A recent scientific report from Israel shows how healthcare workers previously infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present with higher Immunoglobulin G (IgG) titers after receiving one dose of Pfizer–BioNTech COVID-19 vaccine in comparison to their fully vaccinated, never-infected counterparts. Conversely, the occurrence of post-vaccination infection does not increase IgG titers. The research paper is currently available on the medRxiv* preprint server.
As of April 2021, Israel is the country with the highest vaccine coverage against coronavirus disease 2019 (COVID-19), and their primary approach is the use of mRNA Pfizer–BioNTech vaccine. Consequently, the impact of such herculean public health endeavor on SARS-CoV-2 transmission is now clearly visible, primarily as a substantial decrease of viral spread.
Vaccinating previously infected individuals with only a single dose of the aforementioned vaccine is thought to generate a boost-type response in IgG antibodies up to 10 months following the infection. Therefore, some countries (including Israel) are starting to endorse a single dose of vaccine in infected individuals, as the benefit of the second one in this group of patients remains unclear.
Furthermore, a fraction of patients will get infected after vaccination, usually within the period of fourteen days. In Israel, these individuals are not offered a second dose; however, the exact immunogenicity parameters in patients infected after one dose of the vaccine have not been thoroughly evaluated.
The aim of a group of researchers, led by Dr. Kamal Abu Jabal from the Ziv Medical Centre and Bar-Ilan University in Safed (Israel), was to evaluate IgG response in a cohort of vaccinated healthcare workers in accordance with their SARS-CoV-2 infection status (i.e., never infected or infected before/after vaccination) and to subsequently inform vaccination policy.
Healthcare workers and IgG antibodies
In the methodological approach, all employees of Ziv Medical Centre (which is a hospital center in Northern Israel) were offered vaccination with the Pfizer–BioNTech COVID-19 vaccine from December 2020. IgG antibody levels were measured before vaccination, and all individuals with detectable IgG antibodies at baseline (or evidence of an earlier positive COVID-19 test) were considered previously infected.
Moreover, all healthcare workers who developed symptoms compatible with COVID-19 during the study period (i.e., between December and March 2021) were tested using polymerase chain reaction (PCR). Consequently, subjects with a positive PCR test were considered infected post-vaccination.
Finally, IgG antibody levels against SARS-CoV2 were compared among groups of healthcare workers according to the number of doses received and their infection status (i.e., uninfected or infected prior/after vaccination) in order to obtain the exact immunogenicity profile.
A boost-type immune response after infection
In comparison to uninfected individuals, previously infected healthcare employees who received one vaccine dose exhibited high IgG levels or titers 21 days after receiving the shot, which remained high approximately 50 days post-vaccination. More specifically, this was more than twice higher than previously uninfected individuals who received two vaccine doses.
In the group of those previously infected who received a second dose, IgG antibody titers 50 days following the first dose (and approximately 30 days after the second dose) have decreased in comparison to pre-dose 2 levels and were not significantly higher than those who received a single dose.
Finally, 50 days following the vaccination, IgG antibody titers among the 20 patients infected after the first dose and tested at this time point has been comparable to those previously uninfected who received a single dose – and actually lower than either those uninfected who received two doses, or those infected before starting with a vaccination protocol.
Implications for vaccination policy
In any case, such a strong and persisting immune response after only one dose in previously infected individuals was a reason why several countries (including Israel and France) recommend one vaccine dose for such cases, which is an approach supported by the data from this study as well.
“Interpreting the clinical significance of the difference in IgG levels in the absence of correlates of protection remains a challenge”, say the authors of this study. “Nevertheless, this study demonstrates no benefit in receiving a second dose among individuals infected prior to vaccination, and more importantly, that infection after vaccination (dose 1 or dose 2) seems to have very little effect on immunogenicity”, they add.
In any case, a change in vaccination policy may be on the horizon, although studies with more power regarding sample size and those that measure other components of the immune system are needed in order to obtain a full picture.
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.