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.

Covid-19 Vaccination Induced Minimal Changed Disease

Introduction: Minimal change disease (MCD) accounts for approximately 15% of adults with idiopathic nephrotic syndrome (NS). We report the case of minimal change disease in a patient who presented with signs and symptoms of NS following Covid-19 immunisation vaccine. Method(s): Case: A 58-year-old male with negligible past medical history developed generalised swelling 2 days following receiving the Pfizer Covid-19 booster. On examination, he had a blood pressure of 130/80 and anasarca. Relevant laboratory results include a creatinine of 123, estimated glomerular filtration rate (eGFR) of 55, albumin of 9, urine protein: creatinine ratio of 713, and hyaline casts of moderate quantity. A kidney biopsy revealed glomerular sclerosis appropriate for age, and normal vessels and tubules. Immunofluorescence showed negative serology. A diagnosis of minimal change disease was made. The patient was treated with high dose prednisone at 1mg/kg/day and went into remission. The patient was followed up 2 months after admission, and investigations revealed a creatinine of 70, eGFR of >90, albumin of 34 and urine protein:creatine ratio of 58. Result(s): / Conclusion(s): Discussion and conclusion: This is the first case of Covid-19 vaccination induced NS reported in New Zealand. Theorised mechanism of injury includes T-cell mediated immune dysregulation, leading to glomerular disease (Sahin et al., 2020). Different glomerular diseases have been reported to occur for the first time following the Covid-19 vaccination (Klomjit et al., 2021). There has also been reports of reactivation of disease following Covid-19 immunisation (Hartley et al., 2022 and Leong et al., 2021). mRNA vaccination induced NS should be considered in all patients presenting with apparent idiopathic NS. This is especially important as we continue to learn more about the Covid-19 vaccination. No conflict of interestCopyright © 2023

PATHOMORPHOLOGICAL FEATURES OF ACUTE RESPIRATORY DISTRESS SYNDROME IN COMPETING LUNG DISEASES: COVID-19 AND SARCOIDOSIS.

The COVID-19 pandemic is a worldwide problem. The clinical spectrum of SARS-CoV-2 infection varies from asymptomatic or paucity-symptomatic forms to conditions such as pneumonia, acute respiratory distress syndrome and multiple organ failure. Objective was to describe a clinical case of SARS-CoV-2 infection in the patient with sarcoidosis and cardiovascular pathology developing acute respiratory syndrome and lung edema. Material and methods. There were analyzed accompanying medical documentation (outpatient chart, medical history), clinical and morphological histology data (description of macro- and micro-preparations) using hematoxylin and eosin staining. Results. Lung histological examination revealed signs of diffuse alveolar damage such as hyaline membranes lining and following the contours of the alveolar walls. Areas of necrosis and desquamation of the alveolar epithelium in the form of scattered cells or layers, areas of hemorrhages and hemosiderophages are detected in the alveolar walls. In the lumen of the alveoli, a sloughed epithelium with a hemorrhagic component, few multinucleated cells, macrophages, protein masses, and accumulated edematous fluid were determined. Pulmonary vessels are moderately full-blooded, surrounded by perivascular infiltrates. Signs of lung sarcoidosis were revealed. Histological examination found epithelioid cell granulomas consisting of mononuclear phagocytes and lymphocytes, without signs of necrosis. Granulomas with a proliferative component and hemorrhage sites were determined. Giant cells with cytoplasmic inclusions were detected - asteroid corpuscles and Schauman corpuscles. Non-caseous granulomas consisting of clusters of epithelioid histiocytes and giant Langhans cells surrounded by lymphocytes were detected in the lymph nodes of the lung roots. Hamazaki-Wesenberg corpuscles inside giant cells were found in the zones of peripheral sinuses of lymph nodes. In the lumen of the bronchi, there was found fully exfoliated epithelium, mucus. Granulomas are mainly observed subendothelially on the mucous membrane, without caseous necrosis. Histological examination of the cardiovascular system revealed fragmentation of some cardiomyocytes, cardiomyocyte focal hypertrophy along with moderate interstitial edema, erythrocyte sludge. Zones of small focal sclerosis were determined. The vessels of the microcirculatory bed are anemic, with hypertrophy of the walls in small arteries and arterioles. Virological examination of the sectional material in the lungs revealed SARS-CoV-2 RNA. Conclusion. Based on the data of medical documentation and the results of a post-mortem examination, it follows that the cause of death of the patient R.A., 50 years old, was a new coronavirus infection COVID-19 that resulted in bilateral total viral pneumonia. So-morbidity with competing diseases such as lung sarcoidosis and cardiovascular diseases aggravated the disease course, led to the development of early ARDS and affected the lethal outcome. Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.

