A case of possible drug-induced liver injury due to COVID-19 vaccine.

The patient presented with nausea, appetite loss, and fatigue. She had received two doses of Pfizer/BioN-Tech BNT162b2 mRNA vaccine (COMIRNATY) for coronavirus disease 2019 (COVID-19). Acute liver injury was noted 14 days after the first dose of the vaccine. Re-exposure through the second dose worsened the liver injury. After liver biopsy on the third day of admission, methylprednisolone (1000 mg) was administered. Liver histology showed acute hepatitis with diffuse lobular inflammation/necrosis and lymphocyte-dominant infiltra-tion in the portal areas. The patient was diagnosed with drug-induced liver injury due to the COVID-19 vaccine based on the Digestive Disease Week Japan 2004 (DDW-J) scale, which assesses the temporal relationship, liver biopsy, and laboratory findings. With improvements in the blood test parameters, prednisolone was gradually tapered and stopped. One month later, no biochemical signs of relapse were noted. To our knowledge, this is the first report describing liver injury after the administration of the Pfizer COVID-19 vaccine in Japan.Copyright © 2022 The Japan Society of Hepatology.

Multifactorial Effects of Covid-19: A Review of Published Autopsy Reports

Introduction: SARS-CoV-2 is responsible for the current global pandemic. SARS-CoV-2 infection underlies the novel viral condition coronavirus disease 2019 (COVID-19). COVID-19 causes significant pulmonary sequelae contributing to serious morbidities. The pathogenesis of COVID-19 is complex with a multitude of factors leading to varying levels of injury numerous extrapulmonary organs. This review of 124 published articles documenting COVID- 19 autopsies included 1,142 patients. Method(s): A PubMed search was conducted for COVID-19 autopsy reports published before March 2021 utilizing the query COVID-19 Autopsy. There was no restriction regarding age, sex, or ethnicity of the patients. Duplicate cases were excluded. Findings were listed by organ system from articles that met selection criteria. Result(s): Pulmonary pathology (72% of articles;866/1142 patients): diffuse alveolar damage (563/866), alveolar edema (251/866), hyaline membrane formation (234/866), type II pneumocyte hyperplasia (165/866), alveolar hemorrhage (164/866), and lymphocytic infiltrate (87/866). Vascular pathology (41% of articles;771/1142 patients): vascular thrombi (439/771)-microvascular predominance (294/439)-and inflammatory cell infiltrates (116/771). Cardiac pathology (41% of articles;502/1142 patients): cardiac inflammation (186/502), fibrosis (131/502), cardiomegaly (100/502), hypertrophy (100/502), and dilation (35/502). Hepatic pathology (33% of articles;407/1142 patients): steatosis (106/402) and congestion (102/402). Renal pathology (30% of articles;427/1142 patients): renal arteries arteriosclerosis (111/427), sepsis-associated acute kidney injury (81/427) and acute tubular necrosis (77/427). Conclusion(s): This review revealed anticipated pulmonary pathology, along with significant extrapulmonary involvement secondary to COVID-19, indicating widespread viral tropism throughout the human body. These diverse effects require additional comprehensive longitudinal studies to characterize short-term and long-term COVID-19 sequelae and inform COVID-19 treatment.

Lung pathology

The series of autopsies reported since the beginning of the pandemic have highlighted several patterns of lung damage, both isolated and combined. The factors influencing the occurrence of these different tissue responses to viral aggression by SARS-CoV-2 have not yet been determined. In asymptomatic patients or patients with respiratory symptoms who were not ventilated, lymphocyte pneumonia associated with type II pneumocyte atypical hyperplasia and a few hyaline membranes or focal lesions of acute fibrinous pneumonia have been observed. In critically ill patients, the most frequent pattern is diffuse alveolar damage with interstitial lymphoid infiltration, type II pneumocyte atypia and, very often, capillary or arteriolar microthromboses and/or endothelitis. The precise description of these lesions, which is becoming more and more consensual, makes it possible to understand the favourable effects of corticosteroid therapy in seriously ill patients and the evolution under ventilation towards fibrosis.Copyright © ERS 2021.

Complications Of A Severe Case Of Multisystem Inflammatory Syndrome In Children

Case Presentation: A 10 year old male with prior COVID-19 exposure presented with 7 days of fever, rash, cough, vomiting, and hypotension. Laboratory evaluation was notable for SARS-CoV2 antibodies, elevated cardiac enzymes, BNP, and inflammatory markers. Initial echocardiogram showed normal cardiac function and a small LAD coronary aneurysm. He was diagnosed with Multisystemic Inflammatory Syndrome in Children (MIS-C) and given methylprednisolone and IVIG. Within 24 hours, he developed severe LV dysfunction and progressive cardiorespiratory failure requiring VA-ECMO cannulation and anticoagulation with bivalirudin. Cardiac biopsy demonstrated lymphocytic infiltration consistent with myocarditis. On VA-ECMO, he had transient periods of complete AV block. With immunomodulator treatment (anakinra, infliximab) and 5 days of plasmapheresis, inflammatory symptoms and cardiac function improved. He weaned off ECMO, and anticoagulation was transitioned to enoxaparin. He had left sided weakness 5 days later, and brain MRI revealed an MCA infarct. Ten days later, he had focal right sided weakness and repeat MRI showed multiple hemorrhagic cortical lesions, thought to be thromboembolic with hemorrhagic conversion secondary to an exaggerated inflammatory response to an MSSA bacteremia in the setting of MIS-C. Enoxaparin was discontinued. After continued recovery and a slow anakinra and steroid wean, he has normal coronary arteries, cardiac function, and baseline ECG but requires ongoing neurorehabilitation. Discussion(s): COVID-19 infection in children is often mild, but MIS-C is an evolving entity that can present with a wide range of features and severity. This case highlights two concepts. While first degree AV block is often reported in MIS-C, there is potential for progression to advanced AV block. Close telemetry monitoring is critical, especially if there is evidence of myocarditis. MIS-C shares features with Kawasaki disease, with a notable difference being a higher likelihood of shock and cardiac dysfunction in MIS-C. In MIS-C patients with cardiovascular collapse requiring ECMO, there is a risk for stroke. There should be a low threshold for neuroimaging and multidisciplinary effort to guide anticoagulation in these complex cases.

