https://orcid.org/0000-0002-7843-8876
Abstract
Background
Despite the widespread administration of coronavirus disease 2019 (COVID-19) vaccines, the impact on patients with asymptomatic to mild illness remains unclear. Here, we aimed to assess the efficacy of various vaccine doses and types on the duration of isolation duration and discharge rates, the viral shedding duration, and negative rates in asymptomatic to mild COVID-19 patients.
Methods
We included adult patients at the Fangcang isolation centres in Pazhou or Yongning between November and December 2022. We analysed data on basic demographics, admission details, laboratory indicators and vaccination information.
Results
A total of 6560 infected patients were included (3584 from Pazhou and 2976 from Yongning). Of these, 90.6% received inactivated vaccines, 3.66% received recombinant SARS-CoV-2 spike protein subunit vaccines and 0.91% received adenovirus vaccines. Among the 6173 vaccinated individuals, 71.9% received a booster dose. By day 9, the isolation rate reached 50% among vaccinated patients. On day 7.5, the positive rate among vaccinated individuals reached 50%.
Conclusions
Full vaccination was effective, with heterologous vaccines showing greater efficacy than inactivated vaccines alone. However, there was no significant difference in the vaccine protective effect 12 months after vaccination.
Introduction
Since the emergence of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, the worldwide tally of infections has surpassed 700 million, leading to over 6 million fatalities as of February 2023 [Citation1]. COVID-19 vaccines have been widely developed and distributed globally, with approximately 69.5% of the world’s population receiving at least one dose and over 13 billion doses administered globally [Citation2]. Studies consistently underscore the efficacy of vaccines in significantly reducing disease incidence and mortality [Citation3–6]. However, although vaccines significantly curb severe cases, their effectiveness in halting transmission and preventing asymptomatic illness remains relatively poor [Citation7]. This highlights the crucial role played by unvaccinated individuals in perpetuating virus transmission, particularly in regions with high vaccination coverage, thereby increasing the susceptibility of the unvaccinated populations to severe illness. Hence, comprehensive vaccination strategies remains imperative to mitigate effect of infection overall and protect vulnerable communities [Citation8].
As the ongoing COVID-19 pandemic evolves, the emergence of SARS-CoV-2 genetic variants has led to increased transmissibility and the ability to evade host immunity [Citation9–12]. Variants B.1.351 and P.1 have raised concerns, potentially compromising existing preventive measures and treatments. Notably, the BNT162b2 vaccine may offer less robust protection against these variants [Citation12]. Furthermore, declining immune response rates over time underscore the need to consider heterologous boosting, a focus highlighted by the World Health Organization (WHO) [Citation13]. Multiple factors, including co-infection, concurrent use of biomedicines [Citation14] and demographic variables such as sex, age and socioeconomic status, influence vaccine efficacy [Citation14]. And vaccination may have an impact on the isolation rate [Citation15,Citation16]. Therefore, accurate estimation of vaccine effectiveness (VE) [Citation17] and addressing vaccine hesitancy require pivotal population-based studies, which serve as crucial evaluations for future vaccine rollouts and policy decisions [Citation17].
Asymptomatic infection, identified as a potential contributor to virus transmission [Citation17], has garnered considerable attention. Vaccines have proven efficacy in preventing asymptomatic infection [Citation18], prompting a hypothesis that the COVID-19 vaccines might shorten the duration of isolation and viral shedding in patients with asymptomatic illness, potentially reducing virus transmission. To validate this hypothesis, a multicentre study was conducted to determine the impact of COVID-19 vaccines on the isolation rates and duration of viral shedding. These results could explain the likelihood of vaccination regimens curtailing virus spread and provide a scientific basis for selecting an appropriate vaccine regimen.
Materials and methods
Patients
We recruited adult individuals aged 18 years or older with first-time COVID-19 infection who were admitted to the Fangcang isolation centres in Pazhou or Yongning between November and December 2022. All included patients were asymptomatic or had mild illness and were not categorized as having severe or critical illness. Those with underlying illnesses or other special conditions were excluded (Table E1). The reporting of this study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (Online Supplement 2) [Citation19]. This study received approval from the ethics committee of The First Affiliated Hospital of Guangzhou Medical University (approval number ES-2023-116-01).
