Atrial inflammation and microvascular thrombogenicity are increased in deceased COVID-19 patients.

BACKGROUND: Histopathological studies have shown inflammation, cardiomyocyte injury, and microvascular thrombosis in the ventricular myocardium of patients with coronavirus disease 2019 (COVID-19). However, although atrial dysfunction is common in COVID-19, little is known about histopathological changes in the atria of the heart. We therefore analyzed inflammation, cardiomyocyte injury, and microvascular thrombogenicity in the atria of deceased patients with COVID-19. METHODS: Atrial tissue was obtained from autopsied COVID-19 (n=16) patients and control patients (n=10) and analyzed using immunohistochemistry. The infiltration of CD45+ leukocytes, CD3+ T lymphocytes, CD68+ macrophages, MPO+ neutrophils, and Tryptase+ mast cells were quantified as well as cardiomyocyte damage and microvascular thrombosis. In addition, Tissue Factor (TF) and Factor XII (FXII) were quantified as markers of microvascular thrombogenicity. RESULTS: The numbers of lymphocytes, macrophages, and neutrophils were significantly increased in the atrial myocardium and epicardial atrial adipose tissue of COVID-19 patients compared with the control group. This was accompanied by dispersed cardiomyocyte injury, the occasional presence of microvascular thrombosis, and an increased presence of TF and FXII in the microvascular endothelium. CONCLUSIONS: Severe COVID-19 induces inflammation, cardiomyocyte injury, and microvascular thrombosis in the atria of the heart.

COVID-19 pulmonary pathology: a multi-institutional autopsy cohort from Lviv and Lviv Region

Introduction. Worldwide, more than 182 million cases of COVID-19 and more than 3.9 million deaths have been confirmed since the virus was first identified. Advanced age and some comorbid conditions, such as diabetes and cardiovascular diseases, are considered risk factors for the adverse course of the discussed pathology. In recent years, several reports have been published about the results of the pathological examination of patients with COVID-19. Most often, in fatal cases, diffuse alveolar damage is described, which is characterized by intraalveolar edema, the appearance of "hyaline” membranes and the proliferation of pneumocytes and fibroblasts. However, the nature of the damage caused by SARS-CoV-2 remains unclear. The study of pathomorphological changes in severe fatal cases of COVID-19 is important for a better understanding of pathogenetic mechanisms of the development of pulmonary complications and the development of new effective methods of antiviral treatment. The aim of the current study is to evaluate the gross and microscopic findings in COVID-19 patients' autopsy to investigate the clinicopathologic basis for adverse outcomes with a fatal course of the disease. Methods. A retrospective analysis of 1036 consecutive autopsies associated with COVID-19 in 2020 was conducted based on Lviv Regional Office for Autopsy and Lviv Railway Clinical Hospital. The diagnosis of COVID-19 was confirmed by clinical signs of viral pneumonia, nasopharyngeal smear analysis, and radiological changes. A statistical study was performed with IBM SPSS Statistics 24.0. Results. The majority (72.4%) were elderly (60+) males (54.1±1.5%) and females (45.9±1.5%), with an age range from 19 to 93 years (mean age 66.9 ± 0.4 years). All examined patients had pneumonia, which was detected during a clinical examination with CT diagnosis and confirmed at autopsy. The acute exudative phase of pneumonia was diagnosed in 18.5±1.2% of cases, proliferative phase - in 18.5±1.2%, and fibrotic phase - in 5.9±0.7%. And in 53.5±1.5% of cases, signs of progressive fibrosis associated with exudative lesions prevailed. COVID-19 was the single original cause of death in 88.7±1.0% of cases. The following were identified in the lungs: typical virus-induced changes in epithelial cells of the trachea, bronchi, bronchioles and alveoli (100%, n=1036);different phases of diffuse alveolar damage in the majority of cases (96.5±0.6%);manifestations of innate immunity were described;pathological changes in the microvasculature (large vessel thrombi were detected in 37.9±1.5%). Conclusion. Our study results prove the importance of pathological examination of tissues during autopsies to determine the pathophysiological mechanisms and underlying causes of death of patients with COVID-19. © Yuliia Kuzyk, Olena Gavrilyuk, Marta Semko, Borys Ribun, Anna Arefyeva, 2022.

