Higher prevalence of pulmonary macrothrombi in SARS-CoV-2 than in influenza A: autopsy results from 'Spanish flu' 1918/1919 in Switzerland to Coronavirus disease 2019

Abstract

Similar to the influenza A pandemic in 1918/1919, the new Coronavirus disease 2019 (COVID-19) has spread globally. The causes of death in COVID-19 are frequently compared to a seasonal influenza outbreak. Complete COVID-19 autopsy studies were almost non-existent in the first months of the outbreak and are still rare with respect to the number of deaths. It has been recently reported that capillary microthrombi are significantly more prevalent in patients with COVID-19 than in patients with influenza A. To date, the contribution of macrothrombi, i.e. visible thrombi in pulmonary arteries, to the death of patients with influenza A in comparison to COVID-19 remains unaddressed. Here, we report autopsy findings in 411 patients who died from the 'Spanish' influenza A pandemic between May 1918 and April 1919 at the University Hospital Zurich, Switzerland. We compare these results with influenza A autopsies from 2009 to 2020, other influenza A autopsy series and all COVID-19 autopsies published to date. No descriptions of any macroscopic thromboembolic events were mentioned in influenza A autopsy reports. In 75 published COVID-19 autopsies, pulmonary artery thrombosis/embolism was reported in 36%. The direct comparison of macroscopic autopsy findings suggests a significantly greater degree of grossly visible pulmonary macrothrombi in patients with COVID-19 in comparison to influenza A autopsies even though most patients received empiric thromboprophylaxis. This is consistent with the concept of a SARS-related de novo coagulopathy with generalised in situ clot formation, which could explain the high incidence of pulmonary thrombosis/embolism with or without underlying deep vein thrombosis and in the absence of a history of venous thromboembolic events.

Keywords: COVID-19; autopsy; influenza A; pulmonary embolism.

Figure 1

Post‐mortem pulmonary gross findings in an influenza A patient. (A) Gross appearance of the lung of a 61‐year old female patient showing diffuse haemorrhagic consolidation suggestive of bronchopneumonia, predominantly in the lower lobe (arrows). (B,C) Higher magnification from the same lung reveals open vessels and consolidation (arrows).

Figure 2

Histopathological findings in lungs of influenza A patients. (A) Lung of a 22‐year old female with influenza A infection. There are acutely congested alveolar spaces and interstitial capillaries, and many granulocytes related to secondary bacterial pneumonia in the alveolar spaces in a patchy distribution pattern. (B) High power view of the same patient shows congested vessels, intra‐alveolar bronchopneumonia and scattered reactive enlarged endothelial cells (arrow) without any evidence of endotheliitis. (C) Higher power view of a lung from a 84‐year old female patient with influenza A showing congested vessels (arrows) and intra‐alveolar bronchopneumonia. There is no evidence of fibrin thrombus formation. All images H&E stains.

Figure 3

Post‐mortem pulmonary gross findings in a COVID‐19 patient. (A) Lung of a 81‐year old male patient with coronary heart disease and arterial hypertension showing several thrombotic occlusions of large (white arrow) and medium sized (black arrows) arteries. Higher power views of thrombotic occlusion of (B) a large pulmonary artery (white arrow) and (C) medium sized arteries (black arrows).

Figure 4

Post‐mortem cardiac and hepatic gross findings in COVID‐19 patients. (A) Cardiac macrothrombosis in a 54‐year old male patient with a history of renal transplantation due to diabetic nephropathy who developed progressive respiratory failure despite mechanical ventilation. There are large thrombi in the left (white arrow) and right (black arrow) ventricles. (B) Higher power view of intra‐ventricular thrombus in the left (white arrow) and right (black arrow: proportion of histologically confirmed thrombus) ventricles. (C) Liver of a 76‐year old male patient showing a large venous thrombus (arrow). Inset: Higher power view (rotated).

Figure 5

Histopathological findings in lungs of COVID‐19 patients. (A) Lung of a male COVID‐19 patient with pre‐existing lung fibrosis. Diffuse alveolar damage with hyaline membranes (arrow) and congested interstitial capillaries (H&E stain) are present. Inset: intra‐vascular fibrin formation in a small sized vessel (arrow) (SFOG trichrome stain). (B) Lung of a male COVID‐19 patient with hyperplastic type II alveolar epithelial cells (star), desquamation and pronounced endotheliitis of a medium sized pulmonary vessel (arrows). (C) Pulmonary fibrin thrombus in a male COVID‐19 patient in a medium sized arterial vessel (H&E stain). (D) Leucocytic intra‐vascular thrombus (‘leucocytic clot’) with minimal fibrin formation (H&E stain).