The persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses in patients on immunosuppressive therapy compared to healthy controls-a prospective cohort study

Abstract

Background: The durability of vaccine-induced humoral immunity against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy is not known. The aim of this study was to compare the persistence of anti-Spike antibodies following two-dose SARS-CoV-2 vaccination between IMID patients and healthy controls and to identify factors associated with antibody decline.

Methods: IMID patients on immunosuppressive medication enrolled in the prospective observational Nor-vaC study were included. Participants received two-dose SARS-CoV-2 vaccination. Serum collected at two time points following vaccination (first assessment within 6-48 days, second within 49-123 days) were analyzed for antibodies binding the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. Multivariable regression models estimated percent reduction in anti-RBD over 30 days and factors associated with reduction.

Results: A total of 1108 patients (403 rheumatoid arthritis, 195 psoriatic arthritis, 195 spondyloarthritis, 124 ulcerative colitis, 191 Crohn's disease) and 134 controls provided blood samples within the defined intervals (median 19 days [IQR 15-24] and 97 days [87-105] after second vaccine dose). Antibody levels were lower in patients compared to controls at both time points, with median anti-RBD 2806 BAU/ml [IQR 1018-6068] in patients and 6187 BAU/ml [4105-7496] in controls (p<0.001) at first assessment, and 608 BAU/ml [IQR 58-1053] in patients and 1520 BAU/ml [979-3766] in controls (p<0.001) at second assessment. At second assessment, low anti-RBD antibody levels (defined as <200 BAU/ml) were found in 449 (41%) patients, and 6 (5%) controls (p<0.001). The change was - 83% in patients and - 66% in controls (p<0.001). Patients had a greater estimated 30 days percent reduction in anti-RBD levels compared to controls - 4.9 (95% CI - 7.4 to - 2.4), (p<0.05). Among therapies, mono- or combination treatment with tumor necrosis factor inhibitors was associated with the greatest decline.

Conclusions: Within 4 months after vaccination, antibody levels declined considerably in both IMID patients and controls. Patients had lower initial antibody levels and a more pronounced decline compared to healthy controls and were therefore more likely to decline to low antibody levels. These results support that IMID patients need additional vaccine doses at an earlier stage than healthy individuals.

Keywords: COVID-19; Inflammatory bowel disease; Rheumatic diseases; SARS-CoV-2 vaccine; Serologic response.

Conflict of interest statement

TKK reports grants from AbbVie, Amgen, BMS, MSD, Novartis, Pfizer, UCB, consulting fees from AbbVie, Amgen, Biogen, Celltrion, Eli Lilly, Gilead, Mylan, Novartis, Pfizer, Sandoz, Sanofi, speakers bureaus Amgen, Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz, Sanofi. JJ reports grants from Abbvie, Pharmacosmos, Ferring, consulting fees from Abbvie, Boerhinger Ingelheim, BMS, Celltrion, Ferring, Glihead, Janssen Cilag, MSD, Napp Pharma, Novartis, Orion Pharma, Pfeizer, Pharmacosmos, Takeda, Sandoz, Unimedic Pharma, speakers bureaus Abbvie, Astro Pharma, Boerhinger Ingelheim, BMS, Celltrion, Ferring, Glihead, Hikma, Janssen Cilag, Meda, MSD, Napp Pharma, Novartis, Oriuon Pharma, Pfeizer, Pharmacosmos, Roche, Takeda, Sandoz. LAM reports funding from KG Jebsen foundation, support for infrastructure and biobanking from the University of Oslo and Oslo University Hospital, grants from the Coalition of Epidemic Preparedness Innovations CEPI, speakers bureaus Novartis, Cellgene. JTV reports grant from the Coalition of Epidemic Preparedness Innovations (CEPI). GG reports consulting fees from the Norwegian System of Compensation to Patients, AstraZeneca, speakers bureaus Bayer, Sanofi Pasteur, and Thermo Fisher. FLJ reports grant from the Coalition of Epidemic Preparedness Innovations (CEPI), grant from South-East region Health authority. KKJ reports speakers bureaus from Roche and BMS, advisory board Celltrion and Norgine. GLG reports funding from The Karin Fossum foundation, Diakonhjemmet Hospital, Oslo University Hospital, Akershus University Hospital, Trygve Gydtfeldt og frues Foundation, South-East region Health authority, consulting fees AbbVie and Pfizer, speaker’s fees AbbVie, Pfizer, Sandoz, Orion Pharma, Novartis and UCB, advisory board Pfizer, AbbVie. IEC, IJ, SWS, ATT, TTT, JS, SAP, SM, DJW, GBK, and EAH report nothing to disclose.

