[weyo/Adobe Stock]
To date, there have been more than 770 million confirmed COVID-19 cases and nearly 7 million deaths from the virus, according to the World Health Organization (WHO). Vaccines remain one of the most potent tools in blunting the severity of SARS-CoV-2 infection, and vaccine developers have distributed more than 13.5 billion vaccine doses to date.
As the global fight against COVID-19 continues, the emphasis on vaccine safety remains a priority. While COVID-19 vaccines from Moderna, Pfizer and J&J vaccines show higher reactogenicity than other commonly administered vaccines, SARS-CoV-2 remains a dangerous virus. Beyond the immediate threat of infection, the prolonged impact of ‘long COVID‘ is considerable. The National Center for Health Statistics (NCHS) reveals that more than 40% of U.S. adults have had a COVID-19 infection, with nearly 19% of these individuals still grappling with long COVID symptoms. This translates to one in 13 adults in the U.S. experiencing symptoms that persist for months after an initial infection.
When contemplating the benefit-risk calculus of vaccines, the risk of COVID-19 itself remains a vital part of the equation — especially when considering that many of the adverse events from COVID-19 vaccines are minor and transient.
Minor adverse events dominate top vaccine reactions
Nature of adverse events: According to a cumulative analysis of Vaccine Adverse Event Reporting System (VAERS) data from the beginning of the pandemic up to August 25, 2023, the most commonly reported adverse events are generally mild symptoms such as headache, fever, fatigue, pain, chills, and muscle pain.
In the ranking below, we identified likely COVID-19 cases from the VAERS data by filtering and classifying records based on specific keywords reflecting confirmed, suspected, or past infections. This approach involved jointly considering terms such as “BREAKTHROUGH COVID-19” for vaccinated individuals, “SUSPECTED COVID-19” and “SARS-COV-2 RNA” for active infections.
Gender gap: Women experience multiple vaccine adverse reactions more frequently
Women are more likely than men to report five or more adverse reactions across all three doses of the vaccine, according to a Danish study of patients aged 16 to 65. For recipients of the first vaccine dose, 9% of women reported five or more adverse reactions compared to 3% of men. This trend persisted for the second and third doses. For the second, some 12% of women and 5% of men reported five or more adverse reactions. By the third dose, the numbers were 7% for women and 3% for men.
Across the three shots, men had between 40% to 51% of the odds of reporting five or more adverse reactions compared to women.
In the study, individuals who received the ChAdOx1-2 (AstraZeneca) and mRNA-1273 (Moderna) vaccines were more likely to report five or more adverse reactions after a first dose compared to those vaccinated with BNT162b2 (Pfizer-BioNTech). This trend held steady for recipients of the second and third doses of the mRNA-1273 vaccine.
The finding is not novel. A 2019 CDC analysis reached similar conclusions about the rate of severe allergic reactions stemming from vaccines and reports of hypersensitivity were more common in female recipients of the 2009-10 H1N1 (swine flu) pandemic vaccine, according to an article in the journal Vaccine.
Younger age groups report more side effects
Younger individuals, notably those between the ages of 16 and 25, were more likely to report at least 5 adverse reactions compared to older age groups, according to the Danish study mentioned earlier. As age increases, the odds of reporting multiple adverse reactions decreased across all three doses.
How vaccine types stack up in terms of adverse reactions
When it comes to the type of vaccine, there are clear differences. AstraZeneca’s ChAdOx1-2 vaccine had a notably higher odds ratio for the first dose, reflecting a higher likelihood of individuals reporting 5 or more adverse reactions relative to those who received the Pfizer-BioNTech BNT162b2 vaccine, according to the same Danish study. Moderna’s mRNA-1273 vaccine also reflected increased odds, especially for the second dose.
A separate study also suggested a link between the Moderna vaccine and hives for a limited number of recipients.
Although not included in the Danish study, the Novavax COVID-19 vaccine is available in the U.S. Based on VAERS data from 2022 to present, common side effects linked with that vaccine include pain at the injection site, fatigue, headache, muscle pain, chills fever, and nausea, according to VAERS. As of May 31. the Health Sciences Authority (HSA) in Singapore has reported four cases of non-serious adverse reactions out of 2,792 Novavax doses.
Prior COVID cases see more adverse reactions post-vaccination
Individuals with a prior COVID-19 infection have a higher likelihood of reporting 5 or more adverse reactions across all doses compared to those without a prior infection.
An analysis from CDC concluded that despite a higher incidence of side effects in some demographics and for certain vaccines, the benefits of COVID-19 vaccination continue to outweigh the risks for most people. Such risks includes the extremely rare, but serious, adverse events like anaphylaxis, Guillain-Barré Syndrome (GBS), myocarditis and pericarditis, and thrombosis with thrombocytopenia syndrome (TTS).