechanisms. The presence of vascular alteration in portal tracts suggests derangement of hepatic vasculature related to systemic hypercoagulable state induced by the viral infection. It remains to be established if the histological changes are related to direct viral insult or to the systemic response caused by the viral attack.

Prognostic value of biochemical parameters among severe COVID-19 patients admitted to an intensive care unit of a tertiary hospital in South Africa.

Background: Data on biochemical markers and their association with mortality rates in patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) in sub-Saharan Africa are scarce. An evaluation of baseline routine biochemical parameters was performed in COVID-19 patients admitted to the ICU, in order to identify prognostic biomarkers. Methods: Demographic, clinical, and laboratory data were collected prospectively from patients with PCR-confirmed COVID-19 admitted to the adult ICU of a tertiary hospital in Cape Town, South Africa, between October 2020 and February 2021. Robust Poisson regression methods and the receiver operating characteristic (ROC) curve were used to explore the association of biochemical parameters with severity and mortality. Results: A total of 82 patients (median age 53.8 years, interquartile range 46.4-59.7 years) were enrolled, of whom 55 (67%) were female and 27 (33%) were male. The median duration of ICU stay was 10 days (interquartile range 5-14 days); 54/82 patients died (66% case fatality rate). Baseline lactate dehydrogenase (LDH) (adjusted relative risk 1.002, 95% confidence interval 1.0004-1.004; P = 0.016) and N-terminal pro B-type natriuretic peptide (NT-proBNP) (adjusted relative risk 1.0004, 95% confidence interval 1.0001-1.0007; P = 0.014) were both found to be independent risk factors of a poor prognosis, with optimal cut-off values of 449.5 U/l (sensitivity 100%, specificity 43%) and 551 pg/ml (sensitivity 49%, specificity 86%), respectively. Conclusions: LDH and NT-proBNP appear to be promising predictors of a poor prognosis in COVID-19 patients in the ICU. Studies with a larger sample size are required to confirm the validity of this combination of biomarkers.

A cross-sectional study of gastrointestinal manifestations in COVID-19 Egyptian patients.

BACKGROUND: The latest novel corona virus disease (COVID-19) pandemic shows a significant health concern. We aimed to study the prevalence of gastrointestinal symptoms among COVID-19 Egyptian patients. METHODS: A cross-sectional study was carried out on 860 patients with COVID-19 infection classified according to Ministry of Health Program (MOHP) into three groups (280 patients with mild infection, 258 patients with moderate disease and 322 patients with severe disease). All patients were subjected to medical history, clinical examination, laboratory investigations, high-resolution computed tomography chest (HRCT chest) and other investigations when needed in some patients e.g., upper gastro-intestinal (GI) endoscopy, abdomino-pelvic ultrasound and ECHO. RESULTS: Gastro-intestinal symptoms were present in 27.2% of the studied patients. The most common reported GIT symptoms were vomiting, diarrhea, abdominal/gastric pain, followed by nausea. GIT symptoms presence was significantly higher in severe cases in comparison to mild or moderate cases. C-reactive protein (CRP), serum ferritin, Aspartate aminotransferase (AST), bilirubin, and creatinine were significantly associated with the presence of GI symptoms. CONCLUSIONS: GI symptoms are prevalent among COVID-19 patients, the most common were vomiting and diarrhea and were associated with COVID-19 severity.

The Outcome in Cirrhosis after Hospital Discharge is Not Worsened with COVID-19 Infection: A Propensity Score-matched Analysis.

