Long Covid and Vaccines: Separating Facts From Falsehoods

Hallie Levine

July 14, 2023

Editor's note: Find the latest long COVID news and guidance in Medscape's Long COVID Resource Center.

The COVID-19 vaccines have been a game changer for millions of people worldwide in preventing death or disability from the virus. Research suggests that they offer significant protection against long COVID.

Studies have consistently found that these vaccines prevent the new onset of long COVID as well as flare-ups for people who already have the condition.

False and unfounded claims made by some antivaccine groups that the vaccines themselves may cause long COVID persist and serve as barriers to vaccination.

To help separate the facts from falsehoods, here's a checklist for doctors on what scientific studies have determined about vaccination and long COVID.

What the Research Shows

Doctors who work in long COVID clinics have for years suspected that vaccination may help protect against the development of long COVID, noted Lawrence Purpura, MD, MPH, an infectious disease specialist at New York–Presbyterian/Columbia University Irving Medical Center, who treats patients with long COVID in his clinic.

Over the past year, several large, well-conducted studies have borne out that theory, including the following studies:

  • In the RECOVER study, published in May in the journal Nature Communications, researchers examined the electronic health records of more than 5 million people who had been diagnosed with COVID and found that vaccination reduced the risk that they would develop long COVID. Although the researchers didn't compare the effects of having boosters to being fully vaccinated without them, experts have suggested that having a full round of recommended shots may offer the most protection. "My thoughts are that more shots are better, and other work has shown compelling evidence that the protective effect of vaccination on COVID-19 wanes over time," said study co-author Daniel Brannock, MS, a research scientist at RTI International in Research Triangle Park, North Carolina. "It stands to reason that the same is true for long COVID."

  • A review published in February in BMJ Medicine concluded that 10 studies showed a significant reduction in the incidence of long COVID among vaccinated patients. Even one dose of a vaccine was protective.

  • A meta-analysis of six studies published last December in Antimicrobial Stewardship and Healthcare Epidemiology found that one or more doses of a COVID-19 vaccine were 29% effective in preventing symptoms of long COVID.

  • In a June meta-analysis published in JAMA Internal Medicine, researchers analyzed more than 40 studies that included 860,000 patients and found that two doses of a COVID-19 vaccine reduced the risk of long COVID by almost half.

The message? COVID vaccination is very effective in reducing the risk of long COVID.

"It's important to emphasize that many of the risk factors [for long COVID] cannot be changed, or at least cannot be changed easily, but vaccination is a decision that can be taken by everyone," said Vassilios Vassiliou, MBBS, PhD, clinical professor of cardiac medicine at Norwich Medical School in the United Kingdom, who co-authored the article in JAMA Internal Medicine.

Why Vaccines May Be Protective

The COVID-19 vaccines work well to prevent serious illness from the virus, noted Aaron Friedberg, MD, clinical co-leader of the Post COVID Recovery Program at the Ohio State University Wexner Medical Center. That may be a clue to why the vaccines help prevent long COVID symptoms.

"When you get COVID and you've been vaccinated, the virus may still attach in your nose and respiratory tract, but it's less likely to spread throughout your body," he explained. "It's like a forest fire — if the ground is wet or it starts to rain, it's less likely to create a great blaze. As a result, your body is less likely to experience inflammation and damage that makes it more likely that you'll develop long COVID."

Friedberg stressed that even for patients who have had COVID, it's important to get vaccinated — a message he consistently delivers to his own patients.

"There is some protection that comes from having COVID before, but for some people, that's not enough," he said. "It's true that after infection, your body creates antibodies that help protect you against the virus. But I explain to patients that these may be like old Velcro: they barely grab on enough to stay on for the moment, but they don't last long term. You're much more likely to get a reliable immune response from the vaccine."

In addition, a second or third bout of COVID could be the one that gives patients long COVID, Friedberg adds.

"I have a number of patients in my clinic who were fine after their first bout of COVID but experienced debilitating long COVID symptoms after they developed COVID again," he said. "Why leave it to chance?"

