ABSTRACT
Introduction: COVID-19 vaccination substantially reduces morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe illness. However, despite effective COVID-19 vaccines many questions remain about the efficacy of vaccines and the durability and robustness of immune responses, especially in immunocompromised persons. The NCI-funded Serological Sciences Network (SeroNet) is a coordinated effort including 11 sites to advance research on the immune response to SARS-CoV-2 infection and COVID-19 vaccination among diverse and vulnerable populations. The goals of the Pooling Project are: (1) to conduct real-world data (RWD) analyses using electronic medical records (EMR) data from four health care systems (Kaiser Permanente Northern California, Northwell Health, Veterans Affairs-Case Western, and Cedars-Sinai) to determine vaccine effectiveness in (a) cancer patients;(b) autoimmune diseases and (c) solid organ transplant recipients (SOTR);(2) to conduct meta-analyses of prospective cohort studies from eight SeroNet institutions (Cedars-Sinai, Johns Hopkins, Northwell Health, Emory University, University of Minnesota, Mount Sinai, Yale University) to determine post-vaccine immune responses in (a) lung cancer patients;(b) hematologic cancers/hematopoietic stem cell transplant (HSCT) recipients;(c) SOTR;(d) lupus. Method(s): For our RWD analyses, data is extracted from EMR using standardized algorithms using ICD-10 codes to identify immunocompromised persons (hematologic and solid organ malignancy;SOTR;autoimmune disease, including inflammatory bowel disease, rheumatoid arthritis, and SLE). We use common case definitions to extract data on demographic, laboratory values, clinical co morbidity, COVID-19 vaccination, SARS-CoV-2 infection and severe COVID-19, and diseasespecific variables. In addition, we pool individual-level data from prospective cohorts enrolling patients with cancer and other immunosuppressed conditions from across network. Surveys and biospecimens from serology and immune profiling are collected at pre-specified timepoints across longitudinal cohorts. Result(s): Currently, we have EMR data extracted from 4 health systems including >715,000 cancer patients, >9,500 SOTR and >180,000 with autoimmune conditions. Prospective cohorts across the network have longitudinal data on >450 patients with lung cancer, >1,200 patients with hematologic malignancies, >400 SOTR and >400 patients with lupus. We will report results examining vaccine effectiveness for prevention of SARS-CoV-2 infection, severe COVID-19 and post-acute sequelae of COVID-19 (PAS-C or long COVID) in cancer patients compared to other immunocompromised conditions. Conclusion(s): Our goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in immunocompromised populations.
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