Antibody Responses After SARS-CoV-2 mRNA Vaccination in Adults With Inflammatory Bowel Disease
Authors: Gil Y. Melmed, Gregory J. Botwin, Kimia Sobhani, Dalin Li, John Prostko, Jane Figueiredo, Susan Cheng, Jonathan Braun, Dermot P.B. McGovern
Journal: Annals of Internal Medicine (2021)

Letters12 October 2021Antibody Responses After SARS-CoV-2 mRNA Vaccination in Adults With Inflammatory Bowel DiseaseFREECorrection(s) for this article:CorrectionsDec 2021Correction: Antibody Responses After SARS-CoV-2 mRNA Vaccination in Adults With Inflammatory Bowel DiseaseFREEGil Y. Melmed, MD, MS, Gregory J. Botwin, BS, Kimia Sobhani, PhD, Dalin Li, PhD, John Prostko, MS, Jane Figueiredo, PhD, Susan Cheng, MD, MMSc, MPH, Jonathan Braun, MD, PhD, Dermot P.B. McGovern, MD, PhDGil Y. Melmed, MD, MSInflammatory Bowel and Immunobiology Research Institute, Karsh Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CaliforniaSearch for more papers by this author, Gregory J. Botwin, BSInflammatory Bowel and Immunobiology Research Institute, Karsh Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CaliforniaSearch for more papers by this author, Kimia Sobhani, PhDDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CaliforniaSearch for more papers by this author, Dalin Li, PhDInflammatory Bowel and Immunobiology Research Institute, Karsh Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CaliforniaSearch for more papers by this author, John Prostko, MSApplied Research and Technology, Abbott Diagnostics, Abbott Park, IllinoisSearch for more papers by this author, Jane Figueiredo, PhDDepartment of Medicine and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CaliforniaSearch for more papers by this author, Susan Cheng, MD, MMSc, MPHDepartments of Medicine, Cardiology, and Biomedical Sciences and Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CaliforniaSearch for more papers by this author, Jonathan Braun, MD, PhDInflammatory Bowel and Immunobiology Research Institute, Karsh Division of Digestive and Liver Diseases, Department of eMedicine, and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CaliforniaSearch for more papers by this author, Dermot P.B. McGovern, MD, PhDInflammatory Bowel and Immunobiology Research Institute, Karsh Division of Digestive and Liver Diseases, Department of eMedicine, and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CaliforniaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-2483 Annals Author Insight Video - Gil Y. Melmed, MD, MS In this video, Gil Y. Melmed, MD, MS, offers additional insight into the article, "Antibody Responses After SARS-CoV-2 mRNA Vaccination in Adults With Inflammatory Bowel Disease." (Duration 4:00) SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: The effects of immunosuppression on responses to SARS-CoV-2 vaccine are unclear given that patients receiving immune-modifying therapies, who constitute 2.8% of commercially insured adults, were underrepresented in vaccine trials (1). Fewer than half of organ transplant recipients receiving antimetabolite therapies developed antibodies after 2 doses of mRNA vaccine (2). Patients with inflammatory bowel disease (IBD) receiving infliximab were less likely than those receiving vedolizumab to develop antibodies after 1 dose of BNT162b2 (Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccine (3), although other researchers have shown that seroconversion occurs in most patients with IBD after 2 doses of mRNA vaccine (4, 5).Objective: To contextualize these findings relative to nonimmunosuppressed persons by assessing responses after mRNA vaccination in adults with IBD receiving various medication regimens.Methods: We assessed antibody titers in adults with IBD who received mRNA SARS-CoV-2 vaccination who were referred from 18 U.S. gastroenterology practices and a social media campaign (January to July 2021). Participants completed baseline surveys detailing medical history at the time of vaccination. Local participants at Cedars-Sinai Medical Center were offered antibody assessments after dose 1 (from 5 days after dose 1 until the day of dose 2); after dose 2 (from 2 to 13 days after dose 2); and at 2 weeks (14 to 29 days), 8 weeks (30 to 84 days), and 16 weeks (85 to 140 days) after dose 2; geographically distant participants were offered at-home sampling using Tasso-SST (Tasso) at 8 weeks. We analyzed plasma