Table 1.
Categorization of the proposed medications for COVID-19 smell and taste loss.
| Medication | Mechanism of action | Outcomes (study design) | Class of recommendation/Level of evidence | References |
|---|---|---|---|---|
| Pentoxifylline | PDE inhibitor | Promising results in smell loss (post-marketing surveillance study), No beneficial effects in patients with post-traumatic anosmia (case series) | IIb/B-NR | (Gudziol and Hummel, 2009; Whitcroft et al., 2020) |
| Caffeine | PDE inhibitor, Adenosine receptors antagonist | Direct correlation between coffee consumption and smell scores in patients with Parkinson's disease (retrospective cohort), 65 mg of caffeine showed no beneficial effects in patients with hyposmia related with upper respiratory tract infection or sinus node dysfunction (RCT) | IIb/B-R | (Meusel et al., 2016; Siderowf et al., 2007) |
| Theophylline | PDE inhibitor | Improved the smell and taste dysfunction caused by various diseases (two non-RCT) | IIb/B-NR | (Henkin et al., 2009, 2012) |
| Intranasal insulin | Neuroprotective | Beneficial effects in olfactory dysfunction caused by infection (non-RCT), COVID-19 (non-RCT), and other diseases (RCT) | IIa/B-R | (Mohamad et al., 2021; Rezaeian, 2018; Schöpf et al., 2015) |
| Statins | Neuroprotective, anti-inflammatory | Improved anosmia in mice models (two animal studies) | IIb/C-EO | (Kim et al., 2010, 2012) |
| Minocycline | Neuroprotective | Inhibit apoptosis of OSNs in rat models (Histological analysis) | IIb/C-EO | Kern et al. (2004b) |
| Zinc | Trace element, growth factor | Reports of anosmia with intra-nasal zinc gluconate, No beneficial effects of zinc sulfate in chemotherapy-induced taste and smell loss (RCT) | III/B-R | (Davidson and Smith, 2010; Lyckholm et al., 2012) |
| Intranasal vitamin A | Anti-neurodegenerative | Beneficial effects in post-infectious smell dysfunction (retrospective cohort study) | IIb/C-LD | Hummel et al. (2017) |
| Omega-3 | Neuroprotective | Beneficial effects in olfactory loss caused by tumors (RCT) | IIb/B-R | Yan et al. (2020) |
| Intranasal mometasone | Anti-inflammatory | No beneficial effects in COVID-19 smell loss (RCT) | III/B-R | Abdelalim et al. (2021) |
| Intranasal fluticasone | Anti-inflammatory | Beneficial effects in COVID-19 smell loss (non-RCT) | IIa/B-NR | Singh et al. (2021) |
| Oral triamcinolone paste | Anti-inflammatory | Beneficial effects in COVID-19 dysgeusia (non-RCT) | IIa/B-NR | Singh et al. (2021) |
| Melatonin | Neuroprotective, anti-inflammatory | Inhibit apoptosis of OSNs in rat models (animal study) | IIb/C-EO | Koc et al. (2016) |
PDE, phosphodiesterase; RCT, randomized clinical trial.