An exploratory analysis of the response to ChAdOx1 nCoV-19 (AZD1222) vaccine in males and females
Open accessAbstract
BACKGROUND: There are known differences in vaccine reactogenicity and immunogenicity by sex. Females have been shown to report greater reactogenicity and generate higher humoral and cellular immune responses than males following vaccination with several different vaccines. Whether this is also the case for COVID-19 vaccines is currently unknown, as COVID-19 vaccine study data disaggregated by sex are not routinely reported. Therefore, we have assessed the influence of sex on reactogenicity, immunogenicity and efficacy of COVID-19 vaccine ChAdOx1 nCoV-19. METHODS: Vaccine efficacy was assessed in 15169 volunteers enrolled into single-blind randomised controlled trials of ChAdOx1 nCoV-19 in Brazil and the UK, with the primary endpoint defined as nucleic acid amplification test (NAAT)-positive symptomatic SARS-CoV-2 infection. All participants were electronically randomised to receive two standard doses of vaccine or the control product. Logistic regression models were fitted to explore the effect of age and sex on reactogenicity, and linear models fitted to log-transformed values for immunogenicity data. Reactogenicity data were taken from self-reported diaries of 788 trial participants. Pseudovirus neutralisation assay data were available from 748 participants and anti-SARS-CoV-2 spike IgG assay data from 1543 participants. FINDINGS: 7619 participants received ChAdOx1 nCoV-19 and 7550 received the control. Vaccine efficacy in participants after two doses of ChAdOx1 nCoV-19 (4243 females and 3376 males) was 66.1% (95% CI 55.9-73.9%) in males and 59.9% (95% CI 49.8-67.9%) in females; with no evidence of a difference in efficacy between the sexes (vaccine by sex interaction term P=0.3359). A small, statistically significant difference in anti-spike IgG was observed (adjusted GMR 1.14; 95% CI 1.04-1.26), with higher titres in females than males, but there were no statistically significant differences in other immunological endpoints. Whilst the majority of individuals reported at least one systemic reaction following a first dose of ChAdOx1 nCoV-19, females were twice as likely as males to report any systemic reaction after a first dose (OR 1.95; 95% CI 1.37-2.77). Measured fever of 38°C or above was reported in 5% of females and 1% of males following first doses. Headache and fatigue were the most commonly reported reactions in both sexes. INTERPRETATION: Our results show that there is no evidence of difference in efficacy of the COVID-19 vaccine ChAdOx1 nCoV-19 in males and females. Greater reactogenicity in females was not associated with any difference in vaccine efficacy. FUNDING: Studies were registered with ISRCTN 90906759 (COV002) and ISRCTN 89951424 (COV003) and follow-up is ongoing. Funding was received from the UK Research and Innovation, Engineering and Physical Sciences Research Council, National Institute for Health Research, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research Oxford Biomedical Research Centre, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Thames Valley and South Midlands NIHR Clinical Research Network, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil, and AstraZeneca.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Marchevsky et al. found a small, statistically significant difference in anti-spike IgG titers, with higher titers in female participants, and twice as many systemic reactions reported by women.
“These findings contrast with sex-disaggregated data published by Marchevsky et al.37 where a small, statistically significant difference was found in the anti-spike IgG titers, with higher titers in female participants and there were twice as many systemic reactions reported by women.”
