Materials & Methods
We conducted a cross-sectional study in Peru.

The population comprised people over 18 years old who had received a minimum of 2 doses of the COVID-19 vaccine and who were living in Peru at the time of the survey. This was verified in the informed consent form with the following question: “Do you provide your informed consent to voluntarily participate in this research by declaring that you are 18 years of age or older and have at least 2 doses of the vaccine against COVID-19?”. To ensure that participants resided in Peru, they were asked in the survey about the current department of residence. The sample was calculated with the STATA v.16.0 program (StataCorp LP, College Station, TX, USA), with a test of proportions for 2 samples, with a difference of 11% in the IBV between the population living in the city and the rural area according to background ( Herrera-Añazco et al., 2021a ). We used a power of 80%, a p -value of 0.05, and a design effect of 1.4. We estimated a 15% loss rate, estimating a minimum of 897 participants in total. Patient selection was by convenience sampling.

A virtual survey form using Google Forms was developed in Spanish and distributed across different departments of Peru through the social networks Facebook and WhatsApp with the help of collaborators during the period from July 1 to 16, 2022. Likewise, physical surveys were conducted in public places without providing any incentives to the study participants. The physical survey should be understood as the survey carried out by qualified personnel, authors and collaborators, and self-administered by the participant himself when he requested it. To control whether an individual accessed the questionnaire twice, each participant was asked to respond individually and only once, and socio-demographic aspects were also checked to search for duplicates. The virtual questionnaire had mandatory questions that did not allow continuing to the next questions. The physical surveys did not have mandatory questions to continue. The questionnaire was available for two weeks and no specific time was established for its completion. There was no follow-up, and no reminders were sent. At the end of this period, the databases of each collaborator were downloaded in Microsoft Excel 2016 format for their respective processing. It is important to mention that a previous pilot study was not carried out.

Data was collected by means of an online survey consisting of 35 questions. The survey consisted of a main interface detailing the purpose of the study,including informed consent, and three sections: the first (16 items) assessed general characteristics and sociodemographic factors; the second (eight items) explored booster dose perception factors; and the third (11 items), focused onclinical factors. We adapted these questions from the survey conducted by the University of Maryland, USA, adding the word “booster” for the questions related to primary vaccination (available at: https://umdsurvey.umd.edu/jfe/form/SV_6DnpVXXm2aYdnSe?token=VtALR8zAmXZUCli5Ud&Q_CreateFormSession=1&Q_Language=ES ), which was conducted via Facebook ( Neumann-Böhme et al., 2022 ).

In the last section, to measure depressive symptoms, the subscale of the DASS-21 instrument was used, in which each item responds according to the presence and intensity of each depressive symptom in the last week on a Likert-format response scale, ranging from 0 (“It did not happen to me”) to 3 points (“It happened to me a lot or most of the time”). The corresponding subscale presents seven items in total, and its score is calculated with the sum of them. The DASS-21 is a reliable instrument with adequate construct validity and solid internal consistency ( Antúnez & Vinet, 2012 ).

The survey questionnaire underwent a face validation process with expert judgment, including Likert-format scale options to assess coherence, clarity, and relevance. The V-Aiken calculation was used to estimate the questionnaire’s main objective. If the calculation resulted in an estimate greater than 0.75 for coherence, clarity, and relevance, survey participants were then selected.

We conducted a post-hoc analysis to assess the internal structure using Chronbach’s alpha of the items in the Stata statistical software with the alpha function.

The dependent variable was IBV, which was measured with the question “Do you agree to apply a booster dose to COVID-19? (Booster dose is understood as the third or fourth dose)”. This question had four possible answers: “Definitely yes”, “Probably yes”, “Probably no”, “Definitely no”. The first two responses were grouped as positive IBV, while the last two as negative IBV. This categorization was made according to a previous study ( Herrera-Añazco et al., 2021a ). We grouped the IBV of the first and second booster doses. In addition, those who had already received 2 booster doses were considered IBV positive.

Some questions were categorized according to the following antecedents ( Herrera-Añazco et al., 2021a ), while others were categorized at the discretion of the researchers:

We considered the variables sex, age, region, area of residence, religion, economic insecurity (defined as family income less than the minimum wage in Peru, i.e., less than 1,025 soles ($271.27) ( El Peruano, 2023 )), have children, education (highest academic level completed), employment status, and food insecurity. This last variable was assessed with the following question: “Are you worried about having enough food for the next week?”. The responses to this question were “Very worried”, “Somewhat worried”, “Not very worried”, “Not at all worried”. To obtain an accurate measure of food insecurity, we considered the first two responses as “Yes” and the last two as “No”.

