Modified Banff Criteria in Assessing SARS-CoV-2-Associated Renal Pathology: An Autopsy Study.

Introduction SARS-CoV-2 is an epitheliotropic viral agent with epithelial tropism. Although the clinical significance and severity of affection is the most pronounced in the respiratory system, other organs and systems are also infected and, hence affected, such as the central nervous system, gastrointestinal tract, cardiovascular, and urinary systems. Herein, we set out to evaluate the presence and degree of morphological changes within the renal parenchyma and its relation to disease outcome. Materials and methods A retrospective non-clinical approach was utilized for the means of the study. All patients with real-time reverse transcriptase-polymerase chain reaction proven infection, subject to an autopsy performed in a period of two calendar years, were included in the study. Kidney tissue histopathology samples were analyzed using a modified Banff criteria system for acute onset and chronic changes. The results were compared for statistical significance with overall patient survival from symptom onset to death. Furthermore, SARS-CoV-2 viral presence was evaluated in renal structures by means of immunohistochemistry. Results A total of 40 patients were included in the study. Immunohistochemistry showed viral presence within a myriad of renal structured - endothelial cells, tubular cells, and podocytes. Modified Banff criteria showed significant acute changes within the parenchyma, including endotheliitis, glomerulitis, mesangial matrix expansion, tubulitis, capillaritis, arteritis, thrombosis (including thrombotic microangiopathy in four patients), and hemorrhages. Individual cases also presented with signs of rhabdomyolysis - myoglobulin casts. Signs of chronic injury were also present in most patients. However, when calculated as scores, neither acute nor chronic changes showed a correlation with time from symptom onset to death. Conclusion The results of the present study show both viral presence and a myriad of induced changes in the contents of SARS-CoV-2 infection within the renal parenchyma. The lack of correlation with the degree of changes, when compared to survival, is an encouraging fact that the changes are unlikely to play a role in direct tanatogenesis while having the potential to manifest as chronic kidney disease in the future.

COVID-19-Associated Encephalopathy (COVEP): Basic Aspects of Neuropathology

SARS-CoV-2, a member of the betacoronavirus group and causative agent of COVID-19, is a virus affecting multiple systems, not only the respiratory. One of the systems affected by the virus is the central nervous system, with neuropathological studies reporting a wide set of morphological phenomena-neuroinflammation, vascular and blood-brain barrier alterations, neurodegeneration, and accelerated aging, while contradicting data is present on the direct neuroinvasive potential of the virus and active viral replication within neurons. The depicted changes, other than an acute effect (which may contribute to the death of the patient) also have chronic sequelae in the context of post-COVID syndrome cognitive impediments, sleep, and mood disorders. The following chapter describe the basic neuropathological aspects of SARS-CoV-2 as based on the present evidence in scientific literature and propose the term COVEP-COVID-associated encephalopathy-to unite the undisputed effects of the infection on nervous system morphology and function.

SARS, MERS and COVID-19-Associated Renal Pathology

Coronaviruses are a large group of RNA viruses, the most notable representatives of which are SARS-CoV, MERS-CoV and SARS-CoV-2. Human coronavirus infections were first documented in the 1960s, when members causing seasonal common colds were successfully replicated in human embryonal trachea and kidney cell cultures and classified based on electron microscopy. The history of coronaviruses stretched far back to that point, however, with some representatives causing disease in animals identified several decades prior and evolutionary data pointing towards the origin of this viral group more than 55 million years ago. In the short time period of research since they were discovered, coronaviruses have shown significant diversity, genetic peculiarities and varying tropism, resulting in the three identified causative agents of severe disease in humans-SARS, MERS and the most recent one, COVID-19, which has surpassed the previous two due to causing a pandemic resulting in significant healthcare, social and political consequences. Coronaviruses are likely to have caused pandemics long before, such as the so-called Asian or Russian influenza. Despite being epitheliotropic viruses and predominantly affecting the respiratory system, these entities affect multiple systems and organs, including the kidneys. In the kidneys, they actively replicate in glomerular podocytes and epithelial cells of the tubules, resulting in acute kidney injury, seen in a significant percentage of severe and fatal cases. Furthermore, the endothelial affinity of the viruses, resulting in endotheliitis, increases the likelihood of thrombotic microangiopathy, damaging the kidneys in a two-hit mechanism. As such, recently, COVAN has been a suggested nomenclature change indicating renal involvement in coronavirus infections and its long-lasting consequences.

SARS-CoV-2 Associated Pulmonary Pathology

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel entry in the betacoronaviridae group of coronaviruses. This is the second member of this group, and the third of the family overall to emerge in the last 20 years, which has caused significant health concerns due to the clinical severity and spread of the disease it causes-coronavirus disease identified in 2019 (COVID-19). While initially emerging as a respiratory disease, and while most cases experience symptoms predominantly from this system, SARS-CoV-2 has emerged as a multisystem pathogen. From a pathomorphological point of view, the severity of changes in the respiratory system can be summed up as diffuse alveolar damage-desquamation of the alveolar epithelium with exudative and proliferative changes-pulmonary hyaline membranes, Clara cell hyperplasia, squamous cell metaplasia, and fibrosis. The second most prominent way the disease affects the lung is through endotheliitis-damage to the endothelial cells of the pulmonary vasculature, predominantly affecting the medium and large caliber blood vessels that cause the well-established clinical phenomenon of thrombosis/thromboembolism of the pulmonary vasculature. As the spread of the disease continues with the emergence of new variants and the number of cases continues to grow, including a large percentage of recurrent cases, it is essential to remember that the viral effects are not only acute but, due to the proliferative phenomena, can produce chronic sequelae. Therefore, in the background of dwindling publication interest, it is critical to focus on the histopathological aspects of the pulmonary disease, with the goal of better understanding the effects of the virus on the organism and identifying probable future complications after infection.

Cerebral Palsy, COVID-19, and Neurolipidosis in an 18-Year-Old Female.

Since the novel coronavirus (COVID-19) pandemic started, children and young adults have seldom been placed in high-risk groups, despite reports that they are at increased risk of severe forms of the disease and death in the presence of comorbidities. Herein we report an autopsy case of an 18-year-old female with a history of cerebral palsy (CP), recurrent respiratory infections, and newly diagnosed COVID-19, and who expired 22 days after presenting with symptoms of the disease. Gross findings were concurrent with CP-significant hypotrophy, with deep and wide brain sulci. The lungs grossly were with increased weight and blood-filled. Histopathology of the respiratory system showed the well-established COVID-19-associated alveolar multinucleated cells, type two pneumocyte hyperplasia, and vascular changes. Furthermore, foci of groups of enlarged cells with foamy cytoplasm were identified in the pulmonary interstitium. Similar changes were also seen in the spleen, liver, and central nervous system, concurrent with an unrecognized lipid storage disease. The clinically unrecognized neurolipidosis, corresponding morphologically and clinically to Niemann-Pick disease type B, leading to interstitial lung disease and recurrent respiratory infections, inevitably played a role in the severity and progression of COVID-19 in our case, despite the age.