Activated CD8 T-cell hepatitis in children: a single institution experience

Background: Pediatric acute liver failure is a rare and serious life-threatening situation, principally for the 30 to 50% of children in whom the etiology of their liver failure is unclear or indeterminate. Treating these patients is challenging, requiring constant assessment over time with regular evaluation for possible liver transplantation. Children with pediatric acute liver failure of undetermined etiology have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. Emerging evidence suggests that a subgroup of patients with indeterminate pediatric acute liver failure have clinical, laboratory, and liver biopsy features of immune dysregulation with a dense infiltration of CD8 T cells. Method(s): In 2022, we received percutaneous liver biopsies from three children with acute hepatic dysfunction that showed an increased number of lymphocytes including CD8 T cells. For each case, routine H&E stains with levels, special stains and immunostains were performed. The first biopsy was from an 18-month-old male who presented with COVID infection, pancytopenia, elevated transaminases, and synthetic liver dysfunction (elevated INR). The second was from a 9-year-old female with a history of elevated liver enzymes with no clear cause. The third case was from a 2-year-old male with elevated liver enzymes, coagulopathy, and cholestasis. Result(s): The three cases showed similar histopathologic findings;an acute liver injury pattern with lobular architectural disarray, giant cell formation, reactive changes, single cell necrosis, cholestasis and marked mixed lymphocytic infiltrates. The infiltrates were predominantly composed of CD8-positive T-lymphocytes with scattered neutrophils, eosinophils and rare plasma cells. Portal areas were mildly expanded with mild bile ductular proliferation and mild to moderate lymphocytic infiltrates. Immunostains for CD8 demonstrated that the infiltrates were predominantly composed of CD8-positive T-lymphocytes. All three patients received steroids and responded to treatment evidenced by normalization of liver enzymes and function. Conclusion(s): Dense hepatic CD8 T-cell infiltration is a major finding inactivated CD8 T-cell hepatitis. However, the percentage distribution of lymphocyte subtypes in the setting of hepatitis is not well established, and CD8 T-cell infiltration has also been described in cases of drug-induced hypersensitivity reactions, viral hepatitis, hemophagocytic lymphohistiocytosis, and macrophage activation syndrome, as well as autoimmune hepatitis. Further investigation is needed to better understand the diagnostic criteria in this disease.

Novel heterozygous PLCG2 variant presenting with very early-onset perianal abscess

Case report Background: Mutations in the PLCG2 gene can cause PLCG2-associated antibody deficiency and immune dysregulation (PLAID) or auto-inflammation with PLCG2-associated antibody deficiency and immune dysregulation (APLAID). PLAID is characterized by urticarial eruptions triggered by evaporative cooling along with cutaneous granulomas. APLAID may present with early-onset skin inflammation and non-infectious granulomas, uveitis, and colitis. Method(s): Case report and literature review. We performed in silico analysis for variants of uncertain significance (VUS). Result(s): A 29-day-old boy presented to emergency department for failure to thrive. He was found to be SARS-CoV2 positive, had an E. coli UTI in the setting of bilateral perinephric masses which subsequently resolved. He also had a perianal soft tissue abscess measuring 4cm in diameter. Mom reported a similar infection when she was age 2. She also reported intermittent diffuse urticaria triggered following perspiration evaporation.Abscess wall histology showed diffuse neutrophil and lymphocytic infiltration, with cultures growing polymicrobial enteric flora. His serum immunoglobulins G, A, M, and E were within reference range. Naive and memory CD4, CD8, CD19 lymphocyte subsets (including NK cells) were also within age-appropriate reference range. He had a normal neutrophil oxidative burst measured using dihydrorhodamine (DHR) flow cytometry following PMA stimulation, which ruled out a diagnosis of chronic granulomatous disease. On evaporative cooling, the patient had a 2mm wheal with surrounding erythema which resolved rapidly with warming. A targeted primary immunodeficiency panel showed a heterozygous VUS in PLCG2, c.688C > G (p.Leu230Val). The variant was absent from major databases and had a calculated CADD score of 17.77. He had symptomatic resolution after completing 3 weeks of ceftriaxone and metronidazole antimicrobials. Given the concern for PLCG2-associated very early-onset inflammatory bowel disease (VEO-IBD), a fecal calprotectin was obtained at 3 months and found to be elevated (157 mcg/g [ < = 49 mcg/g]). However, he had no symptomatic or macroscopic evidence for VEO-IBD. Conclusion(s): Presence of very early onset abscesses has not been previously described in patients with heterozygous PLCG2 deficiency. This case adds to the expanding variable phenotype of PLCG-2-associated immune dysregulation.

