COVID-19-associated acute pancreatitis: a systematic review of case reports.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) mainly involves the respiratory system but can also affect the digestive system and cause several gastrointestinal manifestations. Acute pancreatitis has been reported as one of the rare presentations of COVID-19. This study aimed to systematically review case reports on COVID-19-associated acute pancreatitis. METHODS: Publications were retrieved through a comprehensive search in four databases on October 1, 2021. Eligible ones that demonstrated the potential association of acute pancreatitis and COVID-19 were included for data extraction. RESULTS: After screening 855 citations, 82 articles containing 95 cases were included, and their data were extracted. The most common presentation was abdominal pain (88/95, 92.6%), followed by nausea/vomiting (61/95, 64.2%). Mortality was reported in 10.5% of cases. The initial presentation was acute pancreatitis, COVID-19, and concomitant in 32.6% (31/95), 48.4% (46/95), and 18.9% (18/95) of cases, respectively. Among the included cases, acute pancreatitis severity was associated with ICU admission, COVID-19 severity, and the outcome. Also, the initial presentation was associated with COVID-19 severity (P values ˂0.05). CONCLUSIONS: Current evidence indicates that acute pancreatitis can present before, after, or concomitant with COVID-19. Appropriate investigations should be performed in cases with suspicious clinical presentations. Longitudinal studies should address whether or not, there is a causative relationship between COVID-19 and acute pancreatitis.

Nausea, Vomiting, and Diarrhea Are Common in Community-Acquired Acute Viral Respiratory Illness.

BACKGROUND: Gastrointestinal (GI) symptoms are recognized sequelae of acute respiratory illness (ARI), but their prevalence is not well documented. Our study aim was to assess the incidence of GI symptoms in community ARI cases for persons of all ages and their association with clinical outcomes. METHODS: We collected mid-nasal swabs, clinical, and symptom data from Seattle-area individuals during the 2018-2019 winter season as part of a large-scale prospective community surveillance study. Swabs were tested by polymerase chain reaction (PCR) for 26 respiratory pathogens. Likelihood of GI symptoms given demographic, clinical, and microbiological covariates were analyzed with Fisher's exact, Wilcoxon-rank-sum, and t-tests and multivariable logistic regression. RESULTS: In 3183 ARI episodes, 29.4% had GI symptoms (n = 937). GI symptoms were significantly associated with pathogen detection, illness interfering with daily life, seeking care for the illness, and greater symptom burden (all p < 0.05). Controlling for age, > 3 symptoms, and month, influenza (p < 0.001), human metapneumovirus (p = 0.004), and enterovirus D68 (p = 0.05) were significantly more likely to be associated with GI symptoms than episodes with no pathogen detected. Seasonal coronaviruses (p = 0.005) and rhinovirus (p = 0.04) were significantly less likely to be associated with GI symptoms. CONCLUSION: In this community-surveillance study of ARI, GI symptoms were common and associated with illness severity and respiratory pathogen detection. GI symptoms did not track with known GI tropism, suggesting GI symptoms may be nonspecific rather than pathogen-mediated. Patients presenting with GI and respiratory symptoms should have respiratory virus testing, even if the respiratory symptom is not the primary concern.

Case report: Tissue positivity for SARS-CoV-2 in a preterm born infant death of thrombosis: possible intrauterine transmission.

Intrauterine transmission of SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) is still matter of debate among scientists and there is limited information concerning this aspect of research. This could lead to severe complications of the growing fetus and, theoretically, of the newborn as well. We report the case of a male infant of 1,100 grams, born at 27th week of gestation to a SARS-CoV-2 mother, tested negative for viral detection at delivery. He was immediately admitted to neonatal Intensive Care Unit (ICU) for severe complications, where he died after 37 days by pulmonary embolism and thrombosis of the superior vena cava. After autopsy, SARS-CoV-2 N-protein and Spike RBD were detected in several tissues, particularly in the esophagus, stomach, spleen, and heart, with a significantly higher H-Score than the placenta. In conclusion, immunohistochemical analysis demonstrated SARS-CoV-2 NP and Spike RBD positivity in different tissues suggesting a possible intrauterine transmission. Newborn thrombo-embolism could be a complication of SARS-CoV-2 infection as observed in adult patients.

Coronavirus murine hepatitis virus strain 3 induces intestinal injury via caspase 3 dependent apoptosis

