
==== Front
F1000Res
F1000Res
F1000Research
2046-1402
F1000 Research Limited London, UK

39221026
10.12688/f1000research.123395.2
Research Article
Articles
Effects of vaccination against COVID-19 on the emotional health of older adults
[version 2; peer review: 1 approved

Alarcon-Ruiz Christoper A. Conceptualization Data Curation Formal Analysis Investigation Methodology Project Administration Writing – Original Draft Preparation Writing – Review & Editing https://orcid.org/0000-0003-3907-2784
a1
Romero-Albino Zoila Conceptualization Data Curation Investigation Methodology Project Administration Resources Supervision Writing – Review & Editing https://orcid.org/0000-0003-2519-2945
23
Soto-Becerra Percy Formal Analysis Investigation Methodology Resources Supervision Writing – Original Draft Preparation Writing – Review & Editing 1
Huarcaya-Victoria Jeff Data Curation Investigation Methodology Project Administration Supervision Writing – Review & Editing 45
Runzer-Colmenares Fernando M. Investigation Methodology Writing – Review & Editing 6
Romani-Huacani Elisa Investigation Methodology Writing – Review & Editing 78
Villarreal-Zegarra David Investigation Methodology Writing – Review & Editing https://orcid.org/0000-0002-2222-4764
910
Maguiña Jorge L. Conceptualization Funding Acquisition Investigation Methodology Project Administration Resources Supervision Validation Writing – Review & Editing 1
Apolaya-Segura Moises Conceptualization Funding Acquisition Investigation Methodology Project Administration Resources Supervision Validation Writing – Review & Editing 1
Cuba-Fuentes Sofía Conceptualization Investigation Methodology Project Administration Resources Supervision Validation Writing – Review & Editing https://orcid.org/0000-0001-7394-7092
211
1 Dirección de Investigación en Salud, Instituto de Evaluación de Tecnologías en Salud e Investigación – IETSI, EsSalud, Lima, Peru
2 Gerencia de la Persona Adulta Mayor y Prestaciones Sociales, EsSalud, Lima, Peru
3 Carrera de Medicina Humana, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
4 Unidad de Psiquiatría de Enlace, Departamento de Psiquiatría, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Peru
5 Escuela Profesional de Medicina Humana, Universidad Privada San Juan Bautista, Filial, Peru
6 Facultad de Ciencias de la Salud, Universidad Científica del Sur, Lima, Peru
7 Asociación benéfica PRISMA, Lima, Peru
8 Facultad de Ciencias de la Salud, Universidad Cesar Vallejo, Lima, Peru
9 Instituto Peruano de Orientación Psicológica, Lima, Peru
10 South American Center for Education and Research in Public Health, Universidad Privada Norbert Weiner, Lima, Peru
11 Facultad de Medicina Alberto Hurtado, Universidad Peruana Cayetano Heredia, Lima, Peru
a christoper.alarconr20@gmail.com
No competing interests were disclosed.

16 5 2023
2022
11 86817 4 2023
Copyright: © 2023 Alarcon-Ruiz CA et al.
2023
https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: The COVID-19 pandemic significantly impacted the mental and emotional health of the elderly, especially those from low to middle-income countries. However, COVID-19 vaccination may reduce this influence. Therefore, we aimed to estimate the effect of vaccination against COVID-19 on the emotional health of older adults.

Methods: We selected a national, random, and stratified sample of non-hospitalized adults aged 60 to 79 years from Peru who intended to receive or had already received the COVID-19 vaccine during recruitment. During June and July 2021, the assessed outcomes were the fear, anxiety, and worry about COVID-19, general anxiety, and depression at baseline and after a month. We estimated the adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for each altered emotional health outcomes in those who had one and two doses, compared with those who were not vaccinated using multilevel logistic regression with mixed effects.

Results: We recruited 861 older adults with 20.8% of loss to follow-up. At baseline, 43.9% had received only one dose of the vaccine, and 49.1% had two doses. In the analysis during follow-up, those who had two doses had less fear (aOR: 0.19; CI 95%: 0.07 to 0.51) and anxiety to COVID-19 (aOR: 0.45; CI 95%: 0.22 to 0.89), compared to unvaccinated. We observed no effects in those with only one dose.

Conclusions: Two doses of COVID-19 vaccination in older adults improves their perception of COVID-19 infection consequences. This information could be integrated into the vaccination campaign as an additional beneficial effect.

Aged
COVID-19
Mental Health
Anxiety
Depression
Peru
Dirección de Investigación en Salud, Instituto de Evaluación de Tecnologías en Salud e Investigación – IETSI, EsSaludGerencia de la Persona Adulta Mayor y Prestaciones Sociales, EsSaludThis study was funded by the Dirección de Investigación en Salud, Instituto de Evaluación de Tecnologías en Salud e Investigación – IETSI, EsSalud, and the Gerencia de la Persona Adulta Mayor y Prestaciones Sociales, EsSalud. The funders had no role in the study design, data collection, analysis, and interpretation of results, writing of the report, and in the decision to submit the article for publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Revised Amendments from Version 1

This new version acknowledges all the suggestions by reviewers and updated the references. First, we correct the phrasing of our results in all the manuscript avoiding using cause-effects terms because this is a cross-sectional study. Second, we updated the main analysis considering the type of vaccine preference as a confounding variable for the association between vaccination and mental health outcomes. In addition, we also added a new analysis using the group with only one dose as the control group compared to the group with two doses of the vaccine. This new analysis was included in the abstract and in the results section (Tables 2 and 3). Also, we compared the characteristics between the no vaccinated, one-dose, and two doses groups using hypothesis tests (Table 1) for a better understanding of differences between groups and potential confounding factors. Then, we acknowledge all the main limitations of our study design and analysis, to have a better understanding of our results. Finally, we added an institutional affiliation for two of our authors because of their support during the present study and in this new version.
==== Body
pmcAbbreviations

CAM: Centers for the eldery

CAS: Coronavirus Anxiety Scale

EsSalud: Social Health Insurance of Peru

FCV-19S: Fear of COVID-19 Scale

GAD-2: Generalized Anxiety Disorder

PHQ-2: Patient Health Questionnaire

PRE-COVID-19: Scale to measure worry for contagion of the COVID-19

Introduction

The COVID-19 pandemic has resulted a significant impact on the mental health of people worldwide. 1 Approximately 15% of older adults had a mental health disorder before the pandemic ( https://www.who.int/news-room/fact-sheets/detail/mental-health-of-older-adults), but older adults have reported greater declines in social communication, exercise, and finances during the pandemic years compared to young adults. 2 , 3 In addition, the high contagiousness of COVID-19 and higher risk of death and complications in the elderly population, 4 , 5 may have caused a worsening of sleep quality, well-being, depressive, and anxious symptoms, since the beginning of the pandemic. 6 It is estimated that the damage has been especially profound in older adults in low- and middle-income countries compared to those in developed countries. 7 Furthermore, the ministries of health from Latin American countries have not prioritized strategies or policies that deal with emotional and mental health problems during the pandemic, which could cause the impact on these aspects to be greater. 8 For instance, Peru is one of the countries with the highest mortality rate from COVID-19 per million inhabitants in the world 9 and it has had a significant economic and social impact. 10 In this context, high levels of worry, anxiety, and fear of COVID-19 have been described in people living in Peru. 11 – 13

Vaccination against COVID-19 has meant a change in the pandemic dynamics 14 due to its proven effectiveness in reducing severe cases and deaths from COVID-19 in the general population and older adults. 15 , 16 Mental health status during the pandemic could be related to COVID-19 vaccination in different ways ( Figure 1). First, mood disorders such as stress, depression, and loneliness can decrease the immune system response caused by the COVID-19 vaccine. 17 In addition, in older adults, having a mental disorder may be associated favorably 18 , 19 or negatively 20 , 21 with the willingness to be vaccinated against COVID-19. On the other hand, doubts about the COVID-19 vaccine correlate with high levels of anxiety, depression, and post-traumatic stress, 22 which can cause acute episodes of anxiety immediately after receiving the COVID-19 vaccine. 23 Finally, studies in the general population of the United States 24 – 26 and in health professionals in Turkey 27 suggest that receiving the COVID-19 vaccine may have a direct effect in reducing levels of anxiety and depression.

Figure 1. Relationship between vaccination against COVID-19 and mental health in the general population.

Older adults are a priority group to receive the COVID-19 vaccine 28 which it may positively affect their emotional health ( https://www.northwell.edu/coronavirus-covid-19/covid-19-vaccine-can-boost-mental-health-too). However, this population is underrepresented in studies evaluating this association. A better understanding of the relationship between vaccination against COVID-19 and emotional health would improve knowledge of the positive determinants of health in the population. 29 The positive effect that vaccination against COVID-19 could generate in the older adult population would imply an improvement in their quality of life during the pandemic, and policies and promotion of vaccination could be oriented in this direction. So, it is necessary to know how receiving the COVID-19 vaccine could affect the perception of pandemic and risk of disease in older adults. The aim of the present study was to assess the effect of receiving the COVID-19 vaccine on emotional health in a representative group of older adults in Peru during the year 2021.

