ABSTRACT
SESSION TITLE: Late Breaking Insights In Management of Asthma and COPD SESSION TYPE: Original Investigations PRESENTED ON: 10/18/2022 09:15 am - 10:15 am PURPOSE: SARS-CoV-2 vaccines have greatly reduced the impact of the COVID-19 pandemic. However, immune responses and their ability to protect against SARS-CoV-2 infection and severe clinical outcomes vary amongst vaccinees. Understanding who remains at high risk for severe infection despite vaccination and who may need additional vaccine boosters is critical for the control of this and future pandemics. We recently reported a reduced humoral immune response after mRNA SARS-CoV-2 vaccination in patients with severe asthma or atopic dermatitis on biologic therapies three months after the second vaccination, compared to healthy controls. The purpose of this study is to characterize the immune response of these patients six months after vaccination. METHODS: We conducted a prospective observational trial from February 2021 to February 2022 and enrolled 77 adults with severe asthma or atopic dermatitis treated with benralizumab, mepolizumab or dupilumab, receiving a SARS-CoV-2 mRNA vaccination, in addition to 45 healthy controls. We analyzed pseudovirus neutralization against wild-type, Delta variant and Omicron variant SARS-CoV-2, using a pseudotyped lentivirus. RESULTS: After excluding patients with prior COVID-19 or significant immunosuppression, we analyzed 28 patients (5 patients on benralizumab, 20 patients on dupilumab, 3 patients on mepolizumab) in addition to 34 healthy controls at 6 months after vaccination. We found that patients with severe asthma or atopic dermatitis treated with biologics had lower pseudovirus neutralization titer at 6 months, compared to healthy controls. The mean 50% inhibitory dilution against wild-type SARS-CoV-2 among patients on biologics were lower at 2.313 log10 compared to 2.743 log10 in the healthy control group, p-value <0.0001. Additionally, the patients on biologics had lower neutralizing antibody titers against Delta variant and Omicron variant SARS-CoV-2. CONCLUSIONS: Our data shows that patients with severe asthma or atopic dermatitis on biologic therapies have lower neutralization titer after SARS-CoV-2 mRNA vaccination compared to healthy controls 6 months after the second vaccination. Large population studies have recently shown that severe or active asthma is associated with worse COVID-19 outcomes and several studies have shown that lower humoral immunity after vaccination is associated with less protection against disease. It is therefore critical to provide booster vaccinations to these vulnerable patients. CLINICAL IMPLICATIONS: Clinicians should encourage patients with severe asthma or atopic dermatitis on biologic therapies to receive SARS-CoV-2 booster vaccinations as they may unknowingly remain at high risk for severe disease. DISCLOSURES: No relevant relationships by Fabliha Anam No relevant relationships by Suneethamma Cheedarla No relevant relationships by Narayanaiah Cheedarla No relevant relationships by John Daiss No relevant relationships by Natalie Haddad No relevant relationships by Ian Hentenaar No relevant relationships by Fernando Holguin No relevant relationships by Caroline Kim No relevant relationships by Pedro Lamothe No relevant relationships by Frances Lee No relevant relationships by ANDREW NEISH No relevant relationships by wendy neveu No relevant relationships by Rahulkumar Patel No relevant relationships by Carmen Polito No relevant relationships by Richard Ramonell No relevant relationships by Mayuran Ravindran No relevant relationships by John Roback No relevant relationships by Martin Runnstrom Consultant relationship with BLI, Inc. Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Royalty Consultant relationship with Bristol Meyers Squibb/Celgene Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Consulting fee Speaker/Speaker's Bureau relationship with Bristol Meyers Squibb/Celgene Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=H noraria Consultant relationship with GlaxoSmithKline Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Consulting fee Speaker/Speaker's Bureau relationship with GlaxoSmithKline Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Honoraria Consultant relationship with Janssen Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Consulting fee Speaker/Speaker's Bureau relationship with Janssen Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Honoraria Consultant relationship with Visterra Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Consulting fee Speaker/Speaker's Bureau relationship with Visterra Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Honoraria Consultant relationship with Kyverna Please note: past 36 months Added 07/18/2022 by Ignacio Sanz, value=Consulting fee No relevant relationships by Sunita Sharma No relevant relationships by Colin Swenson No relevant relationships by Robert Swerlick
ABSTRACT
Introduction: Obesity is a complex disease that exhibits alteration in immune function. Due to the imbalance between anti-and pro-inflammatory mediators secreted by adipocytes and immune cells, the scales are tipped toward a chronic inflammatory state. As the body mass index (BMI) increases, the visceral adipocytes have been found to secrete higher levels of pro-inflammatory cytokines such as interleukin (IL-) 6, which contribute to alterations in coagulation signaling. These findings raise concerns that obesity-mediated inflammation may be responsible for the observed findings of higher risk of severity from SARS-CoV-2 in this population. This study examines the effect of obesity on levels of inflammatory markers and severity of illness from COVID-19 in a cohort of critically ill patients. Methods: Data were collected from the electronic medical record (EMR) by the Emory COVID-19 Quality and Clinical Research Collaborative. We analyzed data of patients admitted with COVID-19 within the Emory Healthcare System between March 6, 2020 and May 5, 2020 who spent any time in the intensive care unit during their hospitalization. We used the Chi-square test to determine if death or intubation were associated with obesity (BMI > 30) and t-tests when comparing inflammatory markers between obese and non-obese patients. Multivariate logistic regression was completed to evaluate the role of BMI and severity of illness on death. Results: Results for BMI were available for 285 patients in the cohort, and 149 patients (52.3%) were considered obese with a BMI of 30 or greater. Obese patients in our cohort were younger on average by 10 years (59 years vs. 69 years, p<0.0001), and there was no significant difference in gender. Intubation rates were significantly higher in the obese population (80.5% vs. 64.7%, p=0.0026), and death rates were significantly lower in this group with a BMI greater than 30 (26.2% vs. 43.4%, p=0.0022). Values for inflammatory markers (CRP, IL-6, D-dimer, and WBC) were not significantly different between obese and nonobese individuals. Multivariate logistic regression analysis determined that patients with higher BMIs had a significantly lower risk of mortality when controlled for severity of illness as indicated by sequential organ failure assessment (SOFA) score and age (OR 0.94, 95% CI 0.90-0.98, p=0.0014). Conclusions: In our cohort of critically ill patients with COVID-19, obesity is associated with a greater risk of mechanical ventilation, but a lower risk of death even when accounting for severity of illness and age.