Purpose: This study was performed to investigate humoral immune response and adverse events upon the heterologous prime-boost with a single dose of the mRNA-1273 vaccine among fully CoronaVac-vaccinated, infection-naïve healthcare workers in Indonesia. Materials and Methods: One hundred twenty-five eligible healthcare workers were recruited from one hospital for this prospective cohort study. Blood collection was conducted twice, i.e., on 7 days before and 28 days after the booster vaccination. The titer of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies was quantified accordingly. The post-vaccination adverse event was recorded for both CoronaVac and mRNA-1273 vaccinations. Any breakthrough infection was monitored during the follow-up period. Wilcoxon matched-pairs signed rank test was used to test differences between groups. Results: A significant increase was observed in the titer of anti-SARS-CoV-2 RBD antibodies upon receiving the mRNA-1273 booster (geometric mean titers of 65.57 and 47,445 U/mL in pre- and post-booster, respectively), supporting the argument to use heterologous prime-boost vaccination to improve the protection against COVID-19 in a high-risk population. The mRNA-1273 vaccine, however, caused a higher frequency of adverse events than the CoronaVac vaccine. Nonetheless, the adverse events were considered minor medical events and temporary as all subjects were not hospitalized and fully recovered. Of note, no breakthrough infection was observed during the follow-up to 12 weeks post-booster. Conclusion The heterologous prime-boost vaccination of healthcare workers with a single dose of the mRNA-1273 vaccine generated a significant elevation in humoral immune response towards RBD of SARS-CoV-2 and was associated with a higher frequency, but minor and transient, adverse events.

PURPOSEHost response to polytrauma occasionally has unpredictable outcomes. Immune response is a major factor influencing patient's outcome. This study evaluated the interaction of two main cytokines in immune response after major trauma, specifically interleukin-6 (IL-6) and interleukin-10 (IL-10). Plasma level of these cytokines is determined by mRNA expression of these cytokines genes which may decide the outcome of polytrauma patients.

METHODSThis prospective multicenter trial held at four trauma centers enrolled 54 polytrauma patients [Injury Severity Score (ISS) ≥ 16]. Plasma levels and mRNA expression of IL-6 and IL-10 were measured for 5 days after trauma. Clinical evaluation was conducted to observe whether patients endured multiple organ dysfunction syndrome (MODS) and death. MODS evaluation was performed using sequential organ failure assessment (SOFA). Trauma load which in this study is represented with ISS, plasma level, expression of cytokine genes and patient's outcome were examined with correlation test and statistical analysis.

RESULTSThe elevated IL-6/IL-10 ratio indicated increased activity of systemic inflammation response, especially pro-inflammation response which bears higher probability of progressing to MODS and death. The decline of IL-6/IL-10 ratio with heavy trauma load (ISS > 30) showed that compensatory anti-inflammation response syndrome (CARS) state was more dominant than systemic inflammatory response syndrome (SIRS), indicating that malfunction and failure of immune system eventually lead to MODS and deaths. The statistical significance in plasma level of cytokines was found in the outcome group which was defined as bearing a low trauma load but mortality.

CONCLUSIONThe pattern of cytokine levels in inflammation response has great impact on the outcome of polytrauma patients. Further study at the genetic level is needed to investigate inflammation process which may influence patient's outcome.