Multivariate Analysis of Adverse Reactions and Recipient Profiles in COVID-19 Booster Vaccinations: A Prospective Cohort Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Investigation Methods for Adverse Reactions and the Backgrounds of the Recipients
2.3. Statistical Analysis
2.4. Ethical Review
3. Results
3.1. Profile of Study Participants and Adverse Reactions to Vaccinations
3.2. Comparison of Adverse Reactions to the Third and Fourth Doses
3.3. Association between Adverse Reactions and Recipient Profiles in Booster Vaccination
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Third Dose | Fourth Dose | |
---|---|---|
Mean age (SD, range) | 45.6 (12.9, 20–75) | 47.6 (13.1, 24–78) |
Sex | ||
Male: n (%) | 76 (39.2) | 46 (35.1) |
Female: n (%) | 118 (60.8) | 85 (64.9) |
Underlying diseases | ||
Yes: n (%) | 40 (20.6) | 33 (25.4) |
No: n (%) | 154 (79.4) | 98 (74.8) |
Vaccine type | ||
Monovalent Pfizer vaccine (original): n (%) | 178 (91.8) | 48 (36.6) |
Monovalent Moderna vaccine (original): n (%) | 16 (8.2) | 72 (55.0) |
Bivalent Pfizer vaccine (BA.1/BA.4-5): n (%) | 0 | 10 (7.6) |
Bivalent Moderna vaccine (BA.1/BA.4-5): n (%) | 0 | 1 (0.8) |
Homologous or heterologous vaccination | ||
Homologous vaccination: n (%) | 175 (90.2) | 56 (42.7) |
Heterologous vaccination: n (%) | 19 (9.8) | 75 (57.3) |
Mean interval: days since last vaccination (SD, range) | 242.1 (19.3, 183–322) | 204.9 (26.4, 151–296) |
Grade 0 | Grade 1 | Grade 2 | Grade 3 | |
---|---|---|---|---|
Third Dose/Fourth Dose n (%) | Third Dose/Fourth Dose n (%) | Third Dose/Fourth Dose n (%) | Third Dose/Fourth Dose n (%) | |
Injection site reaction | 23 (11.9)/18 (13.7) | 103 (53.1)/67 (51.1) | 60 (30.9)/42 (32.1) | 8 (4.1)/4 (3.7) |
Fatigue | 57 (29.4)/41 (31.3) | 69 (35.6)/38 (29.0) | 51 (26.3)/45 (34.4) | 17 (8.8)/7 (5.3) |
Chills | 137 (70.6)/105 (80.2) | 43 (22.2)/24 (18.3) | 14 (7.2)/2 (1.5) | |
Fever | 143 (73.7)/100 (76.3) | 41 (21.1)/28 (21.4) | 10 (5.2)/3 (2.3) | |
Arthralgia | 117 (60.3)/83 (63.4) | 49 (25.3)/26 (19.8) | 21 (10.8)/18 (13.7) | 7 (3.6)/4 (3.1) |
Myalgia | 107 (55.2)/84 (64.1) | 61 (31.4)/29 (22.1) | 20 (10.3)/18 (13.7) | 6 (3.1)/0 (0) |
Headache | 95 (49.0)/70 (53.4) | 57 (29.4)/32 (24.4) | 33 (17.0)/23 (17.6) | 9 (4.6)/6 (4.6) |
Diarrhea | 185 (95.4)/126 (96.2) | 9 (4.6)/5 (3.8) | ||
Nausea | 160 (82.5)/112 (85.5) | 20 (10.3)/11 (8.4) | 9 (4.6)/8 (6.1) | 5 (2.6)/0 (0) |
Worst adverse reaction | 10 (5.2)/8 (6.1) | 85 (43.8)/55 (42.0) | 77 (39.7)/56 (42.7) | 22 (11.3)/12 (9.2) |
Grade 0 | Grade 1–3 | χ2 (df = 1) | OR (95% CI) | p Value | |
---|---|---|---|---|---|
Third Dose/Fourth Dose n (%) | Third Dose/Fourth Dose n (%) | ||||
Injection site reaction | 23 (11.9)/18 (13.7) | 171 (88.1)/113 (86.3) | 0.25 | 0.84 (0.44–1.64) | 0.62 |
Fatigue | 57 (29.4)/41 (31.3) | 137 (70.6)/90 (68.7) | 0.14 | 0.91 (0.56–1.48) | 0.71 |
Chills | 137 (70.6)/105 (80.2) | 57 (29.4)/26 (19.8) | 3.74 | 0.60 (0.35–1.01) | 0.05 |
