The Influence of Time of Day of Vaccination with BNT162b2 on the Adverse Drug Reactions and Efficacy of Humoral Response against SARS-CoV-2 in an Observational Study of Young Adults
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Eligibility and Exclusion Criteria for the Circadian Population
2.3. Blood Collection
2.4. Measurement of Antibodies
2.5. Statistical Analysis
3. Results
3.1. Incidence of ADR Related to the BNT162b2 COVID-19 Vaccine in Young Adults
3.2. Number of ADR Does Not Depend on the Time-of-Day of Vaccination
3.3. Time-of-Day of Vaccination Does Not Alter Levels of Anti-S Antibody
3.4. Past Infection with COVID-19 Elicits a Stronger Humoral Immune Response upon Vaccination
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Largeron, N.; Lévy, P.; Wasem, J.; Bresse, X. Role of Vaccination in the Sustainability of Healthcare Systems. J. Mark. Access Health Policy 2015, 3, 27043. [Google Scholar] [CrossRef] [PubMed]
- Meslé, M.M.; Brown, J.; Mook, P.; Hagan, J.; Pastore, R.; Bundle, N.; Spiteri, G.; Ravasi, G.; Nicolay, N.; Andrews, N.; et al. Estimated Number of Deaths Directly Averted in People 60 Years and Older as a Result of COVID-19 Vaccination in the WHO European Region, December 2020 to November 2021. Eurosurveillance 2021, 26, 2101021. [Google Scholar] [CrossRef] [PubMed]
- Emerging Concepts in the Science of Vaccine Adjuvants|ature Reviews Drug Discovery. Available online: https://www.nature.com/articles/s41573-021-00163-y (accessed on 8 February 2022).
- Ho, N.I.; Huis In ’t Veld, L.G.M.; Raaijmakers, T.K.; Adema, G.J. Adjuvants Enhancing Cross-Presentation by Dendritic Cells: The Key to More Effective Vaccines? Front. Immunol. 2018, 9, 2874. [Google Scholar] [CrossRef] [PubMed]
- Benedict, C.; Cedernaes, J. Could a Good Night’s Sleep Improve COVID-19 Vaccine Efficacy? Lancet Respir. Med. 2021, 9, 447–448. [Google Scholar] [CrossRef]
- Sleep Enhances the Human Antibody Response to Hepatitis a Vaccination-PubMed. Available online: https://pubmed.ncbi.nlm.nih.gov/14508028/ (accessed on 8 February 2022).
- Eskola, J.; Ruuskanen, O.; Soppi, E.; Viljanen, M.K.; Järvinen, M.; Toivonen, H.; Kouvalainen, K. Effect of Sport Stress on Lymphocyte Transformation and Antibody Formation. Clin. Exp. Immunol. 1978, 32, 339–345. [Google Scholar] [PubMed]
- Bruunsgaard, H.; Hartkopp, A.; Mohr, T.; Konradsen, H.; Heron, I.; Mordhorst, C.H.; Pedersen, B.K. In Vivo Cell-Mediated Immunity and Vaccination Response Following Prolonged, Intense Exercise. Med. Sci. Sports Exerc. 1997, 29, 1176–1181. [Google Scholar] [CrossRef] [PubMed]
- Edwards, K.M.; Burns, V.E.; Reynolds, T.; Carroll, D.; Drayson, M.; Ring, C. Acute Stress Exposure Prior to Influenza Vaccination Enhances Antibody Response in Women. Brain Behav. Immun. 2006, 20, 159–168. [Google Scholar] [CrossRef] [PubMed]
- Kohut, M.L.; Cooper, M.M.; Nickolaus, M.S.; Russell, D.R.; Cunnick, J.E. Exercise and Psychosocial Factors Modulate Immunity to Influenza Vaccine in Elderly Individuals. J. Gerontol. Ser. A Biol. Sci. 2002, 57, M557–M562. [Google Scholar] [CrossRef][Green Version]
- Long, J.E.; Ring, C.; Bosch, J.A.; Eves, F.; Drayson, M.T.; Calver, R.; Say, V.; Allen, D.; Burns, V.E. A Life-Style Physical Activity Intervention and the Antibody Response to Pneumococcal Vaccination in Women. Psychosom. Med. 2013, 75, 774–782. [Google Scholar] [CrossRef]
- Zimmermann, P.; Curtis, N. Factors That Influence the Immune Response to Vaccination. Clin. Microbiol. Rev. 2019, 32, e00084-18. [Google Scholar] [CrossRef][Green Version]
- Frontiers|Potential Association between Dietary Fibre and Humoral Response to the Seasonal Influenza Vaccine|Immunology. Available online: https://www.frontiersin.org/articles/10.3389/fimmu.2021.765528/full (accessed on 8 February 2022).
