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Introduction: Acute pancreatitis affects a significant population globally. Usual etiologies are gallstones, alcohol, hypertriglyceridemia, medications;less frequent are trauma, hypercalcemia, infections, toxins, ischemia, anatomic anomalies, vasculitis, and idiopathic. Pancreatitis post coronary intervention is an uncommon cause with only 19 published cases in the last two decades. Being cognizant of this etiology is important given the increasing number of patients undergoing angiography. Case Description/Methods: An 81-year-old female with hypertension, diabetes, peripheral arterial disease, prior cholecystectomy underwent left lower extremity angioplasty at an outside center. Within a few hours, she started having severe epigastric pain radiating to her back, nausea, vomiting and loose bloody stool. She presented to the emergency department 24 hours after symptom onset. Epigastric tenderness was present on exam. Labs revealed leukocytosis (24,450/muL), elevated lipase (1410 U/L), elevated creatinine (1.3 mg/dL), lactate (3.1 mmol/L), calcium 9.4 mg/dL and triglycerides 161 mg/dL. Incidentally, found to be positive for COVID-19. Normal common bile duct diameter seen on sonogram. CT angiogram of the abdomen/pelvis showed acute pancreatitis, duodenal and central small bowel enteritis (Figure). She was not on any medications known to cause pancreatitis and denied alcohol use. Patient improved with analgesics and intravenous fluids. She had no recurrence of bloody stools and hemoglobin remained stable. On day 4, she was able to tolerate a regular diet, and leukocyte count and creatinine normalized. Patient did not have any COVID respiratory symptoms, and was discharged. Discussion(s): Given the temporal association to angioplasty and no other identifiable cause, acute pancreatitis was presumed to be due to the contrast used during angioplasty. Other possibilities included cholesterol embolism but no peripheral signs of cholesterol embolism were seen. Patient was an asymptomatic COVID-19 case. Although, there are case series of pancreatitis due to COVID, those were found in very sick symptomatic patients. On review of literature, cholesterol embolism was identified as a definite cause only on autopsy or laparotomy (Table). Other possible mechanisms are: high viscosity of the contrast media leading to ischemia and necrosis, contrast causing NF-kB activation followed by epithelial damage, and vasospasm. Pancreatitis after coronary angiography is rare, nonetheless, an important differential especially if there is a temporal relationship.
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Background: Better understanding of host inflammatory changes that precede development of severe COVID-19 could improve delivery of available antiviral and immunomodulatory therapies, and provide insights for the development of new therapies. Method(s): In plasma from individuals with COVID-19, sampled <=10 days from symptom onset from the All-Ireland Infectious Diseases Cohort study, we measured 61 biomarkers, including markers of innate immune and T cell activation, coagulation, tissue repair, lung injury, and immune regulation. We used principal component analysis (PCA) and k-means clustering to derive biomarker clusters, and univariate and multivariate ordinal logistic regression to explore association between cluster membership and maximal disease severity, adjusting for risk factors for severe COVID-19, including age, sex, ethnicity, BMI, hypertension and diabetes. Result(s): From March 2020-April 2021, we included 312 individuals, (median (IQR) age 62 (48-77) years, 7 (4-9) days from symptom onset, 54% male) in the analysis. PCA and clustering derived 4 clusters. Compared to cluster 1, clusters 2-4 were significantly older and of higher BMI but there were no significant differences in sex or ethnicity. Cluster 1 had low levels of inflammation, cluster 2 had higher levels of markers of tissue repair and endothelial activation (EGF, VEGF, PDGF, TGFalpha, serpin E1 and p-selectin). Cluster 3 and 4 were both characterised by higher overall inflammation, but compared to cluster 4, cluster 3 had downregulation of growth factors, markers of endothelial activation, and immune regulation (IL10, PDL1), but higher alveolar epithelial injury markers (RAGE, ST2). In univariate analysis, compared to cluster 1, cluster 3 had the highest odds of severe disease (OR (95% CI) 9.02 (4.62-18.31), followed by cluster 4: 5.59 (2.75-11.72) then cluster 2: 4.5 (2.38-8.81), all p < 0.05). Cluster 3 remained most strongly associated with severe disease in fully adjusted analyses;cluster 3: OR(95% CI) 5.99 (2.69-13.35), cluster 2: 3.14 (1.54-6.42), cluster 4: 3.13 (1.36-7.19), all p< 0.05). Conclusion(s): Distinct early inflammatory profiles predicted maximal disease severity independent of known risk factors for severe COVID-19. A cluster characterised by downregulation of growth factor and endothelial markers and early evidence of alveolar injury was associated with highest risk of developing severe COVID19. Whether this reflects a dysregulated inflammatory response that could improve targeted treatment requires further study. Heatmap of biomarker derived clusters and forest plot of association between clusters and disease severity. A: Heatmap demonstrating differences in biomarkers between clusters B: Forest plot demonstrating odds ratio of specific clusters for progressing to moderate or severe disease (reference Cluster 1), calculated using ordinal logistic regression. Odds ratio (95% CI) presented as unadjusted and fully adjusted (for age, sex, ethnicity, BMI, hypertension, diabetes, immunosuppression, smoking and baseline anticoagulant use). Maximal disease severity graded per the WHO severity scale.