IDIOPATHIC MULTICENTRIC CASTLEMAN DISEASE (IMCD) AS A MANIFESTATION OF POST-COVID-19 INFLAMMATORY SYNDROME

SESSION TITLE: Pulmonary Manifestations of Infections SESSION TYPE: Case Reports PRESENTED ON: 10/17/2022 03:15 pm - 04:15 pm INTRODUCTION: Post-acute COVID-19 inflammatory syndrome is defined as persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms of original infection (1). These can manifest in various ways, but pulmonary, cardiac, and renal complications are the most common (1), with IL-6 thought to be an important mediator (2). We report what we believe to be the first case of Idiopathic Multicentric Castleman's Disease (iMCD) as a manifestation of post-acute COVID-19 inflammatory syndrome. CASE PRESENTATION: A 36-year old male with history of hypertension and childhood asthma (not on current therapy), and recently resolved COVID-19 from 4 weeks prior, is admitted to the hospital with progressive shortness of breath, cough, fevers and significant fatigue. Prior COVID-19 symptoms included fevers, cough, and shortness of breath, which improved after 2 weeks without treatment. Symptoms returned 2 weeks later and worsened. On admission, he was tachycardic to 108 with temp of 37.8C, and otherwise stable vitals. Pertinent labs included WBC 17 (neutrophil predominant), Hgb 11.6, Cr 2.52, Na 126 and albumin 2.7 (normal baselines). SARS-CoV2 PCR was negative. CT chest with PE protocol showed no PE but moderate bilateral pleural effusions and extensive mediastinal lymphadenopathy. 1.2L clear fluid (transudative with lymphocyte predominance) was removed via thoracentesis. Microbiology, flow cytometry and cytology were unremarkable. Renal and mediastinal lymph node biopsies were taken. Lymph node sampling was non-diagnostic x2, but renal biopsy showed acute microangiopathy without thrombi, concerning for acute glomerulonephritis. Serologic vasculitis and CTD workup were entirely negative. He was treated with a course of prednisone and improved, however as outpatient, had recurrence of all these issues. Repeat thoracentesis x3 was unrevealing. He was again admitted and had an excisional inguinal node biopsy, showing findings consistent with hyaline vascular Castleman Disease. Further heme/onc evaluation and discussion showed diagnosis meeting criteria for iMCD. DISCUSSION: Multicentric Castleman's Disease is most often associated with HHV-8 infection in the setting of HIV. If HHV-8 is negative, the disease is termed idiopathic (iMCD). In these cases, disease is mediated predominantly by IL-6, but the direct cause is unknown, though existing theories include non-specific viral infections, malignancy and autoimmune diseases (3). Our patient had no evidence of malignancy or autoimmune phenomena. Thus COVID-19 illness was the most plausible explanation, especially given known IL-6 activity in COVID-19 inflammatory syndromes. CONCLUSIONS: Post-acute COVID-19 inflammatory syndromes are extensive and can affect any organ system. iMCD is another possible manifestation, and must be diagnosed with excisional lymph node biopsy. High index of suspicion should be maintained to make this diagnosis. Reference #1: Nalbandian, Ani et al. "Post-acute COVID-19 syndrome." Nature medicine vol. 27,4 (2021): 601-615. Reference #2: Phetsouphanh, Chansavath et al. "Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection.” Nature immunology vol. 23,2 (2022): 210-216. Reference #3: Dispenzieri, Angela, and David C Fajgenbaum. "Overview of Castleman disease." Blood vol. 135,16 (2020): 1353-1364. DISCLOSURES: No relevant relationships by Kyle Halligan No relevant relationships by Chris Yan

