key: cord-0814882-4dsbk60c authors: Yong, Shin Jie title: Diseased lungs may hinder COVID-19 development: A possible reason for the low prevalence of COPD in COVID-19 patients date: 2021-06-09 journal: Med Hypotheses DOI: 10.1016/j.mehy.2021.110628 sha: 5b7ce68d56be8dd16a227f450bfae87723b0a685 doc_id: 814882 cord_uid: 4dsbk60c Presently, it remains unclear why the prevalence of lung diseases, namely chronic obstructive pulmonary disease (COPD), is much lower than other medical comorbidities and the general population among patients with coronavirus disease 2019 (COVID-19). If COVID-19 is a respiratory disease, why is COPD not the leading risk factor for contracting COVID-19? The same odd phenomenon was also observed with other pathogenic human coronaviruses causing severe acute respiratory distress syndrome (SARS) and Middle East respiratory syndrome (MERS), but not other respiratory viral infections such as influenza and respiratory syncytial viruses. One commonly proposed reason for the low COPD rates among COVID-19 patients is the usage of inhaled corticosteroids or bronchodilators that may protect against COVID-19. However, another possible reason not discussed elsewhere is that lungs in a diseased state may not be conducive for the severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) to establish COVID-19. For one, COPD causes mucous plugging in large and small airways, which may hinder SARS-CoV-2 from reaching deeper parts of the lungs (i.e., alveoli). Thus, SARS-CoV-2 may only localize to the upper respiratory tract of persons with COPD, causing mild or asymptomatic infections requiring no hospital attention. Even if SARS-CoV-2 reaches the alveoli, cells therein are probably under a heavy burden of endoplasmic reticulum (ER) stress and extensively damaged where it may not support efficient viral replication. As a result, limited SARS-CoV-2 virions would be produced in diseased lungs, preventing the development of COVID-19. the severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) to establish COVID-23 19. For one, COPD causes mucous plugging in large and small airways, which may hinder SARS- East respiratory syndrome (MERS), where COPD was rarely found (i.e., 0.4-2%) as medical 44 comorbidity among patients [3] [4] [5] [6] [7] [8] . In contrast, the prevalence of COPD is often higher than other 45 comorbidities at 20-40% among patients with other common respiratory viral infections, such as 46 influenza and respiratory syncytial viruses [9] [10] [11] [12] [13] [14] . In a meta-analysis of 11 studies, the pooled prevalence of COPD among COVID-19 50 patients was only 1.76%, which equated to a 54% reduced risk of hospitalization compared to the 51 general population [15] . Other meta-analyses synthesizing more studies have also found a low 52 prevalence of COPD among COVID-19 patients at around 2-10% (Table 1) . Notably, in a meta-53 analysis of 77 studies covering 38,906 COVID-19 patients, only 9% had COPD. Intriguingly, this 54 meta-analysis also calculated that, among the Chinese, the prevalence of smoking history and 55 COPD was only 11% and 4% among COVID-19 patients, respectively, which are lower than the 56 general population at 25% and 14% [16] . Using more appropriate data collection methods and 57 analyses, a nationwide study has found that 10-20% of adults in China have COPD [17] . Globally, 58 the prevalence of COPD stands at 13.1% [18] . In contrast, the global prevalence of hypertension, 59 diabetes, and cardiovascular diseases is 30%, 9%, and 6%, respectively [19] [20] [21] , which is similar 60 to or lower than that observed among COVID-19 patients (Table 1) . However, all meta-analyses found COPD as the leading risk factor for poor clinical outcomes of COVID-19 with odds ratio, 62 relative ratio, or case fatality rate similar to or greater than other comorbidities (Table 1) . Notably, these meta-analyses mainly investigated studies performed in China, with a few 65 in the United States (Table 1 In addition to large and small airways dysfunction, COPD also involves alveolar damage 189 and apoptosis due to mechanisms such as oxidative stress, inflammation, and vascular activation such as 10-50% for diabetes, 10-30% for cardiac diseases, and 30-50% for hypertension [3] [4] [5] [6] [7] [8] . The 203 latter three comorbidities are also the three most common ones among COVID-19 patients (Table 204 1). Importantly, their causative agents, SARS-CoV-1 and MERS-CoV, also mainly target the 205 alveolar epithelial cells in the lower respiratory tract to cause diseases [82, 101, 102] . In contrast, COPD is more prevalent among patients infected with influenza and respiratory syncytial viruses 207 at 20-40% of cases [9] [10] [11] [12] [13] [14] , higher than the general population at 10-15% [17, 18] . Notably, in response to different respiratory viral infections would also be an area of research interest. Discovering why COPD is remarkably rare in patients with COVID-19 may also cast light on new 266 aspects of the disease not previously understood. No funding was received for this work. The author states that there is no conflict of interest to disclose. SJY confirms that he is the sole author of this paper. The author would like to thank Yap Wei Yuen for his intellectual input, as well as the editor and 276 peer-reviewers involved in the publication process of this paper. Characteristics of SARS-CoV-2 and COVID-19 Chronic obstructive pulmonary disease: an overview. 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