- Penkert, R.R.; Rowe, H.M.; Surman, S.L.; Sealy, R.E.; Rosch, J.; Hurwitz, J.L. Influences of Vitamin A on Vaccine Immunogenicity and Efficacy. Front. Immunol. 2019, 10, 1576. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Rayman, M.P.; Calder, P.C. Optimising COVID-19 Vaccine Efficacy by Ensuring Nutritional Adequacy. Br. J. Nutr. 2021, 126, 1919–1920. [Google Scholar] [CrossRef] [PubMed]
- Baxter, M.; Ray, D.W. Circadian Rhythms in Innate Immunity and Stress Responses. Immunology 2020, 161, 261–267. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Keller, M.; Mazuch, J.; Abraham, U.; Eom, G.D.; Herzog, E.D.; Volk, H.-D.; Kramer, A.; Maier, B. A Circadian Clock in Macrophages Controls Inflammatory Immune Responses. Proc. Natl. Acad. Sci. USA 2009, 106, 21407–21412. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Gibbs, J.E.; Blaikley, J.; Beesley, S.; Matthews, L.; Simpson, K.D.; Boyce, S.H.; Farrow, S.N.; Else, K.J.; Singh, D.; Ray, D.W.; et al. The Nuclear Receptor REV-ERBα Mediates Circadian Regulation of Innate Immunity through Selective Regulation of Inflammatory Cytokines. Proc. Natl. Acad. Sci. USA 2012, 109, 582–587. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Gibbs, J.; Ince, L.; Matthews, L.; Mei, J.; Bell, T.; Yang, N.; Saer, B.; Begley, N.; Poolman, T.; Pariollaud, M.; et al. An Epithelial Circadian Clock Controls Pulmonary Inflammation and Glucocorticoid Action. Nat. Med. 2014, 20, 919–926. [Google Scholar] [CrossRef][Green Version]
- Cermakian, N.; Stegeman, S.K.; Tekade, K.; Labrecque, N. Circadian Rhythms in Adaptive Immunity and Vaccination. Semin. Immunopathol. 2021, 44, 193–207. [Google Scholar] [CrossRef]
- Nobis, C.C.; Laramée, G.D.; Kervezee, L.; Sousa, D.M.D.; Labrecque, N.; Cermakian, N. The Circadian Clock of CD8 T Cells Modulates Their Early Response to Vaccination and the Rhythmicity of Related Signaling Pathways. Proc. Natl. Acad. Sci. USA 2019, 116, 20077–20086. [Google Scholar] [CrossRef][Green Version]
- Druzd, D.; Matveeva, O.; Ince, L.; Harrison, U.; He, W.; Schmal, C.; Herzel, H.; Tsang, A.H.; Kawakami, N.; Leliavski, A.; et al. Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses. Immunity 2017, 46, 120–132. [Google Scholar] [CrossRef][Green Version]
- Feigin, R.D.; Jaeger, R.F.; McKinney, R.W.; Alevizatos, A.C. Live, Attenuated Venezuelan Equine Encephalomyelitis Virus Vaccine. II. Whole-Blood Amino-Acid and Fluorescent-Antibody Studies Following Immunization. Am. J. Trop. Med. Hyg. 1967, 16, 769–777. [Google Scholar] [CrossRef]
- Poellmann, L.; Poellmann, B. Circadian Variations of the Efficiency of Hepatitis b Vaccination. Annu. Rev. Chronopharmacol. 1988, 5, 45–48. [Google Scholar]
- Long, J.E.; Drayson, M.T.; Taylor, A.E.; Toellner, K.M.; Lord, J.M.; Phillips, A.C. Morning Vaccination Enhances Antibody Response over Afternoon Vaccination: A Cluster-Randomised Trial. Vaccine 2016, 34, 2679–2685. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Langlois, P.H.; Smolensky, M.H.; Glezen, W.P.; Keitel, W.A. Diurnal Variation in Responses to Influenza Vaccine. Chronobiol. Int. 1995, 12, 28–36. [Google Scholar] [CrossRef] [PubMed]
