Numerous studies have measured the immune response in healthcare workers to both SARS-CoV-2 infection and vaccines. Drawing on this bibliography, we compared our data with those from studies focused on similar variables (those assessing humoral immune response following vaccination with Pfizer and with follow-ups at several months). The healthcare professionals included in other studies have similar profiles to those of our sample, with an average age of 54.4 years and a mean of 46.3. The mean ages typically range between 40 and 48 (23) (24) (25), although some studies use a younger population with a mean age of between 33 and 37 (26), (27) and (28). In all cases, there is a greater proportion of woman, ranging from just over 50% (26), around 60–69% (27),(24), (25) and more than 70% (28), as in our study, with 76% of women. Some of the works include populations of which more than 80% are women (23), (29) and (30). The findings on age-related variations in the immune response are conditioned by this limited diversity in the ages of the health service employees. As regards the sex-related variations, given the largely female populations and the scant number of men in some groups, the differences reported are, arguably, not always significant or clear.
The incidence of previous exposure to SARS-CoV-2 in healthcare workers is typically higher than among the general population in their respective countries, which is in line with the results of our study. The incidence data vary greatly and tend to be reported as a percentage of persons infected, ranging between 7% and 25%. The range of values is as follows: studies with the lowest incidence rates of 7% and 7.8% (27) (30) (31); around 10% (32); others with figures similar to our 19.3%, such as 19.22% (24); and others with higher incidence rates of 23% (14) 25% (26) and 32,1% (33).
Based on a cutoff point of 50 AU/mL for IgG Spike positivity (RBD), 100% of the participants in our study had antibodies following vaccination, in line with other studies (14)(30). These results are described in some studies as seroconversion, as they present data compared with baseline levels, finding that all vaccinated employees without prior COVID-19 infection have positive IgG levels (9), or percentages close to 100% (30)(31)(32)(36). Discrepant data were also reported with 22.9%, being seronegative (19).
Terpos et al. followed up a group of healthcare workers for several months after vaccination, finding persistent but attenuated anti-SARS-CoV-2 humoral immunity at 3 months after second vaccination with BNT162b2 in healthy individuals (34) (32). Several studies have established peak level circulating antibodies at 3–4 weeks after the second vaccination, and there is a considerable consensus on the decrease in levels over time, especially after the third month (26). Additionally, most of the studies presents dispersion in the values in coherence with our findings.
The study by Rode et al. reported that most of the participants present positive values, from 50 to 2000 AU/mL was the most representative range of antibody titers in almost 80% of subjects (35). The interquartile range for our data at 6 months was slightly higher although the conclusions of immune response efficacy are mostly similar.
Among the factors related to differences in IgG levels on which there is more evidence, the most notable are age and previous infection. Regarding age, evidence suggests that younger individuals tend to present higher levels of immunoglobulin G anti-SARS-CoV-2 (19, 29 y 30). In our work, no association was found between IgG level and age.
We found no differences in IgG levels by sex, which is consistent with the findings of other studies (35 and 39). However, some studies have detected higher IgG levels in women in the initial immune responses after vaccination (9, 19, 21, 30, 32 and 34).
Comparisons of antibody levels in persons with previous infection and subsequent vaccination confirm hybrid immunity is more robust in IgG measurements a few weeks after vaccination. Individuals with prior infection present higher IgG levels at all time points (31) and these differences are maintained various months after vaccination (9)(25)(35), although they are more pronounced in the early weeks post-vaccination. Seropositivity was significantly higher in healthcare workers with prior COVID-19 infection, according to the cross-sectional study by El-Ghitany et al. (33). In our study, the differences in IgG levels remained significantly higher in persons with prior infection both 6 and 9 months after vaccination.
Hansen et al. found that a single dose of the BNT1622b vaccine induces a robust antibody response in individuals with previous infection and that, in immunogenicity, is equivalent to a double dose of the vaccine (30). Consequently, it is considered that a single dose might be sufficient in individuals with previous infection, regardless of the time elapsed since the diagnosis (24). Nonetheless, a generalized decline in antibody levels over time has been found in vaccinated individuals both with and without prior infection.
Some works have found an impact on immune response levels of other factors, such as chronic diseases, smoking and high BMI. Nonetheless, the findings are inconclusive (9)(26). El-Ghitany et al. found a relationship with smoking, with antibody positivity being significantly lower in smokers (61.9%) compared to non-smokers (87.7%) (p = 0.003) (33). Our study also confirms that smoking inhibits immune response
As regards BMI, the studies by Hansen et al. (30) and de El-Ghitany et al. provide no conclusive data to support a relationship between high BMI and impaired immune response (33). Papadopoulos et al., however, found an association between older participants, higher BMI and the presence of autoimmune diseases with negative effects on the development of anti-SARS-CoV-2 antibodies 9 months after full-vaccination (36).
Our findings point to durable immunity despite the decline in antibody levels 9 months post-vaccination. Other works coincide with our findings. Studies indicate a decline from peak levels in neutralizing antibody titers, although these remained detectable in most participants 6 months post-vaccination (29) (37)(38). The data reported by Rode et al. at 6 months after full vaccination (mean IgG 966.0 AU/mL) are similar to those in our study (35).
The recent systematic review by Notarte et al., characterizing the kinetics of anti-SARS-CoV-2 antibodies following the second dose of a primary cycle of mRNA vaccination, revealed that the peak humoral response was reached at 21–28 days after the second dose. Subsequently, serum levels progressively decreased at 4–6 months post-vaccination. and the results showed that, regardless of age, sex, serostatus and presence of comorbidities, there is an antibody decay (39).
The studies that offer findings more than 6 months after vaccination (in general they do not exceed 8 or 9 months) show antibodies largely remain active, despite a notable decline in levels (37) (40), with important variations according to groups of subjects (41).
There is concern about whether the vaccines will be less effective against the new variants of the virus (Delta, Omicron, Omicron B.A.2). Although studies have already been published on Omicron and the Delta and Beta variants and RNA vaccines are reported to provide protection against severe and lethal forms of COVID-19 but infection persists against these SARS-CoV-2 variants (37)(41).
There is considerable agreement on implementing booster doses in high-risk population, such as daily alcohol drinkers, frail elderly, smokers and other groups, in whom both a greatly diminished humoral and cellular immune response has been evidenced, and in which booster doses may be warranted (16) (41) (42). Some studies point towards the need to customize additional booster doses to achieve an adequate neutralizing response against the new circulating variants, which justifies the decisions on the third dose implemented in European countries and those that may be recommended by health authorities in the coming months (34).
Immunosurveillance studies estimate the duration of immunity and are especially necessary for designing public health responses to the general population, healthcare workers and, particularly, specific population groups with a compromised immune response (43) (44). It is even noted that the heterogeneity of responses to vaccines suggests that personalized recommendations based on COVID-19 history and lifestyle are necessary (45).