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
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Cohort and Design
2.2. Anti-SARS-CoV-2 Antibodies
2.3. IFN-γ-Spike-Specific T cell Response
2.4. Statistical Analysis
3. Results
3.1. Characteristics of the Studied Population
3.2. Incidence of Breakthrough Infections and Clinical Features
3.3. Incidence of Breakthrough Infections and Immune Response
3.4. COVID-19 Severity
3.5. Time of Swab Negativization
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patients’ Characteristics | |
---|---|
Total | 64 (100) |
Age, median (IQR) years | 49 (41.5–55.5) |
Age class, n (%) | |
23–39 | 16 (25.0) |
40–49 | 19 (29.7) |
50–70 | 29 (45.3) |
Gender: Female, n (%) | 43 (67.2) |
Origin: Italian, n (%) | 62 (96.9) |
Presence of comorbidities, n (%) | 14 (21.9) |
BMI (kg/m2), median (IQR) | 24 (21–26) |
Vaccination-First dose with Comirnaty, n (%) | 59 (92.2) |
MS duration, median (IQR) years | 15 (7–25) |
MS treatment, n (%) | |
Cladribine | 6 (9.4) |
Fingolimod | 26 (40.6) |
Interferon beta | 15 (23.4) |
Ocrelizumab | 17 (26.6) |
MS treatment duration, median months (IQR) | 5 (2–9) |
EDSS score, median (IQR) | 2 (0.5–4.3) |
<3 | 37 (58.8) |
≥3 | 27 (42.2) |
MS phenotype, n (%) | |
Primary-progressive (PP) | 5 (7.8) |
Relapsing-Remitting (RR) | 59 (92.2) |
Lymphocytes count × 103/µL, median (IQR) | 1.3 (0.7–1.7) |
Days from booster dose to sample, median (IQR) | 48 (43–51) |
Among PwMS with SARS-CoV-2 breakthrough infection | 28 (43.7) |
Days from 3rd dose to infection, median (IQR) | 155 (108–205) |
Days to negative swab, median (IQR) | 11 (9–15) |
COVID-19 therapy, n (%) | |
Anti-viral therapy | 5 (17.9) |
Monoclonal therapy | 11 (39.3) |
Non-steroidal anti-inflammatory drugs or paracetamol or no therapy * | 12 (42.9) |
Severity of COVID-19, n (%) | |
Mild disease | 21 (75.0) |
Moderate disease | 5 (17.9) |
Severe disease | 2 (7.1) |
Patients’ Characteristics | SARS-CoV-2 BIs | Univariable | Multivariable | ||||||
---|---|---|---|---|---|---|---|---|---|
No | Yes | Total | IRR | 95%CI | p | IRR | 95%CI | p | |
Total, n (%) | 36 (56.3) | 28 (43.8) | 64 (100) | ||||||
Age, median (IQR) years | 50 (45.5–58) | 47.5 (38–53.5) | 49 (41.5–55.5) | ||||||
23–39 | 8 (22.2) | 8 (28.6) | 16 (25.0) | Ref. | |||||
40–49 | 10 (27.8) | 9 (32.1) | 19 (29.7) | 1.01 | 0.39–2.63 | 0.979 | |||
50–70 | 18 (50.0) | 11 (39.3) | 29 (45.3) | 0.66 | 0.27–1.64 | 0.371 | |||
