Atopy is predictive of a decreased need for hospitalization for COVID-19

Abstract

The COVID-19 pandemic has caused high utilization of healthcare resources including hospitalization and intensive care unit treatment. There has been considerable interest in determining which clinical factors stratify patients into high or low risk for severe COVID-19 illness to aid with clinical decision making. Advanced age, cardiovascular disease and diabetes have been associated with increased COVID-19 severity 1 . Asthma appears to be under-represented as a COVID-19 comorbidity compared to its global prevalence of disease 1 , 2 . To date, the effect of atopic conditions on the disease course of COVID-19 has yet to be fully elucidated. This study is a large, two site cohort of COVID-19 positive patients designed to understand the association between atopic conditions and COVID-19 disease severity. The study was approved by the Institutional Review Board of both participating universities. An electronic medical records (EMR) database search was performed to identify patients tested for COVID-19. All encounters of these patients were carefully reviewed and only cases who were active patients at the health systems, with a detailed medical history available prior to the diagnosis of COVID-19, were included in the study. Through extensive chart review, demographic and clinical factors related to allergy evaluations including active or historical diagnoses of asthma, allergic rhinitis (AR), eczema, and food allergy, and variables related to COVID-19 infection severity were retrieved from the EMR. To confirm these allergy-related variables, charts were initially reviewed by trained researchers for ICD-10 codes and the diagnoses were subsequently verified by clinical history and evidence of allergic sensitization via skin prick or serum IgE testing by board-certified allergists. Logistic regressions were used to compare COVID-19 related outcomes in association with pre-existing AR, asthma, eczema and food allergy while adjusting for age, gender, body mass index and race. Patients with a history of AR and/or eczema and/or food allergy were labeled as atopic. Similar regression analysis was performed to compare atopic and non-atopic individuals. Asthmatics were first analyzed as a single group compared to non-asthmatics. Next, asthmatics were divided into allergic asthma, defined as patients with a diagnosis of both AR and asthma, and non-allergic asthma for subgroup analysis. The combined series included 2013 patients with positive nasopharyngeal SARS-CoV-2 PCR test results. Complete data on demographic variables, confirmed allergy diagnoses, and COVID-19 management variables was available for 1043 patients who were used for our analysis. 970 patients were excluded as they were not active patients in the medical center’s EMR prior to their COVID-19 diagnosis. The mean (standard deviation) of age was 50.16 (16.77) years, 43.3% were male and 58.1% were African Americans. There was no significant difference in demographics between the atopic and non-atopic groups. Among these 1043 cases, 257 (24.6%) were atopic. Atopy was associated with significantly lower odds of hospitalization for COVID-19 (Table 1 ); 27.6% of atopic and 37.8% of non-atopic COVID-19 patients were hospitalized (adjusted p=0.004). Furthermore, atopy was associated with a decreased duration of hospitalization for COVID-19. When analyzing AR, eczema and food allergy separately, both AR and eczema were associated with lower odds of COVID-19 related hospitalization (Table 1). AR was also associated with a decreased duration of hospitalization and intubation for COVID-19. Asthma was associated with increased intubation time; mean intubation time was 13.4 vs. 8.1 days in asthmatics vs. non-asthmatics (adjusted p=0.016). When asthmatics were grouped into allergic and non-allergic, only non-allergic asthma was associated with prolonged intubation time (Table 1). There was no difference in mortality between the atopic and non-atopic groups. Treatment regimens for COVID-19 were not notably different between the atopic and non-atopic groups, with minimal use of systemic corticosteroids in this cohort. Table 1 Characteristics and outcomes of COVID-19 patients in association with atopic conditions in 1043 COVID-19 positive patients in a two-center study from U.S. Conditions rowhead Atopy £ Allergic Rhinitis (AR) Eczema Food allergy (FA) Allergic Asthma (AA)€ Non-allergic Asthma (NAA) rowhead