This study evaluates the safety and efficacy of a single mRNA-based vaccine dose in post-SARS-CoV-2 infected individuals. We demonstrate that a single dose induces a strong humoral response regardless of seropositivity in previously infected subjects. Although they had higher rates of adverse events compared to the infection-naïve population, a single vaccine dose was generally safe, and this regimen can be considered for the post-infected population.
The BNT162b2 mRNA vaccine, administered in a two-dose regimen, provides 95% protection against COVID-19 at least seven days after the second dose [1–3]. The reported efficacy after the first dose is 52% [21]. Similar to previous case series that evaluated antibody levels after a single mRNA-based vaccine dose in post-infected individuals [5–7], our post-infected population developed, approximately 10-fold higher antibody titer levels compared to the antibody levels after a second dose in the infection-naïve cohort, two weeks after vaccination. A linear correlation was found between the pre and post-first vaccine dose antibody titers in the post-infected population. Importantly, even among all seronegative participants who had evidence of a previous SARS-CoV-2 infection, a single vaccine dose induced higher titer levels compared to the infection naïve cohort, suggesting immune memory persistence. With the risk of reinfection increasing with time, several COVID-19 reinfection cases have already been documented [22–29]. The fact that most reinfected patients are asymptomatic or mildly symptomatic, raises the possibility that immunity is maintained and reduces the disease symptom severity even in cases of undetectable antibody levels at the time of reinfection. Here, we studied post-infected individuals vaccinated 3–6 months after the infection. Although there was no correlation between the time from the infection and antibody titer levels, a single vaccine dose induced a strong humoral response even in seronegative individuals. Taken together, in post-infected populations, a single dose vaccine along with a serological test may provide an effective alternative regimen.
Local and systemic side effects were reported among BNT162b2 vaccine recipients. Reactogenicity after the first dose was characterized mostly with mild or moderate local reactions, while after the second dose, also systemic side effects were more common and severe. The frequency of severe systemic events was less than 0.9% and 2% after the first and the second vaccine injections respectively [1–3]. In this study, the reported frequency of local and moderate systemic side effect was in agreement with previous studies. However, 6.8% of the post-infection cases required emergency department visits or hospitalization due to over activation of the immune system or allergic reactions that needed medical supervision and care, while none of the infection naïve participants needed medical care. Severe vaccine related side effects were also reported in other studies of post-infected population [4, 5]. This finding should be taken into consideration when vaccinating this population.
Although this study provides clear evidence regarding immune memory persistence in post infected individuals, the study has several limitations. The relatively small sample size of the post-infected population affected the infection-naïve cohort selection, due to the matching procedure, that may not represent the overall population. In addition, we studied COVID-19 post-infected individuals who were mildly symptomatic, with relatively low pre-vaccination titer levels. Whether our safety conclusions could be generalized to previously moderate and severe COVID-19 infected patients [30], has yet to be determined.
In conclusion, this study demonstrates that in previously SARS-CoV-2 infected populations, a single dose of an mRNA-based vaccine is sufficient to induce an intense immune response regardless of seropositivity. This vaccine-induced response correlates with the pre-vaccination IgG-S antibody concentration. The overall safety profile of the post-infected cohort is similar to the infection naive population, supporting the notion that a single dose vaccination approach can be considered in this population.