Monocytic HLA-DR Expression in Immune Responses of Acute Pancreatitis and COVID-19.

Acute pancreatitis is a common gastrointestinal disease with increasing incidence worldwide. COVID-19 is a potentially life-threatening contagious disease spread throughout the world, caused by severe acute respiratory syndrome coronavirus 2. More severe forms of both diseases exhibit commonalities with dysregulated immune responses resulting in amplified inflammation and susceptibility to infection. Human leucocyte antigen (HLA)-DR, expressed on antigen-presenting cells, acts as an indicator of immune function. Research advances have highlighted the predictive values of monocytic HLA-DR (mHLA-DR) expression for disease severity and infectious complications in both acute pancreatitis and COVID-19 patients. While the regulatory mechanism of altered mHLA-DR expression remains unclear, HLA-DR-/low monocytic myeloid-derived suppressor cells are potent drivers of immunosuppression and poor outcomes in these diseases. Future studies with mHLA-DR-guided enrollment or targeted immunotherapy are warranted in more severe cases of patients with acute pancreatitis and COVID-19.

Trends in gastrointestinal disease hospitalizations and outcomes during the first year of the coronavirus pandemic.

BACKGROUND: The impact of the coronavirus on hospitalizations for gastrointestinal (GI) disease, particularly at a population level is understudied. AIM: To investigate trends in hospitalizations, inpatient endoscopy resource utilization, and outcomes during the first year of the coronavirus pandemic and subsequent lockdowns. METHODS: Using the California State Inpatient Database for 2018-2020, we explored year-to-year and 2020 month-to-month trends in hospitalizations, length of stay, and inpatient mortality (all-cause & viral pneumonia-specific) for common inpatient GI diagnoses including acute pancreatitis, diverticulitis, cholelithiasis, non-infectious gastroenteritis, upper and lower GI bleeding (LGIB), Clostridium difficile, viral gastroenteritis, inflammatory bowel disease, and acute cholangitis. RESULTS: Disease-specific hospitalizations decreased for all included conditions except nonvariceal upper GI bleeding (NVUGIB), LGIB, and ulcerative colitis (UC) (ptrend < 0.0001). All-cause inpatient mortality was higher in 2020 vs 2019, for acute pancreatitis (P = 0.029), diverticulitis (P = 0.04), NVUGIB (P = 0.003), and Crohn's disease (P = 0.004). In 2020, hospitalization rates were lowest in April, November, and December. There was no significant corresponding increase in inpatient mortality except in UC (ptrend = 0.048). Viral pneumonia and viral pneumonia complicated by respiratory failure increased (P < 0.001) among GI hospitalizations. Endoscopy utilization within 24 h of admission was unchanged for GI emergencies except NVUGIB (P < 0.001). CONCLUSION: Our findings suggest that hospitalization rates for common GI conditions significantly declined in California during the COVID pandemic, particularly in April, November and December 2020. All-cause mortality was significantly higher among acute pancreatitis, diverticulitis, NVUGIB, and Crohn's disease hospitalizations. Emergency endoscopy rates were mostly comparable between 2020 and 2019.

Utility of monocyte distribution width for diagnosing colonic diverticulitis in the emergency department: a retrospective cohort study (preprint)

Background Colonic diverticulitis is a leading cause of abdominal pain. The monocyte distribution width (MDW) is a novel inflammatory biomarker with prognostic significance for coronavirus disease and pancreatitis; however, no study has assessed its correlation with the severity of colonic diverticulitis. Methods This single-center retrospective cohort study included patients older than 18 years who presented to the emergency department between November 1, 2020, and May 31, 2021, and received a diagnosis of acute colonic diverticulitis after abdominal computed tomography. The characteristics and laboratory parameters of patients with simple versus complicated diverticulitis were compared. The significance of categorical data was assessed using the chi-square or Fisher’s exact test. The Mann–Whitney U test was used for continuous variables. Multivariate regression analysis was performed to identify predictors of complicated colonic diverticulitis. Receiver operator characteristic (ROC) curves were used to test the efficacy of inflammatory biomarkers in distinguishing simple from complicated cases. Results Of the 160 patients enrolled, 21 (13.125%) had complicated diverticulitis. Although right-sided was more prevalent than left-sided colonic diverticulitis (70% versus 30%), complicated diverticulitis was more common in those with left-sided colonic diverticulitis (61.905%, p = 0.001). Age, white blood cell (WBC) count, neutrophil count, C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and MDW were significantly higher in the complicated diverticulitis group (p < 0.05). Logistic regression analysis indicated that the left-sided location and the MDW were significant and independent predictors of complicated diverticulitis. The area under the ROC curve (AUC) was as follows: MDW, 0.870 (95% confidence interval [CI], 0.784–0.956); CRP, 0.800 (95% CI, 0.707–0.892); NLR, 0.724 (95% CI, 0.616–0.832); PLR, 0.662 (95% CI, 0.525–0.798); and WBC, 0.679 (95% CI, 0.563–0.795). The MDW had the largest AUC for diagnosing complicated diverticulitis; when the MDW cutoff was 20.38, the sensitivity and specificity were maximized to 90.5% and 80.6%, respectively. Conclusions Patients with complicated diverticulitis were significantly older and predominantly had left-sided colonic diverticulitis. A large MDW was a significant and independent predictor of complicated diverticulitis. The MDW may aid in planning antibiotic therapy for patients with colonic diverticulitis in the emergency department.