Background: Diarrhea was typical symptoms of the coronavirus disease 2019 (COVID-19). However, the underlying mechanism had not been fully understood. Aim(s): The study aimed to explore the mechanism of intestinal injury during COVID-19 in a coronavirus murine hepatitis virus strain 3 (MHV-3) induced acute mouse model. Method(s): MHV-3 induced acute infection Balb/cJ mice model was established. Intestine samples were collected at indicated time points as 0 h, 24 h, 48 h and 60 h post infection. The mRNA and protein expression of IL1b, TNFalpha, IL6, caspase 3 and cleaved caspase 3 were examined by real-time quantitative PCR (qPCR) and western blot respectively. The intestine injury and apoptosis were measured by HE staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Moreover, Z-DEVD-FMK (caspase 3 inhibitor) pre-treated MHV-3 infection mice model were established, in which the apoptosis of intestine was evaluated as well. Meanwhile, the murine intestinal cell MODE-K was infected by MHV-3 in vitro for evaluation of virus induced apoptosis. Result(s): Post MHV-3 infection, the histopathology of intestine tissue showed extraordinary injury with time dependence, as well as high level of TUNEL positivity. The mRNA levels of inflammatory cytokine IL1b, TNFalpha and IL6 were significantly increased. The protein expressions of caspase 3 and cleaved caspase 3 in the intestine was found significantly elevated from 24 to 48 h post MHV-3 infection. Z-DEVD-FMK pretreatment inhibited caspase 3 and cleaved caspase 3 expression and decreased TUNEL positivity. Meanwhile, alleviated gut injury and inhibited TNFalpha expression were observed. In vitro treated by MHV-3, intestinal cell line MODE-K showed nine-fold increase of apoptosis by comparison with saline treated ones. The expressions of apoptosis crucial protein caspase3 and cleaved caspase3 significantly elevated, as well as TNFalpha. Conclusion(s): Coronavirus murine hepatitis virus strain 3 induces intestinal injury via caspase 3 dependent apoptosis, which might shed light on the treatment of intestinal complications in COVID-19.

Diarrhea as an Independent Risk Factor for COVID-19 Severity and Inpatient Mortality

Introduction: Multiple meta-analyses have shown that over 15% patients with COVID-19 have at least one gastrointestinal complaint, most commonly diarrhea. The effects on the gastrointestinal system are thought to be mediated by the high expression of angiotensin-converting enzyme 2 (ACE2) and cellular serine proteases (TMPRSS2) in enterocytes, which cause altered intestinal permeability. The purpose of this study was to determine the incidence of diarrhea as it relates to COVID-19 infection and to determine if having concomitant diarrhea had a significant impact on disease course. Method(s): A retrospective chart review of 164,730 patients in a hospital system who were older than 18 years of age and had a positive SARS-CoV-2 test from March 2020 to February 2022 was completed. Diarrhea was determined using ICD code or patient's symptoms. Patients with confounding variables such as IBD, IBS, Celiac, Clostridium difficile, and pancreatic insufficiency were excluded. Demographic clinical characteristics and outcomes, including inpatient admission and mortality, were compared in patients with and without diarrhea. The Mann-Whitney test and Fisher's exact or Chi-square test was used for continuous and categorical variables respectively and multivariate logistic regression was used to evaluate for significant differences in disease outcome between the two groups. (Table) Results: Of the 164,730 patients included, 14,648 (8.89%) had diarrhea at the time of SARS-CoV-2. 6,748/33,464 (20.16%) of inpatient admissions were associated with diarrhea. On multivariate analysis, diarrhea was an independent risk factor for inpatient hospitalization (OR 2.39, CI 95% 2.28-2.51, P, 0.001) and inpatient mortality (OR 1.15, CI 96% 1.06-1.26, P= 0.001) after controlling for age, gender, race, comorbidities that could impact patient outcome, use of immunomodulators and outpatient antibiotics. Conclusion(s): These findings show that, even with controlling for comorbidities with COVID-19, diarrhea was an independent factor for predicting inpatient mortality and inpatient admission in general. Patients who had diarrhea and COVID-19 were sicker, having more comorbid conditions than those without diarrhea in our cohort. Attention should be given to not only respiratory complaints of COVID-19, but also gastrointestinal complaints, as they are an indicator of poor prognosis and mortality.

Resiliency among Older Adults Receiving (Roar) Lung Cancer Treatment: A Feasibility Study

PURPOSE/HYPOTHESIS: Poor physical performance and negative mood are two risk factors for functional decline among older adults with lung cancer. Yet, targeted interventions to maintain independence prevent functional decline are not well studied. Our primary objective was to assess the feasibility of a novel virtual health physical therapy (PT) plus progressive muscle relaxation (PMR) intervention with longitudinal microbiome biospecimen collection delivered to older adults with advanced lung cancer. Secondary objectives were to characterize functional status and clinical factors pre and post-study intervention. NUMBER OF SUBJECTS: We accrued adults aged >=60 years with advanced non-small cell or extensive-stage small cell lung cancer receiving treatment at The Ohio State University James Comprehensive Cancer Center (OSU-JCCC) in the Thoracic Oncology department (N=22). There were no exclusion criteria pertaining to Eastern Cooperative Oncology Group (ECOG) performance status, laboratory values, prior cancer diagnoses, presence of comorbidities, or brain metastases. MATERIALS AND METHODS: Participants were asked about functional status, symptoms, mood through the PHQ-9, GAD-7, POMS, and acceptability questions about the program. PT evaluation and assessment included SPPB and 2- or 6-minute walk test outcomes. The study sought to collect gut microbiome samples for every in-person visit and activity monitoring data (Actigraph) on a subset. Feasibility was defined as successfully collecting specimens, wearing an Actigraph activity monitor, and adhering to the intervention. PT and psychologists evaluated participants in-person at the first and final visit. The rest of the 12-week intervention was conducted via virtual health. Physical therapy intervention consisted of endurance, strength, and flexibility exercises. RESULT(S): In total, 22 patients consented and 18 started the intervention (81.8%). Seven microbiome samples were collected from four participants. Six patients collected activity monitoring data. Among the 18 participants, 11 participants (61.1%) completed 70% or more of all the intervention visits. The SPPB data show a moderate effect size (Cohen's d=0.24) from pre- to post-data. On average patients improved by 1.8 total points on the SPPB. Patients demonstrated improvement on timed walk tests throughout intervention from an average of 108 feet pre-intervention to an average of 138.4 feet post intervention. CONCLUSION(S): Despite the challenges of the COVID-19 pandemic, longitudinal biospecimen and correlative data collection were feasible in the context of PT and PMR intervention among older adults with advanced lung cancer. Virtual physical therapy interventions can be safely delivered to improve physical performance as demonstrated by a moderate effect size for the SPPB in this patient population. CLINICAL RELEVANCE: Based on the feasibility study results, delivering a virtual PT intervention to older patients with lung cancer can improve SPPB score leading to decreased frailty and improve quality of life among patients.