Background: Patients with cirrhosis and coronavirus disease-2019 (COVID-19) have high in-hospital mortality. The information on the outcome of cirrhosis patients in the posthospitalization period is limited. Aims: We aimed to study the outcome of cirrhosis patients with COVID-19 after hospital discharge. Methods: The records of the cirrhosis patients discharged after COVID-19 were reviewed. Their data were compared with a similar number of cirrhosis patients without COVID-19 after propensity score matching for age, sex, etiology of cirrhosis, and model for end-stage liver disease (MELD) score. Results: Cirrhosis patients with (n = 92) or without (n = 92) COVID-19 were included in 1:1 ratio. The mortality among COVID-19 (22; 23.9%) and non-COVID-19 (19; 20.7%) were comparable (HR 1.224; 95% CI 0.663-2.263, P = 0.520), over a similar duration of follow-up [186 (86-271) vs. 183 (103-274)]. Among COVID-19 patients, 45; 48.9% developed a new acute decompensation-increased ascites (40; 43.5%), hepatic encephalopathy (20; 21.7%), or variceal bleeding (8; 8.7%) whereas 25 (27.2%) patients needed rehospitalization. A proportion of participants continued to have either fatigue/weakness (24/80; 30.0%), sleep disturbances (11/80; 13.7%), or joint pains (16/80; 20.0%). The most common causes of death in patients of both groups were end-stage liver disease: 16 (72.7%) vs. 9 (47.4%), followed by multiorgan dysfunction: 4 (18.2%) vs. 6 (31.6%), GI bleeding: 2 (9.1%) vs. 4 (21.0%), P = 0.484. A lower albumin level, higher international normalized ratio, bilirubin, Child-Turcotte-Pugh, and MELD scores at discharge predicted mortality in the COVID-19 group. Conclusion: Short-term outcomes of patients with cirrhosis who survive the initial insult of COVID-19 are not different from patients without COVID-19, and survival is determined by the severity of liver disease at discharge.

Outcomes of COVID-19 in Patients with Cirrhosis or Liver Transplantation.

Coronavirus disease 2019 (COVID-19) is associated with a significant morbidity and mortality in patients with cirrhosis. There is a significantly higher morbidity and mortality due to COVID-19 in patients with decompensated cirrhosis as compared to compensated cirrhosis, and in patients with cirrhosis as compared to noncirrhotic chronic liver disease. The fear of COVID-19 before or after liver transplantation has lead to a significant reduction in liver transplantation numbers, and patients with decompensated cirrhosis remain at risk of wait list mortality. The studies in liver transplantation recipients show that risk of mortality due to COVID-19 is generally driven by higher age and comorbidities. The current review discusses available literature regarding outcomes of COVID-19 in patients with cirrhosis and outcomes in liver transplant recipients.

Predictors of in-hospital Outcomes in Patients With Cirrhosis and Coronavirus Disease-2019.

Background: Coronavirus disease-2019 (COVID-19) cases continue to increase globally. Poor outcomes in patients with COVID-19 and cirrhosis have been reported; predictors of outcome are unclear. The existing data is from the early part of the pandemic when variants of concern (VOC) were not reported. Aims: We aimed to assess the outcomes and predictors in patients with cirrhosis and COVID-19. We also compared the differences in outcomes between the first wave of pandemic and the second wave. Methods: In this retrospective analysis of a prospectively maintained database, data on consecutive cirrhosis patients (n = 221) admitted to the COVID-19 care facility of a tertiary care center in India were evaluated for presentation, the severity of liver disease, the severity of COVID-19, and outcomes. Results: The clinical presentation included: 18 (8.1%) patients had compensated cirrhosis, 139 (62.9%) acute decompensation (AD), and 64 (29.0%) had an acute-on-chronic liver failure (ACLF). Patients with ACLF had more severe COVID-19 infection than those with compensated cirrhosis and AD (54.7% vs. 16.5% and 33.3%, P < 0.001). The overall mortality was 90 (40.7%), the highest among ACLF (72.0%). On multivariate analysis, independent predictors of mortality were high leukocyte count, alkaline phosphatase, creatinine, child class, model for end-stage liver disease (MELD) score, and COVID-19 severity. The second wave had more cases of severe COVID-19 as compared to the first wave, with a similar MELD score and Child score. The overall mortality was similar between the two waves. Conclusion: Patients with COVID-19 and cirrhosis have high mortality (40%), particularly those with ACLF (72%). A higher leukocyte count, creatinine, alkaline phosphatase, Child class, and MELD score are predictors of mortality.

