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. 2021 Sep 8;16(9):e0256406. doi: 10.1371/journal.pone.0256406

COVID-19 vaccines and mental distress

Francisco Perez-Arce 1,*, Marco Angrisani 2, Daniel Bennett 2, Jill Darling 2, Arie Kapteyn 2, Kyla Thomas 2
Editor: Chung-Ying Lin3
PMCID: PMC8425550  PMID: 34496006

Abstract

Background

The COVID-19 pandemic brought about large increases in mental distress. The uptake of COVID-19 vaccines is expected to significantly reduce health risks, improve economic and social outcomes, with potential benefits to mental health.

Purpose

To examine short-term changes in mental distress following the receipt of the first dose of the COVID-19 vaccine.

Methods

Participants included 8,003 adults from the address-based sampled, nationally representative Understanding America Study (UAS), surveyed at regular intervals between March 10, 2020, and March 31, 2021 who completed at least two waves of the survey. Respondents answered questions about COVID-19 vaccine status and self-reported mental distress as measured with the four-item Patient Health Questionnaire (PHQ-4). Fixed-effects regression models were used to identify the change in PHQ-4 scores and categorical indicators of mental distress resulting from the application of the first dose of the COVID-19 vaccine.

Results

People who were vaccinated between December 2020 and March 2021 reported decreased mental distress levels in the surveys conducted after receiving the first dose. The fixed-effects estimates show an average effect of receiving the vaccine equivalent to 4% of the standard deviation of PHQ-4 scores (p-value<0.01), a reduction in 1 percentage point (4% reduction from the baseline level) in the probability of being at least mildly depressed, and of 0.7 percentage points (15% reduction from the baseline level) in the probability of being severely depressed (p-value = 0.06).

Conclusions

Getting the first dose of COVID-19 resulted in significant improvements in mental health, beyond improvements already achieved since mental distress peaked in the spring of 2020.

Introduction

The COVID-19 pandemic has affected several aspects of people’s lives, including their employment and finances, health risks and opportunities to socialize, all of which can affect mental health. COVID-19 patients suffered psychological consequences [1] but mental distress issues arose in the general population as well. Several studies document elevated levels of psychological distress, including anxiety and suicidal thoughts, in many countries around the world [2]. In the US, mental health distress rose sharply early in the pandemic and then recovered partially. Mental health distress rose to a peak in April, but improved since then and by August had returned to a level comparable to that of early March [3].

Several factors contributed to the rise in mental health problems in the pandemic. Some studies have suggested that economic concerns were the most strongly associated with worsening mental health, while concerns about their own health and social distance were also correlated though less strongly [4]. The improvement in economic conditions and the release of public economic support in the form of unemployment insurance and stimulus checks may have been a factor in the recovery of mental health since April 2020. Studies show that sleep problems were common during the COVID-19 crisis and this was associated with depression among the general population [5].

A growing literature studies the determinants of vaccine hesitancy and willingness to get vaccinated [68]. Factors in the willingness to get vaccinated include age [9], sources of information [10], fear of COVID-19 [11] and perceived severity of COVID-19 [12]. In earlier studies, fear of COVID-19 was associated with increased increased future career anxiety and decreased job satisfaction [13]. A study by Kejriwal and Shen [14] found a positive correlation between willingness to get vaccined hesitancy and negative affect (in particular, those reporting more worry and anxiety reported more willingness to vaccinate). To the extent that those who were more anxious about COVID-19 get vaccinated, the vaccine rollout may have improved mental health by reducing that anxiety. Vaccine uptake may improve quality of life and economic outlook, enabling people to resume previous activities, become more socially active, return to working in person, or become employed.

In this paper, we focus on the direct and short-term effects of being vaccinated on mental health in the first few months of the rollout, by estimating fixed-effects models that allow us to compare change over time in the mental health of those who received a vaccine compared to those who did not receive a vaccine. We note that there could be indirect effects too, which we do not study here. Indirect effects would arise, for instance, through the reduction in risk for those who are not vaccinated but stand to benefit from increased herd immunity.

Studying how mental health evolves as the country recovers from the pandemic can shed light on the relationship between mental health and pandemic-related stressors.

Methods

The Understanding America Study (UAS) is a nationally representative longitudinal study of adult Americans 18 and over. Respondents are recruited through address-based sampling from the U.S. Postal Service Delivery Sequence files. Respondents without internet access are provided with a tablet, internet access and training on how to use the tablets if necessary. UAS respondents are paid $20 per 30 minutes of survey time [15].

