Older Age, a High Titre of Neutralising Antibodies and Therapy with Conventional DMARDs Are Associated with Protection from Breakthrough Infection in Rheumatoid Arthritis Patients after the Booster Dose of Anti-SARS-CoV-2 Vaccine
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population and Design
2.2. Study Procedures
2.3. Anti-SARS-CoV-2 Antibody Testing
2.4. IFN-γ-Specific T-Cell Response against SARS-CoV-2
2.5. Statistical Analysis
3. Results
3.1. Patients
3.2. Risk of Breakthrough Infections and Clinical Parameters
3.3. Risk of Breakthrough Infection and B and T Cell Immune-Specific Responses
3.4. Severity of Breakthrough Infection
3.5. Comparison between the Risk of Breakthrough Infection in RA and HCWs
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patients’ Characteristics | RA Patients |
---|---|
Total | 194 (100) |
Age, median (IQR) years | 63 (54–71) |
Age class, n (%) | |
19–49 | 22 (11.3) |
50–59 | 49 (25.3) |
60–69 | 66 (34.0) |
70–87 | 57 (29.4) |
Gender: Female, n (%) | 137 (70.6) |
Presence of comorbidities, n (%) | 130 (67.0) |
No | 64 (33.0) |
Yes, one | 78 (40.2) |
Yes, two or more | 52 (26.8) |
BMI, median (IQR) | 26.9 (23.3–28.4) |
Smoking habits, n (%) | 39 (20.1) |
Flu vaccination (2021/2022), n (%) | 112 (57.7) |
Vaccination booster type, n (%) | |
Comirnaty | 190 (97.9) |
Spikevax/other | 4 (2.1) |
Rheumatoid arthritis disease | |
Disease duration, median (IQR) months | 120 (72–186) |
Immunosuppressive drugs; regimens containing: | |
Conventional DMARDs, n (%) | 62 (32.0) |
TNFα-i, n (%) | 39 (20.1) |
IL6R-i, n (%) | 18 (9.3) |
CTLA4-Ig, n (%) | 38 (19.6) |
JAK-i, n (%) | 49 (25.3) |
CD20-i, n (%) | 11 (5.7) |
Corticosteroids, n (%) | 33 (17.1) |
Immunogenicity data, Samples available, n (%) | 41 (21.1) |
Days from booster dose to sample, median (IQR) | 28 (28–73) |
Among 82 RA patients with breakthrough infection | |
Days from 3rd dose to infection, median (IQR) | 176 (118–268) |
Early therapy with antivirals or monoclonal antibodies, n (%) | |
Yes | 22 (26.8) |
No | 60 (73.2) |
Severity of COVID-19 disease, n (%) | |
Asymptomatic | 8 (9.8) |
Pauci-symptomatic | 67 (81.7) |
Hospitalised * | 7 (8.5) |
Characteristics | Uninfected | Breakthrough Infection | Cox Regression | |||||
---|---|---|---|---|---|---|---|---|
Univariable | Multivariable | |||||||
HR | 95% CI | p | aHR | 95% CI | p | |||
Overall | 112 (57.7) | 82 (42.3) | ||||||
Age in years, median (IQR) | 66 (57–72) | 62 (53–71) | 0.74 * | 0.61–0.90 | 0.003 | |||
Age class under/over 50 years, n (%) | ||||||||
19–49 | 7 (31.8) | 15 (68.2) | 1 | 1 | ||||
50–87 | 105 (61.0) | 67 (39.0) | 0.41 | 0.24–0.73 | 0.002 | 0.38 | 0.20–0.74 | 0.004 |
Gender, n (%) | ||||||||
Male | 30 (52.6) | 27 (47.4) | 1 | |||||
Female | 82 (59.9) | 55 (40.1) | 1.14 | 0.72–1.81 | 0.568 | |||
Presence of comorbidities, n (%) | ||||||||
No | 30 (46.9) | 34 (53.1) | 1 | |||||
Yes | 82 (63.1) | 48 (36.9) | 0.59 | 0.38–0.91 | 0.018 | 0.68 | 0.43–1.10 | 0.113 |
BMI | 27 (23.5–28.6) | 26 (22.7–28) | 0.94 | 0.89–1.00 | 0.050 | 0.96 | 0.90–1.02 | 0.218 |
Smoking habits, n (%) | ||||||||
No | 94 (60.7) | 61 (39.4) | 1 | 1 | ||||
Yes | 18 (46.2) | 21 (53.8) | 1.68 | 1.02–2.76 | 0.040 | 1.61 | 0.97–2.68 | 0.066 |
Flu vaccination (season 2021/2022), n(%) | ||||||||
No | 46 (56.1) | 36 (43.9) | 1 | |||||
