Discussion
In this report, we present an autopsy case of COVID-19 with anti-viral and anti-inflammatory therapy. Pulmonary pathology revealed severe hemorrhagic change, but the findings of DAD and subpleural fibrosis were not so prominent. Autopsy findings of COVID-19 have been reported from worldwide countries, including the United States13, and those from Europe14-16, Asia12, 17, 18, and Africa19. No national differences have been described, and most reports stated that DAD is a major cause of respiratory failure, which is different from the present case.
Since this pandemic occurred, efforts have been made to overcome the exaggerated host immune reactions, and a living WHO guideline on drugs for COVID-19, for example, was repeatedly updated20. Autopsy of the present case was performed in April, 2021 during the 4th pandemic wave in Japan, and the patient was treated with anti-inflammatory therapy with dexamethasone and tocilizumab. Thus, the absence of active DAD and severe fibrosis would be due to the therapeutic effects. Subpleural fibrosis was also restricted. Thus, we interpret that the direct cause of death was severe hemorrhage, but not DAD.
The reason why severe hemorrhage occurred remain undetermined. In the kidney, microvascular thrombosis was seen in the glomerular vessels, resembling pathology of DIC, although the last platelet count was over 90,000/µl in the peripheral blood. The patient was also under anticoagulation therapy with warfarin, due to permanent atrial fibrillation. His PT-INR was kept between 1.8-3.8 in the last day. At the autopsy, his stomach was filled with blood, and multiple ulceration was seen accompanying candida colonies. In kidney, bacterial colonies were also present with multiple abscess. Thus, co-infection may relate to the systematic coagulation and fibrinolysis disorder, but it could not be concluded.
In conclusion, we present the autopsy case of COVID-19 treated with remdesivir, dexamethasone, and tocilizumab. The pulmonary pathology suggested the therapeutic effect, but the cause of severe hemorrhage remain unknown. Co-infection would be also a future issue in relation to anti-inflammatory therapy for COVID-19. We hope our analysis contributes to save the global lives from this pandemic disease.