- Phillips, A.C.; Gallagher, S.; Carroll, D.; Drayson, M. Preliminary Evidence That Morning Vaccination Is Associated with an Enhanced Antibody Response in Men. Psychophysiology 2008, 45, 663–666. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Karabay, O.; Temel, A.; Koker, A.G.; Tokel, M.; Ceyhan, M.; Kocoglu, E. Influence of Circadian Rhythm on the Efficacy of the Hepatitis B Vaccination. Vaccine 2008, 26, 1143–1144. [Google Scholar] [CrossRef] [PubMed]
- Gottlob, S.; Gille, C.; Poets, C.F. Randomized Controlled Trial on the Effects of Morning versus Evening Primary Vaccination on Episodes of Hypoxemia and Bradycardia in Very Preterm Infants. NEO 2019, 116, 315–320. [Google Scholar] [CrossRef] [PubMed]
- de Bree, L.C.J.; Mourits, V.P.; Koeken, V.A.C.M.; Moorlag, S.J.C.F.M.; Janssen, R.; Folkman, L.; Barreca, D.; Krausgruber, T.; Fife-Gernedl, V.; Novakovic, B.; et al. Circadian Rhythm Influences Induction of Trained Immunity by BCG Vaccination. J. Clin. Investig. 2020, 130, 5603–5617. [Google Scholar] [CrossRef] [PubMed]
- Zhang, H.; Liu, Y.; Liu, D.; Zeng, Q.; Li, L.; Zhou, Q.; Li, M.; Mei, J.; Yang, N.; Mo, S.; et al. Time of Day Influences Immune Response to an Inactivated Vaccine against SARS-CoV-2. Cell Res. 2021, 31, 1215–1217. [Google Scholar] [CrossRef]
- Wang, W.; Balfe, P.; Eyre, D.W.; Lumley, S.F.; O’Donnell, D.; Warren, F.; Crook, D.W.; Jeffery, K.; Matthews, P.C.; Klerman, E.B.; et al. Time of Day of Vaccination Affects SARS-CoV-2 Antibody Responses in an Observational Study of Health Care Workers. J. Biol. Rhythm. 2022, 37, 124–129. [Google Scholar] [CrossRef]
- Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Pérez Marc, G.; Moreira, E.D.; Zerbini, C.; et al. Safety and Efficacy of the BNT162b2 MRNA Covid-19 Vaccine. N. Engl. J. Med. 2020, 383, 2603–2615. [Google Scholar] [CrossRef]
- Hou, Y.-C.; Lu, K.-C.; Kuo, K.-L. The Efficacy of COVID-19 Vaccines in Chronic Kidney Disease and Kidney Transplantation Patients: A Narrative Review. Vaccines 2021, 9, 885. [Google Scholar] [CrossRef] [PubMed]
- Luxi, N.; Giovanazzi, A.; Capuano, A.; Crisafulli, S.; Cutroneo, P.M.; Fantini, M.P.; Ferrajolo, C.; Moretti, U.; Poluzzi, E.; Raschi, E.; et al. COVID-19 Vaccination in Pregnancy, Paediatrics, Immunocompromised Patients, and Persons with History of Allergy or Prior SARS-CoV-2 Infection: Overview of Current Recommendations and Pre- and Post-Marketing Evidence for Vaccine Efficacy and Safety. Drug Saf. 2021, 44, 1247–1269. [Google Scholar] [CrossRef] [PubMed]
- Thakkar, A.; Gonzalez-Lugo, J.D.; Goradia, N.; Gali, R.; Shapiro, L.C.; Pradhan, K.; Rahman, S.; Kim, S.Y.; Ko, B.; Sica, R.A.; et al. Seroconversion Rates Following COVID-19 Vaccination among Patients with Cancer. Cancer Cell 2021, 39, 1081–1090.e2. [Google Scholar] [CrossRef] [PubMed]
