Liver injury due to COVID-19 in critically ill adult patients. A retrospective study.

INTRODUCTION AND AIM: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing the current pandemic of acute respiratory disease known as COVID-19. Liver injury due to COVID-19 is defined as any liver injury occurring during the course of the disease and treatment of patients with COVID-19, with or without liver disease. The incidence of elevated liver transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ranges from 2.5 to 76.3%. The aim of the present study was to describe the hepatic biochemical abnormalities, after a SARS-CoV-2-positive polymerase chain reaction (PCR) test, and the mortality rate in critically ill patients. MATERIALS AND METHODS: A retrospective study was conducted that included 70 patients seen at a private hospital in Mexico City, within the time frame of February-December 2021. Median patient age was 44.5 years (range: 37-57.2) and 43 (61.4%) of the patients were men. Liver function tests were performed on the patients at hospital admission. RESULTS: Gamma glutamyl transferase (GGT) levels were elevated (p = 0.032), as were those of AST (p = 0.011) and ALT (p = 0.021). The patients were stratified into age groups: 18-35, 36-50, and > 50 years of age. The 18 to 35-year-olds had the highest liver enzyme levels and transaminase levels were higher, the younger the patient. Due to the low mortality rate (one patient whose death did not coincide with a hepatic cause), the multivariate analysis showed an R2 association of 0.689, explained by AST, GGT, and C-reactive protein levels. CONCLUSIONS: Despite the increase in transaminases in our study population during the course of COVID-19, there was no increase in mortality. Nevertheless, hospitalized patient progression should be continuously followed.

Liver injury due to COVID-19 in critically ill adult patients. A retrospective study Lesión hepática por COVID-19 en pacientes adultos criticamente enfermos. Estudio retrospectivo

Graphical Introduction and aim Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing the current pandemic of acute respiratory disease known as COVID-19. Liver injury due to COVID-19 is defined as any liver injury occurring during the course of the disease and treatment of patients with COVID-19, with or without liver disease. The incidence of elevated liver transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ranges from 2.5 to 76.3%. The aim of the present study was to describe the hepatic biochemical abnormalities, after a SARS-CoV-2-positive polymerase chain reaction (PCR) test, and the mortality rate in critically ill patients. Materials and methods A retrospective study was conducted that included 70 patients seen at a private hospital in Mexico City, within the time frame of February-December 2021. Median patient age was 44.5 years (range: 37-57.2) and 43 (61.4%) of the patients were men. Liver function tests were performed on the patients at hospital admission. Results Gamma glutamyl transferase (GGT) levels were elevated (p = 0.032), as were those of AST (p = 0.011) and ALT (p = 0.021). The patients were stratified into age groups: 18-35, 36-50, and > 50 years of age. The 18 to 35-year-olds had the highest liver enzyme levels and transaminase levels were higher, the younger the patient. Due to the low mortality rate (one patient whose death did not coincide with a hepatic cause), the multivariate analysis showed an R2 association of 0.689, explained by AST, GGT, and C-reactive protein levels. Conclusions Despite the increase in transaminases in our study population during the course of COVID-19, there was no increase in mortality. Nevertheless, hospitalized patient progression should be continuously followed.

Lesión hepática por COVID-19 en pacientes adultos criticamente enfermos. Estudio retrospectivo Liver injury due to COVID-19 in critically ill adult patients. A retrospective study

Introducción y objetivo: La pandemia por coronavirus de 2019 (COVID-19), puede causar El síndrome respiratorio agudo grave (SARS-CoV-2) emergió, causando la pandemia actual de enfermedad respiratoria aguda llamada COVID-19. La lesión hepática por COVID-19 se define como cualquier daño hepático que ocurra durante el curso de la enfermedad y el tratamiento de pacientes con COVID-19, con o sin enfermedad hepática. La incidencia de transaminasas hepáticas elevadas, ALT (alanina aminotransferasa) y AST (aspartato aminotransferasa), va de 2.5% a 76.3%. El objetivo del estudio fue describir las anormalidades bioquímicas hepáticas posterior a la prueba reacción en cadena de la polimerasa (PCR) positiva para SARS-CoV-2 y mortalidad en el paciente crítico. Material y métodos: Es un estudio retrospectivo, se incluyeron 70 pacientes, la mediana de edad 44.5 (rango 37-57.2), siendo del sexo masculino 43 (61.4%), de un hospital privado de la Ciudad de México, se midieron al ingreso hospitalario las pruebas de función hepática. Período de febrero-diciembre 2021. Resultados: Encontrando elevación de gamma-glutamil transferasa (GGT) p 0.032, aspartato aminotransferasa (AST) p 0.011, alanina-aminotransferasa (ALT) p 0.021, los pacientes se estratificaron en grupo de edad, 18-35, 36-50 y > 50 años. La mayor elevación fue de 18-35 años, entre más joven mayor elevación de transaminasas, debido a la baja mortalidad, 1 paciente, que no coincide con causa hepática, el análisis multivariado explicó una asociación R2.689 p 0.001, explicado por AST, GGT y proteína C reactiva. Conclusiones: A pesar del incremento de transaminasas durante la infección por COVID 19, en nuestra población no aumentó la mortalidad, si bien, debe darse seguimiento continuo durante la evolución hospitalaria.