CHEST-WALL CASTLEMAN DISEASE MIMICKING THYMOMA DROP METASTASIS

SESSION TITLE: Amazing Chest Imaging Findings SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: Thoracic Castleman disease is challenging to diagnose and can mimic various lymphoproliferative disorders. Herein we present a case of unicentric thoracic castleman disease co-existing with thymoma, mimicking a thymoma drop metastasis. CASE PRESENTATION: A 50-year-old previously healthy Caucasian female presented to the emergency room with COVID-19 related respiratory symptoms. CTA was consistent with COVID-19 pneumonia and incidentally showed a 4.2 x 3.1 cm mass in the right anterosuperior mediastinum abutting the ascending aorta and superior right atrium, and a 3.3 x 2.1 cm mass in right posterior costophrenic sulcus abutting the right 11th rib raising suspicion for thymoma with a "drop metastases.” CT abdomen/pelvis was unrevealing. For proper staging, US guided biopsy of chest wall mass was performed which showed reactive lymphoid tissue. CT guided biopsy of the mediastinal mass revealed a thymoma. Due to ongoing concern for pleural metastases and possible sampling error with prior biopsy of the costophrenic lesion, she underwent surgical resection of the anterior mediastinal mass and chest wall lesion including part of 11th rib. The chest wall lesion was noted to be extrapleural. Surgical biopsy confirmed WHO grade B1 Thymoma and the chest wall lesion showed hyaline vascular Castleman disease. DISCUSSION: Pleural "Drop” metastasis from a thymoma or thymic carcinoma should be considered in patients with an anterior mediastinal mass and pleural based lesions. Imaging shows one or more pleural nodules or masses, which can be smooth, nodular, or diffuse. [1]. In our case, a basilar, discrete, nodular mass was suspicious for a drop metastasis. At the time of surgery, the lesion was noted to be extrapleural. Unicentric Castleman disease is a benign lymphoproliferative disorder which presents as a homogeneous, well-marginated, highly vascularized enhancing mass commonly involving the mediastinum. These lesions can mimic thymoma, lymphoma, sarcoma, hemangiopericytoma, and neural crest derived neoplasms. Pleural Castleman disease can arise from visceral and parietal pleura with extension into the chest wall or lung fissures and can cause pleural effusion. Intercostal disease can resemble other chest wall masses and cause rib erosions [2]. Chest-wall localization is a rare manifestation of Castleman disease often diagnosed due to non-specific thoracic symptoms such as dyspnea, cough, chest-wall pain or generalized malaise.[3] Complete excision of the lesion is generally curative with cure rate of 95-100%, with recurrence reported with partially resected lesions. CONCLUSIONS: Castleman disease located in the chest wall can present diagnostic and management challenges particularly when present in the context of other lesion with metastatic potential. Reference #1: 1.Benveniste, M.F.K., Rosado-de-Christenson, M.L., Sabloff, B.S., Moran, C.A., Swisher, S.G. and Marom, E.M. (2011). Role of Imaging in the Diagnosis, Staging, and Treatment of Thymoma. RadioGraphics, 31(7), pp.1847–1861. Reference #2: 2.Ko, S.-F., Hsieh, M.-J., Ng, S.-H., Lin, J.-W., Wan, Y.-L., Lee, T.-Y., Chen, W.-J. and Chen, M.-C. (2004). Imaging Spectrum of Castleman's Disease. American Journal of Roentgenology, 182(3), pp.769–775 Reference #3: 3. Rena, O., Casadio, C. and Maggi, G. (2001). Castleman's disease: unusual intrathoracic localization. European Journal of Cardio-Thoracic Surgery, 19(4), pp.519–521. DISCLOSURES: No relevant relationships by Peter LaCamera, value=Consulting fee Removed 04/06/2022 by Peter LaCamera No relevant relationships by Peter LaCamera, value=Consulting fee Removed 04/06/2022 by Peter LaCamera No relevant relationships by Alina Wasim