Neurogastroenterology & Motility Manifestations After COVID-19 Infection: A Case Series

Introduction: In a subset of Covid19-convalescent patients, a multitude of long-term sequelae are increasingly being reported. We report 4 cases with varying neuro-GI and motility manifestations after recent COVID-19 infection. Case Description/Methods: Case 1: A 23-year-old man contracted COVID-19 and had a protracted course of respiratory illness. Despite resolution of respiratory symptoms and dysgeusia, he continued to experience early satiety, postprandial nausea, vomiting and unintentional weight loss. Gastric Emptying Scan (GES) revealed gastroparesis (Figure A). Dietary modification and metoclopramide led to symptomatic improvement. Case 2: A 39-year-old woman with migraines, suffered from Covid-19 infection where anosmia and respiratory symptoms lasted for 2 weeks. Despite resolution of initial symptoms, she started experiencing nausea and vomiting, and reported stereotypical symptoms with complete absence of vomiting between episodes. Endoscopic examination, CT head and GES were normal. Urine tox screen was negative for cannabinoids. She responded favorably to amitriptyline and ondansetron. Case 3: A 47-year-old man started experiencing severe constipation associated with abdominal pain and bloating soon after being diagnosed with COVID-19. Three months after resolution of respiratory symptoms, in addition to constipation, he began reporting postprandial fullness, early satiation and epigastric pain. GES showed gastroparesis ( figure B) and a Sitzmarks Study revealed delayed colonic transit (Figure C). Prucalopride was started, leading to improvement in symptoms. Case 4: A 74-year-old woman with obesity and diabetes, was hospitalized and intubated for severe respiratory distress due to COVID-19. After discharge, she had persistent symptoms of brain fog, fatigue, dyspnea as well as diarrhea and abdominal cramping, persisting despite loperamide and dicyclomine. C. difficile toxin, random colonic biopsies and H2 breath test were unremarkable. Her symptoms eventually improved with rifaximin. Discussion(s): We report 4 cases with post-COVID gastroparesis, cyclical vomiting syndrome, pan-gut dysmotility, and post-infectious IBS phenotypes.The pathophysiology of post-infectious-gut-brain disorders is still obscure. The current conceptual framework implicates acquired neuropathy, altered motility, intestinal barrier disruption and persistent intestinal inflammation. Similar pathophysiology may be involved in COVID-19 infection leading to sustained neurogastroenterological dysfunction and gut dysmotility.

Loss of Bifidobacteria in Lyme Disease: Cause or Effect

Introduction: Lyme disease is a poorly understood condition which starts with a rash but may continue with chronic fatigue and neurological symptoms. Approximately 1 in 5 early Lyme disease patients have GI symptoms, such as nausea, anorexia, abdominal pain, or diarrhea. Lyme disease is thought to be cased by microbes in the spirochetes phylum transmitted by black legged ticks. Lyme-related healthcare costs in America exceed 1.3 billion dollars annually. Bifidobacteria are known for their beneficial probiotic actions within the human gut microbiome. Their numbers are reduced in severe COVID-19, Clostridioides difficile infection and Inflammatory Bowel Disease. To our knowledge Bifidobacteria levels have not been studied in Lyme disease patients. Given the importance of Bifidobacterium abundance in other diseases, we focused on relative abundance of Bifidobacterium in fecal samples of patients with Lyme disease compared to controls. Method(s): Fecal samples were assessed for relative abundance of Bifidobacterium in Healthy Control subjects without Lyme disease (n=20) compared to patients with Lyme disease (n=39). The average symptom duration in patients with Lyme disease was 5 years and none were on antibiotics 2 weeks prior to sample collection (range of symptoms from 1 month to 20 years, all treated initially with antibiotics).Metagenomics Next Generation sequencing was performed on fecal samples, where DNA samples were extracted and normalized for library downstream analysis using Shotgun Methodology. Mann- Whitney Statistical test was used for comparison. This study was IRB approved. Result(s): Relative Abundance of bifidobacteria was significantly decreased (p< 0.0001) in patients with Lyme disease. Median and interquartile range (IQR) were: Control (Median:4.175%;IQR:1.72-10.27%) and Lyme disease (Median:0.0014%;IQR:0.00%-0.96%)(Figure). 30/39 Lyme disease patients (77%) were found to possess < 1% relative abundance of Bifidobacterium in their stool sample. Of interest only 1/39 samples showed presence of Spirochetes in stool samples. Conclusion(s): This is the first study that demonstrates low levels of Bifidobacteria in patients with chronic Lyme disease. These results raise three questions;whether the disease was caused by 1. the original microbe creating loss of Bifidobacterium 2. baseline low Bifidobacteria due likely to either diet or medications or 3. excessive treatment. Given Lyme disease comprises a gut dysbiosis issue, therapies should also aim at restoration of depleted Bifidobacteria. (Figure Presented).

