Current smokers and people with chronic obstructive pulmonary disease (COPD) have an increased risk of severe complications and higher mortality with COVID-19 infection, according to a new study published May 11, 2020 in the open-access journal PLOS ONE by Jaber Alqahtani of University College London, UK, and colleagues.

COPD is a common, persistent dysfunction of the lung associated with a limitation in airflow. An estimated 251 million people worldwide are affected by COPD.

Given the effects of the SARS-CoV-2 coronavirus on respiratory function, the authors of the present study sought to understand the prevalence and the effects of COPD in COVID-19 patients.

In the new study, researchers systematically searched databases of scientific literature to find existing publications on the epidemiological, clinical characteristics and features of COVID-19 and the prevalence of COPD in COVID-19 patients.

123 potentially relevant papers were narrowed to 15 that met all quality and inclusion guidelines. The included studies had a total of 2473 confirmed COVID-19 patients. 58 (2.3%) of those patients also had COPD while 221 (9%) were smokers.

Critically ill COVID-19 patients with COPD had a 63% risk of severe disease and a 60% risk of mortality while critically ill patients without COPD had only a 33.4% risk of severe disease (RR 1.88, 95% CI 1.4-2.4) and 55% risk of mortality (RR 1.1, 95% CI 0.6-1.8).

In addition, current smokers were 1.45 times more likely to have severe complications compared to former and never smokers (95% CI 1.03-2.04).

The study was not able to examine whether there was an association between the frequency of COPD exacerbations, or severity of COPD, with COVID-19 outcomes or complications.

The results are limited by the fact that few studies were available to review, as well as the diverse locations, settings, and designs of the included studies.

The authors add: “Despite the low prevalence of COPD and smoking in COVID-19 cases, COPD and current smokers were associated with greater COVID-19 severity and mortality.”

---

Coronavirus Disease 2019 (Covid-19) is now a declared pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1,2. Due to its extremely high infectivity Covid-19 has caused over 292,142 infections and 12,784 deaths world-wide as of 22nd March 2020 (WHO Coronavirus disease situation reports)3.

SARS-CoV-2 primarily invades the pulmonary alveolar epithelial cells. Although most infections with SARS-CoV-2 are thought to be subclinical or mildly symptomatic, it may result in acute respiratory distress syndrome and occasionally into multiorgan failure 4,5.

The impact of underlying respiratory compromises such as the presence of chronic obstructive pulmonary disease (COPD) or ongoing smoking history on the clinical manifestation and course of SARS-CoV-2 infection is uncertain.

A large case series reporting the clinical characteristics and outcomes of Covid-19 patients from China have reported a higher prevalence of COPD in patients with severe presentation and worse outcomes 6.

The same case series also reported a higher prevalence of active-smokers in severe Covid-196. A recent meta-analysis, however, failed to demonstrate any correlation between ongoing smoking history and the severity of Covid-19 7.

The results of a meta- analysis are dependent on the studies included, sample size and frequency of events. A large number of Covid-19 related studies, case reports and case series are reported in native Chinese languages.

A meta-analysis that includes published Chinese literature regarding Covid-19 is likely to improve on the conclusions by increasing the sample size and the number of events. We conducted this meta- analysis by including both English and Chinese language published literature to explore the impact of underlying respiratory illness and smoking history on the severity of COVID-19 manifestations.

Discussion

This meta-analysis which includes studies on SARS-CoV-2 infection from December 2019 up to 22nd March 2020, published in either English or Chinese language, shows that the pre-existing COPD has a 4-fold increased risk of developing severe Covid-19. Active smoking although increased the risk of severe Covid-19, the result was heavily influenced by one study6 and after removing the study from analysis association between active smoking and severe Covid-19 was found to be non-significant.

COPD is characterized by chronic inflammation of the large (central) airways, small (peripheral) bronchioles and destruction of lung parenchyma. The functional consequence of these abnormalities is expiratory airflow limitation 18.

Pathogenic infections are a common cause of acute exacerbation of COPD, which can result in respiratory failure in many patients 19. The clinical symptomatology of Covid-19 and acute exacerbation of COPD is difficult to differentiate which may potentially result in delayed or inappropriate medical intervention.

It is thus not surprising to find a worse prognosis of Covid-19 in patients with COPD. The result of this meta-analysis, which was stable on sensitivity analysis, confirms that the risk of severe Covid-19 in a patient with pre-existing COPD was 4-fold higher than in patients without COPD.

