Previous SARS-CoV-2 infection associated with more adverse events following mRNA vaccination

The phase 3 trials of the Pfizer and Moderna coronavirus disease 2019 (COVID-19) vaccines did not include those with a known previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Recent evidence indicates that mRNA vaccines may induce more adverse events in these individuals. In a paper recently uploaded to the medRxiv* preprint server, 947 individuals, 265 of which have previously reported SARS-CoV-2 infection, were monitored post-vaccination for adverse events, finding that there could be a link between previous infection and greater incidence of these events.

Study: Previous COVID-19 infection but not Long-COVID is associated with increased adverse events following BNT162b2/Pfizer vaccination. Image Credit: BaLL LunLa / Shutterstock

National Health Service (NHS) workers in the UK completed an electronic survey regarding the occurrence of adverse events following vaccination, categorized between severity, duration, and onset. A composite score was then computationally attributed to each report to provide an estimate of adverse event-related morbidity, and these results were compared between demographics and those with and without a history of COVID-19. PCR and antibody testing was also performed on a subset of these individuals as a sensitivity control to confirm whether or not these individuals had previously been infected with SARS-CoV-2 for certain, and being generally in-line with the whole-cohort results.

The occurrence of adverse events

Of those suffering any adverse events following vaccination, 75% reported them within 24 hours, and the remainder within 48. Women experienced a greater number and duration of symptoms, and symptoms significantly lessened with age. Importantly, after controlling for these factors, adverse event frequency, duration, and intensity were strongly correlated with previous reports of COVID-19.

In particular, five events were associated with previous SARS-CoV-2 infection: fever, fatigue, myalgia, arthralgia, and lymphadenopathy. Events occurring locally to the vaccine injection site, such as redness and swelling, were not associated with a history of COVID-19, nor were gastrointestinal symptoms, and no difference in vaccine-illness time interval was noted for those with prior COVID-19. Thirty of the participants had reported suffering from long-covid, and for these, there was no significant difference in symptom frequency or intensity when compared to the general prior-COVID-19 group.

The most commonly reported event amongst any group was pain, with almost 30% of those with no history reporting compared with around 35% of those with prior COVID-19. The other most frequently occurring events, in descending order, were for those without history: fatigue (20%), headache (18%), myalgia (15%), and anthralgia (7%), while those with history experienced: myalgia (30%), fatigue (29%), headache (22%), and arthralgia (17%). Other events with a notable difference between groups included fever, at only 2% in those with no history versus around 8% for those with prior COVID-19, and lymphadenopathy, with less than 1% of those with no history of COVID-19 reporting this event, and 4% of those with prior infection.

This work has demonstrated that the mRNA vaccines present an increased risk of adverse events in those with a history of SARS-CoV-2 infection. However, severity was not indicated by the presence of long-COVID-19. The authors suggest that administration of the second vaccine dose may need to be reconsidered in those with prior COVID-19, assuming effective immunity is obtained, particularly given reports of more intense adverse events following the second dose. 27% of the participants had reported prior COVID-19, higher than the likely true numbers due to responder bias. Further, only a very low number of long-covid sufferers were included in the study, and thus the conclusions drawn regarding non-significant differences could be erroneous. In any case, this large study has demonstrated an association between previous SARS-CoV-2 infection and increased occurrence, duration, and severity of adverse events following mRNA vaccination.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Michael Greenwood

Michael graduated from Manchester Metropolitan University with a B.Sc. in Chemistry in 2014, where he majored in organic, inorganic, physical and analytical chemistry. He is currently completing a Ph.D. on the design and production of gold nanoparticles able to act as multimodal anticancer agents, being both drug delivery platforms and radiation dose enhancers.