A little over two weeks ago, Akiko Iwasaki and colleagues published “Immunological and Antigenic Signatures Associated with Chronic Illnesses after Covid-19 Vaccination” on medRxiv. You don’t need to be a scientist to understand the implications of the authors’ suggestion that the COVID-19 vaccine could lead to long-term health complications in a small subset of individuals. A publication from a renowned Yale lab, with such an explosive and eye-catching title was immediately pounced on by the anti-vaccine community — including Elon Musk — who reposted an article highlighting one of the main conclusions to an audience of over 200 million. These public figures have every right to take information that’s been thrust into the public sphere and amplify it to a wider audience. The authors did exactly that by coordinating with The New York Times for a write-up of their pre-print just one day later. With a topic this sensitive, there is an expectation of scientific precision — well-designed experiments and trials, strong data and unshakable conclusions. Instead, this paper didn’t just miss the mark — it didn’t even hit the target.
Criticism of this article rightly begins with its publication choice. medRxiv is not a peer-reviewed journal but a preprint server — one co-founded by senior author Harlan Krumholz. While platforms like bioRxiv and medRxiv play a role in rapidly sharing research, there was no urgency in this case, making the decision to bypass traditional peer review questionable. Even Iwasaki and Krumholz admitted in the New York Times and YaleNews that their research is still in its early stages and requires validation in larger studies. All scientific research begins on a small scale, gradually progressing to a published study, a larger trial, or, as scientists often experience, fading away without further development. The difference here is that by making a conscious decision to push unverified findings into the public sphere, Iwasaki and Krumholz could fuel misinformation, erode confidence in legitimate research and undermine the very trust they claim to uphold. Scientists have a responsibility to consider the societal impact of their work and to prioritize rigorous peer review over using their reputation to bypass scrutiny and shape public opinion.
Turning to the data, the authors of this study claim to have found an immune signature linked to post-vaccination syndrome, or PVS, a condition where people experience a non-specific set of symptoms including numbness, fatigue, brain fog, anxiety and trouble exercising after receiving a COVID-19 vaccine. Their study compared 42 people with PVS to 22 individuals in the control group. They found differences in certain immune cells, with PVS participants having lower levels of some cells and/or antibodies that help the body recognize infections and fight them off. Additionally, blood tests suggested that the Epstein-Barr virus (EBV) — which causes mono and can stay dormant in the body — had been recently reactivated in more PVS participants than in the control group. The researchers also reported that people with PVS had slightly higher levels of spike protein, the same protein found in the COVID-19 vaccine, still circulating in their blood compared to controls.
While these findings might sound important, several major flaws weaken the study’s conclusions. First, the patients in the PVS group had their blood tested much later than those in the control group — an average of 585 days after vaccination compared to just 199 days for the controls. Since the study only captured immune responses at one point in time, it’s not surprising that the PVS group had lower levels of certain immune cells and antibodies. They had been vaccinated much earlier, so their immune response had more time to weaken. On the other hand, the control group likely received more booster shots, which would have kept their immunity stronger and their antibody levels higher.
Second, the study’s control group of 22 “healthy individuals” from a single region does not represent the nearly 70 percent of the global population that has received at least one series of the COVID-19 vaccine. Immune differences, like the ones found between PVS participants and controls, can be explained by any number of factors including backgrounds, regions, stress and genetic makeup. With such a small and homogenous group, the study cannot draw strong conclusions about how common or unique to COVID-19 vaccination these immune changes are.
Finally, and most importantly, the study does not establish causation. There is no direct evidence linking the immune changes the authors describe to the symptoms reported by PVS patients. While the researchers hint that reactivation of EBV could be playing a role, their only supporting evidence is a small increase in antibodies to one EBV protein in the PVS group. This is not enough to prove that EBV reactivation is actually happening, let alone that it is causing these long-term symptoms.
Serious adverse events following vaccination must be thoroughly investigated to ensure public trust, improve vaccine safety and guide appropriate medical responses. However, this preprint irresponsibly fuels vaccine skepticism based on a tiny sample size and inconclusive data. When research lacks clear conclusions but is aggressively promoted, it is fair to question the authors’ motives.
In today’s climate of heightened distrust in science, researchers must carefully consider their responsibility in public communication. Publishing speculative findings with sensationalist framing does not advance scientific understanding — it undermines it and endangers public health. Unfortunately, the damage from careless publication practices may be permanent. Once sensational headlines spread and people latch onto information that confirms their biases, few will pay attention to the scientific community’s corrections or concerns.
JOHN ATTANASIO is a doctoral candidate in immunobiology at Yale. He can be reached at john.attanasio@yale.edu.