Clinical, Histological and Serological Features of Autoimmune-Like Acute Liver Injury after Sars-Cov-2 Vaccination

Introduction and Objectives: Acute autoimmune-like liver injury has been increasingly reported after vaccination against SARS-CoV-2. Pathogenesis, steroid requirement and long-term prognosis are unknown. This study aimed to evaluate clinical, serological and histological features, response to treatment and prognosis in patients with post-vaccination acute hepatitis. Material(s) and Method(s): We included patients without known pre-existing liver diseases with transaminase levels >= 2.5 upper limits of normal within 90 days after the SARS-CoV-2 vaccine with an available liver biopsy. Clinical data and outcomes after a six months follow-up were collected. Result(s): 17 patients were included,12 females, median age 60 (51,5/66) exposed to vectorial (Sputnik V n=7, AstraZeneca n=6), inactivated (Sinopharm n=3) or ARNm Vaccines (Moderna=1). In 8 patients, liver injury developed after the first dose and in 7 after the second dose and in 2 after the third dose. The median time to the development of injury was 33(23,50/53,50) days. Eight patients had a history of extrahepatic autoimmune disease and five patients had metabolic syndrome and used statins. Immune serology showed anti-antinuclear antibody in 10 (58,8%), anti-smooth muscle antibody in 5(29,4%). 14/17 patients presented with elevated IgG levels. Liver histology showed lobular hepatitis in 13/17, portal hepatitis in 17/17 with plasmocytic lymphocytic infiltrate and 4/17 had eosinophils, 6/17 with severe interface hepatitis, and one patient had fibrosis Ishak stage >=3. 12/17 (70,5%) were treated with steroids. Transaminases improved in 17 cases and normalized in 6/12 by month 6. Only 1/17 developed liver function deterioration, yet no patient required liver transplantation. Most patients tolerated the tapering of steroids and in 6 azathioprine was started before month 3. Conclusion(s): Long-term follow-up might help to differentiate between induced classical autoimmune hepatitis, autoinflammatory self-limited events, or drug-induced liver injury in these patients.Copyright © 2023

Pathogenetic Aspects of the Development of Acute Kidney Injury in Covid 19: Own Observation Data

Introduction: The coronavirus infections ( disease) (COVID-19) pandemic 2019 caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) began in December 2019 and has affected millions of lives worldwide, even though many aspects of the disease are still unknown.Current data shows that many hospitalized patients with COVID-19 suffer from kidney damage manifesting as proteinuria, hematuria, or acute kidney injury (AKI). AKI is especially common among severely and critically ill patients with COVID-19 and may be a predictor of mortality.The pathophysiology of AKI associated with COVID-19 may be due to non-specific mechanisms, but also to mechanisms specific to COVID. Evaluation of morphological changes in the kidneys and their mechanisms could help determine their spectrum and immediate or long-term effects. The aim of our study was to compare the initial clinical and laboratory data of patients with COVID 19 who developed AKI and to analyze the morphological changes in the kidneys that underwent autopsy when patients died of COVID 19 with AKI. Method(s): We conducted a preliminary retrospective analysis of cured patients with COVID 19 and AKI during the pandemic period of July 2021 - December 2021. We analyzed the clinical and laboratory parameters of 2 groups of patients: thise who survived and thise who died of AKI caused by COVID 19. We also studied he main frequently detected morphological changes in the renal biopsy: the subject ground was a dead group. Statistical processing of the obtained data was performed using the STATA program. The two groups were compared, and the statistical significance of the scores of the two groups was calculated using the Mann Whitney analysis and the chi-quadrant Results: According to the results of analyzes of clinical and laboratory parameters, it can be summarized that in the group of the dead in 80% of patients, the volume of lung damage is more than the deceased than the survivors. There is a deep lymphopenia and thrombinemia in the group of the dead. The level of azotemia also prevails in the group of the deceasedAccording to our studies, out of 10 lethal cases, 90% of the histology of samples taken from the kidneys of those who died from COVID 19 revealed the following changes: edema and plethora of renal glomeruli, atrophy and sclerosis from 10-50% of the glomeruli. In the tubules, total necrosis of the epithelium. In the stroma, vascular thrombosis, focal sclerosis with lymphoid infiltration, small focal hemorrhages [Formula presented] Conclusion(s): Acute kidney injury remains a fairly common and serious manifestation of the severe course of COVID 19. Regardless of the type of development of the mechanism, it is often associated with high mortality. Our results of the study can serve as a subject for further research. No conflict of interestCopyright © 2023

Morphological changes in testicles of patients with idiopathic infertility after novel coronavirus infection (COVID-19)

Introduction. SARS-CoV-2 causes several negative processes in the body and complicates the course of chronic somatic diseases, causing dysfunction and having a negative effect on many organs and systems of the body, including organs of the reproductive system. Objective. To study morphological changes in testicles of patients who have undergone a new coronavirus infection. Materials and methods. Objects of morphological research were testicular tissues obtained by intraoperative biopsy under intravenous anesthesia served. Material sampling was carried out in 12 patients aged 25–29 years with idiopathic infertility who underwent COVID-19. Patients showed ultrasound signs of fibrosis in the testicles, which were absent before infection with SARS-CoV-2. The biopsy was performed 12 months after COVID-19. Results. In all observations, changes were observed that are characteristic of the inflammatory process, nonbacterial autoimmune genesis. Histio-lymphocytic infiltration of testicular tissue with destruction of single tubules and parenchyma atrophy, combined with varying degrees of sclerosis, was verified. Conclusion. In testicular biopsy specimens from patients who have undergone COVID-19, an autoimmune inflammatory process is recorded, manifested by lymphocytic infiltration of testicular tissue, which was combined with varying degrees of sclerosis. © Vestnik Urologii 2022.

