SARS-CoV-2 variants of concern exhibit differential gastro-intestinal tropism and pathogenesis in the Syrian golden hamster model. (preprint)

The Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has taken its toll on worldwide public health infrastructure. SARS-CoV-2 is reported to exhibit wide tissue tropism, contributing to its severe pathogenicity that often culminates in multiple-organ failure. The onslaught of this disease has intensified due to the emergence of variants of concern (VOC), such as Delta and Omicron. These variants have been linked to gastrointestinal (GI) symptoms, suggesting a potential fecal-oral route of viral transmission. Here we compared the broad tissue tropism of ancestral Hong-Kong SARS-CoV-2 (SARS-CoV-2 HK) against Delta and Omicron VOCs in aa hamster model by analyzing tissue samples collected from the upper and lower respiratory system and the GI tract. We observed an overall increase in vRNA load and pro-inflammatory cytokines, especially in GI tracts of animals infected with Delta virus, indicating selective virus tropism and pathology in these tissues. However, no apparent spike in Delta viral load was observed in the large intestine and fecal matter. Overall, our research investigates the wide range of tissues that various SARS-CoV-2 strains can infect in hamsters and presents evidence supporting the increased preference of Delta VOCs for infecting the GI tract.

Laparoscopic Paraesophageal Hernia (PEH) Repair, Roux-en-Y Gastric Bypass, and Per Oral Endoscopic Myotomy (POEM) in a Patient with Achalasia After Sleeve Gastrectomy.

BACKGROUND: GERD and Achalasia are two known complications after sleeve gastrectomy. Treatment towards each of these complications varies and requires a tailored approach. METHODS: We present a 55-year-old female with class II obesity and a previous history of sleeve gastrectomy who developed significant gastroesophageal reflux disease refractory to medical management. After a covid infection in fall of 2020, she began to report new symptoms of dysphagia that progressed from solids to liquids. She underwent extensive workup including upper endoscopy, upper GI barium swallow, manometry, pH impedence, and EndoFlip leading to a diagnosis of Achalasia type II as well as a paraesophageal hernia. RESULTS: Given these findings, she underwent a combined paraesophageal hernia repair with conversion of sleeve gastrectomy to Roux-en-Y gastric diversion and an intra-operative peroral endoscopic myotomy. Intraoperatively, she was noted to have significant lower abdominal adhesions leading to performing the Roux-en-Y reconstruction through a supramesocolic defect in a retrocolic fashion. CONCLUSIONS: While the development of heartburn and achalasia after sleeve gastrectomy is rare, it requires interventions dedicated towards each etiology. This case demonstrates treatment of both these symptoms is feasible in a single operation.

Predictors of Mortality in Hospitalized Patients with COVID-19: A One-Year Case-Control Study (preprint)

Objective: To determine the associated factors with mortality, in addition to age and sex, in a high-complexity hospital in Bogota, Colombia, during the first year of the pandemic. Design: A case-control study. Setting: High-complexity center above 2,640 meters above sea level (masl) in Colombia. Methods: A case-control study was conducted on 564 patients admitted to the hospital with confirmed COVID-19. Deceased patients (n: 282) and a control group (n: 282), matched by age, sex, and month of admission, were included. Clinical and paraclinical variables were retrospectively obtained by systematic revision of clinical records. Multiple imputations by chained equation (MICE) were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalization. Results: Most of the patients included were males in the seventh decade of life. Most of the admissions occurred between July and August 2021. Surprisingly, recovered patients reported heterogeneous symptomatology, whereas deceased patients were most likely to present respiratory distress, dyspnea, and seizures on admission. In addition, the latter group exhibited a higher burden of comorbidities and alterations in laboratory parameters. After the imputation of datasets, CART analysis estimated 14 clinical profiles based on respiratory distress, LDH, dyspnea, hemoglobin, D-dimer, ferritin, blood urea nitrogen, C-reactive protein, PaO2/FiO2, dysgeusia, total bilirubin, platelets, and gastroesophageal reflux disease. The accuracy model for prediction was 85.6% (P < 0.0001). Conclusion: Multivariate analysis yielded a reliable model to predict mortality in COVID-19. This analysis revealed new interactions between clinical and paraclinical features in addition to age and sex. Furthermore, this predictive model could offer new clues for the personalized management of this condition in clinical settings. Keywords: SARS-CoV-2, COVID-19, Mortality, Predictors, Risk Factors

Tele-visits for GERD: "Ecofriendly, efficient and effective".