Yes | 66 (58.9) | 46 (41.1) | 0.92 | 0.59–1.42 | 0.703 | |||
Third-dose vaccine, n (%) | ||||||||
Comirnaty | 110 (57.9) | 80 (42.1) | 1 | |||||
Spikevax/other | 2 (50.0) | 2 (50.0) | 1.03 | 0.25–4.19 | 0.967 | |||
Rheumatoid arthritis disease | ||||||||
Disease duration in months, median (IQR) | 126 (72–198) | 120 (65–180) | 1 | 1.00–1.00 | 0.956 | |||
Immunosuppressive drugs: regimens containing | ||||||||
Conventional DMARDs, n (%) | ||||||||
No | 68 (51.5) | 64 (48.5) | 1 | 1 | ||||
Yes | 44 (71.0) | 18 (29.0) | 0.61 | 0.36–1.03 | 0.065 | 0.52 | 0.30–0.90 | 0.021 |
TNFα-i, n (%) | ||||||||
No | 88 (56.8) | 67 (43.2) | 1 | |||||
Yes | 24 (61.5) | 15 (38.5) | 0.89 | 0.51–1.56 | 0.688 | |||
IL6-i, n (%) | ||||||||
No | 105 (59.7) | 71 (40.3) | 1 | 1 | ||||
Yes | 7 (38.9) | 11 (61.1) | 2.09 | 1.11–3.95 | 0.023 | 2.01 | 1.03–3.89 | 0.039 |
CTLA4-Ig, n (%) | ||||||||
No | 88 (56.4) | 68 (43.6) | 1 | |||||
Yes | 24 (63.2) | 14 (36.8) | 0.68 | 0.38–1.22 | 0.200 | |||
JAK-i, n (%) | ||||||||
No | 83 (57.2) | 62 (42.8) | 1 | |||||
Yes | 29 (59.2) | 20 (40.8) | 0.89 | 0.54–1.48 | 0.657 | |||
CD20-i, n (%) | ||||||||
No | 108 (59.0) | 75 (41.0) | 1 | 1 | ||||
Yes | 4 (36.4) | 7 (63.6) | 1.74 | 0.80–3.78 | 0.162 | 2.88 | 1.27–6.51 | 0.011 |
Corticosteroids, n (%) | ||||||||
No | 90 (55.9) | 71 (44.1) | 1 | |||||
Yes | 22 (66.7) | 11 (33.3) | 0.86 | 0.45–1.68 | 0.666 |
Univariable | Multivariable | ||||||||
---|---|---|---|---|---|---|---|---|---|
Characteristics | SARS-CoV-2 BI | ||||||||
No | Yes | p | HR | 95% CI | p | aHR | 95% CI | p | |
Total, n (%) | 25 (61%) | 16 (39%) | |||||||
Immune responses | |||||||||
anti-S/RBD (BAU/mL), n (%) | |||||||||
<809 | 7 (43.8) | 9 (56.3) | 1 | ||||||
≥809 | 18 (72.0) | 7 (28.0) | 0.43 | 0.16–1.15 | 0.092 | 0.60 | 0.21–1.74 | 0.346 | |
Neutralising antibodies, n (%) * | |||||||||
<20 | 2 (25.0) | 6 (75.0) | 1 | 1 | |||||
≥20 | 22 (71.0) | 9 (29.0) | 0.27 | 0.10–0.74 | 0.011 | 0.36 | 0.12–1.07 | 0.067 | |
T cell-specific response detected by IFN-γ, n (%) | |||||||||
<16 | 10 (52.6) | 9 (47.4) | 1 | 1 | |||||
≥16 | 15 (68.2) | 7 (31.8) | 0.352 | 0.69 | 0.26–1.85 | 0.457 | 1.07 | 0.35–3.28 | 0.906 |
Hospitalisation | ||||
---|---|---|---|---|
No | Yes | Total | p | |
Overall | 75 (91.5) | 7 (8.5) | 82 (100) | |
Age, median (IQR) | 61 (53–71) | 67 (52–80) | 62 (53–71) | 0.778 |
Age class, over 50, n (%) | 1.000 | |||
19–49 | 14 (93.3) | 1 (6.7) | 15 (100) | |
50–87 | 61 (91.0) | 6 (8.9) | 67 (100) | |
Age class, over 65, n (%) | 0.694 | |||
19–64 | 43 (93.5) | 3 (6.5) | 46 (100) | |
65–87 | 32 (88.9) | 4 (11.1) | 36 (100) | |
Gender, n (%) | ||||
Female | 51 (92.7) | 4 (7.3) | 55 (100) | 0.679 |
Male | 24 (88.9) | 3 (11.1) | 27 (100) | |
Comorbidities, n (%) | 0.127 | |||
None | 33 (97.1) | 1 (2.9) | 34 (100) | |
At least one | 42 (87.5) | 6 (12.5) | 48 (100) | |
BMI, median (IQR) | 26 (23–28) | 27 (20–27) | 26 (22.7–28) | 0.601 |
Smoking habits,n (%) | 0.274 | |||
No | 57 (93.4) | 4 (6.6) | 61 (100) | |
Yes | 18 (85.7) | 3 (14.3) | 21 (100) | |
Flu vaccination (2021/2022), n (%) | 0.382 | |||
No | 34 (94.4) | 2 (5.6) | 36 (100) | |
Yes | 41 (89.1) | 5 (10.9) | 46 (100) | |
Disease duration (months), median (IQR) | 120 (74–181) | 60 (60–96) | 120 (65–180) | 0.045 |
Regimens containing: | ||||
Conventional DMARDs, n (%) | 0.645 | |||
