Although there has been a large number of studies focusing on the role of airways in coronavirus disease 2019 (COVID-19), the relationship still remains unclear. With the disruption of the defense mechanism of the airways, including the intact mucus barrier, ciliary activity, and normal cough reflex, sticky and difficult-to-remove sputum becomes the main problem and the cough becomes the main symptom. Although interferons are considered the main elements of the defense against the virus, the pathogenesis of COVID-19 is complex and cannot be elucidated with only elevated interferon levels; there is more. The progression of the disease is mainly determined by the type and the levels of interferons and the affected part of the respiratory system. The airways have an important role in the pathogenesis of COVID-19, as the microorganism uses the airways as a gateway to the body, being the first element of defense against the virus, the importance of its relationship with the immune system, and its importance in the treatment.