0701: Reduced Humoral but Maintained Cellular Immune Response to a 3^rd COVID-19 Vaccination in Patients with Immune-Mediated Inflammatory Diseases as Compared to Healthy Controls over a 3-months Observational Period

Daniel Mrak¹, Felix Kartnig¹, Daniela Sieghart¹, Elisabeth Simader¹, Helga Radner¹, Peter mandl², Lisa Göschl¹, Philipp Hofer³, Thomas Hummel¹, Thomas Deimel⁴, Irina Gessl⁴, Renate Kain⁵, Stefan Winkler⁶, Josef Smolen⁴, Thomas Perkmann⁷, Helmuth Haslacher⁷, Daniel Aletaha⁸, Leonhard Heinz¹ and Michael Bonelli¹, ¹Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, ²Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Wien, Austria, ³Department of Pathology, Medical University of Vienna, Vienna, Austria, ⁴Medical University of Vienna, Vienna, Austria, ⁵Department of Pathology, Medical University of Vienna, Vienna, ⁶Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria, ⁷Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria, ⁸Medical University Vienna, Wien, Austria

Background/Purpose: A third COVID-19 vaccination is currently recommended for patients under immunosuppression. However, a fast decline of antibodies against the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein has been reported. Currently it remains unclear whether immunosuppressive therapy affects stability of a humoral and cellular immune response.

Methods: 51 patients with immune-mediated inflammatory diseases (IMID) under immunosuppression and 45 healthy controls (HCs) received a 3rd dose of an mRNA-based vaccination and were monitored over a 12-weeks period. Humoral immune response was assessed 4 and 12 weeks after 3^rd dose. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay against the receptor-binding domain (RBD) of the spike protein. SARS-CoV-2-specific T cell responses were analyzed 1 and 12 weeks after 3^rd dose and were quantified by IFN-γ ELISpot assays. Adverse events, including SARS-CoV-2 infections, were monitored over a 12-week period.

Results: At week 12 reduced anti-RBD antibody levels were observed in IMID patients as compared HCs (median antibody level 5400 BAU/ml [2074, 10400] versus 9500 BAU/ml [6610, 16300], p=0.003). Relative reduction in antibody levels was significantly higher in IMID patients as compared to HCs at week 12 (p=0.003). Lowest levels of anti-RBD antibody levels were detected in IMID patients who received a combination therapy with conventional synthetic and biological diseases modifying anti-rheumatic drugs. Number of SARS-CoV-2 specific T cells remained stable over 12 weeks in IMID patients and HCs. No serious adverse events were reported. Two IMID patients and two HCs were tested positive for SARS-CoV-2 between week 4 and 12.

Conclusion: A fast decline in anti-RBD antibodies was observed in IMID patients under immunosuppression. A 4^th vaccination should therefore be considered in this vulnerable group of patients.
Figure 1: Humoral immune response 4 and 12 weeks after 3rd vaccine dose in healthy controls (HCs) and patients. Antibodies to the receptor-binding domain (RBD) of the viral spike (S) protein were determined using an anti-SARS-CoV-2 immunoassay.

Figure 2: Relative change of anti-SARS-CoV-2 RBD antibodies between week 4 and week 12 after 3rd vaccine dose in healthy controls (HCs) as compared to patients
Disclosures: D. Mrak, Pfizer; F. Kartnig, Boehringer-Ingelheim, Eli Lilly; D. Sieghart, None; E. Simader, Boehringer-Ingelheim; H. Radner, None; P. mandl, AbbVie, Bristol-Myers Squibb(BMS), Celgene, Janssen, Eli Lilly, Novartis, Merck/MSD, Roche, UCB; L. Göschl, None; P. Hofer, None; T. Hummel, None; T. Deimel, None; I. Gessl, Eli Lilly, Boehringer-Ingelheim, Gilead; R. Kain, None; S. Winkler, None; J. Smolen, AbbVie, AstraZeneca, Eli Lilly, Novartis, Amgen, Bristol Myers Squibb, Galapagos-Gilead, Janssen, Merck-Sharp-Dohme, Novartis-Sandoz, Pfizer, Roche-Chugai, Samsung, UCB; T. Perkmann, None; H. Haslacher, Glock Health, BlueSky Immunotherapies, Neutrolis; D. Aletaha, Novartis, SoBi, Sanofi, Amgen, Lilly, Merck, Pfizer, Roche, Sandoz, Janssen, AbbVie; L. Heinz, None; M. Bonelli, Eli Lilly.