[Liver injury due to COVID-19 in critically ill adult patients. A retrospective study]. / Lesión hepática por COVID-19 en pacientes adultos criticamente enfermos. Estudio retrospectivo.

INTRODUCTION AND AIM: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing the current pandemic of acute respiratory disease known as COVID-19. Liver injury due to COVID-19 is defined as any liver injury occurring during the course of the disease and treatment of patients with COVID-19, with or without liver disease. The incidence of elevated liver transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ranges from 2.5 to 76.3%. The aim of the present study was to describe the hepatic biochemical abnormalities, after a SARS-CoV-2-positive polymerase chain reaction (PCR) test, and the mortality rate in critically ill patients. MATERIALS AND METHODS: A retrospective study was conducted that included 70 patients seen at a private hospital in Mexico City, within the time frame of February-December 2021. Median patient age was 44.5 years (range: 37-57.2) and 43 (61.4%) of the patients were men. Liver function tests were performed on the patients at hospital admission. RESULTS: Gamma glutamyl transferase (GGT) levels were elevated (p = 0.032), as were those of AST (p = 0.011) and ALT (p = 0.021). The patients were stratified into age groups: 18-35, 36-50, and > 50 years of age. The 18 to 35-year-olds had the highest liver enzyme levels and transaminase levels were higher, the younger the patient. Due to the low mortality rate (one patient whose death did not coincide with a hepatic cause), the multivariate analysis showed an R2 association of 0.689, explained by AST, GGT, and C-reactive protein levels. CONCLUSIONS: Despite the increase in transaminases in our study population during the course of COVID-19, there was no increase in mortality. Nevertheless, hospitalized patient progression should be continuously followed.

Association of arterial stiffness with all-cause mortality among hospitalized covid-19 patients

Objective: Older age and cardiovascular comorbidities are well-known risk factors for all-cause mortality in COVID-19 patients. Hypertension (HT) and age are the two principal determinants of arterial stiffness (AS). The objective of this study is to estimate AS in COVID-19 patients requiring hospital admission and analyze its association with all-cause mortality. Design and method: This cross-sectional, observational, retrospective multicenter study includes 122170 patients who required hospital admission in 150 Spanish centers, included in the nationwide SEMI-COVID-19 Network. We compared estimated AS as pulse pressure > 60 mmHg and compared clinical characteristics between survivors and nonsurvivors. Results: Mean age was 67.5±16.1 years, 42.5% were women. Most patients were white (90.0%). Globally, 2606 (21.4%) subjects died. Blood pressure (BP) < 120 mmHg and BP > 140 at admission predicted higher all-cause mortality (23.5% and 22.8%, respectively, p<0.001), compared to BP between 120-140 mmHg (18.6%). 4379 patients with AS (36.0%) were older and had higher systolic and lower diastolic BP. Multivariate analysis showed that even adjusting for gender (males, OR: 1.6, p=0.0001), age tertiles (second and third tertiles, OR: 2.0 and 4.7, p=0.0001), Charlson-Index (second and third tertiles, OR: 4.8 and 8.6, p=0.0001), heart failure, previous and in-hospital antihypertensive treatment, AS and BP < 120 mmHg significantly and independently predicted all-cause mortality (OR: 1.27, p=0.0001 and OR: 1.48, p=0.0001, respectively). Conclusions: Our data show that arterial stiffness, defined as pulse pressure above 60 mmHg at hospital admission, and BP at admission < 120 mmHg were important determinants with independent prognostic value for all-cause mortality in COVID-19 patients requiring hospitalization.

