Histopathological Features of SARS-CoV-2 in Extrapulmonary Organ Infection: A Systematic Review of Literature

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health concern responsible for the ongoing pandemic. Histopathological pieces of evidence on COVID-19 are not fully investigated. This review aims to provide, through microscopy investigations, a histopathological overview of COVID-19 structural and ultrastructural alterations in different organs and tissues, excluding the respiratory system. The authors systematically reviewed the literature over the period February 2020-July 2022. Selected databases were PubMed, Scopus, and Google Scholar. The search strategy included the following terms: "COVID-19" or SARS-CoV-2 and "histopathology" or "pathology"; and "microscopy" and "liver", "myocardium"," spleen", "testis", and "placenta". Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Thirty-one articles included in this systematic review demonstrated, at a histopathological level, that COVID-19 exerts detrimental effects on tissues, often promoting degenerative processes. Even if COVID-19 shows a histopathological tropism for the respiratory system, other tissues, from cardiovascular to reproductive, are affected by COVID-19. Therefore, this paper provides an up-to-date view of histopathological observations of the structural and ultrastructural alterations associated with COVID-19 and may contribute to a better knowledge of the physiopathological bases of this disease.

Keywords: COVID-19; SARS-CoV-2; autopsy; biopsy; histology; pathology; post-mortem.

Figure 1

PRISMA flowchart illustrating the experimental study search and selection process.

Figure 2

Histopathological findings in the cardiovascular system: the heart. (Courtesy: Bradley, B.T.; Maioli, H.; Johnston, R.; Chaudhry, I.; Fink, S.L.; Xu, H.; Najafian, B.; Deutsch, G.; Lacy, J.M.; Williams, T.; Yarid, N.; Marshall, D.A. Histopathology and Ultrastructural Findings of Fatal COVID-19 Infections in Washington State: A Case Series. Lancet 2020). (A) Light microscopy examinations on myocardial biopsy, derived from patients infected by SARS-CoV-2, reveal a significant myocyte damage. Haematoxylin and Eosin; Magnification: 40×. (B) By light microscopy, a considerable myocyte necrosis (arrowhead) is detected. Haematoxylin and Eosin; Magnification: 400×.

Figure 3

Histopathological findings in male reproductive tissue: testis. (Original labeling and Courtesy: Yang, M.; Chen, S.; Huang, B.; Zhong, J.M.; Su, H.; Chen, Y.J.; Cao, Q.; Ma, L.; He, J.; Li, X.F.; Li, X.; Zhou, J.J.; Fan, J.; Luo, D.J.; Chang, X.N.; Arkun, K.; Zhou, M.; Nie, X. Pathological Findings in the Testes of COVID-19 Patients: Clinical Implications. Eur. Urol. Focus 2020). (A) Defoliated and edematous Sertoli cells, characterized by vacuolation and cytoplasmic rarefaction. (B) Scattered Leydig cells (arrow). Hematoxylin and Eosin.