Study design
Demographic information was collected, including sex, age, marital status, ethnicity, occupation and province of residence. In addition, admission details, such as length of hospital stay, date of health code turning yellow, date of nucleic acid test (NAT) and laboratory indicators such as NAT results and cycle threshold (Ct) values, were meticulously documented. Moreover, we gathered information regarding vaccination, including the type of vaccine administered and date of vaccination. The discharge criteria for patients were as follows: (1) normal body temperature for at least three consecutive days; (2) significant improvement in respiratory symptoms; (3) significant improvement in acute infiltrative lesions observed on pulmonary imaging; (4) seven days of centralized medical observation in the Fangcang hospital, with nasal and pharyngeal swabs collected for NAT on days 6 and 7 (with a minimum sampling interval of 24 h). If both the nucleocapsid (N) gene and open reading frame (ORF1ab) gene Ct values in the two NATs were ≥35 (using fluorescence quantitative PCR detection method with a threshold of 40), or test results were negative (using a fluorescence quantitative PCR detection method with a Ct value lower than 35), the patient could be discharged from the centralized medical observation in the Fangcang hospital. If the above criteria were not met, the patient continued isolation in the Fangcang isolation centre until the discharge criteria were fulfilled. The discharge rate was defined as the percentage rate of patients successfully discharged from the isolation centre. The isolation rate was defined as 1 – discharged rate.
In this study, the duration of viral shedding duration was defined as the interval between the first day when a patient had a positive NAT and the first day the patient began to have continuous negative tests. Full vaccination was defined as receiving the complete series of primary vaccine doses, and booster referred to additional doses administered after achieving full vaccination status [Citation16]. The negative rate was defined as the percentage rate of patients began to have continuous test. The positive rate was defined as 1 – negative rate.
Statistical analysis
Continuous variables with a normal distribution are presented as mean ± standard deviation (SD), and those with a non-normal distribution are described as median and interquartile range. Categorical data are expressed as frequency and percentage. Group comparisons were conducted using an analysis of variance, a Kruskal–Wallis test, a Chi-square test or Fisher’s exact test as appropriate. Multiple Cox regression models were used to assess the impact of vaccination on isolation duration and viral shedding duration. The negativity rates and discharge rates between different vaccine types and different vaccine dosage groups were compared using Kaplan–Meier’s curves and multiple Cox regression. For missing Ct values, imputation was performed based on the NAT result on the same day. Specifically, if the NAT result was positive, the median Ct value of the positive group was recorded; if negative, the median Ct value of the negative group was used for imputation. To mitigate the impact of sample size disparity across vaccine regimens, we applied propensity score matching analysis in our sensitivity analysis. The matched samples were obtained by performing nearest neighbour matching, with a calliper width set at 0.2 SD of the probit of the propensity score in a 1:1 ratio between groups. A p value of <.05 was considered to be statistically significant. All data were analysed using R version 4.1.2 (R Project for Statistical Computing, Vienna, Austria) software.
Results
Patient recruitment and baseline characteristics
We enrolled a total of 6560 of individuals infected with COVID-19 (3584 from Pazhou and 2976 from Yongning). The basic information of patients is presented in . Among them, 69 patients received heterologous vaccination, which included inactivated vaccines and recombinant protein vaccines. Of the total cases, 47.9% were women, and the median age was 39.0 years; 80.5% of patients were married. Upon admission, the Ct values of the nucleocapsid gene (N gene) and the ORF gene were 31.6 and 29.0, respectively.
Table 1. Demographic and clinical characteristics of patients from two Fangcang isolation centres.
In this study, 90.6% of patients received inactivated vaccines, 3.06% received recombinant SARS-CoV-2 spike protein subunit vaccines and 0.85% received adenovirus vaccines. Among the 6173 vaccinated individuals, 71.9% received a booster dose; 67.3% received the final dose of vaccine within 12 months of infection.
Comparison of isolation duration and discharge rates between vaccinated and unvaccinated patients
On day 9, the isolation rate among vaccinated patients reached 50%, and 50% of unvaccinated patients were discharged from the isolation centre on day 10, p < .001 (). A baseline comparison between the vaccinated and unvaccinated populations is presented in . After adjusting for sex, age, marriage and geographical factors, the rate of hospital discharge within 14 days was significantly higher in vaccinated than in unvaccinated individuals (hazard ratio (HR): 1.211, 95% confidence interval (CI) = 1.084–1.351, p < .001) ().
