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COVID-19 severity in hospitalized patients with asthma: A matched cohort study

2020; Elsevier BV; Volume: 9; Issue: 1 Linguagem: Inglês

10.1016/j.jaip.2020.10.021

2213-2201

Lacey B. Robinson, Xiaoqing Fu, Ingrid V. Bassett, Virginia A. Triant, Andrea S. Foulkes, Yuqing Zhang, Carlos A. Camargo, Kimberly G. Blumenthal,

Chronic Obstructive Pulmonary Disease (COPD) Research

Clinical Implications•In this matched cohort study conducted in Boston, asthma was not a risk factor for worse outcomes from coronavirus disease 2019 (COVID-19) infection. Further understanding the association between asthma and COVID-19 is critical in guiding patient care as the pandemic continues. •In this matched cohort study conducted in Boston, asthma was not a risk factor for worse outcomes from coronavirus disease 2019 (COVID-19) infection. Further understanding the association between asthma and COVID-19 is critical in guiding patient care as the pandemic continues. Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health crisis. The United States (US) became an epicenter for COVID-19, reporting the highest of number cases and deaths in the world.1World Health OrganizationCoronavirus disease 2019 situation report 195; 2020.https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reportsDate accessed: September 15, 2020Google Scholar In the spring of 2020, Massachusetts experienced a significant epidemic. Viral respiratory infections are known to be more severe in patients with asthma.2Busse W.W. Lemanske Jr., R.F. Gern J.E. Role of viral respiratory infections in asthma and asthma exacerbations.Lancet. 2010; 376: 826-834Abstract Full Text Full Text PDF PubMed Scopus (586) Google Scholar Whether asthma is associated with worse COVID-19 outcomes is unclear, but of clinical importance to approximately 20 million adult US asthma patients.3National Center for Environmental Health, Centers for Disease Control and PreventionNational Current Asthma Prevalence. Atlanta, GA: National Center for Environmental Health; 2018.https://www.cdc.gov/asthma/most_recent_data.htmDate accessed: September 15, 2020Google Scholar We sought to understand the relation of asthma to COVID-19 severity in a registry of hospitalized patients from Massachusetts General Hospital (MGH). We performed a matched cohort study using data from the MGH COVID-19 Data Registry for confirmed SARS-CoV-2 infected patients hospitalized at MGH.4Bassett I.V. Triant V.A. Bunda B.A. Selvaggi C.A. Shinnick D.J. He W. et al.Massachusetts General Hospital Covid-19 Registry reveals two distinct populations of hospitalized patients by race and ethnicity.medRxiv. Accessed October 12, 2020; (2020.09.08.20190421)Google Scholar The registry included 866 COVID-19 inpatients (hospitalized March 8, 2020, to April 27, 2020) and was created using both manual chart review and coded data extraction from the electronic health record in the Mass General Brigham Enterprise Data Warehouse. Trained chart reviewers extracted demographics, comorbid conditions, intensive care unit (ICU) admission, clinical complications, and death. We identified adult (≥18 years of age) registry patients with a positive SARS-CoV-2 polymerase chain reaction test and diagnosis of asthma by chart review, with chart verification by a board-certified allergist/immunologist (LBR). For each COVID-19 asthma inpatient, we identified up to 5 COVID-19 non-asthma inpatient comparators matched on age (within 5 years), sex, and date of positive SARS-CoV-2 test (within 7 days). For patients with multiple test dates, the earliest date was used. We excluded patients with other chronic lung disease (eg, chronic obstructive pulmonary disease [COPD], cystic fibrosis, interstitial lung disease) from both asthma and comparator cohorts. The primary outcomes considered were ICU admission, mechanical ventilation, and death. Person-days of follow-up for each patient were computed as the amount of time from the date of the hospitalization to the date of the ICU (or mechanical ventilation, or death) or discharge from hospital. We examined the relation of asthma to COVID-19 outcomes using multivariable-adjusted