The Centers for Disease Control and Prevention (CDC) posted on their website that side effects from the second COVID-19 vaccination may be more severe than those from the first. These symptoms are normal signs that the body is constructing defenses and should subside within a few days. So far, reactions to booster shots are almost like those reported after two-dose or single-dose primary shots. The foremost common side effects were fever, headache, fatigue, and pain at the injection site, with the bulk of side effects being mild to moderate. Serious side effects, like the two-dose or single-dose primary shots, are uncommon but can occur.

mRNA-Based COVID-19 Vaccines

COVID-19 vaccination is currently performed by intramuscular injection or injection deep into the muscles.

Scientists are looking into an alternative type of shot called subcutaneous injection, where a short needle can inject medication into the tissue between the skin and the muscle, Science Tech Daily reports.

Researchers discovered that subcutaneous injection of COVID-19 mRNA vaccines reduces the negative post-vaccination effects, such as fatigue while maintaining similar immune-system responses in mice.

Despite their high efficacy against SARS-CoV-2, mRNA-based COVID-19 vaccines are linked to negative side effects such as fatigue after vaccination.

Mouse Experiments

Ayesa Syenina from the Duke NUS Medical School in Singapore, together with her colleagues, reports that a new analysis of blood samples from people vaccinated for COVID-19 has identified distinct molecular characteristics that are linked to an increased risk of post-vaccination fatigue. The data was presented in their study published on May 31 in the open-access journal PLOS Biology.

Experiments on mice also suggest that changing the vaccine injection strategy could help alleviate these side effects.

People's willingness to get vaccinated or receive a booster dose may be influenced by adverse post-vaccination effects, hampering efforts to reduce COVID-19's spread and severity. However, the molecular mechanisms underlying adverse post-vaccination effects remain unknown.

Syenina and colleagues analyzed blood samples from 175 healthcare workers who received BNT162b2, the Pfizer-BioNTech COVID-19 vaccine, to gain a better understanding. The team used the blood samples in examining the snapshots of each participant's gene expression, or which genes are active or inactive.

This study revealed that people who felt moderately severe fatigue after vaccination had higher baseline expression of genes related to T cell and natural killer cell activity, two important cell types in the human immune system.

In addition, the researchers used mice to test two different vaccination injection strategies. BNT162b2 was given to some mice via intramuscular injection, which is the current method for administering the vaccine to human patients. Other mice were given a subcutaneous injection, which involves injecting the vaccine into the tissue just beneath the skin.

Compared to mice who received intramuscular vaccination, mice who received subcutaneous vaccination showed immune-system responses that were consistent with a lower risk of side effects like fatigue. The vaccine's protective effects did not appear to be harmed by the subcutaneous injection.

More research is needed to build on these findings and investigate their clinical implications. Nonetheless, they contribute to a better understanding of post-vaccination fatigue and suggest a strategy for reducing its occurrence.

Co-author Eng Eong Ooi added that their research provides the first molecular understanding of a side effect that many people have experienced after receiving mRNA vaccination. The researchers hope that this discovery will spur more research into the mechanisms that underpin vaccine-related side effects, allowing them to develop even more tolerable vaccines.