Gender, n (%) | |||||||||
Female | 28 (77.8) | 15 (53.6) | 43 (67.2) | Ref. | |||||
Male | 8 (22.2) | 13 (46.4) | 21 (32.8) | 2.19 | 1.04–4.6 | 0.038 | |||
Country of birth, n (%) | |||||||||
Italy | 34 (94.4) | 28 (100) | 62 (96.9) | - | - | - | |||
Abroad | 2 (5.6) | 0 (0) | 2 (3.1) | - | - | - | |||
Presence of comorbidities, n (%) | |||||||||
No | 27 (75.0) | 23 (82.1) | 50 (78.1) | Ref. | |||||
Yes | 9 (25.0) | 5 (17.9) | 14 (21.9) | 0.69 | 0.26–1.83 | 0.460 | |||
BMI (kg/m2), median (IQR) | 24 (20.9–25.9) | 24 (22–26.6) | 24 (21.3–26.2) | ||||||
≤24 | 18 (50.0) | 14 (50.0) | 32 (50.0) | Ref. | |||||
>24 | 18 (50.0) | 14 (50.0) | 32 (50.0) | 1.03 | 0.49–2.16 | 0.938 | |||
Vaccination-First dose, n (%) | |||||||||
Comirnaty | 33 (91.7) | 26 (92.9) | 59 (92.2) | Ref. | |||||
Other | 3 (8.3) | 2 (7.1) | 5 (7.8) | 1.06 | 0.25–4.45 | 0.940 | |||
MS duration (years), median (IQR) | 16.2 (8.5–23.1) | 12.9 (5.8–25) | 15 (7.5–24.5) | ||||||
≤15 | 17 (47.2) | 16 (57.1) | 33 (51.6) | Ref. | |||||
>15 | 19 (52.8) | 12 (42.9) | 31 (48.4) | 0.79 | 0.37–1.67 | 0.539 | |||
MS treatment, n (%) | |||||||||
Cladribine | 5 (13.9) | 1 (3.6) | 6 (9.4) | 0.32 | 0.04–2.69 | 0.297 | |||
Fingolimod | 16 (44.4) | 10 (35.7) | 26 (40.6) | 0.97 | 0.35–2.66 | 0.948 | |||
Interferon beta | 9 (25.0) | 6 (21.4) | 15 (23.4) | Ref. | |||||
Ocrelizumab | 6 (16.7) | 11 (39.3) | 17 (26.6) | 2.21 | 0.82–5.97 | 0.118 | |||
MS treatment duration (years), median (IQR) | 6.5 (2–9.1) | 3.7 (1.8–7.9) | 5.1 (1.9–8.6) | ||||||
≤5 | 14 (38.9) | 17 (60.7) | 31 (48.4) | Ref. | |||||
>5 | 22 (61.1) | 11 (39.3) | 33 (51.6) | 0.49 | 0.23–1.04 | 0.062 | |||
EDSS score, median (IQR) | 3 (0.5–5) | 1.8 (0.5–3) | 2 (0.5–4.3) | ||||||
<3 | 17 (47.2) | 20 (71.4) | 37 (58.8) | Ref. | Ref. | ||||
≥3 | 19 (52.8) | 8 (28.6) | 27 (42.2) | 0.40 | 0.18–0.9 | 0.029 | 0.22 | 0.08–0.66 | 0.006 |
MS phenotype, n (%) | |||||||||
Primary-progressive (PP) | 1 (2.8) | 4 (14.3) | 5 (7.8) | Ref. | Ref. | ||||
Relapsing-Remitting (RR) | 35 (97.2) | 24 (85.7) | 59 (92.2) | 0.33 | 0.11–0.94 | 0.039 | 0.12 | 0.03–0.46 | 0.002 |
Lymphocytes count × 103/µL, median (IQR) | 1.3 (0.7–1.6) | 1.3 (0.7–1.8) | 1.28 (0.65–1.67) | ||||||
≤1.28 | 18 (54.6) | 11 (45.8) | 29 (50.9) | Ref. | |||||
>1.28 | 15 (45.4) | 13 (54.2) | 28 (49.1) | 1.35 | 0.61–3.02 | 0.461 |
Immune Response | No BI | BI | Total | Univariable | Multivariable | ||||
---|---|---|---|---|---|---|---|---|---|
