Asthma is associated with increased risk of intubation but not hospitalization or death in coronavirus disease 2019

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused considerable morbidity and mortality. COVID-19 often presents with respiratory symptoms; however, the role of asthma in COVID-19 has not been well established. Although studies from China suggested that asthma was not a risk factor for severe COVID-19, other studies have revealed higher rates of asthma among hospitalized patients.1Li X. Xu S. Yu M. et al.Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan.J Allergy Clin Immunol. 2020; 146: 110-118Abstract Full Text Full Text PDF PubMed Scopus (1294) Google Scholar,2Garg S. Kim L. Whitaker M. et al.Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 - COVID-NET, 14 states, March 1-30, 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 458-464Crossref PubMed Scopus (3) Google Scholar Therefore, the primary aim of this study was to assess the associations between asthma and hospitalization, intensive care unit (ICU) admission, or death among patients with COVID-19. Secondary objectives were to assess the associations between asthma and intubation, duration of intubation and hospitalization, and inflammatory markers in COVID-19. This retrospective study was conducted at the George Washington University School of Medicine and Health Sciences in Washington, DC, and approved by its institutional review board. Patients were identified by an electronic medical record search of positive SARS-CoV-2 polymerase chain reaction test results between March and May 2020. Patients with underlying lung disease other than asthma were excluded. Demographics, clinical history, and laboratory markers (trough white blood cell, platelet, and lymphocyte counts; peak D-dimer, ferritin, C-reactive protein [CRP], lactate dehydrogenase [LDH], and interleukin-6 [IL-6] levels) were collected. Diagnosis of asthma was based on the International Classification of Diseases, Tenth Revision codes and verified by clinical history by a board-certified allergist. A total of 787 patients with confirmed SARS-CoV-2 were identified. A total of 60 patients were excluded owing to unknown medical history or pulmonary disease other than asthma, resulting in 727 patients in the final analysis. We assessed whether asthma was associated with hospitalization using a multivariable logistic regression model, adjusting for age, body mass index, race, and a number of comorbidities (chronic kidney disease, coronary artery disease or congestive heart failure, diabetes, and hypertension). In addition, we assessed whether asthma was associated with outcome severity after hospitalization using an adjusted proportional odds model.3Christensen R.H.B. Ordinal - regression models for ordinal data. R package version 2019.12-10.https://CRAN.R-project.org/package=ordinalDate accessed: September 28, 2020Google Scholar We used multivariate imputation by chained equations to generate 100 datasets with imputed values for 209 patients with missing body mass index measurements.4Van Buuren S. Groothuis-Oudshoorn K. mice: multivariate imputation by chained equations in R.J Stat Softw. 2011; 45: 1-67Google Scholar The imputation model included all levels of outcome severity and the covariates in our primary regression models. We assessed whether intubation was associated with asthma using a Fisher’s exact test, with exact confidence intervals.5Fay M.P. Confidence intervals that match Fisher’s exact or Blaker’s exact tests.Biostatistics. 2010; 11: 373-374Crossref PubMed Scopus (100) Google Scholar Differences in mean duration of hospitalization and intubation were compared using 2-sided t tests. We used Wilcoxon ranked sum tests to assess the relationship between biomarkers and asthma. Statistical significance was summarized using nominal P values. All analyses were carried out using the R software, version 4.0.2 (The R Foundation, Vienna, Austria).6R Core TeamR Foundation for Statistical Computing. R: a language and environment for statistical computing.https://www.R-project.org/Date accessed: October 20, 2020Google Scholar Of the 727 patients, 274 (37.6%) were admitted to the hospital but did not require ICU-level care, 68 (9.3%) required ICU care but were discharged, and 61 (8.3%) died. A total of 105 patients (14.4%) had asthma. The proportion of patients with asthma treated as an outpatient vs those hospitalized were similar (14.6% vs 14.2%, respectively). Patient characteristics are summarized in Table 1.Table 1Clinical CharacteristicsCharacteristicOverall, N = 727 (100%)Non asthma, N = 622 (85.6%)Asthma, N = 105 (14.4%)Age, mean (SD)49.46 (17.93)49.95 (18.16)46.61 (16.28)BMI, mean (SD)30.56 (8.14)29.91 (7.57)33.73 (9.92)Allergic asthma36 (4.9)0 (0.0)36 (34.3)Race White82 (11.3)75 (12.0)7 (6.7) African American380 (52.2)315 (50.6)65 (61.9) Asian31 (4.3)29 (4.7)2 (1.9) Latino70 (9.6)61 (9.8)9 (8.6) Other or unknown164 (22.6)143 (23.0)22 (21.0)Risk factors CKD63 (8.7)58 (9.3)5 (4.8) Diabetes165 (22.7)145 (23.3)20 (19.0) CHF or CAD27 (3.7)26 (4.2)1 (1.0) HTN278 (38.2)243 (39.0)35 (33.3)Number of risk factors 0405 (55.7)342 (54.9)64 (61.0) 1157 (21.6)132 (21.2)25 (23.8) 2104 (14.3)92 (14.8)12 (11.4) 344 (6.0)41 (6.6)3 (2.9) 415 (2.1)14 (2.2)1 (1.0) 52 (0.3)2 (0.3)0 (0.0)Outcomes Hospitalization with eventual discharge274 (37.6)235 (37.7)39 (37.1) ICU admission with