In subgroup analysis, this effect remained statistically significant in the subgroup of those death or ICU requirements. These findings highlight the importance of strict control of Covid-19 spread and an urgent need for mitigation strategies in patients with preexisting COPD.

The impact of active, ongoing smoking on Covid-19 progression is controversial. Lippi et al. 7 showed that active smoking was not associated with the severity of Covid-19, which is contrary to our conclusion. The results of our study show that active smoking increases the risk of developing severe Covid-19 by around 2 folds.

However, in the subgroup analysis, this effect was no longer significant in either subgroup. The weight of a single study on the overall sample size could be a possible explanation. When the study with the largest sample size6was excluded from sensitivity analysis, the effect of smoking on the severity of Covid-19 was no longer significant.

Another possible explanation is that most studies did not differentiate between current and ex-smokers except for the study from Guan et al 6. Additionally, smoking duration was not reported in all available, included studies.

It is well known that cessation of smoking improves pulmonary function, however, this benefit is less among older smokers due to the cumulative injury to lung over a prolonged period of time 20. These results indicate a complicated relationship between smoking history and the severity of Covid-19.

One of the important limitations of our study is that all the included studies were case-series; however, due to the rapid spread of COVID-19, randomized controlled trial or prospective studies have not been possible so far.

Even though all the literatures included in this study were case series, the heterogeneity in terms of the impact of COPD in Covid-19 was relatively low, and the sensitivity analysis showed that the results were stable without any publication bias. The impact of ongoing and ex-smoking remains an area of further evaluation.

Although a majority of the included cases are from Asia and that may be a limitation of this study, however, so far to the best of our knowledge, there is no report of any ethnic differences in the pathogenesis of COVID-19.

In conclusion, the results of this study indicate that pre-existing COPD is likely to worsen the progression and prognosis of Covid-19. Strong efforts should be directed to ovoid infection in patients with underlying COPD.

Reference

1. El Zowalaty ME, Järhult JD. From SARS to COVID-19: A previously unknown SARS- related coronavirus (SARS-CoV-2) of pandemic potential infecting humans – Call for a One Health approach. One health (Amsterdam, Netherlands). 2020;9:100124.
2. He F, Deng Y, Li W. Coronavirus disease 2019: What we know? Journal of medical virology. 2020.
3. WHO Coronavirus disease situation reports, 22 March 2020,
4. Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. Journal of medical virology. 2020.
5. Cao Y, Liu X, Xiong L, Cai K. Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2: A systematic review and meta-analysis. Journal of medical virology. 2020.
6. Guan W-j, Ni Z-y, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China.New England Journal of Medicine. 2020.
7. Lippi G, Henry BM. Active smoking is not associated with severity of coronavirus disease 2019 (COVID-19). European journal of internal medicine. 2020.
8. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
9. Liu Y, Yang Y, Zhang C, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Science China Life sciences. 2020;63(3):364- 374.
10. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020.
11. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS- CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory medicine. 2020.
12. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020.
13. Zhang JJ, Dong X, Cao YY, et al. Clinical characteristics of 140 patients infected with SARS- CoV-2 in Wuhan, China. Allergy. 2020.
14. Wang Z, Yang B, Li Q, Wen L, Zhang R. Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis. 2020.
15. Gao Y, Li T, Han M, et al. Diagnostic Utility of Clinical Laboratory Data Determinations for Patients with the Severe COVID-19. Journal of medical virology. 2020.
16. Xi Chen, Jin Tong, Jianhua Xiang, Jingjing Hu. Retrospective study on the epidemiological characteristics of 139 patients with novel coronavirus pneumonia on the effects of Severity. Chongqing Medicine. 2020:1-9.
17. Liu W, Tao ZW, Lei W, et al. Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Chinese medical journal. 2020.
18. Saetta M, Turato G, Maestrelli P, Mapp CE, Fabbri LM. Cellular and Structural Bases of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2001;163(6):1304- 1309.
19. Leung JM, Tiew PY, Mac Aogáin M, et al. The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD. Respirology (Carlton, Vic). 2017;22(4):634-650.
20. Burns DM. Cigarette smoking among the elderly: disease consequences and the benefits of cessation. American journal of health promotion: AJHP. 2000;14(6):357-361.

---

More information: Jaber S. Alqahtani et al, Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis, PLOS ONE (2020). DOI: 10.1371/journal.pone.0233147