Methods

Context

Peru is a country with a fragmented and heterogeneous health system. Among them, the Social Health Insurance of Peru (EsSalud) is one of the most important health systems in the country and is managed by the Ministry of Labor and Employment Promotion. 30 EsSalud gives medical attention to formal workers, retirees, and their families. The executive function of EsSalud is divided through the 29 healthcare networks, representative of each region in the country. EsSalud provides health coverage to almost a third of Peruvians, including more than 1 890 000 older adults, of which 100 000 of them are users of the Centers for the Elderly (CAM, in Spanish) present in each healthcare network in the country. 31 The CAMs provide health services that seek to improve the functional, mental, and social capacity of people aged 60 or older affiliated with EsSalud. 32

The vaccination process against COVID-19 in Peru, organized by the Ministry of Health, was carried out by age groups, and began on April 16, 2021, with adults over 80 years old. Vaccination started on April 28, 2021, for adults over 70 years old, and on May 27, 2021, for adults over 60 years old. During that period, the BNT162b2 (BioNTech, Pfizer), ChAdOx1-S (Oxford, AstraZeneca), and BBIBP-CorV (Sinopharm) vaccines were available in Peru. However, the Peruvian Ministry of Health indicated that vaccination should be prioritized with BNT162b2 (BioNTech, Pfizer) for older adults with 60 years or older ( https://cdn.www.gob.pe/uploads/document/file/1893194/Directiva%20%20Sanitaria%20N%C2%B0%20133-MINSA-2021-DGIESP%20.pdf). As a result, as of December 29, 2021, 80.8% of older adults who received at least one dose of the COVID-19 vaccine received BNT162b2 (BioNTech, Pfizer), while 10.5% and 8.7% had received the ChAdOx1-S vaccine (Oxford, AstraZeneca) and BBIBP-CorV (Sinopharm), respectively ( https://www.minsa.gob.pe/reunis/data/vacunas-covid19.asp). However, the vaccination of older adults occurred during a political and health scandal in the country; Inoculation of the BBIBP-CorV (Sinopharm) vaccine candidate, outside the clinical trial, to 470 people in Peru, including health personnel and politicians. 33 , 34 For several months, this caused a credibility crisis for COVID-19 vaccines, particularly BBIBP-CorV (Sinopharm). 35

Study design

A prospective cohort study was conducted that aimed to estimate the effect of the COVID-19 vaccine on the following emotional health outcomes of older adults affiliated to EsSalud CAMs: (a) Perception of fear, (b) anxiety, and (c) worry about COVID-19, (d) general depression, and (e) general anxiety.

Population

We identified non-hospitalized adults aged 60 to 79 years affiliated to EsSalud and registered in the CAM available database at national level. The database represented 0.5% of all older adults affiliated to EsSalud. We included those older adults who had already been vaccinated (with any of the available vaccines) or who had planned to be vaccinated against COVID-19 according to the Peruvian Ministry of Health vaccination schedule at a vaccination site in Peru. We excluded adults aged 80 years or older because more than one month had elapsed since the start of vaccination in this age group by the initiation of the recruitment. We also excluded those who had some impediment to adequate communication with the interviewer via the telephone call, were diagnosed with COVID-19 in the last three months, had symptoms related to COVID-19, or refused to participate during the interview. The recruitment period was from May 27 to June 30, 2021.

Sample size calculation

Based on the recommendation of Cohen et al., 36 , 37 we consider an effect size of 0.20 standard deviations for the smallest effect 36 estimated between any of the outcomes (perception score for fear, anxiety, and worry about COVID-19, general depression, and anxiety) and the exposure factor (unvaccinated vs. vaccinated with only one dose or vaccinated with two doses) in older adults. Assuming a significance level of 5%, statistical power of 80%, and equal variances between groups, we calculated a minimum sample of 788 older adults. Then, we corrected this value by a factor of 1.2, following the methodology proposed by Vititingghoff E. et al., 38 considering the primary analysis with adjustment for potential confounding variables. Thus, we obtained a minimum sample size of 946 older adults. Finally, we considered a rejection rate of 10% and a loss to follow-up rate of 10%; then, we planned to invite 1168 participants to the study. Further details are found in the extended data (Supplementary methods: Sample size calculation). 39

Sampling

After excluding those who did not meet the selection criteria or did not have identification or contact data, we took 7 685 older adults from the registered CAMs into the database as a sample frame. From them, we chose a randomized and stratified sample for each of the 30 healthcare networks (n = 1 686). In addition, the sampling was carried out independently for two age subpopulations: 60 to 69 years (n = 846) and 70 to 79 (n = 840) years. For each subpopulation, we chose half of the calculated total sample size (allocation ratio 1:1). We decided to choose two age subpopulations because the recruitment period was during the start of vaccination of adults older than 60 to 69 years and one month after the initiation of vaccinations to adults older than 70 to 79 years ( https://cdn.www.gob.pe/uploads/document/file/1893194/Directiva%20%20Sanitaria%20N%C2%B0%20133-MINSA-2021-DGIESP%20.pdf). The characteristics of the eligible population and selected sample are found in the extended data (Supplementary methods: Characteristics of the eligible population). 39 To reduce non-response bias, we adjusted sample weights to account for non-response using weighting class adjustment. 40 , 41 Further details are found in the extended data (Supplementary: Sampling weights calculations). 39

Outcomes

We assessed five outcomes in emotional health: fear of COVID-19, anxiety about COVID-19, worry about COVID-19, general anxiety, and general depression, perceived by the respondents during the last two weeks before responding to the survey. Fear of COVID-19 was measured with the Spanish version of the Fear of COVID-19 Scale (FCV-19S) with seven items that are answered on a Likert scale from 1 (strongly disagree) to 5 (strongly agree). 42 This scale measures the emotional and somatic fear response to COVID-19. It has adequate internal consistency (Cronbach’s α = 0.88) and convergent validity with other mental health covariates in two non-probabilistic samples of adults and older adults from Lima, Peru. 42 , 43 The anxiety about COVID-19 was measured using the Spanish version of the Coronavirus Anxiety Scale (CAS), which measures persistent and excessive concern about COVID-19 that is accompanied by physical symptoms 44 and has five items that are answered on a Likert scale from 0 (not at all) to 4 (almost every day). 45 It is a unidimensional scale with adequate internal consistency (Cronbach’s α = 0.89 and 0.91), convergent validity with anxiety, and adjustment rates between females and males, and between older adults aged 60 to 65 years and 66 to 86 years. However, estimations in samples of adults and older adults from Lima, Peru, using Item Response Theory models, suggest that the instrument is more reliable in those with high anxiety levels to COVID-19. 46 , 47 The outcome ‘worry about COVID-19’ was measured with the scale to measure worry about contagion of COVID-19 (PRE-COVID-19, in Spanish), which contains six items that are answered on a Likert scale of 1 (never or rarely) to 4 (almost all the time). This scale measures the degree of worry about possible COVID-19 infection in the respondent and how this concern affects their state of mind and their ability to carry out their daily activities. It was developed in a non-probabilistic sample of adults between 18 and 50 years of age from Lima and Callao, Peru, and it proved to be unidimensional, to have adequate content validity, internal consistency (ω coefficient = 0.90), and convergent validity with other mental health covariates. 12 A higher total score on each scale means a higher respondent’s outcome level. Then, we dichotomized the total scores for each outcome and considered the upper quartile as a high outcome level.

The general anxiety outcome was measured with the Spanish version of the Generalized Anxiety Disorder (GAD-2), which contains two items that are answered on a Likert scale from 0 (never) to 3 (almost every day). 48 A total score of two or more points can diagnose clinically relevant anxiety in older adults, with 67% sensitivity and 90% specificity. 49 The general depression outcome was measured with the Spanish version of the Patient Health Questionnaire (PHQ-2), which contains two items that are answered on a Likert scale from 0 (no day) to 3 (almost every day). 50 A total score of three or more points can diagnose clinically relevant depression in older adults without cognitive impairment with 79% sensitivity and 82% specificity. 51

Exposure variable

We asked about self-reported COVID-19 vaccination status (no dose, only first dose, and two doses of vaccine) and the time in days since they received each dose of the vaccine.

Covariables

In addition, we asked about sociodemographic variables, previous mental health diagnosis and treatment, and personal and family history of COVID-19. Also, we asked about the preference between BNT162b2 (BioNTech, Pfizer), ChAdOx1-S (Oxford, AstraZeneca), and BBIBP-CorV (Sinopharm) vaccine. Additionally, we assessed the comorbidity with the Geriatric Comorbidity Index. This index measures the severity degree of 15 clinical conditions, classifying them from 0 to 4 each (0: no disease, 1: asymptomatic disease, 2: asymptomatic disease with treatment, 3: uncontrolled disease despite treatment, and 4: very serious or life-threatening disease). After presenting the severity degree classification and giving simple and standardized examples about each clinical condition, the interviewers asked the responders to identify their current situation for each clinical condition. According to these scores, the degree of comorbidity was grouped into classes: without comorbidity (all conditions absent), class I (one or more conditions with a severity degree of 1 or less), class II (one or more conditions with a severity degree of 2), class III (one condition with a severity degree of 3), and class IV (two or more conditions with a severity degree of 3, or at least one condition with a severity degree of 4). 52

Data collection

We conducted a pilot with trained interviewers for data collection for one day using a random sample from the sampling frame of approximately 120 participants. During the pilot, we evaluated the data collection capacity of the interviewers and the availability to participate of the selected older adults. Then, we identified and corrected deficiencies for formal data collection.

After sampling, we assign an identification code to each selected older adult to facilitate recognition and monitoring within the program. Then, the interviewers contacted the selected participants through telephone calls, using the telephone numbers registered in the CAM database. Previously trained interviewers made the calls and collected data. In case of not answering two calls on two different days, the older adult was excluded from the study. During the call, the interviewers identified the older adult by asking them for their identity document number. Then, the older adult was invited to participate in the study by requesting their verbal informed consent. If the older adult agreed to participate in the survey, the interviewer asked about the selection criteria. Then, the interviewers collected the baseline data. The data collection interview took approximately 20 minutes.