Acute pancreatitis masquerading as mesentric growth in COVID-19 patient: A case report.

COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It commonly affects the respiratory system, producing pneumonia-like symptoms. Among extrapulmonary manifestations, involvement of the gastrointestinal tract is common with symptoms of nausea, vomiting, diarrhea, and abdominal pain. Coronavirus acts by targeting the ACE-2 receptors in the alveoli of the lungs, but because these receptors are also present in other organs, such as the pancreas, it can affect the pancreas as well, thus causing acute pancreatitis. We here discuss a case of a 72-year-old hypertensive male with COVID-19 who presented with atypical presentation of acute abdominal pain and a few episodes of vomiting. Laboratory investigations were inconclusive. Imaging findings were suggestive of small bowel obstruction and perforation; thus, an exploratory laparotomy was done in which a mesenteric growth was found, reported as acute pancreatitis on histopathology. Therefore, attention should be paid to the pancreatic involvement and atypical presentations in COVID-19 patients.

SARS-CoV-2 and the pancreas: What do we know about acute pancreatitis in COVID-19 positive patients?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause pancreatic damage, both directly to the pancreas via angiotensin-converting enzyme 2 receptors (the transmembrane proteins required for SARS-CoV-2 entry, which are highly expressed by pancreatic cells) and indirectly through locoregional vasculitis and thrombosis. Despite that, there is no clear evidence that SARS-CoV-2 is an etiological agent of acute pancreatitis. Acute pancreatitis in coronavirus disease 2019 (COVID-19) positive patients often recognizes biliary or alcoholic etiology. The prevalence of acute pancreatitis in COVID-19 positive patients is not exactly known. However, COVID-19 positive patients with acute pancreatitis have a higher mortality and an increased risk of intensive care unit admission and necrosis compared to COVID-19 negative patients. Acute respiratory distress syndrome is the most frequent cause of death in COVID-19 positive patients and concomitant acute pancreatitis. In this article, we reported recent evidence on the correlation between COVID-19 infection and acute pancreatitis.

Acute pancreatitis in pregnancy following COVID-19 vaccine: a case report.

BACKGROUND: Since the approval of the Pfizer-BioNTech (BNT162b2) mRNA vaccine for COVID-19 infection, a few adverse effects have been reported. Acute pancreatitis has been reported in a few patients. However, there is currently no research showing a direct relationship between the vaccine and acute pancreatitis. Here, we report a case of acute pancreatitis following Pfizer vaccination in a young healthy pregnant woman without any known risk factors. To our knowledge, this is the first case report of possible vaccine-induced pancreatitis in a pregnant woman. CASE PRESENTATION: The patient, a 24-year-old South-Asian female, at 31 weeks of gestation, presented with severe epigastric pain radiating to the back and worsening on lying supine, associated with nausea and vomiting. She was diagnosed with acute pancreatitis with a serum lipase level of 4376 U/L and an ultrasound showing features of pancreatitis. The patient received her first dose of the Pfizer vaccine 1 week prior to these symptoms. Detailed evaluation did not show any etiological cause of pancreatitis. The patient had a spontaneous vaginal delivery and the baby was shifted to the neonatal intensive care unit in a stable condition. A computed tomography scan postpartum (day 2) demonstrated acute interstitial edematous pancreatitis. The patient was managed conservatively in the intensive care unit and discharged home in a stable condition. CONCLUSION: This report highlights the importance of a detailed history and evaluation, and the close monitoring of any patient presenting with abdominal pain after vaccination. Acute pancreatitis can be fatal if not picked up early.

Novel insight on marker genes and pathogenic peripheral neutrophil subtypes in acute pancreatitis.

