Anti-SARS-CoV-2 B and T-Cell Immune Responses Persist 12 Months After mRNA Vaccination with BNT162b2 in Systemic Lupus Erythematosus Patients Independently of Immunosuppressive Therapies
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Cohort and Design
- IS: including those who were receiving an immune-suppressor drug at the time of vaccination, regardless of hydroxychloroquine, and/or any corticosteroids at a dosage higher than 5 mg prednisone equivalent per day;
- Non-IS: including only patients who were not receiving any immune-suppressor drug at the time of vaccination [e.g., hydroxychloroquine or corticosteroids alone (at a dosage lower or equal to 5 mg prednisone equivalent per day) or their eventual combination or patients not receiving any therapies].
2.2. Humoral and Cellular Immune Responses
2.3. Statistical Analyses
2.4. Ethics Statement
3. Results
3.1. Characteristics of the Enrolled Population
3.2. Humoral and Cellular Response
3.2.1. Immune Response’s Longitudinal Observation
3.2.2. Possible Factors Influencing the Immune Response
3.3. Vaccine’s Safety
3.3.1. Adverse Events
3.3.2. Disease Activity
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- World Health Organization. COVID-19 Cases|WHO COVID-19 Dashboard. Available online: https://data.who.int/dashboards/covid19/cases (accessed on 11 March 2025).
- Landewé, R.B.; Machado, P.M.; Kroon, F.; Bijlsma, H.W.; Burmester, G.R.; Carmona, L.; Combe, B.; Galli, M.; Gossec, L.; Iagnocco, A.; et al. EULAR Provisional Recommendations for the Management of Rheumatic and Musculoskeletal Diseases in the Context of SARS-CoV-2. Ann. Rheum. Dis. 2020, 79, 851–858. [Google Scholar] [CrossRef] [PubMed]
- Furer, V.; Eviatar, T.; Zisman, D.; Peleg, H.; Paran, D.; Levartovsky, D.; Zisapel, M.; Elalouf, O.; Kaufman, I.; Meidan, R.; et al. Immunogenicity and Safety of the BNT162b2 mRNA COVID-19 Vaccine in Adult Patients with Autoimmune Inflammatory Rheumatic Diseases and in the General Population: A Multicentre Study. Ann. Rheum. Dis. 2021, 80, 1330–1338. [Google Scholar] [CrossRef] [PubMed]
- Curtis, J.R.; Johnson, S.R.; Anthony, D.D.; Arasaratnam, R.J.; Baden, L.R.; Bass, A.R.; Calabrese, C.; Gravallese, E.M.; Harpaz, R.; Sadun, R.E.; et al. American College of Rheumatology Guidance for COVID-19 Vaccination in Patients with Rheumatic and Musculoskeletal Diseases: Version 1. Arthritis Rheumatol. 2021, 73, 1093–1107. [Google Scholar] [CrossRef]
- Danza, A.; Ruiz-Irastorza, G. Infection Risk in Systemic Lupus Erythematosus Patients: Susceptibility Factors and Preventive Strategies. Lupus 2013, 22, 1286–1294. [Google Scholar] [CrossRef] [PubMed]
- Pego-Reigosa, J.M.; Nicholson, L.; Pooley, N.; Langham, S.; Embleton, N.; Marjenberg, Z.; Barut, V.; Desta, B.; Wang, X.; Langham, J.; et al. The Risk of Infections in Adult Patients with Systemic Lupus Erythematosus: Systematic Review and Meta-Analysis. Rheumatology 2021, 60, 60–72. [Google Scholar] [CrossRef]
- Fu, X.-L.; Qian, Y.; Jin, X.-H.; Yu, H.-R.; Du, L.; Wu, H.; Chen, H.-L.; Shi, Y.-Q. COVID-19 in Patients with Systemic Lupus Erythematosus: A Systematic Review. Lupus 2022, 31, 684–696. [Google Scholar] [CrossRef]
- Grainger, R.; Kim, A.H.J.; Conway, R.; Yazdany, J.; Robinson, P.C. COVID-19 in People with Rheumatic Diseases: Risks, Outcomes, Treatment Considerations. Nat. Rev. Rheumatol. 2022, 18, 191–204. [Google Scholar] [CrossRef]
- Rao, M.; Mikdashi, J. A Framework to Overcome Challenges in the Management of Infections in Patients with Systemic Lupus Erythematosus. Open Access Rheumatol. 2023, 15, 125–137. [Google Scholar] [CrossRef]
- Urowitz, M.B.; Bookman, A.A.; Koehler, B.E.; Gordon, D.A.; Smythe, H.A.; Ogryzlo, M.A. The Bimodal Mortality Pattern of Systemic Lupus Erythematosus. Am. J. Med. 1976, 60, 221–225. [Google Scholar] [CrossRef]