The follow-up calls were made between July 1st and July 27th, 2021, considering the date of the baseline interview. During these calls, the interviewers followed the same procedure mentioned above. Again, we considered a lost record if the older adult did not answer the call twice on two days. Emotional health outcomes were asked directly using the questionnaires, but in a different order than before, with items in different places. At the end of the interview, they asked about vaccination against COVID-19.

Trained interviewers registered the collected information through the Google Form platform (Questionnaire in Spanish and English in the extended data: Supplementary methods 39 ), using the identification code of each participant. The principal investigator monitored this database every two days, looking for errors during data collection. In case of suspecting a wrong registration, we coordinated with the responsible interviewer to evaluate the need to re-register said entry.

Data analysis

All the information collected was automatically recorded in a Microsoft Excel 2021 sheet (Microsoft, WA, United States). Before the analysis, we joined the baseline database with the follow-up database considering the identification code of each older adult interviewed. We reviewed the database for inconsistencies in responses about vaccination. We considered the response in the baseline measurement as the valid one if it was inconsistent with the responses during the follow-up measurement. Then, we performed the descriptive analysis of the results in the total number of recruits and separately according to the vaccination status against COVID-19. We describe the relative and absolute frequencies of the qualitative variables and the mean ± standard deviation of the quantitative variables. The baseline prevalence of altered emotional health outcomes and their 95% confidence intervals (95% CI) were plotted for the total sample and separated according to COVID-19 vaccination status. We calculated the 95% CI with the logit adjust method for the design degrees of freedom. 53

We compared the frequency of altered emotional health outcomes with the Chi-squared test.

We assessed, in the baseline, the association between the vaccination situation and the outcomes in emotional health. We estimated the odds ratios (aOR) and 95% CI for having adjusted altered emotional health outcomes by sex, age, time in days since receiving the last dose of vaccine (unvaccinated were assigned with zero), living with someone, comorbidity, vaccine preference, history of emotional health, and history of COVID-19, using a logistic regression model.

Finally, we assessed the association between vaccination status and altered emotional health outcomes, performing multilevel logistic regression models with mixed effects with a three-level structure. In addition to the first individual level of each measurement, we used random intercepts for the healthcare network and each individual as the other two levels. This analysis allows us to calculate the effects considering the stratum of the care network and the correlations of the two responses over time within the same individual, thus allowing a longitudinal and stratified assessment. In addition, we adjusted the regression model for the confounding variables: time in days since receiving their last dose of vaccine, sex, age, living with someone, comorbidity, vaccine preference, history of mental health disease, history of COVID-19, and time in days since the basal measurement (The basal measurement records had a value of 0).

In all the previously mentioned analyses, we consider the study’s sample weights and the stratum using the svyset command. A value of p < 0.05 was considered statistically significant to reject the null hypothesis in all statistical tests. Statistical software STATA MP v17 (StataCorp, Texas, USA) was used for the analysis.

Ethics

Each participant gave verbal informed consent before being included in the study. The anonymity of the interviewees was always maintained, assigning each one an identification code. Therefore, the survey didn’t collect personally identifiable information. In cases where a participant had an acute event in her mental health, the interviewer immediately referred the participant to a psychiatrist free of charge who managed the event by telephone. The protocol is registered in the PRISA repository of the Peruvian National Institute of Health (ID code: EI00000001999), and it was approved by the Institutional Review Board of the Instituto Nacional del Corazón - EsSalud (Certificate of approval 25/2021-CEI).

Results

Recruitment and baseline measurement

We randomly selected and invited 1,686 older adults to the study. A total of 51.1% (n = 861) of them met the selection criteria for baseline measurement. Among the reasons for not participating in the study were not responding to the call (n = 695), having been diagnosed with COVID-19 in the last three months (n = 57), refusing to participate (n = 51), not wanting to be vaccinated (n = 11), have symptoms related to COVID-19 at the time of the interview (n = 8) and have been vaccinated in another country (n = 3). Then, 20.8% (n = 179) refused to participate or did not respond to the call for follow-up measurement ( Figure 2). The frequency distribution of gender and mean age were similar between those who did not participate in the baseline measurement or during the follow-up measurement compared to the recruited patients (Table S1 in the underlying data: Supplementary results 39 ).

Figure 2. Participant’s selection flowchart.

The main characteristics of older adults aged 60 to 79 years affiliated with EsSalud’s CAMs are in Table 1. 54.5% of widowers and divorcees older adults had been in that status for less than a year. Since the pandemic’s start, 20.8% have been hospitalized among those ever diagnosed with COVID-19. On the other hand, among older adults who had at least one family member, whom they live, with a diagnosis of COVID-19, since the start of the pandemic, 17.2% of them had at least one family member who died due to COVID-19. We observed that the age, geriatric comorbidity index, and previous COVID-19 personally or family diagnosis were associated with the vaccination status.

Table 1. Baseline characteristics of older adults recruited from May 27th to June 30th, 2021: Total and according to vaccination status (n = 861).

Characteristics	n	Weighted %	Unvaccinated (n = 67)	One dose of vaccine (n = 395)	Two doses of vaccine (n = 399)	p-value	
Age (years) *	71.5	72.2	68.2	0.65	71.4	0.2	73.4	0.19	<0.001	
Women	655	75.7	50	75.6	308	77.7	297	73.9	0.141	
Civil status									0.103	
 Single	101	11.4	6	8.3	55	13.7	40	9.7	
 Married or living with partner	507	58.5	41	61.8	223	54.7	243	61.4	
 Widowed	211	25.7	15	24.8	93	25.7	103	25.8	
 Divorced	40	4.5	4	5.2	24	5.9	12	3.1	
Living with someone	775	90.9	60	91.1	350	87.8	365	93.7	0.070	
Geriatric comorbidity index									0.002	
 No comorbidities	286	34.3	21	30.6	111	28.5	154	40.0	
 Class I	72	8.1	9	12.5	36	8.5	27	7.1	
 Class II	252	26.9	17	24.4	125	28.4	110	25.9	
 Class III	137	16.8	12	20.7	62	16.9	63	16.1	
 Class IV	114	14.0	8	11.8	61	17.7	45	10.9	
Mental health disease history	56	5.4	7	9.8	25	5.5	24	4.8	0.137	
Psychotherapy history **	21	38.2	4	55.2	9	37.4	8	34.2	0.576	
Psychotropic drug history **	29	56.9	6	85.4	12	60.0	11	46.2	0.196	
COVID-19 history	87	9.6	10	13.6	53	12.9	24	6.1	0.010	
COVID-19 history in family ***	123	14.8	16	25.5	69	19.2	38	9.5	<0.001	
† Some variables do not have 861 observations due to missing data.

* Absolute mean and weighted mean.

** Proportion based on total people with a mental health disease history.

*** Proportion based on the total number of people living with someone.

Regarding the vaccination situation, at the baseline measurement, 43.9% of the respondents received only one dose with an average time of 15.6 days from the date they received the vaccine, and 49.1% received the two doses with an average time of 16.9 days from the date they received the vaccine. On the other hand, 5.4% of older adults reported having a previous diagnosis of a mental health disorder. However, we found the prevalence of general anxiety, assessed with GAD-2, to be 16.4% (95% CI: 14.1 to 19.1), and the prevalence of general depression, estimated by PHQ-2, was 8.0% (95% CI: 6.3 to 10.0). In addition, we found that those who had two doses of the vaccine had less likely to have fear of COVID-19 (p<0.001), anxiety about COVID-19 (p<0.001), worry about COVID-19 (p<0.001), and general anxiety (p<0.001) compared to those who were unvaccinated or those who had one dose of the vaccine. However, we didn’t observe a trend in the case of the outcome of general depression (p=0.099) ( Figure 3).

Figure 3. Baseline prevalence of emotional health outcomes in total and according to vaccination status in older adults recruited from May 27th to June 30th, 2021 (n = 861).

Association between vaccination status and emotional health outcomes at baseline

During the baseline measurement, we observed that older adults who had two doses of the vaccine had less fear of COVID-19 (aOR: 0.27; 95% CI: 0.13 to 0.56) than those who were unvaccinated. Similarly, we observed a lower anxiety about COVID-19, worry about COVID-19, and general anxiety in those who had two doses of the vaccine, but without statistical significance. Meanwhile, those who had one or two doses of the vaccine were more likely to have general depression than those who were unvaccinated, although this was not statistically significant. However, those who had two doses of the vaccine were significantly less likely to had fear of COVID-19, anxiety about COVID-19, worry about COVID-19, and general anxiety, compared to those with only one dose ( Table 2).

Table 2. Association between vaccination status and emotional health outcomes during baseline measurement (n = 861).

