Post-COVID pulmonary sequelae: Mechanisms and potential targets to reduce persistent fibrosis

After the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) pandemic, the emergence of long-term sequelae post-infection poses a new healthcare challenge. Following initial infection with SARS-CoV-2, approximately 1 in 10 people experience post-acute sequelae of COVID-19 (PASC), also known as long COVID. PASC can affect the entire body, with the airways and lungs being a primary target of the initial viral infection. Many post-COVID symptoms have been associated with fibrotic lung lesions and diminished respiratory function. The reversibility, persistence, or progression of post-COVID-19 pulmonary fibrosis is still a topic of debate. We aimed to compare current findings and examined similar viral infections from the past, to increase understanding of prevalence, persistence and possible pharmacological targets of post-COVID-19 pulmonary fibrosis. Recent studies have documented PASC symptoms persisting up to 3 years post-recovery, and lung impairments present after 15 years after infection with the similar SARS-CoV virus in 2003. These findings suggest the potential for long-term pulmonary fibrosis following SARS-CoV-2 infection, highlighting the need for new anti-fibrotic treatments capable of reversing pulmonary fibrosis. Besides the approved anti-fibrotics, pirfenidone and nintedanib, other promising treatments include histone deacetylase inhibitors, angiotensin receptor blockers and mesenchymal stem cells. The pathophysiological mechanisms underlying post-COVID-19 pulmonary fibrosis are still incompletely understood, necessitating future research to clarify the development of persistent post-COVID-19 pulmonary fibrosis following SARS-CoV-2 infection. Given the widespread transmission of SARS-CoV-2, even a low prevalence of persistent post-COVID-19 pulmonary fibrosis would represent a significant public health concern for which therapeutic strategies are essential to identify.