CRYPTOGENIC ORGANIZING PNEUMONIA: A DIAGNOSTIC DILEMMA IN A WORLD DOMINATED BY COVID-19 PNEUMONIA

SESSION TITLE: Pulmonary Involvement in Critical Care Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Cryptogenic organizing pneumonia (COP), also known as bronchiolitis obliterans organizing pneumonia (BOOP), is one of the idiopathic interstitial lung diseases that affects the alveolar epithelium and surrounding interstitium. Its diagnosis is usually delayed due to similar clinical presentation as other illnesses (e.g. pneumonia) [1]. CASE PRESENTATION: A 65-year-old male presented with rapidly progressive respiratory failure. Computed tomography (CT) of chest showed multifocal ground glass opacities. He had suboptimal response to antibiotics and had to be intubated on day 9 due to worsening respiratory failure. Bronchoscopy with bronchoalveolar lavage was performed, cytology of which revealed severe acute inflammation and mononuclear infiltration. Decision was made to perform open lung biopsy which showed polypoid plugs of organizing fibroblasts and myofibroblasts in the distal airways and alveoli with focal hyaline membrane and alveolar damage, consistent with acute onset fulminant COP. As expected, the patient responded fairly well to high-dose corticosteroids and was extubated on day 9 of intubation. DISCUSSION: Even though it is very rare, COP should be kept in differentials especially when initial interventions fail (as in our patient). There is no single laboratory study or intervention to diagnose this condition. Hence it is imperative to rule out other causes of similar presentation like pneumonia (using cultures, urine antigen testing, and viral polymerase chain reaction tests). The clinical picture is combined with supportive evidence like elevated erythrocyte sedimentation rate, leukocytosis, imaging findings, and bronchoscopic and histopathology evaluation [2]. Once diagnosed, it is important to rule out any associated CTD, for it can change management and prevent additional complications. The majority of patients with COP exhibit rapid response to glucocorticoid treatment. For fulminant disease, intravenous glucocorticoids (e.g. methylprednisolone 125-250 mg every six hours) should be initiated based on the clinical experience and case reports [3]. CONCLUSIONS: Diagnoses of interstitial lung diseases should be pursued in a systemic fashion from more common to less common. However, anchoring to common diagnoses should be avoided to negate delay in diagnoses and allow timely management. If initial workup is unrevealing, bronchoscopy and open lung biopsies should be performed while the patient is stable enough to undergo the interventions to avoid antibiotic resistance, morbidity and mortality associated with rapidly progressive noninfectious illnesses like fulminant COP. Reference #1: Drakopanagiotakis F, Polychronopoulos V, Judson MA. Organizing pneumonia. The American journal of the medical sciences. 2008 Jan 1;335(1):34-9. Reference #2: Cordier JF. Cryptogenic organising pneumonia. European Respiratory Journal. 2006 Aug 1;28(2):422-46. Reference #3: Nizami IY, Kissner DG, Visscher DW, Dubaybo BA. Idiopathic bronchiolitis obliterans with organizing pneumonia: an acute and life-threatening syndrome. Chest. 1995 Jul 1;108(1):271-7 DISCLOSURES: No relevant relationships by Fareeha Abid No relevant relationships by Vipin Garg No relevant relationships by Qirat Jawed No relevant relationships by Asnia Latif No relevant relationships by Ahmed Mowafy No relevant relationships by Muniba Naqi No relevant relationships by Muhammad Atif Masood Noori No relevant relationships by Hasham Saeed

Multisystem Inflammatory Syndrome in Children: A Diagnostic Conundrum in a Young Kenyan Boy, October 2021

Introduction/ Background: Multisystem inflammatory syndrome in children is a severe manifestation of COVID-19 infection in children and adolescents. It causes a significant hyper inflammatory response in children and is related to SARS-CoV-2 infection. There is paucity of data on this subject, especially in Sub-Saharan Africa, leading to challenges and delays in diagnosis. Methods: A case of a 17-year Kenyan boy who presented to a tertiary-level facility in Nairobi with abdominal pain and diarrhea for five days, difficulty in breathing and conjunctival injection for 1 day. Three weeks prior to this he had a dry cough and associated sore throat. He hadn't received Covid-19 vaccination. There had been a COVID-19 outbreak at school. Examination at admission revealed he was hypotensive, tachycardic, tachypnoeic, afebrile with normal oxygen saturations. He had distended neck veins with hyperactive precordium and elevated jugular venous pressure, a distended abdomen, tender in the right upper quadrant and a hepatomegaly of 16cm. Results: Investigations revealed multiple organ dysfunction (MOD) including heart failure with reduced ejection fraction (LVEF-30%), acute kidney injury, acute congestive hepatopathy, coagulopathy, elevated inflammation markers and positive SARS-CoV-2 IgG and IgM and a negative COVID 19 PCR test. He received IV antibiotics, daily hemodialysis sessions, inotropic support, high dose steroid therapy and Tocilizumab. He succumbed 8 days after admission. A postmortem revealed necrosis of the glomeruli and tubules, acute hemorrhagic necrosis of hepatocytes with fatty change, hyaline covering alveoli sac inkeeping with acute respiratory distress syndrome. Impact: MIS-C presents a diagnostic challenge and is often mistaken for other medical conditions. This often leads to inappropriate or delayed treatment, hence poor outcomes. A high index of suspicion is warranted. This may present a wakeup call for consideration of extending vaccination to the pediatric age group. Conclusion: Multi-system inflammatory syndrome is a rare COVID 19 complication affecting children and adolescents. It presents difficulty in diagnosis in Kenya considering most adolescents are managed as adults. This case hopes to increase vigilance among health care workers and that more preventive interventions can be implemented to reduce infection in children.