Pediatric home confinement due to COVID-19: Somatic and anxiety spectrum consequences.

AIMS AND OBJECTIVES: We aimed to determine the impact of COVID-19 related home confinement on the paediatric population by focusing on anxiety, behavioural disturbances and somatic symptoms. BACKGROUND: To limit the spread of the COVID-19 outbreak, governments have imposed nationwide lockdowns to prevent direct contact; this has affected everyday lives and activities such as attending school classes. Such isolation may have impacted children's anxiety levels. DESIGN AND METHODS: We conducted a cross-sectional observational study using a web-based anonymous questionnaire from 22-26 April, 2020, among children (N = 2,292) in Spain. For children below 7 years of age, parents reported the children's behavioural, emotional and somatic symptoms and family environment data on a questionnaire designed by the researchers. Children over 7 years answered the Revised Children's Manifest Anxiety Scale either independently or with their parents' assistance. RESULTS: Children over 7 years, boys in particular, scored high on the anxiety spectrum. Moreover, participants who knew someone who had suffered from COVID-19 at home or whose parent was directly involved in the pandemic, obtained higher Total Anxiety scores. Significantly high values were found in all aspects of anxiety among those who feared infection or whose parents been unemployed. Of the children below 7 years, 56.3% had four or more anxiety-related symptoms, the most frequent of which were tantrums, emotional changes, restlessness and fear of being alone. The number of symptoms reported was significant when someone in the family home had been infected with COVID-19. CONCLUSIONS: The COVID-19 home confinement had a significant impact on children, causing anxiety, behavioural problems and somatic manifestations. RELEVANCE TO CLINICAL PRACTICE: Nurses play a key role in screening children who have experience confinement owing to the COVID-19 pandemic in order to detect early anxiety symptoms using tele-health. Suitable direct interventions can then be implemented or interdisciplinary manage could be started.