36 (56.3) | 28 (43.8) | 64 (100) | IRR | 95%CI | p | aIRR | 95%CI | p | |
anti-RBD IgG (BAU/mL) | |||||||||
continuous, median (IQR) | 352 (24–5513) | 135 (1–1337) | 272 (8–4222) | ||||||
score: Negative (<7.1) | 5 (13.9) | 11 (39.3) | 16 (25.0) | Ref. | Ref. | ||||
score: Positive (≥7.1) | 31 (86.1) | 17 (60.7) | 48 (75.0) | 0.33 | 0.15–0.7 | 0.004 | 0.40 | 0.17–0.97 | 0.042 |
IFN-γ T cell-specific response (pg/mL) | |||||||||
continuous, median (IQR) | 30 (1–222) | 188 (1–578) | 79 (1–349) | ||||||
<16 | 17 (47.2) | 10 (35.7) | 27 (42.2) | Ref. | Ref. | ||||
≥16 | 19 (52.8) | 18 (64.3) | 37 (57.8) | 1.61 | 0.74–3.49 | 0.228 | 0.55 | 0.22–1.34 | 0.187 |
Neutralizing antibodies | |||||||||
continuous, median (IQR) | 15 (5–320) | 5 (5–160) | 8 (5–320) | ||||||
<10 | 17 (47.2) | 15 (53.6) | 32 (50.0) | Ref. | Ref. | ||||
≥10 | 19 (52.8) | 13 (46.4) | 32 (50.0) | 0.83 | 0.39–1.74 | 0.618 | 0.68 | 0.30–1.55 | 0.362 |
Patients’ Characteristics | COVID-19 Severity | ||||
---|---|---|---|---|---|
Mild Disease | Moderate Disease | Severe Disease | Total | p | |
Total | 21 (75.0) | 5 (17.9) | 2 (7.1) | 28 (100) | |
Age, median (IQR) years | 47 (39–53) | 49 (30–55) | 47.5 (46–49) | 47.5 (38–53.5) | 0.969 |
Age class, n (%) | 0.511 | ||||
23–39 | 6 (28.6) | 2 (40) | 0 (0) | 8 (28.6) | |
40–49 | 6 (28.6) | 1 (20) | 2 (100) | 9 (32.1) | |
50–70 | 9 (42.9) | 2 (40) | 0 (0) | 11 (39.3) | |
Gender, n (%) | 0.293 | ||||
Female | 13 (61.9) | 2 (40) | 0 (0) | 15 (53.6) | |
Male | 8 (38.1) | 3 (60) | 2 (100) | 13 (46.4) | |
Presence of comorbidities, n (%) | 0.696 | ||||
No | 16 (76.2) | 5 (100) | 2 (100) | 23 (82.1) | |
Yes | 5 (23.8) | 0 (0) | 0 (0) | 5 (17.9) | |
BMI (kg/m2), median (IQR) | 24.2 (22.8–26.8) | 22.1 (21.8–23.6) | 24.5 (23.2–25.8) | 24 (22–26.6) | 0.571 |
Vaccination-First dose type, n (%) | 1.000 | ||||
Comirnaty | 19 (90.5) | 5 (100) | 2 (100) | 26 (92.9) | |
Other | 2 (9.5) | 0 (0) | 0 (0) | 2 (7.1) | |
MS duration, median (IQR) months(?) | 15 (5.7–24.8) | 10.7 (9.1–14) | 19.1 (7.9–30.3) | 12.9 (5.8–25) | 0.763 |
MS treatment, n (%) | 0.463 | ||||
Cladribine | 1 (4.8) | 0 (0) | 0 (0) | 1 (3.6) | |
Fingolimod | 8 (38.1) | 1 (20) | 1 (50) | 10 (35.7) | |
Interferon beta | 6 (28.6) | 0 (0) | 0 (0) | 6 (21.4) | |
Ocrelizumab | 6 (28.6) | 4 (80) | 1 (50) | 11 (39.3) | |
MS treatment duration, median (IQR) months | 4.7 (1.9–8) | 1.9 (1.8–4.1) | 6.7 (3.4–9.9) | 3.7 (1.8–7.9) | 0.310 |
