Effect of a hospital-wide campaign on COVID-19 vaccination uptake among healthcare workers in the context of raised concerns for life-threatening side effects

Min Hyung Kim; Nak-Hoon Son; Yoon Soo Park; Ju Hyun Lee; Da Ae Kim; Yong Chan Kim

doi:10.1371/journal.pone.0258236

. 2021 Oct 1;16(10):e0258236. doi: 10.1371/journal.pone.0258236

Effect of a hospital-wide campaign on COVID-19 vaccination uptake among healthcare workers in the context of raised concerns for life-threatening side effects

Min Hyung Kim ^1,^#, Nak-Hoon Son ^2,^3,^#, Yoon Soo Park ¹, Ju Hyun Lee ⁴, Da Ae Kim ⁴, Yong Chan Kim ^1,^*

Editor: Etsuro Ito⁵

PMCID: PMC8486118 PMID: 34597333

Abstract

Background

All healthcare workers (HCWs) in Yongin Severance Hospital were allocated to receive the ChAdOx1 nCov-19 vaccine according to national policy. A report of thrombosis and thrombocytopenia syndrome (TTS) associated with ChAdOx1 nCoV-19 led to hesitancy about receiving the second dose among HCWs who had received the first dose.

Methods

From 7 to 14 May, 2021, we performed a survey to identify the factors associated with hesitancy about receiving the second vaccine dose among HCWs at the hospital who had received the first dose of the vaccine. Based on survey results, a hospital-wide campaign was implemented on 18 May 2021 to improve vaccine coverage. HCWs who completed the second dose completed a self-administered questionnaire to evaluate the effect of the campaign.

Findings

Of 1,171 HCWs who had received the first dose of the vaccine, 71.5% completed the online survey, of whom 3.7% refused to take the second dose and 22.3% showed hesitancy. Hesitancy to receive a second dose was significantly associated with age under 30 years and concerns about TTS, and was less common among those who trusted effectiveness and safety of the vaccine. Among HCWs who received the first dose, 96.2% completed vaccination with the second dose between 27 May and 4 June, 2021. Of those who answered the questionnaire asked about the timing of their decision to receive the second dose, 57.1% reported that they were motivated by the hospital-wide campaign.

Conclusion

A tailored intervention strategy based on a survey can improve COVID-19 vaccination uptake among HCWs.

Introduction

Globally, as of 2 July 2021, there were over 182 million confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including 3.95 million deaths reported to the World Health Organization (WHO) [1]. In hopes of combating the disease by creating herd immunity, private and public institutions developed vaccines against SARS-CoV-2 at an unprecedented pace [2]. WHO launched COVID-19 Vaccines Global Access (COVAX) to ensure rapid development, manufacturing, and distribution of coronavirus disease (COVID-19) vaccine, which has helped accelerate the development of COVID-19 vaccines [3]. However, the accelerated course of vaccine development inevitably accompanies concerns for the potential side effects and complications, considering that vaccine development usually takes several years or even decades [4, 5]. Accordingly, news of serious side effects of new vaccines has raised concerns among many individuals and has become a major reason for vaccine hesitancy [6, 7]. Additionally, the emergence of variants without information on the efficacy of vaccines against these strains and a resurgence of COVID-19 cases worldwide despite increasing vaccination rates appear to have dampened desires for vaccination [8]. Overcoming public fear for the sake of herd immunity has become a major challenge for the worlds’ leaders.

The Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) was the first COVID-19 vaccine authorised for use in the Republic of Korea on 10 February, 2021, and vaccination started on 26 February, 2021 [9]. Subsequently, a report of thrombosis and thrombocytopaenia syndrome (TTS) associated with the ChAdOx1 nCoV-19 vaccine was released from Europe on 9 April, 2021 [10], creating a lot of debate among experts over stopping vaccination with ChAdOx1 nCoV-19. On 12 April, 2021, the Korean guidelines for COVID-19 vaccination were changed due to reports of TTS among young adults who had received the ChAdOx1 nCov-19 vaccine. Considering the risks and benefits of vaccination, unvaccinated adults under 30 years were excluded from vaccination with the ChAdOx1 nCoV-19 vaccine. The Korean government also announced a policy to increase COVID-19 vaccination coverage to grant those who had been vaccinated an exemption from the 14-day mandatory quarantine that had been imposed on the close contacts of confirmed patients, and an exemption from mandatory mask wearing when outdoors [11].