- Bar-On, Y.M.; Goldberg, Y.; Mandel, M.; Bodenheimer, O.; Freedman, L.; Kalkstein, N.; Mizrahi, B.; Alroy-Preis, S.; Ash, N.; Milo, R.; et al. Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel. N. Engl. J. Med. 2021, 385, 1393–1400. [Google Scholar] [CrossRef] [PubMed]
- Sengupta, S.; Brooks, T.G.; Grant, G.R.; FitzGerald, G.A. Accounting for Time: Circadian Rhythms in the Time of COVID-19. J. Biol. Rhythm. 2021, 36, 4–8. [Google Scholar] [CrossRef] [PubMed]
- Amir, M.; Campbell, S.; Kamenecka, T.M.; Solt, L.A. Pharmacological Modulation and Genetic Deletion of REV-ERBα and REV-ERBβ Regulates Dendritic Cell Development. Biophys. Res. Commun. 2020, 527, 1000–1007. [Google Scholar] [CrossRef] [PubMed]
- Born, J.; Lange, T.; Hansen, K.; Mölle, M.; Fehm, H.L. Effects of Sleep and Circadian Rhythm on Human Circulating Immune Cells. J. Immunol. 1997, 158, 4454–4464. [Google Scholar] [PubMed]
- Holtkamp, S.J.; Ince, L.M.; Barnoud, C.; Schmitt, M.T.; Sinturel, F.; Pilorz, V.; Pick, R.; Jemelin, S.; Mühlstädt, M.; Boehncke, W.-H.; et al. Circadian Clocks Guide Dendritic Cells into Skin Lymphatics. Nat. Immunol. 2021, 22, 1375–1381. [Google Scholar] [CrossRef] [PubMed]
- Fortier, E.E.; Rooney, J.; Dardente, H.; Hardy, M.-P.; Labrecque, N.; Cermakian, N. Circadian Variation of the Response of T Cells to Antigen. J. Immunol. 2011, 187, 6291–6300. [Google Scholar] [CrossRef]
- Shimba, A.; Ikuta, K. Glucocorticoids Regulate Circadian Rhythm of Innate and Adaptive Immunity. Front. Immunol. 2020, 11, 2143. [Google Scholar] [CrossRef]
- Wu, Y.; Tao, B.; Zhang, T.; Fan, Y.; Mao, R. Pan-Cancer Analysis Reveals Disrupted Circadian Clock Associates with T Cell Exhaustion. Front. Immunol. 2019, 10, 2451. Available online: https://www.frontiersin.org/articles/10.3389/fimmu.2019.02451/full (accessed on 10 February 2022). [CrossRef] [PubMed]
- Giri, A.; Srinivasan, A.; Sundar, I.K. COVID-19: Sleep, Circadian Rhythms and Immunity–Repurposing Drugs and Chronotherapeutics for SARS-CoV-2. Front. Neurosci. 2021, 15, 674204. Available online: https://www.frontiersin.org/articles/10.3389/fnins.2021.674204/full (accessed on 10 February 2022). [CrossRef] [PubMed]
- Barnoud, C.; Wang, C.; Scheiermann, C. Timing Vaccination against SARS-CoV-2. Cell Res. 2021, 31, 1146–1147. [Google Scholar] [CrossRef] [PubMed]
- Kurupati, R.K.; Kossenkoff, A.; Kannan, S.; Haut, L.H.; Doyle, S.; Yin, X.; Schmader, K.E.; Liu, Q.; Showe, L.; Ertl, H.C.J. The Effect of Timing of Influenza Vaccination and Sample Collection on Antibody Titers and Responses in the Aged. Vaccine 2017, 35, 3700–3708. [Google Scholar] [CrossRef] [PubMed]
- Grubeck-Loebenstein, B. Fading Immune Protection in Old Age: Vaccination in the Elderly. J. Comp. Pathol. 2010, 142 (Suppl. S1), S116–S119. [Google Scholar] [CrossRef] [PubMed]
