Severe Acute Respiratory Syndrome Coronavirus 2 Induces Hepatocyte Cell Death, Active Autophagosome Formation and Caspase 3 Up-Regulation in Postmortem Cases: Stereological and Molecular Study

Severe Acute Respiratory Syndrome Coronavirus 2 Induces Hepatocyte Cell Death, Active Autophagosome Formation and Caspase 3 Up-Regulation in Postmortem Cases: Stereological and Molecular Study

Atefeh Shirazi Tehrani,,^1,2 Fatemeh Sadat Tabatabaei Mirakabad,² Mohammad-Amin Abdollahifar,^1,2 Shamim Mollazadehghomi,³ Shahram Darabi,³ Mehdi Forozesh,⁴ Mostafa Rezaei-Tavirani,⁵ Gholam-Reza Mahmoudiasl,⁴ Behnaz Ahrabi,⁶ Zahra Azimzadeh¹ and Hojjat Allah Abbaszadeh^1,2,6

¹Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
²Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
³Cellular and Molecular Research Center, Research Institute for Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran
⁴Iranian Legal Medicine Organization, Tehran, Iran
⁵Proteomics Research Center, Faculty of Para Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
⁶Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

This research investigated the histopathological changes in the tissue of the lung, heart and liver, hepatocyte cell death, autophagy, and the apoptosis inductions in the postmortem cases. Since December 2019, coronavirus disease 2019 (COVID-19) has become a significant global health concern. In order to clarify the changes in tissues of the lung, heart and liver by COVID-19, samples were taken from five patients who died of COVID-19 and five control cases, and the pathological changes in the lung, liver, and heart tissue were studied by X-ray, computed tomography, histological studies, and stereological analysis. The formation of hyaline membranes, alveolar wall edema, and fibrin exudate was seen on histological analysis of the lungs in the COVID-19 group. Stereological analysis illustrated the number of hepatocytes, volume of the sinusoid, and volume of the liver have been decreased, however the pathological changes in the heart tissue were not observed. Serum levels of alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and angiotensin-converting enzyme significantly increased. Real-time PCR results showed that the Bcl2, Caspase3, ATG5, and LC3 decreased while the Bax increased. COVID-19 causes fibrotic changes in the lung tissue and hepatocyte mortality in the liver tissue. Besides, it elevates the level of apoptosis and autophagy markers.

Keywords —— apoptosis; autophagy; autopsy; COVID-19; histopathology

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Tohoku J. Exp. Med 2022, 256, 309-319.

Correspondence: Hojjat-Allah Abbaszadeh, Laser Application in Medical Sciences Research Center and Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Velenjak Street, Tehran 1985717443, Iran.

e-mail: Dr.abbaszadeh@sbmu.ac.ir