From An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial (2024) · cites this paper as [37]
The Results > Immunogenicity section reports a small, statistically significant increase in anti-spike IgG titres in females. The Results > Reactogenicity section reports nearly twice the adjusted odds of reporting any systemic reaction after the first dose (OR 1.95), not twice as many reactions; it found no significant sex difference in systemic reactions after the second dose. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
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. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2034577 · Cited by 14,592 · see citing works
Sex differences in immune responses
Klein, S. L., & Flanagan, K. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.90 · Cited by 6,370 · see citing works
Folegatti, P. M., Ewer, K. J., Aley, P. K., Angus, B., Becker, S., Belij-Rammerstorfer, S., Bellamy, D., Bibi, S., Bittaye, M., Clutterbuck, E. A., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31604-4 · Cited by 2,419 · see citing works
Self-citationSex differences in immune responses that underlie COVID-19 disease outcomes
Takahashi, T., Ellingson, M. K., Wong, P., Israelow, B., Lucas, C., Klein, J., Silva, J., Mao, T., Oh, J. E., Tokuyama, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2700-3 · Cited by 1,459 · see citing works
Ramasamy, M. N., Minassian, A. M., Ewer, K. J., Flaxman, A. L., Folegatti, P. M., Owens, D. R., Voysey, M., Aley, P. K., Angus, B., Babbage, G., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)32466-1 · Cited by 1,324 · see citing works
Self-citationVoysey, M., Costa Clemens, S. A., Madhi, S. A., Weckx, L. Y., Folegatti, P. M., Aley, P. K., Angus, B., Baillie, V. L., Barnabas, S. L., Bhorat, Q. E., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00432-3 · Cited by 1,119 · see citing works
Self-citationMenni, C., Klaser, K., May, A., Polidori, L., Capdevila, J., Louca, P., Sudre, C. H., Nguyen, L. H., Drew, D. A., Merino, J., et al. (2021) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(21)00224-3 · Cited by 1,031 · see citing works
How sex and age affect immune responses, susceptibility to infections, and response to vaccination
Giefing, C., Berger, P., Lepperdinger, G., & Grubeck‐Loebenstein, B. (2015) · Aging Cell · doi:10.1111/acel.12326 · Cited by 768 · see citing works
Furman, D., Hejblum, B. P., Simon, N., Jojic, V., Dekker, C. L., Thiébaut, R., Tibshirani, R. J., & Davis, M. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321060111 · Cited by 678 · see citing works
Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine
Falsey, A. R., Sobieszczyk, M. E., Hirsch, I., Sproule, S., Robb, M. L., Corey, L., Neuzil, K. M., Hahn, W., Hunt, J., Mulligan, M. J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2105290 · Cited by 670 · see citing works
TLR7 escapes X chromosome inactivation in immune cells
Souyris, M., Cénac, C., Azar, P., Daviaud, D., Canivet, A., Grunenwald, S., Pienkowski, C., Chaumeil, J., Mejía, J. E., & Guéry, J. (2018) · Science Immunology · doi:10.1126/sciimmunol.aap8855 · Cited by 650 · see citing works
Sex and Gender Differences in the Outcomes of Vaccination over the Life Course
Flanagan, K. L., Fink, A. L., Plebanski, M., & Klein, S. L. (2017) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100616-060718 · Cited by 508 · see citing works
Half- vs Full-Dose Trivalent Inactivated Influenza Vaccine (2004-2005)
Engler, R. J. M. (2008) · Archives of Internal Medicine · doi:10.1001/archinternmed.2008.513 · Cited by 319 · see citing works
Barrett, J. R., Belij-Rammerstorfer, S., Dold, C., Ewer, K. J., Folegatti, P. M., Gilbride, C., Halkerston, R., Hill, J., Jenkin, D., Stockdale, L., et al. (2021) · Nature Medicine · doi:10.1038/s41591-020-01179-4 · Cited by 315 · see citing works
Self-citationAlghamdi, I., Hussain, I. I., Alghamdi, M. S., Almalki, S. S. R., Alghamdi, M., & El‐Sheemy, M. (2014) · International Journal of General Medicine · doi:10.2147/ijgm.s67061 · Cited by 245 · see citing works
Sex Differences in Immunity to Viral Infections
Jacobsen, H., & Klein, S. L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.720952 · Cited by 234 · see citing works
Kynurenic acid may underlie sex-specific immune responses to COVID-19
Cai, Y. A., Kim, D. J., Takahashi, T., et al. (2021) · Science Signaling · doi:10.1126/scisignal.abf8483 · Cited by 106 · see citing works
Powell, A. A., Power, L., Westrop, S. J., McOwat, K., Campbell, H. J., Simmons, R., Ramsay, M. E., Brown, K. E., Ladhani, S. N., & Amirthalingam, G. (2021) · Eurosurveillance · doi:10.2807/1560-7917.es.2021.26.28.2100634 · Cited by 58 · see citing works
Tadount, F., Doyon-Plourde, P., Rafferty, E., MacDonald, S. E., Sadarangani, M., & Quach, C. (2019) · Vaccine · doi:10.1016/j.vaccine.2019.10.091 · Cited by 54 · see citing works
Cook, I. F., Pond, D. C., & Härtel, G. (2007) · Vaccine · doi:10.1016/j.vaccine.2007.04.017 · Cited by 43 · see citing works
Gender differences in the reactogenicity of measles-mumps-rubella vaccine.