We evaluated depressive symptomatology using the depression subscale of the DASS-21. We considered with the presence of depressive symptoms those people who had a score higher than 5, this cut-off point has a sensitivity of 88.5% and a specificity of 86.8% ( Román, Santibáñez & Vinet, 2016 ). We assessed the presence of comorbidities, defined as a story of cardiac involvement (such as myocarditis, pericarditis, deep vein thrombosis, myocardial infarction, or pulmonary embolism) and/or pulmonary involvement (such as respiratory failure, acute respiratory syndrome, pulmonary fibrosis, asthma, or pneumonia).

We evaluated the presence of events suspected to be attributed to vaccination or immunization (ESAVI) during the application of any of the doses against COVID-19 according to the participant’s self-report. The variable was grouped into three categories: none, mild-moderate (such as general malaise, headache, pain at the injection site, among others) and severe (including people who reported having had an allergic reaction or requiring hospitalization). Additionally, we evaluated symptomatology suspicious for COVID-19. This was defined as experiencing three or more of the following symptoms 24 h prior to the survey: shortness of breath, cough, chest pain, fever, sore throat, eye pain, headache, fatigue, nausea, muscle pain or loss of smell. These criteria were described by WHO ( World Health Organization, 2023b ) and have already been used in other research ( Herrera-Añazco et al., 2021b ).

We assessed the perception of the efficacy and protective effect of the booster dose with the following question: “Do you think the booster dose is effective and confers a protective effect against COVID-19?”. This question had four possible answers: “Definitely yes”, “Probably yes”, “Probably no”, “Definitely no”. The first two responses were grouped as “Yes”, while the last two as “No” (lack of confidence about the efficacy of the booster dose).

We evaluated concerns of experiencing adverse effects from the booster dose with the following question: “How concerned do you feel about experiencing adverse effects from the booster dose? (Booster dose is understood as the third or fourth dose)”. This question had four possible responses: “Very concerned, ”Moderately concerned”, ”Not at all concerned”, ”Not at all concerned”. The first two answers were grouped as “Yes”, while the last two as “No”.

We assesed the IBV based on the recommendations of various agents, including friends and relatives, physicians and other health professionals, government health authorities such as Ministerio de Salud (MINSA), and politicians. For this purpose, we elaborated a generic question: “How likely are you to accept the booster dose against COVID-19 if it were recommended to you...?”. Complementing with the various agents mentioned above. The possible answers were three: “More likely”, “About the same” and “Less likely”. The first answer indicated a good acceptance of the recommendation of that agent, while the last two were grouped together, indicating a lower acceptance or lack of influence of that agent on the recommendation to be vaccinated with the booster dose.

Statistical analysis was performed in Stata 16.0 (StataCorp, College Station, TX, USA). We categorized all variables and described absolute and relative frequencies. For the bivariate analysis, we used the chi-square test to evaluate the associations of each categorical variable with the IBV after evaluating the assumption of expected frequency. For both the bivariate and multiple regression model, we used the Poisson family generalized linear model function with robust variance and log-link function. Prevalence ratios with 95% confidence intervals were estimated, and significance was set at p < 0.05 for two tails.

The multiple regression analysis was constructed using the statistical model with the stepwise test with forward selection and a criterion of p < 0.20, including the variables sex, age, depressive symptoms, comorbidities, acceptance of the booster dose on the recommendation of friends and family, physicians and other health professionals, MINSA, fear of adverse events and perception of efficacy. This last variable was removed from the final model because it presented collinearity with the acceptance of the booster dose on the recommendation of physicians and other health professionals. Collinearity was assessed using the variance inflation factor.

The research protocol was reviewed and approved by the Institutional Research Ethics Committee of the Avendaño Clinic, Lima, Peru, with the code (031-2022-CIEI). The ethical principles of the Declaration of Helsinki of beneficence, autonomy, and non-maleficence were respected. The questionnaire was anonymous and included a declaration of virtual informed consent for the online surveys. For physical surveys, participants provided their written informed consent through their signature. In both cases, we specified the objective of the study, the use of their data and assured them of anonymity throughout the research. As observational methods were used, our study did not generate greater risk for the participants.