Cox-proportional hazards models; for the outcomes of ICU admission and mechanical ventilation, models accounted for the competing risk of death. Multivariable models included covariates selected a priori. Statistical analyses were completed using SAS (version 9.4; SAS Institute, Inc., Cary, NC), with a 2-tailed P < .05 considered statistically significant. We matched 80 asthma inpatients with COVID-19 to 323 comparators (Table I). Inpatients with asthma were similar to their comparators for matching variables (age, sex), as well as race/ethnicity, smoking status, and comorbid conditions. Asthma patients had a higher mean body mass index than their non-asthma comparators (32.9 kg/m2 vs 30.7 kg/m2, respectively). Asthma patients had documentation of using short-acting beta-agonist (89%), inhaled corticosteroid with long-acting beta-agonist (26%), inhaled corticosteroid (25%), montelukast (13%), and long-acting antimuscarinic antagonists (6%); none were on biologics.Table IClinical characteristics of COVID-19 patients with and without asthmaCharacteristicAsthma (n = 80)No asthma∗Age, sex, and date of SARS-CoV-2 diagnosis matched comparators. (n = 323)P value†Compared using a 2-sample t-test, Mann-Whitney U test, or Fisher-exact test, as appropriate.Age (y), mean (SD)57 (17)59 (16)–Age group– <261 (1)3 (1) 26-357 (8)19 (6) 36-4512 (15)44 (14) 46-5517 (21)65 (20) 56-6518 (23)87 (27) 66-7512 (15)52 (16) 76-857 (9)33 (10) 86-956 (8)20 (6)Female43 (54)169 (52)–Race/ethnicity.92 Non-Hispanic white28 (35)115 (36) Non-Hispanic black10 (13)35 (11) Hispanic34 (43)133 (41) Other8 (10)40 (12)Body mass index (kg/m2), mean (SD)32.9 (7.7)30.7 (6.7).02Body mass index category.05 4013 (16)23 (7)Smoking status.81 Former22 (28)86 (27) Current3 (4)17 (5) Never51 (64)196 (61) Unknown4 (5)24 (7)Diabetes, type I0 (0)1 ( .99Diabetes, type II27 (34)104 (32).79Hypertension38 (48)160 (50).74Coronary artery disease or myocardial infarction11 (14)39 (12).68Congestive heart failure3 (4)25 (8).21Renal disease9 (11)53 (16).25Liver disease9 (11)32 (10).72Cancer8 (10)45 (14).35Rheumatic or autoimmune5 (6)40 (12).12Organ transplantation0 (0)9 (3).21HIV0 (0)6 (2).60Immunodeficiency0 (0)2 ( .99Data are represented by mean (SD) or number (percentage) unless otherwise indicated.COVID-19, Coronavirus disease 2019; SD, standard deviation; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.∗ Age, sex, and date of SARS-CoV-2 diagnosis matched comparators.† Compared using a 2-sample t-test, Mann-Whitney U test, or Fisher-exact test, as appropriate. Open table in a new tab Data are represented by mean (SD) or number (percentage) unless otherwise indicated. COVID-19, Coronavirus disease 2019; SD, standard deviation; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. There were 19 (24%) asthma patients and 108 (33%) comparators who required ICU admission. In the fully adjusted model, the risk of ICU admission was lower among asthma patients than comparators (adjusted hazard ratio [aHR]: 0.52, 95% confidence interval [CI]: 0.30-0.90) (Table II). Mechanical ventilation was used in 12 (15%) asthma patients and 91 (28%) of comparators. In the fully adjusted model, the risk of mechanical ventilation was lower among asthma patients than comparators (aHR: 0.42, 95% CI: 0.21-0.81). Death occurred in 7 (9%) asthma patients and 38 (12%) comparators. In the fully adjusted model, risk of death did not differ between groups (aHR: 0.64, 95% CI: 0.24-1.68). The 7 asthma deaths occurred in patients aged 57 to 88 years, 6 (86%) were male, and all had at least 2 other substantial comorbid conditions, with 4 (57%) having dementia/cognitive impairment that guided prior asthma treatment and code status.Table IIClinical outcomes of COVID-19 patients with asthma and without asthmaOutcomesAsthma (n = 80)No asthma (n = 323)∗Age, sex, and date of SARS-CoV-2 diagnosis matched comparators.Intensive care unit admission No. of events19 (24)108 (33) Rate of event per 1000 person-days3.43 (1.89, 4.98)5.66 (4.59, 6.73) Matched unadjusted hazard ratio (95% CI)†Matched on age, sex, and date of SARS-CoV-2 test.0.64 (0.40, 1.02)1.00 (reference) Partially adjusted hazard ratio (95% CI)‡Matched on age, sex, and