COVID-19 likely associated with high incidence of thromboembolic events

1. In this study of 12 decedents with COVID-19, deep venous thrombosis was observed in over half of the study population.

2. Pulmonary embolism was the direct cause of death in a third of the patients autopsied.

Evidence Rating Level: 4 (Below Average)

Study Rundown: While the majority of people who develop COVID-19 experience a mild disease course, a significant portion of those who are infected fall ill with a more severe presentation. While several risk factors have been identified, the pathogenesis of the disease remains unclear. Identification of the causes of death in affected patients may help clarify the disease course and guide the development of treatment strategies. In this study, complete autopsy of 12 consecutive patients with COVID-19 revealed bilateral deep venous thrombosis of the lower extremities in over half of patient and most died of massive pulmonary embolism. Laboratory testing revealed elevated levels of lactate dehydrogenase, D-dimer, and C-reactive protein, while histopathological findings included diffuse alveolar damage, microvascular thromboemboli, and capillary congestion. Half of the patients showed moderate virema; those without viremia showed negligible viral load in all biopsied tissues aside from the lungs and pharynx. All patients in the study had comorbidities including obesity, asthma, COPD, and diabetes, and all but one had preexisting heart disease. This study had a small sample size, making it difficult to assess the true rate of thromboembolic events in COVID-19 patients. Additionally, viral dynamics could have been affected by postmortem processes, potentially confounding the obtained titers.

Click here to read the study in Annals of Internal Medicine

Relevant Reading: Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease

In-Depth [prospective cohort]: This study conducted in Germany consisted of 12 consecutive autopsies beginning with the first known SARS-CoV-2-positive death that occurred in Hamburg. In addition to external examination and internal dissection, decedents were subjected to postmortem computed tomography (PMCT) as well as histopathological and virological evaluation. For histology, tissue was obtained from the heart, lungs, liver, kidneys, spleen, pancreas, brain, prostate and testes (in males), ovaries (in females), small bowel, saphenous vein, common carotid artery, pharynx, and muscle. For virology, tissue was obtained from the heart, lungs, liver, kidney, saphenous vein, pharynx, and venous blood. The autopsied lungs were heavy, congested, firm, and friable with mild pleurisy and a patchy appearance; PMCT demonstrated mixed patterns of reticular infiltration with severe, dense consolidation. On autopsy, 7 of the 12 patient had evidence of deep vein thrombosis with none having had suspected deep vein thrombosis before death. Four of these patients had died from pulmonary embolism. Major histological findings included hyaline membranes, activated pneumocytes, and protein-enriched interstitial edema. According to quantitative RT-PCR, every patient carried SARS-CoV-2 RNA in the lungs (range, 1.2×104 to 9×109 copies/mL), but only 4 had detectable viral RNA in the brain or saphenous vein. 5 of 6 patients with moderate viremia (<4×104 copies/mL) also had a substantial concentration of viral RNA in the heart, liver, or kidneys.

Image: PD

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