UAS panelists were invited to participate in a bi-weekly tracking survey to understand the impacts of the pandemic, which we named the Understanding Coronavirus in America Study (UCAS) [16]. The University of Southern California Institutional Review Board reviewed and approved the study (UP-14-00148-AM088). Respondents provided written informed consent. All participants were 18 years of age or older. On March 10, 2020, panelists were invited to answer the first survey (which remained open until the end of March). Between April 1 2020 and February 16 2021, UCAS participants were invited to answer surveys every fourteen days. This frequency was chosen to allow tracking how people’s perceptions, behaviors and outcomes evolved throughout the pandemic. After February 16, the bi-weekly cycle was replaced by a four-week cycle, so that since then respondents answer questions every four weeks. Participants were randomly assigned a number between one and fourteen, which determined the day on which they were asked to answer the survey. Upon invitation, the respondent had two weeks to complete the survey. Variables measured every wave include PHQ-4 scores and COVID-19 vaccination status (the latter since December 23, 2020).

Data from every UCAS wave are made available to the research community on the day after the field period closes (https://uasdata.usc.edu/covid19). Questionnaires are available at https://uasdata.usc.edu/page/Covid-19+Documentation. The 25th wave of the survey closed on March 30, 2021. We use all data from surveys completed by March 31st of 2021, which includes partial data from the 26th wave. Overall, our dataset spans the period from March 10, 2020 to March 31st, 2021 [17].

From the 8,955 UAS panelists who were invited to participate in UCAS, 97.1% agreed to participate in UCAS, and 94% answered at least one survey. Across all waves, the response rate was 82% on average. The sample we use consists of answers from 8,027 adults who completed at least two waves of the survey. Altogether, our data comprise 157,227 respondent-wave observations.

Measures

Mental distress

We measure mental distress with the four-item Patient Health Questionnaire (PHQ-4) [18]. Two items measure depressive symptoms and two items measure anxiety symptoms. Responses to each item are scored from 0 to 4 and summed to create an index ranging between 0 and 16 with higher numbers indicating higher levels of mental distress.

We use the PHQ-4 score as an outcome variable, as well as three indicator variables based on the thresholds used in [18]: mild mental distress or higher, which takes the value of one if PHQ-4 is equal to or higher than three; moderate mental distress or higher, which equals one if PHQ4 if equal to or higher than six; and severe mental distress which equals one if PHQ-4 is equal to or higher than 9. The validity and reliability of the PHQ-4 is supported by earlier studies [19].

Vaccination

Starting on December 23, 2020, the UCAS surveys asked panelists whether they had received their first shot of a COVID-19 vaccine. From that question, we constructed the indicator ever vaccinated, which equals “0,” or “never vaccinated,” for respondents who were never vaccinated during the study period and “1,” or “ever vaccinated,” for respondents who received a first dose at any point during the study period. We use this indicator first in our analysis to graph the mental health trajectory of respondents who were vaccinated at some point during the study period and compare it to the trajectory of respondents who were never vaccinated.

For our fixed-effects regression analyses, we constructed the point-in-time indicator has vaccine, which, at any given point in time, equals “0,” or “not vaccinated,” for any individual who has not received the first dose of the vaccine and “1,” or “vaccinated,” once an individual indicates that they have received the first dose. For respondents who were not vaccinated by March 2021, has vaccine equals “0” at all time points.

Auxiliary variables

We use demographic indicators for race and ethnicity, educational attainment and gender to study heterogeneity of effects.

Statistical analysis

Trajectories of mental distress over time: Ever vs. never vaccinated

We begin by comparing mental distress trajectory of respondents who received the vaccine at some point during the study period (ever vaccinated = 1) with mental distress trajectory of respondents who never received the vaccine during the study period (ever vaccinated = 0). For each group, we estimate mental distress trajectories using average PHQ-4 scores. We estimate these trajectories using a local polynomial approximation of the date, measured as days passed since the first date in the panel (March 10, 2020) using the lpoly function in STATA.

