Analysis of Protein Biomarkers From Hospitalized COVID-19 Patients Reveals Severity-Specific Signatures and Two Distinct Latent Profiles With Differential Responses to Corticosteroids.

OBJECTIVES: To identify and validate novel COVID-19 subphenotypes with potential heterogenous treatment effects (HTEs) using electronic health record (EHR) data and 33 unique biomarkers. DESIGN: Retrospective cohort study of adults presenting for acute care, with analysis of biomarkers from residual blood collected during routine clinical care. Latent profile analysis (LPA) of biomarker and EHR data identified subphenotypes of COVID-19 inpatients, which were validated using a separate cohort of patients. HTE for glucocorticoid use among subphenotypes was evaluated using both an adjusted logistic regression model and propensity matching analysis for in-hospital mortality. SETTING: Emergency departments from four medical centers. PATIENTS: Patients diagnosed with COVID-19 based on International Classification of Diseases , 10th Revision codes and laboratory test results. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Biomarker levels generally paralleled illness severity, with higher levels among more severely ill patients. LPA of 522 COVID-19 inpatients from three sites identified two profiles: profile 1 ( n = 332), with higher levels of albumin and bicarbonate, and profile 2 ( n = 190), with higher inflammatory markers. Profile 2 patients had higher median length of stay (7.4 vs 4.1 d; p < 0.001) and in-hospital mortality compared with profile 1 patients (25.8% vs 4.8%; p < 0.001). These were validated in a separate, single-site cohort ( n = 192), which demonstrated similar outcome differences. HTE was observed ( p = 0.03), with glucocorticoid treatment associated with increased mortality for profile 1 patients (odds ratio = 4.54). CONCLUSIONS: In this multicenter study combining EHR data with research biomarker analysis of patients with COVID-19, we identified novel profiles with divergent clinical outcomes and differential treatment responses.

Diagnostic and prognostic capabilities of a biomarker and EMR-based machine learning algorithm for sepsis.

Sepsis is a major cause of mortality among hospitalized patients worldwide. Shorter time to administration of broad-spectrum antibiotics is associated with improved outcomes, but early recognition of sepsis remains a major challenge. In a two-center cohort study with prospective sample collection from 1400 adult patients in emergency departments suspected of sepsis, we sought to determine the diagnostic and prognostic capabilities of a machine-learning algorithm based on clinical data and a set of uncommonly measured biomarkers. Specifically, we demonstrate that a machine-learning model developed using this dataset outputs a score with not only diagnostic capability but also prognostic power with respect to hospital length of stay (LOS), 30-day mortality, and 3-day inpatient re-admission both in our entire testing cohort and various subpopulations. The area under the receiver operating curve (AUROC) for diagnosis of sepsis was 0.83. Predicted risk scores for patients with septic shock were higher compared with patients with sepsis but without shock (p < 0.0001). Scores for patients with infection and organ dysfunction were higher compared with those without either condition (p < 0.0001). Stratification based on predicted scores of the patients into low, medium, and high-risk groups showed significant differences in LOS (p < 0.0001), 30-day mortality (p < 0.0001), and 30-day inpatient readmission (p < 0.0001). In conclusion, a machine-learning algorithm based on electronic medical record (EMR) data and three nonroutinely measured biomarkers demonstrated good diagnostic and prognostic capability at the time of initial blood culture.

Gastrointestinal pathophysiology of SARS-CoV2 - a literature review.

SARS-CoV2 is a novel coronavirus responsible for causing COVID-19, first identified in the city of Wuhan, China and officially declared a pandemic by the World Health Organization. SARS-CoV2 expresses high affinity to human ACE2 receptors, including within the gastrointestinal tract. Patients with COVID-19 exhibit a wide spectrum of GI symptoms including anorexia, nausea, vomiting, abdominal pain, and abnormal liver function tests. Pathogenesis behind gastrointestinal symptoms caused by SARS-CoV2 has been postulated to be multifactorial including disruption of the intestinal mechanical barrier integrity, alteration of the gut microbiome and systemic inflammatory response to the virus. SARS-CoV-2 RNA has also been found in stool samples of infected patients for a significantly longer period than in nasopharyngeal samples, though the implication of this finding is unclear at this time. Liver injury in patients with COVID-19 is usually mild, stemming from immune-mediated damage, drug induced hepatotoxicity, or ischemia from sepsis. Patients with pre-existing liver disease may be at a higher risk for hospitalization and mortality. Given the high degree of infectivity of this disease, healthcare providers will need to remain watchful for resurgence of this virus. Strict protocols should be implemented regarding hand hygiene, isolation, personal protective equipment, and appropriate disposal of waste. It is also imperative to identify patients with gastrointestinal symptoms at an early stage as these patients may have a prolonged course between symptom onset and viral clearance.

Jejunal-Ileal Bypass and its Complications: Case Report and Review of the Literature.

Herein, we describe an interesting case of a patient who underwent a jejunal-ileal bypass (JIB). She presented to the hospital with gastrointestinal bleeding after which her hospital course was complicated by electrolyte abnormalities. She was a 76-year-old Caucasian female with a past medical history of hypertension, type II diabetes, atrial fibrillation on warfarin, chronic obstructive pulmonary disease (COPD) treated with 3 liters of oxygen at home, obstructive sleep apnea, and morbid obesity, with history of an unknown type of bariatric procedure done in the 1970s. Her upper endoscopy showed a normal esophagus, stomach, and duodenum despite her history of bariatric surgery. Her colonoscopy revealed stenotic terminal ileum and an incidental colonic anastomosis at 35 cm from the anal verge with spot tattoo ink of unknown significance. Also noted were moderate internal hemorrhoids and large external hemorrhoids which were likely the source of her bleeding. Post endoscopy she had marked derangement in electrolytes, specifically hypocalcemia, hypomagnesemia, and hypo-phosphatemia.  JIB was first popularized in the 1960s for the treatment of obesity. There are two variations of the procedure, colloquially known as the Scott bypass and the Payne bypass. Our patient underwent the Scott JIB. The relatively longer intestinal tract combined with her ileal stenosis may explain her 50 years of relatively stable adaptation. It is imperative that treating physicians have a keen understanding of anatomy and physiology to adequately care for the long-term needs of these patients.