Asthma phenotypes, associated comorbidities, and long-term symptoms in COVID-19

Abstract

Background: It is unclear if asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS-CoV-2. Methods: All patients testing positive for SARS-CoV-2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub-cohort was followed prospectively to evaluate long-term COVID-19 symptoms. Results: 168,190 patients underwent SARS-CoV-2 testing, and 6,976 (4·15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1·12 [95% CI 0·86, 1·45], p=0·40). Among SARS-CoV-2 positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared to non-allergic asthma (OR 0·52 (0·28, 0·91), p=0·026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID-19 disease had lower eosinophil levels during hospitalization compared to patients with mild or asymptomatic disease, independent of asthma status (p=0.0014). In a patient sub-cohort followed longitudinally, asthmatics and non-asthmatics had similar time to resolution of COVID-19 symptoms, particularly lower respiratory symptoms. Conclusions: Asthma is not a risk factor for more severe COVID-19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID-19 compared to non-allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with more severe COVID-19 disease trajectory. Recovery was similar among asthmatics and non-asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms three months post-infection.

Pediatric Asthma Exacerbation in Children with Suspected and Confirmed Coronavirus Disease 2019 (COVID-19): An Observational Study from Saudi Arabia

“…Previous PICU admission, preadmission blood eosinophilic counts, and history of ED visits within the previous year are all known predictors of severe asthma exacerbation requiring hospitalization or critical care admission. 20–34 Furthermore, stratifying asthma phenotyping based on baseline blood eosinophilic counts and total IgE levels did not affect hospitalizations or the need for critical care (data not shown). This effect, however, needs to be studied with a large sample size.…”

“… 13 , 16–19 In addition, several adult studies have suggested that patients with allergic asthma may develop milder COVID-19 disease compared with a non-allergic asthma phenotype. 20 Allergic asthma phenotype is defined as asthma with type 2 driven inflammation characterized endotypically by aeroallergen sensitizations, high total immunoglobulin E level, and high eosinophilic count, which commonly originates in childhood and is associated with other clinical atopic diseases such as allergic rhinitis and eczema. 16 , 18 , 19 , 21 The proposed mechanisms of the allergic asthma protection against COVID-19 disease include lower the angiotensin-converting enzyme (ACE) 2 receptor expression in allergic asthmatics nasal epithelia, eosinophilic-driven reduction of viral load with subsequent attenuation of COVID-19, and downregulation of ACE2 and transmembrane protease serine 2 (TMPRSS2) gene expression using inhaled corticosteroid therapies.…”

Recent advances and developments in COVID‐19 in the context of allergic diseases

“…The asthma phenotype was found to be a strong determinant of disease severity. In a study from Stanford University, allergic asthma was found to mitigate the risk of hospitalization for COVID‐19 compared to patients with non‐allergic asthma (OR, 0.52) 24 . In addition, patients with non‐allergic asthma were more susceptible to SARS‐CoV‐2 infection and unfavorable clinical outcomes than patients with allergic asthma in a South Korean study 25 .…”

“…In addition, patients with non‐allergic asthma were more susceptible to SARS‐CoV‐2 infection and unfavorable clinical outcomes than patients with allergic asthma in a South Korean study 25 . Lower eosinophil counts were a predictive biomarker of severe disease progression independent of asthma phenotype 24 …”

“…There are multiple factors that can account for these inconsistent findings including atopic status, 23 asthma phenotype, 24,25 eosinophil counts, 24 lockdown regulations, 12,26 dietary habits, 27‐31 airborne pollen concentrations, 32,33 air pollution, 34 climate, 35 and comorbidities 12 (Figure 1). Respiratory atopy was suggested to have a protective role against severe lung disease in COVID‐19 patients with viral pneumonia 23 .…”