COPD, IPF Linked to More Severe COVID-19 Outcomes, Mortality Risk

Patients with chronic lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are significantly more likely to experience more severe outcomes and mortality risk within 30 days of COVID-19, and less likely to experience a mild form of the virus than the general population.

A new study from a team of US-based investigators observed correlation between certain chronic lung diseases and worsened COVID-19 outcomes among the Veterans Health Administration (VHA) population. Though consistent with previous research into the association between pre-existing respiratory disease and risk of severe disease from SARS-CoV-2 infection, the new findings add more insight into the absolute and relative risk of specific chronic lung diseases relevant to COVID-19.

A team of investigators led by Kristina Crothers, MD, of the Veterans Affairs Puget Sound Health System and the department of medicine in the division of pulmonary, critical care and sleep medicine at University of Washington, sought to the determine the association of various chronic lung diseases with COVID-19 severity—defined as hospitalization risk, indicators of critical care, and 30-day mortality.

Among the diseases they compared were COPD, IPF, asthma, sarcoidosis and other interstitial lung diseases (ILDs). As the team noted, previous research into the association of respiratory diseases with SARS-CoV-2 infection have given mixed results.

“Asthma generally has not been associated with worse COVID-19 outcomes, except severe asthma may increase risk for hospitalizations, critical illness and death in some reports,” they wrote. “COPD has been more consistently associated with increased risk of mortality in those with COVID-19, but not all studies have found an association with mortality in fully adjusted models.”

Crothers and colleagues used the VHA, the largest national health system in the US, for the analysis—citing both its robust data and the high prevalence of chronic respiratory disease among veterans. They conducted a multinomial regression analysis to determine the risk of 4 mutually exclusive outcomes from COVID-19 within 30 days of diagnosis: outpatient management; hospitalization; hospitalization with indicators of critical illness; and death. Eligible patients were diagnosed with any of COPD (mild or severe disease); asthma (mild, active or severe disease); IPF; sarcoidosis; or other ILDs, and were treated for COVID-19 between March 2020 – April 2021.

The overall proportion for each outcome was calculated including absolute risk difference and risk ratios for each outcome between those with and without chronic respiratory disease. The team additionally sought to describe clinical and laboratory abnormalities per chronic disease type among patients hospitalized with COVID-19.

The final analysis included 208,283 veterans with COVID-19; among them, 35,587 (17%) were diagnosed with a chronic respiratory disease. The median age of patients with respiratory disease was 10 years older (70) versus those without (60). Patients with lung disease were additionally more likely to be White (71% vs 66%), with a smoking history (69% vs 52%), and possess high-risk comorbidities including coronary heart disease (50% vs 24%).

The most common lung disease in the cohort was COPD (12%), of which 29% had severe disease. Another 5.9% of the cohort had asthma, of which 52% had active disease. Only 1.1% of the cohort had any ILD, with nearly half having IPF.

Investigators observed that veterans with chronic lung disease who were hospitalized with COVID-19 were more likely to report low body temperature, mean arterial pressure, oxygen saturation, leukopenia and thrombocytopenia. These patients additionally were more likely to receive oxygen, mechanical ventilation and vasopressors to treat their COVID-19.

What’s more, veterans with chronic lung disease were significantly less likely to have a mild case of COVID-19 (-4.5%; adjusted risk ratio [aRR], 0.94; 95% CI, 0.94 – 0.95) than those without. Additionally, they were more likely to report a moderate (aRR, 1.15; 95% CI, 1.10 – 1.20) or critical (aRR, 1.38; 95% CI, 1.32 – 1.45) case of COVID-19 than those without. The same patients were approximately 15% more likely to die from COVID-19 (aRR, 1.15; 95% CI, 1.10 – 1.20).

Among the observed chronic lung diseases, IPF was most significantly associated with COVID-19 severity; such patients reported an aRR of 1.69 for mortality (95% CI, 1.46 – 1.96). Other ILDs, as well as both mild and severe cases of COPD, were also significantly associated with significant risk of fatal outcomes at 30 days post-COVID.

Interestingly, investigators observed less severe 30-day COVID-19 outcomes among patients with asthma, regardless of disease status.

Since the earliest months of assessment into COVID-19-related comorbidity risks, COPD has frequently been identified as a key risk factor for mortality. Research from October 2020 suggested an up to 3-fold increased risk of mortality among patients with both COPD and COVID-19—despite the prevalence of patients with COPD hospitalized due to COVID-19 was below average at the time.²

Indeed, the new research from Crothers and colleagues further elucidates the relative and absolute risk difference in severe outcomes and clinical manifestations of COVID-19 among patients with chronic lung disease, 4 years since such a concern was first raised.¹

“Veterans with CLD were older and had more comorbidities, and when hospitalized with COVID-19, were more likely to present with hypoxemia, a lower mean arterial pressure and hypo-inflammatory profile, with lower temperature, leukopenia and thrombocytopenia,” they concluded. “Overall, our results provide insight into the relative and absolute risk associated with different CLDs for severity of COVID-19 outcomes and can help inform considerations of healthcare utilization and prognosis. Patients with IPF, other ILDs and COPD should especially be encouraged to receive SARS-CoV-2 vaccinations, which can help reduce risk of severe COVID-19.”

References

1. ^{Crothers K, Adams SV, Turner AP, et al. COVID-19 Severity and Mortality in Veterans with Chronic Lung Disease. Ann Am Thorac Soc. Published online March 26, 2024. doi:10.1513/AnnalsATS.202311-974OC}
2. ^{Kunzmann K. COPD Linked to Three-Fold Greater Mortality Risk in Severe COVID-19 Patients. HCPLive. Published October 18, 2020. https://www.hcplive.com/view/copd-three-fold-greater-mortality-risk-severe-covid-19-patients}