key: cord-0814924-itprddf8 authors: Strauss, Ronald; Jawhari, Nesreen; Attaway, Amy H.; Hu, Bo; Jehi, Lara; Milinovich, Alex; Ortega, Victor E.; Zein, Joe G. title: Intranasal Corticosteroids are Associated with Better Outcomes in Coronavirus Disease 2019 (COVID-19) date: 2021-08-23 journal: J Allergy Clin Immunol Pract DOI: 10.1016/j.jaip.2021.08.007 sha: 2c9a444d31a5d612273341a827243ad7e10b8605 doc_id: 814924 cord_uid: itprddf8 Background Sites of entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly expressed in nasal epithelial cells, however little is known about the impact of intranasal corticosteroids (INCS) on Coronavirus Disease 2019 (COVID-19) related outcomes. Objective Determine the association between baseline INCS use and COVID-19 related outcomes. Methods Using the Cleveland Clinic COVID-19 Research Registry (CCCRR), we performed a propensity score matching for treatment with INCS prior to SARS-CoV-2 infection (April 1, 2020 - March 31, 2021). Of the 82,096 individuals who tested positive, 72,147 met inclusion criteria. Our endpoints included need for hospitalization, admission to the intensive care unit (ICU), or in-hospital mortality. Results Of the 12,608 (17.5%) who were hospitalized, 2,935 (4.1%) required ICU admission and 1,880 (2.6%) died during hospitalization. A significant proportion (n=10,187; 14.1%) were utilizing INCS prior to SARS-CoV-2 infection. Compared to non-users, INCS users demonstrated lower risk for hospitalization (adjusted OR [95% CI]: 0.78 [0.72; 0.85]), ICU admission (adjusted OR [95% CI]: 0.77 [0.65; 0.92]) and in-hospital mortality (adjusted OR [95% CI]: 0.76 [0.61; 0.94]). These findings were replicated in sensitivity analyses where patients on inhaled corticosteroids, and those with allergic rhinitis were excluded. The beneficial effect of INCS was significant after adjustment for baseline blood eosinophil count (measured prior to SARS-CoV-2 testing) in a subset of 30,289 individuals. Conclusion INCS therapy is associated with a lower risk for COVID-19-related hospitalization, ICU admission, or death. Future randomized control trials are needed to determine if INCS reduces the risk for severe outcomes related to COVID-19. Angiotensin Repository at www.jaciinpractice.org) (16, 17) 166 167 Study Outcomes and Groups Definition. The primary outcome was COVID-19 related-hospitalizations. We also studied the 170 following secondary outcomes: the rate of ICU admission, and mortality during index 171 hospitalization. We also performed three sensitivity analyses. Quality (AHRQ) definition of immunocompromised state diagnosis), (24) and the month of 209 testing (see Figure E2 in this article's Online Repository at www.jaciinpractice.org). The Figure E2 ]. (19, 28) We also repeated all analyses using the original complete non- To account for the confounding effect of "allergic rhinitis", we had a two-pronged 314 approach. First, we adjusted for "allergic rhinitis" in all our models (see Figure E2A , E2B, 315 and E2C in this article's Online Repository at www.jaciinpractice.org). Second, we 316 analyzed a subgroup of 65,767 individuals who did not have the diagnosis "allergic 317 rhinitis" recorded in their EHR (see Table E3 confounders is crucial, given that iCS usage was also linked to decreased expression of 353 ACE2 and TMPRSS2 in vitro. (9, 11, 33) To address this important issue, we adjusted for Table E1 . Clinical characteristics, presentation, and outcomes of a subgroup of patients who did not have a presicription for inhaled corticosteroids (iCS) on file prior to the date of SARS-CoV-2 testing. Analysis stratified by the Use of Intranasal Corticosteroids. Table E2 . Clinical characteristics, presentation, and outcomes of patients with available baseline blood absolute eosinophil count* measurements stratified by the use of intranasal corticosteroids. Table E3 . Clinical characteristics, presentation, and outcomes of patients with a positive SARS-CoV-2 test, excluding all individuals who ever receive a diagnosis of allergic rhinitis. Table E4 . Association between intranasal corticosteroids use before and after propensity score (PS) matching using complete cases (i.e. without imputation, and excluding patients with missing data) Figure E1 . Flow chart of patients in final analysis. Figure E2 . Standardized mean differences plots (Love plot) comparing baseline characteristics between patients treated with and without intranasal corticosteroids (INCS) before and after propensity-score matching. Figure E1 . Flow chart of patients in final analysis. J o u r n a l P r e -p r o o f Figure E2 . Standardized mean differences plots (Love plot) comparing baseline characteristics between patients treated with and without intranasal corticosteroids (INCS) before and after propensity-score matching. Analysis stratified into 4 groups: (A) All patients who met inclusion criteria. (B) Patients who did not have an inhaled corticosteroid prescription on file. (C) Patients on whom a blood eosinophil count measurement was obtained at least 14 days prior to the date of a positive SARS-CoV-2 test, but not before 2018. (D)Patients who were never diagnosed with "allergic rhinitis". An absolute standardized difference of 0% indicates no residual bias and values <10% indicate inconsequential bias. 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The New England journal of medicine The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention Extracting and utilizing electronic health data from Epic for research This study uses the CCCRR, which includes all patients tested for SARS-CoV-2 at the Cleveland Clinic Healthcare System (CCHS). Data on patients' demographics, medications, comorbidities, history of SARS-CoV-2 exposure, national and international travel, disease manifestation upon presentation, socioeconomic status, COVID-19 related therapy, disposition, and outcomes were extracted from electronic health records (EHR). (E1) Additionally, data related to hospitalization, critical care needs and outcome were extracted for patients requiring hospitalization. Registry characterization and data collection reflect the clinical characteristics previously published on COVID-19. (E2-E6) Uniform clinical templates were implemented across the CCHS using EHR to standardize the care of patients tested for SARS-CoV-2, and to facilitate data extraction. Data extraction from EHR (Epic®, Epic Systems Corporation, Wisconsin, USA) at the CCHS was performed manually by a trained research team and electronically using predefined processes that have been previously published. (E7) This study and the CCCRR were both approved by the Cleveland Clinic Institutional Review Board (IRB #20-283 and 20-391). Specimens were collected using standardized protocols by trained medical List of systemic medications used to define immunosuppressive therapy. Table E2 . Clinical characteristics, presentation, and outcomes of patients with available baseline blood absolute eosinophil count * measurements stratified by the use of intranasal corticosteroids.