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 . 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.

Pneumocytes are distinguished by highly elevated expression of the ER stress biomarker GRP78, a co-receptor for SARS-CoV-2, in COVID-19 autopsies

“…However, when we limited our analyses to Whites in the COVID-19 and non-COVID-19 groups, the differences in pneumocyte and macrophage GRP78 scores remained unaffected. Our semi-quantitative analyses on increased GRP78 expression of COVID-19 autopsies do not preclude dysregulation and, perhaps, proteostasis collapse per se as has been reported for other cellular processes such as glucose and fatty acid metabolism, immune, angiogenesis and coagulation pathways 25,34 . Plasma levels of GRP78 are not available for our patients.…”

A Prospective Study of Specialized Coagulation Parameters in Admitted COVID-19 Patients and Their Correlation With Acute Respiratory Distress Syndrome and Outcome

“…The underlying mechanisms of COVID-19-related coagulopathy are complex. They involve invasion of the vascular endothelial cells via angiotensin-converting enzyme 2 receptor causing endothelialitis, recruitment of inflammatory cells like polymorphs and monocytes with activation of complement and thrombin generation [ 15 ]. More than 33% of critical COVID-19 patients' are reported with coagulation abnormalities, including elevated levels of D-dimer [ 13 ].…”

COVID-19: Target Selection

“…To help severe patients with COVID-19 pneumonia, significant efforts are being made today to eliminate the manifestations of an inflammatory reaction, which is considered a consequence of the aggression of the pathogen. For example, the" fashionable" trend in this direction is the desire to neutralize cytokines in patients' bodies [18][19][20][21][22]. Currently, the term "cytokine storm" is used to explain one of the main reasons for the severity of the condition of patients with AP.…”