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Introduction: Impairment of lung function and radiological abnormalities are a major concern in COVID-19 survivors, but, as of yet, patients with persistent COVID-19-related ARDS have still not been fully characterized especially regarding long-term lung injury and development of pulmonary fibrosis. The aim of this observational study is to investigate whether long-term pulmonary injury is related to fibroproliferative responses during ICU stay. Method(s): Twenty-eight PCR confirmed COVID-19 patients admitted to the ICU of the Amsterdam University Medical Centers (Amsterdam UMC), location VUmc, who underwent a diagnostic bronchoscopy with broncho-alveolar lavage (BAL) because of non-resolving COVID-19 related ARDS, were included. Bronchoscopy was repeated weekly when no clinical improvement was observed. Markers for epithelial injury and fibroproliferation were measured in BALF and plasma using specific Luminex assays or ELISA. Three and 12 months after hospital discharge, chest CT and lung function parameters were obtained during outpatient visits. Result(s): Pulmonary markers for epithelial injury and fibroproliferation were measured in BALF and compared to healthy controls (HC). Epithelial injury and fibroproliferation markers were significantly increased in critically ill COVID-19 patients as compared to HC. Plasma markers for fibroproliferation were not different as compared to HC. No signs of pulmonary fibrosis were found at 3 and 12 months after hospital discharge. Conclusion(s): Patients with non-resolving COVID-19 related ARDS show a sustained alveolar fibroproliferative response, however such fibroproliferative response is not associated with pulmonary fibrosis.
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Introduction: Persistence of SARS-Cov-2 leads to immunosuppression and lack of viral control. Better understanding of the immune response throughout the course of evolution is important for a better patient management. Method(s): Prospective observational longitudinal study of 91 hospitalised patients with different degrees of severity (moderate, severe, critical). In 72 we obtained >=2 blood samples and classified them into viral phase (1-9 days after clinical onset), early inflammatory (10-16), and late inflammatory (>17). We included clinical data, immune cell counts, proinflammatory cytokine levels, serum inflammatory markers, and tissue damage. Result(s): We observed higher serum IL-6 levels in the more severe groups, from the first sample. In inflammatory phases, we found a significant decrease in IL-6 and LDH in moderate, severe and survivors, and high persistence in critical and deceased patients. The biphasic behavior of IL-6 described, first neutrophil recruitment, epithelial and endothelial damage and then, after achieving viral control, CD4 differentiation, Th cells response and potentiation of Ac response, could explain these differences between those who do not achieve viral control (critical, deceased) and those who do. Conclusion(s): - IL-6 levels at 10-16 days may indicate whether or not viral control is achieved and whether there may be progression to critical stage/death.
