Fibrotic-like CT Alterations in COVID-19: Distinct Patterns of Temporal Evolution
2022 American Thoracic Society poster presentation, San Francisco, USA, C38 Poster 3798, May 17th, 2022 - supplementary material #ATS2022
[Alterações fibróticas-like na tomografia de tórax em COVID-19: diferentes padrões de evolução temporal: material suplementar ao poster a ser apresentado na ATS 2022, 17 de maio de 2022]
Authors: Leticia Kawano-Dourado1,2,3, Juan I. Enghelmayer4, Dyvia Patel5, Roberta Fittipaldi3, Adriana Jardim6, Juliana Puka3, Tarsila Vieceli7, Jennifer Loso5, Daniel Samolski8, Adrian Caser4,9, Carlos R. R. Carvalho3, Marie-Pierre Debray10, Bruno Crestani1,11, Raphaël Borie11.
1 INSERM 1152 – University of Paris. Paris, France
2 HCor Research Institute, Hospital do Coracao, Sao Paulo, Brazil
3 Pulmonary Division, Heart Institute (InCor), University of Sao Paulo, Sao Paulo, Brazil
4 FUNEF Foundation, Buenos Aires, Argentina
5 Division of Pulmonary, Critical Care, and Sleep Medicine; University of Florida
6 Sao Paulo Brazilian Air Force Hospital
7 Internal Medicine Department, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
8 OSDE private health insurance Advisor, Buenos Aires, Argentina
9 Thoracic radiology department, Diagnóstico Médico, Buenos Aires, Argentina
10 Service de Radiologie, Hôpital Bichat, APHP, Paris, France
11 Service de Pneumologie A, Hôpital Bichat, APHP, Paris, France
Conflict of interest: None of the authors declare any conflict of interest related to the work herein presented
Note that the content here has not been reviewed by peers.
Introduction: The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relatively high mortality . The computed tomography (CT) of the chest of acute COVID-19 pneumonia usually shows multifocal or diffuse ground-glass opacities (GGOs) and consolidations, while reticular opacities are less commonly seen . In non-severe cases, CT findings display the greatest intensity around 10 days post symptom onset, showing progressive resolution after the 14th day . Nevertheless, a more protracted course has been observed in 20-30% of hospitalized patients, and it is associated with increased baseline disease severity and the organizing pneumonia pattern. [4,5] In one study that included both non-severe and severe cases, chest CT scans performed close to discharge (24 days, range 10 - 44 days) showed significant residual disease in 94% of the patients . In a small proportion of cases, fibrotic-like CT findings such as intralobular thickening, reticular opacities, traction bronchiectasis, and (rarely) honeycomb may be seen [5,6]. The description of the CT imaging findings’ temporal evolution in COVID-19 cases with fibrotic-like alterations is still scarce in the literature. Thus the purpose of this multicentric case series was to better characterize fibrotic-like alterations in COVID-19 by describing the temporal CT evolution in these patients.
Methods: Transversal study where the present authors, mostly interstitial lung disease (ILD) specialists, from 04 different countries, identified at the moment of contact what were the cases they were seeing that met the following eligibility criteria: age 18 years or older, confirmed COVID-19 infection by RT-PCR where fibrotic-like changes were present on a CT scan, called index CT. Additionally, the cases must have had a baseline CT scan without fibrotic-like changes. A qualitative assessment of the baseline and index (follow-up) CT scans were performed by two readers (LKD and MPD). Data are presented as mean or median when appropriate and median comparisons were made using the Mann-Whitney test. Ethical approval was obtained in Brazil (CAPESQ 4.009.759), USA (University of Miami IRB202002364-2020), France (Paris Nord CEERB 00006477), and Argentina (Diagnostico Medico IRB 09/2021).
Results: 34 COVID-19 patients were retrieved. 7 cases were excluded due to lack of baseline CT, and 4 cases were excluded due to the absence of fibrotic-like alterations on the index (follow-up) CT scan after central review (LKD and MPD). 23 patients with a mean of 2.3±0.5 scans/patient were therefore included in the final analysis. The sample was comprised of 61% of males, mean age of 63±9.8 years. The most common comorbidities were: 74% arterial hypertension, 30% diabetes, 23% obesity, and 18% COPD. On baseline CTs, the most common finding was diffuse or multifocal GGOs in 87% of the scans.
