Abstract
This survey study assesses the occurrence of short-term adverse events in adults 60 years or older who received a booster dose of the BNT162B2 mRNA vaccine.
Introduction
On July 29, 2021, concerns of waning immunity after Pfizer-BioNTech BNT162B2 mRNA vaccination led the Israeli Ministry of Health to start a campaign to administer booster (third) doses to individuals who received their second dose at least 5 months prior.1,2 The booster was initially approved for individuals 60 years or older. This survey study assessed the occurrence of adverse effects (AEs) in adults 60 years or older who received a booster dose.
Methods
This study was conducted among members of Clalit Health Services (CHS), which insures more than half of the Israeli population. Study participants were individuals 60 years or older who received the booster dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine in the first 5 days of the campaign (July 30 to August 3, 2021). The CHS institutional review board approved this study, with a waiver of informed consent because deidentified survey data were used. This study followed the AAPOR reporting guideline for survey studies.
Individuals aged 60 to 79 years were sent a text message with a request to complete an online survey (eTable in the Supplement) regarding AEs. For those 80 years or older, a random sample (41.8%) was contacted by telephone and interviewed.
The survey process comprised 2 sequential surveys conducted 5 to 11 days (August 8-10, 2021) and 20 to 28 days (August 23-26, 2021) after the initiation of the campaign. For participants who responded to both surveys, we considered only the latter response. Individuals’ demographic and clinical characteristics were extracted from their electronic health records.
Results
Of 82 392 CHS members 60 years or older who received a booster dose during the study period, 66 094 were contacted, with 27 046 (40.9%) responding to the survey. The median age of respondents was 71 years (IQR, 66-75 years); 43.6% of respondents were aged 60 to 69 years; 44.5%, 70 to 79 years; and 12.0%, 80 years or older. The proportion of female respondents was 45.3%, and 49.2% had at least 1 risk factor for severe COVID-19 (Table 1).
Table 1. Baseline Characteristics of the Study Population.
| Characteristic | No. (%) | |
|---|---|---|
| Respondents (N = 27 046) | Nonrespondents (N = 39 020) | |
| Age, median (IQR) | 71 (65-75) | 71 (66-76) |
| Age group | ||
| 60-69 | 11 779 (43.6) | 16 212 (41.5) |
| 70-79 | 12 035 (44.5) | 18 257 (46.8) |
| ≥80 | 3232 (12.0) | 4551 (11.7) |
| Sex | ||
| Female | 12 258 (45.3) | 18 619 (47.7) |
| Male | 14 788 (54.7) | 20 401 (52.3) |
| Population sector | ||
| General Jewish | 25 781 (95.3) | 36 124 (92.6) |
| Ultra-Orthodox Jewish | 544 (2.0) | 1056 (2.7) |
| Arab | 719 (2.7) | 1835 (4.7) |
| Other | 2 (<0.1) | 5 (<0.1) |
| Socioeconomic status | ||
| Low | 3925 (14.5) | 8762 (22.5) |
| Medium | 11 977 (44.3) | 17 185 (44.0) |
| High | 10 970 (40.6) | 12 618 (32.3) |
| Missing | 174 (0.6) | 455 (1.2) |
| Nursing home resident | 320 (1.2) | 1331 (3.4) |
| Risk factors for severe COVID-19a | ||
| 0 | 13 740 (50.8) | 18 157 (46.5) |
| 1 | 9100 (33.6) | 13 576 (34.8) |
| 2 | 3092 (11.4) | 5264 (13.5) |
| ≥3 or more | 1114 (4.1) | 2023 (5.2) |
Based on US Centers for Disease Control and Prevention criteria.
Of the respondents, 30.0% reported at least 1 AE, 24.8% reported local reactions, and 16.6% reported systemic reactions. The most common AEs included pain at the injection site (23.5%), fatigue (9.7%), and malaise (7.2%) (Table 2).