Fixed-effects regression analysis of effect of vaccination on mental distress

We estimated regression models as in Eq 1 below, where Yit is the outcome variable of interest (mental distress) for individual i in survey wave t, αi is an individual fixed effect (to capture differences across subjects, which may correlate with vaccination status), τt are survey wave fixed effects (to capture differences across time which are common among those vaccinated and not), and Vaccit is the indicator of whether the individual has been vaccinated by survey wave t (has vaccine). β is the coefficient of interest, and represents the association of has vaccine with mental distress after accounting for idiosyncratic differences of those who got vaccinated as well as for common time effects.

Yit=αi+τt+βVaccit+εit (1)

In further specifications, Yit is an indicator for the three thresholds for mental distress: mild mental distress or higher, moderate mental distress or higher, and severe mental distress. In all cases, we cluster standard errors at the individual level.

To analyze heterogeneity in the impact of vaccination on different groups, we estimated equations like (1) above but separately for different groups (men and women, college educated and not-college educated, White and non-White). Let βA denote the coefficient for has vaccine for group A (for instance, women) and βB for group B (for instance, men). For pairs of groups A and B, we performed Wald tests to determine whether the hypotheses βA = βB can be rejected.

Inference

Statistical significance was assessed at the p < .05 level. Analyses were conducted using Stata version 14 (StataCorp Inc., College Station, TX). Data was analyzed in April of 2021.

Results

Descriptive statistics

As shown in Table 1, the ever vaccinated and never vaccinated groups differ significantly in their demographic composition as well as in baseline levels of mental health. The differences are likely a result both from the vaccine eligibility rules applicable during the period that we study as well as different levels of vaccine enthusiasm or hesitancy across demographic groups. Notable differences include: mean age (60.4 years among the vaccinated, 47.1 among the not vaccinated, p-value of the difference<0.01), education level (68% college educated in the vaccinated and 52% in the not vaccinated groups, p-value<0.01), race and ethnicity (87% White among the vaccinated, 6% Black, 11% Hispanic among the vaccinated, 82% White, 11% Black and 18% Hispanic among the non-vaccinated, in all cases p-value of differences <0.01). While we do not have data on the occupation of respondents, it is likely that the ever vaccinated group contains a larger percentage of health care and other essential workers who were prioritized in the vaccination rollout.

Table 1. Backround characteristics.

(1) Never Vaccinated (2) Ever Vaccinated (1) vs. (2), p-value
Average Age 47.12 60.37 <0.001
(0.21) (0.42)
Percentage Male 40.4% 44.3% 0.008
(0.7) (1.30
Percentage with college degree 51.9% 68.4% <0.001
(0.7) (1.2)
Perecentage White 81.6% 87.2% <0.001
(0.5) (0.9)
Percentage Black 10.9% 5.9% <0.001
(0.4) (0.6)
Percentage Spanish/Hispanic/Latino 17.9% 11.1% <0.001
(0.5) (0.8)
N 6,384 1,643

Note: Unweighted sample composition by vaccination status over the study period (March 10 2020 to March 31, 2021). Vaccinated: ever vaccinated respondents are those who reported having received at least a dose between March 10, 2020 and March 14, 2021, Never vaccinated respondents are those who did not report receiving a vaccine dose between March 10, 2020 and March 14, 2021.

Trajectory of mental distress over time: Ever vs. never vaccinated

Fig 1 shows the trajectory of average PHQ-4 scores among the ever vaccinated and the never vaccinated groups. While the levels differ at baseline, the trajectories are similar across the two groups until around December 2020 when the vaccines became available. From March 10 2020 (“day 0”) onward mental distress increased sharply during the first 30 days, and then recovered. For both groups, it reached the level of March 10 2020 before day 100, and remained fairly stable until vaccine rollout started for both groups. After that, we see a divergence of trajectories until the last day of the study period.

Fig 1. Trajectory of mental distress over time by vaccination group.

Fig 1

Note. PHQ-4 scores are standardized to have a mean of 0 and a standard deviation of 1. Ever vaccinated respondents are those who reported having received at least a dose by March 14, 2021, Never vaccinated respondents are those who did not report receiving a vaccine dose between by March 14, 2021. Local polynomial approximation to date (days since the initial panel date-March 10, 2020).

We observe that the never-vaccinated group exhibits a higher PHQ-4 score than the ever-vaccinated group throughout the study period. Although a detailed explanation of this difference is beyond the scope of this paper, we note that at least part of the difference can be ascribed to the different composition of the groups. For instance, on average, individuals over 65 have systematically shown better mental health during the pandemic than younger age groups (https://covid19pulse.usc.edu).

