key: cord-0743089-svjem6g1
authors: Callegaro, Annapaola; Borleri, Daniela; Farina, Claudio; Napolitano, Gavino; Valenti, Daniela; Rizzi, Marco; Maggiolo, Franco
title: Antibody response to SARS‐CoV‐2 vaccination is extremely vivacious in subjects with previous SARS‐CoV‐2 infection
date: 2021-04-08
journal: J Med Virol
DOI: 10.1002/jmv.26982
sha: e90052129e923f971fe38a9dd26000830ee16f94
doc_id: 743089
cord_uid: svjem6g1

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic calls for rapid actions, now principally oriented to a world‐wide vaccination campaign. In this study we verified if, in individuals with a previous SARS‐CoV‐2 infection, a single dose of messenger RNA (mRNA) vaccine would be immunologically equivalent to a full vaccine schedule in naïve individuals. Health care workers (184) with a previous SARS‐CoV‐2 infection were sampled soon before the second dose of vaccine and between 7 and 10 days after the second dose, the last sampling time was applied to SARS‐CoV‐2 naïve individuals, too. Antibodies against SARS‐CoV‐2 were measured using Elecsys Anti‐SARS‐CoV‐2 S immunoassay. The study was powered for non‐inferiority. We used non parametric tests and Pearson correlation test to perform inferential analysis. After a single vaccine injection, the median titer of specific antibodies in individuals with previous coronavirus disease 2019 was 30.527 U/ml (interquartile range [IQR]: 19.992–39.288) and in subjects with previous SARS‐CoV‐2 asymptomatic infection was 19.367.5 U/ml (IQR: 14.688–31.353) (p = .032). Both results were far above the median titer in naïve individuals after a full vaccination schedule: 1974.5 U/ml (IQR: 895–3455) (p < .0001). Adverse events after vaccine injection were more frequent after the second dose of vaccine (mean: 0.95; 95% confidence interval [CI]: 0.75–1.14 vs. mean: 1.91; 95% CI: 1.63–2.19) (p < .0001) and in exposed compared to naïve (mean: 1.63; 95% CI: 1.28–1.98 vs. mean: 2.35; 95% CI: 1.87–2.82) (p = .015). In SARS‐CoV‐2 naturally infected individuals a single mRNA vaccine dose seems sufficient to reach immunity. Modifying current dosing schedules would speed‐up vaccination campaigns.

individuals with pre-existing immunity experience more severe reactogenicity after the first doses compared to naïve individuals.

The present study was designed to verify if, in individuals with a previous SARS-CoV-2 infection, a single administration of BNT162b2/Pfizer vaccine would elicit an immunological response superimposable to a full vaccine schedule in naïve individuals, assuming that, for individuals with pre-existing immunity to SARS-CoV-2, the first vaccine dose could immunologically resemble the booster dose in naïve individuals.

The study was carried out on 184 health care workers. Individuals with a previous COVID-19 symptomatic disease or a SARS-CoV-2 asymptomatic infection were sampled for measuring SARS-CoV-2 antibody responses soon before the second dose of vaccine and between 7 and 10 days after the second dose, the last sampling time was applied to SARS-CoV-2 naïve individuals, too.

Antibodies against SARS-CoV-2 in serum samples were mea- 

The study had an 80% power to demonstrate no-inferiority (alpha error 0.05) of a single dose in pre-exposed subjects compared to two injections in naïve individuals, provided that the magnitude of immunological response, in terms of proportion of subjects responding to the vaccine was superimposable in the two groups and not inferior to 90%. Data are summarized as medians and interquartile range (IQR), means and 95% confidence intervals (CIs) or percentages. We used Mann-Whitney test, Wilcoxon rank test, and Pearson's correlation test to perform inferential analysis.

The Provincial Ethical Committee approved the study and all participants gave their informed consent.

The study has no external funding. Adverse events were also less frequent in naïve compared to exposed individuals both after the first (mean: 0.77; 95% CI: 0.55-1.00 vs. mean 1.23, 95% CI from 0.89 to 1.50) (p = .002); or the second (mean: 1.63; 95% CI: 1.28-1.98 vs. mean: 2.35; 95% CI:

1.87-2.82) (p = .015) vaccine dose (Figure 2 ).

A world-wide vaccination campaign is an expensive, time and labor consuming effort. Eventually, considering a single vaccine dose in subjects previously exposed to SARS-CoV-2 would offer advantages in terms of costs, timing and possibility to reach a greater number of subjects in a shorter period of time. Our study has some limitations. Being conducted in health care workers, the age of enrolled individuals ranged from 24 to 66 years and we cannot exclude that younger or older subjects could react differently. Furthermore, all our subjects were Caucasian and we therefore cannot extend our observation to different ethnicities.

F I G U R E 1 Panel A: Specific antibody titers after a full vaccination schedule (two injections) in SARS-CoV-2 naïve individuals and a single vaccine injection in subjects with previous exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) either symptomatic or not. Panel B: Specific antibody titers in subjects with previous exposure to SARS-CoV-2 after a single or two doses of vaccine. Panel C: Specific antibody titers in SARS-CoV-2 pre-exposed subjects according to time of infection. Values are differentiated between subjects with previous asymptomatic infection and subjects with previous COVID-19. COVID-19, coronavirus disease 2019

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