Vaccines and "Long Vax"

The COVID vaccines are considered very safe but have been linked to very rare side effects, such as blood clots and heart inflammation. There have also been anecdotal reports of symptoms that resemble long COVID — a syndrome that has come to be known as "long Vax" — an extremely rare condition that may or may not be tied to vaccination.

"I have seen people in my clinic who developed symptoms suggestive of long COVID that linger for months — brain fog, fatigue, heart palpitations — soon after they got the COVID-19 vaccine," said Purpura. But no published studies have suggested a link, he cautions.

A study called LISTEN is being organized at Yale in an effort to better understand post-vaccine adverse events and a potential link to long COVID.

Talking to Patients

Discussions of vaccination with patients, including those with COVID or long COVID, are often fraught and challenging, said Purpura.

"There's a lot of fear that they will have a worsening of their symptoms," he explained. The conversation he has with his patients mirrors the conversation all physicians should have with their patients about COVID-19 vaccination, even if they don't have long COVID. He stresses the importance of highlighting the following components:

  • Show compassion and empathy. "A lot of people have strongly held opinions — it's worth it to try to find out why they feel the way that they do," said Friedberg.

  • Walk them through side effects. "Many people are afraid of the side effects of the vaccine, especially if they already have long COVID," explained Purpura. Such patients can be asked how they felt after their last vaccination, such a shingles or flu shot. Then explain that the COVID-19 vaccine is not much different and that they may experience temporary side effects such as fatigue, headache, or a mild fever for 24–48 hours.

  • Explain the benefits. Eighty-five percent of people say their healthcare provider is a trusted source of information on COVID-19 vaccines, according to the Kaiser Family Foundation. That trust is conducive to talks about the vaccine's benefits, including its ability to protect against long COVID.

Other Ways to Reduce Risk of Long COVID

Vaccines can lower the chances of a patient's developing long COVID. So can the antiviral medication nirmatrelvir (Paxlovid). A March 2023 study published in JAMA Internal Medicine included more than 280,000 people with COVID. The researchers found that vaccination reduced the risk for developing the condition by about 25%.

"I mention that study to all of my long COVID patients who become reinfected with the virus," said Purpura. "It not only appears protective against long COVID, but since it lowers levels of virus circulating in their body, it seems to help prevent a flare-up of symptoms."

Another treatment that may help is the diabetes drug metformin, he added.

A June 2023 study published in The Lancet Infectious Diseases found that when metformin was given within 3 days of symptom onset, the incidence of long COVID was reduced by about 41%.

"We're still trying to wrap our brains around this one, but the thought is it may help to lower inflammation, which plays a role in long COVID," Purpura explained. More studies need to be conducted, though, before recommending its use.


Nature Communications: "Long COVID risk and pre-COVID vaccination in an EHR-based cohort study from the RECOVER program." May 2023. Long COVID risk and pre-COVID vaccination in an EHR-based cohort study from the RECOVER program | Nature Communications

BMJ Medicine: "Effect of COVID-19 vaccination on long COVID: Systematic review." February 2023. e000385.full.pdf (bmj.com)

Cambridge University Press: "The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post-COVID-19 conditions: A systematic literature review and meta-analysis." December 2022. The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post–COVID-19 conditions: A systematic literature review and meta-analysis | Antimicrobial Stewardship & Healthcare Epidemiology | Cambridge Core

JAMA Internal Medicine: "Risk factors associated with post-COVID-19 condition: A systematic review and meta-analysis." June 2023. Risk Factors Associated With Post-COVID-19 Condition: A Systematic Review and Meta-analysis - PubMed (nih.gov)

medRxiv: "Neuropathic symptoms with SARS-CoV-2 vaccination." May 2022. Neuropathic symptoms with SARS-CoV-2 vaccination - PubMed (nih.gov)

JAMA Internal Medicine: "Association of treatment with nirmatrelvir and the risk of post-COVID-19 condition." March 2023. Association of Treatment With Nirmatrelvir and the Risk of Post–COVID-19 Condition | Clinical Pharmacy and Pharmacology | JAMA Internal Medicine | JAMA Network

The LANCET Infectious Diseases: "Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomized, quadruple-blind, parallel-group, phase 3 trial." June 8, 2023. Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial - The Lancet Infectious Diseases


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