- Cordtz, R.; Kristensen, S.; Dalgaard, L.P.H.; Westermann, R.; Duch, K.; Lindhardsen, J.; Torp-Pedersen, C.; Dreyer, L. Incidence of COVID-19 Hospitalisation in Patients with Systemic Lupus Erythematosus: A Nationwide Cohort Study from Denmark. J. Clin. Med. 2021, 10, 3842. [Google Scholar] [CrossRef]
- Jiang, X.; Sparks, J.; Wallace, Z.; Deng, X.; Li, H.; Lu, N.; Xie, D.; Wang, Y.; Zeng, C.; Lei, G.; et al. Risk of COVID-19 among Unvaccinated and Vaccinated Patients with Systemic Lupus Erythematosus: A General Population Study. RMD Open 2023, 9, e002839. [Google Scholar] [CrossRef] [PubMed]
- Gianfrancesco, M.; Hyrich, K.L.; Al-Adely, S.; Carmona, L.; Danila, M.I.; Gossec, L.; Izadi, Z.; Jacobsohn, L.; Katz, P.; Lawson-Tovey, S.; et al. Characteristics Associated with Hospitalisation for COVID-19 in People with Rheumatic Disease: Data from the COVID-19 Global Rheumatology Alliance Physician-Reported Registry. Ann. Rheum. Dis. 2020, 79, 859–866. [Google Scholar] [CrossRef] [PubMed]
- Akhlaq, A.; Aamer, S.; Hasan, K.M.; Muzammil, T.S.; Sohail, A.H.; Quazi, M.A.; Khan, M.S.; Sheikh, A.B. Systemic Lupus Erythematosus Is Associated with Increased Risk of Mortality and Acute Kidney Injury in Patients with COVID-19 Hospitalization: Insights from a National Inpatient Sample Analysis. Lupus 2024, 33, 248–254. [Google Scholar] [CrossRef] [PubMed]
- Pappa, M.; Panagiotopoulos, A.; Thomas, K.; Fanouriakis, A. Systemic Lupus Erythematosus and COVID-19. Curr. Rheumatol. Rep. 2023, 25, 192–203. [Google Scholar] [CrossRef]
- Fernandez-Ruiz, R.; Paredes, J.L.; Niewold, T.B. COVID-19 in Patients with Systemic Lupus Erythematosus: Lessons Learned from the Inflammatory Disease. Transl. Res. 2021, 232, 13–36. [Google Scholar] [CrossRef]
- Hejazian, S.S.; Hejazian, S.M.; Farnood, F.; Abedi Azar, S. Dysregulation of Immunity in COVID-19 and SLE. Inflammopharmacology 2022, 30, 1517–1531. [Google Scholar] [CrossRef]
- He, J.; Li, Z. Dilemma of Immunosuppression and Infection Risk in Systemic Lupus Erythematosus. Rheumatology 2023, 62, i22–i29. [Google Scholar] [CrossRef]
- Strangfeld, A.; Schäfer, M.; Gianfrancesco, M.A.; Lawson-Tovey, S.; Liew, J.W.; Ljung, L.; Mateus, E.F.; Richez, C.; Santos, M.J.; Schmajuk, G.; et al. Factors Associated with COVID-19-Related Death in People with Rheumatic Diseases: Results from the COVID-19 Global Rheumatology Alliance Physician-Reported Registry. Ann. Rheum. Dis. 2021, 80, 930–942. [Google Scholar] [CrossRef]
- Tang, W.; Gartshteyn, Y.; Ricker, E.; Inzerillo, S.; Murray, S.; Khalili, L.; Askanase, A. The Use of COVID-19 Vaccines in Patients with SLE. Curr. Rheumatol. Rep. 2021, 23, 79. [Google Scholar] [CrossRef]
- Shaharir, S.S.; Nawi, A.M.; Mariamutu, T.N.; Kamaruzaman, L.; Said, M.S.M.; Rajalingham, S.; Parodis, I.; Sarkar, M.; Shinjo, S.K.; Kadam, E.; et al. Self-Reported Delayed Adverse Events and Flare Following COVID-19 Vaccination Among Patients with Autoimmune Rheumatic Disease (AIRD) in Malaysia: Results From the COVAD-2 Study. Int. J. Rheum. Dis. 2025, 28, e70043. [Google Scholar] [CrossRef]
- Louthrenoo, W.; Tangkum, P.; Kasitanon, N.; Gumtorntip, W.; Winichakoon, P.; Konsamun, S.; Wongthanee, A. Flares and Predicting Factors of Flares in Patients with Systemic Lupus Erythematosus Associated with Different Doses and Types of COVID-19 Vaccines. Vaccines 2024, 12, 1399. [Google Scholar] [CrossRef] [PubMed]
- Tangkum, P.; Kasitanon, N.; Gumtorntip, W.; Winichakoon, P.; Konsamun, S.; Wongthanee, A.; Louthrenoo, W. COVID-19 Vaccination in Patients with Systemic Lupus Erythematosus: Adverse Events and Rating Agreement of Flares Between Patients and Physicians. Int. J. Rheum. Dis. 2024, 27, e70001. [Google Scholar] [CrossRef] [PubMed]
- Dhanasekaran, P.; Karasu, B.T.; Mak, A. Safety, Efficacy, and Immunogenicity of SARS-CoV-2 mRNA Vaccination in Children and Adult Patients with Rheumatic Diseases: A Comprehensive Literature Review. Rheumatol. Int. 2024, 44, 2757–2794. [Google Scholar] [CrossRef]
