In the group of vaccinated individuals from the CRO-VAX HCP study
[38,39[35][36][37],
40], we evaluated the neutralizing response in a cohort of 90 volunteers, of which 60 were uninfected and 30 were previously infected by SARS-CoV-2, having received the complete dose regimen of the BNT162b2 vaccine. NAbs were measured at baseline, i.e., just before the administration of the first dose, and at 14, 28, 42 and 56 days. So far, few reports have investigated the neutralizing response in vaccinated subjects
[41,42,43,44,45,46][38][39][40][41][42][43] and they mainly included few participants, only investigating the effect of the first dose
[42,43[39][40][42],
45], or did not include previously infected individuals
[46][43]. In our study, a significant increase in NAb titers was seen after the first dose (i.e., a 5.1- and a 31.1-fold increase in uninfected and previously infected individuals, respectively) in all participants (
Figure 4). Interestingly, the neutralizing capacity was similar when comparing previously infected individuals at baseline and naive individuals after the first dose, an observation that is similar to that of Manisty et al. using the Roche RBD total assay
[47][44]. After the second dose, a significant increase in NAb titers was only observed in uninfected individuals (i.e., a 22.3-fold increase between day 14 and 28). Afterwards, the peak of the neutralizing capacity seems to have been reached at day 42 (i.e., 613 AU/mL) and a slight but non-significant decrease was observed at day 56 (527 AU/mL), which could be explained by the natural clearance of antibodies via excretion or mostly via catabolism
[48][45]. Terpos et al. obtained similar findings using the cPass™ sVNT from GenScript
[46][43]. All participants were considered positive 7 days after the second dose. In previously infected individuals, NAb titers at days 28 to 56, i.e., 7 and 35 days after the second dose, were not significantly different from those at day 14 after the first dose (
Figure 4). The non-significant differences between the neutralizing capacity after the first dose and after the second dose support the concept only one dose might be sufficient to generate a complete neutralizing antibody response in individuals with a previous SARS-CoV-2 infection (
Figure 4). Using an sVNT, Ebiger et al. also noticed a similar response after the second dose in previously infected individuals, but the number of participants who had received the second dose was low (
n = 11) and they were followed up for a maximum of 28–42 days
[41][38]. Evaluation of the pre-vaccinal serological status could therefore be proposed as a strategy to identify patients who will only require the booster dose
[47][44]. In this context, pan-immunoglobulin assays should be preferred due to their higher sensitivity observed in long-term studies (up to 1 year post-infection)
[13,49][24][46] compared to Nabs, which were negative in eight out of 30 (73.3%) previously infected individuals in our cohort (median days since RT-PCR = 158) (
Figure 4). The NAb titer after the first dose in previously infected individuals was not significantly different from the NAb titers of uninfected individuals after the two-dose regimen (
p-value > 0.05), even if lower mean titers were reported (
Figure 4). This finding is inconsistent with the recent data of Anchini et al., who reported significantly higher NAb titers in previously infected individuals after the first dose compared to the uninfected individuals who had received two doses
[44][41].
In conclusion, we found a stronger neutralizing capacity in moderate–severe versus mild COVID-19 patients, in which a slow decay with time was observed. Vaccinated participants had significantly higher NAb titers after the complete dose regimen of the BNT162b2 vaccine compared to our cohort of COVID-19 patients. In light of these data, we can hypothesize that only one dose of the BNT162b2 vaccine might be sufficient in previously infected individuals to generate sufficient NAb titers to confer a sufficient serological immunity.