A Phase I/II Clinical Trial to evaluate the efficacy of baricitinib to prevent respiratory insufficiency progression in onco-hematological patients affected with COVID19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Baricitinib is supposed to have a double effect on SARS-CoV2 infection. Firstly, it reduces the inflammatory response through the inhibition of the Januse-Kinase signalling transducer and activator of transcription (JAK-STAT) pathway. Moreover, it reduces the receptor mediated viral endocytosis by AP2-associated protein kinase 1 (AAK1) inhibition. We propose the use of baricinitib to prevent the progression of the respiratory insufficiency in SARS-CoV2 pneumonia in onco-haematological patients. In this phase Ib/II study, the primary objective in the safety cohort is to describe the incidence of severe adverse events associated with baricitinib administration. The primary objective of the randomized phase (baricitinib cohort versus standard of care cohort) is to evaluate the number of patients who did not require mechanical oxygen support since start of therapy until day +14 or discharge (whichever it comes first). The secondary objectives of the study (only randomized phase of the study) are represented by the comparison between the two arms of the study in terms of mortality and toxicity at day+30. Moreover, a description of the immunological related changes between the two arms of the study will be reported. TRIAL DESIGN: The trial is a phase I/II study with a safety run-in cohort (phase 1) followed by an open label phase II randomized controlled trial with an experimental arm compared to a standard of care arm. PARTICIPANTS: The study will be performed at the Institut Català d'Oncologia, a tertiary level oncological referral center in the Catalonia region (Spain). The eligibility criteria are: patients > 18 years affected by oncological diseases; ECOG performance status < 2 (Karnofsky score > 60%); a laboratory confirmed infection with SARS-CoV-2 by means of real -time PCR; radiological signs of low respiratory tract disease; absence of organ dysfunction (a total bilirubin within normal institutional limits, AST/ALT≤2.5 X institutional upper limit of normal, alkaline phosphatase ≤2.5 X institutional upper limit of normal, coagulation within normal institutional limits, creatinine clearance >30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal); absence of HIV infection; no active or latent HBV or HCV infection. The exclusion criteria are: patients with oncological diseases who are not candidates to receive any active oncological treatment; hemodynamic instability at time of study enrollment; impossibility to receive oral medication; medical history of recent or active pulmonary embolism or deep venous thrombosis or patients at high-risk of suffering them (surgical intervention, immobilization); multi organ failure, rapid worsening of respiratory function with requirement of fraction of inspired oxygen (FiO2) > 50% or high-flow nasal cannula before initiation of study treatment; uncontrolled intercurrent illness (ongoing or severe active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements); allergy to one or more of study treatments; pregnant or breastfeeding women; positive pregnancy test in a pre-dose examination. Patients should have the ability to understand, and the willingness to sign, a written informed consent document; the willingness to accept randomization to any assigned treatment arm; and must agree not to enroll in another study of an investigational agent prior to completion of Day +28 of study. An electronic Case Report Form in the Research Electronic Data Capture (REDCap) platform will be used to collect the data of the trial. Removal from the study will apply in case of unacceptable adverse event(s), development of an intercurrent illness, condition or procedural complication, which could interfere with the patient's continued participation and voluntary patient withdrawal from study treatment (all patients are free to withdraw from participation in this study at any time, for any reasons, specified or unspecified, and without prejudice). INTERVENTION AND COMPARATOR: Treatment will be administered on an inpatient basis. We will compare the experimental treatment with baricitinib plus the institutional standard of care compared with the standard of care alone. During the phase I, we will define the dose-limiting toxicity of baricitinib and the dose to be used in the phase 2 part of the study. The starting baricitinib dose will be an oral tablet 4 mg-once daily which can be reduced to 2 mg depending on the observed toxicity. The minimum duration of therapy will be 5 days and it can be extended to 7 days. The standard of care will include the following therapies. Antibiotics will be individualized based on clinical suspicion, including the management of febrile neutropenia. Prophylaxis of thromboembolic disease will be administered to all participants. Remdesivir administration will be considered only in patients with severe pneumonia (SatO2 <94%) with less than 7 days of onset of symptoms and with supplemental oxygen requirements but not using high-flow nasal cannula, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO). In the randomized phase, tocilizumab or interferon will not be allowed in the experimental arm. Tocilizumab can be used in patients in the standard of care arm at the discretion of the investigator. If it is prescribed it will be used according to the following criteria: patients who, according to his baseline clinical condition, would be an ICU tributary, interstitial pneumonia with severe respiratory failure, patients who are not on mechanical ventilation or ECMO and who are still progressing with corticoid treatment or if they are not candidates for corticosteroids. Mild ARDS (PAFI <300 mmHg) with radiological or blood gases deterioration that meets at least one of the following criteria: CRP >100mg/L D-Dimer >1,000µg/L LDH >400U/L Ferritin >700ng/ml Interleukin 6 ≥40ng/L. The use of tocilizumab is not recommended if there are AST/ALT values greater than 10 times the upper limit of normal, neutrophils <500 cells/mm3, sepsis due to other pathogens other than SARS-CoV-2, presence of comorbidity that can lead to a poor prognosis, complicated diverticulitis or intestinal perforation, ongoing skin infection. The dose will be that recommended by the Spanish Medicine Agency in patients ≥75Kg: 600mg dose whereas in patients <75kg: 400mg dose. Exceptionally, a second infusion can be assessed 12 hours after the first in those patients who experience a worsening of laboratory parameters after a first favourable response. The use of corticosteroids will be recommended in patients who have had symptoms for more than 7 days and who meet all the following criteria: need for oxygen support, non-invasive or invasive mechanical ventilation, acute respiratory failure or rapid deterioration of gas exchange, appearance or worsening of bilateral alveolar-interstitial infiltrates at the radiological level. In case of indication, it is recommended: dexamethasone 6mg/d p.o. or iv for 10 days or methylprednisolone 32mg/d orally or 30mg iv for 10 days or prednisone 40mg day p.o. for 10 days. MAIN OUTCOMES: Phase 1 part: to describe the toxicity profile of baricitinib in COVID19 oncological patients during the 5-7 day treatment period and until day +14 or discharge (whichever it comes first). Phase 2 part: to describe the number of patients in the experimental arm that will not require mechanical oxygen support compared to the standard of care arm until day +14 or discharge (whichever it comes first). RANDOMISATION: For the phase 2 of the study, the allocation ratio will be 1:1. Randomization process will be carried out electronically through the REDcap platform ( https://www.project-redcap.org/ ) BLINDING (MASKING): This is an open label study. No blinding will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The first part of the study (safety run-in cohort) will consist in the enrollment of 6 to 12 patients. In this population, we will test the toxicity of the experimental treatment. An incidence of severe adverse events grade 3-4 (graded by Common Terminology Criteria for Adverse Events v.5.0) inferior than 33% will be considered sufficient to follow with the next part of the study. The second part of the study we will perform an interim analysis of efficacy at first 64 assessed patients and a definitive one will analyze 128 assessed patients. Interim and definitive tests will be performed considering in both cases an alpha error of 0.05. We consider for the control arm this rate is expected to be 0.60 and for the experimental arm of 0.80. Considering this data, a superiority test to prove a difference of 0.20 with an overall alpha error of 0.10 and a beta error of 0.2 will be performed. Considering a 5% of dropout rate, it is expected that a total of 136 patients, 68 for each study arm, will be required to complete study accrual. TRIAL STATUS: Version 5.0. 14th October 2020 Recruitment started on the 16th of December 2020. Expected end of recruitment is June 2021. TRIAL REGISTRATION: AEMPs: 20-0356 EudraCT: 2020-001789-12, https://www.clinicaltrialsregister.eu/ctr-search/search (Not publically available as Phase I trial) Clinical trials: BARCOVID19, https://www.clinicaltrials.gov/ (In progress) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol."