- Tsyruk, O.; Kaplan, G.G.; Fortin, P.R.; Hitchon, C.A.; Chandran, V.; Larché, M.J.; Avina-Zubieta, A.; Boire, G.; Colmegna, I.; Lacaille, D.; et al. How Safe Are COVID-19 Vaccines in Individuals with Immune-Mediated Inflammatory Diseases? The SUCCEED Study. Vaccines 2024, 12, 1027. [Google Scholar] [CrossRef]
- Petrone, L.; Picchianti-Diamanti, A.; Sebastiani, G.D.; Aiello, A.; Laganà, B.; Cuzzi, G.; Vanini, V.; Gualano, G.; Grifoni, A.; Ferraioli, M.; et al. Humoral and Cellular Responses to Spike of δ SARS-CoV-2 Variant in Vaccinated Patients with Immune-Mediated Inflammatory Diseases. Int. J. Infect. Dis. 2022, 121, 24–30. [Google Scholar] [CrossRef]
- Tan, S.Y.S.; Yee, A.M.; Sim, J.J.L.; Lim, C.C. COVID-19 Vaccination in Systemic Lupus Erythematosus: A Systematic Review of Its Effectiveness, Immunogenicity, Flares and Acceptance. Rheumatology 2023, 62, 1757–1772. [Google Scholar] [CrossRef]
- Yuki, E.F.N.; Borba, E.F.; Pasoto, S.G.; Seguro, L.P.; Lopes, M.; Saad, C.G.S.; Medeiros-Ribeiro, A.C.; Silva, C.A.; de Andrade, D.C.O.; Kupa, L.d.V.K.; et al. Impact of Distinct Therapies on Antibody Response to SARS-CoV-2 Vaccine in Systemic Lupus Erythematosus. Arthritis Care Res. 2022, 74, 562–571. [Google Scholar] [CrossRef]
- Quartuccio, L.; De Marchi, G.; Domenis, R.; Cabas, N.; Guella, S.; Paradiso, A.; Fabro, C.; Beltrami, A.P.; De Vita, S.; Curcio, F. Humoral and T-Cell Mediated Response after the Third Dose of mRNA Vaccines in Patients with Systemic Lupus Erythematosus on Belimumab. J. Clin. Med. 2023, 12, 1083. [Google Scholar] [CrossRef]
- De Santis, M.; Motta, F.; Isailovic, N.; Clementi, M.; Criscuolo, E.; Clementi, N.; Tonutti, A.; Rodolfi, S.; Barone, E.; Colapietro, F.; et al. Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases. Vaccines 2022, 10, 801. [Google Scholar] [CrossRef]
- Izmirly, P.M.; Kim, M.Y.; Samanovic, M.; Fernandez-Ruiz, R.; Ohana, S.; Deonaraine, K.K.; Engel, A.J.; Masson, M.; Xie, X.; Cornelius, A.R.; et al. Evaluation of Immune Response and Disease Status in Systemic Lupus Erythematosus Patients Following SARS-CoV-2 Vaccination. Arthritis Rheumatol. 2022, 74, 284–294. [Google Scholar] [CrossRef]
- Zhang, C.; Zhang, Y.-Q.; Liu, R.-B.; Ma, Y.-T.; Zhao, L.-K.; Yin, F.-Q.; Tu, J.; Yao, Y.-Y. Growing Attention of Immunogenicity among Patients with Autoimmune Diseases Post-SARS-CoV-2 Vaccination: Meta-Analysis and Systematic Reviews of the Current Studies. Ann. Med. 2025, 57, 2478319. [Google Scholar] [CrossRef] [PubMed]
- Assawasaksakul, T.; Sathitratanacheewin, S.; Vichaiwattana, P.; Wanlapakorn, N.; Poovorawan, Y.; Avihingsanon, Y.; Assawasaksakul, N.; Kittanamongkolchai, W. Immunogenicity of the Third and Fourth BNT162b2 mRNA COVID-19 Boosters and Factors Associated with Immune Response in Patients with SLE and Rheumatoid Arthritis. Lupus Sci. Med. 2022, 9, e000726. [Google Scholar] [CrossRef] [PubMed]
- Moyon, Q.; Sterlin, D.; Miyara, M.; Anna, F.; Mathian, A.; Lhote, R.; Ghillani-Dalbin, P.; Breillat, P.; Mudumba, S.; de Alba, S.; et al. BNT162b2 Vaccine-Induced Humoral and Cellular Responses against SARS-CoV-2 Variants in Systemic Lupus Erythematosus. Ann. Rheum. Dis. 2022, 81, 575–583. [Google Scholar] [CrossRef] [PubMed]
- Sette, A.; Sidney, J.; Crotty, S. T Cell Responses to SARS-CoV-2. Annu. Rev. Immunol. 2023, 41, 343–373. [Google Scholar] [CrossRef]
- Sette, A.; Saphire, E.O. Inducing Broad-Based Immunity against Viruses with Pandemic Potential. Immunity 2022, 55, 738–748. [Google Scholar] [CrossRef]
- Tarke, A.; Grifoni, A.; Sette, A. Bioinformatic and Experimental Analysis of T Cell Immune Reactivity to SARS-CoV-2 and Its Variants. Front. Bioinform. 2022, 2, 876380. [Google Scholar] [CrossRef]