In the Republic of Korea, healthcare workers (HCWs) were prioritised in vaccine allocation, and many HCWs were scheduled to receive the ChAdOx1 nCoV-19 vaccine. As of 22 March, 2021, the vaccine coverage ratio among the eligible Korean population was only 1.57% [12], largely due to constraints on vaccine supply and delivery around the world at that time [13]. We assumed that young HCWs had concerns about vaccination with ChAdOx1 nCoV-19, and that national policy alone would not be sufficient to address the issue. This study was conducted at a university affiliated hospital, where the percentage of individuals who completed the first dose of vaccination with the ChAdOx1 nCoV-19 vaccine was 63.3%. We conducted a survey to evaluate HCWs’ demands and to determine their intention regarding receiving a second dose of ChAdOx1 nCoV-19. Afterwards, we conducted a hospital-wide campaign based on the survey results to boost the vaccination rate of the second dose of ChAdOx1 nCoV-19 among HCWs.

Methods

Study population and study design

The Yongin Severance Hospital is a secondary care teaching hospital, with 708 beds, in the Republic of Korea. In accordance with the domestic policy for COVID-19 vaccination, all HCWs in the hospital were allocated to receive the ChAdOx1 nCov-19 vaccine, a replication-deficient adenoviral vector vaccine against COVID-19. The first dose of the vaccine was provided to HCWs from 8 to 19 March, 2021. Among a total of 1,851 HCWs, 1,171 (63.3%) received the vaccine during the period. After the release of the report of TTS associated with the ChAdOx1 nCoV-19 vaccine, hesitancy about accepting the second dose was observed among HCWs who had received the first dose. Measures were needed to resolve their concerns and to increase vaccination coverage of the second dose in HCWs.

Survey

We prepared an online survey to evaluate HCWs’ perception regarding the ChAdOx1 nCov-19 vaccine. The survey was administered to HCWs who had received the first dose of vaccine during 7–14 May, 2021. The survey consisted of questions that assessed their demographic characteristics, experience of adverse events after the first dose, COVID-19 experience and risk perception about COVID-19 severity, attitude regarding government recommended vaccinations and perception of COVID-19 vaccines, and their intention to accept the second dose of ChAdOx1 nCov-19 vaccine. Completing the questionnaire was voluntary, and participants were able to withdraw participation at any time. The questionnaire used in the research can be found in S1 Appendix.

Hospital-wide campaigns

The results of the survey showed considerable hesitancy about receiving the second dose of ChAdOx1 nCov-19 vaccine among HCWs who are under the age of 30. Based on the results of the survey, a hospital-wide campaign was implemented from 18 May, 2021. The following measures were applied during the campaign: (1) the importance of COVID-19 vaccination was reemphasised through a large electronic display in the hospital lobby; (2) e-mail reminders were sent to HCWs to inform them that vaccination with the second dose was due, almost due, or past due date; (3) accurate information about ChAdOx1 nCov-19 vaccine was provided through education; and (4) a specialised clinical team for HCWs was created to respond promptly to any adverse events after vaccination. All HCWs who developed any symptoms after vaccination could visit the clinic at any time during working hours. The team paid special attention to severe adverse events, and were particularly alert to any cases of TTS. They checked the platelet count if a HCW developed symptoms suggestive of TTS, such as headache, dyspnoea, chest pain, and abdominal pain.

To evaluate the effect of the campaign, we conducted an additional survey for HCWs who completed the second dose. A simple, self-administered questionnaire asked about the timing of decision to receive the second dose. If participants answered ‘decided after the hospital campaign’, they were asked to select the reason why they decided to receive the second dose.

