Asthma associated with lower mortality among patients hospitalized for COVID-19
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Key takeaways:
- Patients with asthma had 35% lower odds for mortality of COVID-19 than those with no airway disease.
- Patients with eosinophil counts of 200 cells/µL or higher had lower odds for mortality.
Patients with asthma who were hospitalized for COVID-19 had less severe disease and lower mortality rates than patients with no airway disease, according to a study published in The Journal of Allergy or Clinical Immunology: In Practice.
However, patients with COPD who were hospitalized for COVID-19 had more severe disease and higher mortality rates than those with no airway disease, Yunqing Liu, MS, PhD, department of biostatistics, Yale School of Public Health, and colleagues wrote.
The study examined data from 8,395 patients admitted to Yale New Haven Health System between March 1, 2020, and April 1, 2021, for COVID-19. These patients included 969 with asthma, 1,132 with COPD, 768 with both asthma and COPD and 5,526 with no airway disease.
The 11.5% prevalence of asthma in this population was comparable with the 10.5% prevalence of asthma throughout Connecticut, the researchers said. COPD prevalence included 13.5% in the study cohort and 6.1% in the state, indicating increased risk for hospitalization for COVID-19 for patients with COPD, the researchers continued.
Patients with no airway disease had a median sequential organ failure assessment (SOFA) score of 0.32. Comparatively, patients with asthma had a significantly lower median SOFA score, at 0.15 (P < .01), and the patients with COPD had a significantly higher median score, at 0.86 (P < .01).
Compared with the absolute mortality rate of 11% among those with no airway disease, patients with asthma showed a significantly lower rate at 5%, whereas those with COPD showed a significantly higher rate at 21% (P < .01 for both). However, at 14%, the absolute mortality rate among those with asthma and COPD did not significantly differ from the no airway disease group, suggesting that asthma and COPD may have offsetting effects on the severity of COVID-19, the researchers wrote.
Specifically, compared with the no airway disease group, a multivariate logistic regression analysis showed patients with asthma had 35% lower adjusted odds for mortality of COVID-19 (OR = 0.65; 95% CI, 0.48-0.89) whereas patients with COPD had 40% higher odds for mortality (OR = 1.4; 95% CI, 1.16-1.67).
Patients with no airway disease and those with both asthma and COPD had comparable odds for mortality (OR = 0.99; 95% CI, 0.77-1.26), further suggesting that asthma may offset the risk for severe COVID-19 among patients with COPD, the researchers wrote.
Further, the researchers found significant associations between mortality and higher total white blood cell counts, immature granulocyte counts and neutrophil counts in all four disease groups.
Elevated blood eosinophil counts, which the researchers noted are biomarkers of T2 inflammation, were associated with lower risks for mortality in all four disease groups, especially for patients with asthma. Also, patients with asthma, including those with both asthma and COPD, had higher levels of eosinophils on admission.
Specifically, after adjusting for cofounders, patients with absolute eosinophil counts of 200 cells/µL or higher had lower odds for mortality compared with patients with lower eosinophil counts (OR = 0.52; 95% CI, 0.33-0.8).
But after adjusting for eosinophil levels, these differences in mortality between the groups persisted, including an odds ratio of 0.67 (95% CI, 0.49-0.92) for the asthma group and 1.38 (95% CI, 1.15-1.66) for COPD, indicating that peripheral eosinophilia does not fully explain the protection associated with asthma, according to the researchers.
Noting significant differences in exposure to systemic corticosteroids between the groups, the researchers also found an overall increase in mortality associated with IV methylprednisolone therapy (OR = 4.77; 95% CI, 3.69-6.17), which they called expected due to its selective use in patients with severe COVID-19.
Yet multiple regression analysis adjusted for exposure to systemic corticosteroids still showed a significant increase in mortality among patients with COPD and a significant decrease in patients with asthma and eosinophilia.
Patients at risk for severe COVID-19 require more intensive mitigation strategies such as social distancing, vaccine boosters and early outpatient pharmacotherapy, the researchers wrote, making their identification critical.
Based on these results, patients with COPD are at higher risk for severe COVID-19 and patients with asthma are at lower risk, the researchers continued. These differences may be due to protection conferred by T2 inflammation, the researchers added, but further clinical and mechanistic studies would be needed to confirm this association.
Perspective
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One of the most interesting findings is that differences in mortality between patients with asthma and COPD persisted even after adjustment for serum eosinophil counts. This suggests that peripheral eosinophilia might not be the main nor the only factor associated with lower mortality of COVID-19 in patients with asthma.
This might explain why patients with asthma on biologics working on the T2 pathway do not have worse COVID-19 outcomes than those not on monoclonal biologics. Likewise, COPD worsened outcomes even among those with high eosinophil counts. This demonstrates fundamental differences between asthma and COPD.
The results that COVID-19 patients with higher absolute eosinophil counts (greater than 200 cells/µL) had lower odds of mortality compared with those with lower serum eosinophil levels are similar with our prior published data in our Bronx asthmatic population.
Since the beginning of the pandemic, we noticed that our patients with asthma do better in terms of COVID-19 outcomes compared with those who do not have asthma. Even now, 3 years after the COVID-19 pandemic started, we cannot fully explain these observations. However, clinical and mechanistic research studies have emerged since that hopefully will shed more light in this field.
It is possible that the differences in lung inflammation in those with pre-existing asthma and pre-existing COPD are important in COVID-19 outcomes, as well as the age and associated comorbidities. It is known that COPD patients are older, a factor that is associated by itself with worse COVID-19 outcomes.
Although at this time there are no differences in the way we treat COVID-19 patients with asthma and COPD, current findings suggest that COVID-19 prevention strategies and early outpatient treatment for SARS-CoV-2 infection should be implemented with priority for patients with COPD.
Although there is overlap in the medications used to treat these chronic respiratory conditions, this is a clear demonstration of how these two differ. Characterizing respiratory disease accurately as asthma or COPD is important to risk assess patients and to provide them anticipatory guidance.
The exact mechanism through which patients with asthma have lower odds for dying of COVID-19 is not clear. More data are also needed to identify if the odds for mortality of COVID-19 vary based on other allergic disorders, such as allergic rhinitis, rhinosinusitis and atopic dermatitis. Identifying these mechanisms might develop into new treatment and preventative modalities.
It is important to extend this observation to other respiratory viral infections. Does eosinophilia help prevent other viral asthma or COPD exacerbations? We need to understand if eosinophils are the cells that help fight or prevent serious COVID-19 infections. Alternatively, they could be markers of a milieu that is unfavorable to COVID-19. Understanding how the eosinophilic state reduces COVID-19 morbidity and mortality is an important next step.
Manish Ramesh, MD, PhD, associate professor and chief of the division of allergy-immunology, Albert Einstein College of Medicine/Montefiore Medical Center, also contributed to this Perspective.
Reference:
Ferastraoaru DE, et al. J Allergy Clin Immunol Pract. 2021;doi:10.1016/j.jaip/2020.12.045.
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Liu Y, et al. J Allergy Clin Immunol Pract. 2023;doi:10.1016/j.jaip.2023.07.006.
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