- Aiello, A.; Coppola, A.; Ruggieri, S.; Farroni, C.; Altera, A.M.G.; Salmi, A.; Vanini, V.; Cuzzi, G.; Petrone, L.; Meschi, S.; et al. Longitudinal Characterisation of B and T-Cell Immune Responses after the Booster Dose of COVID-19 mRNA-Vaccine in People with Multiple Sclerosis Using Different Disease-Modifying Therapies. J. Neurol. Neurosurg. Psychiatry 2022, 94, 290–299. [Google Scholar] [CrossRef]
- Palomares Cabeza, V.; Kummer, L.Y.L.; Wieske, L.; Hagen, R.R.; Duurland, M.; Konijn, V.A.L.; van Dam, K.P.J.; Stalman, E.W.; van de Sandt, C.E.; Boekel, L.; et al. Longitudinal T-Cell Responses After a Third SARS-CoV-2 Vaccination in Patients with Multiple Sclerosis on Ocrelizumab or Fingolimod. Neurol. Neuroimmunol. Neuroinflamm. 2022, 9, e1178. [Google Scholar] [CrossRef]
- Torres, P.; Sancho-Saldaña, A.; Gil Sánchez, A.; Peralta, S.; Solana, M.J.; Bakkioui, S.; González-Mingot, C.; Quibus, L.; Ruiz-Fernández, E.; San Pedro-Murillo, E.; et al. A Prospective Study of Cellular Immune Response to Booster COVID-19 Vaccination in Multiple Sclerosis Patients Treated with a Broad Spectrum of Disease-Modifying Therapies. J. Neurol. 2023, 270, 2380–2391. [Google Scholar] [CrossRef]
- Aiello, A.; Ruggieri, S.; Navarra, A.; Tortorella, C.; Vanini, V.; Haggiag, S.; Prosperini, L.; Cuzzi, G.; Salmi, A.; Quartuccio, M.E.; et al. Anti-RBD Antibody Levels and IFN-γ-Specific T Cell Response Are Associated with a More Rapid Swab Reversion in Patients with Multiple Sclerosis after the Booster Dose of COVID-19 Vaccination. Vaccines 2024, 12, 926. [Google Scholar] [CrossRef]
- Farroni, C.; Aiello, A.; Picchianti-Diamanti, A.; Laganà, B.; Petruccioli, E.; Agrati, C.; Garbuglia, A.R.; Meschi, S.; Lapa, D.; Cuzzi, G.; et al. Booster Dose of SARS-CoV-2 Messenger RNA Vaccines Strengthens the Specific Immune Response of Patients with Rheumatoid Arthritis: A Prospective Multicenter Longitudinal Study. Int. J. Infect. Dis. 2022, 125, 195–208. [Google Scholar] [CrossRef] [PubMed]
- Mitchell, J.; Connolly, C.M.; Chiang, T.P.-Y.; Alejo, J.L.; Werbel, W.A.; Segev, D.L.; Massie, A.B. Comparison of SARS-CoV-2 Antibody Response After 2-Dose mRNA-1273 vs BNT162b2 Vaccines in Incrementally Immunosuppressed Patients. JAMA Netw. Open 2022, 5, e2211897. [Google Scholar] [CrossRef] [PubMed]
- Khan, Q.J.; Bivona, C.R.; Martin, G.A.; Zhang, J.; Liu, B.; He, J.; Li, K.H.; Nelson, M.; Williamson, S.; Doolittle, G.C.; et al. Evaluation of the Durability of the Immune Humoral Response to COVID-19 Vaccines in Patients with Cancer Undergoing Treatment or Who Received a Stem Cell Transplant. JAMA Oncol. 2022, 8, 1053–1058. [Google Scholar] [CrossRef] [PubMed]
- Manothummetha, K.; Chuleerarux, N.; Sanguankeo, A.; Kates, O.S.; Hirankarn, N.; Thongkam, A.; Dioverti-Prono, M.V.; Torvorapanit, P.; Langsiri, N.; Worasilchai, N.; et al. Immunogenicity and Risk Factors Associated with Poor Humoral Immune Response of SARS-CoV-2 Vaccines in Recipients of Solid Organ Transplant: A Systematic Review and Meta-Analysis. JAMA Netw. Open 2022, 5, e226822. [Google Scholar] [CrossRef]
- Petrone, L.; Tortorella, C.; Aiello, A.; Farroni, C.; Ruggieri, S.; Castilletti, C.; Meschi, S.; Cuzzi, G.; Vanini, V.; Palmieri, F.; et al. Humoral and Cellular Response to Spike of Delta SARS-CoV-2 Variant in Vaccinated Patients with Multiple Sclerosis. Front. Neurol. 2022, 13, 881988. [Google Scholar] [CrossRef]
- Aringer, M.; Costenbader, K.; Daikh, D.; Brinks, R.; Mosca, M.; Ramsey-Goldman, R.; Smolen, J.S.; Wofsy, D.; Boumpas, D.T.; Kamen, D.L.; et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019, 71, 1400–1412. [Google Scholar] [CrossRef]
- Petri, M.; Kim, M.Y.; Kalunian, K.C.; Grossman, J.; Hahn, B.H.; Sammaritano, L.R.; Lockshin, M.; Merrill, J.T.; Belmont, H.M.; Askanase, A.D.; et al. Combined Oral Contraceptives in Women with Systemic Lupus Erythematosus. N. Engl. J. Med. 2005, 353, 2550–2558. [Google Scholar] [CrossRef]
