LAUSR

To the Editor, Post‐coronavirus disease 2019 (COVID‐19) interstitial lung disease (PC‐ILD) is an emerging medical condition with several aspects that need clarification, including its natural course. Extensive and persistent fibrotic changes can be observed radiologically and histopathologically in PC‐ILD. We encountered an intriguing case suggesting that PC‐ILD may not simply be a post‐acute inflammation. It may also harbor an ongoing, smoldering inflammatory process that leads to patchy interstitial fibrosis. A 71‐year‐old woman who was a former smoker (quit smoking at 55 years old) was referred to our hospital for the evaluation of a 1.5‐cm solid lung nodule detected during hospitalization for COVID‐19 3 months before (Supporting Information: Figure S1A). The patient received supplemental oxygen via nasal cannula, dexamethasone, remdesivir, baricitinib, and edoxaban. The patient's respiratory symptoms gradually improved, and she was discharged after 3 weeks. She had no history of idiopathic pulmonary fibrosis (Supporting Information: Figure S1D), hypersensitive pneumonitis (HP), collagenous diseases, or gastroesophageal reflux disease. A computed tomography (CT) scan showed ground‐ glass opacities with a bilateral, multilobar distribution after the onset of COVID‐19, but these almost disappeared after 3 months (Supporting Information: Figure S1A–C). Parenchymal band‐like changes and fine subpleural reticulation with mild traction bronchiectasis remained on CT images just before the operation. The patient had no respiratory symptoms at the time of operation. A right lower lobectomy was performed after confirming that the patient was negative for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by polymerase chain reaction (PCR). Gross examination of the resected lung revealed a 2‐cm nodule that was confirmed to be a stage IB pT2aN0M0 solid adenocarcinoma (Union for International Cancer Control TNM) (Supporting Information: Figure S2A). The remaining lung parenchyma appeared normal, except for small, ill‐defined, gray‐ white areas (Supporting Information: Figure S2B–D). Histopathologically, there were scattered foci of fibrosed or inflammatory/fibrosing lesions that represented two different phases of lung injury. One lesion had thick, rod‐shaped, or micronodular areas of avascular, dense collagenous scar tissue with myofibroblasts that commonly obliterated the alveolar ducts, alveoli, and alveolar walls (Figure 1a,b; Supporting Information: S3). These features essentially suggest cicatricial organizing pneumonia (CiOP), but a significant alveolar wall damage was also apparent, unlike in typical CiOP (Figure 1b; Supporting Information: S3B). The other lesion consisted of microscopic foci in various developmental stages—from initial focal lymphocytic alveolitis with intra‐alveolar fibrinous exudates (Figure 1c–f; Supporting Information: S4) to young fibromyxoid tissues as intra‐alveolar polypoid plugs or fibroblastic foci and foci with increased deposition of dense collagenous fibers (Figure 1e,f). The initial exudative lesion somewhat resembled acute fibrinous and organizing pneumonia (AFOP), albeit very minute. The lesion size ranged from a few alveoli to around 1mm in its largest dimension. These active lesions appeared to be vaguely perilobular in distribution, often in close vicinity to lymphocytic infiltrates around small pulmonary veins. Alveolar macrophages were commonly observed, which occasionally formed multinucleated giant cells and microgranulomatous foci (Supporting Information: Figure S4B). Microgranulomatous foci were seen in association with lymphocytic infiltrates around small veins and in association with young organizing fibrous plugs in alveolar spaces, but these were almost never observed within respiratory bronchioles (Supporting Information: Figure S4K). Immunohistochemistry for SARS‐CoV‐2 antigens and real‐time reverse‐transcription PCR (RT‐PCR) for SARS‐CoV‐2 RNA were both negative or below the limit of detection. These findings have important implications. First, PC‐ILD may histologically include an old scar tissue element and an ongoing, smoldering inflammatory element causing a new fibrosis. The observed old scar tissue that obliterated the airspaces and alveolar walls may be best explained as a consequence of the initial acute pneumonia, which was possibly AFOP‐like