Pathological findings in COVID-19: A conventional autopsy-based study from India.

Background & objectives: Autopsy study has been considered the gold standard method for studying the effects of any disease on the body. Since COVID-19 is a novel disease, autopsy is crucial to understand its pathophysiology. This study was conducted to analyze the microscopic and macroscopic findings of various organs in COVID-19 and to associate those findings with clinical observations and laboratory findings. Methods: Conventional invasive autopsies were performed on 33 patients with COVID-19 from September 7, 2020 to December 23, 2020. All the organs were removed by routine dissection techniques and preserved in 10 per cent formalin. The tissues were processed and stained according to standard practices using haematoxylin-eosin (H & E) and periodic acid-schiff (PAS) stain. Results: The study included 28 males and 5 females with a median age of 61 yr (range 30-90 yr). Massive pulmonary oedema and thrombi in the lungs were the characteristic features macroscopically. On microscopic examination, diffuse alveolar damage in the exudative/proliferative phase was found in 29 (87.88%) cases. Among the other notable microscopic findings were bronchopneumonia and lung abscesses due to secondary bacterial infection (n=17, 51.52%), acute tubular injury (n=21, 63.64%) and thrombi in the lungs, heart, and kidneys. Interpretation & conclusions: COVID-19 primarily affected the respiratory and the renal systems in the vast majority of severely affected patients in our study. We also found signs of hypercoagulability, as evidenced by widespread thrombi in multiple organs, along with a raised d-dimer level and a hyperinflammatory state manifested by elevated inflammatory markers. Our autopsy findings and altered laboratory investigations support the role of immune-mediated cellular injury along with direct virus-mediated cellular damage.

Pathological changes in COVID-19 pneumonia on limited post-mortem sampling of lung: A saga of inflammation and thrombosis.

We describe three postmortem open lung-biopsy findings among patients with COVID-19 pneumonia who were on anticoagulant therapy. The spectrum of histopathological findings included lung inflammation in the form of diffuse alveolar damage (DAD) in exudative and organizing phases, with or without pulmonary artery thrombosis in different stages of evolution. This spectrum of inflammation and thrombosis may be indicative of a natural history of severe COVID-19 pneumonia or demonstrative of variation in therapeutics.

Anticoagulation for left ventricular thrombi secondary to COVID-Is 3 months too long?

The length of anticoagulation for thrombotic events related to COVID-19 is unknown. We present a patient with COVID-19 complicated by a thrombotic anterior STEMI and multiple left ventricular (LV) thrombi that resolved after 8 weeks of anticoagulation. We suggest a shorter length of anticoagulation with COVID-19-related LV thrombus.

Successful Systemic Heparinization for Treatment of Acute Arterial Occlusion of Tibial Artery and Aortic Mural Thrombi in a Patient With COVID-19 Infection: A Case Report

The present case report described a 60-year-old woman who developed multiple isolated acute arterial occlusions of the left anterior tibial artery, peroneal artery, and posterior tibial artery with aortic mural thrombi in the infrarenal aorta during treatment of COVID-19 pneumonia. The patient underwent conservative treatment by systemic heparinization and switched to low molecular weight heparin. She experienced clinical improvement within hours of medical treatment and complete resolution of the tibial artery thrombosis after two weeks of treatment. The aortic mural thrombi was evaluated by computed tomography angiography (CTA) abdomen and lower extremities and resolved after six weeks of anticoagulant administration. © 2022 JOURNAL OF THE MEDICAL ASSOCIATION OF THAILAND.

Histopathology of persistent long COVID toe: A case report.