Outcomes	Vaccination against COVID-19 status	
Unvaccinated (n = 67)	One dose (n = 395)	Two doses (n = 399)	
Fear of COVID-19 (FCV-19S)				
 aOR (95% CI) for high fear of COVID-19 (twelve points or more)	Ref.	0.65 (0.34–1.29)	0.27 (0.13–0.56)	
	Ref.	0.41 (0.28-0.62)	
Anxiety for COVID-19 (CAS)				
 aOR (95% CI) for high anxiety about COVID-19 (one point or more)	Ref.	1.15 (0.61–2.20)	0.65 (0.33–1.23)	
	Ref.	0.56 (0.39-0.81)	
Worry for COVID-19 (PRE-COVID-19)				
 aOR (95% CI) for high worry about COVID-19 (twelve points or more)	Ref.	1.21 (0.60–2.43)	0.75 (0.36–1.55)	
	Ref.	0.62 (0.42-0.91)	
General anxiety (GAD-2)				
 aOR (95% CI) for general anxiety (two points or more)	Ref.	0.79 (0.39–1.61)	0.49 (0.22–1.06)	
	Ref.	0.61 (0.39-0.97)	
General depression (PHQ-2)				
 aOR (CI 95%) for general depression (three points or more)	Ref.	2.33 (0.47–11.66)	1.69 (0.32–8.89)	
	Ref.	0.73 (0.36-1.47)	
IQR: Interquartile range; aOR: Adjusted odds ratio for days since receiving the last vaccine dose, sex, age, living with someone, comorbidity, history of mental health disease, history of COVID-19 diagnosis, and vaccine preference; 95% CI: 95% confidence interval; CAS: Coronavirus Anxiety Scale; FCV-19S: Fear of COVID-19 Scale; GAD-2: Generalized Anxiety Disorder; PHQ-2: Patient Health Questionnaire; PRE-COVID-19: Scale to measure worry for contagion of the COVID-19.

Association between vaccination and mental health problems at one month of follow-up

The mean follow-up time for 661 older adults was 31.4 ± 0.14 days. Considering the one-month follow-up period, we observed that older adults with two doses of the COVID-19 vaccine had less fear of COVID-19 (aOR: 0.19; 95% CI: 0.07 to 0.53) and less anxiety about COVID-19 (aOR: 0.45; 95% CI: 0.22 to 0.89), compared to those who were unvaccinated. In addition, those with two doses of the vaccine were significantly less likely to had fear of COVID-19, anxiety about COVID-19, and worry about COVID-19, compared to those who had only one dose. We observed similar results in the outcomes of worry about COVID-19 and general anxiety; however, there is high uncertainty about these estimates ( Table 3).

Table 3. Association between vaccination status and emotional health outcomes for one month follow-up (n = 661).

Outcomes	One dose of vaccine against COVID-19	Two doses of vaccine against COVID-19	
aOR	95% CI	aOR	95% CI	
Fear of COVID-19 (FCV-19S)					
 High fear (twelve points or more)	0.56	(0.22–1.40)	0.19	(0.07–0.53)	
0.35*	(0.21-0.59)*	
Anxiety for COVID-19 (CAS)					
 High anxiety about COVID-19 (one point or more)	0.94	(0.48–1.81)	0.45	(0.22–0.89)	
0.48*	(0.34-0.68)*	
Worry for COVID-19 (PRE-COVID-19)					
 High worry about COVID-19 (twelve points or more)	1.27	(0.52–3.09)	0.74	(0.30–1.86)	
0.58*	(0.37-0.94)*	
General anxiety (GAD-2)					
 General anxiety (two points or more)	0.69	(0.25–1.95)	0.43	(0.14–1.28)	
0.62*	(0.34-1.13)*	
General depression (PHQ-2)					
 General anxiety (three points or more)	2.04	(0.35–11.98)	1.49	(0.26–8.48)	
0.73*	(0.34-1.54)*	
Reference category: Unvaccinated; *Reference category: One dose of vaccine; aOR: Adjusted odds ratio for days since receiving the last vaccine dose, sex, age, living with someone, comorbidity, history of mental health disease, history of COVID-19 diagnosis, vaccine preference, and follow-up time in days; 95% CI: 95% confidence interval; CAS: Coronavirus Anxiety Scale; FCV-19S: Fear of COVID-19 Scale; GAD-2: Generalized Anxiety Disorder; PHQ-2: Patient Health Questionnaire; PRE-COVID-19: Scale to measure worry for contagion of the COVID-19.

Discussion

Summary of results

We hypothesize that vaccination has a causal effect in reducing fear, anxiety, and worry about COVID-19 and, also in general anxiety and depression. Our study, conducted in a cohort from a nationally representative sample of older adults affiliated to EsSalud, partially confirmed our hypothesis. We found evidence that those older adults with two doses of the COVID-19 vaccine, compared with unvaccinated and with only one dose, had less likelihood of high levels of fear and anxiety about COVID-19. However, we were unable to confirm these findings for any outcome in those who had received only one dose compared with unvaccinated. To our knowledge, this is the first study that assesses the effect of vaccination on emotional health in a representative sample of older adults, using novel COVID-19 perception outcomes.

Effect of vaccination against COVID-19 in the emotional health of older adults.

High fear and anxiety about COVID-19 were significantly less likely in those who had two doses of the COVID-19 vaccine than those who were unvaccinated or had only one dose. Interestingly, the scales that measured both constructs (FCV-19S and CAS, respectively) focus mainly on the emotional and physical reaction to thoughts related to COVID-19 and its possible contagion. 54 , 55 However, the PRE-COVID-19 scale, which measured the worry about COVID-19, focused on daily dysfunction caused by thoughts about the possibility of getting COVID-19. 12 This difference is relevant, as it would mean that vaccination could affect older adults by improving their mental well-being and reducing more intense psychosomatic symptoms of stress related to the pandemic (fear/anxiety of COVID-19) 56 ; but without reducing daily thoughts and behaviors associated with the possibility of contagion (COVID-19 concern).

On the other hand, although we observed a slight decrease in general anxiety, the effect of vaccination on general depression and anxiety outcomes, measured with PHQ-2 and GAD-2, respectively, was not significant. However, previous studies conducted in adults from the United States, 24 Turkey, 57 Argentina, 58 and China, 59 and health professionals from Turkey 27 reported that those with at least one dose of the vaccine against COVID-19 have lower scores on the depression scales, measured with the PHQ-4, PHQ-9, and the Beck Depression Inventory, and on anxiety scales, measured with the GAD-7 and the Beck Anxiety Inventory. The mechanisms and causes of depression and anxiety in older adults are related to psychosocial factors of loneliness and loss, and neuroendocrine and vascular disorders. 60 , 61 Previous mentioned studies included adults in general with low representation of older adults, so, according to our results, the effect of vaccination would not be sufficient to significantly reduce these outcomes in emotional health in older adults, since they would respond to other intrinsic and extrinsic factors that were not measured in the present study.

On the other hand, the evaluation of the effect of vaccination against COVID-19 on emotional health could be affected by the perception of the vaccine’s effectiveness or worries about adverse events. 62 Older adults are particularly susceptible to fake news or misinformation, 63 which could influence their perception of vaccination against COVID-19 and diminish its effect on their mental health. This effect should be evaluated in future studies. Similarly, the perception of effectiveness and vaccination intention could also be affected by the type of vaccine manufacturer, with the BNT162b2 vaccine (BioNTech, Pfizer) being the most preferred, and the ChAdOx1-S vaccine (Oxford, AstraZeneca) the least preferred in developed countries. 64 Thus, even though most older adults were vaccinated with the BNT162b2 vaccine (BioNTech, Pfizer), the political scandal in Peru regarding the BBIBP-CorV (Sinopharm) vaccine 33 may have partially affected the effect of vaccination on the emotional health of this population.

Second dose of vaccine against COVID-19

We observed the effect on emotional health from the second dose and not in those who had only one dose of the vaccine. This result is different from previous studies where all those who had at least one dose were included in the vaccinated group, regardless of whether they had both doses or not. 24 , 27 , 57 , 59 In addition, one study from Sweden report lower anxiety and depressive symptoms after a short-time period after first and second dose. 65 Clinical effectiveness studies have shown the need for a second dose of the vaccine to have greater effectiveness in preventing mortality and severe disease from COVID-19 in older adults. 15 , 66 This information was communicated promptly to the population, making most people aware of the need for a second dose, especially those willing to be vaccinated. 67 , 68 This may explain that in the context where the communicational emphasis was placed on the need for the second dose of the COVID-19 vaccine, the effect on emotional health could mainly be observed in those who received two doses of the vaccine. Considering the high proportion of older adults who have had two doses of the vaccine, 69 the effect of vaccination reported in other studies may have been carried by those who had both doses, compared to those who had only one dose of the vaccine against COVID-19.

However, the presence of new variants of concern, such as B.1.1.529, could affect the population’s mental health 70 , 71 due to their greater infectivity and immune escape from vaccination. 72 Given this, the need for a third, 73 or even a fourth, 74 COVID-19 vaccine booster is currently under discussion. So, considering that the perception of the vaccine’s effectiveness correlates with the level of concern about the new variants, 75 it is important to continue monitoring mental health in the most vulnerable populations such as the elderly, and its evolution during future vaccination policies against COVID-19.

Public health relevance

As of January 2022, the two-dose vaccination rate in adults aged 60 years and older in different countries was around 80% ( https://ourworldindata.org/grapher/covid-fully-vaccinated-by-age?country). Among the reasons for older adults to decide to be vaccinated is the fear of developing the disease and the perception of the vaccine’s effectiveness to prevent the disease. 76 , 77 However, the lack of reliable information, the fear of possible adverse effects, and the limited access to receive the vaccines mean that many older adults do not get vaccinated or do not have the opportunity to get vaccinated. 76 In this sense, the communication strategy to promote vaccination against COVID-19 could be complemented with the message of reducing fear and anxiety about being infected with COVID-19. Thus, integrating with other elements necessary to have an adequate vaccination rate, such as the empowerment of the first level of care and the availability and access to vaccines, 78 it could improve citizen confidence in the vaccination process.