For the ever-vaccinated, Fig 2 below shows the change in standardized PHQ-4 scores by number of days before and after receiving the first dose. In order to abstract from common time effects, it uses residuals from a regression of PHQ-4 scores on wave dummy variables. The residuals are plotted against the number of days before and after receiving the first dose. The graph shows PHQ-4 scores fall after receiving the first vaccination dose.

Fig 2. Mental distress before and after receiving the first dose.

Fig 2

Note. PHQ-4 scores are standardized to have a mean of 0 and a standard deviation of 1. Residuals are taken from a linear regression of standardized PHQ-4 scores against wave dummy variables and an indicator for ever vaccinated. For the ever vaccinated, the residual is plotted against the number of days before or since receiving the first dose. Observations are grouped by wave. Vertical line denotes the date when a vaccination dose was first reported.

Fixed effects regression analysis of the effect of vaccination on mental distress

As Table 2 shows, the coefficient β, our estimate of the effect of receiving at least one dose of the vaccine (has vaccine = 1) on standardized PHQ-4 scores, equaled -0.04 (p-value<0.01), so that receiving a vaccine dose reduced PHQ-4 scores by 4% of a standard deviation. Receiving the vaccine was associated with a 1 percentage point decrease (4% from the baseline level) in the probability of being at least mildly depressed (p-value = 0.06); and a 0.7 percentage point (15% from the baseline level) decrease in the probability of being severely depressed (p-value = 0.01). The effect on the probability of experiencing moderate mental distress was non-significant (p-value = 0.26).

Table 2. Fixed effects regression models.

PHQ-4 Score (standardized) Mild mental distress or higher1 Moderate mental distress or higher2 Severe mental distress3
Has vaccine -0.0352*** -0.0104* -0.00422 -0.00681**
Standard error (0.0109) (0.00548) (0.00372) (0.00272)
P-value 0.001 0.059 0.256 0.012
Mean dependent variable 0.000 0.291 0.106 0.0446
Observations 157,228 157,228 157,228 157,228
R-squared 0.722 0.617 0.530 0.506

Respondent fixed effects and survey-wave dummies included in the regression. Standard errors clustered at the individual level

*** p-value<0.01

** p-value<0.05

* p-value<0.

1Mild mental distress or higher is an indicator variable that takes the value of one if PHQ-4 is equal to or higher than three and 0 otherwise

2Moderate mental distress or higher is an indicator variable that takes the value of one if PHQ-4 is equal to or higher than six and 0 otherwise

3Severe mental distress is an indicator variable that takes the value of one if PHQ-4 is equal to or higher than six and 0 otherwise.

In the supplementary materials, we provide estimates from a model where we include an interaction of Vaccit with time passed since first reporting a vaccine dose. The results show that the effect does not fade out as time passes (at least within the study period). On average, the standardized PHQ-4 score fell by 0.03 standard deviations(p-value<0.01) immediately after vaccination and was further reduced by 0.003 standard deviations per ten days after vaccination, although not significantly (p-value = 0.27)

Heterogeneity

Table 3 shows the results of the heterogeneity analyses. The effect on standardized PHQ4-scores is found to be higher for women, βFemale = -0.4, p-value <0.01, than for men, βMale = -0.02, p-value = 0.08, although we cannot rule out that the effects are equal for men and women (p-value for the test of βFemale = βMale equals 0.36).

Table 3. Heterogeneity analysis.

Panel A. Gender
PHQ-4 Score (standardized) Mild mental distress or higher1 Moderate mental distress or higher2 Severe mental distress3
Has vaccine X Male -0.025* -0.003 -0.006 -0.005
Standard error (0.014) (0.008) (0.005) (0.004)
Has vaccine X Female -0.044*** -0.016** -0.003 -0.008**
Standard error (0.016) (0.008) (0.005) (0.004)
p-val (βFemale = βMale) 0.357 0.220 0.721 0.551
Observations 157,227 157,227 157,227 157,227
R-squared 0.722 0.617 0.530 0.506
Panel B. Race
PHQ-4 Score (standardized) Mild mental distress or higher Moderate mental distress or higher Severe mental distress
Has vaccine X White -0.033*** -0.013** -0.002 -0.005
Standard error (0.012) (0.006) (0.004) (0.003)
Has vaccine X Non-white -0.044* -0.0032 -0.012 -0.013**
Standard error (0.0233) (0.0112) (0.007) (0.005)
p-val (βWhite = βNon-white) 0.680 0.446 0.224 0.174
Observations 156,987 156,987 156,987 156,987
R-squared 0.722 0.617 0.529 0.506
Panel C. Education
Gender PHQ-4 Score Mild mental distress or higher Moderate mental distress or higher Severe mental distress
Has vaccine X College Educated -0.032** -0.016** -0.002 -0.004
Standard error (0.013) (0.007) (0.005) (0.003)
Has vaccine X Not college educated -0.038* -0.001 -0.006 -0.012**
Standard error (0.019) (0.009) (0.00657) (0.00526)
p-val (βCollege = βNon-college) 0.797 0.203 0.709 0.221
Observations 157,186 157,186 157,186 157,186
R-squared 0.722 0.617 0.529 0.506