Acute pancreatitis is a common critical and acute gastrointestinal disease worldwide, with an increasing percentage of morbidity. However, the gene expression pattern in peripheral blood has not been fully analyzed. In addition, the mechanism of coronavirus disease 2019 (COVID-19)-induced acute pancreatitis has not been investigated. Here, after bioinformatic analysis with machine-learning methods of the expression data of peripheral blood cells and validation in local patients, two functional gene modules in peripheral blood cells of acute pancreatitis were identified, and S100A6, S100A9, and S100A12 were validated as predictors of severe pancreatitis. Additionally, through a combination analysis of bulk sequencing and single-cell sequencing data of COVID-19 patients, a pivotal subtype of neutrophils with strong activation of the interferon-related pathway was identified as a pivotal peripheral blood cell subtype for COVID-19-induced acute pancreatitis. These results could facilitate the prognostic prediction of acute pancreatitis and research on COVID-19-induced acute pancreatitis.

Nafamostat Mesylate for Treatment of COVID-19 in Hospitalised Patients: A Structured, Narrative Review.

The search for clinically effective antivirals against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is ongoing. Repurposing of drugs licensed for non-coronavirus disease 2019 (COVID-19) indications has been extensively investigated in laboratory models and in clinical studies with mixed results. Nafamostat mesylate (nafamostat) is a drug licensed in Japan and Korea for indications including acute pancreatitis and disseminated intravascular coagulation. It is available only for continuous intravenous infusion. In vitro human lung cell line studies with nafamostat demonstrate high antiviral potency against SARS-CoV-2 (half maximal inhibitory concentration [IC50] of 0.0022 µM [compared to remdesivir 1.3 µM]), ostensibly via inhibition of the cellular enzyme transmembrane protease serine 2 (TMPRSS2) preventing viral entry into human cells. In addition, the established antithrombotic activity is hypothesised to be advantageous given thrombosis-associated sequelae of COVID-19. Clinical reports to date are limited, but indicate a potential benefit of nafamostat in patients with moderate to severe COVID-19. In this review, we will explore the pre-clinical, pharmacokinetic and clinical outcome data presently available for nafamostat as a treatment for COVID-19. The recruitment to ongoing clinical trials is a priority to provide more robust data on the safety and efficacy of nafamostat as a treatment for COVID-19.

COVID-19 and Acute Pancreatitis: A Systematic Review of Case Reports and Case Series.

BACKGROUND: Coronavirus disease 2019 (COVID-19) presents mainly with mild symptoms and involvement of the respiratory system. Acute pancreatitis has also been reported during the course of COVID-19. OBJECTIVE: Our aim is to review and analyze all reported cases of COVID-19 associated acute pancreatitis, reporting the demographics, clinical characteristics, laboratory and imaging findings, comorbidities and outcomes. DATA SOURCES: We conducted a systematic search of Pubmed/MEDLINE, SciELO and Google Scholar to identify case reports and case series, reporting COVID-19 associated acute pancreatitis in adults. STUDY SELECTION: There were no ethnicity, gender or language restrictions. The following terms were searched in combination:"COVID-19" OR "SARS-CoV-2" OR "Coronavirus 19" AND "Pancreatic Inflammation" OR "Pancreatitis" OR "Pancreatic Injury" OR "Pancreatic Disease" OR "Pancreatic Damage". Case reports and case series describing COVID-19 associated acute pancreatitis in adults were included. COVID-19 infection was established with testing of nasal and throat swabs using reverse transcription polymerase chain reaction. The diagnosis of acute pancreatitis was confirmed in accordance to the revised criteria of Atlanta classification of the Acute Pancreatitis Classification Working Group. Exclusion of other causes of acute pancreatitis was also required for the selection of the cases. DATA EXTRACTION: The following data were extracted from each report: the first author, year of publication, age of the patient, gender, gastrointestinal symptoms due to acute pancreatitis, respiratory-general symptoms, COVID-19 severity, underlying diseases, laboratory findings, imaging features and outcome. DATA SYNTHESIS: Finally, we identified and analyzed 31 articles (30 case reports and 1 case series of 2 cases), which included 32 cases of COVID-19 induced acute pancreatitis. CONCLUSION: COVID-19 associated acute pancreatitis affected mostly females. The median age of the patients was 53.5 years. Concerning laboratory findings, lipase and amylase were greater than three times the ULN while WBC counts and CRP were elevated in the most of the cases. The most frequent gastrointestinal, respiratory and general symptom was abdominal pain, dyspnea and fever, respectively. The most common imaging feature was acute interstitial edematous pancreatitis and the most frequent comorbidity was arterial hypertension while several patients had no medical history. The outcome was favorable despite the fact that most of the patients experienced severe and critical illness. LIMITATIONS: Our results are limited by the quality and extent of the data in the reports. More specifically, case series and case reports are unchecked, and while they can recommend hypotheses they are not able to confirm robust associations. CONFLICT OF INTEREST: None.