Accompaniment of patients at the end of life during the COVID-19 pandemic

Objectives: This study describes how patients were accompanied and bidden farewell in their last few days of life at hospitals and nursing homes. It also describes the attitudes of health professionals towards the care of patients in the last days of life during the COVID-19 pandemic. Method: A cross-sectional descriptive study was conducted in nurses. Data collection was done by an ad-hoc questionnaire in April and May 2020 through Google Forms. Collected variables included social demographics, work environment, training, satisfaction variables, motivation, work-related stress, and an attitude towards patients at the end of life scale. A descriptive univariate analysis of the subjects in the sample was carried out using the SPSS 22.0 software including proportions, frequencies, measurements of central tendency, and distribution. Results: According to professionals, an important number of patients diagnosed with Covid-19 (38.8%, n = 110) were not accompanied in their last 48 hours of life. This was limited to a few hours (56.4%, n = 154), and saying goodbye was done in a majority of cases before death (44.1%, n = 143). A great number of professionals have noticed changes in accompanying and saying goodbye (77.3%, n = 211), including their way of caring. A total of 52.4%, n = 143, said that they had found patients dead on entering the room;53.1%, n = 178 were aware of accompanying protocols. Conclusions: It is obviously clear that many patients were alone during their last hours in spite of accompaniment protocols and the efforts of the staff looking after them. Professionals have modified the care given to patients at the end of life during the pandemic, generating conflicts and negative emotional attitudes. Isolation has a great emotional cost for the staff and for families during bereavement, which is important to study and evaluate in the mid-term.

Prognostic implications of neutrophil-lymphocyte ratio in COVID-19.

BACKGROUND: The clinical presentation of COVID-19 ranges from a mild, self-limiting disease, to multiple organ failure and death. Most severe COVID-19 cases present low lymphocytes counts and high leukocytes counts, and accumulated evidence suggests that in a subgroup of patients presenting severe COVID-19, there may be a hyperinflammatory response driving a severe hypercytokinaemia which may be, at least in part, signalling the presence of an underlying endothelial dysfunction. In this context, available data suggest a prognostic role of neutrophil-lymphocyte ratio (NLR) in various inflammatory diseases and oncological processes. Following this rationale, we hypothesized that NLR, as a marker of endothelial dysfunction, may be useful in identifying patients with a poor prognosis in hospitalized COVID-19 cases. DESIGN: A retrospective observational study performed at Hospital Universitario HM Puerta del Sur, Madrid, Spain, which included 119 patients with COVID-19 from 1 March to 31 March 2020. Patients were categorized according to WHO R&D Expert Group. RESULTS: Forty-five (12.1%) patients experienced severe acute respiratory failure requiring respiratory support. Forty-seven (12.6%) patients died. Those with worse outcomes were older (P = .002) and presented significantly higher NLR at admission (P = .001), greater increase in Peak NLR (P < .001) and higher increasing speed of NLR (P = .003) compared with follow-up patients. In a multivariable logistic regression, age, cardiovascular disease and C-reactive protein at admission and Peak NLR were significantly associated with death. CONCLUSIONS: NLR is an easily measurable, available, cost-effective and reliable parameter, which continuous monitoring could be useful for the diagnosis and treatment of COVID-19.