Statistical analysis

Categorical variables are presented as frequencies and percentages and were compared using the Chi-square test or Fisher’s exact test. Logistic regression was performed to identify predictive factors. With variables exhibiting significance in univariate analysis, as well as those with clinical relevance, we performed multivariate analysis. The validity of the variables was confirmed using the statistical variable selection method. All statistical analyses were performed using the R software version 4.0.2 (R Development Core Team, Vienna, Austria) and SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA). Two-sided p-values < 0.05 were considered statistically significant.

Ethics statement

This study was approved by the Institutional Review Board of Yonsei University Health System Clinical Trial Centre, and the study protocol adhered to the tenets of the Declaration of Helsinki. As the study was retrospective and the questionnaire was anonymous, the Institutional Review Board waived the requirement for written informed consent from the participants.

Results

Fig 1 shows a process of vaccination, survey, and hospital-wide campaign and a flowchart of study population.

Characteristics of healthcare workers who had received the first dose of the vaccine

Of 1,171 HCWs who had received the first dose of the vaccine, 837 (71.5%) completed the online survey. The characteristics of the respondents are summarised in Table 1. Of the respondents, 548 (65.5%) were women, and 514 (61.9%) were aged under 40 years. The most common adverse event reported was myalgia (N = 601, 71.8%), followed by injection site pain (N = 585, 69.9%), fatigue (N = 582, 69.5%), and fever (N = 468, 55.9%). Of the respondents, 206 (24.6%) reported that adverse events decreased their ability to work for several days. Most respondents did not have a history of COVID-19 and believed that if they contracted the disease, they were unlikely to develop severe disease. Overall, 746 (89.1%) respondents reported good compliance with recommended vaccinations in the past. Although 749 (89.5%) answered that they considered the ChAdOx1 nCov-19 vaccine to be effective, about half of the respondents (N = 401, 47.9%) reported that they did not consider the vaccine to be safe, and 643 (76.8%) had concerns about TTS related with the ChAdOx1 nCov-19 vaccine, with 123 (14.7%) overestimating the prevalence of TTS. Of the respondents, 619 (74.0%) reported that they intended to receive a second dose of the vaccine, while 218 (26.0%) reported that they were hesitant or intended to refuse the second dose of the vaccine.

Table 1. Characteristics of healthcare workers who had received the first dose of ChAdOx1 nCov-19 vaccine in the hospital.

