key: cord-255525-7w5u789h authors: de Sales, Anderson Ribeiro; de Melo Casagrande, Emerson; Hochhegger, Bruno; Zanetti, Glaucia; Marchiori, Edson title: The Reversed Halo Sign and COVID-19: Possible Histopathological Mechanisms Related to the Appearance of this Imaging Finding date: 2020-07-27 journal: Arch Bronconeumol DOI: 10.1016/j.arbres.2020.06.029 sha: doc_id: 255525 cord_uid: 7w5u789h nan The authors declare that they have no conflicts of interest to express. Related to the Appearance of this Imaging Finding El signo de halo invertido y la covid-19: Posibles mecanismos histopatológicos relacionados con la aparición de este hallazgo radiológico The disease presents challenging clinical, pathophysiological, laboratory, and histopathological aspects that have been the subject of research in practically all countries in the world. This complexity of aspects also applies to imaging findings. High-resolution chest CT is the most effective radiological examination for the evaluation of lung involvement by COVID-19. The predominant CT findings of COVID-19 pneumonia are multifocal, bilateral, peripheral, and basal-predominant ground-glass opacities, often with round and/or oval morphology and/or consolidation. The crazypaving pattern may also be observed, particularly when the disease progresses. These CT findings are not specific to COVID-19; similar results can be obtained for other infectious and non-infectious diseases. Nonetheless, normal chest CT findings do not exclude this diagnosis. [1] [2] [3] Another tomographycal finding recently related to COVID-19 pneumonia is the reversed halo sign (RHS). This sign is defined as a focal rounded area of ground-glass opacity surrounded by a complete or near-complete ring of consolidation observed on chest computed tomography, 4 has been reported in association with a wide variety of clinical entities, including infectious and noninfectious diseases. 5, 6 The presence of the RHS in patients with COVID-19 has been reported, 1,7-10 with a highly variable incidence among published studies. Bai et al 7 reported that the RHS was present in 5% of 219 patients, whereas the incidence was much lower in other casuistic studies; Bernheim et al 1 observed the RHS in only 1 of 121 patients, and Ai et al 3 did not report the presence of the sign in any of their 1,014 patients. Although some authors have reported the appearance of the RHS in later stages of the disease, during the evolution of the pulmonary infectious process, 1,2 other authors have described its presence in the first days after symptom onset. 8, 9 Recently a 48-year-old man presented to our hospital with a 5-day history of fever, cough and myalgia. He reported having systemic arterial hypertension and type 2 diabetes mellitus. On admission, the patient was in good general condition; he was tachypneic, his body temperature was 38.2•C, and cardiac and pulmonary auscultation was normal. Laboratory Hydroxychloroquine and symptomatic medication were administered. The patient recovered uneventfully, with the disappearance of symptoms and normalization of laboratory tests. He was discharged after 14 days in an asymptomatic state. To understand RHS formation, an understanding of the pathogenesis of lung injury is very important. Although few reports on the histopathological characteristics of COVID-19 have emerged to date, early stages of organization (fibroblast proliferation) have been observed to follow initial diffuse alveolar damage. 11, 12 Potential courses of this typical response to lung injury are known; if the stimulus for injury is removed and the basement membranes are intact, then the intraluminal fibroblastic tissue is remodeled into the interstitium or removed by the fibrinolytic system, and the normal architecture is reestablished. If the stimulus for injury persists and the integrity of the basement membranes has been lost, then the alveoli collapse, their basement membranes fuse, fibroblast activation persists, and the self-reinforcing formation of organizing fibroblastic tissue progresses to fibrosis. 13 In COVID-19 cases, the predomination of fibroblastic tissue organization and development of fibrosis have been observed after the first week of the symptom onset. This process can be characterized as organizing pneumonia, which appears histologically as organizing fibroblastic plugs of spindle-shaped cells in a palestaining matrix. 13 Also, presence of alveolar exudative inflammation, interstitial inflammation, fibrin exudation and alveolar hemorrhage has been described, and can compose the appearance of ground glass opacities seen in the RHS. 14,15 Consistently, histopathological examination of a transthoracic-needle lung biopsy sample from a patient who died 3 weeks after COVID-19 diagnosis showed diffuse alveolar damage in the organizing phase, with intra-alveolar fibrinous exudates, interstitial fibrosis, intraalveolar fibrous plugs and organizing fibrin at most foci. 12 This finding suggests that the disease course of COVID-19 might be similar to those of other viral infections, with early progression to organizing pneumonia and presentation of the RHS. Enhanced images (C and D) obtained at the same levels as A and B 3 days later show multiple reversed halo signs (arrows) in both lungs. Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection. Related to COVID-19. Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease Fleischner Society: Glossary of terms for thoracic imaging Reversed halo sign: high-resolution CT scan findings in 79 patients The reversed halo sign: update and differential diagnosis Performance of radiologists in differentiating COVID-19 from viral pneumonia on chest CT Use of Chest CT in Combination with Negative RT-PCR Assay for the 2019 Novel Coronavirus but High Clinical Suspicion CT imaging of one extended family cluster of corona virus disease 2019 (COVID-19) including adolescent patients and "silent infection Longitudinal CT Findings in COVID-19 Pneumonia: Case Presenting Organizing Pneumonia Pattern Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19 Organization and fibrosis as a response to lung injury in diffuse alveolar damage, organizing pneumonia, and acute fibrinous and organizing pneumonia Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19 The Emerging Spectrum of Cardiopulmonary Pathology of the Coronavirus Disease 2019 (COVID-19): Report of 3 Autopsies From Houston, Texas, and Review of Autopsy Findings From Other United States Cities A Pathological Report of Three COVID-19 Cases by Minimal Invasive Autopsies