COVID-19-Associated Encephalopathy (COVEP): Basic Aspects of Neuropathology: Comparison
Please note this is a comparison between Version 2 by Sirius Huang and Version 1 by George Stoyanov Stoyanov.

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-CoV-2
  • COVID-19
  • central nervous system
  • anosmia
  • neuropathology
  • encephalopathy

The novel coronavirus disease, which began its outbreak in 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a multisystem disease [1,2,3][1][2][3]. While initially regarded as a respiratory system disease, one of the earliest peculiarities of the disease was the development of anosmia (loss of smell sensation) and ageusia (loss of taste perception) by those infected, which pointed toward nervous system involvement as well [4,5,6,7,8,9][4][5][6][7][8][9]. Since then, many other aspects of the disease have emerged, such as renal involvement (COVAN), myopericarditis and endotheliitis, gastrointestinal system disorders, and many more [10,11,12,13,14,15,16,17][10][11][12][13][14][15][16][17]. With the emergence of new variants of SARS-CoV-2 that cause severe disease in significantly fewer people while also being severely more infective, the scientific focus has gradually shifted toward the chronic sequelae of infection: post-COVID syndromes where once more the nervous system takes center stage [18,19,20,21,22,23][18][19][20][21][22][23].

References

  1. Guarner, J. Three Emerging Coronaviruses in Two DecadesThe Story of SARS, MERS, and Now COVID-19. Am. J. Clin. Pathol. 2020, 153, 420–421.
  2. Gorbalenya, A.E.; Baker, S.C.; Baric, R.S.; de Groot, R.J.; Drosten, C.; Gulyaeva, A.A.; Haagmans, B.L.; Lauber, C.; Leontovich, A.M.; Neuman, B.W.; et al. The species Severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 2020, 5, 536–544.
  3. Li, X.; Zai, J.; Zhao, Q.; Nie, Q.; Li, Y.; Foley, B.T.; Chaillon, A. Evolutionary history, potential intermediate animal host, and cross-species analyses of SARS-CoV-2. J. Med. Virol. 2020, 92, 602–611.
  4. Borczuk, A.C.; Salvatore, S.P.; Seshan, S.V.; Patel, S.S.; Bussel, J.B.; Mostyka, M.; Elsoukkary, S.; He, B.; Del Vecchio, C.; Fortarezza, F.; et al. COVID-19 pulmonary pathology: A multi-institutional autopsy cohort from Italy and New York City. Mod. Pathol. 2020, 33, 2156–2168.
  5. Stoyanov, G.S.; Yanulova, N.; Stoev, L.; Zgurova, N.; Mihaylova, V.; Dzhenkov, D.L.; Stoeva, M.; Stefanova, N.; Kalchev, K.; Petkova, L. Temporal Patterns of COVID-19-Associated Pulmonary Pathology: An Autopsy Study. Cureus 2021, 13, e20522.
  6. Rockx, B.; Kuiken, T.; Herfst, S.; Bestebroer, T.; Lamers, M.M.; Munnink, B.B.O.; De Meulder, D.; Van Amerongen, G.; Van Den Brand, J.; Okba, N.M.A.; et al. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science 2020, 368, 1012–1015.
  7. Paolo, G. Does COVID-19 cause permanent damage to olfactory and gustatory function? Med. Hypotheses 2020, 143, 110086.
  8. Butowt, R.; von Bartheld, C.S. Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection. Neuroscientist 2020, 27, 582–603.
  9. Stoyanov, G.S.; Petkova, L.; Dzhenkov, D.L.; Sapundzhiev, N.R.; Todorov, I. Gross and Histopathology of COVID-19 with First Histology Report of Olfactory Bulb Changes. Cureus 2020, 12, e11912.
  10. Velez, J.C.Q.; Caza, T.; Larsen, C.P. COVAN is the new HIVAN: The re-emergence of collapsing glomerulopathy with COVID-19. Nat. Rev. Nephrol. 2020, 16, 565–567.
  11. Ng, J.H.; Zaidan, M.; Jhaveri, K.D.; Izzedine, H. Acute tubulointerstitial nephritis and COVID-19. Clin. Kidney J. 2021, 14, 2151–2157.
  12. Siripanthong, B.; Nazarian, S.; Muser, D.; Deo, R.; Santangeli, P.; Khanji, M.Y.; Cooper, L.T.; Chahal, C.A.A. Recognizing COVID-19–related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management. Heart Rhythm 2020, 17, 1463–1471.
  13. Varga, Z.; Flammer, A.J.; Steiger, P.; Haberecker, M.; Andermatt, R.; Zinkernagel, A.S.; Mehra, M.R.; Schuepbach, R.A.; Ruschitzka, F.; Moch, H. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020, 6736, 19–20.
  14. Aloysius, M.M.; Thatti, A.; Gupta, A.; Sharma, N.; Bansal, P.; Goyal, H. COVID-19 presenting as acute pancreatitis. Pancreatology 2020, 20, 1026–1027.
  15. Kainth, M.K.; Goenka, P.K.; Williamson, K.A.; Fishbein, J.S.; Subramony, A.; Barone, S.; Belfer, J.A.; Feld, L.M.; Krief, W.I.; Palumbo, N.; et al. Early Experience of COVID-19 in a US Children’s Hospital. Pediatrics 2020, 146, 2020003186.
  16. Bradley, B.T.; Maioli, H.; Johnston, R.; Chaudhry, I.; Fink, S.L.; Xu, H.; Najafian, B.; Deutsch, G.; Lacy, J.M.; Williams, T.; et al. Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: A case series. Lancet 2020, 396, 320–332.
  17. Buja, L.M.; Wolf, D.; Zhao, B.; Akkanti, B.; McDonald, M.; Lelenwa, L.; Reilly, N.; Ottaviani, G.; Elghetany, M.T.; Trujillo, D.O.; et al. The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID-19): Report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities. Cardiovasc. Pathol. 2020, 48, 107233.
  18. Hoffmann, M.; Krüger, N.; Schulz, S.; Cossmann, A.; Rocha, C.; Kempf, A.; Nehlmeier, I.; Graichen, L.; Moldenhauer, A.S.; Winkler, M.S.; et al. The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic. Cell 2022, 185, 447–456.e11.
  19. Karim, S.S.A.; Karim, Q.A. Omicron SARS-CoV-2 variant: A new chapter in the COVID-19 pandemic. Lancet 2021, 398, 2126.
  20. Del Rio, C.; Omer, S.B.; Malani, P.N. Winter of Omicron—The Evolving COVID-19 Pandemic. JAMA 2022, 327, 319–320.
  21. Shaw, B.; Daskareh, M.; Gholamrezanezhad, A. The lingering manifestations of COVID-19 during and after convalescence: Update on long-term pulmonary consequences of coronavirus disease 2019 (COVID-19). Radiol. Med. 2021, 126, 40–46.
  22. Ellul, M.A.; Benjamin, L.; Singh, B.; Lant, S.; Michael, B.D.; Easton, A.; Kneen, R.; Defres, S.; Sejvar, J.; Solomon, T. Neurological associations of COVID-19. Lancet Neurol. 2020, 19, 767–783.
  23. Torres-Castro, R.; Vasconcello-Castillo, L.; Alsina-Restoy, X.; Solis-Navarro, L.; Burgos, F.; Puppo, H.; Vilaró, J. Respiratory function in patients post-infection by COVID-19: A systematic review and meta-analysis. Pulmonology 2021, 27, 328.
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