EDSS score, median (IQR) | 2 (0–2.5) | 1.5 (1–1.5) | 6.5 (6.5–6.5) | 1.8 (0.5–3) | 0.064 |
<3 | 16 (76.2) | 4 (80.0) | 0 (0) | 20 (71.4) | 0.089 |
≥3 | 5 (23.8) | 1 (20.0) | 2 (100) | 8 (28.6) | |
MS phenotype, n (%) | 0.253 | ||||
Primary-progressive (PP) | 2 (9.5) | 1 (20) | 1 (50) | 4 (14.3) | |
Relapsing-Remitting (RR) | 19 (90.5) | 4 (80) | 1 (50) | 24 (85.7) | |
Lymphocytes count × 103/µL, median (IQR) | 1.3 (0.7–1.7) | 1.5 (1.2–1.7) | 1.5 (0.2–2.7) | 1.3 (0.7–1.8) | 0.912 |
COVID-19 therapy, n(%) | 0.098 | ||||
Anti-viral therapy | 4 (19.1) | 1 (20.0) | 0 (0) | 5 (17.9) | |
Monoclonal therapy | 7 (33.3) | 4 (80.0) | 0 (0) | 11 (39.3) | |
NSAIDs, paracetamol or no therapy | 10 (47.6) | 0 (0) | 2 (100) | 12 (42.9) | |
Days from booster dose to infection, median (IQR) | 153 (105–169) | 204 (154–204) | 263 (258–268) | 154.5 (108–204.5) | 0.129 |
anti-RBD IgG (BAU/mL), median (IQR) | |||||
continuous | 407 (2–2319) | 1 (0–4) | 268 (0–537) | 135 (1–1337) | 0.160 |
<7.1, n (%) | 6 (28.6) | 4 (80) | 1 (50) | 11 (39.3) | 0.090 |
≥7.1, n (%) | 15 (71.4) | 1 (20) | 1 (50) | 17 (60.7) | |
IFN-γ T cell-specific response (pg/mL), median (IQR) | |||||
continuous | 166 (1–564) | 238 (207–353) | 365 (0–729) | 188 (1–578) | 0.957 |
<16, n (%) | 8 (38.1) | 1 (20) | 1 (50) | 10 (35.7) | 0.823 |
≥16, n (%) | 13 (61.9) | 4 (80) | 1 (50) | 18 (64.3) | |
Neutralizing antibodies, median (IQR) | |||||
continuous | 20 (5–160) | 5 (5–5) | 23 (5–40) | 5 (5–160) | 0.323 |
<10, n (%) | 10 (47.6) | 4 (80) | 1 (50) | 15 (53.6) | 0.655 |
≥10, n (%) | 11 (52.4) | 1 (20) | 1 (50) | 13 (46.4) |
Quantile Regression Model | ||||||
---|---|---|---|---|---|---|
Patient’s Characteristic | Univariable | Multivariable | ||||
Coefficient * | 95%CI | p | Coefficient ** | 95%CI | p | |
Age class, years n (%) | ||||||
23–39 | Ref. | |||||
40–49 | 3.00 | −3.07; 9.07 | 0.317 | |||
50–70 | 0.00 | −5.78; 5.78 | 1.000 | |||
Gender, n (%) | ||||||
Female | Ref. | |||||
Male | 0.00 | −5.03; 5.03 | 1.000 | |||
Presence of comorbidities, n (%) | ||||||
No | Ref. | |||||
Yes | −5.00 | −10.6; 0.6 | 0.078 | |||
BMI (kg/m2), median (IQR) | −0.21 | −0.79; 0.37 | 0.459 | |||
Vaccination-First dose, n (%) | ||||||
Comirnaty | Ref. | |||||
Other | −3.00 | −11.63; 5.63 | 0.479 | |||
MS duration, median (IQR) years | 0.00 | −0.29; 0.29 | 1.000 | |||
MS treatment, n (%) | ||||||
Cladribine | 0.00 | −8.52; 8.52 | 1.000 | |||
Fingolimod | 7.00 | 2.84; 11.16 | 0.002 | |||