Currently, the COVID-19 pandemic has a significant impact on mental health, which will continue in the medium and long term. 79 From the point of view of positive epidemiology, our results propose vaccination against COVID-19 as a positive determinant of mental health in older adults. 29 So, vaccination against COVID-19 could contribute to the partial improvement of the emotional health of older adults. However, we must consider that the mental health of older adults depends on various intrinsic and extrinsic factors that not only respond to the COVID-19 pandemic. 60 , 61

Limitations and strengths

The interpretation of the results of this study must consider the following limitations. First, we were unable to obtain the planned sample size for the primary analysis, for the unvaccinated group. This made the statistical power of our results insufficient to find statistically significant results. Thus, we do not rule out the effect of the vaccine on worry about COVID-19 and general anxiety, which should be evaluated in future studies. Second, the low representativeness of the older adults affiliated with EsSalud registered in the CAM database, the high refusal to participate in the study, and the loss during follow-up could have caused selection bias. Thus, it is likely that older adults in CAMs have greater access to receiving the vaccine and to activities that improve their mental health, so the effect that we measured in the study may be overestimated. Third, the way to determine the vaccination status was by self-report, so the measurement of this variable could have been overestimated due to the social desirability bias. Fourth, even though we did not conduct clinical interviews to evaluate the emotional health in the present study, we used different specific psychometric instruments for the perception of COVID-19 and general anxiety and depression. These tools have robust evidence of psychometric validity in our population of interest, making the constructs that we measured reliable. Fifthly, we used short and general questionnaires to measure anxiety and depressive symptoms (i.e. PHQ-2 and GAD-2), which are not specific to vaccination settings. Therefore, it is possible that significant differences would have been found if instruments specifically designed for these settings had been used. Similarly, it is possible that the use of more comprehensive versions measuring depressive and anxiety symptoms, such as the PHQ-9 and GAD-7, which include emotional and somatic indicators, might have increased the variability of the measures and found significant results. However, we believe that using the PHQ-2 and GAD-2 captures the core symptoms of anxiety and depression. Sixth, it is possible that the change in outcomes such as anxiety or depressive symptoms in older adults was not solely dependent on COVID-19 vaccination. Social determinants of health or other factors may be more influential and not accounted for in our study (i.e., family support, economic status, or quality of life). Therefore, we invite other researchers to design future studies with greater methodological rigour, taking into account the considerations mentioned in our limitations.

Conclusions

Vaccination against COVID-19 with two doses in older adults reduces fear and anxiety about COVID-19, compared to those who were unvaccinated or had only one dose. However, we observed no effect in general anxiety and general depression, nor in those who only had one vaccine dose compared to those who were unvaccinated.

Data availability

Underlying data

Figshare: Underlying data for ‘Effects of vaccination against COVID-19 on the emotional health of older adults’, https://doi.org/10.6084/m9.figshare.20134994. 80

This project contains the following underlying data:

Data file 1: VacMentHe_DataBase.xlsx (The database has been anonymized and it has not distorted the scientific meaning.)

Extended data

Figshare: Extended data for ‘Effects of vaccination against COVID-19 on the emotional health of older adults’, https://doi.org/10.6084/m9.figshare.20135000. 39

This project contains the following extended data: Supplementary material:

• Supplementary methods:

▪ Sample size calculation

▪ Characteristics from the eligible population and selected sample

▪ Sampling weights calculation

▪ Questionnaire (in Spanish)

▪ Questionnaire (in English)

• Supplementary results:

▪ Table S1. Comparison of selected sample, sample in baseline measurement and sample reached in follow-up at one month

Reporting guidelines

Figshare: Strobe checklist for ‘Effects of vaccination against COVID-19 on the emotional health of older adults’, https://doi.org/10.6084/m9.figshare.20135051. 81

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

Author contributions

Christoper A. Alarcon-Ruiz: Conceptualization, methodology, formal analysis, investigation, data curation, writing-original draft, writing-review & editing, visualization, supervision, project administration.

Zoila Romero-Albino: Methodology, investigation, resources, writing-review & editing, data curation, supervision, project administration.

Percy Soto-Becerra: Methodology, formal analysis, investigation, resources, writing-original draft, writing-review & editing, data curation, supervision, project administration.

Jeff Huarcaya-Victoria: Methodology, investigation, resources, writing-review & editing, data curation, supervision, project administration.

Fernando M. Runzer-Colmenares: Methodology, investigation, writing-review & editing.

Elisa Romani-Huacani: Methodology, investigation, writing-review & editing.

David Villarreal-Zegarra: Methodology, investigation, writing-review & editing.

Jorge L. Maguiña: Methodology, investigation, resources, writing-original draft, writing-review & editing, data curation, supervision, project administration, funding acquisition.

Moises Apolaya-Segura: Methodology, investigation, resources, writing-review & editing, data curation, supervision, project administration, funding acquisition.

Sofía Cuba-Fuentes: Methodology, resources, writing-review & editing, supervision, project administration.

Consent

Each participant gave verbal informed consent before being included in the study because the recruitment and the data collection were by phone calls. During the informed consent, the interviewer acknowledged the research aims, the themes to discuss during the interview, the benefits and risks of participation in the study, and how the researchers will manage the collected data during the study. The Institutional Review Board approved this process and the verbal informed consent, which was documented during the phone call.

Acknowledgments

To the workers from the Gerencia de la Persona Adulta Mayor y Prestaciones Sociales, EsSalud for participating in the data collection process.

10.5256/f1000research.146973.r173813
Reviewer response for version 2
Mariani Javier 1Referee https://orcid.org/0000-0002-9372-6817

1 Department of Cardiology, Hospital El Cruce Néstor C. Kirchner, Buenos Aires, Argentina
14 9 2024 Copyright: © 2024 Mariani J
2024
https://creativecommons.org/licenses/by/4.0/ This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Version 2recommendationapprove-with-reservations
The authors addressed appropriately almost all comments. However, the conclusions (both in the abstract and in the main text) remain causal: "Two doses of COVID-19 vaccination in older adults improves their perception of COVID-19 infection consequences" (abstract).

"Vaccination against COVID-19 with two doses in older adults reduces fear and anxiety about COVID-19, compared to those who were unvaccinated or had only one dose" (main text). 

This should be reconsidered since it is not possible to affirm that the perceptions are caused by the vaccine's number of doses. Instead, the study found an association between the number of doses received and the perceptions of fear and anxiety. Also, the second sentence of the conclusion: "However, we observed no effect in general anxiety and general depression, nor in those who only had one vaccine dose compared to those who were unvaccinated", should be reconsidered, since the study did not find an association.

Is the work clearly and accurately presented and does it cite the current literature?

Yes

If applicable, is the statistical analysis and its interpretation appropriate?

Partly

Are all the source data underlying the results available to ensure full reproducibility?

Yes

Is the study design appropriate and is the work technically sound?

Partly

Are the conclusions drawn adequately supported by the results?

No

Are sufficient details of methods and analysis provided to allow replication by others?

Yes

Reviewer Expertise:

Cardiology - COVID.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

10.5256/f1000research.146973.r206873
Reviewer response for version 2
Ahmad Aftab 1Referee https://orcid.org/0000-0002-6445-6432

1 Department of Community Medicine, Teerthanker Mahaveer Medical College and Research Center, Moradabad, India
29 8 2024 Copyright: © 2024 Ahmad A
2024
https://creativecommons.org/licenses/by/4.0/ This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Version 2recommendationapprove
A good research article which has been done in a scientifically sound manner, The authors have written the discussion and conclusion very well, without overarching on the study findings. However, the topic has lost its relevance in the current scenario. Nonetheless, this is an importance piece of research and warrants indexing for academic purposes.

Is the work clearly and accurately presented and does it cite the current literature?

Yes

If applicable, is the statistical analysis and its interpretation appropriate?

Yes

Are all the source data underlying the results available to ensure full reproducibility?

Yes

Is the study design appropriate and is the work technically sound?

Yes

Are the conclusions drawn adequately supported by the results?

Yes

Are sufficient details of methods and analysis provided to allow replication by others?

Yes

Reviewer Expertise:

Mental Health, Epidemiology

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

10.5256/f1000research.135497.r159978
Reviewer response for version 1
Mariani Javier 1Referee https://orcid.org/0000-0002-9372-6817

1 Department of Cardiology, Hospital El Cruce Néstor C. Kirchner, Buenos Aires, Argentina
30 1 2023 Copyright: © 2023 Mariani J
2023
https://creativecommons.org/licenses/by/4.0/ This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Version 1recommendationapprove-with-reservations
The authors report the results of an observational study assessing the association between vaccination status and mental health outcome variables at two-time points.

Overall, the study is very interesting and the addressed theme is relevant. However, the manuscript has several issues that should be reconsidered. The study aimed to evaluate the effects of vaccination on mental health outcomes, and this study design is not the most appropriate to accomplish that objective. The study evaluated the association between mental health measures and vaccination status (indeed participants were already vaccinated -the exposure- when outcomes were measured. This should be recognized and the paper reformulated consequently; that is, there are several causal relationship sentences, for example: “High fear and anxiety about COVID-19 significantly decreased in those who had two doses of the COVID-19 vaccine than those who were unvaccinated” (Discussion, second paragraph), that should be reconsidered.

Table 1 does not have measures of association between groups and the variables in the table. Please, include p values or uncertainty measures that help to understand the distribution of baseline characteristics among study groups.

The analysis of the outcome as a dichotomic variable could affect the power to detect differences. As an example, the medians and IQR for general anxiety and depression are 0 for almost all groups (only the group one-dose has a general anxiety 75 th percentile of 1); the dichotomization at 2 and 3 points, respectively, leaves most participants as 0. Also, the presentation medians and IQR in the results tables, do not represent the analyses, if this analysis strategy will be maintained, the tables should show the number and proportion of participants with the outcome. Other strategies, such as Poisson regression models (or some variant for zero-inflated data) could have some advantages.

