The Hidden Pandemic of COVID-19-Induced Organizing Pneumonia

Abstract

Since the beginning of the COVID-19 pandemic, clinical, radiological, and histopathological studies have provided evidence that organizing pneumonia is a possible consequence of the SARS-CoV2 infection. This post-COVID-19 organizing pneumonia (PCOP) causes persisting dyspnea, impaired pulmonary function, and produces radiological abnormalities for at least 5 weeks after onset of symptoms. While most patients with PCOP recover within a year after acute COVID-19, 5-25% of cases need specialized treatment. However, despite substantial resources allocated worldwide to finding a solution to this problem, there are no approved treatments for PCOP. Oral corticosteroids produce a therapeutic response in a majority of such PCOP patients, but their application is limited by the anticipated high-relapse frequency and the risk of severe adverse effects. Herein, we conduct a systematic comparison of the epidemiology, pathogenesis, and clinical presentation of the organizing pneumonias caused by COVID-19 as well as other viral infections. We also use the clinical efficacy of corticosteroids in other postinfection OPs (PIOPs) to predict the therapeutic response in the treatment of PCOP. Finally, we discuss the potential application of a candidate anti-inflammatory and antifibrotic therapy for the treatment of PCOP based on the analysis of the latest clinical trials data.

Keywords: COVID-19 sequelae; SARS-CoV-2 pneumonia; corticosteroids; organizing pneumonia.

Figure 1

The prevalence of the pulmonary gas exchange impairment, depending on the severity of the disease and the time elapsed since the infection onset. (see Table S1 for more information).

Figure 2

OP-like COVID-19 sequelae 2022 forecast in the USA, UK, and Germany.

Figure 3

Pathogenesis of secondary PIOP and OP-like PCPS. (A) Virus-induced alveolar injury with alteration and necrosis of alveolar epithelial cells. (B) Aberrant inflammatory-induced chemotaxis of macrophages and neutrophils to the lung tissue. (C) Inflammatory-induced ROS production and epithelial and endothelial damage, vascular leakage with alveolar hemorrhage, and intra-alveolar edema. (D) Alveolar spaces colonization by pulmonary fibroblasts and myofibroblasts. Extracellular myxoid matrix deposition in the intra-alveolar space. (E) Progressive organization of intra-alveolar granulation tissue into mature fibrotic collagen-rich bundles. (F) Recurring cycles of alveolar epithelial cells damage and subsequent regeneration lead to gradually interlobular and intralobular septal thickening associated with bronchial dilations, suggesting the development of fibrosis. (G) The intra-alveolar buds are remodeled into the interstitium, and the collagen bundles (fibroblastic plugs) are covered with type I alveolar epithelial cells.