Association between Reactogenicity and Immunogenicity in a Vaccinated Cohort with Two mRNA SARS-CoV-2 Vaccines at a High-Complexity Reference Hospital: A Post Hoc Analysis on Immunology Aspects of a Prospective Cohort Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Collected Data
2.2. Statistical Analysis
2.2.1. Sample Size Calculation and Planned Analyses
2.2.2. Study Endpoints
2.2.3. Statistical Analysis
3. Results
3.1. Immunogenicity and Reactogenicity Results
3.1.1. Main Analysis (Main Population, N = 215)
Immunogenicity Assessed as Positive/Negative Antibody Titres
Immunogenicity Assessed as Antibody Titres above/below Median
3.1.2. Sensitivity Analysis 1 (N = 3563)
Immunogenicity Assessed as Positive/Negative Antibody Titres
Immunogenicity Assessed as Antibody Titres above/below Median
Cellular Immunogenicity
Descriptive Analysis According to Type of Vaccine and Population
3.1.3. Sensitivity Analysis 2 (N = 597)
Immunogenicity Assessed as Positive/Negative Antibody Titres
Immunogenicity Assessed as Antibody Titres above/below Median
3.1.4. Overall Reactogenicity and Immunogenicity Analysis
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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Covariates | Total Population (N = 215) |
---|---|
Age | |
N | 215 |
Mean (SD) | 41.13 (12.71) |
Gender | |
Male (n, %) | 70 (32.6) |
Female (n, %) | 145 (67.4) |
Occupational SARS-CoV-2 contact | |
In contact with SARS-CoV-2 patients | 105 (48.8) |
Without contact with SARS-CoV-2 patients | 110 (51.2) |
a Previous SARS-CoV-2 infection | |
Yes | 78 (36.3) |
No | 137 (63.7) |
Comorbidities | |
b Any comorbidity | 83 (38.6) |
Arterial hypertension | 12 (5.6) |
Diabetes mellitus | 3 (1.4) |
Heart failure | 1 (0.5) |
Asthma | 8 (3.7) |
Rheumatic/immune-mediated disease | 1 (0.5) |
Drug allergies | 17 (7.9) |
Food allergies | 10 (4.7) |
Type of administered vaccine | |
BNT16b2 | |
First dose: | 194 (90.2) |
Second dose: | 138 (64.2) |
mRNA-1273 | |
First dose: | 21 (9.8) |
Second dose: | 17 (7.9) |
Humoral immunogenicity (antibody positiveness on semiquantitative antibody titres) | |
Number of vaccinees with positive antibody titres (titres of >1.0) (n, %) | 151 (70) |
Number of vaccinees with negative antibody titres (titres of <1.0) (n, %) | 64 (30) |
Humoral immunogenicity (antibody semiquantitative titres above/below median) | |
Median value of antibody titres (P25, P75) * | 7.69 (0.73,10.00) |
Number of vaccinees with antibody titres above median (n, %) | 93 (43%) |
Number of vaccinees with antibody titres below median (n, %) | 122 (57%) |
Main Analysis | |||||||
---|---|---|---|---|---|---|---|
N = 215 | Antibody Positiveness | p-Value | Antibody Titres | p-Value | |||
Negative Antibody Titres (n = 64) | Positive Antibody Titres (n = 151) | Antibody Titres below Median * (n = 93) | Antibody Titres above Median * (n = 122) | ||||
Proportion of AR (% of vaccinees with an AR) | Any mild AR after 1st dose (%) | 19 (29.7) | 28 (18.5) | 0.071 n | 22 (23.7) | 25 (20.5) | 0.578 |