- Gross, P.A.; Hermogenes, A.W.; Sacks, H.S.; Lau, J.; Levandowski, R.A. The Efficacy of Influenza Vaccine in Elderly Persons. A Meta-Analysis and Review of the Literature. Ann. Intern. Med. 1995, 123, 518–527. [Google Scholar] [CrossRef] [PubMed]
- Hood, S.; Amir, S. The Aging Clock: Circadian Rhythms and Later Life. J. Clin. Investig. 2017, 127, 437–446. [Google Scholar] [CrossRef]
n | % of Group | Mean ± SD /Median (Q1;Q3) | Range | |
---|---|---|---|---|
N | 1324 | 100.0 | ||
Sex, female | 959 | 77.7 | ||
Age at first dose, years | 1320 | 23.34 ± 0.05 | 20–37 | |
Body mass index (BMI) | 1324 | 21.86 ± 0.09 | 15.79–45.51 | |
COVID-PCR positive before first dose | 57 | 4.6 | ||
COVID-PCR positive between first and second dose | 3 | 0.2 | ||
COVID-PCR positive after second dose | 3 | 0.2 | ||
Cancer | 7 | 0.5 | ||
Autoimmune disease | 128 | 9.7 | ||
Type I-IV hypersensitivity disease | 210 | 15.9 | ||
Primary immunodeficiency | 7 | 0.5 | ||
Transplant recipient | 1 | 0.1 | ||
Taking steroids or other immunomodulatory drugs | 28 | 2.1 | ||
Pharmacological treatment of mental disorders | 134 | 10.1 | ||
Alcohol overuse | 10 | 0.8 |
Studied Timepoint/Sex | MD (95% CI) | p | ||
---|---|---|---|---|
First Dose | Second Dose | |||
Number of ADR (all participants) | 1.00 (0.00;2.00) | 1.00 (0.00;4.00) | 0.00 (0.0000;0.0000) | <0.001 |
Females | Males | |||
Number of ADR after first dose | 1.00 (0.00;2.00) | 1.00 (0.00;1.00) | 0.00 (0.0000;0.0000) | 0.040 |
Number of ADR after second dose | 1.00 (0.00;4.00) | 1.00 (0.00;3.00) | 0.00 (−0.0001;0.0000) | 0.059 |
Females | Males | RR (95% CI) | p | |
---|---|---|---|---|
ADR after first dose, n (%) | ||||
Pain at the injection site | 571 (59.5%) | 202 (55.3%) | 0.93 (0.84;1.03) | 0.186 |
Reddening at the injection site | 67 (7.0%) | 27 (7.4%) | 1.06 (0.69;1.63) | 0.888 |
Elevated body temperature (>37.5 °C) | 59 (6.2%) | 23 (6.3%) | 1.02 (0.64;1.63) | >0.999 |
Chills | 69 (7.2%) | 21 (5.8%) | 0.80 (0.50;1.28) | 0.418 |
Headache | 125 (13.0%) | 31 (8.5%) | 0.65 (0.45;0.95) | 0.028 |
Muscle pain | 140 (14.6%) | 40 (11.0%) | 0.75 (0.54;1.04) | 0.102 |
Arthralgia | 54 (5.6%) | 16 (4.4%) | 0.78 (0.45;1.34) | 0.442 |
Cough | 5 (0.5%) | 0 (0.0%) | n/a | 0.378 |
Dyspnea | 2 (0.2%) | 0 (0.0%) | n/a | 0.935 |
Insomnia | 35 (3.6%) | 10 (2.7%) | 0.75 (0.38;1.50) | 0.518 |
Tiredness | 22 (2.3%) | 9 (2.5%) | 1.07 (0.50;2.31) | >0.999 |
Nausea | 9 (0.9%) | 2 (0.5%) | 0.58 (0.13;2.69) | 0.718 |
Lymphadenopathy | 22 (2.3%) | 14 (3.8%) | 1.67 (0.86;3.23) | 0.176 |
Diarrhea | 7 (0.7%) | 2 (0.5%) | 0.75 (0.16;3.60) | >0.999 |
ADR after second dose, n (%) | ||||
Pain at the injection site | 494 (51.5%) | 177 (48.5%) | 0.94 (0.83;1.06) | 0.357 |
Reddening at the injection site | 60 (6.3%) | 30 (8.2%) | 1.31 (0.86;2.00) | 0.252 |
Elevated body temperature (>37.5 °C) | 248 (25.9%) | 78 (21.4%) | 0.83 (0.66;1.03) | 0.105 |
Chills | 262 (27.3%) | 82 (22.5%) | 0.82 (0.66;1.02) | 0.084 |
Headache | 291 (30.3%) | 89 (24.4%) | 0.80 (0.65;0.99) | 0.038 |