Review on acute pancreatitis attributed to COVID-19 infection.

The coronavirus disease 2019 (COVID-19) is known to cause gastrointestinal symptoms. Recent studies have revealed COVID-19-attributed acute pancreatitis (AP). However, clinical characteristics of COVID-19-attributed AP remain unclear. We performed a narrative review to elucidate relation between COVID-19 and AP using the PubMed database. Some basic and pathological reports revealed expression of angiotensin-converting enzyme 2 and transmembrane protease serine 2, key proteins that aid in the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the pancreas. The experimental and pathological evaluation suggested that SARS-CoV-2 infects human endocrine and exocrine pancreas cells, and thus, SARS-CoV-2 may have a direct involvement in pancreatic disorders. Additionally, systemic inflammation, especially in children, may cause AP. Levels of immune mediators associated with AP, including interleukin (IL)-1ß, IL-10, interferon-γ, monocyte chemotactic protein 1, and tumor necrosis factor-α are higher in the plasma of patients with COVID-19, that suggests an indirect involvement of the pancreas. In real-world settings, some clinical features of AP complicate COVID-19, such as a high complication rate of pancreatic necrosis, severe AP, and high mortality. However, clinical features of COVID-19-attributed AP remain uncertain due to insufficient research on etiologies of AP. Therefore, high-quality clinical studies and case reports that specify methods for differential diagnoses of other etiologies of AP are needed.

The impact of COVID-19 on prescribing of pancreatic enzyme replacement therapy for people with unresectable pancreatic cancer in England. A cohort study using OpenSafely-TPP (preprint)

Background: Cancer treatments were variably disrupted during the COVID-19 pandemic. Despite UK national guidelines recommending pancreatic enzyme replacement therapy to all people with unresectable pancreatic cancer, observational studies demonstrate under-prescribing. Aim: To investigate the impact of the COVID-19 pandemic on the prescribing of pancreatic enzyme replacement to people with unresectable pancreatic cancer. Methods: With the approval of NHS England, we conducted a cohort study using 24 million health records through the OpenSAFELY-TPP research platform. We modelled the effect of COVID-19 with multivariable linear regression. Results: We found no reduction in pancreatic enzyme replacement therapy during the COVID-19 pandemic. Overall, since 2015, the rates of prescribing increased steadily over time by 1% every year. The national rates ranged from 41% in 2015 to 48% in 2022. There was substantial regional variation. The highest rates of 50% to 60% were in the West Midlands and lowest (20% to 30%) in London. Conclusions: In contrast to many other treatments, prescribing of pancreatic enzyme replacement therapy was not affected during the COVID-19 pandemic. Although overall rates increased over time, substantial under-prescribing existed at the end of this study (March 2022). At just under 50% in 2022, the rates were still below the recommended 100% standard. Prior work evaluating quality of care in this area relied on manual audits which come at increased cost and reduced frequency of updates. With the methodological advantage of OpenSAFELY, we established an automated audit which allows for regular updates.

ACUTE PANCREATITIS CAUSED BY COVID-19 TREATMENT (preprint)

Remdesivir can precipitate fatal acute necrotizing pancreatitis especially in patients who previously suffer from hypertriglyceridemia.

Evaluation of patients with acute pancreatitis associated with SARS-CoV-2 (COVID-19); The importance of lipase/lymphocyte ratio in predicting mortality.

BACKGROUND: SARS-CoV-2 is the cause of a pandemic with high mortality. In the present study, the effects of the lipase/lymphocyte ratio on mortality were investigated in cases diagnosed with Covid-19 and acute pancreatitis. METHODS: A total of 21 patients who were diagnosed with Covid-19 and acute pancreatitis, 34 patients who were not diagnosed with COVID-19 but diagnosed with acute pancreatitis, and 55 healthy control groups were divided into 3 groups and included in the study retrospectively. The patients who had positive RT-PCR (real­time polymerized chain reaction) test results were included in the study. Complete blood count and biochemical values ​​of the patients were compared with those of the control group. RESULTS: When the data of the cases diagnosed with COVID-19 and acute pancreatitis were examined retrospectively, the amylase, lipase, lipase/lymphocyte ratio, and D-dimer levels were found to be significantly higher than in the control group (p < 0.01). In the ROC analysis, the amylase, lipase, and lipase/lymphocyte ratio had a high AUC (area under the curve) value (0.993 / 0.949 / 0.978, respectively). CONCLUSION: The lipase/lymphocyte ratio can be used in cases diagnosed with Covid-19 and acute pancreatitis to predict mortality (Tab. 3, Fig. 3, Ref. 23).