Variables	All respondents (N = 837)	Intention to receive the second dose of ChAdOx1 nCoV-19 vaccine
Variables	All respondents (N = 837)	Likely (N = 619)	Undecided or unwilling (N = 218)	P-value
Demographic factors
Gender				< .001
Female	548 (65.5%)	373 (60.3%)	175 (80.3%)
Male	289 (34.5%)	246 (39.7%)	43 (19.7%)
Age, years				< .001
Under 30	241 (29.0%)	140 (22.8%)	101 (46.5%)
30–39	273 (32.9%)	192 (31.3%)	81 (37.3%)
40–49	156 (18.8%)	133 (21.7%)	23 (10.6%)
Over 50	161 (19.4%)	149 (24.3%)	12 (5.5%)
Occupation				< .001
Nurse	331 (39.6%)	210 (33.9%)	121 (55.5%)
Doctor	109 (13.0%)	90 (14.5%)	19 (8.7%)
Others	397 (47.4%)	319 (51.5%)	78 (35.8%)
Smoking				0.01
Yes, including former smokers	93 (11.1%)	79 (12.8%)	14 (6.4%)
No	744 (88.9%)	540 (87.2%)	204 (93.6%)
Alcohol				0.439
Yes	422 (50.4%)	317 (51.2%)	105 (48.1%)
No	415 (49.6%)	302 (48.8%)	113 (51.8%)
Comorbidities				0.279
Yes	167 (20.0%)	129 (20.8%)	38 (17.4%)
No	670 (80.1%)	490 (79.2%)	180 (82.6%)
Children in household				< .001
Yes	360 (43.0%)	301 (48.6%)	59 (27.1%)
No	477 (57.0%)	318 (51.4%)	159 (72.9%)
Parents in household				0.119
Yes	279 (33.3%)	197 (31.8%)	82 (37.6%)
No	558 (66.7%)	422 (68.2%)	136 (62.4%)
Experience of adverse event to the first dose
Fever				< .001
Yes	468 (55.9%)	310 (50.1%)	158 (72.5%)
No	369 (44.1%)	309 (49.9%)	60 (27.5%)
Vomiting				< .001
Yes	25 (3.0%)	8 (1.3%)	17 (7.8%)
No	812 (97.0%)	611 (98.7%)	201 (92.2%)
Diarrhoea				< .001
Yes	47 (5.6%)	26 (4.2%)	21 (9.6%)
No	790 (94.4%)	593 (95.8%)	197 (90.4%)
Headache				< .001
Yes	416 (49.7%)	278 (44.9%)	138 (63.3%)
No	421 (50.3%)	341 (55.1%)	80 (36.7%)
Fatigue				< .001
Yes	582 (69.5%)	398 (64.3%)	184 (84.4%)
No	255 (30.5%)	221 (35.7%)	34 (15.6%)
Chill				< .001
Yes	450 (53.8%)	296 (47.8%)	154 (70.6%)
No	387 (46.2%)	323 (52.2%)	64 (29.4%)
Myalgia				< .001
Yes	601 (71.8%)	419 (67.7%)	182 (83.5%)
No	236 (28.2%)	200 (32.3%)	36 (16.5%)
Arthralgia				< .001
Yes	221 (26.4%)	137 (22.1%)	84 (38.5%)
No	616 (73.6%)	482 (77.9%)	134 (61.5%)
Others				0.013^a
Yes	14 (1.7%)	6 (1.0%)	8 (3.7%)
No	823 (98.3%)	613 (99.0%)	210 (96.3%)
Injection site pain				< .001
Yes	585 (69.9%)	408 (65.9%)	177 (81.2%)
No	252 (30.1%)	211 (34.1%)	41 (18.8%)
Injection site redness				< .001
Yes	160 (19.1%)	99 (16.0%)	61 (28.0%)
No	677 (80.9%)	520 (84.0%)	157 (72.0%)
Injection site swelling				< .001
Yes	187 (22.3%)	120 (19.4%)	67 (30.7%)
No	650 (77.7%)	499 (80.6%)	151 (69.3%)
Decrease in work efficiency due to adverse event				< .001
Yes	206 (24.6%)	107 (17.3%)	99 (45.4%)
No	631 (75.4%)	512 (82.7%)	119 (54.6%)
COVID-19 experience and risk perception about COVID-19 severity
Did you experience with COVID-19 symptoms without confirmed diagnosis?				0.029
Yes	127 (15.2%)	84 (13.6%)	43 (19.7%)
No	710 (84.8%)	535 (86.4%)	175 (80.3%)
Did you have a test for COVID-19 ever?				0.081
Yes	180 (21.5%)	124 (20.0%)	56 (25.7%)
No	657 (78.5%)	495 (80.0%)	162 (74.3%)
Do you know someone who had been confirmed with COVID-19?				0.106
Yes	101 (12.1%)	68 (11.0%)	33 (15.1%)
No	736 (87.9%)	551 (89.0%)	185 (84.9%)
How do you think you are likely to be when infected to SARS-CoV-2?				0.032
Severe	147 (17.6%)	99 (16.0%)	48 (22.0%)
Moderate	522 (62.4%)	385 (62.2%)	137 (62.8%)
Mild	168 (20.1%)	135 (21.8%)	33 (15.1%)
Variables related to vaccination with the second dose
Previous compliance with recommended vaccination				0.009
Always	746 (89.1%)	562 (90.8%)	184 (84.4%)
Sometimes or never	91 (10.9%)	57 (9.2%)	34 (15.6%)
Do you think that ChAdOx1 nCoV-19 vaccine is effective?				< .001
Yes	749 (89.5%)	588 (95.0%)	161 (73.9%)
No	88 (10.5%)	31 (5.0%)	57 (26.2%)
Do you think that ChAdOx1 nCoV-19 vaccine is safe?				< .001
Yes	436 (52.1%)	405 (65.4%)	31 (14.2%)
No	401 (47.9%)	214 (34.6%)	187 (85.8%)
Do you have concerns about the vaccine induced thrombotic thrombocytopenia?				< .001
Yes	643 (76.8%)	429 (69.3%)	214 (98.2%)
No	194 (23.2%)	190 (30.7%)	4 (1.8%)
Perceived prevalence of the vaccine induced thrombotic thrombocytopenia				0.002
<1/1,000,000	427 (51.0%)	338 (54.6%)	89 (40.8%)
1/100,000~1/1,000,000	287 (34.3%)	194 (31.3%)	93 (42.7%)
>1/100,000	123 (14.7%)	87 (14.1%)	36 (16.5%)

