Histopathological findings and clinicopathologic correlation in COVID-19: a systematic review

Abstract

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) pandemic has had devastating effects on global health and worldwide economy. Despite an initial reluctance to perform autopsies due to concerns for aerosolization of viral particles, a large number of autopsy studies published since May 2020 have shed light on the pathophysiology of Coronavirus disease 2019 (COVID-19). This review summarizes the histopathologic findings and clinicopathologic correlations from autopsies and biopsies performed in patients with COVID-19. PubMed and Medline (EBSCO and Ovid) were queried from June 4, 2020 to September 30, 2020 and histopathologic data from autopsy and biopsy studies were collected based on 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 58 studies reporting 662 patients were included. Demographic data, comorbidities at presentation, histopathologic findings, and virus detection strategies by organ system were collected. Diffuse alveolar damage, thromboembolism, and nonspecific shock injury in multiple organs were the main findings in this review. The pathologic findings emerging from autopsy and biopsy studies reviewed herein suggest that in addition to a direct viral effect in some organs, a unifying pathogenic mechanism for COVID-19 is ARDS with its known and characteristic inflammatory response, cytokine release, fever, inflammation, and generalized endothelial disturbance. This study supports the notion that autopsy studies are of utmost importance to our understanding of disease features and treatment effect to increase our knowledge of COVID-19 pathophysiology and contribute to more effective treatment strategies.

Fig. 1

Histopathologic findings of COVID-19 in the lung. A Normal lung with open alveoli and delicate alveolar septa containing thin capillaries lined by an attenuated alveolar epithelium (hematoxylin-eosin; original magnification ×200). B Acute diffuse alveolar damage (DAD) with hyaline membranes lining alveolar spaces, pneumocyte hyperplasia, desquamation of alveolar epithelial cells into the alveolar spaces, inflammatory infiltrates, and capillary congestion (hematoxylin-eosin; original magnification ×200). C Perivascular inflammation (hematoxylin-eosin; original magnification ×400). D Organizing pneumonia with granulation tissue plugs within the lumen of respiratory bronchioles (hematoxylin-eosin; original magnification ×200).

Fig. 2

Histopathologic findings of COVID-19 in the kidney, small bowel and spleen. A Thrombotic microangiopathy with glomerular capillary loop and arteriole fibrin thrombi (hematoxylin-eosin; original magnification ×400). B Glomerulus with segmental capillary collapse and overlying podocyte hyperplasia (Jones methenamine silver; original magnification ×400). C Small bowel thrombus and mucosal ischemic changes (hematoxylin-eosin; original magnification ×100). D Spleen hilar thrombus (hematoxylin-eosin; original magnification ×200). E Detail of Fig. D with transmural vascular inflammation (hematoxylin-eosin; original magnification ×400). F Splenic thrombosis and infarct (hematoxylin-eosin; original magnification ×100).

Fig. 3

Cutaneous lesions in COVID-19. Livedo reticularis of skin in a patient with COVID-19.