CLINICAL AND MORPHOLOGICAL FEATURES OF KIDNEY DAMAGE IN PATIENTS WITH ARTERIAL HYPERTENSION DIED OF SARSCOV- 2 INFECTION

Objective: To assess clinical and pathomorphological features of kidney damage in patients with arterial hypertension (AH) who died of the new coronavirus infection COVID-19. Design and method: A complex analysis of 268 kidney autopsies was carried out, including the study of macro- and microscopic changes reflected in the protocols of pathological and anatomical autopsies and identified during the histological examination. In 224 patients (83.6%) with AH, the diagnosis was confirmed by isolating the SARS-CoV-2 RNA using the polymerase chain reaction;in 44 (16.4%) - through computed tomography of the lungs. The causes of deaths were the following: in 31 patients (11.6%) acute myocardial infarction;in 40 (14.9%) cerebrovascular accident;in 11 (4.1%) pulmonary embolism;222 patients (83%) had acute respiratory distress syndrome. The analysis included 130 men aged 36 to 92 (72.6 years old on average) and 138 women aged 40 to 106 (77.1 years old on average). Results: In the kidneys we detected ischemic changes caused by disturbances in the microvasculature. These are stases, sludges, erythrocyte and fibrin thrombi predominantly in the medulla. In the glomeruli diapedesis hemorrhages, mesangial cells proliferation, basement membrane thickening and fibrinoid necrosis of the capillary wall were observed. In the epithelium of the convoluted tubules, a granular, hyaline-drop dystrophy and a necrosis as the extreme degree of the damage were noted. In the kidneys, a pronounced lymphoid and leukocyte infiltration was detected. These changes were accompanied by inflammation and renal failure symptoms. In particular, the level of C-reactive protein was 140.6 ± 7.42 mg/l;blood ferritin 1258.0 ± 110.1 mcg/l;blood leukocytes 15.0 ± 0.67 10

SPM analysis of a brain 18F-FDG PET/CT in a patient with neurological impairment after covid-19 infection

Background-Aim: A 46 years old housewife patient with a bachelor's degree in Law contracted Covid-19 at the end of March 2021. She had a flu-like form with associated asthenia and drowsiness and no lack of sense of smell. It has been resolved in 25 days. Later, she developed progressive immediate memory loss, word-finding issues, motor and thinking slowing down. Methods: CT brain scan appeared as within the norm as well as liver enzymes, TSH, Vitamin B12, Folate and Rapid Plasma Reagine. Anti- ENA DNA ANA HIV TPO TG were negative too. In October, the patient had a further neuropsychological assessment that showed an overall picture characterized by partial orientation to space, working memory disorders, writing and comprehension (of complex tasks) issues, and immediate memory loss (possible sign both of attention span and concentration reduction). The auto-antibodies were assessed in November and they resulted negative. Moreover, the brain MRI scan and EEG (dated at the end of November) were both within the range. CSF neurodegenerative biomarkers and anti-neuronal antibodies appeared in the norm too. Results: Ultimately, in December 2021 she underwent an 18F-FDG PET brain scan and the SPM analysis showed an extensive hypometabolism in the bilateral frontal cortex and bilateral straight gyrus. Spared the cingulate cortex. Conclusions: The patient contracted Covid in March 2021. She developed neurological deterioration identified by FDG-PET. Negative autoantibodies and CSF biomarkers. PET scan was the only exam to define the brain damage in the patient above. Symmetrical bilateral frontal cortex and bilateral straight gyrus hypo-metabolism have been observed, the last one at the direct level of the olfactory bulb. In this area, in patients who died from Covid-19 it has been histologically demonstrated (data to be published) the presence of cellular inclusions named Corpore Amylacea. They would be a small hyaline mass that functions as a waste container that accumulates in the human brain in aging and in neurodegenerative and infectious processes. It is hypothesized to be that it can be involved in a sort of brain cleaning process1. Recently it has been described that they contain some neoepitopes that are recognized by natural IgMs, revealing a possible link between them and the natural immune system2. However, to now in our patient, the only diagnostic tool to evaluate the brain condition has been the 18F-FDG PET.

