RATIONALE: Fibrosing interstitial pneumonitis can be the common end result to many different lung diseases, including chronic viral inflammations, as COVID-19. Some SARS-CoV-2 infected patients develop the acute respiratory distress syndrome. This condition is histopathologically known as diffuse alveolar damage which may be followed by a proliferative phase. Whereas COVID-19 has showed a longer disease outcome until clinical cure or death compared to other chronic infections, our hypothesis is that COVID-19 patients tend to develop a more prominently proliferative phase, even those who progress to death, with an exacerbated fibroblast and myofibroblast proliferation. METHODS: Minimally invasive autopsy(MIA) was performed on 47 confirmed COVID- 19 patients for lung samples. Clinical, demographic, mechanical ventilation parameters and radiological data were collected by electronic medical record. A detailed histomorphological analysis by two pulmonary pathologists was performed by H&E staining. Verhoeff, picrosirius red and SMA staining were performed for histomorphometric analysis of interstitial fibrosis according to ATS/ERS morphometric guidelines. RT-qPCR was performed to detect the viral genome of SARS-CoV-2, targeting the E and N2 genes, in lung tissue collected from all patients at MIA. RESULTS: Patients were equally distributed in men and women and the mean age was 67 years old. The average time of death after the onset of typical COVID-19 symptoms was approximately 18 days. Regarding the most common comorbidities, 55% of the patients had systemic arterial hypertension, 40% were obese, 25% were smokers and 22% had chronic cardiovascular and respiratory diseases. In the radiological exams, ground glass was the most prevalent finding. The clinical and histomorphological correlation revealed two phenotypes: 1) Poor lung outcome - a progressive decline in PaO2/FiO2 ratio and high complacency levels, closely related to fibrosing interstitial pneumonitis (P&lt;0.05) together with an increased collagen fibers deposition (P&lt;0.05), SMA+ stained cells (P&lt;0.05), elastic rarefaction (P&lt;0.05) and higher viral load;2) Better lung outcome - a progressive increase in PaO2/FiO2 ratio and low complacency levels, usual pattern of elastic and collagen fibers and SMA+ cells, but sudden death due to acute pulmonary thromboembolism. Moreover, SARS-CoV-2 viral genome was detected in all lung tissue collected(47), with a mean of 3,403,775 and 90,683,263 copies/mg for N2 and E genes respectively. CONCLUSIONS: The fibrotic septal thickening is related to poor lung outcome by progressive decline in PaO2/FiO2 ratio and late death. This pathophysiological process may be an important sequel in pos- COVID19 patients to trigger a fibrosing interstitial pneumonitis. Further investigations with larger studies are warranted. .
Respiratory disease, and treatment / thematic poster session COVID-19 outcome-based pathology reveals the birth of fibrosing interstitial pneumonitis