Complex breathlessness in postural tachycardia syndrome and autonomic dysfunction

Breathlessness can occur in a number of autonomic conditions, often in the form of dysfunctional breathing. The exact mechanism remains uncertain, but reduced perfusion of blood pressure receptors and chemoreceptors in the carotid sinus and carotid body, leading to hyperventilation, is postulated. This is recognised to occur in vasovagal syncope and in cases of significant autonomic dysfunction. It also occurs in PoTS, a condition predominantly affecting young women and often precipitated by another illness and increasingly by coronavirus disease 2019. It is characterised by cardiovascular and respiratory symptoms when upright, is relieved by recumbency and is associated with a significant heart rate increase. Other autonomic symptoms of organ dysfunction can occur, in the gastrointestinal and genitourinary system for example. There are guidelines and therapies that can produce significant symptomatic improvements, but maintaining a high level of suspicion for the diagnosis is important, as it can easily be overlooked.Copyright © ERS 2021.

Tropism of COVID-19 to digestive organs. Features of damage and approaches to treatment

Coronavirus disease 2019 (COVID-19) began in December 2019 in Wuhan, Hubei, People's Republic of China. On March 11, 2020, COVID-19 was recognized by the World Conservation Organization (WHO) as a pandemic. As of May 31, 2020, more than 6 million cases were recorded in almost all countries. The etiological factor of the disease is a new coronavirus of severe acute respiratory syndrome-2 (SARS-CoV-2), which belongs to the genus b-coronaviruses, as well as other already known pathogens of this family — SARS and coronavirus of Middle Eastern respiratory syndrome (MERS). About 350 thousand people died as a result of the disease. More than 2.5 million people have recov-ered. To date, it has been proven that SARS-CoV-2 can affect all organs and systems of the body (lungs — pneumonia, respiratory distress syndrome, brain — encephalitis, cardiovascular system, kidneys, gastrointestinal tract). The main clinical symptoms of COVID-19 include: fever and other manifestations of the respiratory system (headache, rarely — runny nose, loss and/or change in taste and smell, dry cough, shortness of breath, chest pain, etc.), and also symptoms of the gastrointestinal tract (GI tract), such as loss of appetite, nausea and/or vomiting, diarrhea, abdominal pain, increased liver transaminases, exacerbation of chronic gastrointestinal diseases (inflammatory bowel disease, etc.). Data from Chinese studies have shown that SARS-CoV-2 RNA is present not only in airway material but also in faecal samples from infected patients. These data demonstrate the ability of SARS-CoV-2 to actively affect and replicate in the gastrointestinal tract, which is important for the choice of tactics for the diagnosis and treatment of the disease, as well as to prevent the spread of infection. Numerous studies have shown varying degrees of liver damage in patients infected with SARS-CoV-2. The COVID-19 case studies did not pinpoint the exact cause of liver damage, and there is no clear evidence of an interaction between liver damage and COVID-19. Research is ongoing. Due to the low level of awareness of physicians about the effects of COVID-19 on the gastrointestinal tract, it is advisable to review exist-ing data in order to increase the effectiveness of diagnosis, treatment and dynamic supervision of patients. This article discusses the effects of SARS-CoV-2 on the gastrointestinal tract. Particular attention is paid to liver damage in COVID-19, as well as the impact of liver complications on the effectiveness of COVID-19 treatment and prognosis. © 2020, Publishing Company VIT-A-POL. All rights reserved.