BACKGROUND AND AIM: Sars-CoV-19 pandemic necessitated a transition to telemedicine for many healthcare encounters. The environmental impact of this transition in gastroenterology (GI) combined with user experience has not been studied. METHODS: We conducted a retrospective cohort study of patients who underwent telemedicine visits (telephone and video) at a GI clinic at West Virginia University. Distance of patients' residence from clinic × 2 was calculated, and Environmental Protection Agency calculators utilized to calculate greenhouse gas (GHG) emissions that were avoided from tele-visits. Patients were reached by telephone and were asked questions to fill in a validated Telehealth Usability Questionnaire with Likert scales (1-7). Variables were also collected via chart review. RESULTS: A total of 81 video and 89 telephone visits were conducted for gastroesophageal reflux disease (GERD) between March 2020 and March 2021. A total of 111 patients were enrolled, with a response rate of 65.29%. Mean age was lower in the video visit cohort compared with the telephone visit cohort (43.45 ± 14.32 years vs 52.34 ± 17.46 years). Most patients had medications prescribed during the visit (79.3%), and a majority had laboratory testing orders placed (57.7%). We calculated a total distance of 8732 miles that the patients would have traveled if they were to present for in-person visits (including return trips). A total of 393.3 gallons of gasoline would have been required to transport these patients to and from the healthcare facility to their residence. A total of 3.5 metric tons of GHG's were saved by avoiding 393.3 gallons of gasoline for travel. In relatable terms, this is equivalent to burning more than 3500 pounds of coal. This averages to 31.5-kg GHG emissions and 3.54 gallons of gasoline saved per patient. CONCLUSION: Telemedicine for GERD resulted in significant environmental savings and was rated highly for access, satisfaction, and usability by patients. Telemedicine for GERD can be an excellent alternative to in-person visits.

Risks of digestive diseases in long COVID: Evidence from a large-scale cohort study (preprint)

Objectives: This study aims to evaluate the effect of coronavirus disease 2019 (COVID-19) on the long-term risk of digestive diseases in the general population. Design: Large-scale population-based cohort study based on a prospective cohort. Setting: UK Biobank cohort linked to multiple nationwide electronic health records databases. Participants: The cohort consisted of 112,311 individuals who survived the initial 30 days following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as two control groups: a contemporary group (n = 359,671) without any history of COVID-19, and a historical control group (n = 370,979) that predated the COVID-19 outbreak. Main outcome measures: Main outcomes were predefined digestive diseases. Hazard ratios and corresponding 95% confidence intervals (CI) were computed utilizing the Cox regression models after inverse probability weighting. Results: Compared with the contemporary control group, patients with previous COVID-19 infection had higher risks of digestive diseases, including functional gastrointestinal disorders (hazard ratios [HR] 1.95 (95% CI 1.62 to 2.35)); peptic ulcer disease (HR 1.27 (1.04 to 1.56)); gastroesophageal reflux disease (GERD) (HR 1.46 (1.34 to 1.58)); inflammatory bowel diseases (HR 1.40 (1.02 to 1.90)); gallbladder disease (HR 1.28 (1.13 to 1.46)); severe liver disease (HR 1.46 (1.12 to 1.90)); non-alcoholic liver disease (HR 1.33 (1.15 to 1.55)); and pancreatic disease (HR 1.43 (1.17 to 1.74)). The risks of GERD were stepwise increased with severity of the acute phase of COVID-19 infection. The results were consistent when using the historical cohort as the control group. Conclusions: Our study provides important insights into the association between COVID-19 and the long-term risk of digestive system disorders. COVID-19 patients are at a higher risk of developing gastrointestinal disorders, with stepwise increased risk with the severity and persisting even after one year follow-up.

Effect of laparoscopic sleeve gastrectomy vs laparoscopic sleeve + Rossetti fundoplication on weight loss and de novo GERD in patients affected by morbid obesity: a randomized clinical study.