Muscle pain | 307 (32.0%) | 98 (26.8%) | 0.84 (0.69;1.02) | 0.079 |
Arthralgia | 144 (15.0%) | 33 (9.0%) | 0.60 (0.42;0.86) | 0.006 |
Cough | 7 (0.7%) | 4 (1.1%) | 1.50 (0.44;5.10) | 0.751 |
Dyspnea | 7 (0.7%) | 2 (0.5%) | 0.75 (0.16;3.60) | >0.999 |
Insomnia | 72 (7.5%) | 30 (8.2%) | 1.09 (0.73;1.65) | 0.750 |
Tiredness | 41 (4.3%) | 19 (5.2%) | 1.22 (0.72;2.07) | 0.562 |
Nausea | 20 (2.1%) | 3 (0.8%) | 0.39 (0.12;1.32) | 0.181 |
Lymphadenopathy | 71 (7.4%) | 17 (4.7%) | 0.63 (0.38;1.05) | 0.095 |
Diarrhea | 10 (1.0%) | 2 (0.5%) | 0.53 (0.12;2.39) | 0.600 |
n | % of Group | Means ± SD /Median (Q1;Q3) | Range | |
---|---|---|---|---|
Number of participants | 435 | 100.0 | ||
Sex, female | 331 | 76.1 | ||
Age at first dose, years | 435 | 23.25 ± 1.79 | 20–29 | |
BMI | 435 | 21.71 ± 3.26 | 16.11–45.42 | |
Anti-N, positive (>1) | 91 | 20.9 | ||
Anti-S, BAU/mL × 1000 | 435 | 102.92 ± 59.97 | 3.58–323.00 | |
First dose time | ||||
Before 11 am | 182 | 41.8 | ||
11:01 am–2:59 pm | 16 | 3.7 | ||
After 3 pm | 237 | 54.5 | ||
Second dose time | ||||
Before 11 am | 173 | 39.8 | ||
11:01 am–2:59 pm | 83 | 19.1 | ||
After 3 pm | 179 | 41.1 | ||
COVID-PCR positive before first dose | 31 | 7.1 | ||
COVID-PCR positive between first and second dose | 1 | 0.2 | ||
COVID-PCR positive after second dose | 1 | 0.2 | ||
Part-time job during the night | 12 | 2.8 | ||
Part-time job during the night for at least 2 weeks with at least 3 night shifts per week | 4 | 0.9 | ||
Declared chronotype | ||||
No preferences | 107 | 24.6 | ||
Early bird (usually sleeps between 11 pm–7 am) | 169 | 38.9 | ||
Night owl (usually sleeps between 2–10 am) | 159 | 36.6 | ||
Experienced at least 1 ADR after first dose | 263 | 60.5 | ||
Pain at the injection site | 255 | 58.6 | ||
Reddening at the injection site | 33 | 7.6 | ||
Elevated body temperature (>37.5 °C) | 27 | 6.2 | ||
Chills | 23 | 5.3 | ||
Headache | 51 | 11.7 | ||
Muscle pain | 59 | 13.6 | ||
Arthralgia | 13 | 3.0 | ||
Cough | 2 | 0.5 | ||
Dyspnea | 0 | 0.0 | ||
Diarrhea | 4 | 0.9 | ||
Insomnia | 16 | 3.7 | ||
Lymphadenopathy | 11 | 2.5 | ||
Anaphylaxis | 0 | 0.0 | ||
Acute peripheral facial palsy | 0 | 0.0 | ||
Experienced at least 1 ADR after second dose | 262 | 60.2 | ||
Pain at the injection site | 217 | 49.9 | ||
Reddening at the injection site | 26 | 6.0 | ||
Elevated body temperature (>37.5 °C) | 100 | 23.0 | ||
Chills | 107 | 24.6 | ||
Headache | 121 | 27.8 | ||
Muscle pain | 136 | 31.3 | ||
Arthralgia | 60 | 13.8 | ||
Cough | 6 | 1.4 | ||
Dyspnea | 4 | 0.9 | ||
Diarrhea | 3 | 0.7 | ||
Insomnia | 33 | 7.6 | ||
Lymphadenopathy | 39 | 9.0 | ||
Anaphylaxis | 0 | 0.0 | ||
Acute peripheral facial palsy | 0 | 0.0 | ||
Number of ADR after first dose | 494 | n/a | 1.00 (0.00;2.00) | 0–12 |
Number of ADR after second dose | 852 | n/a | 1.00 (0.00;4.00) | 0–11 |
Studied Population | MD (95% CI) | p | ||
---|---|---|---|---|
Group 1 + 2 | Group 3 + 4 | |||