N=257 N=171 N=58 N=80 N=86 N=179 COVID-19 Outcomesrowhead Odds ratio(95%CI) or beta(95%CI) p value ¥ Odds ratio(95%CI) or beta(95%CI) P value ¥ Odds ratio(95%CI) or beta(95%CI) p value ¥ Odds ratio(95%CI) or beta(95%CI) p value ¥ Odds ratio(95%CI) or beta(95%CI) p value ¥ Odds ratio(95%CI) or beta(95%CI) p value ¥ Hospitalizedrowhead 0.62(0.44-0.86) 0.004 0.64(0.43-0.92) 0.02 0.51(0.25-0.90) 0.045 0.97(0.57-1.62) 0.90 0.77(0.57-1.03) 0.08 1.03(0.75-1.41) 0.85 Duration of hospitalization, mean (SD)rowhead -1.67(-2.9-[-0.4]) 0.008 -2.33(-3.6-[0.9]) 0.001 -2.2(-4.5-0.2) 0.07 1.79(-0.57-4.17) 0.13 -0.68(1.81-0.45) 0.24 1.00(0.26-2.27) 0.12 Admitted to ICUrowhead 0.75(0.46-1.17) 0.21 0.71(0.40-1.19) 0.21 0.65(0.22-1.55) 0.37 0.97(0.41-2.01) 0.93 1.02(0.69-1.51) 0.90 1.31(0.85-1.99) 0.22 Intubated,rowhead 0.61(0.33-1.07) 0.10 0.75(0.38-1.37) 0.37 0.18(0.01-0.87) 0.09 0.71(0.21-1.83) 0.53 1.06(0.66-1.68) 0.81 1.45(0.87-2.36) 0.14 Duration of Intubation, mean (SD)rowhead -1.1(-2.3-+0.2) 0.10 -1.4(2.80-[-0.07]) 0.039 -0.93(-3.4-1.5) 0.46 1.08(-2.08-4.25) 0.50 0.21(-1.00-1.44) 0.72 1.18(0.41-3.21) 0.011 £= Atopy is defined as presence of allergic rhinitis and/or eczema and/or food allergy. €= Allergic asthma is defined by asthma diagnosed based on GINA guidelines and evidence of inhalant allergen sensitization and non-allergic asthma are asthmatics without inhalant allergen sensitization. In this paper. those with comorbid asthma and allergic rhinitis are considered allergic asthma and asthmatics without allergic rhinitis are grouped in non-allergic asthma. ¥= P.values for categorical variables are calculated by logistic regression comparing categorical variables adjusted for age, race, sex and body mass index (BMI) , or analysis of covariance (ANCOVA) comparing the adjusted means of continuous variables adjusting for age, race, sex and BMI. Odds ratio (95%confice interval) are reported for categorical variables and beta is reported for continuous variables. In our series, AR and eczema were associated with a lower rate of hospitalizations, and AR was associated with a lower duration of hospitalization and intubation for COVID-19 infections. This adds greater credence to an earlier report from China in which respiratory allergies were not identified as risk factors for severe COVID-19 illness 1 . In a recent study, Jackson et al. demonstrated that expression of angiotensin-converting enzyme 2 (ACE2), the cell receptor utilized by SARS-CoV-2 for cell entry, was decreased in atopic individuals 3 . Interestingly, reductions in ACE2 expression levels correlate with allergic sensitization, higher levels of total IgE and Type 2 inflammatory (Th-2) cytokines3, 4, 5. Interleukin (IL)-13, a major Th-2 cytokine, is shown to significantly reduce ACE2 expression in airway epithelial cells 5 . Our findings of the association of allergic rhinitis and eczema with decreased need of hospitalization for COVID-19 provides robust clinical data to support these mechanistic findings. The role of asthma and its association with COVID-19 severity is more complicated 6 , 7 . Asthma was not reported in previously published cohorts of COVID-19 from China 1 , 2 ; while data from the Centers for Disease Control indicates that asthma is present in as high as 27% of hospitalized COVID-19 patients in the United States in the 20-49 year age range 6 . This could be explained by the lower rates of asthma in China (2-4%) compared to the United States (8-11%)8,9. In the current report, allergic asthma was not associated with any COVID-19 outcome variable despite allergic rhinitis being protective against hospitalization. Furthermore, non-allergic asthma was associated with a prolonged intubation time which confirms an earlier study 10 . It is possible that asthma, as a chronic pulmonary disease prone to viral-induced exacerbations, places those with more severe COVID-19 illness at risk for more prolonged lung involvement. However, a co-existing atopic background may mitigate the severe inflammatory response syndrome of COVID-19 in allergic asthmatics, leading to the absence of the prolonged intubation time seen in non-allergic asthmatics. The knowledge that atopy is associated with less severe COVID-19 outcomes can be instructive in clinical risk stratification. Further studies are needed to understand the underlying mechanism of these apparent protective physiologic factors which may prove advantageous in future prevention and treatment strategies. Uncited reference 9..