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To the editor,
We thank N. Hürsoy and colleagues for their interest in our study of patients four months after severe COVID-19 . We agree that there needs to be continued development of terms describing the radiographic appearance of post-COVID fibrotic-like patterns. We acknowledge that without the benefit of histopathology or serial imaging, our ability to define pulmonary fibrosis is limited.
The authors posit that parenchymal bands, irregular densities, and ground glass opacities, may be considered fibrotic-like patterns. We have included irregular densities, characterized as reticulations or traction bronchiectasis, as fibrotic-like changes. We did not include parenchymal bands , as these can be associated with atelectasis, which is common in COVID and can disappear over time . Similarly, we did not include isolated ground glass opacities as fibrotic-like changes, as these have been found to decrease over time in CT lung cancer screening cohorts  and in other post COVID-19 cohorts [5, 6].
A priori, we evaluated for both previously established interstitial lung abnormality categories , as well as categories of radiographic abnormalities reported in Acute Respiratory Distress Syndrome (ARDS) survivors using an established scoring system . This inclusive approach should facilitate meta-analyses and comparisons with future studies of COVID-19 survivors, interstitial lung disease studies, and studies of non-COVID ARDS survivors. Fu...
A priori, we evaluated for both previously established interstitial lung abnormality categories , as well as categories of radiographic abnormalities reported in Acute Respiratory Distress Syndrome (ARDS) survivors using an established scoring system . This inclusive approach should facilitate meta-analyses and comparisons with future studies of COVID-19 survivors, interstitial lung disease studies, and studies of non-COVID ARDS survivors. Furthermore, it allows for future post-hoc analyses if alternate definitions of fibrotic-like patterns in COVID-19 survivors are established. Additionally, we showed that objective quantitative analyses closely agreed with visual assessments (Figure S2). These types of quantitative imaging analyses may facilitate the convergence of data from multiple centers if imaging protocols become more standardized .
Efforts are underway to characterize pulmonary impairments and radiographic abnormalities in our cohort over time in order to assess longitudinal evolution. We acknowledge that our findings do not exclude the possibility of pre-existing lung disease and we therefore look forward to reviewing independent studies, such as the Collaborative Cohort of Cohorts for COVID-19 Research (C4R)  project, which will provide better understanding of radiographic changes by comparing chest imaging studies before and after SARS-CoV-2 infection.
1. McGroder, C.F., et al., Pulmonary fibrosis 4 months after COVID-19 is associated with severity of illness and blood leucocyte telomere length. Thorax, 2021.
2. Pulmonary Parenchymal Band. Available from: https://www.ncbi.nlm.nih.gov/medgen/978776.
3. Kong, M., et al., Evolution of chest CT manifestations of COVID-19: a longitudinal study. J Thorac Dis, 2020. 12(9): p. 4892-4907.
4. Jin, G.Y., et al., Interstitial lung abnormalities in a CT lung cancer screening population: prevalence and progression rate. Radiology, 2013. 268(2): p. 563-71.
5. Nagpal, P., et al., Case Studies in Physiology: Temporal Variations of the Lung Parenchyma and Vasculature in Asymptomatic COVID-19 Pneumonia: A Multi-Spectral CT Assessment. J Appl Physiol (1985), 2021.
6. Liu, D., et al., The pulmonary sequalae in discharged patients with COVID-19: a short-term observational study. Respir Res, 2020. 21(1): p. 125.
7. Hatabu, H., et al., Interstitial lung abnormalities detected incidentally on CT: a Position Paper from the Fleischner Society. Lancet Respir Med, 2020. 8(7): p. 726-737.
8. Burnham, E.L., et al., Chest CT features are associated with poorer quality of life in acute lung injury survivors. Crit Care Med, 2013. 41(2): p. 445-56.
9. Nagpal, P., et al., Quantitative CT imaging and advanced visualization methods: potential application in novel coronavirus disease 2019 (COVID-19) pneumonia. BJR Open, 2021. 3(1): p. 20200043.
10. Collaborative Cohort of Cohorts for COVID-19 Research. Available from: https://c4r-nih.org/content/overview.
We have read with great interest the article investigating the relationship between computed tomography (CT) findings of the patients with fibrotic-like patterns and telomere length after four months of acute COVID-19 infection. According to the literature and our experience, post-COVID interstitial lung disease is a potential public health problem. Thus, we aimed to share our concerns about the fibrotic-like patterns in this group of patients.
Post-COVID fibrosis is not as the same as the other interstitial lung diseases. In the article, the authors describe CT findings of fibrotic-like patterns as limited to reticulation, honeycomb cysts, and traction bronchiectasis. However, post-COVID fibrosis CT findings were shown to be more varied and may include parenchymal bands, irregular densities, and ground-glass areas (1–3). As we move towards the future, all of us need to create a common language, a lingua franca in the definition of post-COVID fibrosis. To achieve this, we need brainstorming and close cooperation.
It will also be helpful to elaborate the characteristics of the non-fibrotic pattern in the table. The clinical importance of the ground glass areas, which persist four months after active infection but not defined as fibrotic, is unknown. We consider that these patterns cannot be separated from fibrotic-like patterns precisely. Additionally, we can also classify parenchymal bands as fibrosis-like appearance. In our experience...
It will also be helpful to elaborate the characteristics of the non-fibrotic pattern in the table. The clinical importance of the ground glass areas, which persist four months after active infection but not defined as fibrotic, is unknown. We consider that these patterns cannot be separated from fibrotic-like patterns precisely. Additionally, we can also classify parenchymal bands as fibrosis-like appearance. In our experience, subpleural parenchymal bands are not uncommon. Furthermore, respiratory symptoms may persist in patients with parenchymal bands. So, this pattern should be considered as a part of fibrotic-like pattern.
Another challenge is the lack of proof regarding fibrosis development due to COVID-19 infection. For example, honeycomb cysts are an indicator of irreversible fibrosis, and it is uncertain whether they are present in the previous CT images or not. A similar condition may apply to irregular reticulation and traction bronchiectasis. The development of fibrotic patterns may also differ from the images during the active infection (4). It may be instructive to examine the process by which signs of active involvement evolve into fibrosis, as well as the development of a fibrotic-like pattern.
We need a more precise interpretation of the development of fibrotic-like patterns. Therefore, we suggest analysing subtypes of post-COVID fibrosis, compare present findings on CT with long-term follow-up images. Also, it might be beneficial to show, if possible, that there is no fibrotic pattern in the CTs before acute Covid 19 infection.
1. Huang W, Wu Q, Chen Z, Xiong Z, Wang K, Tian J, et al. The potential indicators for pulmonary fibrosis in survivors of severe COVID-19. Vol. 82, Journal of Infection. 2021.
2. Myall KJ, Mukherjee B, Castanheira AM, Lam JL, Benedetti G, Mak SM, et al. Persistent Post-COVID-19 Interstitial Lung Disease. An Observational Study of Corticosteroid Treatment. Ann Am Thorac Soc. 2021;18(5).
3. Shah AS, Wong AW, Hague CJ, Murphy DT, Johnston JC, Ryerson CJ, et al. A prospective study of 12-week respiratory outcomes in COVID-19-related hospitalisations. Vol. 76, Thorax. 2021.
4. Guan CS, Wei LG, Xie RM, Lv Z Bin, Yan S, Zhang ZX, et al. CT findings of COVID-19 in follow-up: Comparison between progression and recovery. Diagnostic Interv Radiol. 2020;26(4):301–7.