There are no p values for association tests reported, please add this information to figure 3 and tables 2 and 3.

The unvaccinated group was small, which could affect the study's power to detect between-group differences.

Please, include comparisons between one-dose and two-doses groups in tables 2 and 3, and in figure 3.

Minor comment Check the spelling.

Is the work clearly and accurately presented and does it cite the current literature?

Yes

If applicable, is the statistical analysis and its interpretation appropriate?

Partly

Are all the source data underlying the results available to ensure full reproducibility?

Yes

Is the study design appropriate and is the work technically sound?

Partly

Are the conclusions drawn adequately supported by the results?

No

Are sufficient details of methods and analysis provided to allow replication by others?

Yes

Reviewer Expertise:

Cardiology - COVID.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Alarcon-Ruiz Christoper A. Universidad Científica del Sur, Peru

12 4 2023 1. “The study aimed to evaluate the effects of vaccination on mental health outcomes, and this study design is not the most appropriate to accomplish that objective. The study evaluated the association between mental health measures and vaccination status (indeed participants were already vaccinated -the exposure- when outcomes were measured. This should be recognized and the paper reformulated consequently; that is, there are several causal relationship sentences, for example: “High fear and anxiety about COVID-19 significantly decreased in those who had two doses of the COVID-19 vaccine than those who were unvaccinated” (Discussion, second paragraph), that should be reconsidered.”

Response: Thanks for the suggestion, we corrected the phrasing of our results, according to the study design.

2. "Table 1 does not have measures of association between groups and the variables in the table. Please, include p values or uncertainty measures that help to understand the distribution of baseline characteristics among study groups.”

Response: We added p values in Table 1 and described them in the results section.

3.“The analysis of the outcome as a dichotomic variable could affect the power to detect differences. As an example, the medians and IQR for general anxiety and depression are 0 for almost all groups (only the group one-dose has a general anxiety 75th percentile of 1); the dichotomization at 2 and 3 points, respectively, leaves most participants as 0. Also, the presentation medians and IQR in the results tables, do not represent the analyses, if this analysis strategy will be maintained, the tables should show the number and proportion of participants with the outcome. Other strategies, such as Poisson regression models (or some variant for zero-inflated data) could have some advantages.”

Response: We agree with the suggestions. We excluded the analysis comparing medians and IQR of the outcomes. We are using a validated cut-off for all our outcomes, considering the interpretation of our results, considering them as clinical relevant outcomes for the participants.

4. “There are no p values for association tests reported, please add this information to figure 3 and tables 2 and 3.”

Response: Thanks for the suggestion. However, we are reporting 95%CI of the estimates. These values are better to understand the statistical significance of our results.

5. “The unvaccinated group was small, which could affect the study's power to detect between-group differences.”

Response: We acknowledge this situation as a limitation in the final paragraph of the Discussion section.

6. “Please, include comparisons between one-dose and two-doses groups in tables 2 and 3, and in figure 3.”

Response: Thanks for the suggestions. We added these analysis in tabls 2 and 3, and included on the discussion of our results. The figure 3 already included this comparison.

10.5256/f1000research.135497.r146036
Reviewer response for version 1
Rosas-Carrasco Oscar 1Referee https://orcid.org/0000-0002-0564-5882

1 Evaluation and intervention Center of Older People, Multi-component exercise Unit, Health department, Ibero-American University, Mexico City, Mexico
30 8 2022 Copyright: © 2022 Rosas-Carrasco O
2022
https://creativecommons.org/licenses/by/4.0/ This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Version 1recommendationapprove-with-reservations
The ideal study to demonstrate the effectiveness of vaccination in mental health are intervention studies. However, this follow-up study may provide sufficient evidence to demonstrate the association between improved mental health status in the group that received two vaccines versus those that received no or one dose. Therefore, the knowledge provided by this study is relevant and should be reported.

In the introduction, the percentages of vaccination with three vaccines are described, in its majority it is commented that they were vaccinated with Pfizer, that the Ministry of Health gave preference to this vaccine for older adults, however, in the methods it is not specified if it was a exclusion criterion having been vaccinated with other types of vaccines. In this case, if they had been selected add this variable as it is confusing. On the other hand, the adverse effects of vaccines occur frequently, if they occur they could have an effect contrary to the reduction of fear, anxiety, etc. due to COVID-19. Could the effects or adverse reactions be quantified? If so, include them as another confounding variable in the methodology.

It is necessary to deepen in the section because no significant differences were found in terms of depression and anxiety. Perhaps a paragraph should be included on the fact that using general questionnaires for anxiety and depression decreases their sensitivity for the detection of very specific changes such as that of vaccination? Had questionnaires developed (for this work) been used for this specific purpose, a significant change could have been found.

Another line that can be included in the discussion is that the presentation of depression and anxiety and its change does not only depend on the vaccination against COVID-19, it depends on many factors that can exert a greater weight than the vaccination itself and that for this reason an impact could not be obtained, future studies with greater strength in the operational definition of the variables or with an intervention design could help to clarify these two aspects of mental health.

The part in the argument that three or four doses could further improve mental health status is well supported.

Is the work clearly and accurately presented and does it cite the current literature?

Yes

If applicable, is the statistical analysis and its interpretation appropriate?

Yes

Are all the source data underlying the results available to ensure full reproducibility?

Yes

Is the study design appropriate and is the work technically sound?

Partly

Are the conclusions drawn adequately supported by the results?

Yes

Are sufficient details of methods and analysis provided to allow replication by others?

Yes

Reviewer Expertise:

Internal Medicine, Geriatric Medicine, clinical research

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Alarcon-Ruiz Christoper A. Universidad Científica del Sur, Peru

12 4 2023 1. “The ideal study to demonstrate the effectiveness of vaccination in mental health are intervention studies. However, this follow-up study may provide sufficient evidence to demonstrate the association between improved mental health status in the group that received two vaccines versus those that received no or one dose. Therefore, the knowledge provided by this study is relevant and should be reported.”

Response: Thanks.

2. “In the introduction, the percentages of vaccination with three vaccines are described, in its majority it is commented that they were vaccinated with Pfizer, that the Ministry of Health gave preference to this vaccine for older adults, however, in the methods it is not specified if it was a exclusion criterion having been vaccinated with other types of vaccines. In this case, if they had been selected add this variable as it is confusing. On the other hand, the adverse effects of vaccines occur frequently, if they occur they could have an effect contrary to the reduction of fear, anxiety, etc. due to COVID-19. Could the effects or adverse reactions be quantified? If so, include them as another confounding variable in the methodology.”

Response: We included all participants independently of vaccine preference or the type of received vaccine (We are adding this information in the methods section). In addition, we had the variable vaccine preference in the database, and it was included in the multivariable analysis. However, we didnt collect information about the adverse effects of the vaccines, but we are acknowledging that as a limitation.

3. “It is necessary to deepen in the section because no significant differences were found in terms of depression and anxiety. Perhaps a paragraph should be included on the fact that using general questionnaires for anxiety and depression decreases their sensitivity for the detection of very specific changes such as that of vaccination? Had questionnaires developed (for this work) been used for this specific purpose, a significant change could have been found.”

Response: We agree with the reviewer and add the following text to the limitations section:

“Fifthly, we used short and general questionnaires to measure anxiety and depressive symptoms (i.e. PHQ-2 and GAD-2), which are not specific to vaccination settings. Therefore, it is possible that significant differences would have been found if instruments specifically designed for these settings had been used. Similarly, it is possible that the use of more comprehensive versions measuring depressive and anxiety symptoms, such as the PHQ-9 and GAD-7, which include emotional and somatic indicators, might have increased the variability of the measures and found significant results. However, we believe that using the PHQ-2 and GAD-2 captures the core symptoms of anxiety and depression.”

4. “Another line that can be included in the discussion is that the presentation of depression and anxiety and its change does not only depend on the vaccination against COVID-19, it depends on many factors that can exert a greater weight than the vaccination itself and that for this reason an impact could not be obtained, future studies with greater strength in the operational definition of the variables or with an intervention design could help to clarify these two aspects of mental health.”

Response: We have included this information in the limitations section, as we believe it is an issue not covered in our study:

“Sixth, it is possible that the change in outcomes such as anxiety or depressive symptoms in older adults was not solely dependent on COVID-19 vaccination. Social determinants of health or other factors may be more influential and not accounted for in our study (i.e., family support, economic status, or quality of life). Therefore, invite other researchers to design future studies with greater methodological rigour, taking into account the considerations mentioned in our limitations.”

Competing interests: No competing interests were disclosed.

Competing interests: No competing interests were disclosed.

Competing interests: No competing interests were disclosed.

Competing interests: No competing interests were disclosed.

Competing interests: No competing interests were disclosed.

