Post-COVID lung fibrosis: The tsunami that will follow the earthquake

The SARS-CoV-2 pandemic has already infected in excess of 50 million people worldwide and resulted in 1.2 million deaths. While the majority of those infected will not have long-term pulmonary sequelae, 5%-10% will develop severe COVID-19 pneumonia and acute respiratory distress syndrome (ARDS). The natural history of these severely affected patients is unclear at present, but using our knowledge of closely related coronavirus outbreaks like severe acute respiratory distress syndrome (SARS) and middle east respiratory syndrome (MERS), we would hypothesize that the majority will stabilize or improve over time although some patients will progress to advanced lung fibrosis or post-COVID interstitial lung disease (PC-ILD). Unlike the SARS and MERS outbreaks which affected only a few thousands, the sheer scale of the present pandemic suggests that physicians are likely to encounter large numbers of patients (potentially hundreds of thousands) with PC-ILD. In this review, we discuss the pathogenesis, natural history, and radiology of such patients and touch on clinical, laboratory, and radiographic clues at presentation which might help predict the future development of lung fibrosis. Finally, we discuss the responsible use of antifibrotic drugs such as pirfenidone, nintedanib, and some newer antifibrotics, still in the pipeline. The biological rationale of these drugs and the patient groups where they may have a plausible role will be discussed. We conclude by stressing the importance of careful longitudinal follow-up of multiple cohorts of post-COVID survivors with serial lung function and imaging. This will eventually help to determine the natural history, course, and response to therapy of these patients.