Fever | 143 (73.7)/100 (76.3) | 51 (26.3)/31 (23.7) | 0.29 | 0.87 (0.52–1.45) | 0.59 |
Arthralgia | 117 (60.3)/83 (63.4) | 77 (39.7)/48 (36.6) | 0.31 | 0.88 (0.56–1.39) | 0.58 |
Myalgia | 107 (55.2)/84 (64.1) | 87 (44.8)/47 (35.9) | 2.60 | 0.69 (0.44–1.09) | 0.11 |
Headache | 95 (49.0)/70 (53.4) | 99 (51.0)/61 (46.6) | 0.62 | 0.84 (0.54–1.30) | 0.43 |
Diarrhea | 185 (95.4)/126 (96.2) | 9 (4.6)/5 (3.8) | 0.13 | 0.82 (0.27–2.49) | 0.72 |
Nausea | 160 (82.5)/112 (85.5) | 34 (17.5)/19 (14.5) | 0.52 | 0.80 (0.43–1.47) | 0.47 |
Any adverse reaction | 10 (5.2)/8 (6.1) | 184 (94.8)/123 (93.9) | 0.14 | 0.84 (0.32–2.18) | 0.71 |
Number of Vaccinations | Age (10+) | Sex | Underlying Diseases | Type of Vaccination | Vaccination Interval (30+) | |
---|---|---|---|---|---|---|
OR (95% CI) | OR (95% CI) | OR (95% CI) | OR (95% CI) | OR (95% CI) | OR (95% CI) | |
Univariate model | ||||||
Injection site reaction | 0.84 (0.44–1.64) | 0.52 ** (0.39–0.68) | 2.39 * (1.23–4.64) | 0.76 (0.36–1.61) | 1.98 (0.94–4.21) | 1.29 (0.92–1.81) |
Fatigue | 0.91 (0.56–1.48) | 0.72 ** (0.60–0.87) | 2.11 ** (1.30–3.42) | 0.72 (0.42–1.26) | 0.93 (0.61–1.42) | 1.09 (0.85–1.39) |
Chills | 0.60 (0.35–1.01) | 0.69 ** (0.56–0.85) | 2.11 ** (1.21–3.69) | 0.39 * (0.19–0.80) | 0.93 (0.59–1.47) | 1.28 (0.98–1.67) |
Fever | 0.87 (0.52–1.45) | 0.72 ** (0.58–0.88) | 2.07 * (1.18–3.61) | 0.25 ** (0.11–0.57) | 1.05 (0.67–1.65) | 1.13 (0.87–1.47) |
Arthralgia | 0.88 (0.56–1.39) | 0.70 ** (0.59–0.85) | 1.56 (0.98–2.51) | 0.44 ** (0.25–0.80) | 0.89 (0.59–1.34) | 1.12 (0.89–1.42) |
Myalgia | 0.69 (0.44–1.09) | 0.87 (0.73–1.03) | 1.49 (0.94–2.37) | 0.54 * (0.31–0.94) | 0.75 (0.49–1.13) | 1.25 (0.99–1.58) |
Headache | 0.84 (0.54–1.30) | 0.67 ** (0.56–0.80) | 3.98 ** (2.46–6.46) | 0.61 (0.36–1.03) | 1.29 (0.87–1.93) | 1.34 * (1.06–1.69) |
Diarrhea | 0.82 (0.27–2.49) | 0.51 ** (0.31–0.85) | 1.53 (0.47–4.98) | 0.26 (0.03–1.99) | 1.31 (0.54–3.16) | 0.89 (0.51–1.54) |
Nausea | 0.80 (0.43–1.47) | 0.87 (0.69–1.10) | 2.63 ** (1.30–5.34) | 0.31 * (0.12–0.82) | 0.92 (0.53–1.59) | 1.22 (0.89–1.66) |
Any adverse reaction | 0.84 (0.32–2.18) | 0.27 ** (0.16–0.45) | 4.72 ** (1.64–13.60) | 0.34 * (0.13–0.88) | 1.64 (0.58–4.66) | 1.19 (0.73–1.95) |
Multivariate model | ||||||
Injection site reaction | 0.51 (0.16–1.66) | 0.54 ** (0.39–0.73) | 1.54 (0.74–3.22) | 1.52 (0.65–3.52) | 2.05 (0.79–5.35) | 0.84 (0.51–1.40) |
Fatigue | 1.06 (0.46–2.42) | 0.74 ** (0.60–0.91) | 1.94 * (1.16–3.26) | 1.02 (0.56–1.87) | 0.73 (0.41–1.30) | 0.93 (0.65–1.33) |
Chills | 0.51 (0.21–1.23) | 0.75 * (0.60–0.94) | 1.84 * (1.03–3.31) | 0.52 (0.25–1.11) | 1.14 (0.61–2.11) | 0.94 (0.64–1.37) |
Fever | 0.84 (0.36–2.00) | 0.79 * (0.63–0.99) | 1.77 (0.99–3.17) | 0.31 ** (0.14–0.73) | 1.00 (0.54–1.84) | 0.94 (0.65–1.38) |
Arthralgia | 1.09 (0.50–2.36) | 0.74 ** (0.61–0.91) | 1.35 (0.82–2.23) | 0.57 (0.31–1.06) | 0.76 (0.44–1.33) | 0.98 (0.70–1.38) |
Myalgia | 1.06 (0.50–2.26) | 0.95 (0.78–1.15) | 1.45 (0.89–2.37) | 0.60 (0.33–1.08) | 0.69 (0.40–1.20) | 1.17 (0.84–1.63) |