Isolated cerebral mucormycosis in post-COVID-19 pneumonia

Background: Rhino-orbital-cerebral and isolated cerebral involvement of basal ganglia by mucormycosis are two different manifestations of CNS mucormycosis. The former variant caused by inhaled fungal spores and is common with immunosuppressive conditions. The latter form is caused by intravascular inoculation of spores as seen in intravenous drug abusers. Case report: Here we describe a case of young, non-addict patient with a history of recent mild COVID-19 pneumonia who presented with isolated cerebral mucormycosis involving bilateral basal ganglia. Discussion(s): The pulmonary vasculitis associated with COVID-19 is probably the cause of direct intravascular entry of inhaled fungal spores leading to direct isolated cerebral involvement. Such condition may rapidly turn fatal. Conclusion(s): This is the first reported case of isolated cerebral mucormycosis following post-COVID-19 infection. Early tissue diagnosis and intravenous amphotericin B is the key management.Copyright © 2022

Pathologic Characteristics of Digestive Tract and Liver in Patients with Coronavirus Disease 2019.

With the high prevalence of coronavirus disease-2019 (COVID-19), there has been increasing understanding of the pathologic changes associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review summarizes the pathologic changes in the digestive system and liver associated with COVID-19, including the injuries induced by SARS-CoV2 infection of GI epithelial cells and the systemic immune responses. The common digestive manifestations associated with COVID-19 include anorexia, nausea, vomiting, and diarrhea; the clearance of the viruses in COVID-19 patients with digestive symptoms is usually delayed. COVID-19-associated gastrointestinal histopathology is characterized by mucosal damage and lymphocytic infiltration. The most common hepatic changes are steatosis, mild lobular and portal inflammation, congestion/sinusoidal dilatation, lobular necrosis, and cholestasis.

Sars-Cov-2 Induces a Sjogren's Syndrome-Like Phenotype

Sjogren's syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration and the development of dry eyes and dry mouth due to the secretory dysfunction of the lacrimal and salivary glands. In recent years, infectious pathogens have been proved to be associated with SS, including Cytomegalovirus, Coxsackie, EBV, and lymphotropic virus-1 (HTLV-1). Studies suggest that infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger an autoimmune response, as evidenced by increased autoantibodies in patients diagnosed with Coronavirus disease 2019 (COVID-19). To investigate the relationship between SARS-CoV-2 and SS, the study was performed by infecting humanized ACE2 mice with SARS-CoV-2. Mice infected with the virus showed a decreased saliva flow rate, elevated antinuclear antibodies (ANAs) and anti-SSB/La, and lymphocyte infiltration in the lacrimal and salivary glands. We detected the viral nucleocapsid protein in mice exocrine glands with significant apoptotic bodies by the acinar cells. Confirmed with clinical data, we also observed the elevation of SS-specific autoantibodies (ANA, anti-SSB/Ro52, and anti-SSA/La) and specific ANA patterns in sera from COVID-19 patients. One unique aspect of SS is the high degree of sexual dimorphism, with women being affected 10-20 times more than men. To determine whether COVID-19 patients exhibited an element of sexual dimorphism in the autoantibody response, we grouped the sera by sex. We found the male patients showed elevated anti-SSA/Ro52 compared to female patients (p=0.0029), and female patients had more diverse ANA patterns. Lastly, monoclonal antibodies isolated from recovered patients using singlecell antibody nanowells technology were shown to recognize the nuclear antigens. Overall, by observing SS-like phenotypes in mouse models and patients, our study confirms a direct pathogenic role of SARS-CoV-2 in SS.

