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

Abstract

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.

Keywords: Antifibrotics; fibrosis; post COVID ILD; post-COVID fibrosis; post-COVID sequelae.

Figure 1

Postulated mechanism of SARS-CoV-2 induced fibrosis stressing the pivotal role of Angiotensin 2

Figure 2

Rapid progression of COVID-19 to end-stage post-COVID interstitial lung disease in <30 days

Figure 3

The natural history of post-COVID lung fibrosis is unclear with one of three possible courses. Antifibrotic may have a rationale in those who progress

Figure 4

(a) Initial computed tomography chest of a 60-year-old lady admitted in the intensive care unit showing bilateral ground-glass opacities. (b) Within 3 month of COVID-19 pneumonia, the patient developed fibrosis with traction bronchiectasis and honeycombing despite being on steroids through most of her hospital stay