tetano
Editor, Senior Moderator
J Allergy Clin Immunol
. 2020 Jun 9;S0091-6749(20)30828-9.
doi: 10.1016/j.jaci.2020.05.051. Online ahead of print.
Expression of SARS-CoV-2 Receptor ACE2 and Coincident Host Response Signature Varies by Asthma Inflammatory Phenotype
Matthew J Camiolo[SUP] 1 [/SUP], Marc Gauthier[SUP] 1 [/SUP], Naftali Kaminski[SUP] 2 [/SUP], Anuradha Ray[SUP] 3 [/SUP], Sally E Wenzel[SUP] 4 [/SUP]
Affiliations
Abstract
Background: Over 300 million people carry a diagnosis of asthma with data to suggest they are at higher risk for infection or adverse outcomes from SARS-CoV-2. Asthma is remarkably heterogenous and it is currently unclear how patient intrinsic factors may relate to COVID-19.
Objective: Identify and characterize subsets of asthmatics at increased risk for SARS-CoV-2 infection.
Methods: Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to ACE2 expression within bronchial epithelium. ACE-2 correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets.
Results: Stratifying by Type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the SARS-CoV-2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with Type 1 and 2 interferon signatures, normally induced by viral infections. T cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe COVID-19, including male sex, history of hypertension, low peripheral blood and elevated BAL lymphocytes.
Conclusion: ACE2 expression is linked to upregulation of viral response genes in a subset of Type-2 low asthmatics with characteristics resembling known risk factors for severe COVID-19. Therapies targeting the interferon family and T cell activating factors may therefore be of benefit in a subset of patients.
Clinical implication: Type-2 low asthmatics may be at increased risk for adverse outcome from COVID-19 and deserve increased vigilance upon developing symptoms.
Keywords: ACE2; Asthma; COVID-19; Coronavirus; Immunopathology; Interferons; SARS-CoV-2; Viral Response.
. 2020 Jun 9;S0091-6749(20)30828-9.
doi: 10.1016/j.jaci.2020.05.051. Online ahead of print.
Expression of SARS-CoV-2 Receptor ACE2 and Coincident Host Response Signature Varies by Asthma Inflammatory Phenotype
Matthew J Camiolo[SUP] 1 [/SUP], Marc Gauthier[SUP] 1 [/SUP], Naftali Kaminski[SUP] 2 [/SUP], Anuradha Ray[SUP] 3 [/SUP], Sally E Wenzel[SUP] 4 [/SUP]
Affiliations
- PMID: 32531372
- PMCID: PMC7283064
- DOI: 10.1016/j.jaci.2020.05.051
Abstract
Background: Over 300 million people carry a diagnosis of asthma with data to suggest they are at higher risk for infection or adverse outcomes from SARS-CoV-2. Asthma is remarkably heterogenous and it is currently unclear how patient intrinsic factors may relate to COVID-19.
Objective: Identify and characterize subsets of asthmatics at increased risk for SARS-CoV-2 infection.
Methods: Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to ACE2 expression within bronchial epithelium. ACE-2 correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets.
Results: Stratifying by Type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the SARS-CoV-2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with Type 1 and 2 interferon signatures, normally induced by viral infections. T cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe COVID-19, including male sex, history of hypertension, low peripheral blood and elevated BAL lymphocytes.
Conclusion: ACE2 expression is linked to upregulation of viral response genes in a subset of Type-2 low asthmatics with characteristics resembling known risk factors for severe COVID-19. Therapies targeting the interferon family and T cell activating factors may therefore be of benefit in a subset of patients.
Clinical implication: Type-2 low asthmatics may be at increased risk for adverse outcome from COVID-19 and deserve increased vigilance upon developing symptoms.
Keywords: ACE2; Asthma; COVID-19; Coronavirus; Immunopathology; Interferons; SARS-CoV-2; Viral Response.