- Aiello, A.; Coppola, A.; Vanini, V.; Petrone, L.; Cuzzi, G.; Salmi, A.; Altera, A.M.G.; Tortorella, C.; Gualano, G.; Gasperini, C.; et al. Accuracy of QuantiFERON SARS-CoV-2 Research Use Only Assay and Characterization of the CD4+ and CD8+ T Cell-SARS-CoV-2 Response: Comparison with a Homemade Interferon-γ Release Assay. Int. J. Infect. Dis. 2022, 122, 841–849. [Google Scholar] [CrossRef]
- Picchianti-Diamanti, A.; Aiello, A.; Laganà, B.; Agrati, C.; Castilletti, C.; Meschi, S.; Farroni, C.; Lapa, D.; Najafi Fard, S.; Cuzzi, G.; et al. ImmunosuppressiveTherapies Differently Modulate Humoral- and T-Cell-Specific Responses to COVID-19 mRNA Vaccine in Rheumatoid Arthritis Patients. Front. Immunol. 2021, 12, 740249. [Google Scholar] [CrossRef]
- Aiello, A.; Najafi Fard, S.; Petruccioli, E.; Petrone, L.; Vanini, V.; Farroni, C.; Cuzzi, G.; Navarra, A.; Gualano, G.; Mosti, S.; et al. Spike Is the Most Recognized Antigen in the Whole-Blood Platform in Both Acute and Convalescent COVID-19 Patients. Int. J. Infect. Dis. 2021, 106, 338–347. [Google Scholar] [CrossRef]
- Ferraioli, M.; Prevete, I.; Chimenti, M.S.; De Marco, L.; Meschi, S.; Mariotti, D.; Aiello, A.; Vanini, V.; Cuzzi, G.; Salmi, A.; et al. AB0077 Immunogenicity and safety prospective study of anti-SARS-CoV-2 mrna vaccination in a real-life setting of systemic lupus erythematosus patients. Ann. Rheum. Dis. 2024, 83, 1268–1269. [Google Scholar] [CrossRef]
- Hussein, K.; Dabaja-Younis, H.; Szwarcwort-Cohen, M.; Almog, R.; Leiba, R.; Weissman, A.; Mekel, M.; Hyams, G.; Horowitz, N.A.; Gepstein, V.; et al. Third BNT162b2 Vaccine Booster Dose against SARS-CoV-2-Induced Antibody Response among Healthcare Workers. Vaccines 2022, 10, 1741. [Google Scholar] [CrossRef] [PubMed]
- Lasagna, A.; Cassaniti, I.; Arena, F.; Bergami, F.; Percivalle, E.; Comolli, G.; Sarasini, A.; Ferrari, A.; Cicognini, D.; Schiavo, R.; et al. Persistence of Immune Response Elicited by Three Doses of mRNA Vaccine against SARS-CoV-2 in a Cohort of Patients with Solid Tumors: A One-Year Follow-Up. Int. J. Mol. Sci. 2023, 24, 6731. [Google Scholar] [CrossRef]
- Larsen, E.S.; Nilsson, A.C.; Möller, S.; Voss, A.B.; Johansen, I.S. Immunogenicity and Risk of Disease Flare after a Three-Dose Regimen with SARS-CoV-2 Vaccination in Patients with Systemic Lupus Erythematosus: Results from the Prospective Cohort Study COVAC-SLE. Clin. Exp. Rheumatol. 2023, 41, 676–684. [Google Scholar] [CrossRef]
- Sartori, N.S.; Machado, K.L.L.L.; Miyamoto, S.T.; Pretti, F.Z.; Gouveia, M.d.P.G.; de Oliveira, Y.G.P.; da Silva, V.G.; Faé, F.; Burian, A.P.N.; Tapia, K.R.L.; et al. Immunogenicity of SARS-CoV-2 Vaccination Schedules Including a Booster Dose in Patients with Systemic Lupus Erythematosus: Data from a Prospective Multicenter Study. Vaccines 2025, 13, 127. [Google Scholar] [CrossRef] [PubMed]
- Schiavoni, I.; Olivetta, E.; Natalucci, F.; Olivieri, G.; Lo Presti, A.; Fedele, G.; Stefanelli, P.; Ceccarelli, F.; Conti, F. Evidence of Immune Response to BNT162b2 COVID-19 Vaccine in Systemic Lupus Erythematosus Patients Treated with Belimumab. Lupus 2023, 32, 394–400. [Google Scholar] [CrossRef]
- Grifoni, A.; Alonzi, T.; Alter, G.; Noonan, D.M.; Landay, A.L.; Albini, A.; Goletti, D. Impact of Aging on Immunity in the Context of COVID-19, HIV, and Tuberculosis. Front. Immunol. 2023, 14, 1146704. [Google Scholar] [CrossRef]
- Tunitsky-Lifshitz, Y.; Maoz-Segal, R.; Niznik, S.; Shavit, R.; Haj Yahia, S.; Langevitz, P.; Agmon-Levin, N. The Third Dose of BNT162b2 COVID-19 Vaccine Is Efficacious and Safe for Systemic Lupus Erythematosus Patients Receiving Belimumab. Lupus 2023, 32, 675–679. [Google Scholar] [CrossRef]