Proportion of specific AR (% of vaccinees with an AR) | Malaise after any dose (%) | 4 (6.3) | 24 (15.9) | 0.055 n | 9 (9.7) | 19 (15.6) | 0.203 |
Malaise after 2nd dose (%) | 3 (4.7) | 19 (12.6) | 0.081 n | 8 (8.6) | 14 (11.5) | 0.491 | |
Severe malaise after any dose (%) | 1 (1.6) | 15 (9.9) | 0.033 | 4 (4.3) | 12 (9.8) | 0.126 | |
Severe malaise after 2nd dose (%) | 1 (1.6) | 13 (8.6) | 0.056 n | 4 (4.3) | 10 (8.2) | 0.251 | |
Fever after 1st dose (%) | 4 (6.3) | 20 (13.2) | 0.136 | 5 (5.4) | 19 (15.6) | 0.019 | |
Severe fever after any dose (%) | 0 (0.0) | 7 (4.6) | 0.080 n | 0 (0.0) | 7 (5.7) | 0.019 | |
Severe fever after 2nd dose (%) | 0 (0.0) | 5 (3.3) | 0.141 | 0 (0.0) | 5 (4.1) | 0.048 | |
Severe fatigue after any dose (%) | 9 (14.1) | 10 (6.6) | 0.079 n | 13 (14.0) | 6 (4.9) | 0.020 | |
Arm pain after any dose (%) | 15 (23.4) | 38 (25.2) | 0.788 | 17 (18.3) | 36 (29.5) | 0.058 n | |
Arm pain after 1st dose (%) | 9 (14.1) | 27 (17.9) | 0.493 | 10 (10.8) | 26 (21.3) | 0.040 | |
Lymphadenopathy after any dose (%) | 0 (0.0) | 6 (4.0) | 0.106 | 0 (0.0) | 6 (4.9) | 0.030 | |
Lymphadenopathy after 2nd dose (%) | 0 (0.0) | 5 (3.3) | 0.141 | 0 (0.0) | 5 (4.1) | 0.048 | |
Severe myalgia after 1st dose (%) | 2 (3.1) | 7 (4.6) | 0.613 | 0 (0.0) | 4 (3.3) | 0.078 n | |
Severe injection site swelling after any dose (%) | 0 (0.0) | 4 (2.6) | 0.189 | 0 (0.0) | 4 (3.3) | 0.078 n | |
Severe injection site swelling after 1st dose (%) | 0 (0.0) | 4 (2.6) | 0.189 | 0 (0.0) | 4 (3.3) | 0.078 n |
Sensitivity Analysis 1 | |||||||
---|---|---|---|---|---|---|---|
N = 3563 | Antibody Positiveness | p-Value | Antibody Titres | p-Value | |||
Negative Antibody Titres (n = 76) | Positive Antibody Titres (n = 3487) | Antibody Titres below Median * (n = 440) | Antibody Titres above Median * (n = 3123) | ||||
Intensity (maximum intensity grade; % vaccinees at each grade) | Grade 1 after any vaccine dose (%) | 15 (23.8) | 350 (12.2) | 0.020 | 62 (16.9) | 303 (11.8) | 0.017 |
Grade 2 after any vaccine dose (%) | 23 (36.5) | 1132 (39.3) | 142 (38.7) | 1013 (39.3) | |||
Grade 3 after any vaccine dose (%) | 25 (39.7) | 1397 (48.5) | 163 (44.4) | 1259 (48.9) | |||
Grade 1 after 2nd vaccine dose (%) | 12 (27.3) | 261 (11.6) | 0.003 | 47 (17.0) | 226 (11.2) | 0.006 | |
Grade 2 after 2nd vaccine dose (%) | 19 (43.2) | 949 (42.3) | 121 (43.8) | 847 (42.1) | |||
Grade 3 after 2nd vaccine dose (%) | 13 (29.5) | 1036 (46.1) | 108 (39.1) | 941 (46.7) | |||
Intensity (mean, SD Likert score) | After any dose (mean, SD) | 5.48 (2.47) | 6.15 (2.36) | 0.031 | 5.91 (2.17) | 6.16 (2.38) | 0.067 n |
After 2nd dose (mean, SD) | 4.95 (2.37) | 6.10 (2.06) | 0.001 | 5.64 (2.14) | 6.14 (2.05) | 0.003 | |
Proportion of ARs (% of vaccinees with an AR) | Any AR after 1st dose (%) | 56 (73.7) | 2222 (63.7) | 0.074 n | 295 (67.0) | 1983 (63.5) | 0.147 |
Any AR after 2nd dose (%) | 45 (59.2) | 2335 (67.0) | 0.156 | 291 (66.1) | 2089 (66.9) | 0.753 | |
Any mild AR after any dose (%) | 29 (38.2) | 1089 (31.2) | 0.198 | 168 (38.2) | 950 (30.4) | 0.001 | |
Any mild AR after 1st dose (%) | 21 (27.6) | 667 (19.1) | 0.063 n | 102 (23.2) | 586 (18.8) | 0.028 | |
