Research on post-vaccination antibody dynamics has become pivotal in estimating COVID-19 vaccine efficacy. We studied anti-SARS-CoV-2 Spike RBD IgG levels in 587 healthcare workers (2038 sera) who completed BNT162b2 vaccination. Average antibody titer 3 weeks after the first dose in COVID-19-naïve participants (median 873.5 AU/mL) was 18-fold higher than the test threshold, with a significant increase 1 month (median 9927.2 AU/mL) and an exponential decrease 3 (median 2976.7 AU/mL) and 6 (median 966.0 AU/mL) months after complete vaccination. Participants with a history of COVID-19 prior to vaccination showed significantly higher antibody levels, particularly after the first dose (median 14,280.2 AU/mL), with a slight decline 1 month (median 12,700.0 AU/mL) and an exponential decline in antibody titers 3 (median 4831.0 AU/mL) and 6 (median 1465.2 AU/mL) months after vaccination. Antibody levels of COVID-19-naïve subjects after the first dose were moderately correlated with age (r = −0.4). Multivariate analysis showed a strong independent correlation between IgG levels 6 months after vaccination and both IgG titers after the first dose and 1 month after vaccination (R² = 0.709). Regardless of pre-vaccination COVID-19 history, IgG levels 6 months after vaccination were comparable to antibody levels reached by COVID-19-naïve participants after the first vaccine dose.

Anti-SARS-CoV-2 IgG titer decreases rapidly after primovaccination, leading to a mandatory booster vaccination. We analysed anti-SARS-CoV-2 Spike RBD IgG levels (positive ≥ 50 AU/mL) in 405 healthcare workers (3010 sera) who received a booster dose (BD) 9 months after two-dose BNT162b2 primovaccination. Median antibody titer at the time of BD (582.6 AU/mL) was 1.7-fold and 16.4-fold lower than the peak titer after the first (961.5 AU/mL) and the second vaccine dose (SVD) (10,232.6 AU/mL), respectively. One month after vaccination, IgG titer increased 40.6-fold after BD compared with a 10.8-fold increase after primovaccination. Three months after vaccination, post-booster antibodies decreased significantly slower (2.2-fold) than after primovaccination (3.3-fold). At six months, antibodies decreased slower after BD (4.5-fold; median 5556.0 AU/mL) than after primovaccination (9.6-fold; median 1038.5 AU/mL). Antibody titers before and one month after BD correlated weakly (r = 0.30) compared with a strong correlation (r = 0.65) between the corresponding post-primovaccination titers. Pre-vaccination COVID-19 had no effect on IgG levels after BD compared with a positive effect after primovaccination. Despite high post-booster IgG levels, 22.5% of participants contracted mild COVID-19. The trend of IgG decline indicates the need for further revaccination, but the vaccine type should be defined according to viral mutations.

Tick-borne encephalitis (TBE) is a common arbovirus infection in Croatia. The aim of the study was to analyse 17 years of data on TBE seroprevalence and acute TBE cases in correlation with winter temperature, precipitation and wildlife abundance to identify possible patterns that may be predictive indicators of TBE incidence. Clinical diagnosis of TBE was confirmed by determining IgM and IgG anti-TBE antibodies. Of the 19,094 analysed patients, 4.2% had acute TBE, significantly more often in older age (p < 0.001) and male gender (p < 0.001). Overall seroprevalence of TBE among the tested population was 5.8% and varied annually from 2.8% to 10.7%. The mean acute TBE incidence rate was 1.1/100,000 population with significant regional differences: 1.7/100,000 in the continental vs. 0.2/100,000 and 0.5/100,000 in the Mediterranean and Alpine regions, respectively. A particularly high incidence of 3.1/100,000 was recorded in northern Croatia. TBE displayed a seasonal pattern, peaking in June and July. Moderate negative correlations were observed between TBE acute cases and winter temperatures from December to February (r = −0.461; p = 0.062), relative rodent abundance (r = −0.414; p = 0.098) and yearly precipitation from one year before (r = −0.401; p = 0.123). The analysis showed that more acute TBE cases are recorded after a warmer winter and a negative correlation between the abundance of forest Apodemus sp. and the number of TBE cases in the same year.