PURPOSE: To compare sleeve gastrectomy (SG) to SG associated with Rossetti fundoplication (SG + RF) in terms of de novo gastro-esophageal reflux disease (GERD) after surgery, weight loss, and postoperative complications. MATERIALS AND METHODS: Patients affected by morbid obesity, without symptoms of GERD, who were never in therapy with proton pump inhibitors (PPIs), were randomized into two groups. One group underwent SG and the other SG + RF. The study was stopped on February 2020 due to the COVID pandemic. RESULTS: A total of 278 patients of the programmed number of 404 patients were enrolled (68.8%). De novo esophagitis was considered in those patients who had both pre- and postoperative gastroscopy (97/278, 34.9%). Two hundred fifty-one patients (90.3%) had completed clinical follow-up at 12 months. SG + RF resulted in an adequate weight loss, similar to classic SG at 12-month follow-up (%TWL = 35. 4 ± 7.2%) with a significantly better outcome in terms of GERD development. One year after surgery, PPIs were necessary in 4.3% SG + RF patients compared to 17.1% SG patients (p = 0.001). Esophagitis was present in 2.0% of SG + RF patients versus 23.4% SG patients (p = 0.002). The main complication after SG + RF was wrap perforation (4.3%), which improved with the surgeon's learning curve. CONCLUSION: SG + RF seemed to be an effective alternative to classic SG in preventing de novo GERD. More studies are needed to establish that an adequate learning curve decreases the higher percentage of short-term complications in the SG + RF group.

Case-control study of the association of chronic acid suppression and social determinants of health with COVID-19 infection.

Acid suppressants are widely-used classes of medications linked to increased risks of aerodigestive infections. Prior studies of these medications as potentially reversible risk factors for COVID-19 have been conflicting. We aimed to determine the impact of chronic acid suppression use on COVID-19 infection risk while simultaneously evaluating the influence of social determinants of health to validate known and discover novel risk factors. We assessed the association of chronic acid suppression with incident COVID-19 in a 1:1 case-control study of 900 patients tested across three academic medical centers in California, USA. Medical comorbidities and history of chronic acid suppression use were manually extracted from health records by physicians following a pre-specified protocol. Socio-behavioral factors by geomapping publicly-available data to patient zip codes were incorporated. We identified no evidence to support an association between chronic acid suppression and COVID-19 (adjusted odds ratio 1.04, 95% CI 0.92-1.17, P = 0.515). However, several medical and social features were positive (Latinx ethnicity, BMI ≥ 30, dementia, public transportation use, month of the pandemic) and negative (female sex, concurrent solid tumor, alcohol use disorder) predictors of new infection. These findings demonstrate the value of integrating publicly-available databases with medical data to identify critical features of communicable diseases.

Gastrointestinal bleeding and endoscopic findings in critically and non-critically ill patients with corona virus disease 2019 (COVID-19): Results from Lean European Open Survey on SARS-CoV-2 (LEOSS) and COKA registries.

BACKGROUND: Corona virus disease 2019 (COVID-19) patients are at increased risk for thromboembolic events. It is unclear whether the risk for gastrointestinal (GI) bleeding is also increased. METHODS: We considered 4128 COVID-19 patients enrolled in the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. The association between occurrence of GI bleeding and comorbidities as well as medication were examined. In addition, 1216 patients from COKA registry were analyzed focusing on endoscopy diagnostic findings. RESULTS: A cumulative number of 97 patients (1.8%) with GI bleeding were identified in the LEOSS registry and COKA registry. Of 4128 patients from the LEOSS registry, 66 patients (1.6%) had a GI bleeding. The rate of GI bleeding in patients with intensive care unit (ICU) admission was 4.5%. The use of therapeutic dose of anticoagulants showed a significant association with the increased incidence of bleeding in the critical phase of disease. The Charlson comorbidity index and the COVID-19 severity index were significantly higher in the group of patients with GI bleeding than in the group of patients without GI bleeding (5.83 (SD = 2.93) vs. 3.66 (SD = 3.06), p < 0.01 and 3.26 (SD = 1.69) vs. 2.33 (SD = 1.53), p < 0.01, respectively). In the COKA registry 31 patients (2.5%) developed a GI bleeding. Of these, the source of bleeding was identified in upper GI tract in 21 patients (67.7%) with ulcer as the most frequent bleeding source (25.8%, n = 8) followed by gastroesophageal reflux (16.1%, n = 5). In three patients (9.7%) GI bleeding source was located in lower GI tract caused mainly by diverticular bleeding (6.5%, n = 2). In seven patients (22.6%) the bleeding localization remained unknown. CONCLUSION: Consistent with previous research, comorbidities and disease severity correlate with the incidence of GI bleeding. Also, therapeutic anticoagulation seems to be associated with a higher risk of GI bleeding. Overall, the risk of GI bleeding seems not to be increased in COVID-19 patients.

