COVID-19 Bimodal Clinical and Pathological Phenotypes (preprint)

BackgroundPatients with coronavirus disease-2019 (COVID-19) present varying clinical complications. Different viral load and host response related to genetic and immune background are probably the reasons for these differences. We aimed to sought clinical and pathological correlation that justifies the different clinical outcomes among COVID-19 autopsies cases. MethodsMinimally invasive autopsy was performed on forty-seven confirmed COVID-19 patients from May-July, 2020. Electronic medical record of all patients was collected and a comprehensive histopathological evaluation was performed. Immunohistochemistry, immunofluorescence, special stain, western blotting and post-mortem real-time reverse transcriptase polymerase chain reaction on fresh lung tissue were performed. ResultsWe show that 5/47 (10,6%) patients present a progressive decline in oxygenation index for acute respiratory distress syndrome (PaO2/FiO2 ratio), low compliance levels, interstitial fibrosis, high -SMA+ cells/protein expression, high collagens I/III deposition and NETs(P<0.05), named as fibrotic phenotype (N=5). Conversely, 10/47 (21,2%) patients demonstrated progressive increase in PaO2/FiO2 ratio, high pulmonary compliance levels, preserved elastic framework, increase thrombus formation and high platelets and D-dimer levels at admission (P<0.05), named as thrombotic phenotype. While 32/47 (68,1%) had a mixed phenotypes between both ones. ConclusionsWe believe that categorization of patients based on these two phenotypes can be used to develop prognostic tools and potential therapies since the PaO2/FiO2 ratio variation and D-dimer levels correlate with the underlying fibrotic or thrombotic pathologic process, respectively; which may indicate possible clinical outcome of the patient.

SARS-CoV-2 Pneumonia Phenotyping on Imaging: Correlation with Minimally Invasive Autopsy (preprint)

Background: Imaging has played a key role in the evaluation of the new coronavirus SARS-Cov-2 disease (COVID-19), especially with chest radiography(CXR) and computed tomography(CT) for the viral pneumonia diagnosis. Despite all studies that have described the imaging findings of SARS-Cov-2 pneumonia, pathologic studies remain scarce, and adequate correlation of pathology with imaging features are occasionally reported.Methods: This unicentric retrospective observational study included 46 patients with confirmed COVID-19 who underwent minimally invasive autopsy (MIA). Autopsy was performed prospectively in consecutive patients, while imaging analysis was retrospective, using exams of the clinical routine. All images available were reviewed and classified for the presence and grade of viral pneumonia, as well as disease evolution on imaging. On CT exams, phenotypes were described as consistent with mild, moderate, or severe viral pneumonia, with or without radiological signs of organizing pneumonia(OP). In cases of severe pneumonia, when appropriate, CT phenotype could be classified as a diffuse form of OP or diffuse alveolar damage(DAD).Findings: Only three patients(7%) showed no pulmonary opacities on admission CXR, while 33 patients(72%) presented CXR findings consistent with moderate or severe viral pneumonia. Interestingly, most patients showed stability or improvement (reduction of opacities) on imaging during hospitalization, before death. Consolidations on CT, performed on 15 patients, were found in most patients (87%), more frequently showing features consistent with OP than signs of radiological DAD. Radiological signs of fibro-reparation were also prevalent on CT images. These findings correlate with histopathological features of organizing plugs and/or fibrin “balls”(87%), indicating OP and/or acute fibrinous and organizing pneumonia(AFOP). Also, in the CT exams, interstitial fibrosis was the most prevalent pathological feature and was described as a nonspecific interstitial pneumonia (NSIP)-simile pattern.Interpretation: The role of imaging as a potential prediction tool of evolution to pulmonary fibrosis in patients with SARS-CoV-2 pneumonia is yet to be established. In this study, a correlation was shown between imaging findings and MIA pathological patterns of lung disease. Signs of organization and fibrosis were prevalent on both imaging and pathology and, differently from what has been described in the majority of previous studies, DAD was not the most important radio-pathological pattern in this study. Based on these findings, authors believe that the report of radiological signs of organization on CT, in the form of OP foci, as a diffuse form of OP or radiological DAD is likely as important as, or even more important than the description and quantification of the burden of opacities. Furthermore, it would be crucial to identify and describe the fibro-reparative radiological signs. This imaging phenotyping, which correlates with the pathological findings, might indicate a higher probability of developing post-COVID pulmonary fibrosis and other complications.Funding: No external funding support.Declaration of Interests: The authors declare no conflict of interest.Ethics Approval Statement: This study was approved by the local Research Ethics Committee and written informed consent for the use of radiological imaging exams and MIA results was waived.