No evidence that persistent symptoms are more frequent after COVID-19 vaccination than after infection, contrary to an op-ed in The Hill

In early March 2024, a screenshot of a Telegram post circulated on Instagram and Twitter. It claimed that “[a]fter examining over 1,000 patients, U.S. doctors found that ’long Covid’ developed in 70 percent of cases after vax injection, not after infection”.

The original post, published on the Telegram channel Disclose.tv, had received over 200,000 views at the time of writing. The post linked to a website with the same name that reproduced an op-ed by physicians Pierre Kory and Paul Marik published in The Hill on 6 March 2024.

Disclose.tv is a Germany-based outlet that operates as a news aggregator. According to an investigation by Logically, the site originated from a forum focused on conspiracy theories.

The website itself no longer seems to publish overt conspiracies. However, Logically and Deutsche Welle (DW) News found that Disclose.tv continues to share conspiracy theories, pseudoscience, and hate content through its social media accounts, which have around five million followers. In 2017, PolitiFact included Disclose.tv in its list of websites “containing deliberately false or fake stories”.

Kory and Marik are the president and chief scientific officer, respectively, of the fringe medical group Front Line COVID-19 Critical Care (FLCCC) Alliance. This group extensively promoted the use of ivermectin off-label to prevent and treat COVID-19 despite a lack of evidence supporting this use.

FLCCC Alliance has also promoted other unproven therapies, like nattokinase, for treating long COVID and post-vaccination symptoms.

As we will demonstrate below, Kory and Marik’s op-ed is yet another example of such unsupported claims. The op-ed doesn’t provide credible evidence indicating that COVID-19 vaccination is behind most cases of long COVID. Instead, the authors relied on unverifiable anecdotes that can’t support their claim, as we will show below.

Cases of post-vaccination symptoms resembling long COVID have been reported to the U.S. Vaccine Adverse Event Reporting System (VAERS). However, studies suggest they are rare and far less common than cases of long COVID after infection, as this review will explain.

The 70% figure relies on unverifiable personal observations that don’t support the authors’ claim

The op-ed claimed that, after evaluating over 1,000 individuals with long COVID, “[a]pproximately 70 percent of these patients said their reported symptoms occurred in the minutes, hours, days and weeks after COVID vaccination, as opposed to after COVID infection.

The authors based the 70% figure on data from a private practitioner who is also a member of the fringe medical group FLCCC Alliance. The op-ed didn’t include any explanation about the methodology used to calculate the 70% figure. This is important, as it provides the necessary information to assess the validity of the results. In addition, other issues make the 70% figure unreliable.

First, the fact that these symptoms began after vaccination alone isn’t enough to demonstrate that the vaccine caused them, despite what the op-ed seemed to imply. A temporal association, while a necessary component for determining if there is a causal effect, is only the first step and requires further investigations.

Second, the figure is based exclusively on the patients’ perceptions of symptoms developed after they received a COVID-19 vaccine. There is no indication that the evaluation included analyses or tests that objectively assessed the presence and severity of these symptoms.

Finally, the op-ed didn’t indicate whether the evaluation considered factors other than vaccination as a cause or contributing factor to the observed symptoms. These include, for example, a previous SARS-CoV-2 infection or the existence of underlying medical conditions.

In other words, the claim is entirely based on anecdotal descriptions of symptoms that patients self-reported from a single private practice. The problem with such data is that it is highly prone to biases, as neurologist Steven Novella explained in Science-Based Medicine.

For instance, the patients who go to that specific private practice might not be representative of the general population (selection bias), meaning the observations may not be generalizable to everyone. The fact that the observations relied on self-reporting also introduces a risk of recall bias due to the patients’ inaccurate or partial recollection of events. Data collected in this way is also subject to distortions (reporting bias) and biased interpretations that support either the patient’s or the doctor’s preexisting beliefs (confirmation bias).

There’s no evidence that the physician or Kory and Marik attempted to account for these potential biases in their interpretation of the data.

The high risk of bias, the lack of information about the data and methodology, and the FLCCC Alliance’s record of spreading misinformation cast serious doubts over the figure’s credibility.