Respondent fixed effects and survey-wave by group dummies included in the regression. Standard errors clustered at the individual level.

*** p-value<0.01

** p-value<0.05

* p-value<0.1.

1Mild mental distress or higher is an indicator variable that takes the value of one if PHQ-4 is equal to or higher than three and 0 otherwise

2Moderate mental distress or higher is an indicator variable that takes the value of one if PHQ-4 is equal to or higher than six and 0 otherwise

3Severe mental distress is an indicator variable that takes the value of one if PHQ-4 is equal to or higher than six and 0 otherwise.

The effects for mild mental distress or higher, and severe mental distress are statistically significant for women but not for men. The coefficients imply that getting vaccinated reduced the probability of being at least mildly depressed for women by 1.6 percentage points (5% reduction compared to the base value, p-value<0.01 and the probability of being severely depressed or higher by 0.8 percentage points (15% reduction, p-value<0.01)

The coefficients for PHQ-4 scores for both White and non-White respondents were negative and insignificantly different across the two groups (βWhite = -0.03, βNon-white = -0.04, p-value of difference = 0.68). They were also not significantly different for college educated versus non-college educated respondents (βCollege = -0.03 βNon-college = -0.04, p-value of the difference = 0.80). These results suggest that the improvements in mental health following vaccination were not circumscribed within specific racial or education attainment groups.

Discussion

Earlier work showed that the prevalence of mental distress peaked in mid-April to early May 2020 and declined thereafter; it also showed how those trajectories differed for demographic groups. In this paper, we document how mental health distress has diverged between those who have been vaccinated and those who have not (or at least not yet). By comparing the trajectories of these two groups, we learn about the short-term impact of vaccination on mental health.

The results here should be interpreted as the short-term direct effects of getting a first vaccine dose. The overall contribution of vaccine uptake on improving mental health outcomes is potentially much larger, as it affects not only those vaccinated but also the unvaccinated. An unvaccinated individual may still benefit from the reduced prevalence rates in the population, may become less worried about loved ones, and may benefit from increased social and economic opportunities if the vaccine rollout results in more social and economic activity due to lower disease risk.

There are some limitations to this research. In particular, it is possible that the difference in trajectories across the vaccinated and not vaccinated groups arose not due to a causal effect of receiving the vaccine dose but from sorting at the time of the vaccine rollout, such that individuals with an increased likelihood of becoming less depressed were also more likely to decide to get vaccinated. In order to investigate that possibility, one can take advantage of different dates at which individuals in different groups have become eligible for vaccination. We leave that to future work.

The effects we identify could arise from one of or a combination of mechanisms. Those recently vaccinated may become less worried about getting infected, they may become more active socially, or they may venture into different work opportunities. Future research should investigate the mechanisms through which the vaccine shot achieved such effects.

The vaccination effects are likely to be heterogeneous on characteristics beyond the ones analyzed here. Since people who get the vaccines at different times are different in several dimensions, this implies that the effects may be different for the people who get vaccinated after the period studied here. Another reason why the effects may be different in a later period is that the conditions may be different. For instance, if COVID-19 cases are substantially reduced, then getting the vaccine may have a lower impact on the vaccinee’s health concerns. Whether that is the case can be studied at a later date using a methodology similar to the one used here.

Supporting information

S1 Appendix. Effects as a function of time elapsed since first vaccination.

(PDF)

Data Availability

All datasets are available from the Understanding America Study database uasdata.usc.edu.