Competing interests: None
==== Refs
References

1 Santomauro DF Herrera AMM Shadid J : Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet. 2021 Nov 6;398 (10312 ):1700–1712. 10.1016/S0140-6736(21)02143-7 34634250
2 García-Fernández L Romero-Ferreiro V López-Roldán PD : Mental Health in Elderly Spanish People in Times of COVID-19 Outbreak. Am. J. Geriatr. Psychiatry. 2020 Oct 1;28 (10 ):1040–1045. 10.1016/j.jagp.2020.06.027 32718855
3 Turna J Zhang J Lamberti N : Anxiety, depression and stress during the COVID-19 pandemic: Results from a cross-sectional survey. J. Psychiatr. Res. 2021 May 1;137 :96–103. 10.1016/j.jpsychires.2021.02.059 33667763
4 Tiruneh SA Tesema ZT Azanaw MM : The effect of age on the incidence of COVID-19 complications: a systematic review and meta-analysis. Syst. Rev. 2021 Mar 20;10 (1 ):80. 10.1186/s13643-021-01636-2 33743821
5 Biswas M Rahaman S Biswas TK : Association of Sex, Age, and Comorbidities with Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis. Intervirology. 2021;64 (1 ):36–47. 10.1159/000512592 33296901
6 De Pue S Gillebert C Dierckx E : The impact of the COVID-19 pandemic on wellbeing and cognitive functioning of older adults. Sci. Rep. 2021 Feb 25;11 (1 ):4636. 10.1038/s41598-021-84127-7 33633303
7 Babulal GM Torres VL Acosta D : The impact of COVID-19 on the well-being and cognition of older adults living in the United States and Latin America. EClinicalMedicine. 2021;35 :100848. 10.1016/j.eclinm.2021.100848 33997742
8 Bonilla-Cruz NJ Cudris-Torres L Mendoza-Rincon BM : Health Strategies in Latin America for the Elderly in relation to COVID-19. Gac. Med. Caracas. 2020;128 (Supl 2 ):S301–S311. 10.47307/GMC.2020.128.s2.17
9 Taylor L : Covid-19: Why Peru suffers from one of the highest excess death rates in the world. BMJ. 2021 Mar 9;372 :n611. 10.1136/bmj.n611 33687923
10 Varona L Gonzales JR : Dynamics of the impact of COVID-19 on the economic activity of Peru. PLoS One. 2021 Jan 8;16 (1 ):e0244920. 10.1371/journal.pone.0244920 33417613
11 Mejia CR Rodriguez-Alarcon JF Garay-Rios L : Perception of exaggeration or fear propagated by the media among the Peruvian population during the COVID-19 pandemic. Rev Cuba Investig Bioméd. 2020 Jun;39 (2 ):e698E.
12 Caycho-Rodríguez T Ventura-León J Barboza-Palomino M : Design and validation of a scale to measure worry for contagion of the COVID-19 (PRE-COVID-19). Enferm. Clin. 2021 Jun;31 (3 ):175–183. 10.1016/j.enfcle.2020.10.012 38620588
13 Porter C Favara M Hittmeyer A : Impact of the COVID-19 pandemic on anxiety and depression symptoms of young people in the global south: evidence from a four-country cohort study. BMJ Open. 2021 Apr 15;11 (4 ):e049653. 10.1136/bmjopen-2021-049653
14 Carbone M Lednicky J Xiao SY : Coronavirus 2019 Infectious Disease Epidemic: Where We Are, What Can Be Done and Hope For. J. Thorac. Oncol. Off. Publ. Int. Assoc. Study Lung Cancer. 2021 Apr;16 (4 ):546–571. 10.1016/j.jtho.2020.12.014
15 Bernal JL Andrews N Gower C : Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study. BMJ. 2021 May 13;373 :n1088.33985964
16 Ranzani OT Hitchings MDT Dorion M : Effectiveness of the CoronaVac vaccine in older adults during a gamma variant associated epidemic of covid-19 in Brazil: test negative case-control study. BMJ. 2021 Aug 20;374 :n2015. 10.1136/bmj.n2015 34417194
17 Madison AA Shrout MR Renna ME : Psychological and Behavioral Predictors of Vaccine Efficacy: Considerations for COVID-19. Perspect. Psychol. Sci. 2021 Mar 1;16 (2 ):191–203. 10.1177/1745691621989243 33501900
18 Lawrence T Zubatsky M Meyer D : The association between mental health diagnoses and influenza vaccine receipt among older primary care patients. Psychol. Health Med. 2020 Oct;25 (9 ):1083–1093. 10.1080/13548506.2020.1717557 31958989
19 Marrie RA Walld R Bolton JM : Uptake of influenza vaccination among persons with inflammatory bowel disease, multiple sclerosis or rheumatoid arthritis: a population-based matched cohort study. CMAJ Open. 2021 Apr;9 (2 ):E510–E521. 10.9778/cmajo.20200105 33990365
20 Andrew MK McNeil S Merry H : Rates of influenza vaccination in older adults and factors associated with vaccine use: a secondary analysis of the Canadian Study of Health and Aging. BMC Public Health. 2004 Aug 11;4 :36. 10.1186/1471-2458-4-36 15306030
21 Bazargan M Wisseh C Adinkrah E : Influenza Vaccination among Underserved African-American Older Adults. Biomed. Res. Int. 2020 Nov 10;2020 :1–9. 10.1155/2020/2160894
22 Palgi Y Bergman YS Ben-David B : No psychological vaccination: Vaccine hesitancy is associated with negative psychiatric outcomes among Israelis who received COVID-19 vaccination. J. Affect. Disord. 2021 May 15;287 :352–353. 10.1016/j.jad.2021.03.064 33819733
23 Hause AM Gee J Johnson T : Anxiety-Related Adverse Event Clusters After Janssen COVID-19 Vaccination - Five U.S. Mass Vaccination Sites, April 2021. MMWR Morb. Mortal. Wkly Rep. 2021 May 7;70 (18 ):685–688. 10.15585/mmwr.mm7018e3 33956781
24 Perez-Arce F Angrisani M Bennett D : COVID-19 vaccines and mental distress. PLoS One. 2021 Sep 8;16 (9 ):e0256406. 10.1371/journal.pone.0256406 34496006
25 Chen S Aruldass AR Cardinal RN : Mental health outcomes after SARS-CoV-2 vaccination in the United States: A national cross-sectional study. J. Affect. Disord. 2022 Feb 1;298 :396–399. 10.1016/j.jad.2021.10.134 34774648
26 Nguyen M : The Psychological Benefits of COVID-19 Vaccination. Adv Public Health. 2021 Nov 3;2021 :1–9. 10.1155/2021/1718800
27 Sugihara G Hirai N Takei N : COVID-19 vaccination and mental health in hospital workers. Brain Behav. 2021;11 (11 ):e2382. 10.1002/brb3.2382 34661977
28 Brenner H : Focusing COVID-19 vaccinations on elderly and high-risk people. Lancet Reg Health – Eur. 2021 Mar 1;2 :100044. 10.1016/j.lanepe.2021.100044 34173633
29 VanderWeele TJ Chen Y Long K : Positive Epidemiology? Epidemiology. 2020 Mar;31 (2 ):189–193. 10.1097/EDE.0000000000001147 31809344
30 Alcalde-Rabanal JE Lazo-González O Nigenda G : Health system in Peru. Salud Pública México. 2011 Jan;53 :s243–s254.
31 Tenorio-Mucha J Romero-Albino Z Vidal V : Quality of life of older adults in Peruvian Social Security during the COVID-19 pandemic. Rev Cuerpo Méd HNAAA. 2021 Nov 13;14 (Sup1 ):41–48. 10.35434/rcmhnaaa.2021.14Sup1.1165
32 Romero-Albino Z Ortigueria-Sánchez L : Social prescription and trust in older adults: a view in COVID-19 context. Rev Cuerpo Méd HNAAA. 2021 Nov 13;14 (Sup1 ):62–69. 10.35434/rcmhnaaa.2021.14Sup1.1176
33 Mayta-Tristán P Aparco JP : Use of experimental vaccine outside of clinical trial: the “Vacunagate” case. Rev Peru Med Exp Salud Pública. 2021 Aug 30;38 :203–205. 10.17843/rpmesp.2021.382.8694 34468565
34 Chauvin L : Peruvian COVID-19 vaccine scandal spreads. Lancet. 2021 Feb 27;397 (10276 ):783. 10.1016/S0140-6736(21)00508-0 33640052
35 Arango Olarte R Chanca Flores A Caso Álvarez JG : Social dimension of pain and VIP vaccines in Peru. Rev Científica Arbitr Fund MenteClara. 2021 Apr 30;6 (222 ):1–26. 10.32351/rca.v6.222
36 Cohen J : Statistical Power Analysis for the Behavioral Sciences. 2nd ed. New York: Routledge;2013.
37 Lakens D : Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front. Psychol. 2013 Nov 26;4 :863. 10.3389/fpsyg.2013.00863 24324449
38 Vittinghoff E Glidden DV Shiboski SC : Linear Regression. Vittinghoff E Glidden DV Shiboski SC , editors. Regression Methods in Biostatistics: Linear, Logistic, Survival, and Repeated Measures Models. Boston, MA: Springer US;2012; p.69–138.
39 Supplementary material and results. Figshare. figshare. 2022 [cited 2022 Jul 4]. 10.6084/m9.figshare.20135000
40 Valliant R Dever JA Kreuter F : Practical Tools for Designing and Weighting Survey Samples. 2nd ed. New York, US: Springer Publishing;2018.
41 Valliant R Dever JA : Survey Weights: A Step-by-Step Guide to Calculation. Texas, US: Stata Press;2018.
42 Huarcaya-Victoria J Villarreal-Zegarra D Podestà A : Psychometric Properties of a Spanish Version of the Fear of COVID-19 Scale in General Population of Lima, Peru. Int. J. Ment. Health Addict. 2020 Jun 22;20 :249–262. 10.1007/s11469-020-00354-5 32837434
