TABLE 1.
Potential therapeutic options for COVID-19-induced pulmonary fibrosis.
| Therapeutic substance | Indication | Therapeutic target | Mechanism | Study progress | References |
|---|---|---|---|---|---|
| Nintedanib | COVID-19-induced PF | EGFR, FGFR, PDGFR, and VEGFR | Reduces the expression of ACE2 and the body’s response to SARS-CoV-2 | Confirmed | Shen et al. (2021) |
| Umemura et al. (2021) | |||||
| Natalizumab | COVID-19-induced PF | Integrins | Inhibits integrin signaling, and virus entry | Unclear | Sigrist et al. (2020) |
| Saifi et al. (2022) | |||||
| Pirfenidone | COVID-19-induced PF | Serum and lung IL-6 levels | Inhibits lung damage, and reduces serum and lung IL-6 levels | Confirmed | Zhang et al. (2020a) |
| Shen et al. (2021) | |||||
| Poly-(ADP-Ribose) Polymerase inhibitor | COVID-19-induced PF and inflammation | Cytokine storms | Prevents cytokine storm (macrophage hyperactivation) | Confirmed by animal models | Curtin et al. (2020) |
| Propolis | COVID-19-induced PF and inflammation | Propolis block kinase PAK-1 | Blocks the kinase PAK-1, and reduces the excessive inflammatory response | Confirmed | Berretta et al. (2020) |
| Nile et al. (2020) | |||||
| Spironolactone | COVID-19-induced PF | ACE2, mineralocorticoid receptors, TMPRSS2 | Increases the circulating level of ACE2, prevents SARS-COV-2 entry, blocks the mineralocorticoid receptors, Downregulates TMPRSS2 | Confirmed | Cadegiani et al. (2020) |
| Kotfis et al. (2021) | |||||
| Tocilizumab | COVID-19-induced PF | IL-6 | Inhibits IL-6 | Unclear | Gautret et al. (2020) |
| Tocilizumab | PF complicated with COVID-19 | Immunomodulatory effects | Inhibits pulmonary fibrosis and prevents cytokine storms | Confirmed | Gatti et al. (2021) |
| Treamid | COVID-19-induced PF | Inflammation | Suppresses inflammation and restores the diffusing capacity of the lungs | Unclear | Skurikhin et al. (2020) |
| Bazdyrev et al. (2021) | |||||
| Histone deacetylase inhibitors (TGF-β1 inhibitors) | Post COVID-19-induced PF | TGF-β1 signaling | Inhibits TGF-β1 signaling pathway | Confirmed | P et al. (2021) |
| CD147 inhibitors | COVID-19-induced PF | CD147 receptor, TGF-β1 signaling | Inhibits TGF-β1-induced proliferation and differentiation of fibroblasts into myofibroblasts | Confirmed | Ulrich and Pillat (2020) |
| Corticosteroids | Post COVID-19-induced PF | Caveolin-1, TNF-a, TGF-β1, PDGF | Elevates caveolin-1 levels, reduces TNF-α, TGF-β1, and PDGF levels, decreases inflammation in the lungs | Confirmed in animal studies | Bazdyrev et al. (2021) |
| Collagen-Polyvinylpyrrolidone | COVID-19-induced PF | Cytokine storms | Decreases IL-1β, IL-8, TNF-α, TGF-β1, IL-17, Cox-1, leukocyte adhesion molecule (ELAM-1, VCAM-1 and ICAM-1) levels, reduces the expression of other inflammatory mediators, increases IL-10 level, and the amount of Treg cells | Unclear | Bazdyrev et al. (2021) |
| Galectin-3 inhibitor | COVID-19-induced PF | Galectin-3 | Prevents Gal 3 from binding and activating TLR 4 and TREM | Unclear | Shen et al. (2021) |
| Genistein | COVID-19-induced PF | NF-κB | Inactivates NF-κB | Unclear | Bazdyrev et al. (2021) |
| Anakinra | Post COVID-19-induced PF | IL-1, IL-6 | Inhibits IL-1 and IL-6 | Confirmed | George et al. (2020) |
| Deupirfenidon | COVID-19-induced PF | Inflammation | Anti-inflammatory and antifibrotic activity | Unclear | Bazdyrev et al. (2021) |
| Fuzheng Huayu | Post COVID-19-induced PF | Matrix metalloproteinase 2, type IV collagen | Suppresses the activity of matrix metal-loproteinase 2, and type IV collagen expression | Unclear | Bazdyrev et al. (2021) |
| IN01 Vaccine | COVID-19-induced PF | EGF, EGFR | Inhibits the binding of EGF to its receptor, blocks EGFR activation as well | Unclear | Bazdyrev et al. (2021) |
PF, pulmonary fibrosis; EGFR, epidermal growth factor receptor; ACE2, angiotensin-converting enzyme 2; IL-6, interleukin-6; PAK-1, p21-activated protein kinase-1; TMPRSS2, transmembrane serine protease 2; TNF-α, tumor necrosis factor α; TGF-β1, transforming growth factor-β1; PDGF, platelet-derived growth factor; IL-1β, interleukin-1β; IL-8, interleukin-8; IL-17, interleukin-17; ELAM-1, endothelial leukocyte adhesion molecule 1; VCAM-1, vascular cellular adhesion molecule-1; ICAM-1, intercellular adhesion molecule 1; IL-10, interleukin-10; Gal 3, galectin 3; TLR, 4 = toll-like receptor-4; TREM, triggering receptor expressed on myeloid cells; NF-κB, nucleus factor-κB; IL-1, interleukin-1; EGF, epidermal growth factor; FGFR, fibroblast growth factor receptor; PDGFR, platelet-derived growth factor receptor; VEGFR, vascular endothelial growth factor receptor.