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Introduction: Almost 30% of olfactory dysfunction (OD) arises after a viral infection with increased incidence due to COVID-19. Hypothesized SARS-CoV-2 viral attachment to the olfactory epithelium differs from the traditional postviral OD (PVOD) mechanism. Hence, manifestations of OD may differ between the two etiologies. This study evaluates the difference in smell perception between post-COVID-19 OD and postviral or idiopathic etiologies. Method(s): This observational study, approved by the institutional review board, was conducted between September 2020 and January 2022 in adult patients with more than 6 months nontraumatic OD with no perceived improvement in smell even after 3 months of conservative treatment. OD in these patients was categorized as COVID-19 or non-COVID-19 related. Demographics, duration of OD, and Brief Smell Identification Test (B-SIT) scores were analyzed. Continuous variables were compared by t test, while categorical variables were compared by chi2 test using SPSS 27 (IBM Corp). Result(s): Of the 26 patients included in the study, 42.3% reported persistent OD following COVID-19 infection, while 57.7% had non-COVID-19-related OD. The mean B-SIT score in post-COVID-19 OD was 6.81+/-2.15 compared with 3.87+/-2.2 in the non-COVID-19 OD group, with the difference being statistically significant at 3.40 (P=.001). While race and gender ratios were similar between the groups, age (42 vs 54, P=.048) and duration of loss of smell (10 months vs 49 months, P<.001) had significant differences. Conclusion(s): This study shows that patients suffering from COVID-19-related OD may have normal scores on scratch and sniff smell tests, possibly because of the difference in the affected site of the olfactory pathway. Current hypotheses focus on olfactory epithelial damage in COVID-19 vs neuronal in PVOD. Differences seen in age and duration of smell loss between groups may be secondary to newfound worldwide attention to OD, while patients with OD etiologies predating COVID-19 may have newly sought treatment at this time. Olfactory threshold testing may be required for accurate assessment of post- COVID-19 OD. Larger studies are required to help delineate differences between these olfactory disturbance etiologies.
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SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Epiglottitis is an inflammation of the epiglottis which can be life-threatening in the absence of prompt intervention. Although primarily a pediatric condition, streptococcus pneumonia has been identified as a common pathogen in adults. SARS-CoV 2 has been known to affect a multitude of systems including the upper respiratory tract, but rarely the epiglottis. CASE PRESENTATION: A 66-year-old female with a past history of hypertension, and hypothyroidism presented with acute onset pharyngodynia and dysphagia with a feeling of throat closing up due to swelling and difficulty speaking. She had a recent COVID-19 diagnosis and was doing well except for mild fatigue. Upon presentation, she was hemodynamically stable. Physical exam revealed posterior pharyngeal edema without any exudate, mildly edematous uvula, and no stridor. Laboratory data was pristine except for elevated inflammatory markers. Rapid streptococcal test and MRSA swab were negative. Sputum culture showed usual respiratory flora and blood cultures were negative. A neck CT showed diffuse edema without any evidence of abscess. Laryngoscopy performed by the ENT surgeon revealed diffuse edema including epiglottitis. Emergent intubation revealed supra and epiglottis edema sparing the vocal cords. The patient was given Decadron and Benadryl to help with the edema along with clindamycin and subsequently transferred to ICU for further care. She was treated with Ceftriaxone for 7 days due to a chest X-ray finding of pneumonia. As for COVID 19 treatment, she received a course of Remdesivir and Decadron. Decadron was given at an increased interval to reduce edema around the epiglottis. Her ICU course was complicated with hypotension requiring intermittent vasopressor support, and acute kidney injury from ischemic acute tubular necrosis which slowly improved. Repeat CT chest showed bibasilar consolidations with peripheral ground-glass opacities. In view of hospital-acquired pneumonia, she was started on Ertapenem. Her clinical condition improved and she was successfully extubated. She was shifted to the floors from where she was discharged without any further complications. DISCUSSION: There are only two other reported cases of COVID 19 epiglottitis. The patient's advanced age and obesity were non-modifiable risk factors, but the COVID-19 infection played a role. The virus can lead to excessive upregulation of the host inflammatory response through repeat epithelial and endothelial damage leading to a cytokine storm, which may be responsible for this presentation. A great level of attention is to be maintained while attending to these patients given the multitude of systems that can be affected. CONCLUSIONS: COVID-19 is a potential cause of life-threatening acute epiglottitis. Early suspicion and direct visualization of the epiglottis is the key to success for early management. Reference #1: Emberey J, Velala SS, Marshall B, et al. Acute Epiglottitis Due to COVID-19 Infection. Eur J Case Rep Intern Med. 2021;8(3):002280. Published 2021 Mar 3. doi:10.12890/2021_002280 Reference #2: Smith C, Mobarakai O, Sahra S, Twito J, Mobarakai N. Case report: Epiglottitis in the setting of COVID-19. IDCases. 2021;24:e01116. doi: 10.1016/j.idcr.2021.e01116. Epub 2021 Apr 7. PMID: 33842206;PMCID: PMC8025537. DISCLOSURES: No relevant relationships by Arunava Saha