- El-Shitany, N.A.; Bagher, A.M.; Binmahfouz, L.S.; Eid, B.G.; Almukadi, H.; Badr-Eldin, S.M.; El-Hamamsy, M.; Mohammedsaleh, Z.M.; Saleh, F.M.; Almuhayawi, M.S.; et al. The Adverse Reactions of Pfizer BioNTech COVID-19 Vaccine Booster Dose Are Mild and Similar to the Second Dose Responses: A Retrospective Cross-Sectional Study. Int. J. Gen. Med. 2022, 15, 6821–6836. [Google Scholar] [CrossRef]
- Barbhaiya, M.; Levine, J.M.; Siegel, C.H.; Bykerk, V.P.; Jannat-Khah, D.; Mandl, L.A. Adverse Events and Disease Flares after SARS-CoV-2 Vaccination in Patients with Systemic Lupus Erythematosus. Clin. Rheumatol. 2022, 41, 1619–1622. [Google Scholar] [CrossRef]
- Felten, R.; Kawka, L.; Dubois, M.; Ugarte-Gil, M.F.; Fuentes-Silva, Y.; Piga, M.; Arnaud, L. Tolerance of COVID-19 Vaccination in Patients with Systemic Lupus Erythematosus: The International VACOLUP Study. Lancet Rheumatol. 2021, 3, e613–e615. [Google Scholar] [CrossRef] [PubMed]
- Zavala-Flores, E.; Salcedo-Matienzo, J.; Quiroz-Alva, A.; Berrocal-Kasay, A. Side Effects and Flares Risk after SARS-CoV-2 Vaccination in Patients with Systemic Lupus Erythematosus. Clin. Rheumatol. 2022, 41, 1349–1357. [Google Scholar] [CrossRef] [PubMed]
- Khatri, G.; Priya; Shaikh, S.; Aashish; Rai, A.; Cheema, H.A.; Essar, M.Y. Systematic Lupus Erythematous Patients Following COVID-19 Vaccination: Its Flares up and Precautions. Ann. Med. Surg. 2022, 80, 104282. [Google Scholar] [CrossRef]
- Hromić-Jahjefendić, A.; Lundstrom, K.; Adilović, M.; Aljabali, A.A.A.; Tambuwala, M.M.; Serrano-Aroca, Á.; Uversky, V.N. Autoimmune Response after SARS-CoV-2 Infection and SARS-CoV-2 Vaccines. Autoimmun. Rev. 2024, 23, 103508. [Google Scholar] [CrossRef]
- Sachinidis, A.; Garyfallos, A. COVID-19 Vaccination Can Occasionally Trigger Autoimmune Phenomena, Probably via Inducing Age-Associated B Cells. Int. J. Rheum. Dis. 2022, 25, 83–85. [Google Scholar] [CrossRef]
- Noureldine, H.A.; Maamari, J.; El Helou, M.O.; Chedid, G.; Farra, A.; Husni, R.; Mokhbat, J.E. The Effect of the BNT162b2 Vaccine on Antinuclear Antibody and Antiphospholipid Antibody Levels. Immunol. Res. 2022, 70, 800–810. [Google Scholar] [CrossRef]
- Sarin, K.Y.; Zheng, H.; Chaichian, Y.; Arunachalam, P.S.; Swaminathan, G.; Eschholz, A.; Gao, F.; Wirz, O.F.; Lam, B.; Yang, E.; et al. Impaired Innate and Adaptive Immune Responses to BNT162b2 SARS-CoV-2 Vaccination in Systemic Lupus Erythematosus. JCI Insight 2024, 9, e176556. [Google Scholar] [CrossRef]
- Gerosa, M.; Schioppo, T.; Argolini, L.M.; Sciascia, S.; Ramirez, G.A.; Moroni, G.; Sinico, R.A.; Bonelli, G.; Alberici, F.; Mescia, F.; et al. The Impact of Anti-SARS-CoV-2 Vaccine in Patients with Systemic Lupus Erythematosus: A Multicentre Cohort Study. Vaccines 2022, 10, 663. [Google Scholar] [CrossRef]
p value | |||||
---|---|---|---|---|---|
SLE patients | HC | Within SLE cohort | SLE vs. HC * | ||
Total | 36 | 43 | - | ||
Subjects, n (%) | IS | 16 (44.4%) | 0.8 | - | |
Non-IS | 20 (55.6%) | - | |||
Total | 32 (88.9%) | 35 (81.4%) | 0.3 | ||
Females, n (%) | IS | 13 (81.2%) | 0.1 | 0.9 | |
Non-IS | 19 (95%) | 0.1 | |||
Total | 52.9 ± 11.7 | 48.1 ± 10.9 | 0.06 | ||
Age, years, M ± SD | IS | 49.3 ± 11.8 | 0.1 | 0.09 | |
Non-IS | 55.4 ± 10.9 | 0.2 | |||
Disease duration, years, M ± SD | Total | 19.1 ± 7.8 | - | ||
IS | 17.7 ± 6.5 | - | 0.1 | - | |
Non-IS | 20.2 ± 8.8 | - |
SLE | HC | p value | ||||
---|---|---|---|---|---|---|
Within SLE cohort | SLE vs. HC * | |||||
anti-RBD antibodies | Qualitative response, n (%) | Total | 33/36 (91.7) | 43/43 (100) | 0.09 | |
IS | 15/16 (93.7) | >0.9 | 0.2 | |||
Non-IS | 18/20 (90) | 0.09 | ||||
Quantitative response, BAU/mL Median (IQR) | Total | 718.7 (137–2176) | 1010 (529–2348) | 0.1 | ||
IS | 687 (182–1107) | >0.9 | 0.4 | |||
Non-IS | 779 (115.4–2460) | 0.9 | ||||
Neutralizing antibodies | Qualitative response, n (%) | Total | 11/36 (30.6) | 17/43 (39.5) | 0.4 | |
IS | 3/16 (18.7) | 0.2 | 0.2 | |||
Non-IS | 8/20 (40) | >0.9 | ||||
Quantitative response, reciprocal of serum dilution (IQR) | Total | 5 (5–10) | 5 (5–10) | 0.6 | ||