Interferon beta | Ref. | |||||
Ocrelizumab | 3.00 | −1.16; 7.16 | 0.148 | |||
MS treatment duration, median (IQR) years | −0.41 | −0.76; −0.05 | 0.028 | |||
EDSS score, median (IQR) | 0.00 | −1.32; 1.32 | 1.000 | |||
<3 | Ref. | |||||
≥3 | 0.00 | −5.13; 5.13 | 1.000 | |||
MS phenotype, n (%) | ||||||
Primary-progressive (PP) | Ref. | |||||
Relapsing-Remitting (RR) | 0.00 | −7.2; 7.2 | 1.000 | |||
Lymphocytes count × 103/µL, median (IQR) | −2.36 | −6.46; 1.75 | 0.244 | |||
COVID-19 therapy, n (%) | ||||||
Anti-viral therapy | Ref. | |||||
Monoclonal therapy | 4.00 | −2.3; 10.34 | 0.204 | |||
NSAIDs, paracetamol or no therapy | −1.00 | −7.13; 6.13 | 0.738 | |||
Severity of COVID-19, n (%) | ||||||
Mild illness | Ref. | |||||
Moderate illness | 4 | −1.90; 9.90 | 0.174 | |||
Severe illness | 1 | −11.0; 13.0 | 0.865 | |||
Days from booster dose to sample, median (IQR) | 0.04 | −0.3; 0.39 | 0.796 | |||
Anti-RBD IgG (BAU/mL), median (IQR) | ||||||
continuous | −0.0004 | −0.001; 0.0003 | 0.245 | −0.001 | −0.001; 0.0002 | 0.163 |
score: Negative (<7.1), n (%) | Ref. | Ref. | ||||
score: Positive (≥7.1), n (%) | −4.00 | −8.31; 0.31 | 0.067 | −2.73 | −7.27; 1.81 | 0.225 |
<809 | Ref. | Ref. | ||||
≥809 | −6.00 | −10.7; −1.3 | 0.015 | −4.39 | −8.8; 0.01 | 0.051 |
IFN-γ T cell-specific response (pg/mL), median (IQR) | ||||||
continuous | −0.0018 | −0.006; 0.003 | 0.422 | −0.002 | −0.006; 0.003 | 0.446 |
<16, n (%) | Ref. | Ref. | ||||
≥16, n (%) | −5.00 | −9.77; −0.23 | 0.041 | −5.88 | −10.65; −1.10 | 0.018 |
Neutralizing antibodies, median (IQR) | ||||||
continuous | −0.01 | −0.03; 0.01 | 0.178 | −0.01 | −0.03; 0 | 0.135 |
<10, n (%) | Ref. | Ref. | ||||
≥10, n (%) | 0.00 | −3.71; 3.71 | 1.000 | −2.5 | −7.5; 2.5 | 0.310 |
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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. https://doi.org/10.3390/vaccines12080926
Aiello A, Ruggieri S, Navarra A, Tortorella C, Vanini V, Haggiag S, Prosperini L, Cuzzi G, Salmi A, Quartuccio ME, 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(8):926. https://doi.org/10.3390/vaccines12080926
Chicago/Turabian StyleAiello, Alessandra, Serena Ruggieri, Assunta Navarra, Carla Tortorella, Valentina Vanini, Shalom Haggiag, Luca Prosperini, Gilda Cuzzi, Andrea Salmi, Maria Esmeralda Quartuccio, and et al. 2024. "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 12, no. 8: 926. https://doi.org/10.3390/vaccines12080926