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SESSION TITLE: Drug-Induced Lung Injury Pathology Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Daptomycin is an antibiotic that exerts its bactericidal effect by disrupting multiple aspects of bacterial cell membrane function. It has notable adverse effects including myopathy, rhabdomyolysis, eosinophilic pneumonitis, and anaphylactic hypersensitivity reactions. CASE PRESENTATION: A 46-year-old male with a history of type 2 diabetes presented with a 1-week history of dyspnea and productive cough. 2 weeks prior, he was started on vancomycin for MRSA osteomyelitis of the right foot, but was switched to daptomycin due to vancomycin induced nephrotoxicity. On presentation he was afebrile, tachycardic 100, hypertensive 183/109, tachypneic to 26, hypoxemic 84% on room air, which improved to 94% on nasal cannula. Chest exam noted coarse breath sounds in all fields and pitting edema of lower extremities were present. Labs showed leukocytosis of 15.2/L, Na of 132 mmol/L, and creatinine 3.20mg/dL (normal 1 month prior). COVID-19 testing was negative. Chest X-ray noted new bilateral asymmetric opacifications. Daptomycin was discontinued on day 1 of admission, he was started on IV diuretics and ceftaroline. Further study noted peripheral eosinophilia. Computed tomography of the chest showed bilateral centrally predominant ground-glass infiltrates with air bronchograms and subcarinal and paratracheal lymphadenopathy. On day 4, he underwent bronchoscopy with bronchoalveolar lavage. Cytology noted 4% eosinophil with 43% lymphocytes. Eventually, oxygen requirements and kidney function returned to baseline. He was discharged on ceftaroline for osteomyelitis DISCUSSION: Daptomycin-induced acute eosinophilic pneumonitis (AEP) often results in respiratory failure in the setting of exposure to doses of daptomycin >6mg/kg/day. It is characterized by the infiltration of pulmonary parenchyma with eosinophils and is often associated with peripheral eosinophilia. AEP has been associated with certain chemicals, non-steroidal anti-inflammatory agents, and antibiotics including daptomycin. Renal dysfunction is associated with an increased risk for developing AEP. The mechanism for daptomycin-induced lung injury is unknown but is believed to be related to daptomycin binding to pulmonary surfactant culminating in epithelial injury. Diagnostic criteria include recent daptomycin exposure, fever, dyspnea with hypoxemic respiratory failure, new infiltrates on chest radiography, BAL with > 25% eosinophils, and clinical improvement following daptomycin discontinuation. Our patient met four out of six criteria;we believe that BAL results were due to discontinuing daptomycin days before the procedure was performed. Sometimes stopping daptomycin is enough for recovery, however, steroids may be beneficial and were used in some of the cases reported in the literature CONCLUSIONS: Clinicians should consider AEP in a patient on Daptomycin presenting with respiratory failure, as timely discontinuation favors a good prognosis Reference #1: Uppal P, LaPlante KL, Gaitanis MM, Jankowich MD, Ward KE. Daptomycin-induced eosinophilic pneumonia - a systematic review. Antimicrob Resist Infect Control. 2016;5:55. Published 2016 Dec 12. doi:10.1186/s13756-016-0158-8 Reference #2: Kumar S, Acosta-Sanchez I, Rajagopalan N. Daptomycin-induced Acute Eosinophilic Pneumonia. Cureus. 2018;10(6):e2899. Published 2018 Jun 30. doi:10.7759/cureus.2899 Reference #3: Bartal C, Sagy I, Barski L. Drug-induced eosinophilic pneumonia: A review of 196 case reports. Medicine (Baltimore). 2018;97(4):e9688. doi:10.1097/MD.0000000000009688 DISCLOSURES: No relevant relationships by Chika Winifred Akabusi No relevant relationships by Shazia Choudry No relevant relationships by Hector Ojeda-Martinez No relevant relationships by Mario Torres
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Human induced pluripotent stem cell (iPSC) derived intestinal organoids (HIOs) represent an inexhaustible cellular resource that could serve as a valuable tool to study viral infections such as SARS-CoV-2 as well as other enteric viruses that infect the intestinal epithelium. Intestinal symptoms of COVID-19 are present in a significant number of patients, and include nausea, diarrhea, and viral RNA shedding in feces. Using this platform we found that SARS-CoV-2 productively infects both proximally and distally patterned HIOs, leading to the release of infectious viral particles while stimulating a robust transcriptomic response, including a significant upregulation of interferon-related genes that appeared to be conserved across multiple epithelial cell types. These findings illuminate a potential inflammatory epithelial-specific signature that may contribute to both the multisystemic nature of COVID- 19 as well as its highly variable clinical presentation. We are now expanding our studies to investigate the role of Ebola virus infection in intestinal epithelial injury.