date of SARS-CoV-2 test and adjusted for race/ethnicity, body mass index, and smoking status.0.53 (0.31, 0.90)1.00 Fully adjusted hazard ratio (95% CI)§Matched on age, sex, and date of SARS-CoV-2 test and adjusted for race/ethnicity, body mass index, smoking status, and comorbid conditions (diabetes type II, coronary artery disease or myocardial infarction, liver disease, and rheumatic or autoimmune disease).0.52 (0.30, 0.90)1.00Mechanical ventilation No. of events12 (15)95 (28) Rate of event per 1000 person-days1.96 (0.85, 3.07)4.67 (3.73, 5.61) Matched unadjusted hazard ratio (95% CI)†Matched on age, sex, and date of SARS-CoV-2 test.0.52 (0.29, 0.94)1.00 (reference) Partially adjusted hazard ratio (95% CI)‡Matched on age, sex, and date of SARS-CoV-2 test and adjusted for race/ethnicity, body mass index, and smoking status.0.42 (0.22, 0.80)1.00 Fully adjusted hazard ratio (95% CI)§Matched on age, sex, and date of SARS-CoV-2 test and adjusted for race/ethnicity, body mass index, smoking status, and comorbid conditions (diabetes type II, coronary artery disease or myocardial infarction, liver disease, and rheumatic or autoimmune disease).0.42 (0.21, 0.81)1.00Death No. of events7 (9)38 (12) Rate of event per 1000 person-days1.02 (0.26, 1.77)1.40 (0.95, 1.84) Matched unadjusted hazard ratio (95% CI)†Matched on age, sex, and date of SARS-CoV-2 test.0.70 (0.32, 1.52)1.00 (reference) Partially adjusted hazard ratio (95% CI)‡Matched on age, sex, and date of SARS-CoV-2 test and adjusted for race/ethnicity, body mass index, and smoking status.0.78 (0.32, 1.92)1.00 Fully adjusted hazard ratio (95% CI)§Matched on age, sex, and date of SARS-CoV-2 test and adjusted for race/ethnicity, body mass index, smoking status, and comorbid conditions (diabetes type II, coronary artery disease or myocardial infarction, liver disease, and rheumatic or autoimmune disease).0.64 (0.24, 1.68)1.00CI, Confidence interval; COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.∗ Age, sex, and date of SARS-CoV-2 diagnosis matched comparators.† Matched on age, sex, and date of SARS-CoV-2 test.‡ Matched on age, sex, and date of SARS-CoV-2 test and adjusted for race/ethnicity, body mass index, and smoking status.§ Matched on age, sex, and date of SARS-CoV-2 test and adjusted for race/ethnicity, body mass index, smoking status, and comorbid conditions (diabetes type II, coronary artery disease or myocardial infarction, liver disease, and rheumatic or autoimmune disease). Open table in a new tab CI, Confidence interval; COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. In this matched cohort study of MGH inpatients with COVID-19, we identified that asthma patients were less likely to require ICU admission and mechanical ventilation but were not at increased risk for death. Given that asthma exacerbations are triggered by viral respiratory infections and that asthma patients have a higher risk of severe illness from other respiratory viruses,2Busse W.W. Lemanske Jr., R.F. Gern J.E. Role of viral respiratory infections in asthma and asthma exacerbations.Lancet. 2010; 376: 826-834Abstract Full Text Full Text PDF PubMed Scopus (586) Google Scholar asthma was considered a COVID-19 risk factor by the Centers for Disease Control and Prevention.5Centers for Disease Control and PreventionCoronavirus disease 2019 (COVID-19): people at increased risk of severe illness. Atlanta, GA: Centers for Disease Control and Prevention; 2020.https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-at-increased-risk.htmlDate accessed: September 15, 2020Google Scholar Although current research specifically assessing asthma and COVID-19 remains limited, recent reports suggest that asthma is not overrepresented among severe COVID-19 cases and may not be associated with an increased risk of hospitalization or death.6Li X. Xu S. Yu M. Wang K. Tao Y. Zhou Y. 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 (1493) Google Scholar, 7Lieberman-Cribbin W. Rapp J. Alpert N. Tuminello S. Taioli E. The impact of asthma on mortality in patients with COVID-19.Chest. 