IS | 5 (5–5) | 0.5 | 0.6 | |||
Non-IS | 5 (5–17.5) | >0.9 | ||||
Spike-specific IFN-γ T-cell response | Qualitative response, n (%) | Total | 30/36 (83.3) | 40/43 (93.0) | 0.2 | |
IS | 13/16 (81.2) | >0.9 | 0.3 | |||
Non-IS | 17/20 (85) | 0.3 | ||||
Quantitative response, pg/mL Median (IQR) | Total | 66.7 (20.1–219.4) | 154.4 (67.3–345) | 0.01 | ||
IS | 60.5 (17.5–221.6) | >0.9 | 0.09 | |||
Non-IS | 70.9 (23.4–216.5) | 0.1 |
SLE | HC | p value | ||||
---|---|---|---|---|---|---|
Within SLE cohort | SLE vs. HC * | |||||
anti-RBD antibodies | Qualitative response, n (%) | Total | 13/15 (86.7) | 8/8 (100) | 0.5 | |
IS | 7/7 (100) | 0.4 | >0.9 | |||
Non-IS | 6/8 (75) | 0.4 | ||||
Quantitative response, BAU/mL Median (IQR) | Total | 1958 (50.6–5611) | 728.4 (538.7–2487) | 0.7 | ||
IS | 2044 (50.6–5611) | >0.9 | >0.9 | |||
Non-IS | 1739 (340.4–5444) | >0.9 | ||||
Neutralizing antibodies | Qualitative response, n (%) | Total | 8/15 (53.3) | 2/8 (25) | 0.3 | |
IS | 3/7 (42.8) | 0.6 | 0.6 | |||
Non-IS | 5/8 (62.5) | 0.3 | ||||
Quantitative response, reciprocal of serum dilution (IQR) | Total | 10 (5–40) | 5 (5–16.2) | 0.2 | ||
IS | 5 (5–80) | >0.9 | >0.9 | |||
Non-IS | 20 (5–40) | 0.4 | ||||
Spike-specific IFN-γ T-cell response | Qualitative response, n (%) | Total | 13/15 (86.7) | 8/8 (100) | 0.5 | |
IS | 6/7 (85.7) | >0.9 | 0.4 | |||
Non-IS | 7/8 (87.5) | >0.9 | ||||
Quantitative response, pg/mL Median (IQR) | Total | 68.1 (39.3–274.6) | 173.6 (51.6–374.6) | 0.2 | ||
IS | 50.9 (39.3–274.6) | >0.9 | 0.7 | |||
Non-IS | 82 (24.9–315.6) | >0.9 |
T1 n = 15 | T2 n = 15 | p value | ||
---|---|---|---|---|
Qualitative response | anti-RBD Ab responders, n (%) | 12 (80%) | 13 (86.7%) | 0.3 |
Neutralizing Ab responders, n (%) | 4 (26.7%) | 8 (53.3%) | 0.04 | |
Cellular responders, n (%) | 12 (80%) | 13 (86.7%) | 0.5 | |
Quantitative response | anti-RBD titers, BAU/mL, Median (IQR) | 897.5 (101–2358) | 1958 (50.6–5611) | 0.04 |
Neutralizing Ab titers, Median (IQR) | 5 (5–10) | 10 (5–40) | 0.04 | |
spike IFN-γ levels, pg/mL, Median (IQR) | 45.8 (19.4–180.8) | 68.1 (39.3–274.6) | 0.1 |
Characteristics | n (%) | Anti-RBD Ab (BAU/mL) | Neutralizing Ab Titer | IFN-γ (pg/mL) | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Median (IQR) | rho | p | Median (IQR) | rho | p | Median (IQR) | rho | p | ||
Age | ||||||||||
<50 | 11 (30.6) | 1152 (530–4224) | 0.01 | 5 (5–40) | 0.09 | 181 (45–335) | 0.07 | |||
≥50 | 25 (69.4) | 682 (107–1354) | 5 (5–7.5) | 46 (16–166) | ||||||
Sex | ||||||||||
Female | 32 (88.9) | 693 (126–1589) | 0.28 | 5 (5–10) | 0.7 | 71 (20–219) | 0.7 | |||
Male | 4 (11.1) | 1732 (616–2631) | 8 (5–10) | 40 (25–237) | ||||||
BMI | ||||||||||
<25 | 20 (55.6) | 712 (126–3318) | >0.9 | 5 (5–20) | 0.3 | 104 (21–222) | 0.3 | |||
≥25 | 16 (44.4) | 736 (150–1409) | 5 (5–9) | 46 (16–217) | ||||||
ANA | ||||||||||
Negative | 10 (27.8) | 820 (169–1298) | 0.8 | 5 (5–6.2) | 0.4 | 159 (32–253) | 0.2 | |||
Positive | 26 (72.2) | 693 (133–2540) | 5 (5–12.5) | 61 (19–185) | ||||||
Anti-dsDNA | ||||||||||
Negative | 31 (86.1) | 778 (188–2494) | 0.1 | 5 (5–10) | 0.6 | 69 (19–223) | 0.9 | |||
Positive | 5 (13.9) | 138 (0–1428) | 5 (5–12.5) | 34 (22–268) | ||||||
PGA | ||||||||||
0 | 32 (88.9) | 760 (220–2176) | 0.1 | 5 (5–10) | 0.6 | 71 (25–219) | 0.1 | |||
>0 | 4 (11.1) | 68 (0–2042) | 5 (5–8) | 16 (8–231) | ||||||
Lymphocyte count | −0.05 | 0.7 | −0.05 | 0.7 | 0.11 | 0.5 | ||||
C3 | 0.2 | 0.2 | 0.17 | 0.3 | 0.19 | 0.2 | ||||
C4 | 0.1 | 0.5 | −0.07 | 0.6 | −0.12 | 0.4 | ||||
ESR | −0.29 | 0.08 | −0.27 | 0.1 | −0.04 | 0.8 | ||||
CRP | −0.27 | 0.1 | −0.22 | 0.2 | −0.37 | 0.02 | ||||
SELENA-SLEDAI | −0.25 | 0.1 | −0.05 | 0.7 | −0.04 | 0.8 |
SLE patients n = 36 | IS n = 16 | Non-IS n = 20 | p value | |
---|---|---|---|---|
0 to 1 symptom, n (%) | 8 (22.2%) | 4 (25%) | 4 (20%) | 0.7 |