Funding Statement

A.K. the Bill & Melinda Gates Foundation INV-016365 A.K 5U01AG054580 National Institute on Aging under grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Chung-Ying Lin

24 Jun 2021

PONE-D-21-16421

COVID-19 Vaccines and Mental Distress

PLOS ONE

Dear Dr. Perez-Arce,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

An expert in this field and I have reviewed your submission. We both agree that your contribution may add something to the literature. However, there are some essential corrections needed before I reevaluate your contribution. Please pay attention to all the comments made by the reviewer and answered them using a point-by-point response letter. Apart from his comments, I would like you to consider my following comments as well.

1. There is a growth of literature on vaccine hesitancy and the relationship between vaccine and mental distress. However, the present study does not provide a comprehensive literature review in this content. The authors are thus recommended to consult the following references to strengthen their literature review.

Rajabimajd N, Alimoradi Z, Griffiths MD. Impact of COVID-19-related fear and anxiety on job attributes: A systematic review. Asian J Soc Health Behav 2021;4:51-5

Patil ST, Datar MC, Shetty JV, Naphade NM. “Psychological consequences and coping strategies of patients undergoing treatment for COVID-19 at a tertiary care hospital”: A qualitative study. Asian J Soc Health Behav 2021;4:62-8

Rieger MO. Willingness to vaccinate against COVID-19 might be systematically underestimated. Asian J Soc Health Behav 2021;4:81-3

Rieger MO. Triggering altruism increases the willingness to get vaccinated against COVID-19. Soc Health Behav 2020;3:78-82

Yahaghi, R., Ahmadizade, S., Fotuhi, R., Taherkhani, E., Ranjbaran, M., Buchali, Z., Jafari, R., Zamani, N., Shahbazkhania, A., Simiari, H., Rahmani, J., Yazdi, N., Alijani, H., Poorzolfaghar, L., Rajabi, F., Lin, C.-Y., Broström, A., Griffiths, M. D., Pakpour, A. H. (2021). Fear of COVID-19 and perceived COVID-19 infectability supplement Theory of Planned Behavior to explain Iranians’ intention to get COVID-19 vaccinated. Vaccines, 9, 684.

Wang, P.-W., Ahorsu, D. K., Lin, C.-Y., Chen, I.-H., Yen, C.-F., Kuo, Y.-J., Griffiths, M. D., & Pakpour, A. H. (2021). Motivation to Have COVID-19 Vaccination Explained Using an Extended Protection Motivation Theory Among University Students in China: The Role of Information Sources. Vaccines, 9, 380. 

Yeh, Y.-C., Chen, I.-H., Ahorsu, D. K., Ko, N.-Y., Chen, K.-L., Li, P.-c., Yen, C.-F., Lin, C.-Y., Griffiths, M. D., Pakpour, A. H. (2021). Measurement invariance of the Drivers of COVID-19 Vaccination Acceptance Scale: Comparison between Taiwanese and mainland Chinese-speaking populations. Vaccines, 9(3), 297. 

Kukreti, S., Lu, M.-L., Lin, Y.-H., Strong, C., Lin, C.-Y., Ko, N.-Y., Chen, P.-L., & Ko, W.-C. (2021). Willingness of Taiwan’s healthcare workers and outpatients to vaccinate against COVID-19 during a period without community outbreaks. Vaccines, 9(3), 246. 

Alimoradi, Z., Broström, A., Tsang, H. W. H., Griffiths, M. D., Haghayegh, S., Ohayon, M. M., Lin, C.-Y., Pakpour, A. H. (2021). Sleep problems during COVID-19 pandemic and its’ association to psychological distress: A systematic review and meta-analysis. EClinicalMedicine, 36, 100916. 

Pramukti, I., Strong, C., Sitthimongkol, Y., Setiawan, A., Pandin M. G. R., Yen, C.-F., Lin, C.-Y., Griffiths, M. D., Ko, N.-Y. (2020). Anxiety and suicidal thoughts during the COVID-19 pandemic: A cross-country comparison among Indonesian, Taiwanese, and Thai university students. Journal of Medical Internet Research, 22(12), e24487. 

2. The meaning of "Fraction" on Table 1 is unclear. Moreover, what is (1) and (2) in Table 1? Please do not report p at 0.000 because p-value can only be very small but never be 0. Use p < 0.001 instead. The values in the columns of "Never Vaccinated" and "Ever Vaccinated" in Table 1 are unclear what they are.

3. In Table 2, please define what "mild mental distress or higher", "moderate mental distress or higher", and "severe mental distress" are. It is unclear what "mean dependent variable" is in Table 2. 

