**4. Infections and inflammation**

Epidemiological studies point to a connection between respiratory infections in the past and the incidence of COPD. For example, viral pneumonia in childhood increases the risk for the later development of COPD. With an already existing COPD, acute respiratory infections can trigger an exacerbation. In most cases, bacterial infections cause a trigger. Streptococcus pneumoniae, haemophilus influenzae, moraxella catarrhalis, and pseudomonas aeruginosa have been identified to act as triggers, also tuberculosis can cause an exacerbation of COPD. Furthermore, fungi are potential triggers as well. Viruses have not been found to be common triggers; exceptions are rhinoviruses and SARS-CoV-2 [7].

Patients with underlying COPD are vulnerable to COVID-19, and in fact, COPD is one of the high-risk factors for severe illness associated with COVID-19. This may be related to poor underlying lung reserves and increased expression of ACE-2 (angiotensin-converting enzyme-2) receptor in small airways. One research group established an airway epithelium model to study SARS-CoV-2 infection in healthy and COPD lung cells. They found that both the entry receptor ACE2 and the cofactor transmembrane protease TMPRSS2 are expressed at higher levels on non-ciliated goblet cell, a novel target for SARS-CoV-2 infection. They observed that SARS-CoV-2 induced due to an infection of goblet cells syncytium formation and cell sloughing. They also found that SARS-CoV-2 replication is increased in the COPD airway epithelium, likely due to COPD-associated goblet cell hyperplasia [20–22].