Abdominal imaging findings in patients with COVID-19 part 2: solid organs

Since Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first appeared in China in December 2019, the globe has been dealing with an ever-increasing incidence of COVID-19 (Corona Virus Disease 2019). In addition to respiratory disorders, 40% of patients present with gastrointestinal (GI) involvement. Abdominal pain is the most common indication for computed tomography (CT) and ultrasonography. After GI tract involvement, solid visceral organ infarction is the most prevalent abdominal abnormality in COVID-19. This review aims to gather the available data in the literature about imaging features of solid abdominal organs in patients with COVID-19. Gallbladder wall thickening and distension, cholelithiasis, hyperdense biliary sludge, acalculous cholecystitis, periportal edema, heterogeneous liver enhancement, and liver hypodensity and infarction are among hepatobiliary imaging findings in CT, particularly in patients admitted to ICU. Pancreatic involvement can develop as a result of direct SARS-CoV2 invasion with signs of acute pancreatitis in abdominal CT, such as edema and inflammation of the pancreas. Infarction was the most prevalent renal and splenic involvement in patients with COVID-19 who underwent abdominal CT presenting with areas of parenchymal hypodensity. In conclusion, although solid abdominal organs are rarely affected by COVID-19, clinicians must be familiar with the manifestations since they are associated with the disease severity and poor outcome.

Virological Investigation in Synanthropic Rodents in North Italy

Intro: Several rodents, including mice and the brown rat, are synanthropic animals usually found in rural and urban environments in contact with other animals and humans. Rodents are natural reservoirs of infectious agents and could harbour a plethora of zoonotic pathogens of public health importance. Taking advantage of a parallel study on presence and distribution of Hantaviruses, we aimed to investigate the occurrence in mice of other viruses with zoonotic or economic impact. Method(s): From May to July 2022, 41 mice (Mus domesticus) were captured and killed by using baited snap traps in 13 selected cattle, goat and poultry farms located in the Piedmont region. Gut and lung samples were homogenised and tested by PCR methods for pan-Coronavirus (CoV) and SARS-CoV-2, pan-Pestivirus, Mammalian orthoreoviruses, Canine Distemper virus (CDV), Flaviviruses, Influenza A (IAV) and D (IDV) viruses. Finding(s): All captured animals did not present at necropsy lesions related to infectious diseases. Virological investigations detected the presence of CoV in six mice. By sequencing Rodent CoVs was identified in two samples (four more pending). Mammalian orthoreovirus was detected in nine animals and typing and characterization are in progress. One mouse, captured in a bovine farm, tested slightly positive for IDV and confirmation of positivity is in progress by complete sequencing with NGS approach. All samples were negative for Flaviviruses, IAV, CDV, pan-Pestivirus and SARS-CoV-2. Conclusion(s): Rodents are well adapted to a wide range of habitats, including peri-urban and rural environments, where they benefit from human activities. These results, although preliminary, underline the importance of enhancing surveillance in rodents in anthropized areas to better assess the presence of zoonotic agents and the potential risk of transmission.Copyright © 2023

A Case Report of Iatrogenic Esophageal Perforation: Complication of Orogastric Tube Placement

Introduction: Orogastric tube insertion is a routine procedure in medical care. However, misplacement of the tube can cause a variety of complications, which can be life threatening in some instances. Case Description/Methods: 71-year-old male presented with dyspnea, fever, chills, cough, and myalgia for 2 weeks. He had tachycardia, tachypnea, and was hypoxic to 66% in room air. He was found to have acute hypoxic respiratory failure secondary to COVID-19 Pneumonia and was admitted to ICU. But, he continued to be hypoxic and was started on BiPAP. He eventually became altered, and was intubated. Post intubation orogastric tube (OGT) placement was unsuccessful on the first attempt due to resistance. On the second attempt, the nurse was able to advance partially (Figure). But, a chest XR showed OGT in the mediastinum, and OGT was removed. CT of neck and chest revealed pneumomediastinum with possible mid-thoracic esophageal perforation. The patient was started on broad-spectrum antibiotics and thoracic surgery was consulted. Given his mechanical ventilation requirement, surgery deemed him unfit to tolerate thoracotomy and the endoscopic procedure was not available in the hospital. So, recommendation was to manage conservatively. His hospital course was complicated by hypotension requiring vasopressors and metabolic acidosis in setting of acute renal failure requiring CRRT. Code status was changed by the family to Do Not Resuscitate due to his deteriorating condition. Eventually, he had a PEA arrest and was expired. Discussion(s): OGT intubation is performed at hospitals for feeding, medication administration or gastric decompression. Although it is considered a safe procedure, complications can arise due to OGT misplacement or trauma caused by the OGT itself or the intubation process. OGT misplacement is typically endotracheal or intracranial. Misplacement within the upper GI lumen is usually detected by a kink in the oropharynx or esophagus. The subsequent complications are identified by the structure that is perforated (e.g., mediastinitis or pneumothorax). Regardless of whether counteraction is perceived, the physician must be careful not to apply excessive force. The location of the OGT tip should be determined by a chest radiograph;visualization of the tip below the diaphragm verifies appropriate placement. Complications of OGT insertion are uncommon;however, the consequences are potentially serious, and the anatomy of the upper GI tract should be understood by all who are involved in the care.