4. In Table 3, please also define what "mild mental distress or higher", "moderate mental distress or higher", and "severe mental distress" are.

==============================

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PLOS ONE

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3. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 1 and 3 in your text; if accepted, production will need this reference to link the reader to the Table.

4. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewer #1: Yes

**********

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Reviewer #1: N/A

**********

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Reviewer #1: Yes

**********

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Reviewer #1: Yes

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Reviewer #1: Q1: In paragraph 1 of introduction part, the author mentioned the dynamic of mental distress experienced of people due to COVID-19 which is up and down. It would be better to explain more why this fluctuated scheme could happen.

the authors may include the second paragraph into the first paragraph.

Q2: It is questioned that how the authors convinced the readers that vaccine really can improve well-being and mental health? How the vaccine uptake may reduce stress and alleviate fears of passing a COVID-19 infection along to others in social settings?

There is no citation at all for the 3rd par which talk about vaccine intake

Q3:

In the introduction part, there is insufficient reasons why the authors conduct this research? The author may add some crucial information about why the readers will have benefit to know the research result.

Q4:

The authors should provide the scientific reason why the panelists complete the surveys in the 14 days interval?

Q5:

There is no information about the validity and reliability of the PHQ-4?

Q6:

The authors stated “The ever vaccinated and never vaccinated groups differ significantly in their demographic composition as well as in baseline levels of mental health. The differences are likely a result both from the vaccine eligibility rules applicable during the period that we study as well as different levels of vaccine enthusiasm or hesitancy across demographic groups” in result section. Unfortunately, there is no explanation about the occupational background of the respondents, which may explain why they get vaccinated and never vaccinated. For instance the group of health care professionals.

Q7:

1. Table 1 the authors should clearly indicate the column label (number and percentage)

2. The authors need provide the information about the total number of the respondents in the table 1

Q8:

In figure 1 how the authors determined the time/date of group get vaccinated? Since the vaccination for COVID-19 started in December 23, 2020, so why the authors mentioned the interval was between March 10, 2020 and March 14, 2021?

Q9:

It was less information in discussion part that the authors may explain deeper interpretation from the result part. For instance, the comparison from each group of different educational background, and ethnics.

Q10:

There was miss-typed and word redundant

**********

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Reviewer #1: No

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PLoS One. 2021 Sep 8;16(9):e0256406. doi: 10.1371/journal.pone.0256406.r002

Author response to Decision Letter 0


30 Jul 2021

We are deeply grateful for your and the referee’s review and comments. We have revised the paper accordingly and believe it has substantially improved. In particular, per your first comment, we have now better situated the study in the relevant literature.

Below, please find our responses to the individual comments.

I. Response to the Editor’s comments

An expert in this field and I have reviewed your submission. We both agree that your contribution may add something to the literature. However, there are some essential corrections needed before I reevaluate your contribution. Please pay attention to all the comments made by the reviewer and answered them using a point-by-point response letter. Apart from his comments, I would like you to consider my following comments as well.

1. There is a growth of literature on vaccine hesitancy and the relationship between vaccine and mental distress. However, the present study does not provide a comprehensive literature review in this content. The authors are thus recommended to consult the following references to strengthen their literature review.

We agree the original submission was lacking on this respect. We have now better situated the study in the relevant literature, making the connection to the literatures on vaccine hesitancy and mental health effects of COVID-19. For context, it is particularly relevant to show that fear of COVID-19, as well as anxiety in general, are predictors of willingness to vaccinate. Page 4 now discusses this literature, which includes all but one of the references suggested by you as well as a number of other references that we deemed relevant.

2. The meaning of "Fraction" on Table 1 is unclear. Moreover, what is (1) and (2) in Table 1? Please do not report p at 0.000 because p-value can only be very small but never be 0. Use p < 0.001 instead. The values in the columns of "Never Vaccinated" and "Ever Vaccinated" in Table 1 are unclear what they are.

We made the change to use percentages instead of fractions which makes Table 1 clearer in our opinion. We also changed the reporting of p-values to p<0.0001 when applicable, and added the missing column numbers –(1) and (2)- to make the table clearer. With these changes, we hope the contents of Table 1 are now clear.

3. In Table 2, please define what "mild mental distress or higher", "moderate mental distress or higher", and "severe mental distress" are. It is unclear what "mean dependent variable" is in Table 2.