Headache | 0.89 (0.40–1.97) | 0.74 ** (0.60–0.91) | 3.39 ** (2.04–5.62) | 0.93 (0.51–1.69) | 1.14 (0.65–1.98) | 1.16 (0.82–1.64) |
Diarrhea | 0.18 (0.02–1.30) | 0.47 ** (0.27–0.82) | 1.26 (0.37–4.33) | 0.42 (0.05–3.41) | 2.35 (0.66–8.41) | 0.41 (0.17–1.03) |
Nausea | 1.12 (0.41–3.03) | 1.02 (0.79–1.31) | 2.52 * (1.22–5.24) | 0.35 * (0.13–0.93) | 0.78 (0.38–1.60) | 1.18 (0.76–1.81) |
Any adverse reaction | 0.51 (0.08–3.02) | 0.25 ** (0.14–0.46) | 2.43 (0.70–8.47) | 0.95 (0.31–2.96) | 0.86 (0.21–3.54) | 0.55 (0.26–1.14) |
Number of Vaccinations | Age (10+) | Sex | Underlying Diseases | Cross-Vaccination | Vaccination Interval (30+) | |
---|---|---|---|---|---|---|
OR (95% CI) | OR (95% CI) | OR (95% CI) | OR (95% CI) | OR (95% CI) | OR (95% CI) | |
Multivariate model | ||||||
Injection site reaction | 0.68 (0.22–2.05) | 0.53 ** (0.39–0.72) | 1.61 (0.77–3.37) | 1.52 (0.66–3.51) | 0.64 (0.23–1.75) | 0.90 (0.55–1.48) |
Fatigue | 1.08 (0.51–2.31) | 0.73 ** (0.59–0.90) | 1.97 * (1.17–3.30) | 1.02 (0.56–1.87) | 1.64 (0.86–3.15) | 0.92 (0.65–1.30) |
Chills | 0.50 (0.23–1.12) | 0.75 * (0.60–0.94) | 1.84 * (1.03–3.29) | 0.52 (0.25–1.10) | 0.81 (0.41–1.60) | 0.94 (0.65–1.37) |
Fever | 0.82 (0.37–1.80) | 0.79 * (0.63–0.99) | 1.76 (0.98–3.15) | 0.31 ** (0.14–0.73) | 0.95 (0.48–1.86) | 0.94 (0.65–1.36) |
Arthralgia | 0.91 (0.45–1.85) | 0.74 ** (0.61–0.90) | 1.31 (0.80–2.17) | 0.58 ** (0.31–1.07) | 1.10 (0.60–2.02) | 0.95 (0.68–1.31) |
Myalgia | 0.93 (0.46–1.85) | 0.94 (0.78–1.14) | 1.42 (0.87–2.32) | 0.61 * (0.34–1.09) | 1.35 (0.74–2.47) | 1.13 (0.82–1.55) |
Headache | 1.04 (0.50–2.15) | 0.74 ** (0.60–0.91) | 3.47 ** (2.09–5.75) | 0.93 (0.51–1.69) | 1.07 (0.58–2.00) | 1.19 * (0.85–1.67) |
Diarrhea | 0.28 (0.05–1.55) | 0.48 ** (0.28–0.83) | 1.29 (0.38–4.37) | 0.40 (0.05–3.22) | 0.57 (0.15–2.16) | 0.46 (0.19–1.11) |
Nausea | 1.18 (0.48–2.96) | 1.01 (0.78–1.31) | 2.57 * (1.24–5.34) | 0.35 * (0.13–0.93) | 1.61 (0.70–3.69) | 1.18 (0.77–1.79) |
Any adverse reaction | 0.90 (0.17–4.84) | 0.22 ** (0.12–0.43) | 2.85 (0.80–10.20) | 0.95 * (0.30–2.97) | 3.44 (0.67–17.59) | 0.59 (0.29–1.22) |
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Urakawa, R.; Isomura, E.T.; Matsunaga, K.; Kubota, K. Multivariate Analysis of Adverse Reactions and Recipient Profiles in COVID-19 Booster Vaccinations: A Prospective Cohort Study. Vaccines 2023, 11, 1513. https://doi.org/10.3390/vaccines11101513
Urakawa R, Isomura ET, Matsunaga K, Kubota K. Multivariate Analysis of Adverse Reactions and Recipient Profiles in COVID-19 Booster Vaccinations: A Prospective Cohort Study. Vaccines. 2023; 11(10):1513. https://doi.org/10.3390/vaccines11101513
Chicago/Turabian StyleUrakawa, Ryuta, Emiko Tanaka Isomura, Kazuhide Matsunaga, and Kazumi Kubota. 2023. "Multivariate Analysis of Adverse Reactions and Recipient Profiles in COVID-19 Booster Vaccinations: A Prospective Cohort Study" Vaccines 11, no. 10: 1513. https://doi.org/10.3390/vaccines11101513