During the 2020 coronavirus (SARS-CoV-2) pandemic, several cutaneous lesions were identified, including pseudo-chilblain, vesicular, urticarial, maculopapular, and livedo/necrosis. A 59-year-old obese man with probable COVID-19 developed painful cyanosis with histopathologic capillary thrombosis of toes, and the cyanosis persisted for nearly 22 months. Shortly after initial exposure to family members with documented SARS-CoV-2, he developed upper respiratory symptoms, yet his anti-SARS-CoV-2 antibody and nasal swab RT-PCR tests were repeatedly negative. Two family members were hospitalized and one of them succumbed with documented SARS-CoV-2 pneumonia within 10 days of exposure. Biopsy specimen of the distal toe 16 weeks after initial exposure showed papillary dermal capillary thrombosis with endothelial swelling, telangiectasia, and peri-eccrine lymphocytic infiltrates resembling pernio. Overall, this is the first case of biopsy specimen of "long COVID toe" following presumed SARS-CoV-2 exposure, with a demonstration of thrombotic vasculopathy, toe cyanosis, and pernio-like pathology.

Non-ST Segment Elevation Myocardial Infarction Secondary to Coronary Multi-Vessel Thrombosis in the Setting of COVID-19.

Coronavirus disease 2019 (COVID-19) has been shown to impact the cardiovascular system by causing congestive heart failure, arrhythmias, myocarditis, acute coronary syndrome (ACS), or nonischemic cardiomyopathy. The infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggers the overproduction of proinflammatory cytokines, generating systemic inflammation and a procoagulant state that can lead to cardiovascular morbidity and mortality. Symptomatology may not be discrete with presentation of chest pain, dyspnea, and fatigue, so careful consideration should be applied to cardiovascular complications. Serial troponin dosage as well as EKG changes serve as viable prognosis markers. Prompt dissolution of the thrombi will minimize the extent of the myocardial injury.

COVID-19 and renal infarct: To be or not to be on anticoagulation.

We present a unique case of a male veteran with a history of Castleman disease, presenting with multiple arterial and venous vascular thromboses in the setting of recent Coronavirus (COVID-19)-disease diagnosis. We explore this patient's morbidity related to thrombotic complications of his COVID-19 diagnosis that were potentially avoidable with a comprehensive outpatient evaluation of his risk for thrombosis, as well as the initiation of anticoagulation and/or antiplatelet therapy given his high risk. Our case highlights the need for a standardized clinical workup of patients in the outpatient setting for risk assessment of vascular thrombosis associated with COVID-19 infection to direct medical management, in order to minimize adverse outcomes, complications requiring inpatient admission, and the need for additional yet limited medical resources and interventions. We propose a minimum of low-dose aspirin 81 mg daily as a reasonable approach for outpatient clinicians to consider, based on their best clinical judgement, when managing mild COVID-19, while other options, such as novel oral anticoagulants, are undergoing further investigation.

Exceptional Presentation of Heart Thrombi Secondary to Myocardial Infarction Due to COVID-19 Pandemic.

Left ventricular thrombi (LVT) is an uncommon complication that can occur after a myocardial infarction thanks to the discovery of revascularization therapies. Before it, an LVT was described in up to 60% of patients with myocardial infarction. The authors present a case of a 46-year-old female who presented to the emergency department with one week of dyspnea, who had symptoms of chest pain for a week, however, did not show up in the hospital due to the ongoing COVID-19 pandemic. In-patient new-onset heart failure workup during that time was minimized due to the state of emergency COVID-19 pandemic. The patient lost to follow up appointment and then presented again to the hospital with Echocardiogram at that time showing mid to distal septal and apical hypokinesis, EF 30%-35% and a highly mobile circumferential echogenic mass of 2.4x2.4 cm noted in the left ventricle (LV) with differentials of LV thrombus vs cardiac tumor. Hospital complicated by LV thrombus embolization with bilateral lower extremities (LEs) arterial thrombi and limb ischemia. Left cardiac cath with a result of severe triple vessel disease requires either coronary artery bypass grafting (CABG) or complex percutaneous coronary intervention (PCI). A tentative plan was to pursue CABG, however, lower extremities must be healed prior to cardiothoracic surgery.

