Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune-mediated inflammatory diseases
Roya M. Dayam, Jaclyn C. Law, Rogier L. Goetgebuer, Gary Y.C. Chao, Kento T. Abe, Mitchell Sutton, Naomi Finkelstein, Joanne M. Stempak, Daniel Pereira, David Croitoru, Lily Acheampong, Saima Rizwan, Klaudia Rymaszewski, Raquel Milgrom, Darshini Ganatra, Nathalia V. Batista, Melanie Girard, Irene Lau, Ryan Law, Michelle W. Cheung, Bhavisha Rathod, Julia Kitaygorodsky, Reuben Samson, Queenie Hu, W. Rod Hardy, Nigil Haroon, Robert D. Inman, Vincent Piguet, Vinod Chandran, Mark S. Silverberg, Anne-Claude Gingras, Tania H. Watts
Roya M. Dayam, Jaclyn C. Law, Rogier L. Goetgebuer, Gary Y.C. Chao, Kento T. Abe, Mitchell Sutton, Naomi Finkelstein, Joanne M. Stempak, Daniel Pereira, David Croitoru, Lily Acheampong, Saima Rizwan, Klaudia Rymaszewski, Raquel Milgrom, Darshini Ganatra, Nathalia V. Batista, Melanie Girard, Irene Lau, Ryan Law, Michelle W. Cheung, Bhavisha Rathod, Julia Kitaygorodsky, Reuben Samson, Queenie Hu, W. Rod Hardy, Nigil Haroon, Robert D. Inman, Vincent Piguet, Vinod Chandran, Mark S. Silverberg, Anne-Claude Gingras, Tania H. Watts
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Clinical Research and Public Health COVID-19 Immunology

Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune-mediated inflammatory diseases

Abstract

BACKGROUND Limited information is available on the impact of immunosuppressants on COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID).METHODS This observational cohort study examined the immunogenicity of SARS-CoV-2 mRNA vaccines in adult patients with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, or psoriatic disease, with or without maintenance immunosuppressive therapies. Ab and T cell responses to SARS-CoV-2, including neutralization against SARS-CoV-2 variants, were determined before and after 1 and 2 vaccine doses.RESULTS We prospectively followed 150 subjects, 26 healthy controls, 9 patients with IMID on no treatment, 44 on anti-TNF, 16 on anti-TNF with methotrexate/azathioprine (MTX/AZA), 10 on anti–IL-23, 28 on anti–IL-12/23, 9 on anti–IL-17, and 8 on MTX/AZA. Ab and T cell responses to SARS-CoV-2 were detected in all participants, increasing from dose 1 to dose 2 and declining 3 months later, with greater attrition in patients with IMID compared with healthy controls. Ab levels and neutralization efficacy against variants of concern were substantially lower in anti-TNF–treated patients than in healthy controls and were undetectable against Omicron by 3 months after dose 2.CONCLUSIONS Our findings support the need for a third dose of the mRNA vaccine and for continued monitoring of immunity in these patient groups.FUNDING Funded by a donation from Juan and Stefania Speck and by Canadian Institutes of Health (CIHR)/COVID-Immunity Task Force (CITF) grants VR-1 172711 and VS1-175545 (to THW and ACG), CIHR FDN-143250 (to THW), GA2-177716 (to VC, ACG, and THW), and GA1-177703 (to ACG) and the CIHR rapid response network to SARS-CoV-2 variants, CoVaRR-Net (to ACG).

Authors

Roya M. Dayam, Jaclyn C. Law, Rogier L. Goetgebuer, Gary Y.C. Chao, Kento T. Abe, Mitchell Sutton, Naomi Finkelstein, Joanne M. Stempak, Daniel Pereira, David Croitoru, Lily Acheampong, Saima Rizwan, Klaudia Rymaszewski, Raquel Milgrom, Darshini Ganatra, Nathalia V. Batista, Melanie Girard, Irene Lau, Ryan Law, Michelle W. Cheung, Bhavisha Rathod, Julia Kitaygorodsky, Reuben Samson, Queenie Hu, W. Rod Hardy, Nigil Haroon, Robert D. Inman, Vincent Piguet, Vinod Chandran, Mark S. Silverberg, Anne-Claude Gingras, Tania H. Watts

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Figure 1

Ab responses after 1 or 2 doses of mRNA vaccine.

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Ab responses after 1 or 2 doses of mRNA vaccine. (A) Schematic diagram o...
(A) Schematic diagram of the sampling schedule. (B) IgG response to vaccination across all participants at each time point (defined in A). Anti-spike (y-axis) and anti-RBD (x-axis) IgG levels at indicated time points. The dark blue line is the median ratio in convalescent patients (340 samples collected 21–115 days after symptom onset). The red line is the seropositivity threshold, set to pass both a 1% FPR and greater than or equal to 3 SDs from the log10 means of the negative controls. See Supplemental Table 5 for percentage of samples that pass these thresholds. (C) IgG responses to vaccination in patients with IMID. Violin plots show the relative ratios of RBD and spike at the indicated time points in patients with IMID under monotherapy and combination therapy (0.0039 μL sample used, see Supplemental Figure 1 for the second dilution and Supplemental Table 4 for conversion to BAU/mL). T1, n = 111; T2, n = 130; T3, n = 130; and T4, n = 87. The dot colors indicate the type of vaccine; Pfizer refers to BNT162b; Moderna to mRNA-1273; and mRNA mix = first dose BNT162b and second dose mRNA-1273. Black and gray lines indicate median and mean ratio values for each violin, respectively. Plots are faceted based on the groups/treatments. Comparisons were made by Dunn’s multiple comparisons test based only on the BNT162b/BNT162b group. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001. M/A+TNF inh, MTX/AZA+TNF inh.