Figure 1. Effect of vaccination on isolation within 14 days. (A) Comparative isolation rates of vaccinated and unvaccinated patients. Red curve represents the isolation rate of vaccinated patients, and blue curve represents the isolation rate of unvaccinated patients. (B) Odds of isolation centre discharge within 14 days in vaccinated and unvaccinated patients.
Table 2. Baseline comparison between vaccinated and unvaccinated populations.
Comparison of viral shedding duration and negativity rates between vaccinated and unvaccinated patients
By day 7.5, the COVID-19 test results showed a negativity rate of approximately 50% among vaccinated individuals; the same rate was observed among unvaccinated individuals by around day 8 (p < .001) (). After adjusting for sex, age, marital status and geographic factors, the negativity rates within 14 days among vaccinated patients was higher than that of unvaccinated ones (HR: 1.239, 95% CI = 1.113–1.378, p < .001) ().
Figure 2. Impact of vaccination on positivity within 14 days. (A) Comparison of positivity rates among different vaccine doses and types during isolation. Red curve represents the positivity rate among vaccinated patients, and blue curve illustrates the positivity rate among unvaccinated patients. (B) Odds of negativity within 14 days for different vaccine doses and types.
Comparison of isolation duration and discharge rates between heterologous vaccination and pure inactivated vaccine cases
Among vaccinated patients, the discharge rate reached 50% at around day 8, this was around day 9 for unvaccinated patients. Notably, there was a higher rate of discharge within 14 days among patients who received heterologous vaccination compared with other vaccination approaches (p = .029) (). A baseline comparison was conducted among patients who underwent different vaccination approaches, and the results are presented in .
Figure 3. Impact of vaccine dose and type on isolation within 14 days. (A) Comparison of isolation rates for different vaccine doses and types during isolation. Blue curve represents the isolation rate among patients who received only inactivated vaccine, red curve displays the isolation rate among patients who received heterologous vaccination and green curve represents the isolation rate among patients who received other regimens. (B) Odds of discharge within 14 days for different vaccine doses and types.
Table 3. Baseline comparison among patients with different vaccination approaches.
To investigate the potential association between vaccine type and the isolation rate, specifically focusing on the clinical endpoint of isolation centre discharge within 14 days, a comprehensive analysis was conducted, taking into account confounding factors such as sex, age, marital status, residential province and vaccination dose. The results revealed no statistically significant difference in the rate of isolation between patients who received heterologous vaccination and those who received pure inactivated vaccine within the 14-day period (HR: 1.226, 95% CI = 0.963–1.562, p = .099) (). This analysis provided insight into the potential impact of vaccine type on isolation outcomes for patients with COVID-19, indicating comparable results for both vaccination strategies within the specified time frame.
Comparison of viral shedding duration and positive rates between heterologous vaccination and inactivated vaccine cases
During days 6–8, the positive rate for COVID-19 cases reached 50%. Moreover, compared with other patients, the viral shedding duration was shorter in those who received either a simple inactivated vaccine or a heterologous vaccination (p = .015). Specifically, cases with heterologous vaccination had a shorter duration of viral shedding than those who received inactivated vaccine alone (p = .011) ().
Figure 4. Impact of vaccine dose and type on positivity within 14 days. (A) Comparison of positivity rates for different vaccine doses and types during isolation. Blue curve represents the positivity rate among patients who received only inactivated vaccine, red curve displays the positivity rate among patients who received heterologous vaccination and green curve represents the positivity rate among patients who received other regimens. (B) Odds of negativity within 14 days for different vaccine doses and types.
After adjusting for potential confounding factors, we found that patients who received heterologous vaccination had a greater likelihood of viral shedding within a 14-day time frame compared with those who received inactivated vaccine alone (HR: 1.306, 95% CI = 1.025–1.664, p = .031) (). The relationship among the interval of vaccination and discharge rate, and Ct value positivity is shown in Figures E1 and E2.