PATHOLOGICAL CHANGES IN THE KIDNEYS IN PATIENTS WITH ACUTE RENAL INJURY DUE TO CORONAVIRUS INFECTION

INTRODUCTION AND OBJECTIVE: Acute kidney injury (AKI) in coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus is much more common than previously thought and is associated with severe disease and high mortality. Despite the fact that the respiratory and immune systems are the main targets of the COVID- 19 virus, AKI is also observed, identified by the occurrence of proteinuria or hematuria, an increase in serum urea and creatinine levels. The aim of the study is to assess the pathomorphological changes in the kidneys in 100 cases of autopsy of patients with COVID-19 using light microscopy and immunohistochemical diagnostic methods in order to clarify the possible mechanism of AKI. METHODS: The study was carried out using samples obtained from 100 patients, the time interval of the onset of the disease corresponded to the 4th wave of the peak of the incidence in Russia (from June 2021). The age of patients varied from 37 to 94 years 72 (s =12.5), men - 34, women - 66. Patients with chronic kidney disease, diabetes mellitus and cancer were not included in the analysis. The cause of death in all cases was acute respiratory failure, histologically defined as diffuse alveolar injury. AKI in accordance with the KDIGO criteria was detected in 34 patients. RESULTS: On light microscopy, diffuse massive damage to the proximal tubules with loss of the brush border, degeneration of vacuoles was detected in 46 patients, massive necrosis of the tubules in 11 patients. In 65 patients, an extremely pronounced congestion of paretic dilated vessels with widespread paravasal hemorrhages was revealed. Paravasal lymphoid infiltration of the vascular endothelium was detected in 27 patients. Severe sludge syndrome in small and medium-sized vessels in 46 patients. In almost all cases, hemosiderin granules and hyaline casts were found. The quantitative and qualitative composition of tissue macrophages corresponded to the population data, without visible correlations with the disease. CONCLUSIONS: According to the study, the factors contributing to AKI include systemic hypoxia, abnormal coagulation, increased catabolism due to fever, drug-related rhabdomyolysis or hyperventilation with increased serum degradation products. Thus, our research provides evidence for AKI during the progression of COVID-10. These results contribute to a better understanding of the course and progression of SARS-CoV-2 virus infection.

Adrenal Insufficiency: A Unique Presentation of Multicentric Castleman Disease with Human Herpes Virus 8 Positivity and Concomitant Kaposi Sarcoma

Introduction: Multicentric Castleman Disease (MCD) is a lymphoproliferative disorder involving multiple lymph nodes and can be associated with human herpes 8 virus (HHV-8). Hyaline vascular (HV) MCD is rare, occurring in < 10% of cases. MCD with concomitant HIV negative Kaposi Sarcoma (KS) is also uncommon and can peculiarly present with adrenal insufficiency. Case Description: 53-year-old male with biopsy proven diagnosis of HHV-8 positive KS was transferred to our institution with persistent hypotension requiring pressor support. He described a two-week history of night sweats, 20 Ib weight & appetite loss, fatigue, muscles aches, and subjective fevers. Vitals: BP: 99/50 mmHg, HR: 90 bpm, RR: 19 and T: 103oF. Physical exam revealed multiple violaceous, non-blanching plaques on his body, tender inguinal & axillary lymphadenopathy, and bilateral lower extremity edema. Initial labs: Na: 137 mmol/L, K: 3.6 mmol/L, WBC: 5.6 k/uL, Hg: 7.1 gm/dL, Hct: 21%, Plt: 91 k/uL, AM cortisol: 12.5 mcg/dL (5.3-22.5), ACTH < 1 pg/mL, TSH: 7.5 uIU/mL, FTF: 0.63 ng/dL, PRL: 7 ng/mL, Total testosterone: 20 ng/dL, FSH: 4.2 mIU/mL, LH: 8.3 mIU/mL, IGF-1: 77 ng/mL (64-218), ESR >85 mm/hr (< 20), and CRP: 76 mg/dL (< 3). HIV and COVID-19 tests were negative. He was started on oral Levothyroxine and IV Hydrocortisone with significant improvement in his BP leading to discontinuation of pressor support. CT chest/abdomen/pelvis showed diffuse lymphadenopathy consistent with KS with normal adrenal glands. Left axillary lymph node biopsy revealed HV MCD. Additional labs;IL-6: 11.5 pg/mL (< 2), IgG4: 45 mg/dL (1-123), normal CD4 count, renin and aldosterone levels. 21 alpha hydroxylase antibody, T-spot, extensive autoimmune and infectious work-up were negative. Pituitary MRI could not be obtained due to a metal object behind his right orbit. Head CT was negative for pituitary abnormality. He failed his ACTH stimulation test with cortisol level: 13 mcg/dL at 90 minutes (baseline ACTH was not obtained). Thus, he was discharged on physiological oral Hydrocortisone upon clinical improvement. He began chemotherapy 1 week post discharge, however he succumbed to his disseminated and aggressive disease 20 days later. Discussion: MCD with concomitant KS is a rare and rapidly progressive disease which can cause death within weeks. IL-6 overproduction is thought to be associated with its symptom progression. Worse clinical outcomes are correlated with HIV or HHV-8 positivity. It can uncommonly be associated with either primary or secondary adrenal insufficiency requiring prompt evaluation and treatment with systemic steroids to prevent development of adrenal crisis.

