Factors associated with immune responses to SARS-CoV-2 vaccination in individuals with autoimmune diseases
Erik Anderson, Michael Powell, Emily Yang, Ananya Kar, Tung Ming Leung, Cristina Sison, Rebecca Steinberg, Raven Mims, Ananya Choudhury, Carlo Espinosa, Joshua Zelmanovich, Nkemakonam C. Okoye, Eun Jung Choi, Galina Marder, Sonali Narain, Peter K. Gregersen, Meggan Mackay, Betty Diamond, Todd Levy, Theodoros P. Zanos, Arezou Khosroshahi, Ignacio Sanz, Eline T. Luning Prak, Amit Bar-Or, Joan Merrill, Cristina Arriens, Gabriel Pardo, Joel Guthridge, Judith James, Aimee Payne, Paul J. Utz, Jeremy M. Boss, Cynthia Aranow, Anne Davidson
Erik Anderson, Michael Powell, Emily Yang, Ananya Kar, Tung Ming Leung, Cristina Sison, Rebecca Steinberg, Raven Mims, Ananya Choudhury, Carlo Espinosa, Joshua Zelmanovich, Nkemakonam C. Okoye, Eun Jung Choi, Galina Marder, Sonali Narain, Peter K. Gregersen, Meggan Mackay, Betty Diamond, Todd Levy, Theodoros P. Zanos, Arezou Khosroshahi, Ignacio Sanz, Eline T. Luning Prak, Amit Bar-Or, Joan Merrill, Cristina Arriens, Gabriel Pardo, Joel Guthridge, Judith James, Aimee Payne, Paul J. Utz, Jeremy M. Boss, Cynthia Aranow, Anne Davidson
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Research Article

Factors associated with immune responses to SARS-CoV-2 vaccination in individuals with autoimmune diseases

Abstract

Patients with autoimmune diseases are at higher risk for severe infection due to their underlying disease and immunosuppressive treatments. In this real-world observational study of 463 patients with autoimmune diseases, we examined risk factors for poor B and T cell responses to SARS-CoV-2 vaccination. We show a high frequency of inadequate anti–spike IgG responses to vaccination and boosting in the autoimmune population but minimal suppression of T cell responses. Low IgG responses in B cell–depleted patients with multiple sclerosis (MS) were associated with higher CD8 T cell responses. By contrast, patients taking mycophenolate mofetil (MMF) exhibited concordant suppression of B and T cell responses. Treatments with highest risk for low anti–spike IgG response included B cell depletion within the last year, fingolimod, and combination treatment with MMF and belimumab. Our data show that the mRNA-1273 (Moderna) vaccine is the most effective vaccine in the autoimmune population. There was minimal induction of either disease flares or autoantibodies by vaccination and no significant effect of preexisting anti–type I IFN antibodies on either vaccine response or breakthrough infections. The low frequency of breakthrough infections and lack of SARS-CoV-2–related deaths suggest that T cell immunity contributes to protection in autoimmune disease.

Authors

Erik Anderson, Michael Powell, Emily Yang, Ananya Kar, Tung Ming Leung, Cristina Sison, Rebecca Steinberg, Raven Mims, Ananya Choudhury, Carlo Espinosa, Joshua Zelmanovich, Nkemakonam C. Okoye, Eun Jung Choi, Galina Marder, Sonali Narain, Peter K. Gregersen, Meggan Mackay, Betty Diamond, Todd Levy, Theodoros P. Zanos, Arezou Khosroshahi, Ignacio Sanz, Eline T. Luning Prak, Amit Bar-Or, Joan Merrill, Cristina Arriens, Gabriel Pardo, Joel Guthridge, Judith James, Aimee Payne, Paul J. Utz, Jeremy M. Boss, Cynthia Aranow, Anne Davidson

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Figure 2

Serological response to SARS-CoV-2 vaccination in patients with autoimmune diseases versus healthy controls according to SARS-CoV-2 exposure status.

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Serological response to SARS-CoV-2 vaccination in patients with autoimmu...
Patients are divided into anti-nucleocapsid (anti-NC) IgG– (green, no SARS-CoV-2 infection documented throughout the study), anti–NC Acquired (anti–NC Acq) (blue, SARS-CoV-2 infection documented at or after Post V2), and anti-NC+ (black, SARS-CoV-2 infection documented before initial vaccination) groups. (A and B) Anti–spike IgG levels (U/mL) in HC at each visit after the initial (A) and booster vaccination (B). (C) Anti–spike IgG levels in patients with autoimmune diseases at each visit before and after the initial vaccination and after booster vaccination. Statistical analyses are shown in Supplemental Figure 2. (D and E) Trajectory of anti–spike IgG levels after the initial vaccine series in anti-NC– (D) and anti-NC+ (E) HC who responded to the initial vaccination. (F and G) Trajectory of anti–spike IgG levels after the initial vaccine series in anti-NC– (F) and anti-NC+ (G) patients with autoimmune diseases who responded to the initial vaccination. (H) Trajectory of anti–spike IgG levels after the initial vaccine series in anti-NC– patients with autoimmune diseases with an inadequate response (<250 U/mL). (I) Anti–spike IgG levels in anti-NC– patients with autoimmune diseases versus HC before and after booster vaccination according to quartile of prebooster anti–spike IgG levels. (J) Anti–spike IgG levels in anti-NC+ patients with autoimmune diseases versus HC before and after booster vaccination according to the upper and lower 50th percentile of prebooster anti–spike IgG levels. Each data point represents an individual patient. (D–G) Wilcoxon signed-rank test. (I and J) Kruskal-Wallis ANOVA with DSCF correction for multiple comparisons. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Timing of sample collections is shown in Figure 1.