The rapid development of various COVID-19 vaccinations was an important tool in controlling the pandemic and reducing worldwide mortality and morbidity associated with COVID-19 infection. However, due to their accelerated development, it is important to keep monitoring side-effects that can arise especially with the newer technology used in messenger RNA (mRNA) vaccinations. The Pfizer-BioNtech vaccine was the first approved COVID-19 mRNA vaccination, and it targets the COVID-19 spike protein via delivering an mRNA enclosed in a lipid nanoparticle into the deltoid muscle.¹

The majority of side effects following the Pfizer-BioNtech vaccine are not lethal and include fatigue, pain at injection site, fever.¹ Some serious, but rare, adverse effects like myocarditis, and thrombosis, have occurred, and investigations are ongoing.² However, there is limited evidence in the literature that assesses whether a previous infection with COVID-19 could increase the frequency and/or severity of side-effects following vaccination. This is complicated as the collection of the history of prior COVID-19 infection is subjectively based on patient surveys at the point of vaccination that are not linked to hard copies of individual results, potentially yielding less accurate data. Additionally, the incubation period and large subset of asymptomatic infections further complicates the identification of new COVID-19 infections proximal to time of the vaccination.

We conducted a study in a community hospital to assess the side effects associated with Pfizer-BioNTech COVID vaccination and whether a prior history of COVID-19 infection impacts the development of side effects. A survey (Supporting Information: Table S1) was administered on-site to Larkin Community Hospital in Florida, United States from January to February 2021 following the emergency authorization of mRNA vaccinations in the United States in December 2020. During this period, most cases in the United States were due to the original strain of the vaccine before the appearance of the alpha variant. Information about personnel (healthcare workers) demographics, vaccine information and side effects experienced was collected. The control group is healthcare workers who had no history of prior COVID-19 infection when receiving the vaccine, and our experimental group is healthcare workers with a prior history of COVID infection. The hospital's electronic system was also checked to confirm that PCR tests were positive before vaccinations. Statistical analysis to compare the effect of prior COVID-19 infection on side-effects following the Pfizer-BioNtech vaccine was conducted using STATA (version 17.0; StataCorp).³

Seventy-seven healthcare workers (HCWs) fully completed the survey with 67 of those having received the Pfizer COVID-19 vaccination and three chose not to disclose their vaccination type. The most common age group among responders was 30%–39% and 53.2% of participants were female. 20.8% (16) participants reported suffering from a previous COVID-19 infection, all 16 also reported receiving the Pfizer vaccine. The most common demographic groups were Hispanic participants (40.3%) followed by white participants (28.6%).

Only five participants from those who received Pfizer reported experiencing no side-effects on 1st and 2nd dose. 30/67 reported experiencing more than three side-effects and 37/67 reported experiencing less than three side effects. 18/67 reported experiencing more than three side-effects following the 1st dose compared with 25/67 reported experiencing more than three side-effects following the 2nd dose. Pain at injection site within 2 days of vaccination (57/67), fatigue (33/67), chills (30/67), and headaches or dizziness (27/67) were the most experienced side-effects in participants who received Pfizer. There were no serious side-effects reported by the participants.

When comparing patients who experience high frequency of side-effects with those who experienced fewer side-effects, we found HCWs with a prior history of COVID-19 infection to significantly report a higher frequency (>3) of side-effects. 68.75% of HCWs with a prior history of COVID-19 infection reported a high frequency of side effects compared with only 37.2% of HCWs without a prior history of infection (p = 0.027). Table 1 summarizes the comparison of various categorical variables between HCWs that reported a high and low frequency of side effects following Pfizer/BioNTech vaccination.

We further assessed whether the frequency of side-effects differed among those with a prior COVID-19 following the first and second doses of Pfizer/BioNTech vaccination. Our results showed that following the first dose, HCWs with a previous history of infection were significantly more likely to report a higher frequency of side effects while there was no statistically significant difference following the 2nd dose. 50% of HCWs with a prior history of COVID-19 infection reported a high frequency of side effects following the first compared with only 19.6% of HCWs without a prior history of infection (p = 0.017). Table 2 summarizes the comparison of frequency of side-effects following the 1st and 2nd dose of Pfizer/BioNTech vaccination and a history of previous COVID-19 infection.

Our findings seem to be in line with two previous observational studies that revealed that systematic side-effects were about three times more common in individuals with prior COVID-19 infection following Pfizer vaccination compared to individuals with no history of COVID-19 infection.^4-6 It is thought that the increased reactogenicity is directly related to increased immunogenicity as people with previous infections have higher COVID-19 antibody titers compared with those not previously infected.⁵ The findings offered by our analysis aims to improve public health and identify a new pool of individuals for further research to better understand the side-effects of mRNA vaccinations, especially since mRNA vaccinations are under development for viral infections such as HIV.⁷ Larger clinical trials are necessary to fully comprehend the effect a previous infection with virus itself could have on the frequency and severity of side-effects that could arise due to vaccination. Additionally, viral mutation may be combated with further research on individuals with previous infection if they have received a vaccine of a different strain than of their previous infection. Finally, such findings could also influence the choice of vaccination for a select group of individuals.

AUTHOR CONTRIBUTIONS

Conceptualization: Maryam Bayat Mokhtari, Vanessa Samaniego, Arvin Esgandanian; Methodology: Maryam Bayat Mokhtari, Moein Bayat Mokhtari, Vanessa Samaniego, Angela Ishak; Formal analysis: Angela Ishak; Investigation: Maryam Bayat Mokhtari, Moein Bayat Mokhtari, Vanessa Samaniego, Arvin Esgandanian; Writing – Original Draft: Angela Ishak, Maryam Bayat Mokhtari, Vanessa Samaniego; Writing – Review and Editing: Angela Ishak, Maryam Bayat Mokhtari; Supervision: Maryam Bayat Mokhtari.

CONFLICT OF INTEREST

The authors declare no conflict of interest.