A March 16 KFYR-TV article [hat-tip @Laurel] reports:

In a study posted by medRxiv (med archive), researchers report many people who had previously been infected with the virus reported flu-like symptoms after their first dose.


New findings show people like Barth who have previously had COVID might be at a higher risk of more intense reactions to the vaccine due to their antibodies attacking the known spike proteins.

An earlier (Feb 12) claim from an Alabama state health department doctor contradicts that:

But, Dr. Landers said having had COVID-19 before doesn’t really change your chances of experiencing side effects or not.

“I really have not seen that in any scientific literature,” she said.

Do people who have had COVID and then get the vaccine, experience significantly harsher side effects?

  • It looks like there’s some that say it’s true, some that say it’s not. (Your question may attract close votes because it’s not citing a notable source for the claim, but these unreliable sources I found indicate it shouldn’t be closed.) – Laurel Mar 16 at 11:14
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    @Laurel: I have edited those in to get this question on topic. – Oddthinking Mar 16 at 11:51
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    Welcome to Skeptics! – Oddthinking Mar 16 at 11:51
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    At this stage with the vaccinations, questions should be asking "Is it possible...?", "Is it highly likely...?", "What are the chances...?” etc. – Mari-Lou A Mar 16 at 12:30
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    Scientifically/biologically it's not at all implausible. It's well documented that the 2nd dose of Pfizer or Moderna gives worse side effects than the 1st; the reason for this is almost universally thought to be the [level of] pre-existing immunity after the 1st dose. So having had Covid itself recently enough means you'll have some immunity, thus the 1st does acts more like a 2nd one. Not putting this as an answer because it's "theoretical". More conclusive data is yet to be published. – Fizz Mar 16 at 18:48


That is: asking for "do they have" is probably not the best way to ask the question.

They all can have much worse side effects for people who overcame a coronavirus infection naturally on receiving a first dose of the vaccines.

As we see people complaining more about the second shot than the first if they were immuno-naive, the first shot is already the second encounter for the immune system if there was a prior coronavirus infection.

The problematic ingredients like kationic lipids, polythelyene-glycol nano particles, a monkey adenovirus or the most unpleasant effects of the Spike-protein itself are all added on top of a double danger of antibody dependent enhancement, which worsens the disease once a real virus comes along, and the even more obvious danger of immune system overshoot. For the latter reason, alone, the German RKI comes to this conclusion in its current vaccination guidelines:

It can be assumed that persons who have recovered from SARS-CoV-2 infection or COVID-19 have at least some temporary protection against disease. Due to this presumed immunity, to avoid exaggerated side effects (exaggerated systemic vaccination reactions) and in view of the existing vaccine shortage, in the opinion of the STIKO, a single vaccination of persons who have been through infection (laboratory-diagnostically confirmed) should be considered 6 months after recovery at the earliest[…]

If a laboratory-diagnostically confirmed SARS-CoV-2 infection occurs after administration of the 1st vaccine dose, the STIKO is of the opinion that the 2nd vaccine dose can also only be administered at the earliest 6 months after recovery or diagnosis.

As before any vaccination, it should be checked whether the health status of the person to be vaccinated permits vaccination against COVID-19.

RKI: "COVID-19 und Impfen: Antworten auf häufig gestellte Fragen (FAQ) Gesamtstand: 15.3.2021"

Since the original studies of the ongoing phaseIII-trials were botched already by the manufacturers, we need to look at different studies. Two of those, sadly only preprints:

We found that HCW previously infected with SARS-CoV-2, diagnosed via IgG to spike protein, had a classic secondary response to a single inoculation with a spike-based mRNA vaccine. That is, antibody titers started peaking at 7 days, and achieved higher titers and neutralization in 14 days compared to volunteers exposed to SARS-CoV-2 spike protein for the first time. Thus, there was a broad increase in binding and functional antibodies. This occurred for HCW who were both symptomatic and asymptomatic with their SARS-COV-2 infection. Although we did not have peak titers for these individuals after natural infection, the titers developed after single vaccination was higher than peak titers in inpatients and outpatients with COVID-19, similar to what has been described in primary vaccination after 2 doses of the spike-based mRNA vaccines. This secondary response occurs through activation of memory B cells; and this study demonstrates recall responses through the antibody production stages in response to vaccination.

— Saman Saada: "Single Dose Vaccination in Healthcare Workers Previously Infected with SARS-CoV-2" doi: https://doi.org/10.1101/2021.01.30.21250843

For individuals with pre-existing immunity to SARS-CoV-2 the first vaccine dose likely immunologically resembles the booster dose in naïve individuals. Anecdotally, individuals with pre-existing immunity also experience more severe reactogenicity after the first doses compared to naïve individuals. This begs the question if individuals with pre-existing immunity should even receive a second dose of vaccine.

The antibody titers of vaccinees with pre- existing immunity are not only 10-20 times higher than those of naïve vaccines at the same time points (p <0.0001, two tailed Mann Whitney test), but also exceed the median antibody titers measured in naïve individuals after the second vaccine dose by more than 10-fold.