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COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

^aFisher’s Exact Test.

Hesitancy regarding the second dose of the vaccine

Of the respondents, 187 (22.3%) reported hesitancy about receiving the second dose of the ChAdOx1 nCov-19 vaccine (Table 2). In the univariate analysis, hesitancy was associated with female sex; age <40 years; being a nurse, non-smoker, or childless; having experienced an adverse event after receiving the first dose; perceived decreased work ability attributed to vaccination; knowing someone confirmed with COVID-19; perceived severity of the illness if infected with SARS-CoV-2; lower compliance with recommended vaccination in the past; distrust of the effectiveness or safety of the ChAdOx1 nCov-19 vaccine; and concerns about TTS.

Table 2. Factors associated with hesitancy to the second dose of ChAdOx1 nCov-19 vaccine (N = 187).

Variables	Univariate analysis			Multivariable analysis
Variables	OR	95% CI	p value	OR	95% CI	p value
Demographic factors
Gender
Female	2.97	(1.98, 4.45)	< .001	1.57	(0.89, 2.77)	0.121
Male	REF			REF
Age, years
Under 30	8.42	(4.32, 16.42)	< .001	5.8	(2.21, 15.23)	< .001
30–39	4.73	(2.41, 9.26)	< .001	3.52	(1.48, 8.37)	0.004
40–49	2.14	(0.99, 4.6)	0.052	1.56	(0.65, 3.78)	0.320
Over 50	REF			REF
Occupation
Nurse	2.22	(1.56, 3.16)	< .001	1.09	(0.69, 1.74)	0.715
Doctor	0.87	(0.49, 1.56)	0.647	1.01	(0.48, 2.09)	0.987
Others	REF			REF
Smoking
Yes, including former smokers	0.43	(0.22, 0.82)	0.011	0.81	(0.34, 1.92)	0.626
No	REF			REF
Alcohol
Yes	0.98	(0.71, 1.36)	0.922
No	REF
Comorbidities
Yes	0.81	(0.53, 1.24)	0.340
No	REF
Children in household
Yes	0.39	(0.27, 0.55)	< .001	1.87	(1.01, 3.45)	0.047
No	REF			REF
Parents in household
Yes	1.2	(0.85, 1.69)	0.307
No	REF			REF
Experience of adverse event to the first dose
Fever
Yes	2.66	(1.86, 3.8)	< .001	0.91	(0.54, 1.54)	0.733
No	REF			REF
Vomiting
Yes	6.66	(2.78, 15.96)	< .001	2.99	(0.96, 9.32)	0.059
No	REF			REF
Diarrhoea
Yes	2.58	(1.39, 4.78)	0.003	1.42	(0.65, 3.07)	0.380
No	REF			REF
Headache
Yes	2.1	(1.5, 2.94)	< .001	0.68	(0.41, 1.11)	0.122
No	REF			REF
Fatigue
Yes	3.03	(1.97, 4.64)	< .001	1.54	(0.84, 2.81)	0.161
No	REF			REF
Chill
Yes	2.69	(1.89, 3.83)	< .001	1.17	(0.69, 1.99)	0.570
No	REF			REF
Myalgia
Yes	2.31	(1.53, 3.51)	< .001	1.14	(0.63, 2.06)	0.669
No	REF			REF
Arthralgia
Yes	2.11	(1.48, 2.99)	< .001	1.04	(0.65, 1.67)	0.863
No	REF			REF
Others
Yes	3.39	(1.08, 10.63)	0.037	1.25	(0.35, 4.49)	0.728
No	REF			REF
Injection site pain
Yes	2.51	(1.65, 3.79)	< .001	1.06	(0.62, 1.81)	0.841
No	REF			REF
Injection site redness
Yes	1.97	(1.34, 2.9)	0.001	0.93	(0.54, 1.63)	0.810
No	REF			REF
Injection site swelling
Yes	1.82	(1.26, 2.64)	0.001	1.06	(0.62, 1.81)	0.833
No	REF			REF
Decrease in work efficiency due to adverse event
Yes	3.99	(2.8, 5.69)	< .001	1.98	(1.25, 3.14)	0.004