CYSTIC LUNG DISEASE IN A YOUNG MALE WITH SYSTEMIC LUPUS ERYTHEMATOSUS

SESSION TITLE: Challenges in Cystic Fibrosis Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Pulmonary involvement in Systemic Lupus Erythematosus (SLE) is seen in 30-50% of patients (most commonly Nonspecific Interstitial Pneumonitis) but cystic lung disease is extremely rare (1). Lymphoid interstitial pneumonia (LIP) is an inflammatory lung disease that is characterized by infiltration of lymphocytes and plasma cells (2), and associated with lung cysts. Oftentimes, it is associated with HIV, lymphoma, and primary Sjogren's Syndrome (SS) (2), however there are rare reports of LIP associated with SLE (1). We present a case of a young male with incidental lung cysts who was found to have a new diagnosis of SLE. CASE PRESENTATION: A 24-year-old male with a past medical history of premature birth at 5 months and prior mild COVID-19 infection presented with 3 weeks of abdominal pain, nausea, vomiting, fever, and unintentional 15-pound weight loss. He endorsed dry mouth, frequent cavities, and a new rash involving his chest, face, and lower extremities. Physical exam was significant for malar rash and dry mucous membranes. Labs revealed pancytopenia, sedimentation rate 61 mm/hour and C-reactive protein 5.54 mg/L. Computed tomography (CT) of the chest showed several thin-walled cysts in all bilateral lung lobes (predominant in right upper lobe) and bilateral axillary lymph nodes [Figure 1]. CT abdomen and pelvis was unremarkable. Autoimmune work-up resulted in a positive antinuclear antibody >1:1280, double stranded DNA antibody elevated at 34, elevated SSA and SSB antibodies (>8.0 and 1.4 respectively), and decreased Complement 3 (59.5 mg/dl) and 4 (10.1 mg/dl) levels. Peripheral smear, right axillary lymph node and bone marrow biopsies were negative for malignancy. He was started on prednisone and Plaquenil with symptomatic improvement. There is high suspicion of LIP given the clinical and radiological findings. He will follow up in clinic to obtain PFTs and schedule a lung biopsy. DISCUSSION: Interstitial lung disease in SLE presents in middle-aged patients at a later part of their disease course, with a female preponderance (2,3). An initial presentation of SLE and secondary SS in a young male and associated cystic lung disease is rare. The suspicion for LIP in association with SLE is high in our patient given variable size and distribution of lung cysts and coexisting secondary Sjogren's syndrome, although no ground glass or nodular opacities were found on CT chest as reported in typical LIP (3). Though this patient has no pulmonary symptoms, cysts/LIP in SLE tend to progress and have a high incidence of developing lymphomas, gammaglobulinemia and amyloidosis (2,3). CONCLUSIONS: It is important to establish a histopathological diagnosis and obtain baseline PFTs to monitor pulmonary disease manifestations. In addition to controlling the primary disease with antirheumatic drugs, steroids have been found to be useful in acute pulmonary flares (2). Reference #1: Maeda R, Isowa N, Miura H, Tokuyasu H. Systemic lupus erythematosus with multiple lung cysts. Interact Cardiovasc Thorac Surg. 2009 Jun;8(6):701-2. doi: 10.1510/icvts.2008.200055. Epub 2009 Mar 12. PMID: 19282324. Reference #2: Yood RA, Steigman DM, Gill LR. Lymphocytic interstitial pneumonitis in a patient with systemic lupus erythematosus. Lupus. 1995 Apr;4(2):161-3. doi: 10.1177/096120339500400217. PMID: 7795624. Reference #3: Filipek MS, Thompson ME, Wang PL, Gosselin MV, L Primack S. Lymphocytic interstitial pneumonitis in a patient with systemic lupus erythematosus: radiographic and high-resolution CT findings. J Thorac Imaging. 2004 Jul;19(3):200-3. doi: 10.1097/01.rti.0000099464.94973.51. PMID: 15273618. DISCLOSURES: No relevant relationships by Matthew Fain No relevant relationships by Christina Fanous No relevant relationships by Rathnavali Katragadda No relevant relationships by CHRISELYN PALMA

A CASE OF COMMON VARIABLE IMMUNODEFICIENCY (CVID) COMPLICATED BY GRANULOMATOUS LYMPHOCYTIC INTERSTITIAL LUNG DISEASE (GLILD) TRIGGERED BY RECENT COVID-19 INFECTION

SESSION TITLE: Unique Inflammatory and Autoimmune Complications of COVID-19 Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by low serum IgG, IgA and/or IgM, and poor specific antibody production. CVID is estimated to affect as many as 1 in 25,000 individuals. Chronic lung disease is a common problem in patients with CVID. About 10-20% of patients have lymphocytic infiltrates and/or sarcoid-like granulomas, with several histological findings, termed granulomatous and lymphocytic interstitial lung disease (GLILD). CASE PRESENTATION: Patient is a 61-year-old Caucasian woman with a history significant for CVID in remission who presented to the Pulmonary Clinic with a chief compliant of dyspnea of exertion (DOE). Patient was not suffering from any respiratory complaints until the diagnosis of severe COVID-19 pneumonia 4 months prior. For the following months, patient was slowly improving but was still suffering from severe DOE that has negatively impacted her quality of life. Patient has a remote history of smoking, having quit 10 years ago. Patient denied any joint pain, stiffness, swelling, skin rash, muscle ache, or weakness. No known history of SLE, Rheumatoid Arthritis, or other collagen vascular disorders had been reported. Patient denied any exposure to birds. Physical exam was significant only for bilateral basal rales with no wheezing or crackles. No skin rash, joints deformities, or clubbing was noticed. Laboratory studies revealed ESR was 17 with a CRP of 10.6. Negative ANA, SM, RNP, and SSA/SSB antibodies. Her Immunoglobulins levels were low with IgG 382 (nl > 610) and IgA < 2 (nl > 85). Her PFT revealed severe restrictive process with TLC 46% of predicted and severe reduction in DLCO at 35%. CT chest revealed diffuse central groundglass opacities, and interstitial thickening with traction bronchiectasis. Lung biopsy via VATS revealed lung parenchymal with focal, noncaseating granulomas, foci of focal interstitial lymphocytic infiltration and fibrosis;features consistent with Granulomatosis-Lymphocytic Interstitial Lung Disease (GLILD). Systemic steroid initiated and for the following weeks patient reports significant improvement in DOE. Her PFT at 3 month follow up showed significant improvement in FVC (5% increase), TLC (11% increase), and DLCO (5% increase). DISCUSSION: The respiratory manifestations of CVID follow two main mechanisms: injury due to acute or recurrent infections and damage due to poorly understood immune-mediated processes. Severe COVID-19 results in dysregulated immune and inflammatory response that can worsen an underlying lung disease. Previous cases have been reported about CVID with GLILD complicated with COVID-19 infection but not vice versa. CONCLUSIONS: To our knowledge, this is a rare case of CVID complicated by GLILD triggered by recent COVID-19 infection. However, little is known about the association between COVID-19 infection and GLILD and further investigation is needed. Reference #1: Ho HE, Mathew S, Peluso MJ, Cunningham-Rundles C. Clinical outcomes and features of COVID-19 in patients with primary immunodeficiencies in New York City. J Allergy Clin Immunol Pract. 2020;S2213–2198(20):31102–8. Reference #2: Prasse A, Kayser G, Warnatz K. Common variable immunodeficiency-associated granulomatous and interstitial lung disease. Curr Opin Pulm Med. 2013;19:503–9. Reference #3: Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34–48. DISCLOSURES: No relevant relationships by husam nayef No relevant relationships by Arshia Vahabzadeh No relevant relationships by Zaid Yaqoob No relevant relationships by Mohammad Zalt