Vaccine recipients with pre-existing immunity experience systemic side effects with a significantly higher frequency than antibody naïve vaccines (e.g., fatigue, headache, chills, fever, muscle or join pains, in order of decreasing frequency, P < 0.001 for all listed symptoms, Fisher’s exact test, two-sided).

— Florian Krammer et al.: "Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine" doi: https://doi.org/10.1101/2021.01.29.21250653

Effectively, same study also published as correspondence in the NEJM:

enter image description here
Panel A shows the quantitative SARS-CoV-2 spike antibody titers (assessed by means of enzyme-linked immunosorbent assay and expressed as area under the curve [AUC]) for 110 participants. Some participants with preexisting immunity had antibody titers below detection (AUC of 1) at the time point before vaccination. Geometric means with 95% confidence intervals (not adjusted for multiple testing) are shown. Panel B shows the relative frequency of vaccine-associated side effects after the first vaccine dose (230 participants). The local side effects occurred with similar frequency among participants with preexisting immunity and among those without preexisting immunity, whereas the systemic symptoms were more common among participants with preexisting immunity. The bars represent the relative frequency of each symptom, and the numbers at the top of the graph represent the absolute numbers for a given symptom, with a given participant possibly having more than one symptom.

— Florian Krammer: "Antibody Responses in Seropositive Persons after a Single Dose of SARS-CoV-2 mRNA Vaccine", March 10, 2021, DOI: 10.1056/NEJMc2101667

Both studies as evaluated by a peer:

But those with pre-existing immunity experienced systemic side effects such as fatigue, headache, chills, fever, and muscle or joint pains with considerably higher frequency.

— Jacqui Wise: "Covid-19: People who have had infection might only need one dose of mRNA vaccine", BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n308 (Published 02 February 2021)

These two studies show:

  • that natural immunity from natural infection provides somewhat good immunity against currently circulating variants of the virus
  • that side effects increase significantly for those with natural immunity already present, and that vaccination after an infection should be postponed

Both preprints match in parts already properly peer-reviewed, albeit very small, studies like this one:

Side effects occurred with comparable frequency in Group 1 and Group 2 subjects, with the exception of local pain, which was reported more frequently by Group 1. In both groups, side effects were more frequent after the second vaccine dose.

— Federico Gobbi et al.: "Antibody Response to the BNT162b2 mRNA COVID-19 Vaccine in Subjects with Prior SARS-CoV-2 Infection", Viruses, 13, 422, March 2021. https://doi.org/10.3390/ v13030422

This study is giving a comparison of:

                  prior infection     no prior covid exposure
                  1st  dose  2nd      1st  dose  2nd
 local pain       100%       83%      33%        44%
 adenopathy        17%        0%       0%         0%

It is the current opinion of RKI, PEI, HAS (official German and French institutions) based on studies like the one above. This emerging evidence might of course still change somewhat, but it seems necessary to point out that quite a few more experts have shared their trust in the validity of these findings already:

“Should I get the vaccine if I already had covid-19?” The Centers for Disease Control and Prevention says yes, with a narrow exception for those who have been infected in the past 90 days and received convalescent plasma or antibody therapy.

But this is outdated and fails to take natural immunity seriously. As a result of this flawed guidance, Americans with natural immunity Many in the medical field have been playing down natural immunity. In the noble effort to overcome vaccine hesitancy, they argue that everyone should get the vaccine to reach herd immunity and reopen society. But we need to stick to the science. Let me be clear: I believe the vaccine is safe and strongly recommend that we vaccinate all Americans, but doing so is not a requirement to achieve herd immunity. Given that close to a third of all Americans and perhaps more have had covid-19 infections, it’s possible that herd immunity is closer than we think.

— Marty Makary (Professor at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health. Editor-in-Chief of Medpage Today: "People who previously had covid-19 should go to the back of the vaccine line", Washington Post, Jan 22, 2021.

The concerns for a perhaps enough already or even 'too strong' immune response in people previously infected – as cited from the RKI guideline – is highlighted not only with the two studies mentioned, but also evidently based on two research letters in the Lancet:

In summary, we show that individuals with previous SARS-CoV-2 infection generate strong humoral and cellular responses to one dose of BNT162b2 vaccine, with evidence of high titres of in-vitro live virus neutralisation. In contrast, most individuals who are infection-naive generate both weak T-cell responses and low titres of neutralising antibodies.

— Maria Prendecki et al.: "Effect of previous SARS-CoV-2 infection on humoral and T-cell responses to single-dose BNT162b2 vaccine" The Lancet, February 25, 2021 DOI:https://doi.org/10.1016/S0140-6736(21)00502-X

We reasoned that previous infection could be analogous to immune priming.