No	REF			REF
COVID-19 experience and risk perception about COVID-19 severity
Did you experience with COVID-19 symptoms without confirmed diagnosis?
Yes	1.47	(0.95, 2.26)	0.083
No	REF
Did you have a test for COVID-19 ever?
Yes	1.34	(0.91, 1.97)	0.136
No	REF
Do you know someone who had been confirmed with COVID-19?
Yes	1.61	(1.02, 2.55)	0.042	1.32	(0.74, 2.33)	0.349
No	REF			REF
How do you think you are likely to be when infected to SARS-CoV-2?
Severe	1.97	(1.13, 3.43)	0.017	1.45	(0.72, 2.9)	0.298
Moderate	1.57	(0.99, 2.49)	0.055	1.57	(0.89, 2.77)	0.116
Mild	REF			REF
Variables related to vaccination with the second dose
Previous compliance with recommended vaccination
Always	0.55	(0.34, 0.89)	0.016	0.49	(0.26, 0.9)	0.021
Sometimes or never	REF			REF
Do you think that ChAdOx1 nCoV-19 vaccine is effective?
Yes	0.17	(0.1, 0.27)	< .001	0.3	(0.17, 0.54)	< .001
No	REF			REF
Do you think that ChAdOx1 nCoV-19 vaccine is safe?
Yes	0.11	(0.07, 0.16)	< .001	0.27	(0.16, 0.43)	< .001
No	REF			REF
Do you have concerns about the vaccine induced thrombotic thrombocytopenia?
Yes	20.26	(7.42, 55.36)	< .001	7.54	(2.44, 23.25)	< .001
No	REF			REF
Perceived prevalence of the vaccine induced thrombotic thrombocytopenia
<1/1,000,000	0.73	(0.44, 1.19)	0.202
1/100,000~1/1,000,000	1.28	(0.78, 2.11)	0.330
>1/100,000	REF

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COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Multivariate analysis showed a strong association (P < 0.001) between hesitancy and some variables. Respondents under 30 years of age were more likely to hesitate to receive a second dose than those over 50 years (adjusted odds ratio [aOR]: 5.8, 95% CI: 2.21–15.23, P < 0.001). In contrast, respondents who trusted the effectiveness (aOR: 0.3, 95% CI: 0.17–0.51, P < 0.001) and safety (aOR: 0.27, 95% CI: 0.16–0.43, P < 0.001) were less likely to hesitate to receive the second dose compared with those who distrusted the vaccine. Concerns about the ChAdOx1 nCov-19 vaccine-induced TTS were significantly associated with hesitancy (aOR: 7.54, 95% CI: 2.44–23.25, P < 0.001).

Effect of hospital-wide campaign

Among 1,171 HCWs who received the first dose of the vaccine, 1,127 (96.2%) completed vaccination with the second dose during the week of 27 May to 4 June, 2021. During this period, 944 (83.8%) HCWs answered the questionnaire about the timing of the decision to receive the second dose of the vaccine (Fig 2). Overall, 220 respondents (23.3%) reported that they had decided to receive the second dose after the hospital-wide campaign. Among them, 125 (56.8%) selected ‘hospital-wide campaign’ as the motive for their decision. The second most common reason was ‘national policy’ (N = 46, 20.9%), followed by ‘recommendation by others’ (N = 31, 14.1%) and ‘positive information obtained from media’ (N = 17, 7.7%).

