The COVID-19 vaccines have been crucial in preventing millions of deaths during the pandemic. However, post-vaccination, a few reported some side effects such as fatigue, exercise intolerance, brain fog, tinnitus, and dizziness. A recent study by Yale researchers has delved deep into this little-understood, persistent condition, referred to as post-vaccination syndrome (PVS).
In the study posted online, the researchers have characterized this condition and also studied the immunological patterns that differentiate those with PVS from others.
“This work is still in its early stages, and we need to validate these findings,” Akiko Iwasaki, Sterling Professor of Immunobiology at Yale School of Medicine (YSM) and co-senior author of the study published Feb. 19 as a preprint on
MedRxiv said in a release. “But this is giving us some hope that there may be something that we can use for diagnosis and treatment of PVS down the road.”
The chronic symptoms of PVS include:
- exercise intolerance
- excessive fatigue
- brain fog
- Insomnia
- dizziness
These symptoms develop shortly after vaccination, which is within a day or two, and can get more severe in the days that follow.
“It’s clear that some individuals are experiencing significant challenges after vaccination. Our responsibility as scientists and clinicians is to listen to their experiences, rigorously investigate the underlying causes, and seek ways to help,” Harlan Krumholz, the Harold H. Hines, Jr. Professor of Medicine (Cardiology) at YSM and co-senior author of the study adds.
Researchers analyzed blood samples from people in their Listen to Immune, Symptom, and Treatment Experiences Now (LISTEN) study to understand long COVID and post-vaccine syndrome (PVS). They compared 42 people with PVS symptoms to 22 people without symptoms after COVID-19 vaccination.
They found differences in immune cells between the two groups. Those with PVS had lower levels of effector CD4+ T cells and higher levels of TNF-alpha+ CD8 T cells — both are types of white blood cells — among other differences.
They also found differences in antibody levels. People with PVS who never had COVID-19 had lower levels of antibodies against the virus's spike protein. This was likely because they received fewer vaccine doses than those without PVS. With fewer shots and no prior infection, their immune systems had less chance to build protection against the virus.
Additionally, they found that some people with PVS had higher levels of the SARS-CoV-2 spike protein, even if they had never been infected. Normally, the spike protein stays in the body for only a few days after vaccination, but in some PVS cases, it was still present more than 700 days later. This lingering spike protein has also been linked to long COVID.
“That was surprising, to find spike protein in circulation at such a late time point. We don’t know if the level of spike protein is causing the chronic symptoms, because there were other participants with PVS who didn’t have any measurable spike protein. But it could be one mechanism underlying this syndrome,” Iwasaki noted.
Krumholz further added that PVS might be similar to other infections that lead to chronic symptoms, each through different biological pathways. “One person might develop chronic symptoms due to immune dysregulation, while another experiences lingering effects from viral reactivation. We need to map these different pathways carefully to understand what is happening in each case. This work is just beginning, and further studies are essential to guide diagnosis and treatment,” he said.
The COVID-19 vaccine may also cause some mild side effects such as fatigue, headache, and a low-grade fever. These symptoms typically resolve within a few days. They indicate that the immune system is responding to the vaccine.
The researchers added that a deeper understanding of PVS is required to make better
vaccines, with fewer side effects. “For instance, if we can determine why spike protein is persisting for as long as it is in some people, maybe we can remove it — with monoclonal antibodies, for example — and maybe that could help reduce PVS symptoms,” Iwasaki, a professor of dermatology and of molecular, cellular, and developmental biology in Yale’s Faculty of Arts and Sciences, a professor of epidemiology at Yale School of Public Health, and an investigator of the Howard Hughes Medical Institute added.
“We’re only just starting to make headway in understanding PVS. Every medical intervention carries some risk, and it’s important to acknowledge that adverse events can occur with vaccines. Our focus must remain on understanding what these people are experiencing through rigorous science and addressing the needs of those affected with compassion and an open mind,” Krumholz added.
According to the CDC, Vaccines, like any medical product, can have side effects. Side effects reported after COVID-19 vaccination vary from person to person. Most common side effects are usually mild, such as soreness in the area where the shot was given. Everyone who gets a COVID-19 vaccine may be monitored onsite for at least 15 minutes after vaccination (people who experience or have experienced non-severe allergic reactions to COVID-19 vaccines may be monitored for 30 minutes).
"Since 2021, more than 13 billion COVID-19 vaccine doses have been administered globally. As with all vaccines, WHO and regulatory authorities continuously monitor the use of COVID-19 vaccines to identify and respond to any safety issues that might arise. Serious reactions to COVID-19 vaccines are extremely rare. Through this process, we establish that COVID-19 vaccines remain safe worldwide," WHO says.
"If adverse reactions last longer than four weeks, one speaks of the long post-COVID vaccination syndrome (LPCVS) in analogy to the long-COVID syndrome," another study finds.
Scientists further stated that more studies are needed to understand the prevalence of PVS. They want to further validate these findings in a larger group of people “This is far from a final answer on PVS,” said Iwasaki.