43 Caycho-Rodríguez T Tomás JM Barboza-Palomino M : Assessment of Fear of COVID-19 in Older Adults: Validation of the Fear of COVID-19 Scale. Int. J. Ment. Health Addict. 2021 Jan 6;20 :1231–1245. 10.1007/s11469-020-00438-2 33432265
44 Silva WAD Sampaio Brito TR de Pereira CR : COVID-19 anxiety scale (CAS): Development and psychometric properties. Curr. Psychol. 2020 Nov 13:1–10.
45 Caycho-Rodríguez T Barboza-Palomino M Ventura-León J : Spanish translation and validation of a brief measure of anxiety by the COVID-19 in students of health sciences. Ansiedad Estrés. 2020 Jul 1;26 (2 ):174–180. 10.1016/j.anyes.2020.08.001
46 Caycho-Rodríguez T Vilca LW Carbajal-León C : Coronavirus Anxiety Scale: New psychometric evidence for the Spanish version based on CFA and IRT models in a Peruvian sample. Death Stud. 2021 Jan 10:1–11. 10.1080/07481187.2021.1900453 33764854
47 Caycho-Rodríguez T Vilca LW Peña-Calero BN : Measurement of coronaphobia in older adults: Validation of the Spanish version of the Coronavirus Anxiety Scale. Rev. Esp. Geriatr. Gerontol. 2021 Nov 12. S0211-139X(21)00177-3.
48 García-Campayo J Zamorano E Ruiz MA : The assessment of generalized anxiety disorder: psychometric validation of the Spanish version of the self-administered GAD-2 scale in daily medical practice. Health Qual. Life Outcomes. 2012 Sep 19;10 :114. 10.1186/1477-7525-10-114 22992432
49 Wild B Eckl A Herzog W : Assessing Generalized Anxiety Disorder in Elderly People Using the GAD-7 and GAD-2 Scales: Results of a Validation Study. Am. J. Geriatr. Psychiatry. 2014 Oct;22 (10 ):1029–1038. 10.1016/j.jagp.2013.01.076 23768681
50 Caneo C Toro P Ferreccio C : Validity and Performance of the Patient Health Questionnaire (PHQ-2) for Screening of Depression in a Rural Chilean Cohort. Community Ment. Health J. 2020 Oct 1;56 (7 ):1284–1291. 10.1007/s10597-020-00605-8 32193853
51 Boyle LL Richardson TM He H : How do the phq-2, the phq-9 perform in aging services clients with cognitive impairment? Int. J. Geriatr. Psychiatry. 2011 Sep;26 (9 ):952–960. 10.1002/gps.2632 21845598
52 Rozzini R Frisoni GB Ferrucci L : Geriatric Index of Comorbidity: validation and comparison with other measures of comorbidity. Age Ageing. 2002 Jul;31 (4 ):277–285. 10.1093/ageing/31.4.277 12147566
53 Dean N Pagano M : Evaluating Confidence Interval Methods for Binomial Proportions in Clustered Surveys. J. Surv. Stat. Methodol. 2015 Dec;3 (4 ):484–503. 10.1093/jssam/smv024
54 Mertens G Duijndam S Smeets T : The latent and item structure of COVID-19 fear: A comparison of four COVID-19 fear questionnaires using SEM and network analyses. J. Anxiety Disord. 2021 Jun;81 :102415.33962142
55 Lee SA : Coronavirus Anxiety Scale: A brief mental health screener for COVID-19 related anxiety. Death Stud. 2020 Jul 2;44 (7 ):393–401. 10.1080/07481187.2020.1748481 32299304
56 Chandu VC Marella Y Panga GS : Measuring the Impact of COVID-19 on Mental Health: A Scoping Review of the Existing Scales: Indian. J. Psychol. Med. 2020 Aug 18;42 (5 ):421–427.
57 Bilge Y Keles E Baydili KN : The Impact of COVID-19 Vaccination on Mental Health. J. Loss Trauma. 2021 Aug 18;27 :285–288. 10.1080/15325024.2021.1963558
58 Benedetti P Barbuzza A Moscato F : Second Wave of COVID-19 Pandemic in Argentinian Population: Vaccination Is Associated With a Decrease in Depressive Symptoms. Front. Psychiatry. 2022 Jun 23;13 :832352. 10.3389/fpsyt.2022.832352 35815024
59 Yuan Y Deng Z Chen M : Changes in Mental Health and Preventive Behaviors before and after COVID-19 Vaccination: A Propensity Score Matching (PSM) Study. Vaccines. 2021 Sep;9 (9 ):1044. 10.3390/vaccines9091044 34579281
60 Alexopoulos GS : Mechanisms and treatment of late-life depression. Transl. Psychiatry. 2019 Dec;9 (1 ):188. 10.1038/s41398-019-0514-6 31383842
61 Hellwig S Domschke K : Anxiety in Late Life: An Update on Pathomechanisms. Gerontology. 2019;65 :465–473. 10.1159/000500306 31212285
62 Chen L Liang H Liu L : The association between adverse events of COVID-19 vaccination and anxiety and willingness to receive a booster dose. Hum. Vaccin. Immunother. 2023 Dec 31;19 (1 ):2176643. 10.1080/21645515.2023.2176643 36798968
63 Moore RC Hancock JT : Older Adults, Social Technologies, and the Coronavirus Pandemic: Challenges, Strengths, and Strategies for Support. Soc Media Soc. 2020 Jul 1;6 (3 ):2056305120948162.
64 Merkley E Loewen PJ : The correlates and intensity of COVID-19 vaccine brand preferences in Canada [Preprint]. OSF Preprints. 2021 [cited 2022 Jan 6]. Reference Source
65 Chourpiliadis C Lovik A Kähler AK : Short-term improvement of mental health after a COVID-19 vaccination. PLoS One. 2023 Feb 15;18 (2 ):e0280587. 10.1371/journal.pone.0280587 36791070
66 Kissling E Hooiveld M Martín VS : Vaccine effectiveness against symptomatic SARS-CoV-2 infection in adults aged 65 years and older in primary care: I-MOVE-COVID-19 project, Europe, December 2020 to May 2021. Eurosurveillance. 2021 Jul 22;26 (29 ):2100670. 10.2807/1560-7917.ES.2021.26.29.2100670 34296676
67 Goldfarb JL Kreps S Brownstein JS : Beyond the First Dose — Covid-19 Vaccine Follow-through and Continued Protective Measures. N. Engl. J. Med. 2021 Jul 8;385 (2 ):101–103. 10.1056/NEJMp2104527 33909962
68 Stead M Jessop C Angus K : National survey of attitudes towards and intentions to vaccinate against COVID-19: implications for communications. BMJ Open. 2021 Oct 1;11 (10 ):e055085. 10.1136/bmjopen-2021-055085 34711602
69 Kriss JL Reynolds LE Wang A : COVID-19 Vaccine Second-Dose Completion and Interval Between First and Second Doses Among Vaccinated Persons — United States, December 14, 2020−February 14, 2021. Morb. Mortal. Wkly. Rep. 2021 Mar 19;70 (11 ):389–395. 10.15585/mmwr.mm7011e2 33735162
70 Su Z McDonnell D Ahmad J : Mind the “worry fatigue” amid Omicron scares. Brain Behav. Immun. 2022 Mar 1;101 :60–61. 10.1016/j.bbi.2021.12.023 34973394
71 Jain A Jolly TS : Omicron (B.1.1.529) COVID-19 Variant: A Mental Health Perspective on Lessons Learned and Future Challenges. Prim Care Companion CNS Disord. 2021 Dec 16;23 (6 ):38797. 10.4088/PCC.21com03206
72 Ren SY Wang WB Gao RD : Omicron variant (B.1.1.529) of SARS-CoV-2: Mutation, infectivity, transmission, and vaccine resistance. World J. Clin. Cases. 2022 Jan 7;10 (1 ):1–11. 10.12998/wjcc.v10.i1.1 35071500
73 Eroglu B Nuwarda RF Ramzan I : A Narrative Review of COVID-19 Vaccines. Vaccines. 2022 Jan;10 (1 ):62. 10.3390/vaccines10010062
74 Tylicki L Dębska-Ślizień A Muchlado M : Boosting Humoral Immunity from mRNA COVID-19 Vaccines in Kidney Transplant Recipients. Vaccines. 2022 Jan;10 (1 ):56.
75 Temsah MH Aljamaan F Alenezi S : SARS-CoV-2 Omicron variant: healthcare workers’ perceptions and beliefs of vaccine effectiveness and advocacy: a national survey during the first week of the World Health Organization variant alert [PrePrint]. medRxiv. 2021 Dec [cited 2022 Jan 6]; p.2021.12.27.21268431. 10.1101/2021.12.27.21268431v1
76 Bhanu C Gopal DP Walters K : Vaccination uptake amongst older adults from minority ethnic backgrounds: A systematic review. PLoS Med. 2021 Nov 4;18 (11 ):e1003826. 10.1371/journal.pmed.1003826 34735440
77 Caycho-Rodríguez T Carbajal-León C Vivanco-Vidal A : Intention to vaccinate against COVID-19 in Peruvian older adults. Rev. Esp. Geriatr. Gerontol. 2021;56 (4 ):245–246. 10.1016/j.regg.2021.03.005 34116798
78 Castillo C Villalobos Dintrans P Maddaleno M : The successful COVID-19 vaccine rollout in Chile: Factors and challenges. Vaccine X. 2021 Sep 8;9 :100114. 10.1016/j.jvacx.2021.100114 34518818
79 Esterwood E Saeed SA : Past Epidemics, Natural Disasters, COVID19, and Mental Health: Learning from History as we Deal with the Present and Prepare for the Future. Psychiatr. Q. 2020 Dec 1;91 (4 ):1121–1133. 10.1007/s11126-020-09808-4 32803472
80 Database: Figshare. 2022 [cited 2022 Jul 4]. 10.6084/m9.figshare.20134994
81 STROBE CheckList: Figshare. figshare. 2022 [cited 2022 Jul 4]. 10.6084/m9.figshare.20135051
