COVID-19 can result in fatal pulmonary fibrosis, according to a new case report. "We hope that our results will remind clinicians of pulmonary fibrosis as a possibility in patients recovering from COVID-19 who experience continued shortness of breath," said Dr. Hanna Ferloev Schwensen of Aarhus University Hospital, in Denmark. This would allow monitoring and referral to specialists, so that treatment could be considered if the fibrosis turns out to be persistent or progressive, she told Reuters Health by email. As many as 42% of hospitalized patients with COVID-19 develop acute respiratory distress syndrome (ARDS), which is a known cause of pulmonary fibrosis. Dr. Schwensen and colleagues describe the case of a woman in her 80s who was admitted to hospital with COVID-19. The patient developed severe ARDS during her hospitalization and was treated with lung-protective ventilation, heavy sedation/neuromuscular blockade, prone positioning and inhaled nitric oxide, they report in the Journal of Clinical Pathology. CT scan on day 18 revealed large bilateral central pulmonary emboli that were treated with high-dose dalteparin. A CT scan 2.5 months earlier (to monitor her recovery from breast cancer) had been normal. On day 39, three days after testing negative for SARS-CoV-2 for the first time, high-resolution CT scan showed bilateral consolidations, septal thickening, traction bronchiectasis, and infiltrative and parenchymal changes consistent with widespread pulmonary fibrosis. Ultimately, the patient, her family, and treating physicians decided to withdraw active treatment on day 45, and she died a few hours later. Autopsy findings included signs of widespread pulmonary fibrosis, including large areas of disrupted architecture with fibromuscular organization and collagenized fibrosis. Honeycomb-like fibrosis with enlarged air spaces with bronchial metaplasia was present in some areas. Findings consistent with acute diffuse alveolar damage were also seen. "The most interesting result in our case study was the honeycomb (HC) fibrosis we found in our histopathological examination of the lungs," Dr. Schwensen said. "HC fibrosis is commonly found in interstitial lung disease, such as usual interstitial pneumonia, a chronic condition which usually takes months or even years to develop and with a different clinical course than what is observed in our case study. HC fibrosis, however, has to our knowledge not been histopathologically determined as a post-COVID-19 finding prior to our study." The authors caution that causality cannot be drawn based on one case report. Mechanical ventilation can cause ventilator-induced lung injury (VILI), whose pathology is similar to that of ARDS, so the contribution of mechanical ventilation to these histopathological findings is difficult to distinguish from that of COVID-19. Dr. Gisli Jenkins of the University of Nottingham, in the U.K., who recently described candidate SARS-CoV-2 receptors in human lungs, told Reuters Health by email, "What is not clear from this case is what the role of ARDS and ventilation were in being permissive for the development of fibrosis and what the other permissive conditions might be. That is: did this patient develop progressive fibrosis because of the combination of SARS-CoV-2 and ventilation or because of SARS-CoV-2 and another biological factor we have not yet determined (genetic, etc.)?" "This is important, because we are aware that ARDS and VILI can both promote pulmonary fibrosis in the absence of COVID-19, or indeed any other respiratory viral infection," he said, "but the real concern will be if a substantial number of patients who develop COVID-19, but do not develop ARDS or do not require ventilation, start to develop pulmonary fibrosis, that will be a completely different ball game." "In practice what this means for clinicians looking after patients with COVID-19, especially those with ARDS, is that they need to be vigilant for the development of pulmonary fibrosis even after mild disease, and there should be a low threshold for repeating CT scans and lung function in patients who have persisting or worsening breathlessness weeks to months after their acute COVID-19," Dr. Jenkins said. —Will Boggs MD Source