Spontaneous Gastro-pancreatic Fistula: A Rare Complication of Acute Pancreatitis

Introduction: Although Gastrointestinal fistula is a well-recognized complication of acute pancreatitis, it has been rarely reported. Here we present a rare case of spontaneous gastro-pancreatic fistula following acute pancreatitis. Case Description/Methods: 42 y/o female with PMH of SLE with a recent prolonged hospitalization for acute drug-induced pancreatitis with pseudocyst came to ED with fever, abdominal pain, nausea, and vomiting. She was tachycardic, had leukocytosis, and was positive for COVID-19. CT Scan A/P showed multiple infected peripancreatic collections with communication of the left upper quadrant collection with the gastric lumen (Figure). The patient was hospitalized, Kept NPO, and started on fluids and antibiotics. IR evaluated and put 2 pigtail catheters for drainage of peripancreatic collections. The tip of the pigtail catheter in the left peripancreatic/retroperitoneal collection was in the gastric lumen. The surgery team recommended continuing with conservative treatment with parenteral nutrition, and IV antibiotics as the patient were nontoxic with no signs of free perforation, and pancreatitis would more likely erode a staple or suture line and would put the patient at further risk of free perforation if repair attempted. IR was successful in pulling the drain out of the gastric lumen on the second attempt to allow gastric perforation to heal. Antibiotics were upgraded as per the culture and sensitivity results of the drain fluid. Repeated multiple bedside leak tests and CT scans with oral contrast continue to be positive for patent gastro-pancreatic fistula. Pigtails catheter continues to drain significant necrotic collection. The patient continues to be hospitalized and is being managed conservatively with Parenteral nutrition, and IV antibiotics. Discussion(s): Fistula of the GI tract following acute pancreatitis can be caused by multiple reasons. Necrosis of the bowel may occur concomitantly with the pancreatic or peripancreatic tissue. Furthermore, enzyme-rich fluid and necrosis can lead to vascular thrombosis, which compromises the blood supply of the segmental GI tract, eventually leading to bowel necrosis. GI fistulas are more common in patients with necrotizing pancreatitis with infected pancreatic necrosis. Despite pharmacologic suppression of pancreatic exocrine secretion and advances in endoscopic and percutaneous therapeutic techniques, pancreatic fistula continues to be a source of morbidity and mortality following pancreatitis and requires multidisciplinary treatment.

Early Enteral Feeding With Prebiotic-Containing Formula in Critically Ill Mechanically Ventilated Covid-19 Patients

Background: Optimal supportive care which includes adequate nutrient delivery remains the cornerstone in managing critically ill patients with COVID-19. Nutrition guiding principles for critically ill patients with COVID-19 strongly recommend providing early enteral nutrition (EEN) within 24-36 hours of admission to the intensive care unit (ICU) or within 12 hours of placement on mechanical ventilation (MV). Moreover, data show critically ill COVID-19 patients have negative alterations in their gut microbiome which is attributed to many factors including insufficient EN and fiber provision. The success and tolerance of EEN with a prebiotic formula in patients with COVID 19 is unknown. Here we aimed to assess, before and after implementation of an enteral feeding protocol, the achievement of EEN, estimated energy goals, and tolerance of a prebiotic formula in MV patients with COVID-19. Method(s): Data were collected and analyzed retrospectively from June 2020-May 2021 and prospectively from June 2021-January 2022. A protocol to promote EEN and improve nutrition delivery with a prebiotic-containing formula to patients within the seven days of ICU admission was created and implemented in June 2021 in the Medical ICU. Time to start EEN following invasive MV was assessed. Feeding adequacy over the first seven days of ICU admission was calculated by dividing the mean total calories of formula infused over the first seven ICU days by the estimated goal calories/day. The average number of bowel movements (BM) over the first seven ICU days was used to evaluate feeding tolerance. To determine the impact of inflammation and co-morbid conditions on feeding adequacy and tolerance, admission C-reactive protein (CRP) and Charlson Comorbidity Index (CCI) were trended with feeding adequacy. The Institutional Review Board approved the study. Result(s): A total of 343 patient records were analyzed with 203 patients in retrospective (R) and 140 patients in prospective groups (P). The post- MV feeding initiation time was shorter after implementing the feeding protocol (Mean 45.2 vs 33.8 hrs, and Interquartile Range (IQR) of Median (hrs) (18, 51) vs (16, 43) for the R and P groups, respectively (p = 0.04). Achievement of feeding goal rates were similar between groups (30.0 % vs 29.5%) (p >0.05). A prebiotic-containing formula was received in 36.2 % of patients in the R group versus 43.4 % in the P group. Providing a prebiotic formula had no impact on achieving goal nutrition in either period. In the R group, patients receiving the non-prebiotic formula had a higher total 7-days BM occurrence compared to the prebiotic formula group (8 vs 5.9 BMs/7 days, p = 0.03). In the P group there were no differences in the number of BMs between non-prebiotic and prebiotic formula groups (5.3 vs 5.0 BMs/7 days, p >0.05). Higher admission CRP and CCI values trended with higher incidence of inadequate feeding. Mean CCI was 4.42 and 4.17 for patients who received less than 25% goal feeding compared to those who received >80% of their goal feeds, respectively. Mean CRP was 12.3 and 11.4 for patients who received < 25% goal feeds compared to those who received >80% of goal feeds, respectively (p > 0.05). There were no differences in overall ICU length of stay between the R (11.7 days) and P (11.1 days) groups. (p = 0.34) Conclusion(s): EEN protocol implementation decreased time to EEN initiation in mechanically ventilated COVID-19 patients but did not affect patients in achieving goal nutrition in the first week of their ICU stay. Furthermore, COVID-19 patients tolerated EEN with prebiotic containing formulas. Further research is warranted to determine the impact of EEN with a prebiotic formula on the gut microbiome in critically ill MV patients with COVID-19.

