The most extensive COVID-19 vaccine study to date shows that Moderna, Pfizer, and AstraZeneca's COVID-19 vaccines are associated with slight increases in adverse heart, blood, and brain-related events.
The study, conducted by scientists from the World Health Organization's (WHO) Global Vaccine Data Network, examined 99,068,901 vaccinated individuals from 10 sites across eight countries to evaluate the rates of 13 neurological, hematological, and cardiac-related adverse events following COVID-19 vaccination.
The findings, published on February 12 in the journal Vaccine, confirm safety signals identified previously for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis, the study's authors say.
The analysis looked at the expected and observed rates of these "adverse events of special interest" occurring up to 42 days after the participants received a first, second, third, or fourth dose of Pfizer/BioNTech's (BNT162b2) and Moderna's (mRNA-1273) mRNA vaccines. The researchers also examined data of individuals who received the Oxford/AstraZeneca (ChAdOx1) adenovirus-vector vaccine.
After analyzing the data, the team found slight increases in specific brain, heart, and blood-related adverse events.
Neurological disorders linked to Covid-19 vaccines
The results showed a statistically significant increase in Guillain-Barré syndrome — a condition that causes the immune system to attack the nerves — within 42 days after participants received their first Oxford/AstraZeneca vaccine. For example, while 76 Guillain-Barré syndrome cases were expected, the scientists observed a total of 190.
Moreover, recipients of a first dose of Moderna's mRNA vaccine had a 3.8 times higher risk of acute disseminated encephalomyelitis (ADEM) within 42 days. ADEM is a neurological disorder characterized by brain and spinal cord swelling.
A first dose of the Oxford/AstraZeneca vaccine led to a slightly higher risk for transverse myelitis, or spinal cord inflammation, and ADEM. In addition, an initial dose of Pfizer/BioNTech's mRNA vaccine was associated with a small risk of developing Bell's palsy, which causes unexplained facial weakness or paralysis.
There were also increased risks for febrile seizures following a first and second dose of Moderna's shot and for generalized seizures following a first Moderna dose and a fourth Pfizer/BioNTech vaccine.
COVID vaccines and blood-related events
According to the study, after a first dose of the Oxford/AstraZeneca adenovirus-vector vaccine, participants were at slightly higher risk of developing cerebral venous sinus thrombosis — a blood clot in the brain. The researchers say 21 cases of cerebral venous sinus thrombosis were expected. However, 69 actually occurred.
The study's authors say that these findings align with multiple studies, which is likely why this particular shot was withdrawn from vaccine programs.
Other blood-related outcomes identified by the researchers include slight risks of thrombocytopenia or low platelets after a first dose of an Oxford/AstraZeneca, Pfizer/BioNTech, and Moderna vaccine. An initial dose of Oxford/AstraZeneca and Pfizer/BioNTech's vaccines carried a slightly increased risk of immune thrombocytopenia.
All three COVID vaccines were associated with a small risk of pulmonary embolism — a blockage of the blood vessels that bring blood to the lungs — and splanchnic vein thrombosis, a blood clot in the digestive system.
Cardiovascular risks revealed in the study
The researchers found that a first, second, and third dose of Moderna and Pfizer mRNA vaccines were linked with a higher risk of myocarditis or inflammation of the heart muscle. Moderna's vaccine's first and second doses had the highest risk at 6.1 times the expected cases.
Moreover, following a first and fourth dose of Moderna's vaccine, participants showed an increased risk of developing pericarditis, or inflammation of the heart's outer lining.
The researchers say these results confirm the findings of previous studies that identified rare cases of myocarditis and pericarditis following the first and second doses of mRNA vaccines.
Based on the findings, the study's authors suggest that although the risks associated with some observed adverse events are low, they may still hold clinical importance and require further investigation.
Still, multiple studies have shown that COVID-19 itself is linked to a higher risk of Guillain-Barré syndrome, myocarditis, or ADEM. Therefore, risks related to a COVID-19 infection far outweigh the slight risks associated with COVID-19 vaccines outlined in the study.
Moreover, the study looked at data from over 9 million vaccine recipients, with over 180 million doses of BNT162b2, more than 36 million doses of mRNA-1273, and over 23 million doses of ChAdOx1, so adverse events the researchers identified are statistically rare.
According to the latest Centers for Disease Control and Prevention (CDC) data, the 2023-2024 updated COVID booster is about 54% effective against COVID-19.
3 resources
- Vaccine. COVID-19 vaccines and adverse events of special interest: a multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals.
- CDC. Selected adverse events reported after COVID-19 vaccination.
- CDC. Early estimates of updated 2023–2024 (Monovalent XBB.1.5) COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection attributable to co-circulating omicron variants among immunocompetent adults — increasing community access to testing program, United States, September 2023–January 2024.
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