Pathology of Double Lung Transplantation of 12 Cases Following COVID-19

Background: Pulmonary failure is one of the major causes of death in COVID-19 (SARS-CoV-2) patients. Lung transplantation has been evolving to rescue those patients' lives with promising success. Explanted native lungs post COVID-19 are valuable to understand the long-term pulmonary pathology of this deadly disease, as currently available data is very limited. Design: Lung transplantation cases post COVID-19 were collected through the pathology database in our institution from January 2020 through September 2021. Patient clinical courses, CT imaging data prior to transplantation and pathological findings are evaluated. Results: The cohort consisted of 12 male patients with a median age of 46.5 years (range 24 - 67). Co-morbidities were present in 6 patients including obesity, diabetes mellitus and hypertension. No prior known pulmonary specific disease was present in any of the patients. Extracorporeal membrane oxygenation (ECMO) was used in 10 of 12 patients for 54 - 130 days. CT imaging pretransplantation showed extensive bilateral consolidation (5 cases), extensive bilateral ground-glass (3 cases) or extensive infiltration/air space disease (4 cases). All patients survived post double lung transplantation (including one patient with concurrent heart transplantation) and no significant pathologic alteration was identified on most recent surveillance biopsies (26 - 183 days post transplantation). The most prominent pathological finding in the explanted lungs is nonspecific interstitial pneumonia (NSIP)- like interstitial fibrosis (100%, 12 cases). Other findings include collections of numerous hemosiderin-laden macrophages (8 cases), patchy diffuse alveolar damage (DAD) (hyaline membrane formation and/or organizing DAD) (5 cases), intrapulmonary small vessel thrombosis (5 cases), organizing pneumonia (5 cases), necrosis (2 cases), calcifications (5 cases), acute pneumonia (3 cases), peribronchiolar metaplasia (8 cases), and microscopic honeycombing (8 cases). No viral cytopathic changes were seen. The pathologic findings of the two patients who did not receive ECMO are similar to those in patients with variable length of ECMO treatment. Conclusions: Lung transplantation is a successful treatment option for eligible candidates with pulmonary fibrosis and failure post COVID-19. NSIP-like interstitial fibrosis is a universal finding, consistent with a sequala of DAD. A spectrum of acute, subacute, vascular and airway-related changes are also prominent findings in respiratory failure post COVID-19.

Utility of Bronchoalveolar Lavage (BAL) Cytology in SARS-CoV-2 Patients: A Review of Clinical and Cytologic Findings with Cost Analysis