2020; 158: 2290-2291Abstract Full Text Full Text PDF Scopus (62) Google Scholar, 8Halpin D.M.G. Faner R. Sibila O. Badia J.R. Agusti A. Do chronic respiratory diseases or their treatment affect the risk of SARS-CoV-2 infection?.Lancet Respir Med. 2020; 8: 436-438Abstract Full Text Full Text PDF PubMed Scopus (281) Google Scholar, 9Zhu Z. Hasegawa K. Ma B. Fujiogi M. Camargo Jr., C.A. Liang L. Association of asthma and its genetic predisposition with the risk of severe COVID-19.J Allergy Clin Immunol. 2020; 146: 327-329.e4Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar However, most of these studies included other pulmonary conditions (eg, COPD) with asthma cases. Although patients with concomitant asthma-COPD may have a higher risk of severe outcomes, this risk appears to be driven by COPD.5Centers for Disease Control and PreventionCoronavirus disease 2019 (COVID-19): people at increased risk of severe illness. Atlanta, GA: Centers for Disease Control and Prevention; 2020.https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-at-increased-risk.htmlDate accessed: September 15, 2020Google Scholar,9Zhu Z. Hasegawa K. Ma B. Fujiogi M. Camargo Jr., C.A. Liang L. Association of asthma and its genetic predisposition with the risk of severe COVID-19.J Allergy Clin Immunol. 2020; 146: 327-329.e4Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar In this study, we uniquely used a strict diagnosis of asthma and excluded patients with additional chronic pulmonary diseases, thus isolating the association of asthma and risk of worse outcomes among hospitalized COVID-19 patients. With our reduced misclassification of asthma, our findings do not suggest that asthma increases risk of severe outcomes in COVID-19. The factors that underlie our findings of reduced risk of ICU admission and mechanical ventilation among patients with asthma are not currently known.8Halpin D.M.G. Faner R. Sibila O. Badia J.R. Agusti A. Do chronic respiratory diseases or their treatment affect the risk of SARS-CoV-2 infection?.Lancet Respir Med. 2020; 8: 436-438Abstract Full Text Full Text PDF PubMed Scopus (281) Google Scholar Our findings may be explained by immune alterations associated with asthma and allergy, including decreased expression of ACE2—the receptor required for SARS-CoV-2 entry into human cells.9Zhu Z. Hasegawa K. Ma B. Fujiogi M. Camargo Jr., C.A. Liang L. Association of asthma and its genetic predisposition with the risk of severe COVID-19.J Allergy Clin Immunol. 2020; 146: 327-329.e4Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar Future studies should explore the differences in risk associated with asthma phenotypes including allergic and nonallergic asthma. Because all patients in our study were hospitalized for COVID-19, we are unable to estimate the total population effect of asthma on the risk of severe outcomes from COVID-19. Our study may be affected by collider bias because we restricted the study population to patients with COVID-19. Prospective population-based cohort studies that include patients with and without asthma are required to further understand these associations. We did not consider different COVID-19 treatments; however, all patients were cared for at MGH with the same treatment protocols and there was no approved treatment at the time of this study. In summary, among patients hospitalized for COVID-19, asthma was not associated with an increased risk of ICU admission, mechanical ventilation, or death compared with inpatient comparators matched by age, sex, and date of positive SARS-CoV-2 test. We would like to acknowledge all members of the MGH COVID-19 registry for their work on the development and data management for the registry. We thank Christian M. Mancini for his research assistance. L. B. Robinson, Y. Zhang, C. A. Camargo, and K. G. Blumenthal were involved in the study conception or design. L. B. Robinson, I. V. Bassett, V. A. Triant, and A. S. Foulkes acquired the data; X. Fu, A. S. Foulkes, and Y. Zhang analyzed the data. Lacey B. Robinson, Xiaoqing Fu, Y. Zhang, and K. G. Blumenthal drafted the initial report. All authors critically revised the manuscript and involved in the final approval of the manuscript version to be published. The authors agree that they are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.