The preprint by Krumholz et al. doesn’t demonstrate that persistent post-vaccination symptoms frequently occur

To further support the claim that “adverse events from COVID-19 vaccination”, including persistent symptoms, are common, Kory and Marik cited a preprint by Krumholz et al. uploaded to the preprint server medRxiv on 10 November 2023^[1]. A preprint is a preliminary version of a manuscript that has yet to be evaluated by other experts.

As the title of the preprint clearly states, the authors conducted “A Descriptive Analysis of Reported Symptoms and Patient Experiences After Covid-19 Immunization”.

The analysis involved 241 individuals aged 18 and older who participated in the Yale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) study from May 2022 to July 2023. This study, administered online, collects information about symptoms and medical history with the purpose of better understanding long COVID and post-vaccine adverse events.

The researchers’ objective was to characterize chronic post-vaccination syndrome, “defined by self-report in response to whether the individual thought the vaccine had injured them”.

To do that, the authors used surveys to evaluate the type of symptoms, their severity and duration, the treatments participants had tried, and new medical conditions diagnosed since vaccination. The authors excluded people reporting long COVID.

Unlike The Hill op-ed, the preprint fully described the methodology used. The authors also considered variables that could influence the observations, such as demographics (age, gender, race, country of residence, marital status, household income, employment status, and insurance status), preexisting medical conditions, prior SARS-CoV-2 infection, and vaccination status, and the type of COVID-19 vaccine participants received.

The results showed a diverse range of reported symptoms beginning soon after COVID-19 vaccination. In many cases, these symptoms were severe, debilitating, and persisted for a year or more. The authors concluded that people reporting post-vaccination syndrome in the evaluated group were generally highly symptomatic, had poorer health, and had tried many treatment strategies without success.

In contrast to the op-ed, the preprint clearly stated the limitations of the analysis in its Discussion section, including the lack of a control group and the reliance on self-reporting. It also explained that the method of selecting the participants led to discrepancies compared to the overall population. Therefore, the authors concluded that “it is not possible to estimate the incidence or who might be most susceptible to this condition”.

The authors further highlighted that the cause of the reported symptoms remained undetermined. “The net benefit of the covid-19 vaccination program is clear”, the authors stated. However, the temporal relationship between vaccination and the onset of symptoms “suggests a potential relationship” that requires further investigation.

In summary, while the preprint documented and characterized self-reported symptoms following COVID-19 vaccination, it didn’t attribute them to any specific cause. It also didn’t show how common these cases are in the general population, as FactCheck.org explained. Therefore, these results don’t provide sufficient evidence to support Kory and Marik’s claim.

There is so far no clear link between COVID-19 vaccines and post-vaccination symptoms, which seem far less common than long COVID after infection

COVID-19 vaccines are safe and highly effective at reducing the risk of severe COVID-19. But as with other medical interventions, they carry a small risk of rare complications. Certain COVID-19 vaccines are associated with rare cases of severe allergic reactions (anaphylaxis) and a slightly increased risk of blood clotting, Guillain-Barré syndrome, and heart inflammation.

But these severe reactions to vaccination are infrequent. Most people only experience mild side effects that go away in a few days.

A spokesperson from the U.S. Centers for Disease Control and Prevention (CDC) told FactCheck.org that the agency is “aware of reports in the Vaccine Adverse Event Reporting System (VAERS) and in the media of a wide range of long-lasting symptoms following COVID-19 vaccination (such as fatigue, headache, and difficulty concentrating)”.

These symptoms, which usually appear within the first weeks after vaccination, have been popularly called “Long Vax” due to their resemblance with long COVID symptoms. However, the clinical characteristics of these symptoms and their potential link to vaccination are currently unclear.

In July 2023, an article in Science discussed how scientists had begun acknowledging post-vaccination symptoms as a real phenomenon that warrants further research.

Some researchers suggest that post-vaccination symptoms share some similarities with two known medical conditions. The first one is small fiber neuropathy, an uncommon chronic condition that affects a person’s ability to sense pain. This results in numbness, painful tingling, or burning sensations in the feet and hands^[2].

The second one is a condition called postural orthostatic tachycardia syndrome (POTS)^[3,4]. This condition specifically affects people when they transition from lying down to standing up, causing muscle weakness, fast heart rate, fatigue, and brain fog.

About half of the cases of small fiber neuropathy are caused by underlying medical conditions, with diabetes being the most common cause. The other half of the cases happen for no known reason. It is also unknown what causes POTS, and no diagnostic tests are available. These limitations make it difficult to study the potential connection between these conditions and COVID-19 vaccination.