Table 2. Reports of Adverse Events According to Sex and Age Group.
| Variable | Respondents, No. (%) | |||||
|---|---|---|---|---|---|---|
| Total | Sex | Age, y | ||||
| Female | Male | 60-69 | 70-79 | ≥80 | ||
| Any adverse event | 8120 (30.0) | 4778 (39.0) | 3342 (22.6) | 3915 (33.2) | 3005 (25.0) | 1200 (37.0) |
| Local reaction | 6713 (24.8) | 4082 (33.3) | 2631 (17.8) | 3283 (27.9) | 2421 (20.1) | 1009 (31.1) |
| Pain at injection site | 6346 (23.5) | 3853 (31.4) | 2493 (16.9) | 3109 (26.4) | 2288 (19.0) | 949 (29.2) |
| Swelling at injection site | 1399 (5.2) | 1051 (8.6) | 348 (2.4) | 688 (5.8) | 503 (4.2) | 208 (6.4) |
| Axillary swelling in the injected arm | 356 (1.3) | 297 (2.4) | 59 (0.4) | 228 (1.9) | 100 (0.8) | 28 (0.9) |
| Other local reaction | 1116 (4.1) | 773 (6.3) | 343 (2.3) | 560 (4.8) | 437 (3.6) | 119 (3.7) |
| Systemic reaction | 4495 (16.6) | 2811 (22.9) | 1684 (11.4) | 2418 (20.5) | 1635 (13.6) | 442 (13.6) |
| Fatigue | 2634 (9.7) | 1727 (14.1) | 907 (6.1) | 1419 (12.0) | 924 (7.7) | 291 (9.0) |
| Malaise | 1950 (7.2) | 1316 (10.7) | 634 (4.3) | 1114 (9.5) | 660 (5.5) | 176 (5.4) |
| Muscle ache | 1506 (5.6) | 1041 (8.5) | 465 (3.1) | 901 (7.6) | 500 (4.2) | 105 (3.2) |
| Headache | 1326 (4.9) | 908 (7.4) | 418 (2.8) | 771 (6.5) | 445 (3.7) | 110 (3.4) |
| Low-grade fever (<38°C) | 864 (3.2) | 553 (4.5) | 311 (2.1) | 481 (4.1) | 325 (2.7) | 58 (1.8) |
| Joint aches | 670 (2.5) | 471 (3.8) | 199 (1.3) | 399 (3.4) | 202 (1.7) | 69 (2.1) |
| Nausea | 416 (1.5) | 325 (2.7) | 91 (0.6) | 253 (2.1) | 115 (1.0) | 48 (1.5) |
| Temperature >38°C | 423 (1.6) | 290 (2.4) | 133 (0.9) | 258 (2.2) | 135 (1.1) | 30 (0.9) |
| Vomiting or diarrhea | 167 (0.6) | 123 (1.0) | 44 (0.3) | 82 (0.7) | 60 (0.5) | 25 (0.8) |
| Chest pains | 159 (0.6) | 103 (0.8) | 56 (0.4) | 92 (0.8) | 52 (0.4) | 15 (0.5) |
| Shortness of breath | 110 (0.4) | 65 (0.5) | 45 (0.3) | 56 (0.5) | 32 (0.3) | 22 (0.7) |
| Irregular pulse | 135 (0.5) | 103 (0.8) | 32 (0.2) | 79 (0.7) | 40 (0.3) | 16 (0.5) |
| Disseminated rash | 50 (0.2) | 29 (0.2) | 21 (0.1) | 28 (0.2) | 16 (0.1) | 6 (0.2) |
| Facial rash | 12 (0.0) | 11 (0.1) | 1 (0.0) | 8 (0.1) | 2 (0.0) | 2 (0.1) |
| Other systemic reactions | 464 (1.7) | 271 (2.2) | 193 (1.3) | 200 (1.7) | 178 (1.5) | 86 (2.6) |
| Medical attention for any adverse event | 314 (1.2) | 187 (1.5) | 127 (0.9) | 156 (1.3) | 104 (0.9) | 54 (1.7) |
| Symptom duration, d | ||||||
| <1 | 2350 (8.7) | 1265 (10.3) | 1085 (7.3) | 1119 (9.5) | 819 (6.8) | 412 (12.7) |
| 1-3 | 1340 (5.0) | 903 (7.4) | 437 (3.0) | 637 (5.4) | 502 (4.2) | 201 (6.2) |
| >3 | 4330 (16.0) | 2567 (20.9) | 1763 (11.9) | 2115 (18.0) | 1639 (13.6) | 576 (17.7) |
| Cannot recall | 100 (0.4) | 43 (0.4) | 57 (0.4) | 44 (0.4) | 45 (0.4) | 11 (0.3) |
| Adverse events after second dose | ||||||
| Any reaction | 6198 (22.9) | 3733 (30.5) | 2465 (16.7) | 3309 (28.1) | 2238 (18.6) | 651 (20.0) |
| No reaction | 20 384 (75.4) | 8288 (67.6) | 12 096 (81.8) | 8238 (69.9) | 9595 (79.8) | 2551 (78.6) |
| Cannot recall | 464 (1.7) | 237 (1.9) | 227 (1.5) | 232 (2.0) | 187 (1.6) | 45 (1.4) |
| Third-dose reactions vs second-dose reactions | ||||||
