Anti-TNF alpha Treatment Impairs Long-Term Immune Responses to COVID-19 mRNA Vaccine in Patients with Inflammatory Bowel Diseases

Keren Masha Rabinowitz, Michal Navon, Hadar Edelman-Klapper, Eran Zittan, Ariella Bar-Gil Shitrit, Idan Goren, Irit Avni-Biron, Jacob E. Ollech, Lev Lichtenstein, Hagar Banai-Eran, Henit Yanai, Yifat Snir, Maor H. Pauker, Adi Friedenberg, Adva Levy-Barda, Arie Segal, Yelena Broitman, Eran Maoz, Baruch Ovadia, Maya Aharoni GolanEyal Shachar, Shomron Ben-Horin, Nitsan Maharshak, Michal Mor, Haim Ben Zvi, Rami Eliakim, Revital Barkan, Tali Sharar-Fischler, Sophy Goren, Noy Krugliak, Edward Pichinuk, Michael Mor, Michal Werbner, Joel Alter, Hanan Abu-Taha, Kawsar Kaboub, Moshe Dessau, Meital Gal-Tanamy, Dani Cohen, Natalia T. Freund, Iris Dotan, Responses COVID-19 Vaccine Israeli

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNF alpha) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNF alpha (non-anti-TNF alpha) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNF alpha and 57 treated with anti-TNF alpha) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNF alpha had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNF alpha. Importantly, all seronegative subjects were patients with IBD; of those, >90TNF alpha. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients.
Original languageEnglish
Article number1186
Issue number8
StatePublished - 1 Aug 2022
Externally publishedYes


  • COVID-19
  • vaccine
  • mRNA-BNT162b2
  • anti-SARS-CoV-2 antibodies
  • serologic response longevity
  • circulating B cells
  • cross-reactivity


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