Clinicopathological findings in patients with COVID-19-associated ischaemic enterocolitis.

AIMS: Coronavirus disease 2019 (COVID-19) has been recognised as a predominantly respiratory tract infection, but some patients manifest severe systemic symptoms/coagulation abnormalities. The aim of this study was to evaluate the impact of severe COVID-19 infection on the gastrointestinal tract. METHODS AND RESULTS: We examined clinicopathological findings in 28 resected ischaemic bowels from 22 patients with severe COVID-19. Most patients required intubation preoperatively and presented with acute decompensation shortly before surgery. D-dimer levels were markedly elevated in all measured cases (mean, 5394 ng/ml). Histologically, 25 cases (19 patients) showed evidence of acute ischaemia with necrosis. In this group, the most characteristic finding was the presence of small vessel fibrin thrombi (24 of 25 cases, 96%), which were numerous in 64% of cases. Patients with COVID-19 were significantly more likely than a control cohort of 35 non-COVID-19-associated acute ischaemic bowels to show isolated small intestine involvement (32% versus 6%, P < 0.001), small vessel fibrin thrombi (100% versus 43%, P < 0.001), submucosal vessels with fibrinous degeneration and perivascular neutrophils (90% versus 54%, P < 0.001), fibrin strands within submucosal vessels (58% versus 20%, P = 0.007), and histological evidence of pneumatosis (74% versus 34%, P = 0.010). Three cases in this cohort had histopathological findings normally seen in the setting of chronic ischaemia, notably prominent fibroblastic proliferation affecting the outer layer of the muscularis propria. CONCLUSIONS: Herein, we describe the histopathological findings in COVID-19-associated ischaemic bowels and postulate a relationship with the hypercoagulable state seen in patients with severe COVID-19 infection. Additional experience with these cases may further elucidate specific features or mechanisms of COVID-19-associated ischaemic enterocolitis.

A clinicopathological description of COVID-19-induced chilblains (COVID-toes) correlated with a published literature review.

BACKGROUND: The abundance of publications of COVID-19-induced chilblains has resulted in a confusing situation. METHODS: This is a prospective single-institution study from 15 March to 13 May 2020. Thirty-two patients received PCR nasopharyngeal swabs. Of these, 28 patients had a thoracic CT-scan, 31 patients had blood and urine examinations, 24 patients had skin biopsies including immunohistochemical and direct immunofluorescence studies, and four patients had electron microscopy. RESULTS: COVID-19-induced chilblains are clinically and histopathologically identical to chilblains from other causes. Although intravascular thrombi are sometimes observed, no patient had a systemic coagulopathy or severe clinical course. The exhaustive clinical, radiological, and laboratory work-up in this study ruled-out other primary and secondary causes. Electron microscopy revealed rare, probable viral particles whose core and spikes measured from 120 to 133 nm within endothelium and eccrine glands in two cases. CONCLUSION: This study provides further clinicopathologic evidence of COVID-19-related chilblains. Negative PCR and antibody tests do not rule-out infection. Chilblains represent a good prognosis, occurring later in the disease course. No systemic coagulopathy was identified in any patient. Patients presenting with acral lesions should be isolated, and chilblains should be distinguished from thrombotic lesions (livedo racemosa, retiform purpura, or ischemic acral necrosis).

Left ventricular mural thrombi with multisystem thrombosis in patients with COVID-19 and myocardial injury: a case series.

