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Clinical Outcomes of COVID-19 in Patients With COPD


This CHEST series highlights specific studies in the COVID-19 literature that may warrant discourse or reading for members of the chest medicine community. Articles are written by members of CHEST Networks. You can read additional articles in this series.

NOTE: The perspectives shared in this article are those of the author(s) and not those of CHEST.

Clinical Outcomes of COVID-19 in Patients With COPD

By: SM Abdullah Al Mamun, MD, MBBS, FCCP; Muhammad Adrish, MD, MBA, FCCP; Tamer Hudali, MD, MPH; Mahesh Padukudru Anand, DNB, MBBS, FCCP; Fernando Fuentes, MD; Sarang Patil, MD; Kadambari Vijaykumar, MD; and Navitha Ramesh, MD, MBBS, FCCP
Airways Disorders Network

Published: June 15, 2021

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of severe COVID-19 infection.1 A meta-analysis of 39 studies with 698,042 subjects observed that patients with COPD and COVID-19 had increased odds of hospitalization (odds ratio [OR] 4.23, 95% confidence interval [CI] 3.65-4.90), admission to intensive care unit (OR 1.35, 95% CI 1.02-1.78), and in-hospital mortality (OR 2.47, 95% CI 2.18-2.79).2 This is thought to be due to increased susceptibility to viral infections and preexisting abnormalities in lung function.3

Patients with COPD are also susceptible to vascular complications due to endothelial dysfunction.4 It is unclear, however, whether the higher risks of coagulopathy and vascular complications seen in patients with COVID-19 are even greater in patients with COPD.

Comorbidities other than COPD also increase the risk of adverse outcomes with COVID-19.5 A one-point increase in the Charlson Comorbidity Index, for example, increased the odds for all-cause mortality by 1.22 compared with patients with COVID-19 who did not have any comorbidities.6 Social isolation and reduced physical activity also predispose to increased psychological complications.

Mechanisms of Susceptibility to SARS-CoV-2 Infection in Patients With COPD

Recent evidence suggests that patients with COPD who are chronic smokers may overexpress the cellular machinery required for SARS-CoV-2 cellular entry, similar to that seen with SARS-CoV-1, which was responsible for the 2002-2003 SARS epidemic.7 SARS-CoV-2 bears an envelope spike protein that is primed by the cellular serine protease TMPRSS2 to facilitate fusion of the virus with the cell's ACE-2 receptor and subsequent cell entry.8 Studies involving bronchial brush and lavage samples from patients with COPD have shown an increased ACE-2 expression compared with controls.9,10 In addition, in vitro analyses and animal models have established cigarette smoke as an upregulator of ACE-2 expression.11

Sputum studies from patients with COPD who were treated with inhaled corticosteroids (ICS) have shown a reduced expression of ACE-2 receptors.12 These data suggest that patients with COPD who are active smokers have higher ACE-2 receptor expression, thus increasing susceptibility to infection with SARS-CoV-2, while ICS therapy and smoking cessation may reduce this increased risk.

The data on the use of ICS regarding susceptibility or protection against infection with SARS-CoV-2 are conflicting, however. While earlier data did suggest a possible protective role of ICS,11,12 subsequent studies have not shown consistent benefit of this therapy in patients with COVID-19.13,14 Furthermore, data are very limited regarding the use of short-acting bronchodilators, long-acting bronchodilators, roflumilast, or chronic antibiotics and the risk of COVID-19 infection.15

COPD Management During a Pandemic

The COVID-19 pandemic has had a significant impact on the office-based management of patients with COPD, due to decreased in-person clinic visits, interrupted pulmonary rehabilitation, delays in diagnosis, and limitations on routine testing.15 Many health systems switched routine visits to remote platforms in order to overcome these problems.16 Telemonitoring and enhanced multidisciplinary communications between providers, along with home spirometry and remote telerehabilitation, are other ways health systems adapted to the challenges.17

It turned out that these telehealth services have been cost-effective, delivered high-value care to patients, and improved health care access in a safe manner during the pandemic.18 The future holds many questions about how health systems will integrate these telemedicine strategies in the post-pandemic era and the many high-risk interactions of the COPD population and SARS-CoV-2.