Coronavirus disease (COVID-19) exhibits a wide spectrum of clinical severity and has been associated with specific biomarkers linked to disease progression and outcomes. This retrospective study analyzed sera from 1222 adult COVID-19 patients hospitalized at the University Hospital for Infectious Diseases in Croatia. We examined the association between several laboratory biomarker levels measured at patient admission and disease severity, fatal outcomes, viral variants and clinical parameters. Deceased patients and surviving patients with severe COVID-19 exhibited significantly elevated levels of several biomarkers on admission, including hs-troponin T, N-terminal pro-brain natriuretic peptide, creatine kinase, C-reactive protein, procalcitonin, interleukin-6, lactate dehydrogenase, lactate, urea and creatinine. Random forest models identified lymphocyte percentage, D-dimers, and hs-troponin T as the most important biomarkers for fatal outcome prediction, achieving 84.1% accuracy. Patients infected with the Delta SARS-CoV-2 variant exhibited significantly higher levels of proinflammatory, cardiac and renal biomarkers. Vaccination correlated with reduced proinflammatory parameters and higher lymphocyte proportions. Hypertension, chronic renal disease and diabetes were associated with increased cardiac, renal and metabolic biomarker levels, respectively. These findings highlight the association of several laboratory biomarkers with COVID-19 severity, viral variants, vaccination status and comorbidities, potentially offering prognostic insights into COVID-19 outcomes.

Severe COVID-19 is characterized by immune dysregulation, yet reliable biomarkers associated with adverse outcomes remain limited. Immunoglobulin G (IgG) N-glycosylation modulates antibody effector function and reflects the immune system’s inflammatory state. In this study, we investigated whether specific IgG glycosylation profiles are associated with COVID-19 severity, mortality, and clinical course in patients without known prior SARS-CoV-2 infection. Of the 806 admitted COVID-19 patients included in the study, 377 hospitalized patients were longitudinally monitored, and 2001 serum samples were analyzed. Significant alterations in IgG N-glycome composition were observed in patients with severe disease and those who died. The most prominent changes included increased agalactosylation and decreased mono- and digalactosylation, features associated with a more pro-inflammatory IgG glycosylation profile. Nosocomial infections were associated with a more pro-inflammatory IgG glycosylation profile. No statistically significant differences in IgG N-glycome composition were observed between vaccinated and unvaccinated patients, although the small number of vaccinated patients limited this analysis. The observed glycomic profiles likely reflect immune responses characteristic of the early phase of the COVID-19 pandemic. Whether similar glycosylation changes occur in other infectious or inflammatory diseases remains to be established. IgG glycosylation analysis holds promise for personalized risk stratification and early therapeutic intervention in COVID-19 and other severe infectious diseases.

Background/Objectives: Understanding the relationship between reactogenicity and immunogenicity after repeated BNT162b2 vaccination is critical for optimizing vaccination strategies. This study quantified their progressive dissociation across four vaccine doses. Methods: We conducted a prospective longitudinal cohort study among Croatian healthcare workers vaccinated with BNT162b2 from January 2021 to January 2024. Anti-SARS-CoV-2 IgG antibodies were measured at 16 timepoints using chemiluminescent immunoassay. Local (pain, erythema, swelling) and systemic (fever, fatigue, headache, myalgia, arthralgia, nausea) reactions were recorded for 7 days using FDA toxicity scale. Correlations were analyzed with Spearman’s method and Bonferroni correction. Fourth-dose responses were predicted by exponential modeling. Results: Of 631 participants, 524 completed primary immunization, 418 received a third dose (173 with complete data), and 56 received a fourth dose (22 with complete paired data). Local reactions declined from 82.4% after the first dose to 42.9% after the fourth (p < 0.001). Systemic reactions peaked at 44.8% after the second dose, then decreased to 26.0% after the third and 19.6% after the fourth. In contrast, median antibody levels rose from 9910 AU/mL after the primary series to 29,002 AU/mL after the third and 38,274 AU/mL after the fourth. Correlations between reactions and antibody titer progressively weakened: r = 0.37 (95% CI 0.29–0.44, p < 0.001) after the primary series, r = 0.08 (95% CI −0.07 to 0.23, p = 0.30) after the third, and r = 0.04 (95% CI −0.39 to 0.45, p = 0.86) after the fourth dose. Conclusions: Progressive dissociation between reactogenicity and immunogenicity was observed across four BNT162b2 doses. Booster doses maintain robust antibody responses despite reduced reactogenicity, reinforcing that minimal side effects are consistent with sustained humoral responses.