Background: Bronchoalveolar lavage (BAL) cytology is a commonly used test in hospitalized patients with SARS-CoV-2 and its demand has dramatically increased in large medical centers. Currently, there are no standard guidelines for using BAL cytology in SARS-CoV-2. Findings such as lymphocytosis, giant cells, hyaline membranes, and intranuclear inclusions have been reported in BALs from patients with SARS-CoV-2 with varying frequencies. The aim of our study is to evaluate the frequency of these reported morphologic findings and to assess the utility and cost-effectiveness of BAL in the management of SARS-CoV-2 patients. Design: We performed a retrospective review of all BAL specimens from patients with positive SARS-CoV-2 nasopharyngeal PCR at our tertiary care medical center between March 2020 and February 2021. Chart review was performed for clinical findings and microbial culture data. BAL Papanicolaou stained thin prep, as well as special stains (PAS, Fite & GMS) on each case, were reviewed by a board-certified cytopathologist. Billing data was acquired from the laboratory manager. Results: A total of 37 patients were included ranging in age from 27-84 years (median: 58 years). Their clinical findings are summarized in Table 1. The majority of the BALs showed no specific findings that would help guide or alter the clinical management. 12 cases(33%) showed no significant cytologic findings, 16(43%) showed a relative increase in neutrophils, 7(19%) a relative increase in lymphocytes including one with markedly activated forms, and 4(11%) showed non-specific pneumocyte hyperplasia. PAS+ hyaline membranes, giant cells, intranuclear inclusions, and necrotic debris were each seen in 3% of cases. Special stains were negative for microorganisms in all cases. The cost of BAL thin prep and special stains (professional+techinal components) at our institution was $295 and $265, respectively. The total cost of BAL/patient was $1090 (295+265x3) and the overall cost for 37 patients was $40330. Conclusions: In the majority of the cases, BAL specimens from patients with SARS-CoV-2 showed non-specific findings such as a relative increase in neutrophils and lymphocytes, and pneumocyte hyperplasia. More specific morphologic findings such as intranuclear inclusions, PAS+ hyaline membranes, and activated lymphocytosis are only seen in rare instances. Overall, the use of BAL cytology in SARS-CoV-2 is time-consuming, not cost-effective, and does not help guide or alter patient management significantly.

Morphological changes in organs after infection with SARS-CoV-2 against the background of AL-amyloidosis

The article describes a clinical case of death of a 57-year-old patient from idiopathic AL-amyloidosis after infection with SARS-CoV-2. Histological examination revealed signs of pneumonia with symptoms of pneumosclerosis, histologically determined di-apedesic hemorrhages, necrosis and desquamation of the alveolar epithelium, along the contours of the alveolar passages, al-veolar sacs — hyaline membranes. In many areas, the histoarchitectonics of the pulmonary parenchyma was sharply disturbed, connective tissue was determined in the alveolar passages, in the lumens of the alveoli. The interalveolar septa were thickened due to the proliferation of connective tissue. Positive Congo red staining was visualized mainly in the perivascular and interalveo-lar septa, along the vessels;in the heart — between cardiomyocytes, in the kidneys — in the capillary loops of the glomeruli, base-ment membranes of individual tubules of the cortical layer, in the walls of blood vessels. Thus, the cause of death of the patient was the severe course of infection with SARS-CoV-2;the presence of a concomitant disease in the form of idiopathic AL-amyloi-dosis of internal organs and chronic diseases, obviously, aggravated the patient’s condition and contributed to the onset of death.

Pathological Features of Lung in COVID-19 Disease Subjects: A Postmortem Study

Introduction: The current Coronavirus Disease-19 (COVID-19) pandemic is considered as one of the most serious public health crises which caused more than 1.62 million deaths from October 2020 to November 2020. Acute respiratory failure is leading cause of death followed by sepsis, cardiac failure and hemorrhage. Since the pathological findings are diverse in COVID-19 and majority of studies in literature were by open autopsy;the present study was done using percutaneous core needle biopsy. Postmortem lung biopsies are rather easy and quick to perform and decrease the infective risk caused by full autopsies. This could be an essential tool for diagnosis, surveillance and research. Aim: To study the pathological features of lung in COVID-19 deceased patients by postmortem. Materials and Methods: This cross-sectional study was conducted in the Department of Pulmonary Medicine, Dr. Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation, Vijayawada, Andhra Pradesh, India from October 2020 to November 2020. In present study, postmortem percutaneous core needle biopsies from lung were performed within two hours of death from eight deceased patients who died of COVID-19. Clinical history, inflammatory markers and treatment details were collected from case sheets, biopsy was done, specimen was collected and sent for pathological examination. Data was presented in the descriptive form for each variable. Results: Out of eight cases, five were men and three were women with a mean age of 54.12 years. Majority of patients presented with complaints of shortness of breath and fever. Hypertension, type 2 diabetes mellitus, obesity, hypothyroidism, history of pulmonary tuberculosis were the co-morbidities noticed. Four biopsies presented acute lung injury with hyaline membrane changes, Diffuse Alveolar Damage (DAD) with hyaline membrane was seen in two cases, squamous metaplasia was seen in two cases and acute lung injury with organising pneumonia was seen in two cases. Conclusion: Postmortem lung biopsies are safe, easy to perform and provide insights of possible undergoing pathology of the disease with regard to clinical presentation.