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Clin Transl Gastroenterol ; 12(1): e00270, 2020 12 22.
Article in English | MEDLINE | ID: covidwho-1384028

COVID-19 , Humans , SARS-CoV-2
JCI Insight ; 7(15)2022 08 08.
Article in English | MEDLINE | ID: covidwho-1902172


Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation - measured as ß-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared with those without PASC or SARS-CoV-2-negative controls. The higher ß-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-methyl-d-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neurotoxic properties. Mechanistically, ß-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling. Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared with plasma from negative controls. This higher NF-κB signaling was abrogated by piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.

COVID-19 , beta-Glucans , COVID-19/complications , Humans , Inflammation , Lectins, C-Type/metabolism , NF-kappa B/metabolism , SARS-CoV-2 , Syk Kinase , Post-Acute COVID-19 Syndrome
J Clin Gastroenterol ; 56(2): e145-e148, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1238271


Coronavirus disease 2019 (COVID-19) has taken hundreds of thousands of lives globally. Besides the respiratory tract, the virus can affect the gastrointestinal (GI) tract. Data regarding the significance of GI symptoms in the COVID-19 course are limited. In this largest US study to date, the authors reviewed electronic encounters of 1003 consecutive patients who were tested positive for the virus between March 12 and April 3, 2020. Initial GI symptoms were present in up to 22.4% of patients and were associated with worse outcomes after adjustment for demographics, comorbidities, and other clinical symptoms. COVID-19 with GI involvement may define a more severe phenotype.

COVID-19 , Gastrointestinal Diseases , Comorbidity , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/epidemiology , Humans , SARS-CoV-2
Ann Allergy Asthma Immunol ; 125(4): 481-483, 2020 10.
Article in English | MEDLINE | ID: covidwho-716534
Clin Transl Gastroenterol ; 11(7): e00215, 2020 07.
Article in English | MEDLINE | ID: covidwho-681344


INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the pandemic of coronavirus disease 2019 (COVID-19) is a global health crisis. Possible pancreatic involvement has recently been observed in these patients; however, its significance is unclear. The aim of this study was to evaluate the association of significantly elevated lipase with disease outcomes. METHODS: Data about demographics, symptoms, laboratory values, and clinical outcomes were collected for 1,003 consecutive patients testing positive for COVID-19. Elevated lipase was defined as greater than 3 times the upper limit of normal (>3 × ULN). Baseline characteristics among patients with or without elevated lipase were compared using Fisher exact test or Student t-test for categorical or numerical variables, respectively. Logistic regression was used to evaluate the association of lipase levels with primary clinical outcomes (intensive care unit admission and intubation) adjusted for age, sex, body mass index, history of diabetes, and hypertension. RESULTS: Of 1,003 patients with COVID-19, 83 had available lipase levels and were all admitted to the hospital. Of 83, 14 (16.8%) had elevated lipase (>3 × ULN), which was associated with higher rates of leukocytosis (P < 0.001) and abnormal liver enzymes (P < 0.01). Compared with lower lipase levels (<3 × ULN), patients with elevated lipase had higher rates of ICU admission (92.9% vs 32.8%; P < 0.001) and intubation (78.6% vs 23.5%; P 0.002). In a multivariable-adjusted model, higher lipase levels were significantly associated with admission to the ICU and rate of intubation. DISCUSSION: Lipase elevation is seen in COVID-19 and is associated with worse disease outcomes.

Betacoronavirus , Coronavirus Infections , Lipase/blood , Obesity , Pancreas , Pandemics , Pneumonia, Viral , Aged , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , Body Mass Index , COVID-19 , Cohort Studies , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Female , Humans , Male , Middle Aged , Obesity/diagnosis , Obesity/epidemiology , Pancreas/metabolism , Pancreas/physiopathology , Pancreas/virology , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data , United States/epidemiology