— Charlotte Manisty et al.: "Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals", The Lancet, Published: February 25, 2021. DOI:https://doi.org/10.1016/S0140-6736(21)00501-8

The German Robert-Koch-Institut explains this twice, in Epidemiological Bulletins:

On the question of when persons with proven SARS-CoV-2 infection should be offered vaccination, the STIKO cannot yet make a definitive statement on the basis of the evidence currently available. According to the prevailing expert opinion, persons who have undergone a laboratory-diagnostically confirmed infection with SARS-CoV-2 should not be vaccinated for the time being.

— RKI: "Epidemiologisches Bulletin", 2, 2021, 14. January 2021" PDF

And even more drastic and quite clearly, later:

Persons with prior laboratory-confirmed SARS-CoV-2 infection may experience transient increased systemic reactions after vaccination. [...] Due to the immunity after SARS-CoV-2 infection and in view of the continuing vaccine shortage, immunocompetent individuals who have experienced SARS-CoV-2 infection should not be vaccinated for the time being in the opinion of STIKO.
The currently available clinical and immunological data demonstrate a protective effect for at least 6 to 8 months after surviving a SARS-CoV-2 infection. Accordingly, COVID-19 vaccination should be considered at the earliest 6 months after recovery or diagnosis, taking prioritization into account. In this case, one vaccine dose is sufficient, since high antibody titers can already be achieved, which are not further increased by a 2nd vaccine dose. […]

— RKI: "Epidemiologisches Bulletin", 12, 2021, 12. March 2021. PDF

An American evaluation looks like this, also citing the Krammer study:

History of SARS-CoV-2 infection

Individuals with recent, documented SARS-CoV-2 infection (including those who are diagnosed following the first vaccine dose) should have recovered from acute infection and met criteria for discontinuation of isolation precautions before receiving the vaccine (either the initial dose or the second dose of a two-dose series) (see 'Administration' above). It is also reasonable for such individuals to delay any vaccine receipt for a few months after infection […] as the risk of reinfection appears extremely low in this period. The CDC also suggests that individuals who received monoclonal antibodies or convalescent plasma for COVID-19 should delay vaccination for at least 90 days from the time of treatment. This delay also applies to receipt of the second vaccine dose of a two-dose series if antibody-based COVID-19 therapy was administered after the initial vaccine dose.

Several small studies have suggested that after a single mRNA vaccine dose, individuals with evidence of prior SARS-CoV-2 infection mount substantially higher binding and neutralizing antibody responses compared with SARS-CoV-2-naïve individuals. Whether this finding translates into a durable protective response with a single vaccine dose in previously infected individuals is uncertain.

Individuals with a history of SARS-CoV-2 may also be more likely to experience local and systemic adverse effects (eg, fevers, chills, myalgias, fatigue) after the first vaccine dose than SARS-CoV-2-naïve individuals.

— Kathryn M Edwards & Walter A Orenstein: "COVID-19: Vaccines to prevent SARS-CoV-2 infection", Uptodate.com, Feb 2021. last updated: Mar 17, 2021.

From an ethics perspective that includes medical considerations, the WHO iswas on record with:

Therefore, the target group consists solely of persons who have not yet been infected. Persons who have been infected with the pandemic virus strain and have recovered from illness or only had mild disease will already have developed immunity and do not need vaccination. (src, p20)

Disclaimer: this last bit is of course a logical, fundamental truth of science and medicine, and thus we now call such things a 'conspiracy theory'. That's the new normal.

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    Thanks so much for the amazing answer here @LangLangC (+1). It will take me a day to digest it all. When you say "that side effects increase significantly for those with natural immunity already present, after vaccination after infection is very questionable idea", what gives you pause? For individuals who have already had COVID and then get the vaccines, what side effects besides fever chills and headaches existed> I ask because those are also the same side effects listed for individuals who have not had COVID previously, but get the vaccine. Thanks again! – hotmeatballsoup Mar 17 at 12:14
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    Unless you are a qualified medical professional, you are putting the site at risk with the end of your answer (everything following "These two studies show"). Flagged, – David Hammen Mar 17 at 12:26
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    How does the end of LangLangC's answer conflict with the evidence provided in the reports they cited? If there are contradictions, that's one thing, but if they accurately summarize the data in the cited reports, then they're just that -- accurate summaries. – hotmeatballsoup Mar 17 at 12:31
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    @DavidHammen On this site, the working model is that no-one is qualified anything, and 'we do not give medical advice', never. What the bullets present is the summary of what the RKI & PEI (Germany) or the HAS (France) say: at least wait min 3 better 6 months, and refuse the 2nd shot, if a potential vaccinee already had the infection. The risk&cost/benefit seems likely negative under these circumstances. Or do you read those sources differently? If you do, please point that out. Or if eg the CDC contradicts those 3 institutions (couldn't find it yet) that'll work as well. – LangLаngС Mar 17 at 12:35
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    @mmeent Generally, calling other users liars crosses the line for the SE "Be nice" policy. Please refrain from that in the future, and choose language that expresses your point without making it personal. – fredsbend Mar 19 at 1:07

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