Renal ultrastructural findings and COVID-19
Blogged by Nicolas Kozakowski, March 1st, 2021
Unlike other pathologists, most nephropathologists are familiar with electron microscopy (EM). However, compared to some virologists, they are not specially trained in interpreting ultrastructural features connected to viral biology. A manifold of publications misinterpreting sub-cellular structures for coronavirus has arisen after the epidemic outbreak of COVID-19. Other publications have put ultrastructural findings into perspective with data on viral biology, EM of coronaviruses, look-alikes and how to appropriately handle cases1-8.
The detection of viral or viral-like structures in isolation does not allow a definite diagnosis of COVID-19-infection of kidney tissue. A reliable identification requires the cautious interpretation of specific changes establishing local viral replication, supported by appropriate diagnostic material and analyses 7. For instance, routinely formalin- and glutaraldehyde-fixed material does not allow to identify the typical crown, necessitating the addition of tannic acid in fixatives5, 7, 8. Amongst the characteristics of intracellular coronaviruses are double-membrane vesicles, nucleocapsid inclusions and large granular cytoplasmic area. The viral particles are always encountered in vesicles or vacuoles within the cytoplasm of infected cells, but not as free-floating virions1, 4, 5, 7, 8. The nucleocapsid, seen as small electron-dense dots inside particles, represents the most specific EM features of corona viruses4, 5, 8.
Contrarily, coated vesicles, multivesicular bodies, RER structures, Golgi vesicles or lysosomes exemplify various pitfalls3, 7, 8.
Ultimately, only the detection of EM-specific features of viral replication combined with protein or RNA recognition methods (immunogold or in situ hybridization) will permit the reliable diagnosis of COVID-19 infection in renal tissue1, 2, 4, 8.
[1] Goldsmith CS, Tatti KM, Ksiazek TG, Rollin PE, Comer JA, Lee WW, Rota PA, Bankamp B, Bellini WJ, Zaki SR: Ultrastructural characterization of SARS coronavirus. Emerg Infect Dis 2004, 10:320-6.
[2] Goldsmith CS, Miller SE, Martines RB, Bullock HA, Zaki SR: Electron microscopy of SARS-CoV-2: a challenging task. Lancet 2020, 395:e99.
[3] Roufosse C, Curtis E, Moran L, Hollinshead M, Cook T, Hanley B, Horsfield C, Neil D: Electron microscopic investigations in COVID-19: not all crowns are coronas. Kidney Int 2020, 98:505-6.
[4] Cassol CA, Gokden N, Larsen CP, Bourne TP: Appearances Can Be Deceiving – Viral-like Inclusions in COVID-19 Negative Renal Biopsies by Electron Microscopy.
[5] Neil D, Moran L, Horsfield C, Curtis E, Swann O, Barclay W, Hanley B, Hollinshead M, Roufosse C: Ultrastructure of cell trafficking pathways and coronavirus: how to recognise the wolf amongst the sheep .J Pathol 2020, 252:346-57.
[6] Wolff G, Melia CE, Snijder EJ, Barcena M: Double-Membrane Vesicles as Platforms for Viral Replication. Trends Microbiol 2020, 28:1022-33.
[7] Hopfer H, Herzig MC, Gosert R, Menter T, Hench J, Tzankov A, Hirsch HH, Miller SE: Hunting coronavirus by transmission electron microscopy – a guide to SARS-CoV-2-associated ultrastructural pathology in COVID-19 tissues. Histopathology 2021, 78:358-70.
[8] Bullock HA, Goldsmith CS, Miller SE: Best Practices for Correctly Identifying Coronavirus by Transmission Electron Microscopy. Kidney Int 2021.