Number of ADR after first dose | 1.00 (0.00;2.00) | 1.00 (0.00;2.00) | 0.00 (0.0000;0.0000) | 0.319 |
Number of ADR after second dose | 2.00 (0.00;4.00) | 1.00 (0.00;4.00) | −1.00 (0.0000;0.0000) | 0.107 |
second dose before11 am | second dose after 3 pm | |||
Number of ADR after second dose | 2.00 (0.00;4.00) | 1.00 (0.00;4.00) | −1.00 (−0.0001;0.0000) | 0.051 |
Group 1 | Group 3 | |||
Number of ADR after second dose | 2.00 (0.00;4.00) | 1.00 (0.00;4.00) | −1.00 (−0.0001;0.0000) | 0.054 |
Anti-N Positive | Anti-N in Norm | MD (95% CI) | p | |
---|---|---|---|---|
Number of ADR after first dose | 1.00 (0.00;2.00) | 1.00 (0.00;2.00) | 0.00 (0.0000; 0.0001) | 0.092 |
Number of ADR after second dose | 0.00 (0.00;3.00) | 1.50 (0.00;4.00) | 1.50 (0.0000; 1.0000) | 0.001 |
Group 1 + 2 | Group 3 + 4 | MD (95% CI) | p | |
---|---|---|---|---|
All | 104.73 ± 60.41 | 99.53 ± 59.19 | 5.20 (−6.63;17.03) | 0.388 |
All excl. anti-N positive | 98.92 ± 57.48 | 92.11 ± 52.57 | 6.81 (−5.12;18.75) | 0.262 |
Females | 103.57 ± 60.64 | 97.11 ± 54.01 | 6.46 (−6.66;19.58) | 0.333 |
Females excl. anti-N positive | 98.97 ± 58.10 | 90.61 ± 48.96 | 8.36 (−4.92;21.63) | 0.216 |
Males | 108.76 ± 60.20 | 106.40 ± 71.94 | 2.36(−24.23;28.95) | 0.861 |
Males excl. anti-N positive | 98.77 ± 56.00 | 96.85 ± 63.00 | 1.92 (−25.39;29.23) | 0.889 |
Anti-N Positive | Anti-N in Norm | MD (95% CI) | p | |
---|---|---|---|---|
All | 133.32 ± 69.76 | 94.87 ± 54.44 | 38.45 (22.85;54.05) | <0.001 |
Females | 132.43 ± 67.69 | 94.08 ± 52.85 | 38.35 (20.33;56.37) | <0.001 |
Males | 135.43 ± 75.75 | 97.62 ± 59.91 | 37.81 (5.22;70.40) | 0.024 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Matryba, P.; Gawalski, K.; Ciesielska, I.; Horvath, A.; Bartoszewicz, Z.; Sienko, J.; Ambroziak, U.; Malesa-Tarasiuk, K.; Staniszewska, A.; Golab, J.; Krenke, R. The Influence of Time of Day of Vaccination with BNT162b2 on the Adverse Drug Reactions and Efficacy of Humoral Response against SARS-CoV-2 in an Observational Study of Young Adults. Vaccines 2022, 10, 443. https://doi.org/10.3390/vaccines10030443
Matryba P, Gawalski K, Ciesielska I, Horvath A, Bartoszewicz Z, Sienko J, Ambroziak U, Malesa-Tarasiuk K, Staniszewska A, Golab J, Krenke R. The Influence of Time of Day of Vaccination with BNT162b2 on the Adverse Drug Reactions and Efficacy of Humoral Response against SARS-CoV-2 in an Observational Study of Young Adults. Vaccines. 2022; 10(3):443. https://doi.org/10.3390/vaccines10030443
Chicago/Turabian StyleMatryba, Paweł, Karol Gawalski, Iga Ciesielska, Andrea Horvath, Zbigniew Bartoszewicz, Jacek Sienko, Urszula Ambroziak, Karolina Malesa-Tarasiuk, Anna Staniszewska, Jakub Golab, and Rafał Krenke. 2022. "The Influence of Time of Day of Vaccination with BNT162b2 on the Adverse Drug Reactions and Efficacy of Humoral Response against SARS-CoV-2 in an Observational Study of Young Adults" Vaccines 10, no. 3: 443. https://doi.org/10.3390/vaccines10030443