Incidence, characteristics, and outcome of COVID-19 in patients on liver transplant program: a retrospective study in the north of Iran.

The risk of severe coronavirus disease-2019 (COVID-19) disease seems to be higher in individuals with solid organ transplantation. Therefore, the purpose of the present research is to investigate the incidence of COVID-19 and laboratory data and epidemiologic factors in liver transplant recipients and the patients on the waiting list for liver transplantation. In this study, we evaluated the records of patients on the waiting list for liver transplantation and of recipients of a liver transplant. Demographic data, underlying disease, history of drug use and participants' outcomes were collected. The diagnosis of SARS-CoV-2 infection for all patients was confirmed using a nasopharyngeal swab specimen with real-time RT-PCR. During the study period, 172 patients were enrolled, among whom 85 patients (49.4%) were on the waiting list for liver transplantation, and 87 patients (50.6%) were recipients of a liver transplant. Out of them, 10 (5.8%) had a positive result for SARS-CoV-2. Of these patients, 7.05% (6/85) and 4.6% (4/87) of patients on the waiting list and recipients of liver transplants were positive for SARS-CoV-2, respectively. Patients on the waiting list with COVID-19 infection had a higher median of albumin, ALT, AST, TBIL, DBIL, HDL and LDL value. In summary, the incidence of COVID-19 in liver transplant patients was slightly higher. The existence of underlying liver diseases should be well known as one of the poor predictive factors for worse outcomes in patients with COVID-19. So, comparative studies are recommended to identify risk factors for COVID-19 in patients with liver injury.

Eleven routine clinical features predict COVID-19 severity uncovered by machine learning of longitudinal measurements.

Severity prediction of COVID-19 remains one of the major clinical challenges for the ongoing pandemic. Here, we have recruited a 144 COVID-19 patient cohort, resulting in a data matrix containing 3,065 readings for 124 types of measurements over 52 days. A machine learning model was established to predict the disease progression based on the cohort consisting of training, validation, and internal test sets. A panel of eleven routine clinical factors constructed a classifier for COVID-19 severity prediction, achieving accuracy of over 98% in the discovery set. Validation of the model in an independent cohort containing 25 patients achieved accuracy of 80%. The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 0.70, 0.99, 0.93, and 0.93, respectively. Our model captured predictive dynamics of lactate dehydrogenase (LDH) and creatine kinase (CK) while their levels were in the normal range. This model is accessible at https://www.guomics.com/covidAI/ for research purpose.

Severe COVID-19 Associated With Liver Injury in Patients Without Preexisting Liver Disease.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is known to disturb liver function tests (LFTs). Not much literature is available regarding the effect of COVID-19 on LFTs in patients without preexisting liver disease. The study aimed to find the effect of COVID-19 in these patients. METHODS:  This was a single-center, observational study with 142 patients who were admitted with COVID-19 during three months. Seven patients were excluded due to the presence of chronic liver disease.  Results: A total of 135 patients were included in the study aged between 18 and 95 years (mean 57.7 ± 15.6); among them, 93 were males (68.9%). Hypertension was present in 74 patients (54.8%), and diabetes was present in 48 patients (35.6%). Fever was the chief complaint in 112 patients (83%), followed by dyspnea in 93 patients (68.9%) and cough in 79 patients (58.5%). Elevated aspartate aminotransferase (AST) was seen in 35 patients (26%), gamma-glutamyl transferase (GGT) in 43 patients (32%), alanine transaminase (ALT) in 18 patients (24%), alkaline phosphatase in 19 patients (14%), bilirubin in six patients (4%), and low albumin in 27 patients (20%). Severe COVID-19, when compared with mild to moderate disease, was associated with elevated AST > two-time upper limit normal (2ULN) (p = 0.002), GGT > 2ULN (0.026), and lower albumin (p = 0.020), higher systemic inflammatory response syndrome (SIRS) (0.045), raised procalcitonin (p = 0.045), higher ferritin (p = 0.005), lower pO2 (p = 0.044), and higher Sequential Organ Failure Assessment score (SOFA) (p = 0.002) pointing to the inflammatory response as cause of liver injury. Factors predicting mortality with COVID-19 were assessed, which showed that direct bilirubin (p = 0.001), low albumin (p = 0.013), tachypnea (0.002), and leukocytosis (<0.001) were independently associated with increased COVID-19-related mortality. CONCLUSION:  Patients suffering from COVID-19 have evidence of liver injury, which appears to be secondary to an inflammatory response that correlates with the severity of COVID-19.