A CHALLENGING DIAGNOSIS OF CELLULAR NONSPECIFIC INTERSTITIAL PNEUMONIA (NSIP) WITH ORGANIZING PNEUMONIA IN A PATIENT WITH ANTI-JO 1 NEGATIVE DERMATOMYOSITIS

SESSION TITLE: Autoimmune Diffuse Lung Disease Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Nonspecific interstitial pneumonia (NSIP) is an interstitial lung disease (ILD) that can be idiopathic or associated with connective tissue disorders (CTDs). The two subtypes of NSIP are cellular interstitial pneumonitis (CIP) and fibrotic, with CIP being less common. Subtypes can be distinguished through pathology and imaging. NSIP constitutes 14-36% of cases of idiopathic interstitial pneumonias. ILD-associated DM has a higher mortality, making diagnosis crucial. In specific, fibrotic NSIP has a high 10-year mortality rate, making differentiation relevant. CASE PRESENTATION: A 36-year-old female presented with fatigue and erythematous papular lesions on her face, palms, shoulder, and neck for one month. She also developed a fever and dry cough a week before. She denied recent travel or sick contacts. COVID-19 was negative. On exam, she was tachypneic and tachycardic with a maculopapular rash. A pulmonary exam revealed bilateral fine crackles. CXR showed dense left and mild right-sided patchy consolidations. Labs revealed elevated inflammatory markers (ESR-63, CRP-1.9, LDH-982). CPK was high - 517. CBC and procalcitonin were normal. CT showed extensive patchy and confluent areas of opacification of the left lower lobe, including a mass-like area measuring 3.3cm. Infectious workup was negative. Autoimmune testing ( Anti-Jo 1 Ab, ANA, etc) was negative. Bronchoscopic left lower lobe biopsy showed cellular interstitial inflammation composed of lymphocytes, plasma cells, rare eosinophils, and foci of intra-alveolar fibrinous exudates, suggestive of CIP and OP. She was treated successfully with corticosteroids and was discharged on prednisone. Repeat autoimmune antibody workup was negative. Skin biopsy showed a lichenoid lymphocytic infiltrate and necrotic keratinocytes consistent with dermatomyositis. Mycophenolate and rituximab were initiated;prednisone was tapered off. Follow-up chest CT showed cleared infiltrates with symptomatic improvement. DISCUSSION: CIP is an uncommon form of NSIP. On CT, bilateral ground-glass opacities are the most common feature. CIP is characterized histologically by interstitial thickening due to the presence of inflammatory cells and type-II pneumocyte hyperplasia with preserved lung architecture. Treatment is corticosteroids. The prognosis is excellent. ILD associated with DM is strongly associated with a positive Anti-Jo Ab, which was negative here making diagnosis challenging. She was diagnosed with dermatomyositis using histological findings from a skin biopsy. She responded to steroids at acute presentation and treatment was tailored once DM was diagnosed leading to complete recovery. CONCLUSIONS: ILD is not uncommon in CTD, however it is usually associated with a positive Anti-Jo 1 antibody. Our case is unique as the patient had negative Anti- Jo 1 Ab, however was found to have cellular NSIP with DM responding well to treatment following diagnosis. Reference #1: https://ard.bmj.com/content/63/3/297 Reference #2: https://www.ncbi.nlm.nih.gov/books/NBK518974/ Reference #3: https://pubmed.ncbi.nlm.nih.gov/33916864/ DISCLOSURES: No relevant relationships by Nawal Ahmed No relevant relationships by TAIKCHAN LILDAR No relevant relationships by Namratha Shripad No relevant relationships by David Wisa

