Long-Term Adverse Effects After COVID-19 Vaccination Vary by Brand

A cross-sectional study of 429 adults found that chronic fatigue, cognitive impairment, and menstrual irregularity were the most commonly self-reported long-term adverse effects following COVID-19 vaccination, with symptom rates differing across the Oxford AstraZeneca (ChAdOx1 nCoV-19), Pfizer-BioNTech (BNT162b2), and Moderna (mRNA-1273) vaccines.¹

The findings, published in the journal Medicine, are drawn from an online survey of participants who had completed all 3 recommended vaccine doses and were asked to report symptoms that persisted or recurred within 6 months of vaccination.¹

Researchers from Riyadh, Saudi Arabia, conducted the survey between September 10 and October 28, 2025. Participants were adults 18 years and older who had received 3 doses of a COVID-19 vaccine authorized by the Saudi Ministry of Health. Those hospitalized for severe adverse effects immediately after vaccination were excluded.¹

Of the 429 respondents, 243 (56.6%) were male and 186 (43.4%) were female, and 371 (86.5%) were Saudi nationals. Overall, 55.5% of participants reported no change in their health after vaccination, and 44.5% reported changes.¹

Long-Term Effects Varied by Brand and Dose

Chronic fatigue was reported more frequently by Oxford AstraZeneca recipients (34.7% after the first dose) than by Moderna (22.2%) or Pfizer-BioNTech (27.7%) recipients, though the difference was not statistically significant (P = .372). The gap widened after the second dose, when 38.9% of Oxford AstraZeneca recipients reported chronic fatigue compared with 25% of Moderna and 27.3% of Pfizer-BioNTech recipients (P = .133). Cognitive or memory problems were reported at similar rates across all 3 brands after the first dose, at roughly 25%, with none of the differences reaching statistical significance.¹

The vaccines also affected men and women differently. Moderna produced a higher self-reported symptom rate among male participants (50% to 61.5%) than female participants (28% to 33.3%) after the first and second doses, though these differences were not statistically significant.¹

By contrast, the Oxford AstraZeneca and Pfizer-BioNTech vaccines were associated with a higher reported incidence of symptoms among women. After the third dose, Moderna's pattern reversed, affecting more women (46.6%) than men (38.1%), and Oxford AstraZeneca continued to have a greater effect in men.¹

Among female participants, menstrual irregularity after the first and second doses did not differ significantly by vaccine brand. However, that changed with the third dose. Approximately 41.8% of Pfizer-BioNTech recipients reported menstrual irregularity, compared with 31.3% of Oxford AstraZeneca and 18.7% of Moderna recipients, a statistically significant difference (P = .012).¹

The authors noted that these results align "moderately" with an earlier study that also found menstrual disturbances among long-term adverse effects reported by vaccinated physicians and dentists in Jordan and Saudi Arabia.¹

The study additionally tracked COVID-19 infection after vaccination. Moderna recipients were most likely to remain uninfected after the first dose (77.8%), compared with 58.2% of Pfizer-BioNTech and 53.7% of Oxford AstraZeneca recipients. Oxford AstraZeneca recipients had the highest post-vaccination infection rate (46.3%) after the first dose.¹

That pattern shifted by the third dose, when 56.5% of Moderna recipients reported infection, compared with 42.1% for Pfizer-BioNTech and 33.3% for Oxford AstraZeneca. None of the infection-rate differences across doses reached statistical significance.¹

Placing the Findings in Context

The Aldali and Meo study adds to a broader body of literature on vaccine safety monitoring. A separate review of COVID-19 vaccine adverse events published in the Journal of Taibah University Medical Sciences found that more severe reactions, including myocarditis, pericarditis, and thrombosis, are far less common than the mild effects described in the Saudi survey.²

Citing US Vaccine Adverse Event Reporting System data, that review reported 4.94 myocarditis cases and 3.45 pericarditis cases per million vaccine doses administered and noted that more than 95% of individuals experienced only moderate, self-limiting adverse effects, with just 5% requiring medical evaluation or hospitalization.²

Mayo Clinic similarly describes common short-term effects, including pain at the injection site, fever, headache, and fatigue, as effects that "go away in a few days" for most recipients and states that "vaccines rarely cause any long-term [adverse] effects." Mayo Clinic also notes that myocarditis and pericarditis following vaccination are rare, occur mostly in males ages 12 to 39 years, and typically appear within a week of the second dose.³

The authors acknowledged several limitations that temper the findings. Because the data relied on self-reported, cross-sectional survey responses, the study could not clinically confirm whether reported symptoms represented new onset after vaccination, persistent conditions, recurrence, or preexisting issues.¹

The researchers also did not perform multivariable regression analysis, meaning the associations described should be interpreted as unadjusted rather than independent effects, and the relatively short follow-up window limited the ability to capture rarer or more delayed effects. The authors called for further large-scale studies to provide more conclusive evidence.¹

What This Means for Pharmacists

For pharmacists counseling patients on COVID-19 vaccination, the study underscores that fatigue, cognitive complaints, and menstrual changes are among the most frequently self-reported concerns patients may raise well after their vaccination series, even though the authors stress these are self-reported associations rather than confirmed vaccine-caused effects.

Pharmacists fielding these questions can point to the consistent finding across sources that severe adverse events, such as myocarditis or thrombosis, remain rare, while directing patients with persistent or worsening symptoms to follow up with a physician for clinical evaluation.

REFERENCES

1. Aldali JA, Meo SA. Long-term adverse effects following COVID-19 vaccination: A comparative analysis of Oxford AstraZeneca, Pfizer-BioNTech, and Moderna vaccines. Medicine (Baltimore). 2026;105(35):e50282. doi:10.1097/MD.0000000000050282

2. Yaamika H, Muralidas D, Elumalai K. Review of adverse events associated with COVID-19 vaccines, highlighting their frequencies and reported cases. J Taibah Univ Med Sci. 2023;18(6):1646-1661. Published 2023 Sep 5. doi:10.1016/j.jtumed.2023.08.004

3. Mayo Clinic. COVID-19 vaccines: get the facts. Mayo Clinic. Accessed September 2, 2026. https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-vaccine/art-20484859