Shohat, T., Green, M. S., Nakar, O., et al. (2000) · PubMed · Cited by 42 · see citing works
Clinical and Laboratory Findings of SARS in Singapore
Leong, H., Chan, K.-P., Oon, L. L., et al. (2006) · Annals of the Academy of Medicine Singapore · doi:10.47102/annals-acadmedsg.v35n5p332 · Cited by 32 · see citing works
Atabani, S. F., Landucci, G., Steward, M. W., Whittle, H. C., Tilles, J. G., & Forthal, D. N. (2000) · Clinical and Diagnostic Laboratory Immunology · doi:10.1128/cdli.7.1.111-113.2000 · Cited by 25 · see citing works
Alguacil-Ramos, A. M., Muelas-Tirado, J., Garrigues, T., et al. (2016) · Public Health · doi:10.1016/j.puhe.2015.11.010 · Cited by 24 · see citing works
Chapin-Bardales, J., Myers, T., Gee, J., Shay, D. K., Marquez, P., Baggs, J., Zhang, B., Licata, C., & Shimabukuro, T. T. (2021) · Vaccine · doi:10.1016/j.vaccine.2021.10.019 · Cited by 23 · see citing works
Boef, A. G. C., van der Klis, F. R. M., Berbers, G. A. M., Buisman, A., Sanders, E. A. M., Kemmeren, J. M., ENDE, A. V. D., de Melker, H. E., Rots, N. Y., & Knol, M. J. (2017) · Vaccine · doi:10.1016/j.vaccine.2017.11.070 · Cited by 15 · see citing works
Voysey, M., Pollard, A. J., Perera, R., & Fanshawe, T. R. (2016) · BMJ Open · doi:10.1136/bmjopen-2016-011680 · Cited by 10 · see citing works
Self-citationGender Equality: Flying blind in a time of crisis, The Global Health 50/50 Report 2021
50/50, G. H. (2021) · doi:10.56649/zdyq5195 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial
Saraf, A., Gurjar, R., Kaviraj, S., Kulkarni, A., Kumar, D., Kulkarni, R., Virkar, R., Krishnan, J., Yadav, A., Baranwal, E., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-02955-2 · Cited by 66 · see citing works
“These findings contrast with sex-disaggregated data published by Marchevsky et al. 37 where a small, statistically significant difference was found in the anti-spike IgG titers, with higher titers in female participants and there were twice as many systemic reactions reported by women.”
- Authors
- Marchevsky, N. G., Li, G., Aley, P., Costa Clemens, S. A., Barrett, J. R., Belij-Rammerstorfer, S., Bibi, S., Clutterbuck, E., Dold, C., Felle, S., Flaxman, A., Folegatti, P., Jenkin, D., Gilbert, S., Kelly, S., Lambe, T., Plested, E., Ramasamy, M., Singh, N., Smith, H., Taylor, S., Weckx, L., Pollard, A. J., & Voysey, M.
- Affiliations
- University of Oxford (GB)
- Public Health England (GB)
- Universidade Federal de São Paulo (BR)
- Corresponding author
- Li, Grace
- ORCID
- Marchevsky, Natalie Gabrielle
- Li, Grace
- Aley, Parvinder
- Barrett, Jordan Richard
- Bibi, Sagida
- Clutterbuck, Elizabeth
- Dold, Christina
- Felle, Sally
- Flaxman, Amy
- Folegatti, Pedro
- Jenkin, Daniel
- Gilbert, Sarah
- Kelly, Sarah
- Lambe, Teresa
- Plested, Emma
- Ramasamy, Maheshi
- Taylor, Stephen
- Weckx, Lily
- Pollard, Andrew John
- Voysey, Merryn
- Venue
- eBioMedicine
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 81
- Pages
- 104128
- ISSN
- 2352-3964 (ISSN-L)
- PMC
- PMC9242842
- OpenAlex
- W4283723085
- Cited by
- 17
- References
- 28
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 7 · 2022: 1
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- EBioMedicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Funders
- National Institute for Health and Care Research (COV19OxfordVaccine01)
- Medical Research Council (MR/X000656/1)
- Engineering and Physical Sciences Research Council (EP/R013756/1)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- ChAdOx1 nCoV-19 vaccine, AZD1222, COVID-19 vaccines, sex differences, vaccine efficacy, vaccine immunogenicity, vaccine reactogenicity, anti-spike IgG, SARS-CoV-2, vaccine safety
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, ChAdOx1 nCoV-19, Antibodies, Viral, Female, Humans, Immunoglobulin G, Male, Randomized Controlled Trials as Topic, Single-Blind Method
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
