Discussion
To our knowledge this is the first autopsies from lungs, liver and
kidneys in decedents with positive test for SARS-CoV-2 from Iran. In our
study early phase of DAD was the main finding in microscopic examination
of the lungs, characterized by interstitial edema with fibrinous
exudates and hyaline membranes. Our findings were similar to previous
lung pathology studies from china in COVID-19 patients described DAD
with edema, hyaline membranes, and inflammation, features characteristic
of typical ARDS (9-12). There was no evidence of mucus plugging within
airways or eosinophilic infiltration in lung autopsies.
The importance of this study was because some of previous reports
suspected the pathology of lungs in covid-19 patients differ from
diffuse alveolar damage (DAD) and hyaline membrane formation which are
hallmarks of typical ARDS (13, 14).
The main pathology in both of our patients consisted of DAD with typical
histopathologic findings (15).
Intravascular micro-thrombi were detected in one of our patients with
high plasma levels of D-dimer and ferritin (2436 and 1220 ng/ml,
respectively) despite anticoagulation therapy which support the
hypothesis of pulmonary intravascular coagulopathy associated with
elevated D-dimer and ferritin secondary to extensive pulmonary
inflammation (16,17)
It is demonstrated that D-dimer is a significant independent biomarker
of poor prognosis and values above 1000 ng/ml have been associated with
fatal outcome of COVID-19 patients (18).
Increased ferritin and other inflammatory markers (CRP, interleukin-1,
interleukin-6, and tumor necrosis factor) stimulate microvascular
endothelial cell injury, intra-vascular coagulopathy and increased
vessel permeability result in micro-thrombi formation and intra-alveolar
hemorrhage (19).
In contrast to Margo and colleagues reported no viral cytopathic changes
in lung tissues (20), Viral cytopathic changes followed by diffused
alveolar damage and thrombotic microvascular injury was a remarkable
finding of our study.
Due to prevalent organ involvement in COVID-19, pathologic
investigations have essentially focused on respiratory and hematologic
disorders, whereas limited data about kidney injury are released (21).
Clinically, the incidence of acute kidney injury (AKI) in COVID-19
varied from 0.9% to 29% in different centers. New onset proteinuria
was also reported by several institutions (22).
One of our decedents suffered from new onset proteinuria, AKI and
creatinine rise during admission. Renal autopsy revealed acute
tubulointerstitial nephritis (ATIN) with subtle attenuation of tubular
epithelium, interstitial edema and lymphocytic infiltration. Vascular
damage or arteriosclerosis was not detected, whereas the decedent had no
underlying disease. Glomeruli were intact.
Su H and colleagues examined 26 autopsies of patients with COVID-19 and
revealed proximal acute tubule injury (ATI), occlusion of microvascular
lumens mainly by erythrocytes with ensuing endothelial damage, as well
as glomerular and vascular changes indicative of underlying diabetic or
hypertensive disease (21). The researchers suspected SARS-CoV-2 virus
might directly infect the renal tubular epithelium and podocytes, which
was associated with AKI and proteinuria in patients with COVID-19 (21).
Liver biopsy revealed steatosis, lobular and portal inflammation.
Hemorrhage and congestion as well as focal necrosis were also detected.