Sensitivity analysis
Sensitivity analysis with propensity score matching showed a greater likelihood of shorter isolation duration among patients receiving heterologous vaccination than those receiving inactivated vaccine alone (HR: 1.729; 95% CI = 1.197–2.497, p = .004). Similarly, the likelihood of viral shedding within a 14-day time frame was higher among patients who received heterologous vaccination compared with those who received pure inactivated vaccine (HR: 1.577, 95% CI = 1.115–2.232, p = .010). Detailed results of sensitivity analysis results are shown in Tables E2–E4.
Discussion
In this study, we recruited patients with asymptomatic to mild illness from two medical centres with the aim of investigating the impact of vaccination doses and vaccine type on the length of hospital stay and time required to achieve a negative test result among patients with COVID-19 infection. The key findings of this study are as follows: (1) infected patients who received two doses of the COVID-19 vaccine exhibited a higher rate of isolation centre discharge within 14 days than those who were unvaccinated. Furthermore, patients who received heterologous vaccination demonstrated a higher rate of achieving a negative test result than those who received the inactivated vaccine alone. (2) Regardless of whether the duration from the last vaccine dose to symptom onset exceeded 12 months, there was no significant difference in the rate of discharge and rate of achieving a negative test result within 14 days. This finding provides evidence supporting the effectiveness of the COVID-19 vaccine. (3) The efficacy of heterologous vaccination was found to be superior to that of other vaccine regimens.
In this study, we found that complete vaccination was effective in preventing COVID-19 infection, and in reducing COVID-19-related isolation duration [Citation20]. Clinical trials have provided evidence demonstrating that the WIVO4 inactivated vaccine has an effectiveness of 72.8%, and the HB02 inactivated vaccine exhibits an effectiveness of 78.1% [Citation5]. In addition, an observational study conducted in Shanghai revealed that individuals who received the inactivated vaccine experienced milder symptoms than those who were unvaccinated (risk ratio = 0.92, p < .001) [Citation21].
In this study, we conducted an analysis to assess the impact of vaccine boosters on the duration of isolation and viral shedding. Our findings showed no significant difference in the duration of isolation and viral shedding duration among patients who received booster doses of various vaccines. Although vaccination against SARS-CoV-2 variant strains may be reduced, boosters have been shown to reinstate the protective effects. Extensive research data confirm that booster vaccination enhances the neutralizing antibody response and has good efficacy against the Omicron variant [Citation22,Citation23]. Studies have demonstrated that three doses of the vaccine yield greater effectiveness, surpassing the effectiveness of only two doses in combating the Omicron variant. The overall vaccine VE against the Omicron variant was observed to be 55.9% for full vaccination and 80.8% for booster vaccination, thereby raising concerns regarding other vaccines [Citation23]. In a Hong Kong cohort study, patients who received the BNT162b2 booster exhibited fewer symptoms (adjusted HR = 0.59, CI = 0.45–0.77) [Citation24]. Similarly, a cohort study in the United Kingdom reported that vaccination resulted in reduced disease severity across multiple age groups [Citation25]. It is essential to note that the primary purpose of vaccination is to prevent the occurrence of severe disease, although the efficacy of vaccines in preventing mild cases may be limited. Given the evolutionary nature of variants emerging from epidemic strains and their potential ability to evade existing vaccines, sustained efforts may be required to combat new variants, especially if the enhanced vaccine antigen aligns with the prevailing circulating variant. A similar strategy is followed for influenza vaccines, with each year’s vaccine formulated based on the latest data on circulating strains. This approach enhances the likelihood of VE even as virus strains continue to evolve [Citation8].
Several studies have provided evidence supporting the high efficacy of the adenovirus type-5 (Ad5) vectored COVID-19 vaccine [Citation26]. In addition, research suggests that mRNA vaccines exhibit superior efficacy [Citation27]. Furthermore, studies have demonstrated the effectiveness of a single dose of recombinant protein vaccine [Citation28]. Specifically, in the present study, we aimed to address the important scientific question of whether heterologous vaccination is more effective than using inactivated vaccines alone. It has been proposed that mass vaccination with multiple vaccines can effectively enhance vaccination coverage [Citation29]. Notably, our findings indicate that, by the day 8.5 of isolation, 50% of patients who received heterologous vaccination were discharged, with 50% of them achieving a negative test result by day 6.5. Moreover, these patients exhibited higher rates of discharge and viral shedding within the 14-day time frame compared with other patients. Furthermore, the single-dose adenoviral-vectored vaccine, which has completed phase III trials, demonstrated effectiveness rates of 66% within 14 days of vaccination, 67% within 28 days, and 77% against moderate to severe COVID-19 infection [Citation28]. Therefore, our study provides valuable insights into COVID-19 vaccination strategies, highlighting the efficacy of heterologous vaccination and the potential benefits of mass vaccination with multiple vaccines.