During hospitalization, 23 (100%) patients received corticosteroids for at least 10 days (all patients received dexamethasone 6mg/day for 10 days or until death or discharge), while 12 (52%) patients received an additional course of corticosteroid – median cumulative prednisone dose of 1410mg (IQR 937 – 2600). Regarding respiratory support, 8 patients (35%) received no respiratory support other than low flow oxygen, 14 patients (61% ) received non-invasive positive pressure ventilation (NIPPV) or high-flow nasal cannula (HFNC), and 8 patients (35%) received invasive mechanical ventilation (IMV). The mean FiO2 used on NIPPV and/or HFNC was 68%±24, while the mean FiO2 used on IMV was 90%±19.
After a median time of 42 days (range 22 – 130), the index (follow-up) CT scan showed most frequently reticular opacities with architectural distortion (78%) and traction bronchiectasis (53%) followed by GGOs (48%) and/or consolidations (48%). Honeycombing developed on only one scan.
Three distinct temporal CT patterns could be noted from baseline to the index (follow-up) scans (figure 1): worsening/no improvement (12 cases, 52%), improvement in (8 cases, 35%), and improvement in the lung bases with persistent disease in the upper lobes (3 cases, 13%), without difference between groups in the interval between baseline and the index (follow-up) scan (54 days (IQR 32 – 70), 45 days (IQR 28 – 94) and 62 days (IQR 30 – 84), respectively, p-value = 0.69). Interesting to mention, two cases in this series displayed CT imaging worsening for the first 30 days (all patients were on dexamethasone 6mg/d for at least 10 days in this period), which was followed by significant imaging improvement coinciding with the administration of higher doses of steroids (methylprednisolone 250-500mg/d for 3 days) (figure 1, D).
Four (18%) deaths occurred after a median time of hospitalization of 65 days (range 41 – 126): two deaths during the first hospital admission, two deaths after first hospital discharge (all 4 deaths occurred among those classified as overall worsening/no improvement).
Discussion: In our series, where only pre-selected COVID-19 cases with fibrotic-like alterations were included, reticulate and bronchiectasis in the midst of parenchymal distortion were the main findings seen in the follow-up (index) CT scan.  On baseline scans, the main image findings were GGOs and consolidations, not different from what is described in uncomplicated COVID-19 . Three distinct patterns of imaging evolution were observed: worsening/no improvement, improvement, and improvement in the lung bases with persistent alterations in the upper lobes. The pattern displaying improvement in the lung bases but residual alterations in the upper zones have already been described in post-acute respiratory distress syndrome (post-ARDS) and has been thought to be caused by ventilation-induced lung injury (VILI) in the upper zones [7, 8]. However, in our series, only one of the three cases displaying this pattern received IMV. Besides VILI, another possible pathophysiological explanation for this heterogeneous imaging evolution would be self-inflicted lung injury (P-SILI) where the heterogeneous negative pleural pressure generated around the lungs during effort breathing (higher anteriorly and superiorly on a patient lying supine) would be responsible for the upper/anterior sequelae in patients non-invasively ventilated . It is worth mentioning that one-third of the cases from this series have received no respiratory support other than low flow oxygen, supporting the hypothesis that COVID-19 pneumonia itself may evolve into a more complicated course in some cases. All patients received higher doses of steroids, higher than that proposed to treat COVID-19 ARDS , in some of these cases, the additional higher dose of steroid may have caused a significant imaging improvement, which deserves further exploration.
Image resolution was observed in some of our cases demonstrating that there was no fibrosis there. Longer follow-ups may be necessary in order to define permanent lung sequelae (true fibrosis) among those presenting with fibrotic-like CT imaging alterations. Likewise, the best management of these patients needs to be addressed in randomized controlled trials where causal inference between intervention and outcomes can be made.
In conclusion, this case series shows distinct patterns of CT evolution among COVID-19 cases with fibrotic-like alterations on the CT scan. Further studies are needed to determine the prevalence of fibrotic-like alterations, better characterize these cases, and how to best manage them.
We would like to acknowledge the contribution to this case series of Guilherme das Posses Bridi, MD, and Renato Miranda Lima, MD from the Respiratory ICU, Heart Institute (InCor) – Hospital das Clinicas, University of Sao Paulo, Sao Paulo, Brazil.
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Eu sou Leticia Kawano Dourado, doutora em pneumologia pelo HC-FMUSP, médica pneumologista e pesquisadora líder do grupo de pesquisadores do Instituto de Pesquisa do Hospital do Coração em São Paulo. As opiniões aqui veiculadas representam minha posição pessoal e não os das Instituições e Organizações as quais estou ligada.
Projeto Respira Evidência por Leticia Kawano Dourado