The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation

Abstract

The pandemia of coronavirus disease 2019 has caused more than 355,000 confirmed deaths worldwide. However, publications on postmortem findings are scarce. We present the pulmonary findings in four cases of fatal COVID-19 with a spectrum of lung pathology reflecting disease course and duration, invasive therapies, and laboratory features. Early disease is characterized by neutrophilic, exudative capillaritis with microthrombosis and high levels of IL-1beta and IL-6. Later stages are associated with diffuse alveolar damage and ongoing intravascular thrombosis in small to medium-sized pulmonary vessels, occasionally with areas of infarction equivalents, accompanied by laboratory features of disseminated intravascular coagulation. In late stages, organizing pneumonia with extensive intra-alveolar proliferation of fibroblasts and marked metaplasia of alveolar epithelium can be observed. Viral RNA is encountered in the lung, with virus particles in endothelial cells and pneumocytes. In many patients, multi-organ failure with severe liver damage sets in finally, possibly as consequence of an early-onset proinflammatory cytokine storm and/or thrombotic microangiopathy.

Two distinct immunopathological profiles in autopsy lungs of COVID-19

“…The ISG high pattern is observed in patients, who die early after hospitalization and is characterized by high viral load and high levels of pro-inflammatory cytokines, yet relatively intact lung morphology, while the ISG low pattern is characterized by low viral load, massive lung damage, marked lung immune cell infiltrates and late death. Our findings are consistent with epidemiological data showing two peaks of mortality 24 , and another study of four COVID-19 autopsies, where one patient died early after hospital admission, with striking upregulation of pulmonary IL-1b/IL-6 in lungs and little lung damage, while three patients expressed low levels of pulmonary cytokines, massive DAD and delayed death 25 . Therefore our study allows us to propose two immunopathological stages of pulmonary COVID-19.…”

Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage: an autopsy study with clinical correlation and review of the literature

“…Similarly, these reports describe general findings, and the presence of MKs is not further commented. In the remaining autopsy studies, including a review article, there are no references to MKs [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]41]. Various reasons could explain this absence.…”

Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage. An autopsy study with clinical correlation and review of the literature.

“…Similarly, these reports describe general ndings and the presence of MKs is not further commented. In the remaining autopsy studies, including a review article there are no references to MKs [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]41]. Various reasons could explain this absence.…”