Assessing the genetic relationship between gastro-esophageal reflux disease and risk of COVID-19 infection.

Symptoms related with gastro-esophageal reflux disease (GERD) were previously shown to be linked with increased risk for the 2019 coronavirus disease (COVID-19). We aim to interrogate the possibility of a shared genetic basis between GERD and COVID-19 outcomes. Using published GWAS data for GERD (78 707 cases; 288 734 controls) and COVID-19 susceptibility (up to 32 494 cases; 1.5 million controls), we examined the genetic relationship between GERD and three COVID-19 outcomes: risk of developing severe COVID-19, COVID-19 hospitalization and overall COVID-19 risk. We estimated the genetic correlation between GERD and COVID-19 outcomes followed by Mendelian randomization (MR) analyses to assess genetic causality. Conditional analyses were conducted to examine whether known COVID-19 risk factors (obesity, smoking, type-II diabetes, coronary artery disease) can explain the relationship between GERD and COVID-19. We found small to moderate genetic correlations between GERD and COVID-19 outcomes (rg between 0.06 and 0.24). MR analyses revealed a OR of 1.15 (95% CI: 0.96-1.39) for severe COVID-19; 1.16 (1.01-1.34) for risk of COVID-19 hospitalization; 1.05 (0.97-1.13) for overall risk of COVID-19 per doubling of odds in developing GERD. The genetic correlation/associations between GERD and COVID-19 showed mild attenuation towards the null when obesity and smoking was adjusted for. Susceptibility for GERD and risk of COVID-19 hospitalization were genetically correlated, with MR findings supporting a potential causal role between the two. The genetic association between GERD and COVID-19 was partially attenuated when obesity is accounted for, consistent with obesity being a major risk factor for both diseases.

Development of a Post-Acute Sequelae of COVID-19 (PASC) Symptom Lexicon Using Electronic Health Record Clinical Notes (preprint)

Objective: To develop a comprehensive post-acute sequelae of COVID-19 (PASC) symptom lexicon from clinical notes to support PASC symptom identification and research. Methods: We identified 26,117 COVID-19 positive patients from the Mass General Brigham's electronic health records (EHR) and extracted 328,879 clinical notes from their post-acute infection period (day 51-110 from first positive COVID-19 test). The PASC symptom lexicon incorporated Unified Medical Language System (UMLS) Metathesaurus concepts and synonyms based on selected semantic types. The MTERMS natural language processing (NLP) tool was used to automatically extract symptoms from a development dataset. The lexicon was iteratively revised with manual chart review, keyword search, concept consolidation, and evaluation of NLP output. We assessed the comprehensiveness of the lexicon and the NLP performance using a validation dataset and reported the symptom prevalence across the entire corpus. Results: The PASC symptom lexicon included 355 symptoms consolidated from 1,520 UMLS concepts. NLP achieved an averaged precision of 0.94 and an estimated recall of 0.84. Symptoms with the highest frequency included pain (43.1%), anxiety (25.8%), depression (24.0%), fatigue (23.4%), joint pain (21.0%), shortness of breath (20.8%), headache (20.0%), nausea and/or vomiting (19.9%), myalgia (19.0%), and gastroesophageal reflux (18.6%). Discussion and Conclusion: PASC symptoms are diverse. A comprehensive PASC symptom lexicon can be derived using a data-driven, ontology-driven and NLP-assisted approach. By using unstructured data, this approach may improve identification and analysis of patient symptoms in the EHR, and inform prospective study design, preventative care strategies, and therapeutic interventions for patient care.