Another key objective of this study was to explore whether the effectiveness of vaccines is associated with the timing of infection. Our analysis revealed no significant difference in the discharge rate and rate of achieving negativity between patients infected 12 months after their last vaccination and those infected within 12 months post-vaccination. However, evidence-based medical research indicates that the protective efficacy of vaccines gradually declines after 6 months after vaccination [Citation30]. As time progresses, the levels of neutralizing antibodies decrease, yet vaccines continue to demonstrate an effectiveness of over 70% in preventing severe disease and mortality. This finding suggests that the protection against severe disease is not solely dependent on antibody responses but also involves memory responses and cell-mediated immunity, which tend to have longer durations. Consequently, the protective effects of vaccination may have a longer-lasting impact [Citation7,Citation8,Citation30].
The Ct value serves as a relevant indicator used for evaluating virus infectivity. A Ct value higher than 33, obtained from a surface sample, is considered to have limited epidemiological significance [Citation31]. Research evidence suggests that vaccines can reduce the SARS-CoV-2 viral load, as demonstrated in an Irish survey where unvaccinated patients exhibited a viral load 2–4 times higher in nasal mucosa samples with vaccinated individuals [Citation32]. Similarly, another study revealed that partially or fully vaccinated individuals infected with SARS-CoV-2 had a lower average viral RNA load than unvaccinated participants, with a reduction of 40% (95% CI = 16–57) [Citation33]. Furthermore, a study illustrated that vaccination diminished the viral load of Delta BTIs within 2 months of vaccination [Citation34]. However, it is important to note that these findings may not be directly comparable to those of the present study, because our research relied on observational data, and only the Ct value at the time of patient admission was initially recorded. It should be acknowledged that the Ct value tends to increase as the duration to symptom progresses, which may affect the assessment of viral load.
This study has several limitations. First, the scope of this study was limited to asymptomatic or mildly symptomatic patients in isolation centres, which hindered analysis of the impact of vaccination on more severe symptoms of COVID-19 infection. In addition, the reported association between comorbidities, hospital stay duration, and time to achieving a negative test result is noteworthy. However, this study primarily comprised individuals with no symptoms or mild symptoms, because patients with severe diseases were not admitted to the isolation centres and thus were therefore not included. Consequently, the relationship between comorbidities and VE was not addressed in this study. Furthermore, it is essential to acknowledge the high vaccination rate in China, with over 90% of the investigated population having received vaccination. This widespread vaccination coverage results in a smaller representation of individuals opting for heterologous vaccination or remaining unvaccinated. The imbalance in the vaccination rate and resulting sample size disparity across vaccine regimens may introduce bias into our findings. To address this potential bias, we conducted multivariate analysis in sensitivity analysis. Nonetheless, observational studies like ours should be considered as preliminary and the findings should be interpreted with caution. It is crucial to continuously update and thoroughly review the data to ensure that policy development is firmly grounded in scientific evidence [Citation8].
Conclusions
Vaccinated patients displayed a higher rate of viral shedding and experienced shorter isolation duration within a 14-day period compared with unvaccinated patients, suggesting the efficacy of vaccines in combating COVID-19 infection. Moreover, the use of heterologous vaccines demonstrated superior effectiveness in comparison to solely using the inactivated vaccines. Notably, there was no statistically significant difference in the vaccine’s protective effect of vaccination during the 12-month post-vaccination period, indicating its persistent efficacy against the virus.
Author contributions
Conceptualization, J.M. and Y.D.X.; methodology, J.M. and X.T.K.; software, X.T.K.; validation, all authors; formal analysis, X.T.K.; investigation, all authors; resources, Y.D.X., W.Q.H. and Z.J.L.; data curation, Y.D.X. and X.T.K.; writing – original draft preparation, X.T.K.; writing – review and editing, all authors; visualization, X.T.K.; supervision, J.M. and Y.D.X.; project administration, J.M., Y.D.X., W.Q.H. and Z.J.L.; funding acquisition, J.M. and Y.D.X. All authors have read and agreed to the published version of the manuscript.