BACKGROUND: Cardiovascular and thromboembolic complications have been reported in patients with Coronavirus disease-2019 (COVID-19)-related severe respiratory distress syndrome. Although myocarditis associated with COVID-19 pneumonia has been described, evidence of left ventricular (LV) mural thrombi with other multisystem events has not been reported. CASE SUMMARY: We report two cases with severe COVID-19 pneumonia and myocardial injury with large LV thrombi and other multisystem thrombotic events. The first patient represents an unusual case of large LV apical thrombus without concordant regional wall motion abnormality and mildly reduced LV function. A subsequent inferior ST-elevation myocardial infarction (STEMI) was likely related to either an embolic event or in situ coronary thrombosis. We could not ascertain whether the acute right ventricular dysfunction was due to in situ pulmonary thrombosis or inferior STEMI. The catastrophic cerebrovascular accident was likely an embolic phenomenon. Similarly, the second patient demonstrated multiple large pedunculated thrombi occupying one-third of the LV cavity with moderately reduced LV function. A segmental pulmonary embolism was diagnosed on computed tomography chest, confirming multiple territories of in situ thrombosis. DISCUSSION: COVID-19-related inflammatory cytokine release has been linked to activation of coagulation pathways. Marked elevation of ferritin and C-reactive protein levels in both patients were consistent with evidence of a hyperinflammatory state with 'cytokine storm'. Furthermore, the finding of elevated D-dimer levels lends support to the altered coagulation cascade that plausibly explains the multisystem thrombosis observed in our patients. The direct viral endothelial involvement and subsequent endothelial dysfunction may play an important role in the development of thrombosis in different vascular beds, as seen in our patients.

Contrast echocardiography facilitates appropriate management of hospitalized patients with coronavirus disease 2019 (COVID-19) and suspected right ventricular masses: case series.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection is associated with a coagulopathy with high incidence of venous thrombo-embolism. However, bleeding risk is also significant, causing difficulty in initiating and adjusting anticoagulation therapy in case of suspected thrombi. Cardiac masses can be challenging to be identified properly in the context of this disease. The use of bedside contrast echocardiography (CE) can be of a great value in this situation decreasing procedure-related risk and allowing proper diagnosis and management of a cardiac mass. CASES SUMMARY: We present two cases who were admitted with severe COVID-19 infection. Both cases had additional risk factors for hypercoagulability. Un-enhanced echocardiography was performed and revealed right ventricular (RV) dysfunction with a suspected RV mass. The use of bedside CE could confirm a RV thrombus in the first case and exclude it in the second case. Hence, anticoagulation therapy could be adjusted accordingly in both patients. DISCUSSION: Coronavirus disease 2019 infection is associated with peripheral thrombo-embolism and cardiac thrombi. Given the critical condition of many patients affected by COVID-19, imaging for thrombo-embolic events is often restricted. With the use of bedside CE, cardiac masses may be correctly identified, aiding proper adjustment of anticoagulation therapy.

Massive biventricular thrombi complicating new-onset heart failure in a patient with suspected COVID-19.

The World Health Organization nominated SARS-CoV-2 as the cause of the Coronavirus Disease 2019 (COVID-19) and has been granted as a pandemic. COVID-19 is an emerging threat due to the risk of microvascular, venous, and arterial thrombosis, thereby exacerbating organ injury and mortality. Although the exact mechanism of extensive thromboembolism and myocardial injury caused by SARS-CoV-2 is not illuminated, it is clear that COVID-19 related hypercoagulation increasing the fatality of the disease. Herein, we reported a patient with extensive biventricular thrombi along with the new-onset severe systolic dysfunction as an unusual catastrophic presentation of COVID-19. In our patient, there was both a right atrial "clot in transit" from his DVT as well as extensive muralized biventricular thrombus from severe global hypokinesis. We believe that the hypercoagulable state of his COVID-19 infection, along with severe systolic dysfunction, caused this unusual presentation. Although the hypercoagulable state of COVID-19 is well recognized, there have not been any reported cases of extensive de-novo intracardiac thrombus as of yet. We urge awareness of severe and potentially fatal extensive thrombosis and cardiac failure as the initial clinical presentation of possible SARS-CoV-2. .