Multiplex measurements of the impacts of ACE2 sequence and cell surface abundance during SARS-like coronavirus entry

SARS-like coronaviruses, including SARS-CoV and SARS-CoV-2, encode spike proteins that bind human ACE2 protein on the cell surface to enter target cells and cause infection. The efficiency of virus entry depends on ACE2 sequence and expression levels in target cells. A small fraction of humans encodes variants of ACE2, thus altering the biochemical properties at the protein interaction interface. All humans possess cells with vastly differing amounts of ACE2 on the cell surface, ranging from cell types with high expression in the gut and lungs to lower expression in the liver and pancreas. Mastering our understanding of spike-ACE2 interaction and infection requires experiments precisely perturbing both variables. Thus, we developed a synthetic cell engineering approach compatible with high throughput assays for pseudo-typed virus infection. Our assay system is capable of assessing both variables individually and in combination. We adapted an engineered HEK293T DNA recombinase landing pad cell line capable of expressing transgenic ACE2 sequences at highly precise levels. Infection with lentiviruses pseudotyped with the spikes of SARS-like coronaviruses revealed that high ACE2 abundance could mask the effects of impaired binding thereby making it challenging to know the role of affinity altering mutations during infection. We limited the ACE2 abundance on the cell surface by expressing transgenic ACE2 behind a suboptimal Kozak sequence, thereby altering its protein translation rate. This allowed us to understand how ACE2 sequence could impact its interaction with coronavirus spike proteins as two human ACE2 variants at the binding interface, K31D and D355N, exhibited reduced infection. Our experiments suggested that we need to better understand how ACE2 expression determines the susceptibility of cells for SARS-like coronavirus binding and infection. We thus created an ACE2 Kozak library consisting of ~4,096 Kozak variants, each conferring a different ACE2 protein translation rate thus resulting in a range of ACE2 steady-state abundances. Combining fluorescence-activated cell sorting and high-throughput DNA sequencing (FACS-seq) revealed the library to span two orders of magnitude of ACE2 abundance. Challenging this library of cells with spike pseudotyped lentiviruses revealed how ACE2 abundance correlated with infection rate. The library-based experiments yielded a dynamic range wider than traditional single sample infection assay, likely more representative of infection dynamics in vivo. Now that we have characterized the impacts of ACE2 abundance on infectivity in engineered cells, our next goal is to expand the comparison to physiologically relevant cells with endogenously expressed proteins. Modulating protein abundance levels will be key to creating maximally informative functional assays for any protein in cell-based assays, and we have laid the groundwork for being able to simultaneously test the impacts of protein abundance and sequence in combination for proteins involved in diverse cellular processes. This research was supported by a National Institute of Health (NIH) grant GM142886 (KAM).Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

COVID-19 as a probable cause of acute pancreatic injury

Acute pancreatic pseudocysts are increasingly recognized as complications in patients with coronavirus disease 2019 (COVID-19). There-fore, it is important for healthcare providers to be aware of this phenomenon to ensure proper diagnosis and treatment. Up to 17% of patients with severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) infection have been shown to develop pancreatic lesions. These pancreatic lesions can be caused directly by the cytopathic effects of the viral infection or indirectly by systemic responses to inflammation or respiratory failure. Several studies have shown that angio-tensin-converting enzyme 2 (ACE2) is the functional receptor used by SARS-CoV-2 to gain access to target cells, while ACE2 receptors are expressed in significant amounts in the pancreas. In this article, we present 2 cases of COVID-19. patients that presented with similar pancreatic lesions. The first case was a 47-year-old lady who presented to the emergency department (ED) with flu-like symptoms for ten days. Incidental findings on computed tomography (CT) scan showed a large, multiloculated cystic mass in the pancreatic tail. The second case was an 81-year-old Caucasian lady who presented to the outpatient clinic with multiple chronic complaints after an acute COVID-19 infection four months prior. Abdominal CT scan with oral contrast revealed multiple hypodense masses on the pancreas measuring 0.3 cm in diameter. The cases we reported in this article showed the degree of COVID-19's effect on the gastrointestinal system, with pancreatic injury occurring during the early phases of the acute phase of the infection and lasting up to 4 months post-resolution of the infection.Copyright © 2023, The Indonesian Foundation of Critical Care Medicine. All rights reserved.