SEVERE ALLERGIC ERYTHEMATOUS REACTION POSTMESSENGER RNA-BASED COVID-19 VACCINE

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Covid 19 pandemic has infected 125 million people so far (1). The development of safe and effective vaccines is crucial to lessen the impact of SARS-COV 2 on global health. Some adverse events of the covid 19 vaccination have been reported including few dermatological reactions. We report a case of severe allergic erythematous drug reaction that occurred 3 days after the second dose of messenger RNA (mRNA) Pfizer vaccine. CASE PRESENTATION: A 42 year old female with past medical history of Grover's disease and Multiple Sclerosis presented to the Emergency department from the nursing home with complaints of erythematous, scaly, painful rash that occurred 3 days after the second dose of mRNA covid 19 vaccine. Patient states she had a generalized rash after the first dose of vaccine but it resolved spontaneously and did not require treatment. This time the rash started on the scalp and gradually progressed to the rest of the body. It was associated with severe itching, burning and serosanguinous discharge. Patient did not report any change in medication, use of new detergent or contact with an offending agent. The patient denied fever, chills, nausea, vomiting, diarrhea, constipation, abdominal pain, chest pain or palpitations. She had no history of similar complaints in the past. On physical examination, she was afebrile and hemodynamically stable but in severe distress due to pain. The rash covered 95% of the body surface area and was more severe around the mouth, in the axilla, neck and the inframammary area. Erosions could be seen in the skin folds with serosanguinous discharge. The laboratory results were positive for eosinophilia with absolute eosinophil count of 0.7. Remaining laboratory results were within normal limits. The pathology report for the erythematous rash was consistent with drug reaction. A slight vacuolar degeneration along the dermal epidermal junction with few apoptotic keratinocytes were noted. A compact horn and band-like lymphoid infiltrate were also noted. The patient was started on high dose steroids, analgesics and antihistamines. Petroleum gel impregnated gauze was used for dressing. She was placed in the intensive care unit for careful monitoring. Her rash resolved gradually and her symptoms improved. DISCUSSION: mRNA vaccines are associated with type 1 interferon responses that result in inflammation and autoimmune conditions. This could explain the skin manifestations associated with these vaccines. Allergenic components in the vaccines could also be a possible cause of these reactions. A patch test can be performed to prevent these reactions in susceptible individuals. CONCLUSIONS: This report highlights the need for vigilance to detect severe allergic reactions after covid 19 vaccination to improve the safety of the vaccine. Reference #1: WHO coronavirus (COVID-19) dashboard. [ Jul;2021 ];https://covid19.who.int/ 2021 DISCLOSURES: No relevant relationships by Ruhma Ali No relevant relationships by Sneha Bijoy No relevant relationships by Chrystina Kiwan no disclosure on file for Richard Miller;No relevant relationships by Aditya Patel No relevant relationships by jihad slim, value=Honoraria Removed 03/25/2022 by jihad slim No relevant relationships by jihad slim, value=Honoraria Removed 03/25/2022 by jihad slim No relevant relationships by jihad slim, value=Honoraria Removed 03/25/2022 by jihad slim No relevant relationships by jihad slim, value=Honoraria Removed 03/25/2022 by jihad slim No relevant relationships by jihad slim, value=Honoraria Removed 03/25/2022 by jihad slim

ACCELERATED GRANULOMATOUS LYMPHOCYTIC INTERSTITIAL LUNG DISEASE DUE TO COVID-19 IN A PATIENT WITH COMMON VARIABLE IMMUNODEFICIENCY PRESENTING WITH RECURRENT PNEUMOTHORACES

SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Patients with COVID-19 usually recover completely in the acute setting but it has been demonstrated post-infectious complications include continued dyspnea, myalgias, and other long-term complications which are not fully known yet. A case published in the British Medical Journal by Nunna demonstrated the development of a large spontaneous pneumothorax in a middle-aged patient after his Covid-19 infection [1]. Here, we present a 60-year-old female with a history of common variable immunodeficiency (CVID) and hypothyroidism presenting with recurrent pneumothoraxes as a late complication of COVID-19. CASE PRESENTATION: A 60-year-old female with a history of CVID and COVID-19 pneumonia complicated by chronic hypoxic respiratory failure and a right sided loculated hydropneumothorax diagnosed in December of 2020, on 3 to 5 liters of home oxygen, presents to the emergency department due to dyspnea and left-sided pleuritic chest pain in July of 2021. On presentation, the patient was tachypneic, had labored breathing and was requiring 7 liters of oxygen to saturate adequately. Repeat imaging of the chest showed a large tension pneumothorax on the left side with near complete collapse of the lung and tracheal deviation to the right [figure 1]. At that time, a chest tube was placed to re-expand the lung. After 5 days of treatment, repeat imaging showed marked improvement, with the pneumothorax decreasing significantly [figure 2]. Pulmonary function testing in the outpatient setting showed a moderate restrictive lung defect with sever decrease in diffusion capacity. The patient continued to have dyspnea so, the decision was made for the patient to undergo an open lung biopsy. The pathology report showed noncaseating granulomas with focal interstitial fibrosis and lymphocytic infiltrates consistent with granulomatous lymphocytic interstitial lung disease (GLILD), which is a complication of CVID [figure 3]. Roughly 1 in 5 patients with CVID develop histopathological findings consistent with GLILD[2]. We believe these changes were accelerated due to her COVID-19 infection. DISCUSSION: This case habits the importance of continued consideration for long-term complications of COVID-19, especially in patients who are immunocompromised. Reports of diffuse alveolar injury caused by the virus can result in emphysematous changes ultimately leading to alveolar rupture such as in this patient [3]. Although pneumothorax is an uncommon late complication, it should be on the differential diagnosis for COVID-19 patients with sudden respiratory decompensation. As a life-threatening event, it requires prompt recognition and treatment. CONCLUSIONS: Patients who have CVID complicated by GLILD accelerated by COVID-19, are more prone to life-threatening tension pneumothoraxes and they should be encouraged to seek lung transplantation as this could be the only way to stop the formation of these pneumothoraxes. Reference #1: Nunna, K., & Braun, A. B. (2021). Development of a large spontaneous pneumothorax after recovery from mild COVID-19 infection. BMJ Case Reports, 14(1), e238863. Reference #2: Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD): A Spectrum of Pulmonary Histopathological Lesions in Common Variable Immunodeficiency (CVID) - Histological and Immunohistochemical Analysis of 16 cases. (n.d.). Reference #3: Gradica, F. (2020). Spontaneous Pneumothorax in Covid-19 Pneumonia. Case report. Clinical Orthopaedics and Trauma Care, 2(1), 01–03. https://doi.org/10.31579/2694-0248/010 DISCLOSURES: No relevant relationships by Elizabeth Bankstahl No relevant relationships by Talal Bazzi No relevant relationships by Mujtaba Cherri No relevant relationships by Khairya Fatouh

