Fatal pulmonary thromboembolism in asymptomatic COVID-19

Abstract

Background: Coronavirus disease 2019 (COVID-19) has claimed the lives of millions of people globally.

Aims: This study aims to identify the pathological findings at autopsy of asymptomatic COVID-19 death, to compare the incidence of acute bilateral pulmonary thromboembolism (ABPTE) in asymptomatic COVID-19 deaths versus non-COVID-19 deaths and to explore the possible pathogenesis of thrombosis in COVID-19. We also consider the place of COVID-19 in the death certification of 4 cases who died from ABPTE.

Methods: This study primarily reviewed post-mortem reports of 6 asymptomatic COVID-19 deaths. Post-mortem reports for the years 2019 and 2020 were also reviewed to establish the incidence of ABPTE. Each post-mortem report was reviewed for gross examination, histology and toxicology findings. A literature review on COVID-19 autopsy findings, COVID-19 pathogenesis, thrombosis in COVID-19 and asymptomatic SARS-CoV-2 infection was also conducted using PubMed.

Results: Of the 6 asymptomatic COVID-19 deaths, 4 died as a result of ABPTE, 1 died of ischaemic and hypertensive cardiac disease caused by coronary artery disease and ventricular hypertrophy and the remaining case died of heart failure due to dilated cardiomyopathy caused by subendocardial fibrosis. There were 2 cases of bilateral pulmonary thromboembolism (BPTE) in 2019 out of 140 post-mortems. Excluding the 4 cases of ABPTE described already, there was 1 case of ABPTE in 2020 out of 156 post-mortems. A literature review on the pathogenesis of thrombosis in COVID-19 highlighted the significant role that the endothelium plays.

Conclusions: Massive pulmonary thromboembolism may be a significant cause of death in asymptomatic COVID-19 infection.

Keywords: Asymptomatic; COVID-19; Pulmonary thromboembolism; SARS-CoV-2; Thrombosis.

Fig. 1

Acute bilateral pulmonary thromboembolism (ABPTE). A Pulmonary artery occluded by thromboembolism at lung hilum. B Open cross-section of the pulmonary artery tree showing occlusion by thromboembolism

Fig. 2

SARS-CoV-2 entry, replication and exit. Reproduced from Virology, transmission, and pathogenesis of SARS-CoV-2, Cevik M, Kuppalli K, Kindrachuk J, et al., 371, 3862, 2021 with permission from BMJ Publishing Group Ltd

Fig. 3

Host cell inducing interferon production in order to interfere with viral replication

Fig. 4

IL-1 and TNF-α production promoting thrombosis

Fig. 5

The endothelium during homeostasis (left) and activated by IL-1 and TNF-α (right)