Discussion
infection, fever
INFECTION, VIRUS, RECRUITMENT, FEVER CAUSED BY SARS-COV-2
Neutralizing antibodies are reported to act as a correlate of protection against COVID-19; therefore, a boost in these antibodies suggests an induced response associated with vaccine efficacy (The overall infection rate during the nationwide COVID-19 pandemic that followed the Chinese government’s “New ten measures” policy issued on 7 December 2022 (In addition, our study found that compared with male participants, female participants were at an increased risk of fever and general symptoms caused by SARS-CoV-2 and at a greater risk of symptom recovery time ≥3 days, supporting previous findings that the female sex is a risk factor for long COVID-19 (Our study has several limitations. First, only adults with stable medical conditions over 18 years of age were recruited; the inclusion of people who require additional protection against COVID-19 such as immunocompromised individuals may have produced more marked results than those observed. Therefore, the recruitment criteria prevented our results from being representative of the general population. Second, because blank controls (i.e., participants who do not receive a fourth vaccination dose) were not recruited into the study, we could not assess the efficacy of a four-dose immunization regimen against breakthrough infection with SARS-CoV-2. Therefore, the protective effect of the second heterologous booster vaccination regimen remains uncertain. Third, the sample size was too small to investigate the number of potentially severe and fatal cases caused by SARS-CoV-2. A larger sample size would have increased statistical power to allow the identification of influencing factors among subpopulations. Fourth, information on breakthrough infection in the follow-up was based only on participant recall, introducing potential recall bias. Finally, live virus neutralization antibodies against wild-type SARS-CoV-2, Omicron BA.4/5, or other current Omicron subvariants such as BF.7, BQ.1, and XBB that could increase the generalizability of immunogenicity results were not used in our study and must be further explored.In conclusion, a heterologous fourth dose with Ad5-nCoV caused higher antibody levels than a homologous fourth dose with the inactivated SARS-CoV-2 vaccine at 6 months after the last vaccination and decreased the risk of fever caused by SARS-CoV-2 in healthy adults who had been immunized with three doses of the inactivated vaccine. However, the two vaccine types showed equivalent efficacy after the pandemic. Our findings support the heterologous administration of Ad5-nCoV over the homologous administration of the inactivated SARS-CoV-2 vaccine. Furthermore, next-generation vaccines may be needed to provide better protection against COVID-19 by addressing the immune escape of SARS-CoV-2 variants.