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.