2 to 4 symptoms, n (%) | 17 (47.2%) | 8 (50%) | 9 (45%) | 0.7 |
5 to 7 symptoms, n (%) | 11 (30.5%) | 4 (25%) | 7 (35%) | 0.5 |
Injection site’s pain, n (%) | 28 (77.7%) | 11 (68.7%) | 17 (85%) | 0.2 |
Fatigue, n (%) | 19 (52.7%) | 8 (50%) | 11 (55%) | 0.7 |
Arthralgia, n (%) | 17 (47.2%) | 7 (43.7%) | 10 (50%) | 0.7 |
Myalgia, n (%) | 14 (38.8%) | 6 (37.5%) | 8 (40%) | 0.8 |
Fever, n (%) | 17 (47.2%) | 7 (43.7%) | 10 (50%) | 0.7 |
Headache, n (%) | 13 (36.1%) | 6 (37.5%) | 7 (35%) | 0.8 |
Chills, n (%) | 13 (36.1%) | 5 (31.2%) | 8 (40%) | 0.5 |
T0 | T1 | T2 | p T0 vs. T1 | p T0 vs. T2 | p T1 vs. T2 | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SLE patients | IS | Non-IS | p | SLE patients | IS | Non-IS | p | SLE patients | IS | Non-IS | p | ||||||||||
n = 36 | n = 16 | n = 20 | n = 36 | n = 16 | n = 20 | n = 15 | n = 7 | n = 8 | SLE patients | IS | Non-IS | SLE patients | IS | Non-IS | SLE patients | IS | Non-IS | ||||
ANA, n (%) | 26 (72.2%) | 10 (62.5%) | 16 (80%) | 0.2 | 33 (91.6%) | 13 (81.2%) | 20 (100%) | 0.1 | 9 (46.6%) | 3 (42.8%) | 6 (75%) | 0.7 | 0.03 | 0.2 | 0.1 | 0.3 | 0.3 | 0.7 | 0.006 | 0.06 | 0.02 |
Anti-dsDNA ab, n (%) | 5 (13.8%) | 3 (18,7%) | 2 (10%) | 0.4 | 5 (13.8%) | 3 (18.7%) | 2 (10%) | 0.4 | 2 (13.3%) | 0 (0%) | 1 (12.5%) | 0.9 | 0.9 | 0.9 | 0.9 | 0.4 | 0.2 | 0.8 | 0.4 | 0.8 | 0.8 |
PGA, M (IQR) | 0 (0–0.5) | 0 (0–0.0) | 0 (0–0) | 0.4 | 0 (0–1) | 0 (0–0) | 0 (0–0) | 0.6 | 0 (0–0) | 0 (0–2) | 0 (0–2) | 0.4 | 0.8 | 0.6 | 0.6 | 0.3 | 0.6 | 0.4 | 0.6 | 0.5 | 0.7 |
SELENA-SLEDAI, M (IQR) | 1 (0–2) | 2 (0–2.7) | 0 (0–2) | 0.06 | 0.5 (0–2) | 1.5 (0–2) | 0 (0–2) | 0.7 | 0 (0–2) | 1 (0–2) | 0 (0–2) | 0.6 | 0.8 | 0.4 | 0.3 | 0.9 | 0.2 | 0.7 | 0.7 | 0.5 | 0.7 |
SLEDAI flare index | |||||||||||||||||||||
Mild/moderate, n (%) | 0 (0%) | 0 (0%) | 0 (0%) | - | 2 (5.5%) | 0 (%) | 2 (10%) | 0.1 | 0 (0%) | 0 (0%) | 0 (0%) | - | 0.1 | - | 0.1 | - | - | - | 0.1 | 0.5 | 0.3 |
Severe, n (%) | 0 (0%) | 0 (0%) | 0 (0%) | - | 1 (2.7%) | 0 (0%) | 1 (5%) | 0.3 | 1 (6.6%) | 0 (0%) | 1 (12.5%) | 0.3 | 0.3 | - | 0.9 | 0.5 | - | 0.1 | 0.5 | - | 0.4 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ferraioli, M.; Aiello, A.; Prevete, I.; Chimenti, M.S.; De Marco, L.; Meschi, S.; Mariotti, D.; Vanini, V.; Cuzzi, G.; Salmi, A.; et al. Anti-SARS-CoV-2 B and T-Cell Immune Responses Persist 12 Months After mRNA Vaccination with BNT162b2 in Systemic Lupus Erythematosus Patients Independently of Immunosuppressive Therapies. Vaccines 2025, 13, 396. https://doi.org/10.3390/vaccines13040396
Ferraioli M, Aiello A, Prevete I, Chimenti MS, De Marco L, Meschi S, Mariotti D, Vanini V, Cuzzi G, Salmi A, et al. Anti-SARS-CoV-2 B and T-Cell Immune Responses Persist 12 Months After mRNA Vaccination with BNT162b2 in Systemic Lupus Erythematosus Patients Independently of Immunosuppressive Therapies. Vaccines. 2025; 13(4):396. https://doi.org/10.3390/vaccines13040396
Chicago/Turabian StyleFerraioli, Mario, Alessandra Aiello, Immacolata Prevete, Maria Sole Chimenti, Luigi De Marco, Silvia Meschi, Davide Mariotti, Valentina Vanini, Gilda Cuzzi, Andrea Salmi, and et al. 2025. "Anti-SARS-CoV-2 B and T-Cell Immune Responses Persist 12 Months After mRNA Vaccination with BNT162b2 in Systemic Lupus Erythematosus Patients Independently of Immunosuppressive Therapies" Vaccines 13, no. 4: 396. https://doi.org/10.3390/vaccines13040396
APA StyleFerraioli, M., Aiello, A., Prevete, I., Chimenti, M. S., De Marco, L., Meschi, S., Mariotti, D., Vanini, V., Cuzzi, G., Salmi, A., Notari, S., Mellini, V., Puro, V., Maggi, F., Goletti, D., & Sebastiani, G. D. (2025). Anti-SARS-CoV-2 B and T-Cell Immune Responses Persist 12 Months After mRNA Vaccination with BNT162b2 in Systemic Lupus Erythematosus Patients Independently of Immunosuppressive Therapies. Vaccines, 13(4), 396. https://doi.org/10.3390/vaccines13040396