Personalized Prediction of Hospital Mortality in COVID-19-Positive Patients.

OBJECTIVE: To develop predictive models for in-hospital mortality and length of stay (LOS) for coronavirus disease 2019 (COVID-19)-positive patients. PATIENTS AND METHODS: We performed a multicenter retrospective cohort study of hospitalized COVID-19-positive patients. A total of 764 patients admitted to 14 different hospitals within the Cleveland Clinic from March 9, 2020, to May 20, 2020, who had reverse transcriptase-polymerase chain reaction-proven coronavirus infection were included. We used LightGBM, a machine learning algorithm, to predict in-hospital mortality at different time points (after 7, 14, and 30 days of hospitalization) and in-hospital LOS. Our final cohort was composed of 764 patients admitted to 14 different hospitals within our system. RESULTS: The median LOS was 5 (range, 1-44) days for patients admitted to the regular nursing floor and 10 (range, 1-38) days for patients admitted to the intensive care unit. Patients who died during hospitalization were older, initially admitted to the intensive care unit, and more likely to be white and have worse organ dysfunction compared with patients who survived their hospitalization. Using the 10 most important variables only, the final model's area under the receiver operating characteristics curve was 0.86 for 7-day, 0.88 for 14-day, and 0.85 for 30-day mortality in the validation cohort. CONCLUSION: We developed a decision tool that can provide explainable and patient-specific prediction of in-hospital mortality and LOS for COVID-19-positive patients. The model can aid health care systems in bed allocation and distribution of vital resources.

Elevated plasma ICAM1 levels predict 28-day mortality in cirrhotic patients with COVID-19 or bacterial sepsis.

BACKGROUND & AIMS: Endothelial injury and dysfunction play a detrimental role in the pathogenesis of infections. Endothelium-related molecules have been reported as potential diagnostic and/or prognostic biomarkers of infection. The prognostic value of these biomarkers in patients with cirrhosis and infections remains elusive. METHODS: In this study, we investigated the performance of key soluble endothelial injury biomarkers, including intercellular adhesion molecule 1 (ICAM1), von Willebrand factor (vWF), vascular endothelial growth factor receptor 1 (VEGFR1), and angiopoietin 1 and 2 (Ang1, 2) as mortality predictors in patients with cirrhosis and severe COVID-19 or bacterial sepsis. RESULTS: A total of 66 hospitalized patients (admitted to the COVID-19 ward or liver intensive care unit [ICU]) were included. Twenty-two patients had COVID-19 alone, while 20 patients had cirrhosis plus COVID-19. Twenty-four patients had cirrhosis plus bacterial sepsis. Among patients with cirrhosis, the most common aetiology of liver disease was alcohol. ICAM1 was increased (p = 0.003) while VEGFR1 (p <0.0001) and Ang1 (p <0.0001) were reduced in patients with COVID-19 and cirrhosis, compared to patients with COVID-19 alone. Endothelial biomarker levels did not differ significantly between patients with cirrhosis and severe COVID-19 or bacterial sepsis in the ICU. In these patients, ICAM1 levels significantly and independently predicted mortality (hazard ratio 3.24; 95% CI 1.19-8.86) along with model for end-stage liver disease (MELD) score, renal and coagulation failures. The AUC for ICAM1 was 0.74, MELD was 0.60 and combined ICAM1 and MELD was 0.70. ICAM1 also positively correlated with the composite organ failure scores recorded 3-5 days post ICU admission (CLIF-OF and SOFA) in this subgroup of patients. CONCLUSION: The study indicates that in patients with cirrhosis, elevated plasma ICAM1 serves as an independent predictor of severe COVID-19- or sepsis-associated 28-day mortality. LAY SUMMARY: Bacterial sepsis and COVID-19 lead to increased mortality in patients with cirrhosis. In this study, we demonstrate that high plasma levels of ICAM1, an endothelial injury biomarker, is one of the important factors predicting mortality in critically ill cirrhotic patients with severe COVID-19 or bacterial sepsis.