Ethical approval
The First Affiliate Hospital of Guangzhou Medical University Research Ethics Committee reviewed the manuscript and consent for publication (approval number ES-2023-116-01). Participants provided their informed consent.
Consent form
Written informed consent was obtained from all patients for publication.
Supplemental Material
Download Zip (94.2 KB)Supplemental Material
Download Zip (302.6 KB)Acknowledgements
The authors would like to express their sincere appreciation and gratitude to the staff members and involved patients of the First Affiliate Hospital of Guangzhou Medical University, Fangcang isolation centre in Pazhou and Yongning for their tremendous assistance and cooperation in the study.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Additional information
Funding
References
- WHO; 2023 [cited 2023 Jul 5]. Available from: https://www.who.int/data#dashboards
- Mathieu E, Ritchie H, Ortiz-Ospina E, et al. A global database of COVID-19 vaccinations. Nat Hum Behav. 2021;5(7):1–11. doi: 10.1038/s41562-021-01122-8.
- Voysey M, Costa Clemens SA, Madhi SA, et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet. 2021;397(10277):881–891. doi: 10.1016/S0140-6736(21)00432-3.
- Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403–416. doi: 10.1056/NEJMoa2035389.
- Al Kaabi N, Zhang Y, Xia S, et al. Effect of 2 inactivated SARS-CoV-2 vaccines on symptomatic COVID-19 infection in adults: a randomized clinical trial. JAMA. 2021;326(1):35–45. doi: 10.1001/jama.2021.8565.
- Hall VJ, Foulkes S, Saei A, et al. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study. Lancet. 2021;397(10286):1725–1735. doi: 10.1016/S0140-6736(21)00790-X.
- Khoury DS, Cromer D, Reynaldi A, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021;27(7):1205–1211. doi: 10.1038/s41591-021-01377-8.
- Krause PR, Fleming TR, Peto R, et al. Considerations in boosting COVID-19 vaccine immune responses. Lancet. 2021;398(10308):1377–1380. doi: 10.1016/S0140-6736(21)02046-8.
- Krause PR, Fleming TR, Longini IM, et al. SARS-CoV-2 variants and vaccines. N Engl J Med. 2021;385(2):179–186. doi: 10.1056/NEJMsr2105280.
- Zhang Y, Lv Q, Qi F, et al. Comparison of the replication and neutralization of different SARS-CoV-2 Omicron subvariants in vitro. Anim Mod Exp Med. 2023;6(1):51–56. doi: 10.1002/ame2.12302.
- Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–273. doi: 10.1038/s41586-020-2012-7.
- Hoffmann M, Arora P, Groß R, et al. SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell. 2021;184(9):2384–2393.e12. doi: 10.1016/j.cell.2021.03.036.
- World Health Organization. Interim recommendations for heterologous COVID-19 vaccine schedules: interim guidance. Geneva: World Health Organization; 2021.
- Alhinai Z, Park S, Choe YJ, et al. A global epidemiological analysis of COVID-19 vaccine types and clinical outcomes. Int J Infect Dis. 2022;124:206–211. doi: 10.1016/j.ijid.2022.09.014.
- Colavita F, Meschi S, Gruber CEM, et al. Virological and serological characterisation of SARS-CoV-2 infections diagnosed after mRNA BNT162b2 vaccination between December 2020 and March 2021. Front Med. 2021;8:815870. doi: 10.3389/fmed.2021.815870.
- Humphrey L, Thommes EW, Fields R, et al. Large-scale frequent testing and tracing to supplement control of covid-19 and vaccination rollout constrained by supply. Infect Dis Model. 2021;6:955–974. doi: 10.1016/j.idm.2021.06.008.
- Laine C, Cotton D, Moyer DV. COVID-19 vaccine: promoting vaccine acceptance. Ann Intern Med. 2021;174(2):252–253. doi: 10.7326/M20-8008.
