Caffeine:
Among the range of methylxanthines, caffeine is most commonly used for preterm infants with apnea receiving non-invasive respiratory support (Clark et al. 2006). Ventilating preterm infants may result in severe pulmonary adverse like bronchopulmonary dysplasia (BPD) (Moschino et al. 2020). Therefore, as non-invasive respiratory support, caffeine has already shown to reduce apnea of prematurity along with its associated improved lung function at 11 years of age (Jobe 2017). Caffeine treatment on preterm infants at birth also showed significant improvement in minute ventilation and tidal volume (Dekker et al. 2017) as well as extubation success (Henderson-Smart and Davis 2001). In addition to that, caffeine is also of the few known drugs shown to reduce the risk of BPD at 36 weeks post-menstrual age (PMA) (Dobson et al. 2014). These evidences suggest suggests a potential role of caffeine to treat the respiratory symptoms in infants with COVID-19 (Hong et al. 2020). Furthermore, caffeine showed asthma improvement in adults as well. It was reported that people with mild to moderate asthma improved lung function even at a low dose of 5mg/kg body weight (Welsh et al. 2010). Caffeine also showed a significant bronchodilator effect in young patients with asthma (Becker et al. 1984). Among the various proposed mechanisms for the bronchodilator effect, the most well-established mechanism Phosphodiesterase (PDE) inhibition and adenosine receptor antagonism (Tilley 2011). Along with the well-established role in improving pulmonary functions and respiratory symptoms as well as its bronchodilatory role on the upper respiratory tract of patients (Figure 2) , caffeine makes itself a compelling candidate as an adjuvant therapy for COVID-19 patients showing respiratory symptoms.