ACUTE INTERSTITIAL NEPHRITIS AS A PRIMARY PRESENTATION OF CANDIDA INFECTIVE ENDOCARDITIS

Introduction: Acute Interstitial Nephritis (AIN) is an important cause of Acute Kidney Injury (AKI), and infections are the second most common etiology, after the drugs. However, AIN following fungal infections is rare. We describe two cases of AIN, which on the investigation turn out to be candidemia following fungal infective endocarditis. Methods: CASE 1: A 65-year-old man with hypertension and diabetes without diabetic or hypertensive retinopathy and prior normal renal function, presented to us with vague abdominal pain with steadily creeping creatinine to 2mg/dl within 2 weeks, and urine showed no albuminuria and sediments. There was no history of any specific drug intake. His hematological and other parameters were normal. Blood and urine cultures were sterile. He underwent a renal biopsy which revealed acute interstitial nephritis (Figure 1). He was started on prednisolone at 1mg/kg/day for 1-week following which he had a rapidly worsening azotemia requiring hemodialysis. Steroids were stopped. Repeat blood cultures were sent which grew candida albicans resistant to flucytosine. Re-evaluation of the fundus revealed macular infarct in the right eye with vitreoretinitis in the left eye suggestive of endophthalmitis. PET CT showed increased FDG uptake in both kidneys suggestive of pyelonephritis. Trans-esophageal echocardiography (TEE) showed aortic valve vegetations. He was treated with antifungals for 3 months. He was dialysis-dependent for 2 weeks. He gradually regained normal renal function 3 weeks after starting anti-fungal agents. CASE 2: A 57-years-old man with diabetic, hypertensive, and no diabetic retinopathy had severe covid pneumonia in June 2021 requiring oxygen and tocilizumab 80 mg for 4 days, recovered with normal renal function. He presented to us 1 month later with unexplained non-oliguric severe AKI requiring dialysis, with bland urine sediments. Renal biopsy showed lymphocytic infiltrates in the interstitium suggestive of AIN (Figure 2). Blood cultures were sterile, but serum beta-D-glucan was elevated at 333 pg/ml. He was Initiated on 1mg/kg of prednisolone, on the presumption of drug-induced AIN. Simultaneously workup for systemic infection revealed mitral anterior leaflet endocarditis. He was initiated on anti-fungal therapy on the advice of an infectious disease specialist and the steroid was stopped. He continued to be dialysis-dependent after 6 weeks, despite anti-fungal agents. Results: [Formula presented] Conclusions: AIN contributes a significant proportion of cases in unexplained AKI. Prompt evaluation with a renal biopsy is warranted. Acute interstitial nephritis particularly due to candidemia can be oligosymptomatic as seen in our two cases. Since steroids have a significant role in treating early AIN, a dedicated search for underlying silent endocarditis and candidemia is advisable before initiating steroid therapy. Ophthalmic fundus evaluation, TEE, and repeat blood culture may be necessary to identify hidden candidemia. We recommend an evaluation to exclude fungal endocarditis in patients with AIN who present with minimal or no symptoms and no definitive cause for AIN is present. No conflict of interest

HISTOPATHOLOGICAL EFFECT OF CHLORINE HEPATOTOXICITY IN MICE

Chlorine is the most common chemical agent that used in the sterilization of water, whether it be across the board or specifically in Iraq. The aim of this study was to look into the livers of mice that exposed to various chlorine concentrations in drinking water. 30 mature male albino mice were allocated into three groups at random and equally. Each group included ten mice from different labor groups who were given ppm (3, 9 ppm). According to the results of histopathological examination, chlorine consumption generated gross pathogenic effect in clinical practice in livers tissue in entire treatment groups, with varying degrees of illness according to the chlorine concentration. Such as degeneration (D) of hepatocytes with nucleus size increase (NE), congestion in the central vein, which was encircled by lymphocyte infiltration (LI) and increase thickness of blood vessels wall.

Morphological changes in testicles of patients with idiopathic infertility after novel coronavirus infection (COVID-19)

Introduction. SARS-CoV-2 causes several negative processes in the body and complicates the course of chronic somatic diseases, causing dysfunction and having a negative effect on many organs and systems of the body, including organs of the reproductive system. Objective. To study morphological changes in testicles of patients who have undergone a new coronavirus infection. Materials and methods. Objects of morphological research were testicular tissues obtained by intraoperative biopsy under intravenous anesthesia served. Material sampling was carried out in 12 patients aged 25–29 years with idiopathic infertility who underwent COVID-19. Patients showed ultrasound signs of fibrosis in the testicles, which were absent before infection with SARS-CoV-2. The biopsy was performed 12 months after COVID-19. Results. In all observations, changes were observed that are characteristic of the inflammatory process, nonbacterial autoimmune genesis. Histio-lymphocytic infiltration of testicular tissue with destruction of single tubules and parenchyma atrophy, combined with varying degrees of sclerosis, was verified. Conclusion. In testicular biopsy specimens from patients who have undergone COVID-19, an autoimmune inflammatory process is recorded, manifested by lymphocytic infiltration of testicular tissue, which was combined with varying degrees of sclerosis.