To date, only a few studies have addressed long-term symptoms after COVID-19 vaccination.

One preprint uploaded to medRxiv on 17 May 2022 evaluated symptoms of neuropathy after COVID-19 vaccination in 23 participants^[5]. The authors found a variety of neuropathic symptoms following COVID-19 vaccination that improved when treated with corticosteroids in some patients. Corticosteroids are a type of anti-inflammatory drug that also reduces the activity of the immune system. This led the authors to hypothesize that the symptoms observed might be the result of immune reactions, similar to what happens in COVID-19 patients. But these results haven’t been published in a scientific journal yet.

In December 2022, a team at Cedars-Sinai Medical Center published a study analyzing the occurrence of POTS in almost 285,000 people who had received a COVID-19 vaccine^[6]. The study found that the rate of POTS symptoms was 33% higher within the 90 days following vaccination than in the three months before. However, it also found that the rate of POTS symptoms was much higher (52%) after SARS-CoV-2 infection.

Diagnosing post-vaccination symptoms is challenging due to the overlap in the reported symptoms with other conditions, including long COVID, neuropathy, PTOS, and chronic fatigue syndrome. For example, distinguishing between post-vaccine symptoms and long COVID with a high degree of certainty would require demonstrating that the person had no previous SARS-CoV-2 infection. This is difficult, given the large number of infections and the fact that many of them went unnoticed.

Because of the difficulties in making an accurate diagnosis, estimating the rate at which these symptoms occur is also complicated. However  , researchers suggest that the number of cases potentially attributable to COVID-19 vaccination is likely very low, as many suspected post-vaccine symptoms are due to causes other than vaccination.

In May 2023, the Paul-Ehrlich-In­sti­tut (Germany) issued a statement saying it had found “no safety signal for the occurrence of these symptoms after [COVID-19] vaccination”. The agency found that the reporting rate of chronic fatigue syndrome, post-vaccination syndrome, POTS, and post-acute COVID-19 syndrome in the adverse reaction database of the European Medicines Agency was less than one suspected case per 100,000 vaccinations. The agency concluded that persistent symptoms following COVID-19 vaccination “are therefore extremely rarely reported”.

Likewise, the CDC spokesperson explained to FactCheck.org that “to date, no unusual or unexpected patterns of long-lasting symptoms or health problems following vaccination have been linked to vaccination by COVID-19 vaccine safety monitoring systems”.

Conclusion

Mounting evidence suggests that long-term symptoms following COVID-19 vaccination are a genuine phenomenon. However, Kory and Marik’s op-ed doesn’t provide evidence that these post-vaccination symptoms occur frequently in the general population or that COVID-19 vaccines are the cause.

Current evidence instead suggests that long-term post-vaccination symptoms are rare. While the temporal association suggests a potential link between these symptoms and COVID-19 vaccines, a connection between both remains unconfirmed. Further studies are warranted to better understand why these symptoms occur and how to treat them.

REFERENCES

• 1 –  Krumholz et al. (2023) Post-Vaccination Syndrome: A Descriptive Analysis of Reported Symptoms and Patient Experiences After Covid-19 Immunization. medRxiv. [Note: This is a preprint that has yet to be peer-reviewed at the time of this review’s publication.]
• 2 – Abbott et al. (2022) Acute small fiber neuropathy after Oxford-AstraZeneca ChAdOx1-S vaccination: A report of three cases and review of the literature. Journal of the Peripheral Nervous System.
• 3 – Teodorescu et al. (2024) Postural orthostatic tachycardia syndrome after COVID-19 vaccination. Heart Rhythm.
• 4 – Baral & Bhandari (2022) Postural Orthostatic Tachycardia Syndrome: Possibly Covid Vaccine Related. Chest.
• 5 – Safavi et al. (2022) Neuropathic symptoms with SARS-CoV-2 vaccination. medRxiv. [Note: This is a preprint that has yet to be peer-reviewed at the time of this review’s publication.]
• 6 – Kwan et al. (2022) Apparent risks of postural orthostatic tachycardia syndrome diagnoses after COVID-19 vaccination and SARS-Cov-2 Infection. Nature Cardiovascular Research.