We now define these variables in the note to Table 2.

4. In Table 3, please also define what "mild mental distress or higher", "moderate mental distress or higher", and "severe mental distress" are.

We now define these variables in the note to Table 3.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: Q1: In paragraph 1 of introduction part, the author mentioned the dynamic of mental distress experienced of people due to COVID-19 which is up and down. It would be better to explain more why this fluctuated scheme could happen.

the authors may include the second paragraph into the first paragraph.

We added a discussion about a possible explanation for the fluctuation (economic deterioration and recovery) and cited a more extensive literature (page 4).

Q2: It is questioned that how the authors convinced the readers that vaccine really can improve well-being and mental health? How the vaccine uptake may reduce stress and alleviate fears of passing a COVID-19 infection along to others in social settings?

There is no citation at all for the 3rd par which talk about vaccine intake

We have added a discussion of the literature with the corresponding citations. In particular, we cited literature that showed that people with more anxiety are more likely to be willing to be vaccinated. It is then possible that getting the vaccine relieved those fears, which may be the channel through which vaccination improved mental health.

Q3:

In the introduction part, there is insufficient reasons why the authors conduct this research? The author may add some crucial information about why the readers will have benefit to know the research result.

We have added a paragraph in the first page of the introduction. The linkage to the literature suggested by the editor also helps to solve this issue.

Q4:

The authors should provide the scientific reason why the panelists complete the surveys in the 14 days interval?

Page 6 now includes an explanation of the rationale for the periodicity of the surveys.

Q5:

There is no information about the validity and reliability of the PHQ-4?

We now cite the validation and reliability study for the PHQ-4 measure (page 7, second paragraph)

Q6:

The authors stated “The ever vaccinated and never vaccinated groups differ significantly in their demographic composition as well as in baseline levels of mental health. The differences are likely a result both from the vaccine eligibility rules applicable during the period that we study as well as different levels of vaccine enthusiasm or hesitancy across demographic groups” in result section. Unfortunately, there is no explanation about the occupational background of the respondents, which may explain why they get vaccinated and never vaccinated. For instance the group of health care professionals.

The dataset we use does not contain occupation data, unfortunately. We agree that occupations are likely to be different across groups, and in indeed the larger proportion of health care professionals among the “ever vaccinated” may indeed at least partly explain the larger percentage of respondents with a college degree in that group. We now state that in the first paragraph of page 10.

Q7:

1. Table 1 the authors should clearly indicate the column label (number and percentage).

2. The authors need provide the information about the total number of the respondents in the table 1.

The labels in columns 1 and 2 have been added and the total number of respondents is shown in the last row.

Q8:

In figure 1 how the authors determined the time/date of group get vaccinated? Since the vaccination for COVID-19 started in December 23, 2020, so why the authors mentioned the interval was between March 10, 2020 and March 14, 2021?

We agree the statement in the note of Figure 1 was confusing. We change it so that it simply says that the Ever vaccinated are those who received a dose by March 14, and the Never vaccinated are those who had not received any dose by March 14.

Q9:

It was less information in discussion part that the authors may explain deeper interpretation from the result part. For instance, the comparison from each group of different educational background, and ethnics.

We have added a clarification to the description of the heterogeneity analysis.

Q10:

There was miss-typed and word redundant

We revised and corrected the text for typos and redundant words.

Response to Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy as Supporting Information.

The surveys are publicly available at https://uasdata.usc.edu/page/Covid-19+Documentation. We have added the link to the study.

3. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 1 and 3 in your text; if accepted, production will need this reference to link the reader to the Table.

We have added the reference to Tables 1 and 3 in the text.

4. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 1

Chung-Ying Lin

6 Aug 2021

COVID-19 Vaccines and Mental Distress

PONE-D-21-16421R1

Dear Dr. Perez-Arce,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Chung-Ying Lin

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I thank the authors carefully reviewed the comments and addressed all of them in this revision.

Reviewers' comments:

Acceptance letter

Chung-Ying Lin

11 Aug 2021

PONE-D-21-16421R1

COVID-19 Vaccines and Mental Distress

Dear Dr. Perez-Arce:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

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on behalf of

Dr. Chung-Ying Lin

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Appendix. Effects as a function of time elapsed since first vaccination.

    (PDF)

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    Submitted filename: Response to Reviewers.docx

    Data Availability Statement

    All datasets are available from the Understanding America Study database uasdata.usc.edu.


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