| Felt better | 5064 (18.7) | 2266 (18.5) | 2798 (18.9) | 2537 (21.5) | 2171 (18.1) | 356 (11.0) |
| Felt similar | 18 345 (67.8) | 7818 (63.8) | 10 527 (71.2) | 7479 (63.5) | 8412 (70.0) | 2454 (75.6) |
| Felt worse | 3008 (11.1) | 1857 (15.1) | 1151 (7.8) | 1506 (12.8) | 1167 (9.7) | 335 (10.3) |
| Cannot recall | 629 (2.3) | 317 (2.6) | 312 (2.1) | 257 (2.2) | 270 (2.2) | 102 (3.1) |
Most of the respondents (67.8%) reported that their general feeling after the booster was similar to the feeling after the second dose; 18.7% and 11.1% reported a milder or worse response, respectively. Only 1.2% sought medical attention owing to an AE.
Females were more likely than males to report AEs (39.0% vs 22.6%). The proportion of females who reported systemic reactions was nearly double that of males (22.9% vs 11.4%). Individuals aged 60 to 69 years were more likely to report systemic AEs than were individuals 70 years or older (20.5% vs 13.6%).
Discussion
We found that AEs after the BNT162b2 mRNA vaccine booster dose were generally mild and usually did not require medical care. The proportion of self-reported AEs that occurred in our study was similar or lower than that after the administration of the second vaccine dose in several previous studies.3,4 A study by Menni et al4 found a similar proportion of systemic reactions among older individuals after the second vaccine dose as after the third dose in our study (16.4% vs 16.6%).
The proportion of female respondents who reported systemic AEs was greater than the proportion of male respondents, with higher proportions among participants in the younger age group (60-69 years) than in the older age groups. Similar results were reported in previous studies after administration of the second vaccine dose.3,4,5 A limitation of our study was the different survey methods in different age groups, which might have resulted in differences in reported proportions of AEs.
eTable. Survey Questionnaire
References
- 1.Bar-On YM, Goldberg Y, Mandel M, et al. Protection of BNT162b2 vaccine booster against COVID-19 in Israel. N Engl J Med. 2021;385(15):1393-1400. doi: 10.1056/NEJMoa2114255 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Israeli Ministry of Health . Third dose of COVID-19 vaccines and Moderna vaccine usage [in Hebrew]. Published July 30, 2021. Accessed March 20, 2022. https://www.gov.il/BlobFolder/news/30072021-01/he/NEWS_Corona_3rd-and-moderna-30072021.pdf
- 3.Polack FP, Thomas SJ, Kitchin N, et al. ; C4591001 Clinical Trial Group . Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med. 2020;383(27):2603-2615. doi: 10.1056/NEJMoa2034577 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Menni C, Klaser K, May A, et al. Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study. Lancet Infect Dis. 2021;21(7):939-949. doi: 10.1016/S1473-3099(21)00224-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Cuschieri S, Borg M, Agius S, Souness J, Brincat A, Grech V. Adverse reactions to Pfizer-BioNTech vaccination of healthcare workers at Malta's state hospital. Int J Clin Pract. Published online July 19, 2021. doi: 10.1111/ijcp.14605 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eTable. Survey Questionnaire