  1. Centers for Disease Control and Prevention. Certain Medical Conditions and Risk for Severe COVID-19 Illness. Centers for Disease Control and Prevention. Accessed May 28, 2021.
  2. Gerayeli FV, Milne S, Cheung C, et al. COPD and the risk of poor outcomes in COVID-19: a systematic review and meta-analysis. EClinicalMedicine. 2021;33:100789.
  3. Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395(10239):1763-1770.
  4. Ambrosino P, Lupoli R, Iervolino S, et al. Clinical assessment of endothelial function in patients with chronic obstructive pulmonary disease: a systematic review with meta-analysis. Intern Emerg Med. 2017;12(6):877-885.
  5. Dorjee K, Kim H, Bonomo E, et al. Prevalence and predictors of death and severe disease in patients hospitalized due to COVID-19: a comprehensive systematic review and meta-analysis of 77 studies and 38,000 patients. PLoS ONE. 2020;15(12):e0243191.
  6. Lee SC, Son KJ, Han CH, et al. Impact of COPD on COVID-19 prognosis: a nationwide population-based study in South Korea. Sci Rep. 2021;11(1):3735.
  7. Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450-454.
  8. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280.
  9. Leung, JM, Yang CX, Tam A, et al., ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19. Eur Respir J. 2020;55(5):2000688.
  10. Cai G, Bossé Y, Xiao F, et al. Tobacco smoking increases the lung gene expression of ACE2, the receptor of SARS-CoV-2. Am J Respir Crit Care Med. 2020;201(12):1557-1559. doi:10.1164/rccm.202003-0693LE
  11. Smith JC, Sausville EL, Girish V, et al. Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract. Dev Cell. 2020;53(5):514-529.e3. doi:10.1016/j.devcel.2020.05.012
  12. Finney LJ, Glanville N, Farne H, et al. Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon. J Allergy Clin Immunol. 2021;147(2):510-519.e5. Preprint. Posted online October 14, 2020. PMID: 33068560; PMCID: PMC7558236. doi: 10.1016/j.jaci.2020.09.034
  13. Schultze A, Walker AJ, MacKenna B, et al. Risk of COVID-19-related death among patients with chronic obstructive pulmonary disease or asthma prescribed inhaled corticosteroids: an observational cohort study using the OpenSAFELY platform. Lancet Respir Med. 2020;8(11):1106-1120. doi:10.1016/S2213-2600(20)30415-X
  14. Halpin DMG, Singh D, Hadfield RM. Inhaled corticosteroids and COVID-19: a systematic review and clinical perspective. Eur Respir J. 2020;55(5):2001009. doi:10.1183/13993003.01009-2020
  15. Halpin DMG, Criner GJ, Papi A, et al. Global initiative for the diagnosis, management, and prevention of chronic obstructive lung disease. The 2020 GOLD science committee report on COVID-19 and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2021;203(1):24-36. doi:10.1164/rccm.202009-3533SO
  16. van Zelst CM, Kasteleyn MJ, van Noort EMJ, et al. The impact of the involvement of a healthcare professional on the usage of an eHealth platform: a retrospective observational COPD study. Respir Res. 2021;22(1):88. doi:10.1186/s12931-021-01685-0
  17. Lewis A, Knight E, Bland M, et al. Feasibility of an online platform delivery of pulmonary rehabilitation for individuals with chronic respiratory disease. BMJ Open Respir Res. 2021;8(1):e000880. doi:10.1136/bmjresp-2021-000880
  18. Rutkowski S. Management challenges in chronic obstructive pulmonary disease in the COVID-19 pandemic: telehealth and virtual reality. J Clin Med. 2021;10(6):1261. doi:10.3390/jcm10061261

SM Abdullah Al Mamun, MD, MBBS, FCCP, is a Senior Consultant and Coordinator of Respiratory Medicine at Square Hospital in Dhaka, Bangladesh. He is a CHEST Global Governor.

Muhammad Adrish, MD, MBA, FCCP, is a Clinical Assistant Professor of Medicine at BronxCare Health System in the Bronx, New York. He is Vice-Chair of CHEST’s Airways Disorders Network Steering Committee.

Tamer Hudali, MD, MPH, is a Fellow at the University of Alabama at Birmingham. He is a Fellow-in-Training on CHEST’s Airways Disorders Network Steering Committee.

Mahesh Padukudru Anand, DNB, MBBS, FCCP, is a Professor of Respiratory Medicine at JSS Medical College, JSS Academy of Higher Education & Research, in Mysuru, India, and is a member of CHEST’s Airways Disorders Network Steering Committee.

Fernando Fuentes, MD, is a Pulmonary/Critical Care Fellow-in-Training at Virginia Tech Carilion School of Medicine, Carilion Clinic.

Sarang Patil, MD, is an Assistant Professor in the Department of Respiratory, Sleep, and Critical Care Medicine at Maharashtra University of Health Sciences in India.

Kadambari Vijaykumar, MD, is a Fellow at the University of Alabama at Birmingham. She is a Fellow-in-Training on CHEST’s Airways Disorders Network Steering Committee.

Navitha Ramesh, MD, MBBS, FCCP, is an Attending Physician, Pulmonary and Critical Care Medicine, at UPMC Pinnacle in Harrisburg, Pennsylvania, and is a member of CHEST’s Airways Disorders Network Steering Committee.

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