No | 59 (92.2) | 5 (7.8) | 64 (100) | |
Yes | 16 (88.9) | 2 (11.1) | 18 (100) | |
TNFα-i, n (%) | 1.000 | |||
No | 61 (91.0) | 6 (8.9) | 67 (100) | |
Yes | 14 (93.3) | 1 (6.7) | 15 (100) | |
IL6R-i, n (%) | 0.586 | |||
No | 64 (90.1) | 7 (9.9) | 71 (100) | |
Yes | 11 (100) | 0 (0) | 11 (100) | |
CTLA4-Ig, n (%) | 0.597 | |||
No | 61 (89.7) | 7 (10.3) | 68 (100) | |
Yes | 14 (100) | 0 (0) | 14 (100) | |
JAK-i, n (%) | 1.000 | |||
No | 56 (90.3) | 6 (9.7) | 62 (100) | |
Yes | 19 (95.0) | 1 (5.0) | 20 (100) | |
CD20-i, n (%) | 0.001 | |||
No | 72 (96.0) | 3 (4.0) | 75 (100) | |
Yes | 3 (42.9) | 4 (57.1) | 7 (100) | |
Corticosteroids, n (%) | 1.000 | |||
No | 65 (91.5) | 6 (8.5) | 71 (100) | |
Yes | 10 (90.9) | 1 (9.1) | 11 (100) |
Characteristics | RA | HCW | Total | p |
---|---|---|---|---|
Total, n (%) | 194 (16.2) | 1002 (83.8) | 1.196 (100) | |
Age | 64 (54–71) | 45 (34–54) | 48 (36–57) | <0.001 |
Gender, n (%) | 0.435 | |||
Female | 137 (70.6) | 679 (67.8) | 816 (68.2) | |
Male | 57 (29.4) | 323 (32.2) | 380 (31.8) | |
Flu vaccination, n (%) | <0.001 | |||
No | 82 (42.3) | 787 (78.5) | 869 (72.7) | |
Yes | 112 (57.7) | 215 (21.5) | 327 (27.3) | |
Third dose vaccine, n (%) | <0.001 | |||
Comirnaty | 190 (97.9) | 567 (56.6) | 757 (63.3) | |
Spikevax/other | 4 (2.1) | 435 (43.4) | 439 (36.7) | |
Breakthrough infection, n (%) | ||||
Yes | 82 (42.3) | 530 (52.9) | 612 (51.2) | 0.007 |
No | 112 (57.7) | 472 (47.1) | 584 (48.8) |
Characteristics | Univariable | Multivariable | ||||
---|---|---|---|---|---|---|
HR | 95% CI | p | aHR | 95% CI | p | |
RA vs. HCW | 0.74 | 0.59–0.93 | 0.012 | 0.92 | 0.70–1.20 | 0.524 |
Age (10 years increment) | 0.88 | 0.83–0.93 | 0.000 | 0.89 | 0.83–0.95 | 0.001 |
Male vs. Female | 0.77 | 0.64–0.91 | 0.003 | 0.78 | 0.65–0.93 | 0.007 |
Flu vaccination, yes vs. no | 0.96 | 0.80–1.15 | 0.636 | |||
Spikevax/others vs. Comirnaty | 1.09 | 0.93–1.28 | 0.314 |
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Picchianti-Diamanti, A.; Navarra, A.; Aiello, A.; Laganà, B.; Cuzzi, G.; Salmi, A.; Vanini, V.; Maggi, F.; Meschi, S.; Matusali, G.; et al. Older Age, a High Titre of Neutralising Antibodies and Therapy with Conventional DMARDs Are Associated with Protection from Breakthrough Infection in Rheumatoid Arthritis Patients after the Booster Dose of Anti-SARS-CoV-2 Vaccine. Vaccines 2023, 11, 1684. https://doi.org/10.3390/vaccines11111684
Picchianti-Diamanti A, Navarra A, Aiello A, Laganà B, Cuzzi G, Salmi A, Vanini V, Maggi F, Meschi S, Matusali G, et al. Older Age, a High Titre of Neutralising Antibodies and Therapy with Conventional DMARDs Are Associated with Protection from Breakthrough Infection in Rheumatoid Arthritis Patients after the Booster Dose of Anti-SARS-CoV-2 Vaccine. Vaccines. 2023; 11(11):1684. https://doi.org/10.3390/vaccines11111684
Chicago/Turabian StylePicchianti-Diamanti, Andrea, Assunta Navarra, Alessandra Aiello, Bruno Laganà, Gilda Cuzzi, Andrea Salmi, Valentina Vanini, Fabrizio Maggi, Silvia Meschi, Giulia Matusali, and et al. 2023. "Older Age, a High Titre of Neutralising Antibodies and Therapy with Conventional DMARDs Are Associated with Protection from Breakthrough Infection in Rheumatoid Arthritis Patients after the Booster Dose of Anti-SARS-CoV-2 Vaccine" Vaccines 11, no. 11: 1684. https://doi.org/10.3390/vaccines11111684