Increased levels of ferritin on admission predicts intensive care unit mortality in patients with COVID-19.

BACKGROUND: The aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19). METHODS: A total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate (n = 17), severe (n = 40) and critical groups (n = 43). Clinical information and laboratory results were collected and the concentrations of ferritin were compared among different groups. The association between ferritin and mortality was evaluated by logistic regression analysis. Moreover, the efficiency of the predicting value was assessed using receiver operating characteristic (ROC) curve. RESULTS: The amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25 µg/L vs. 501.90 µg/L, p < 0.01). The concentration of ferritin was positively correlated with other inflammatory cytokines, such as interleukin (IL)-8, IL-10, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α. Logistic regression analysis demonstrated that ferritin was an independent predictor of in-hospital mortality. Especially, high-ferritin group was associated with higher incidence of mortality, with adjusted odds ratio of 104.97 [95% confidence interval (CI) 2.63-4185.89; p = 0.013]. Moreover, ferritin had an advantage of discriminative capacity with the area under ROC (AUC) of 0.822 (95% CI 0.737-0.907) higher than procalcitonin and CRP. CONCLUSION: The ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la hiperferritinemia podría ser un factor predictivo de la mortalidad en pacientes hospitalizados con enfermedad por coronavirus de 2019 (COVID-19). MÉTODOS: Se incluyó un total de 100 pacientes hospitalizados con COVID-19 en la unidad de cuidados intensivos (UCI), clasificándose como grupos moderado (n = 17), grave (n = 40) y crítico (n = 43). Se recopiló la información clínica y de laboratorio, comparándose los niveles de ferritina entre los diferentes grupos. Se evaluó la asociación entre ferritina y mortalidad mediante un análisis de regresión logística. Además, se evaluó la eficacia del valor predictivo utilizando la curva ROC (receiver operating characteristic). RESULTADOS: La cantidad de ferritina fue significativamente superior en el grupo de pacientes críticos en comparación con el grupo de pacientes graves. La media de concentración de ferritina fue cerca de 3 veces superior en el grupo de muerte que en el grupo de supervivientes (1.722,25 µg/L vs. 501,90 µg/L, p < 0,01). La concentración de ferritina guardó una correlación positiva con otras citoquinas inflamatorias tales como interleucina (IL)-8, IL-10, proteína C reactiva (PRC) y factor de necrosis tumoral (TNF)-α. El análisis de regresión logística demostró que la ferritina era un factor predictivo independiente de la mortalidad intrahospitalaria. En especial, el grupo de ferritina alta estuvo asociado a una mayor incidencia de la mortalidad, con un valor de odds ratio ajustado de 104,97 [intervalo de confianza (IC) del 95% 2,63-4.185,89; p = 0,013]. Además, el valor de ferritina tuvo una ventaja de capacidad discriminativa en el área bajo la curva ROC (AUC) de 0,822 (IC 95% 0,737-0,907] superior al de procalcitonina y PRC. CONCLUSIÓN: El valor de ferritina medido durante el ingreso puede servir de factor independiente para prevenir la mortalidad intrahospitalaria en los pacientes de COVID-19 en la UCI.

Organizing pneumonia and COVID-19: A report of two cases.

