key: cord-1023638-uh6u7qzv authors: Cao, Lijuan; Lee, Sandra; Krings, James G.; Rauseo, Adriana M.; Reynolds, Daniel; Presti, Rachel; Goss, Charles; Mudd, Philip A.; O'Halloran, Jane A.; Wang, Leyao title: Asthma in COVID-19 suspected and diagnosed patients date: 2021-02-25 journal: Ann Allergy Asthma Immunol DOI: 10.1016/j.anai.2021.02.020 sha: 117b73299faa6908a502c8554a8449ae14e55126 doc_id: 1023638 cord_uid: uh6u7qzv BACKGROUND: Asthma patients are comparatively susceptible to respiratory viral infections and more likely to develop severe symptoms than people without asthma. During the coronavirus disease 2019 (COVID-19) pandemic, it is necessary to adequately evaluate the characteristics and outcomes of the asthma population in the COVID-19 tested and diagnosed population. OBJECTIVE: We performed a study to assess the impact of asthma on COVID-19 diagnosis, presenting symptoms, disease severity, and cytokine profiles. METHODS: This was an analysis of a prospectively collected cohort of patients suspected of having COVID-19 who presented for COVID-19 testing at a tertiary medical center in Missouri, USA between March and September 2020. We classified and analyzed patients according to their preexisting asthma diagnosis and subsequent COVID-19 testing results. RESULTS: COVID-19 suspected patients (n=435) were enrolled in this study. The proportion of patients testing positive for COVID-19 was 69.2% and 81.9% in the asthma and non-asthma groups respectively. The frequency of relevant symptoms are similar between asthma groups with positive and negative COVID-19 test results. In the COVID-19 diagnosed population (n=343), asthma was not associated with several indicators of COVID-19 severity, including hospitalization, admission to an intensive care unit (ICU), mechanical ventilation, death due to COVID-19, and in-hospital mortality after multivariate adjustment. COVID-19 patients with asthma exhibited significantly lower levels of plasma interleukin (IL)-8 compared to patients without asthma (adjusted p=0.023). CONCLUSION: The asthma population is facing a challenge in preliminary COVID-19 evaluation due to overlap in symptoms of COVID-19 and asthma. However, asthma does not increase the risk of COVID-19 severity if infected. Researchers have postulated that asthma patients may be both at high risk of being infected with 13 SARS-CoV-2 and experience more severe outcomes when infected. 7 However, these 14 assumptions have not been clearly demonstrated in numerous studies to date. 8-12 Early findings 15 from Wuhan, China revealed that asthma was under-represented in COVID-19 infected patients, 16 with the prevalence of asthma only at 0.9% among 548 patients with COVID-19, whereas the 17 overall prevalence of asthma was 6.4% in the adult Wuhan population. 13 Similarly, COVID-19 18 infection was noted to be comparatively low in patients in the Severe Asthma Network in Italy, 19 and asthma patients also had comparatively low mortality rates if infected. 14 Even though the 20 prevalence of asthma among COVID-19 patients in Europe and the United States has been 21 substantially higher, ranging from about 8% to 17%, asthma was not observed to be associated To this end, we conducted an analysis using a prospectively collected cohort of patients who We compared different characteristics between COVID-19 positive and negative patients 96 stratified by asthma ( Table 1 ). Regardless of asthma status, the COVID-19 group was older 97 (p=0.0014 in the asthma group and p<0.0001 in the non-asthma group) and had a higher 98 percentage of underlying comorbidities [hypertension (p=0.0012 in the asthma group and 99 p<0.0001 in the non-asthma group) and diabetes (p=0.017 in the asthma group and p<0.0001 in 100 the non-asthma group)]. More males were in the COVID-19 group, but this was only significant 101 for the non-asthma patients. Participants who were diagnosed with COVID-19 were more likely 102 to report their race as Black in the non-asthma group (p<0.0001), but this did not reach statistical 103 significance in the asthma group (p=0.053). In addition, participants diagnosed with COVID-19 104 had a substantially higher BMI (p=0.00096) and percentage of obesity (p=0.0055) than non-105 COVID-19 patients, but statistical significance was only observed in the asthma population. 3. Among the COVID-19 diagnosed population, asthma was not associated with increased risks 119 for severe outcomes. 120 We next focused specifically on patients who tested positive for COVID-19 (n=343) to evaluate 121 whether those with asthma have distinct symptoms and cytokine profiling as compared to those 122 without asthma. Basic characteristics of these participants are shown in Table 2 . COVID-19 123 patients with asthma (n=72) were older compared to those without asthma (n=271, p=0.00066). 124 Males were more prevalent in the non-asthma group (62.6%) than females, but this was not the 125 case in the asthma group (31.9%). BMI was higher in the asthma group compared to the non-126 asthma group (p=0.00038). The presence of obesity (p=0.0040) and COPD (p<0.0001) was 127 higher among patients with asthma, but no significant differences in the prevalence of 128 hypertension and diabetes existed between the two groups. There were also no significant 129 differences with known COVID-19 exposure prior to illness. In order to assess differences in the underlying immune responses between COVID-19 patients 143 with and without asthma, we measured 35 plasma cytokine levels from 42 patients including 21 144 asthma-control pairs matched with age (within 5-year interval) and sex. We found that for 23 out 145 of 35 cytokines, asthma patients had lower median cytokine levels than non-asthma patients and 146 for 11 out of 35 cytokines, asthma patients had higher median cytokine levels (Fig 3A) . A direct 147 comparison further revealed that COVID-19 patients with asthma exhibited significantly reduced 148 levels of IL-8 than those without asthma (Bonferroni adjusted p=0.023, Fig 3B) , but no other 149 measured cytokines demonstrated statistical differences between these two groups. Comparison showed that among COVID-19 suspected patients, those with asthma were more likely to test 156 negative for COVID-19 than those without asthma, which is consistent with results from a large 157 retrospective cohort study in Israel. 26 Furthermore, we found that the presenting symptoms were similar regardless of subsequent COVID-19 diagnosis among patients with and without asthma, Clinical features of patients infected with 2019 novel 229 coronavirus in Wuhan, China Role of viral respiratory infections in asthma and 231 asthma exacerbations Airway Epithelial Orchestration of Innate Immune 233 Function in Response to Virus Infection Rhinovirus-induced lower respiratory illness is 236 increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production Infection-related asthma How rhinovirus infections cause exacerbations of asthma Asthma and COVID-19: Is asthma a risk factor for severe outcomes? Asthma and COVID-19: review of evidence on 245 risks and management considerations COVID-19 and Asthma: Reflection During the Pandemic Does asthma affect morbidity or severity of COVID-19? Do chronic respiratory diseases or their treatment 251 affect the risk of SARS-CoV-2 infection? Asthma in COVID-19 Hospitalizations: An 253 Overestimated Risk Factor? Risk factors for severity and mortality in adult COVID-19 inpatients in 255 COVID-19 in Severe Asthma Network in Italy (SANI) 257 patients: Clinical features, impact of comorbidities and treatments Prevalence and characterization of asthma in 259 hospitalized and nonhospitalized patients with COVID-19 Asthma among hospitalized patients with 262 COVID-19 and related outcomes Differentiating 264 characteristics of patients with asthma in the severe acute respiratory syndrome 265 coronavirus 2 infection Comparison of symptom frequencies reported at enrollment between COVID-19 patients with 17 and without asthma Selective cytokine raw values plotted on a log10 scale. P-values were calculated using Mann-35 Whitney U test and were adjusted for multiple comparison using Bonferroni method. ns: not We appreciate the critical scientific advice from Dr. Gregory Storch (Washington University in St.