The severity of the disease caused by COVID-19 correlates well with the radiological presentations3. CT findings have been meticulously described4. Initial radiological findings appear to be very specific for COVID-19 in the context of the current pandemic. Very little has been published on the end stage of the disease, as critically ill patients usually do not undergo US or CT examinations unless they show signs of complications (pulmonary embolism or a superimposed bacterial pneumonia). In post-mortem examinations the damage is so extensive that some of the specific findings reported in the literature, such as the halo sign, or the distribution of the opacities are not identifiable. Pleural effusions were present in all 6 patients. A pleural effusion is an uncommon or nonspecific feature at early stages of COVID, but it has been identified as a sign of bad prognosis if shown10. Our findings are consistent with both alveolar and interstitial damage on the subsequent histological studies. Signs of pulmonary fibrosis are rare in patients that fully recover not requiring long hospital stays and/or mechanical ventilation6. In our study, there is a perfect correlation between the signs of fibrosis on CT and the subsequent histopathologic study, as discussed below.
The role of US in the management of COVID-19 infected patients has not been fully established. Our study shows a correlation of both US and CT: Areas of pleural thickening were shown as thickened pleura on CT, a B-pattern on ultrasound presented as GGO or crazy paving on CT, and subpleural consolidations as areas of consolidation in contact with the pleura. In our study, US was not as sensitive as CT to detect pleural effusions because examinations only included the anterior segments of the lung.
Our study confirms DAD as the predominant pattern in the lungs of patients infected with COVID-19 virus, most commonly in the proliferative phase. Other publications report exudative DAD as the predominant injury, sometimes associated with the proliferative phase. The presence of the fibrotic phase has been reported by very few groups14. In contrast, we demonstrated fibrotic DAD in most patients, always in association of proliferative DAD. Exudative DAD alone was only seen in a severely ill patient that died after nine days of admission. We believe that the differences found with other studies are related to longer courses of the disease of our cohort.. Our patients presented with symptoms for an average of 40,3 days before deceasing, whilst other groups reported symptoms from 16 days until death17. What is more, our patients were in the intensive care unit for an average of 35,2 days. Other groups report stays in the ICU for 7 to 30 days with an average of 12,5 days.17,16,15,23,14 Only Schaller et al. reports a case with areas of fibrotic DAD in a patient with a 26-day disease-to-death course and mechanical ventilation for 21 days14. AFOP alone, with no DAD, was the only lesion described by one author24. In our study, AFOP was present in two of our cases, but always associated with DAD.
Two patients in our study had been diagnosed with pulmonary embolism during admission, one which had an aortic mural thrombus. Vascular involvement cannot be evaluated on post-mortem CT’s. Therefore, radiopathological correlation was not possible. On histology, two patients showed microvascular thrombosis, a common finding in DAD, but not a necessarily specific feature in patients infected with COVID-19.
Our study findings are limited by different factors. First, the number of patients included in our study is very small. Second, whilst the cause of death of these patients was a result of ARDS, other conditions could have contributed to their death, such a bacterial infection, drug toxicity, or barotrauma. Finally, we have no prior history or examinations of the patients. The fact that fibrosis was present in almost all the mechanically ventilated for over 30 days may indicate that it is factor that could worsen the prognosis. However, fibrosis is not necessarily present in patients with a bad prognosis if they die at an early stage of the alveolar damage.
In conclusion, signs of fibrosis on CT correlated with the histopathological findings. Fibrosis in the context of COVID-19 infection may be an indicator of poor prognosis. CT may be a tool to identify the group of patients that develop fibrosis in the late stage of the disease. Further bigger studies are required to examine our observations.