Organizing pneumonia (OP) is a sub-acute process of pulmonary tissue repair secondary to lung injury, defined histopathologically by intra-alveolar buds of granulation tissue within the lumen of distal pulmonary airspaces. It can be either cryptogenic or secondary (SOP) to different clinical conditions, namely infections. Despite being nonspecific, its diagnosis can be made by the association of clinical and imaging criteria. We report two cases of OP associated to SARS-CoV-2 pneumonia, admitted at a Portuguese tertiary hospital unit dedicated to COVID-19. Both patients presented with severe respiratory failure with need of invasive mechanical ventilation. After initial recovery, there was worsening of dyspnea and hypoxemic respiratory failure with increase in inflammatory markers. Chest CT revealed an OP pattern. Other conditions such as superinfection, auto-immune disease and iatrogenic etiology, were excluded and corticotherapy at a dose of 1 mg/kg/day was administered. Chest CT follow up of both our patients showed complete resolution of OP pattern, with mild to moderate residual pulmonary fibrosis without honeycombing. There is no OP to SARS-CoV-2 case series yet published describing the progress of patients after corticotherapy, although the association between systemic corticosteroids and lower all-cause mortality in patients with COVID-19 has been recently established. It is possible that, as has been described with other viruses, OP secondary to SARS-CoV-2 represents an immunological process after initial infection, presenting with elevation of inflammatory markers and cytokines storm in the bloodstream and lung tissue, which may explain the favorable response to corticosteroids.

Disruption of CCR5 signaling to treat COVID-19-associated cytokine storm: Case series of four critically ill patients treated with leronlimab.

Coronavirus disease 2019 (COVID-19) is associated with considerable morbidity and mortality. The number of confirmed cases of infection with SARS-CoV-2, the virus causing COVID-19 continues to escalate with over 70 million confirmed cases and over 1.6 million confirmed deaths. Severe-to-critical COVID-19 is associated with a dysregulated host immune response to the virus, which is thought to lead to pathogenic immune dysregulation and end-organ damage. Presently few effective treatment options are available to treat COVID-19. Leronlimab is a humanized IgG4, kappa monoclonal antibody that blocks C-C chemokine receptor type 5 (CCR5). It has been shown that in patients with severe COVID-19 treatment with leronlimab reduces elevated plasma IL-6 and chemokine ligand 5 (CCL5), and normalized CD4/CD8 ratios. We administered leronlimab to 4 critically ill COVID-19 patients in intensive care. All 4 of these patients improved clinically as measured by vasopressor support, and discontinuation of hemodialysis and mechanical ventilation. Following administration of leronlimab there was a statistically significant decrease in IL-6 observed in patient A (p=0.034) from day 0-7 and patient D (p=0.027) from day 0-14. This corresponds to restoration of the immune function as measured by CD4+/CD8+ T cell ratio. Although two of the patients went on to survive the other two subsequently died of surgical complications after an initial recovery from SARS-CoV-2 infection.

Patients with SARS-CoV-2 and HBV co-infection are at risk of greater liver injury.

To date, it remains unclear if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection exacerbates liver injury in patients with chronic hepatitis B virus (HBV) infection. In this study, we present a retrospective study of 133 hospitalized confirmed mild coronavirus disease 2019 (COVID-19) cases, including 116 patients with COVID-19 with negative serum hepatitis B antigen and 17 HBV inactive carriers with COVID-19. We found that there were no significant differences for the discharge rate or duration of hospitalization between the two groups. However, inactive HBV carriers with SARS-CoV-2 co-infection are at a higher risk of abnormal liver function tests. The enhanced liver injury induced by SARS-CoV-2 and HBV co-infection was identified as the hepatocyte type rather than the cholangiocyte type. Moreover, the inflammatory response, including abnormal lactate dehydrogenase, D-dimer and interleukin-6 production, may contribute to this injury following SARS-CoV-2 co-infection. Collectively, SARS-CoV-2 and HBV co-infection exacerbates liver function of the patients with COVID-19.