- Yang ZR, Jiang YW, Li FX, et al. Efficacy of SARS-CoV-2 vaccines and the dose–response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials. Lancet Microbe. 2023;4(4):e236–e246. doi: 10.1016/S2666-5247(22)00390-1.
- Cuschieri S. The STROBE guidelines. Saudi J Anaesth. 2019;13(Suppl. 1):S31–S34. doi: 10.4103/sja.SJA_543_18.
- Haas EJ, Angulo FJ, McLaughlin JM, et al. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using National Surveillance Data. Lancet. 2021;397(10287):1819–1829. doi: 10.1016/S0140-6736(21)00947-8.
- Yang D, Weng H, Wang R, et al. Evaluation of COVID-19 vaccines in primary prevention against infections and reduction in severity of illness following the outbreak of SARS-CoV-2 Omicron variant in Shanghai. Front Med. 2023;10:1079165. doi: 10.3389/fmed.2023.1079165.
- Vitiello A, Ferrara F, Troiano V, et al. COVID-19 vaccines and decreased transmission of SARS-CoV-2. Inflammopharmacology. 2021;29(5):1357–1360. doi: 10.1007/s10787-021-00847-2.
- Li T, Luo KQ. Recipients of COVID-19 vaccines face challenges of SARS-CoV-2 variants. Int J Biol Sci. 2022;18(12):4642–4647. doi: 10.7150/ijbs.72424.
- Tsang NNY, So HC, Cowling BJ, et al. Effectiveness of BNT162b2 and CoronaVac COVID-19 vaccination against asymptomatic and symptomatic infection of SARS-CoV-2 Omicron BA.2 in Hong Kong: a prospective cohort study. Lancet Infect Dis. 2023;23(4):421–434. doi: 10.1016/S1473-3099(22)00732-0.
- Nyberg T, Ferguson NM, Nash SG, et al. Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants in England: a cohort study. Lancet. 2022;399(10332):1303–1312. doi: 10.1016/S0140-6736(22)00462-7.
- Sadoff J, Gray G, Vandebosch A, et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against covid-19. N Engl J Med. 2021;384(23):2187–2201. doi: 10.1056/NEJMoa2101544.
- Zeng B, Gao L, Zhou Q, et al. Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: a systematic review and meta-analysis. BMC Med. 2022;20(1):200. doi: 10.1186/s12916-022-02397-y.
- Halperin SA, Ye L, MacKinnon-Cameron D, et al. Final efficacy analysis, interim safety analysis, and immunogenicity of a single dose of recombinant novel coronavirus vaccine (adenovirus type 5 vector) in adults 18 years and older: an international, multicentre, randomised, double-blinded, placebo-controlled phase 3 trial. Lancet. 2022;399(10321):237–248. doi: 10.1016/S0140-6736(21)02753-7.
- Bello-Chavolla OY, Antonio-Villa NE, Valdés-Ferrer SI, et al. Effectiveness of a nationwide COVID-19 vaccination program in Mexico against symptomatic COVID-19, hospitalizations, and death: a retrospective analysis of National Surveillance Data. Int J Infect Dis. 2023;129:188–196. doi: 10.1016/j.ijid.2023.01.040.
- Feikin DR, Higdon MM, Abu-Raddad LJ, et al. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression. Lancet. 2022;399(10328):924–944. doi: 10.1016/S0140-6736(22)00152-0.
- Kampf G, Lemmen S, Suchomel M. Ct values and infectivity of SARS-CoV-2 on surfaces. Lancet Infect Dis. 2021;21(6):e141. doi: 10.1016/S1473-3099(20)30883-5.
- Callaway E. Delta coronavirus variant: scientists brace for impact. Nature. 2021;595(7865):17–18. doi: 10.1038/d41586-021-01696-3.
- Thompson MG, Burgess JL, Naleway AL, et al. Prevention and attenuation of covid-19 with the BNT162b2 and mRNA-1273 vaccines. N Engl J Med. 2021;385(4):320–329. doi: 10.1056/NEJMoa2107058.
- Levine-Tiefenbrun M, Yelin I, Katz R, et al. Initial report of decreased SARS-CoV-2 viral load after inoculation with the BNT162b2 vaccine. Nat Med. 2021;27(5):790–792. doi: 10.1038/s41591-021-01316-7.