Any mild AR after 2nd dose (%) | 17 (22.4) | 622 (17.8) | 0.308 | 99 (22.5) | 540 (17.3) | 0.008 | |
Any severe AR after 2nd dose (%) | 13 (17.1) | 1036 (29.7) | 0.017 | 108 (24.5) | 941 (30.1) | 0.016 | |
Proportion of specific ARs (% of vaccinees with an AR) | Fever after 2nd dose (%) | 11 (14.5) | 974 (27.9) | 0.010 | 114 (25.9) | 871 (27.9) | 0.380 |
Malaise after any dose (%) | 7 (9.2) | 622 (17.8) | 0.050 | 68 (15.5) | 561 (18.0) | 0.200 | |
Malaise after 2nd dose (%) | 4 (5.3) | 517 (14.8) | 0.020 | 56 (12.7) | 465 (14.9) | 0.230 | |
Severe malaise after any dose (%) | 1 (1.2) | 305 (8.8) | 0.010 | 32 (7.3) | 274 (8.8) | 0.290 | |
Severe malaise after 2nd dose (%) | 1 (1.2) | 258 (7.4) | 0.030 | 25 (5.7) | 234 (7.5) | 0.170 | |
Severe arm pain after 2nd dose (%) | 1 (1.3) | 187 (5.4) | 0.120 | 15 (3.4) | 173 (5.5) | 0.060 n | |
Chills after 2nd dose (%) | 2 (2.6) | 385 (11.0) | 0.020 | 35 (8.0) | 352 (11.3) | 0.040 | |
Myalgia after any dose (%) | 5 (6.6) | 709 (20.3) | 0.003 | 94 (21.4) | 620 (19.9) | 0.460 | |
Myalgia after 2nd dose (%) | 4 (5.3) | 621 (17.8) | 0.004 | 79 (18.0) | 546 (17.5) | 0.810 | |
Severe myalgia after 2nd dose (%) | 2 (2.6) | 296 (8.5) | 0.070 n | 29 (6.6) | 269 (8.6) | 0.150 | |
Headache after any dose (%) | 11 (14.5) | 967 (27.7) | 0.010 | 118 (26.8) | 860 (27.5) | 0.750 | |
Headache after 2nd dose (%) | 8 (10.5) | 750 (21.5) | 0.020 | 89 (20.2) | 669 (21.4) | 0.570 | |
Severe headache after any dose (%) | 3 (3.9) | 419 (12.0) | 0.030 | 39 (8.9) | 383 (12.3) | 0.040 | |
Severe headache after 2nd dose (%) | 2 (2.6) | 331 (9.5) | 0.040 | 28 (6.4) | 305 (9.8) | 0.020 |
Sensitivity Analysis 2 | |||||||
---|---|---|---|---|---|---|---|
N = 597 | Antibody Positiveness | p-Value | Antibody Titres | p-Value | |||
Negative Antibody Titres (n = 273) | Positive Antibody Titres (n = 324) | Antibody Titres below Median * (n = 288) | Antibody Titres above Median * (n = 309) | ||||
Intensity (maximum intensity grade; % vaccinees at each grade) | Grade 1 after 1st vaccine dose (%) | 48 (17.6) | 39 (12.0) | 0.050 n | 50 (26.2) | 37 (17.5) | 0.072 n |
Grade 2 after 1st vaccine dose (%) | 79 (28.9) | 94 (29.0) | 81 (42.4) | 92 (43.4) | |||
Grade 3 after 1st vaccine dose (%) | 53 (19.4) | 90 (27.8) | 60 (31.4) | 83 (39.2) | |||
Intensity (mean, SD Likert score) | After 1st dose (mean, SD) | 3.37 (2.99) | 3.83 (3.21) | 0.083 n | 5.28 (2.18) | 5.65 (2.09) | 0.083 n |
After 2nd dose (mean, SD) | 3.63 (3.31) | 3.01 (3.23) | 0.001 | 5.87 (2.13) | 5.77 (2.02) | 0.570 | |
Proportion of ARs (% of vaccinees with) | Any AR after 2nd dose (%) | 187 (68.5) | 188 (58.0) | 0.008 | 193 (67.0) | 182 (58.9) | 0.040 |
Any moderate AR after 1st dose (%) | 99 (36.3) | 139 (42.9) | 0.099 | 103 (35.8) | 135 (43.7) | 0.048 | |
Any moderate AR after 2nd dose (%) | 126 (46.2) | 124 (38.3) | 0.052 n | 129 (44.8) | 121 (39.2) | 0.163 | |
Any severe AR after 1st dose (%) | 53 (19.4) | 90 (27.8) | 0.017 | 60 (20.8) | 83 (26.9) | 0.085 n | |