Unusual presentations of cardiac rupture during COVID-19 pandemic.

The Covid-19 pandemia has many other undesirable consequences apart of virus infection. Less people is hospitalized due to acute coronary syndrome and the delay to seek medical attention has increased. Patients with ST segment elevation myocardial infarction arrive at the hospital too late to be timely treated and we have recently seen mechanical complications that were more frequent in the past decades before the use of reperfusion strategies. In this report we describe the presentation, evolution and detailed imaging evaluation of two patients with unusual presentations of cardiac rupture: left ventricular pseudoaneurysm and left ventricular intramyocardial dissecting hematoma.

Placental Pathology in COVID-19: Case Series in a Community Hospital Setting.

Objective To report the histopathologic findings in the placentas of pregnant women with coronavirus disease-19 (COVID-19). Methods Pregnant women with COVID-19 delivering between April 2020 to June 2020 were identified. A retrospective study of placentas from COVID positive women received in the Department of Pathology, Monmouth Medical Center affiliate of Robert Wood Johnson Barnabas Health were examined and compared to control cohort of placentas from COVID negative women. The mothers were tested for coronavirus through nasopharyngeal swab upon admission to labor and delivery. The placentas from mothers who tested negative for the virus were sent to Pathology for examination based on the obstetrician's clinical judgment. Results Fifty surgical specimens (49 placentas and one product of conception) from patients positive for COVID-19 were examined and compared with fifty placentas from women with negative COVID-19 test results, who delivered during the same period. Most of the neonates had Appearance, Pulse, Grimace, Activity and Respiration (APGAR) scores of 9 and 9 at 1 and 5 minutes, respectively. Increased incidence of the COVID-19 positivity was noted in individuals with Rh-positive blood group A and Jewish heritage. Compared to the control group, the COVID-19 positive placentas showed increased features of malperfusion (microcalcifications, fibrin thrombi, syncytial knotting, and villous agglutination). However, there was no significant dysregulation in other variables, such as inflammation or coagulation. There was no case of maternal or fetal death (greater than eight weeks) or evidence of worse fetal outcomes noted due to a mother's positive COVID-19 status.  Conclusions The COVID-19 positive placentas showed an increased prevalence of microcalcifications and fibrin thrombi, which may reflect an underlying hypercoagulable state induced by COVID-19 infection or could be due to excessive syncytiotrophoblast injury.

[Late Breaking Session Pathology and COVID-19 Report]. / Bericht zur Late-Breaking Session Pathologie und COVID-19.

This paper briefly summarizes the late-breaking session "Pathology and COVID-19" that took place at the virtual congress of the German Society of Pathology on June 6, 2020. The lectures tackled a broad variety of aspects, including the German Registry for COVID-19 autopsies (DeRegCOVID), the detection methods of SARS-CoV­2 in pathological material, the typical lung findings in severe COVID-19 cases, the distinct (micro)vascular changes and the cardiac and gastrointestinal involvement in COVID-19. In summary, in this first scientific meeting in German pathology on the COVID-19 pandemic, it became clear that pathologists in Germany, Austria and Switzerland have reacted very quickly to the pandemic and have established an autopsy program that has led to medically highly relevant findings.

Lesions in the lungs of fatal corona virus disease Covid-19.

The corona virus outbreak in Wuhan, China, at the end of 2019 has rapidly evolved into a pandemic which is still virulent in many countries. An infection with SARS-CoV-2 can lead to corona virus disease (Covid-19). This paper presents an overview of the knowledge gained so far with regard to histopathological lung lesions in fatal courses of Covid-19. The main findings were diffuse alveolar damage and micro-angiopathies. These included the development of hyaline membranes, thrombi, endothelial inflammation, haemorrhages and angiogenesis. Overall, the vessel lesions seemed to be more lethal than the diffuse alveolar damage. There was obvious hyperreactivity and hyperinflammation of the cellular immune system. An expanded T-cell memory may explain the increased risk of a severe course in the elderly.