Immature granulocytes: Innovative biomarker for SARS­CoV­2 infection.

Immature granulocytes (IGs) include metamyelocytes, myelocytes and promyelocytes, and are the precursors of neutrophils. Increased IG counts found in peripheral blood indicate an enhanced bone marrow activity. In addition, IGs have been evaluated in numerous clinical conditions, such as severe acute pancreatitis, systemic inflammatory response syndrome and infectious complications following open­heart surgery under cardiopulmonary bypass. Neutrophils are considered to play a crucial role in the host defense during bacterial and fungal infections, and are involved in the antiviral immune response. Numerous studies have reported the role of neutrophils in coronavirus disease 2019 (COVID­19) infection, concluding that the percentage of neutrophils may be a predictor of the severity of COVID­19 infection. There has been limited research regarding the role of neutrophil precursors in viral infections, including severe acute respiratory syndrome coronavirus 2 infection. The present thus aimed to evaluate the role of the IG count in patients hospitalized due to COVID­19 infection. The patients were predominantly infected with the alpha variant and were all unvaccinated. The IG count was measured and was found to be associated with disease severity, with patient outcomes, with the duration of hospitalization and with the development of complications. The IG count was a significantly associated with the severity of COVID­19 infection, with greater IG count values being detected in severe and critical cases. In addition, greater IG count values were associated with a longer duration of hospitalization. Furthermore, the IG count was found to be an independent prognostic biomarker of intubation and mortality in patients with COVID­19, according to multivariate logistic regression analysis, including age, the male sex and the presence of comorbidities as confounders.

Fatal gastrointestinal bleeding associated with acute pancreatitis as a complication of Covid-19: a case report.

Clinical manifestations of Covid-19 vary widely among patients. Recent studies suggest that up to 15% of patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections develop gastrointestinal symptoms. The location of virus-host cell receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 has an important role in the pathophysiology and presentation of disease. They are expressed in the respiratory tract, as well as other organs and tissues including exocrine and endocrine pancreatic cells. These cells are therefore a possible target for the virus, which could explain the relationship between SARS-CoV-2 infection and pancreatic injury. We report a disastrous collateral effect of the Covid-19 pandemic on a 33-year-old man with chronic renal insufficiency and asymptomatic SARS-CoV-2 infection, who developed acute pancreatitis. Inflammation progressed rapidly toward necrosis and the development of a peripancreatic pseudoaneurysm which subsequently ruptured, causing death.

DOES COVID-19 CAUSE PANCREATITIS?

BACKGROUND: Viral infections can cause acute pancreatitis. Idiopathic pancreatitis has an important proportion in the etiology of acute pancreatitis. OBJECTIVE: To investigate the rate of development of acute pancreatitis (AP) in COVID-19 patients and to determine the rate of idiopathic pancreatitis in the etiology of this pancreatitis. METHODS: A total of 6.467 patients hospitalized with the COVID-19 diagnosis were included in the study. Patients diagnosed with AP based on the Atlanta criteria were identified. Etiological factors were determined in patients who developed acute pancreatitis and compared with the etiological factors in 315 patients with non-COVID-19, hospitalized with the diagnosis of AP before the COVID-19 pandemic. AP was detected in 0.1% of patients with COVID-19. While gallstone was the etiologic factor in 2 (28.6%) of seven patients who developed acute pancreatitis during COVID-19, hyperlipidemia was the factor for 1 (14.3%) patient. Moreover, the etiologic factor could not be determined in 4 (57.1%) patients, and they were regarded as idiopathic pancreatitis patients. Biliary pancreatitis was the most common etiologic factor in 315 (78.4%) patients admitted to the hospital for AP before the COVID-19 pandemic. Idiopathic pancreatitis was ranked second with 16.8%. CONCLUSION: It was observed that there was a significant difference in the incidence of idiopathic pancreatitis between patients with COVID-19 and non-COVID-19 (P=0.015). Results suggest that the SARS-Cov-2 virus may be among the factors leading to AP.