Increased Gut Permeability and Oxidized Lipids in Pasc

Background: Post-acute sequelae of COVID-19 (PASC) is marked by persistent or newly developing symptoms beyond 4 weeks of infection. Investigating gut integrity, oxidized lipids and inflammatory markers is important for understanding PASC pathogenesis. Method(s): A cross-sectional study including COVID+ with PASC, COVID+ without PASC, and COVID- participants. We measured plasma markers by enzyme-linked immunosorbent assay to assess gut-barrier integrity: zonulin for intestinal permeability, lipopolysaccharide-binding protein (LBP) for microbial translocation, and fatty acid binding protein I-FABP for intestinal integrity, and to assess inflammation: high-sensitivity C-reactive protein (hsCRP) and oxidized low-density lipoprotein (Ox-LDL) assays. Result(s): 415 participants were enrolled in our study. 62.17% (n=258) were COVID- and 20.48% (n=85) had PASC. COVID- participants had lower age (43.68+/-13.69 vs. 46.45+/-13.45 years;p=0.04), lower BMI (27.91+/-6.05 vs. 31.28+/-9.03;p< .0001), 39.15% (n=101) were female sex [vs. 54.14% (n=85);p=0.003], and 41.86% (n=108) were non-white race [vs. 32.48% (n=51);p=0.06] compared to COVID+. Zonulin (p< .0001), and Ox-LDL (p< .0001) were associated with COVID and PASC status. The mean Zonulin among COVID- was 3755960.41+/-2541177.0 ng/mL, 3912178.91+/-2649882.95 ng/mL among COVID+ without PASC, and the highest (5899694.16+/-4110456.4 ng/ mL) among PASC. The mean Ox-LDL was lowest (51845.21+/-24328.46 U/L) among COVID-, 60530.09+/-26497.47 U/L among COVID+ without PASC, and 81917.21+/-32148.59 U/L among PASC. The estimated mean difference in Zonulin among PASC compared to COVID- was 2143734+/-368522 ng/mL (p< .0001) and compared to COVID+ without PASC was 1987515+/-471965 ng/mL (p< .0001). The estimated mean difference in Ox-LDL among PASC compared to COVID- was 30072+/-3311.02 U/L (p<.0001) and compared to COVID+ without PASC was 21387+/-4240.41 (p<.0001). Zonulin was positively associated with hs-CRP and Ox-LDL. For every unit increase in Zonulin we would expect hsCRP to increase by 86.14+/-15.09/100000 ng/mL (p<.0001) and OX-LDL to increase by 22.2+/-4.05/10000 ng/mL (p<.0001). Conclusion(s): PASC is associated with increased gut permeability, which in turn is associated with oxidized LDL and hsCRP. (Figure Presented).

The Impact of N-butyldeoxynojirimycin and 1-deoxymannojirimycin on SARS-CoV-2 S1 Subunit and Angiotensin-Converting Enzyme 2 Interaction in Intestinal Epithelial Cells

The severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) targets mainly the respiratory tract. In addition to respiratory symptoms, many extrapulmonary manifestations were observed in the gastrointestinal tract and reported by SARS-CoV-2 patients, including abdominal pain, nausea, and diarrhea. SARS-CoV-2 binds initially to angiotensin-converting enzyme 2 (ACE2) on the host cell surface via its spike (S) protein before it undergoes endocytosis and fusion with the lysosomal membrane. The spike protein of SARS-CoV-2 is a heavily N- and O-glycosylated trimer. Glycosylation is an essential posttranslational modification in the life cycle of membrane and secretory proteins that affects their structural and functional characteristics as well as their trafficking and sorting patterns. This study aimed at elucidating the impact of glycosylation modulation on the trafficking of both S1 subunit and ACE2 as well as their interaction at the cell surface of intestinal epithelial cells. For this purpose, the S1 protein was expressed in COS-1 cells and its glycosylation modified using N-butyldeoxynojirimycin (NB-DNJ), an inhibitor of ER-located alpha-glucosidases I and II, and or 1-deoxymannojirimycin (dMM), an inhibitor of the Golgi-located alpha-mannosidase I. The intracellular and secreted S1 proteins were analyzed by endoglycosidase H treatment. Similarly, ACE2 trafficking to the brush border membrane of intestinal Caco-2 cells was also assessed in the presence or absence of the inhibitors. Finally, the interaction between the S1 protein and ACE2 was investigated at the surface of Caco-2 cells by co-immunoprecipitation. Our data show that NB-DNJ significantly reduced the secretion of S1 proteins in COS-1 cells, while dMM affected S1 secretion to a lesser extent. Moreover, NB-DNJ and dMM differentially affected ACE2 trafficking and sorting to the brush border membrane of intestinal Caco-2 cells. Strikingly, the interaction between S1 and ACE2 was significantly reduced when both proteins were processed by the glycosylation inhibitors, rendering glycosylation and its inhibitors potential candidates for SARS-CoV-2 treatment. This work has been supported by a grant from the German Research Foundation (DFG) grant NA331/15-1 to HYN. M.K. was supported by a scholarship from the Hannover Graduate School for Veterinary Pathobiology, Neuroinfectiology, and Translational Medicine (HGNI) and by the DFG grant NA331/15-1.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.