© 2022. The Author(s).

Figures

Fig. 1

Levels of anti-RBD antibodies at the first and second assessment according to medication group. The orange bars show anti-RBD levels at the first assessment and the purple bars show anti-RBD at the second assessment, 6–48 and 49–123 days after the second vaccine dose, respectively. Bars indicate the lower and upper quartiles. Horizontal lines inside the bars indicate the median. Vertical lines through the bars show the minimum (Q1−1.5×IQR) and maximum value (Q3+1.5×IQR). Dots indicate outliers. A cut-off at 200 BAU/ml is indicated by a red line. MTX mono, methotrexate monotherapy; ILi, interleukin inhibitors including tocilizumab, ustekinumab, iksekizumab, risankizumab, secukinumab; VED, vedolizumab; JAKi, janus kinase inhibitor; TNFi mono, tumor necrosis factor inhibitor in monotherapy; TNFi comb, tumor necrosis factor inhibitor in combination with metabolite inhibitor(s) or vedolizumab; RTX, rituximab. All groups include patients using prednisolone in doses

Fig. 2

a Percentage change in anti-RBD levels between the first and second assessment, stratified by an interval of 30 days. b Percentage change in anti-RBD levels between first and second assessment according to medication group. a The bars show the percentage change in anti-RBD levels stratified by an interval of 30 days for controls (light gray bars) and patients (dark gray bars). b The bars show the percentage change in anti-RBD levels between the first and second assessment in controls (light gray bar) and in patients (dark gray bars) according to medication groups. Bars indicate the lower and upper quartiles. Horizontal lines inside the bars indicate the median. Vertical lines through the bars show the minimum (Q1−1.5×IQR) and maximum value (Q3+1.5×IQR). Dots indicate outliers. MTX mono, methotrexate monotherapy; ILi, Interleukin inhibitors including tocilizumab, ustekinumab, iksekizumab, risankizumab, secukinumab; VED, vedolizumab; JAKi, janus kinase inhibitor; TNFi mono, tumor necrosis factor inhibitor in monotherapy; TNFi comb, tumor necrosis factor inhibitor in combination with metabolite inhibitor(s) or vedolizumab; RTX, rituximab. All groups include patients using prednisolone in doses <10mg/day in combination with other medication

Fig. 3

Percent distribution of anti-RBD levels at the first (a) and second (b) assessment in patients and healthy controls. a Percent distribution of anti-RBD levels at the first assessment 6–48 days after the second vaccine dose in controls and in patients according to medication groups. b Percent distribution of anti-RBD levels at the second assessment 49–123 days after the second vaccine dose in controls and in patients according to medication group. MTX mono, methotrexate monotherapy; ILi, interleukin inhibitors including tocilizumab, ustekinumab, iksekizumab, risankizumab, secukinumab; VED, vedolizumab; JAKi, janus kinase inhibitor; TNFi mono, tumor necrosis factor inhibitor in monotherapy; TNFi comb, tumor necrosis factor inhibitor in combination with metabolite inhibitor(s) or vedolizumab; RTX, rituximab. All groups include patients using prednisolone in doses <10mg/day in combination with other medication