A 61-year-old woman was referred to an emergency department in Rome (Italy) due to sudden loss of consciousness and cardiac arrest. She could not be resuscitated and was declared dead soon after admission. The patient had contact history with confirmed COVID-19 patients, and 32 days before decease was tested positive for SARS-Cov-2 infection without any symptoms. 5 days before death she tested negative; the test was repeated once more at a distance of 48h, confirming negative results. She had no medical co-morbidities or any cause of immunosuppression and presented as healthy individual before SARS-CoV-2 infection, taking no medications. No relevant symptoms have been shown neither at the time of pathogenic test, nor until exitus. To determine the cause of death a complete autopsy was performed.
Whole body complete post-mortem examination was performed at the National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS Hospital (Rome, Italy) according to guidance for biosafety practices autopsies and collection of specimens and approved by the local Clinical Research Ethics Committee (approval number: n° 9/2020).
Macroscopic inspection of the lung revealed pulmonary edema, massive bilateral congestion and regions of dark-colored haemorrhage (Fig S1A). The pleura was inconspicuous except for fibrous adhesions and pleural effusion was absent. The most striking feature was the presence of a large thrombus occluding the main pulmonary artery at bifurcation (Fig 1A). Lungs were bilaterally extensively sampled for a complete histological evaluation. Microscopic analysis has shown heterogeneous pattern of pathological changes in the lung tissue, as well as different stages of diffuse alveolar damage with edema and hemorrhagic areas (Fig S1 D). Numerous vascular thrombi were detected (Figs 1B; S1B). Diffuse interstitial fibrosis with fibroblast proliferation was present (Fig 1D), toghether with inflammatory infiltrate of pulmonary interstitium (Figs 1C; S1D). The alveolar capillaries thickened, and displayed extravasion of erythrocytes into alveolar spaces (Fig S1C). Infiltrating T lymphocytes, both CD4+ (Fig 1E) and CD8+ (Fig S1F), were present into alveolar septa and clustered around capillary vessels, as demonstrated by immunohistochemistry. In addition numerous macrophages (CD68+) were found (Fig 1F). Of note, positivity for CD20 was not detected, indicating the absence of infiltrating B-lymphocytes. Some areas of the lungs appeared not affected and presented no signs of alveolar damage (Fig S1E). Lung samples tested negative for real-time PCR for SARS-Cov-2-infection.
Gross examination of heart revealed decrease in volume and consistency (weight 250 g). Left and right atrium and ventricles appeared dilated. The myocardium was flabby, congested and hemorrhagic (Fig S2A). At histological level myocytes hypertrophy and variable degrees of interstitial and vascular fibrosis were found (Fig S2B). Active myocarditis was characterized predominantly by lymphocytic mononuclear infiltrate, dissociating myocyte fibers (Figs 1G; S2 C,D). The infiltrating cells were mainly represented by CD4+ T lymphocytes (Fig S2E); CD8+ T lymphocytes were instead rare (Fig S2F). CD68+ macrophages were numerous and diffuse (Fig 1H), while B-lymphocytes were not detected.
Other organs analyzed showed some histopathological modifications, as reported in autoptic findings of COVID-19 patients: kidneys displayed swelling of the glomerular endothelial cells, the spleen showed white pulp atrophy and congestion of red pulp and macrovesicular steatosis was of the liver observed.
In the final autopsy report, the cause of death was listed as pulmonary arterial thrombosis.