SARS, MERS and COVID-19-Associated Renal Pathology

Abstract

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.

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

“…The modified criteria used by us for the means of the present study are based on the latest revision of the reporting system and are modified based on the aspects of the tissue sample (greater material overall compared to renal biopsy alone) and some of the known properties of SARS-CoV-2 such as its affinity toward epithelial cells in general, especially endothelial cells when discussing it outside the context of the respiratory system [2]. As the Banff criteria include both cellular and immunological phenomena of tissue damage, they combine multifaceted phenomena observed in different types of organ transplant rejection but can also be applied, as in our case for cases of virally induced damage, wherein again cellular and purely immunological phenomena can coexist and potentiate each other [1][2][3].…”

“…For coronaviruses as a whole, renal involvement is not a new feature, with multiple other family members also having a reported nephrotropism [3][4][5]. One fact to further support this is the cultivation of viral infectious agents, later determined to be coronaviruses, which were initially performed on cell cultures of human embryonal trachea and kidney [1]. Previous entries from this viral group also cause severe diseases in humans.…”

“…SARS/SARS-CoV and Middle Eastern respiratory syndrome coronavirus (MERS/MERS-CoV) have also been reported to cause kidney disease. While the reposts are limited in regards to histomorphology, based on the relatively small number of patients infected and diseased from these infections and even the fewer number of autopsies performed and published, SARS is reported to cause interstitial and necrotic nephritis, with kidney involvement reportedly being a negative prognostic factor and further evidence painting toward not only the replication potential but also the tropism of this virus towards the kidney [ 1 , 6 , 7 ]. Conversely, MERS has been reported to have similar properties, with around 50% of infected cases developing into renal diseases due to acute tubular necrosis [ 1 ].…”

“…SARS-CoV-2, which is the causative agent of the clinical disease entry COVID-19, is an epitheliotropic viral agent with profound tropism to respiratory system epithelia [ 1 ]. Although initially thought to be purely a respiratory disease, and while indeed the majority of patients present with respiratory symptoms, which persist as the most severe throughout the disease course and are the most often cause of death in fatal cases, much has been established about the viral tropism to other sites and organs such as the central nervous system, gastrointestinal tract, cardiovascular and urinary system.…”

“…One of the key aspects of urinary system disease in the context of COVID-19 is direct damage to the kidneys, at first an overlooked mechanism but one grounded on the basic biological properties of coronaviruses as a whole [ 1 ].…”