Objectives SARS-CoV-2 exhibits tropism for the gastrointestinal tract, however lesions in enterocytes and their correlation with disease severity and patient prognosis are still unknown. Methods SARS-CoV-2 patients were enrolled in five medical centres in the São Paulo State, Brazil. Clinical characteristics and laboratory findings of patients were recorded. At admission, 7 th and 14 th day of hospitalisation, plasma and urine samples were collected. The levels of cytokines (IFN-γ, IL-6 and TNF-α) and the biomarker intestinal fatty acid-binding protein (I-FABP) were measured. Results COVID-19 patients displayed ≈48-, 74- and 125-fold increased urinary I-FABP levels at admission ( n= 283; p <0.001), 7 th ( n =142; p <0.01) and 14 th day ( n =75; p <0.01) of hospitalisation, respectively. Critically ill patients and nonsurvivors showed higher I-FABP concentrations compared to those in the infirmary and survivors, respectively, within the same hospital stay periods. At admission, infected patients demonstrated enhanced production of plasma IFN-γ and IL-6. The ROC curve suggested I-FABP as a biomarker for disease severity of COVID-19 at admission ( p <0.0001; Youden index=6.89; AUC=0.699). Patients with I-FABP≥6.89 showed higher IL-6 and C-reactive protein levels ( p <0.001) at admission, as well as prolonged length of hospital stay. Conclusions Our findings revealed damage to enterocytes in SARS-CoV-2 infection, which is associated to illness severity, poor prognosis and exacerbated inflammatory response.

Rationale: Methylene blue (MB) has been used to increase blood pressure in septic shock, acting on the activity of guanylate cyclase and nitric oxide synthase. Patience concerns: The aim of this study is to demonstrate the benefit of MB in early phase of septic shock. Diagnoses: We report 6 cases of patients with septic shock with up to 72 hours of evolution. Interventions: We used MB after fluid replacement, use of norepinephrine and vasopressin. Patients received a loading dose of MB and maintenance for 48 hours. Outcomes: All patients presented a reduction in the dose of vasopressors and lactate levels soon after the administration of the loading dose of MB, an effect that was maintained with the maintenance dose for 48 hours. Interleukin 6 and interleukin 8 were elevated at the beginning of the septic condition, with a progressive and marked reduction after the beginning of MB infusion, demonstrating a role of MB in reducing the inflammatory activity. Lessons: This case series suggests that MB used early in the treatment of septic shock may be useful in reducing vasopressor dose and lactate levels. Further studies are still required to further validate these findings.

Introduction: Septic shock is a lethal disease responsible for a large proportion of deaths in the Intensive Care Unit (ICU), even with therapy centered on fluid resuscitation, use of vasopressors and empirical antibiotic therapy applied within the first hour of diagnosis. Considering the multifactorial pathophysiology of septic shock and the mechanism of action of vasopressors, some patients may not respond adequately, which can lead to the maintenance of vasodilatation, hypotension and increased morbidity, and mortality. This protocol aims to verify whether the use of methylene blue in septic patients with an early diagnosis can contribute to an earlier resolution of a shock compared to standard treatment.Methods and analysis: This is a study protocol for a single-center randomized clinical trial design in an ICU of a tertiary university hospital. In this study, we intend to include 64 patients aged between 18 and 80 years with a diagnosis of septic shock, of any etiology, with up to 72 hours of evolution after volume restoration, using norepinephrine at a dose ≥0.2 mg/kg/min and vasopressin at a dose of 0.04 IU/min. After the initial approach, we will randomize patients into two groups, standard care, and standard care plus methylene blue. The sample size was calculated in order to show 30% differences in septic shock resolution between groups. The Research Ethics Committee approved the study, and all patients included will sign an informed consent form (Clinical registration: RBR-96584w4). Abbreviations: ARDS = acute respiratory distress syndrome, CI = cardiac index, cNOS = constitutive nitric oxide synthase, CO = Cardiac Output, EFG = global ejection fraction, HR = heart rate, IAPF = pulmonary extravascular water index, ICU = Intensive Care Unit, IDFG = global end-diastolic volume index, iNOS = induced nitric oxide synth, IPVP = pulmonary vascular permeability index, IRVSi = systemic vascular resistance index, IVSi = systolic volume index, MAP = mean arterial pressure, PVC = central venous pressure, SAPS-3 = Simplified Acute Physiology Score, SVV = systolic volume variation.

Introduction: Therapy and nutritional status directly interfere in the clinical evolution of critically ill patients, in reducing morbidity and mortality, by maintaining the functional integrity of the gastrointestinal tract, decreasing the catabolic response, besides contributing to the reduction of hospitalization time resulting in less treatment cost. Critical patients and trauma victims suffer early changes in the quantity and quality of muscle mass. Tools to identify the groups most susceptible to these complications are necessary so that interventions can minimize the deleterious effects of malnutrition in critically ill patients. Methods and analysis: The aim of the present study is to measure muscle mass loss by measuring the thickness of the rectus femoris muscle by bedside ultrasound in critically ill patients admitted to the Intensive Care Unit (ICU) of a university hospital. Information will be collected regarding the length of hospital and ICU stay, the reason for admission, anthropometric data at admission and during hospitalization, energy needs, nutritional therapy used, and fasting time. This is a prospective, observational study that will be carried out in a single center in an ICU of a tertiary university hospital. The study population will undergo 3 tomographic images and 3 ultrasounds of the rectus femoris of each patient at different times. We propose, unprecedentedly, performing a validation study of ultrasound with the gold standard Computed tomography to evaluate the musculature of critically ill patients victims of traumatic brain injury. The results got will texto be fundamental for the development of new fields of investigation and certainly contribute to the discovery of a new approach to treat sarcopenia in critically ill patients. The Research Ethics Committee approved the study and all patients included will sign an informed consent form. (Clinical Record: RBR-2bzspnz).