The impact of COVID-19 on children with oesophageal atresia and/or tracheo-oesophageal fistula (OA/TOF) (preprint)

PurposeThe COVID-19 pandemic has resulted in a global health crisis of unparalleled magnitude. The direct risk to the health of children is low. However, disease containment measures have society-wide impacts. This study explored the pandemic experiences of parents of children with oesophageal atresia/tracheo-oesophageal fistula in the UK. DesignAn online forum was conducted using a private group on Facebook, in collaboration with a patient support group. Thematic analysis was used to identify key themes. ResultsThe online forum ran between 7th November-18th December 2020 with 109 participants. Themes related to healthcare and non-healthcare impacts. Parents experienced changes and limitations to healthcare access, anxiety regarding health risks, "collateral" damage to well-being because of isolation and an impact on finances and employment. Parents described a transition from worry about direct health risks to concern about the impact of isolation on socialisation and development. A process of risk-benefit analysis led some to transition to a more "normal life", while others continued to isolate. Benefits to their childs health from isolation, positive experiences with remote healthcare and a gradual easing of anxiety were also identified. Implications and relevanceThis study highlights the wide-ranging impact of the COVID-19 pandemic on children and their families. Although focussed on oesophageal atresia/tracheo-oesophageal fistula, the emerging themes will be relevant to many children with complex, chronic health conditions. There are implications for healthcare delivery, including telehealth, during and after the pandemic period. Accurate and consistent messaging is required. Third sector organisations are ideally positioned support this.

COVID-19 Transmission in a Psychiatric Long-Term Care Rehabilitation Facility: An Observational Study.

OBJECTIVE: To report the clinical characteristics and transmission rate of coronavirus disease 2019 (COVID-19) in a community inpatient long-term care psychiatric rehabilitation facility designed for persons with serious mental illness to provide insight into transmission and symptom patterns and emerging testing protocols, as well as medical complications and prognosis. METHODS: This study examined a cohort of 54 residents of a long-term care psychiatric rehabilitation program from March to April 2020. Baseline demographics, clinical diagnoses, and vital signs were examined to look for statistical differences between positive versus negative severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) groups. During the early phase of the pandemic, the facility closely followed the local shelter-in-place order (starting March 19, 2020) and symptom-based testing. RESULTS: Of the residents, the primary psychiatric diagnoses were schizoaffective disorder: 28 (51.9%), schizophrenia: 21 (38.9%), bipolar I disorder: 3 (5.5%), and unspecified psychotic disorder: 2 (3.7%). Forty (74%) of 54 residents tested positive for SARS-COV-2, with a doubling time of 3.9 days. There were no statistical differences between the positive SARS-COV-2 versus negative groups for age or race/ethnicity. Psychiatric and medical conditions were not significantly associated with contracting SARS-COV-2, with the exception of obesity (n = 17 [43%] positive vs n = 12 [86%] negative, P = .01). Medical monitoring of vital signs and symptoms did not lead to earlier detection. All of the residents completely recovered, with the last resident no longer showing any symptoms 24 days from the index case. CONCLUSION: Research is needed to determine optimal strategies for long-term care mental health settings that incorporate frequent testing and personal protective equipment use to prevent rapid transmission of SARS-COV-2.

Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors.

INTRODUCTION: Proton pump inhibitors (PPIs) increase the risk for enteric infections that is likely related to PPI-induced hypochlorhydria. Although the impact of acid suppression on severe acute respiratory syndrome coronavirus 2 is unknown thus far, previous data revealed that pH ≤3 impairs the infectivity of the similar severe acute respiratory syndrome coronavirus 1. Thus, we aimed to determine whether use of PPIs increases the odds for acquiring coronavirus disease 2019 (COVID-19) among community-dwelling Americans. METHODS: From May 3 to June 24, 2020, we performed an online survey described to participating adults as a "national health survey." A multivariable logistic regression was performed on reporting a positive COVID-19 test to adjust for a wide range of confounding factors and to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Of 53,130 participants, 3,386 (6.4%) reported a positive COVID-19 test. In regression analysis, individuals using PPIs up to once daily (aOR 2.15; 95% CI, 1.90-2.44) or twice daily (aOR 3.67; 95% CI, 2.93-4.60) had significantly increased odds for reporting a positive COVID-19 test when compared with those not taking PPIs. Individuals taking histamine-2 receptor antagonists were not at elevated risk. DISCUSSION: We found evidence of an independent, dose-response relationship between the use of antisecretory medications and COVID-19 positivity; individuals taking PPIs twice daily have higher odds for reporting a positive test when compared with those using lower-dose PPIs up to once daily, and those taking the less potent histamine-2 receptor antagonists are not at increased risk. These findings emphasize good clinical practice that PPIs should only be used when indicated at the lowest effective dose, such as the approved once-daily label dosage of over-the-counter and prescription PPIs. Further studies examining the association between PPIs and COVID-19 are needed.