eventual discharge68 (9.3)57 (9.1)11 (10.5) Death61 (8.4)51 (8.2)10 (9.5) Hospital length of stay9.89 (9.14)9.70 (8.91)11.11 (10.46) Intubation44 (6.1)33 (5.3)11 (10.5) Intubation length11.14 (8.52)11.32 (8.56)10.44 (8.83)Abbreviations: BMI, body mass index; CAD, coronary artery disease; CHF, congestive heart failure; CKD, chronic kidney disease; HTN, hypertension; ICU, intensive care unit. Open table in a new tab Abbreviations: BMI, body mass index; CAD, coronary artery disease; CHF, congestive heart failure; CKD, chronic kidney disease; HTN, hypertension; ICU, intensive care unit. Asthma was not significantly associated with hospitalization, ICU admission, or death. The adjusted odds of hospitalization among the patients with asthma was 1.4 times higher than those without asthma (95% confidence interval [CI], 0.82-2.4; P = .22). The adjusted odds of death vs either hospitalization or ICU admission or equivalently of death or ICU admission vs hospitalization was 1.3 times higher among patients with asthma (95% CI, 0.6-2.8; P = .48). Age, number of comorbidities, and race (non-White vs White; P = .01) were associated with increased odds of hospitalization. The odds of intubation were 2-fold higher among patients with asthma than those without asthma (odds ratio, 2; 95% CI, 1-fold to 4-fold; P = .047). However, there was no significant difference in duration of intubation (P = .44) or hospitalization (P = .44). Asthma was associated with a higher platelet count (208 vs 191; P = .046). However, there was no association between asthma and leukopenia (P = .43), lymphopenia (P = .26), CRP (P = .44), D-dimer (P = .36), LDH (P = .43), ferritin (P = .31), or IL-6 (P = .19). Furthermore, we were unable to evaluate the association between biologic medications for asthma and COVID-19 outcomes, as only 1 patient with asthma was receiving a biologic (omalizumab) and did not require hospitalization. This study assessed whether asthma was associated with COVID-19 severity with regard to outcomes and laboratory biomarkers. The proportion of patients with asthma and COVID-19 treated as an outpatient vs those hospitalized was similar. Our patients had a slightly higher prevalence of asthma than the overall prevalence of asthma in Washington, DC (14.4% vs 11%, respectively),7Centers for Disease Control and PreventionMost recent asthma state or territory data.https://www.cdc.gov/asthma/most_recent_data_states.htm#sourceDate accessed: October 20, 2020Google Scholar suggesting asthma may confer a slightly increased risk of contracting COVID-19. Even with the higher prevalence, asthma was not associated with hospitalization, ICU admission, or death. This is consistent with the study by Chhiba et al8Chhiba K.D. Patel G.B. Vu T.H.T. et al.Prevalence and characterization of asthma in hospitalized and nonhospitalized patients with COVID-19.J Allergy Clin Immunol. 2020; 146 (e4): 307-314Abstract Full Text Full Text PDF PubMed Scopus (178) Google Scholar that also did not find an association between asthma and risk of hospitalization. In this study, patients with asthma were more likely to be intubated than those without asthma. This may reflect a lower threshold for intubating patients with asthma rather than more severe clinical disease. Mahdavinia et al9Mahdavinia M. Foster K.J. Jauregui E. et al.Asthma prolongs intubation in COVID-19.J Allergy Clin Immunol Pract. 2020; 8: 2388-2391Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar found a longer duration of intubation among patients with asthma, but our study revealed no association between asthma and duration of intubation or hospitalization. Inflammatory markers, including leukopenia and lymphopenia, have been associated with severe COVID-19.10Guan W.J. Ni Z.Y. Hu Y. et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (17227) Google Scholar Chhiba et al8Chhiba K.D. Patel G.B. Vu T.H.T. et al.Prevalence and characterization of asthma in hospitalized and nonhospitalized patients with COVID-19.J Allergy Clin Immunol. 2020; 146 (e4): 307-314Abstract Full Text Full Text PDF PubMed Scopus (178) Google Scholar found that patients with asthma had significantly lower levels of ferritin, CRP, and LDH than those without asthma with COVID-19.9Mahdavinia M. Foster K.J. Jauregui E. et al.Asthma prolongs intubation in COVID-19.J Allergy Clin Immunol Pract. 2020; 8: 2388-2391Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar However, we did not find an association between asthma and laboratory parameters except for thrombocytopenia, which was likely not clinically significant. Regarding study limitations, this was a retrospective study at a single medical center. We only had access to the electronic medical record from this center and were unable to identify the patients who may have been hospitalized at other institutions. Because this was a retrospective study, we are unable to make any causative associations. In conclusion, there was no association between asthma and risk of hospitalization, ICU admission, or death among patients with COVID-19. Asthma was associated with increased odds of intubation, but not with duration of intubation or hospitalization. This study adds to the growing literature that patients with asthma may not be at a higher risk of severe outcomes with COVID-19. The authors thank Taha Al-Shaikhly, MbChB, for his contribution in helping to review an earlier version of the article.