antibodies to the receptor-binding domain of the spike protein S1 subunit (IgG(S)) and to the viral nucleocapsid protein (IgG(N)) using the SARS-CoV-2 IgG-II and SARS-CoV-2 IgG assays, respectively (Abbott Labs). We defined an IgG(S) level of 50 AU/mL or higher as a positive result. Qualitatively positive responses were determined after dose 1, after dose 2, and after week 2 (14 to 140 days after dose 2). We excluded recipients of the Ad26.COV2 vaccine (Johnson & Johnson), those with prior COVID-19 defined by a positive IgG(N) result at any time point, and those who did not receive both mRNA doses. Participants provided electronic informed consent, and the Cedars-Sinai institutional review board approved the study. Geometric means and CIs were calculated for log-transformed antibody titers.Findings: The study included 582 participants (mean age, 44 years; 55% female) (Table); 342 (59%) received BNT162b2, and 240 (41%) received mRNA-1273 (Moderna). The proportions of participants receiving no immune suppression, anti-integrin therapy, anti–interleukin-12/23 therapy, immunomodulator monotherapy, anti–tumor necrosis factor monotherapy, Janus kinase inhibition, anti–tumor necrosis factor therapy combined with an immunomodulator, and systemic corticosteroids were 15.8%, 13.7%, 20.4%, 2.1%, 31.4%, 1.2%, 8.6%, and 6.0%, respectively. Those receiving systemic corticosteroids were included in the corticosteroids category regardless of concomitant medications. Four participants were missing medication data. We obtained 854 samples for antibody assessments from 582 participants, including 113 after the first dose, 89 after the second dose, 115 at 2 weeks, 366 at 8 weeks, and 171 at 16 weeks.Table. Participant Characteristics, Seropositivity, and GMTs, by Medication ClassOverall, 49% of participants had positive levels of antibodies after the first dose, 92% after the second dose, and 99% after week 2. Quantitative levels numerically increased from dose 1 to week 2 then decreased at subsequent time points. The Figure shows quantitative levels at week 8 by medication regimen.Figure. Week 8 anti-spike IgG (log10) levels, by medication class.The dotted line represents the threshold for a positive antibody result (50 AU/mL [Abbott Labs]). IL = interleukin; JAK = Janus kinase; TNF = tumor necrosis factor-α. Download figure Download PowerPoint Discussion: Our study has several important findings. First, 99% of participants had detectable antibodies after 2 weeks regardless of medication regimen. Second, quantitative levels peaked at week 2 and decreased across all groups over subsequent time points. Third, mean quantitative levels at 8 weeks were the highest in the “no immunosuppression” group, as well as among those treated with anti-integrin and anti–interleukin-12/23, and lowest among those treated with anti–tumor necrosis factor combination therapy or corticosteroids; however, our study was not powered to assess differences across medication subgroups.These findings showing seroconversion across medication groups are consistent with those seen in other IBD studies (4, 5). In contrast, transplant recipients have lower rates of seroconversion, likely related to B-cell–depleting medications and combined therapies. Whether biologic and small-molecule therapies accelerate waning of titers over time is not yet known, but our results may reassure patients receiving these medications that initial humoral responses to mRNA vaccines are generally robust.Limitations include lack of racial diversity and a tertiary center focus that may diminish generalizability. Further characterization of immunity over time may inform future vaccination strategies for patients with IBD receiving biologic and small-molecule therapies.References1. Wallace BI, Kenney B, Malani PN, et al. Prevalence of immunosuppressive drug use among commercially insured US adults, 2018-2019. JAMA Netw Open. 2021;4:e214920. [PMID: 34014329] doi:10.1001/jamanetworkopen.2021.4920 CrossrefMedlineGoogle Scholar2. Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325:2204-2206. [PMID: 33950155] doi:10.1001/jama.2021.7489 CrossrefMedlineGoogle Scholar3. Kennedy NA, Lin S, Goodhand JR, et al; Contributors to the CLARITY IBD study. Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD. Gut. 2021;70:1884-1893. [PMID: 33903149] doi:10.1136/gutjnl-2021-324789 CrossrefMedlineGoogle Scholar4. Wong SY, Dixon R, Martinez Pazos, et al; ICARUS-IBD Working Group. Serologic response to messenger RNA coronavirus disease 2019 vaccines in inflammatory bowel disease patients receiving biologic therapies. Gastroenterology. 2021;161:715-718.e4. [PMID: 33887219] doi:10.1053/j.gastro.2021.04.025 CrossrefMedlineGoogle Scholar5. Kappelman MD, Weaver KN, Boccieri M, et al; PREVENT-COVID Study Group. Humoral immune response to messenger RNA COVID-19 vaccines among patients with inflammatory bowel disease. Gastroenterology. 2021;161:1340-1343.e2. [PMID: 34144046] doi:10.1053/j.gastro.2021.06.016 CrossrefMedlineGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Gil Y. Melmed, MD, MS; Gregory J. Botwin, BS; Kimia Sobhani, PhD; Dalin Li, PhD; John Prostko, MS; Jane Figueiredo, PhD; Susan Cheng, MD, MMSc, MPH; Jonathan Braun, MD, PhD; Dermot P.B. McGovern, MD, PhDAffiliations: Inflammatory Bowel and Immunobiology Research Institute, Karsh Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CaliforniaDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CaliforniaInflammatory Bowel and Immunobiology Research Institute, Karsh Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CaliforniaApplied Research and Technology, Abbott Diagnostics, Abbott Park, IllinoisDepartment of Medicine and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CaliforniaDepartments of Medicine, Cardiology, and Biomedical Sciences and Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CaliforniaInflammatory Bowel and Immunobiology Research Institute, Karsh Division of Digestive and Liver Diseases, Department of eMedicine, and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CaliforniaAcknowledgment: The authors thank all who have contributed to the CORALE (Coronavirus Risk Associations and Longitudinal Evaluation)-IBD Vaccine study: Keren Appel, Andrea Banty, Brigid Boland, Aline Charabaty, Adam Cheifetz, Erica Cohen, Michael Chiorean, Phillip Debbas, Joseph Ebinger, Edward Feldman, Ann Flynn, Edwin C. Frias, David Fudman, Christina Ha, Melissa Hampton, Mary Hanna, Ergueen Herrera, Amy Hoang, Jason Hou, Arash Horizon, Caroline Hwang, Justina Ibrahim, Sandy Joung, Dmitry Karayev, Elizabeth Khanishian, Benjamin Kretzmann, Rashmi Kumar, Mark Lazarev, Donald Lum, Mark Mattar, Ryan McConnell, Emebet Mengesha, Akil Merchant, Noah Merin, Mark Metwally, Angela Mujukian, Arthur Ostrov, Nimisha Parekh, Valeriya Pozdnyakova, Shervin Rabizadeh, Laura Raffals, Karen Reckamp, Swapna Reddy, David Rubin, Sarah Sheibani, Corey Siegel, Theodore Stein, Sarah Sternbach, James L. Stewart, Gaurav Syal, Stephan Targan, John Valentine, Eric Vasiliauskas, Swami Venuturupalli, Daniel Wallace, Shane White, Doug Wolf, Min Wu, Ziad Younes, Cindy Zamudio, and David Ziring.Financial Support: By the Leona M. and Harry B. Helmsley Charitable Trust, the Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, and grants P01DK046763 and U01DK062413 from the National Institute of Diabetes and Digestive and Kidney Diseases. This study has been additionally supported by the Cedars-Sinai Precision Health initiative, the Erika Glazer Family Foundation, and grant NCI U54-CA260591 from the Serological Sciences Network.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-2483.Reproducible Research Statement: Study protocol, statistical code, and data set: Available from Dr. Melmed (e-mail, gil.melmed@cshs.org).Corresponding Author: Gil Y. Melmed, MD, MS, Inflammatory Bowel and Immunobiology Research Institute, Karsh Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048; e-mail, gil.melmed@cshs.org.Correction: This article was corrected on 22 October 2021 to add three people to the Acknowledgment section who were omitted from the original publication.This article was published at Annals.org on 12 October 2021. PreviousarticleNextarticle Advertisement Annals Author Insight Video - Gil Y. Melmed, MD, MS In this video, Gil Y. Melmed, MD, MS, offers additional insight into the article, "Antibody Responses After SARS-CoV-2 mRNA Vaccination in Adults With Inflammatory Bowel Disease." (Duration 4:00) FiguresReferencesRelatedDetailsSee AlsoCorrection: Antibody Responses After SARS-CoV-2 mRNA Vaccination in Adults With Inflammatory Bowel Disease Metrics Cited byIs Vaccination Against COVID-19 Associated With Inflammatory Bowel Disease Flare? 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