Proportion of specific ARs (% of vaccinees with) | Fatigue after 1st dose (%) | 21 (7.7) | 20 (6.2) | 0.465 | 24 (8.3) | 43 (13.9) | 0.031 |
Fever after 1st dose (%) | 16 (5.9) | 73 (22.5) | <0.001 | 19 (6.6) | 70 (22.7) | <0.001 | |
Severe fever after 1st dose (%) | 0 (0.0) | 11 (3.4) | 0.002 | 1 (0.3) | 10 (3.2) | 0.009 | |
Malaise after any dose (%) | 37 (13.6) | 76 (23.5) | 0.002 | 41 (14.2) | 72 (23.3) | 0.004 | |
Malaise after 1st dose (%) | 5 (1.8) | 36 (11.1) | <0.001 | 7 (2.4) | 34 (11.0) | <0.001 | |
Severe malaise after any dose (%) | 17 (6.2) | 42 (13.0) | 0.006 | 19 (6.6) | 40 (12.9) | 0.009 | |
Severe malaise after 1st dose (%) | 3 (1.1) | 18 (5.6) | 0.003 | 5 (1.7) | 16 (5.2) | 0.023 | |
Chills after 1st dose (%) | 2 (0.7) | 25 (7.7) | <0.001 | 4 (1.4) | 23 (7.4) | 0.004 | |
Myalgia after 1st dose (%) | 9 (3.3) | 36 (11.1) | 0.003 | 9 (3.1) | 36 (11.7) | <0.001 | |
Severe myalgia after 1st dose (%) | 3 (1.0) | 18 (5.8) | 0.003 | 3 (1.0) | 18 (5.8) | 0.002 | |
Other musculoskeletal disorders after 1st dose (%) | 2 (0.7) | 9 (2.8) | 0.064 n | 3 (1.0) | 8 (2.6) | 0.160 | |
Arthralgia after 1st dose (%) | 0 (0.0) | 10 (3.1) | 0.034 | 1 (0.3) | 9 (2.9) | 0.015 | |
Severe arthralgia after 1st dose (%) | 0 (0.0) | 6 (1.9) | 0.024 | 1 (0.3) | 5 (1.6) | 0.120 | |
Headache after 1st dose (%) | 24 (8.8) | 48 (14.8) | 0.024 | 26 (9.0) | 46 (14.9) | 0.028 | |
Severe headache after 1st dose (%) | 6 (2.2) | 20 (6.2) | 0.018 | 6 (2.1) | 20 (6.5) | 0.009 |
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Sáez-Peñataro, J.; Calvo, G.; Bascuas, J.; Mosquera, M.M.; Marcos, M.Á.; Egri, N.; Torres, F. Association between Reactogenicity and Immunogenicity in a Vaccinated Cohort with Two mRNA SARS-CoV-2 Vaccines at a High-Complexity Reference Hospital: A Post Hoc Analysis on Immunology Aspects of a Prospective Cohort Study. Vaccines 2024, 12, 665. https://doi.org/10.3390/vaccines12060665
Sáez-Peñataro J, Calvo G, Bascuas J, Mosquera MM, Marcos MÁ, Egri N, Torres F. Association between Reactogenicity and Immunogenicity in a Vaccinated Cohort with Two mRNA SARS-CoV-2 Vaccines at a High-Complexity Reference Hospital: A Post Hoc Analysis on Immunology Aspects of a Prospective Cohort Study. Vaccines. 2024; 12(6):665. https://doi.org/10.3390/vaccines12060665
Chicago/Turabian StyleSáez-Peñataro, Joaquín, Gonzalo Calvo, Juan Bascuas, Maria Mar Mosquera, Maria Ángeles Marcos, Natalia Egri, and Ferran Torres. 2024. "Association between Reactogenicity and Immunogenicity in a Vaccinated Cohort with Two mRNA SARS-CoV-2 Vaccines at a High-Complexity Reference Hospital: A Post Hoc Analysis on Immunology Aspects of a Prospective Cohort Study" Vaccines 12, no. 6: 665. https://doi.org/10.3390/vaccines12060665
APA StyleSáez-Peñataro, J., Calvo, G., Bascuas, J., Mosquera, M. M., Marcos, M. Á., Egri, N., & Torres, F. (2024). Association between Reactogenicity and Immunogenicity in a Vaccinated Cohort with Two mRNA SARS-CoV-2 Vaccines at a High-Complexity Reference Hospital: A Post Hoc Analysis on Immunology Aspects of a Prospective Cohort Study. Vaccines, 12(6), 665. https://doi.org/10.3390/vaccines12060665