Discussion

COVID-19 vaccination of HCWs is important to provide herd immunity in hospitals and to reduce the risk of nosocomial transmission of SARS-CoV-2 [14]. Even though vaccines may change over time due to newly emerging issues [15, 16], documenting efforts to boost immunization in the context of constraints on vaccine supply and delivery is meaningful. In this study, although all HCWs in the hospital were designated to receive the ChAdOx1 nCov-19 vaccine, the coverage with the first dose was low. Furthermore, in the survey assessing the intention to receive the second dose, 22.3% of respondents were hesitant to receive the second dose and 3.7% of respondents expressed outright refusal. We evaluated factors associated with vaccine hesitancy, and based on the results, a hospital-wide campaign was implemented to increase vaccination coverage of the second dose. After the campaign, the rate of vaccination uptake of the second dose was 96.2% among HCWs who had received the first dose. The survey conducted among HCWs after their second vaccination revealed that 57.1% of those who decided to receive a second dose after the hospital-wide campaign, were motivated by the campaign.

Vaccination rate drops when the perceived side effects of a vaccine outweigh the disease severity [17]. We demonstrated that female sex and young age were risk factors associated with hesitancy to receive the second dose of ChAdOx1 nCov-19 vaccine in univariate analysis. Since initial reports have shown that life-threatening TTS has occurred mainly in young-aged women, persons with one of these factors would likely be hesitant to get vaccinated with a second dose [18]. Other factors such as reduced work efficiency due to adverse events after the first dose and previous poor compliance with other vaccines were also related to vaccine hesitancy, in accordance with previous studies [19]. Compared to previous reports on vaccine hesitancy [6, 16, 20, 21], concerns about life-threatening side effects were very common among respondents. Therefore, efforts were needed to resolve and address the concerns identified in the survey. In addition to offer correct information about TTS, a clinic for vaccinated HCWs was established to manage adverse events after vaccination.

The second survey revealed that 76.7% of participants had decided to accept the second dose of the vaccine before the campaign began. Previous reports on HCWs in France also suggested a similar percentage of vaccine acceptance [6]. In contrast to the general population [22], stronger intentions to receive vaccination have already been established among HCWs regardless of their job type. Responsibility as HCWs and high risk of exposure to COVID-19 might contribute to a favourable attitude towards the vaccine. This reflects the social consensus formed among HCWs confronting an unprecedented pandemic. Therefore, the HCWs of this study might be easily convinced of the necessity of vaccination and lower vaccine hesitancy.

Authentic information and dedicating resources to managing potential adverse events are important motivators for vaccination. Previous reports have revealed that misinformation often leads to vaccine hesitancy, which prompts the need for education of the public [7, 17, 23]. The importance of education targeting HCWs has been emphasized in studies of other vaccines [24]. We strived to correct misinformation related to ChAdOx1 nCov-19 vaccine through education. Several opportunities were provided to HCWs to be educated during a hospital-wide campaign. Such campaigns should be tailored to meet the needs of the public to address the ongoing challenge [25]: For example, cases of TTS were reported among persons who had received the ChAdOx1 nCov-19 vaccine, after which many HCWs who had been vaccinated with first dose expressed concerns about vaccination with the second dose. Therefore, our campaign focused on addressing concerns related to TTS. In addition to providing accurate information about TTS, we developed a specialized clinical team so that HCWs can receive medical consultation promptly whenever they complained of any symptoms after the second dose. Most responders said that the hospital campaign was a major determinant in their decision to accept the second dose of vaccination. Although it was not determined which component of the campaign had the greatest effects on resolving the hesitancy for the second dose, we believe that education and a specialized clinical team for HCWs played a major role in addressing vaccine hesitancy. Our findings provide insight for the direction of national policies to improve vaccine coverage in the general population, especially among young adults who agonize over vaccination due to an imbalance in the associated risks and benefits of vaccination [17]. Further study evaluating the effects of tailored campaign on vaccine uptake in the general population is warranted.

The second major reason for the decision to accept the second dose of vaccine was the incentives provided according to national policy for individuals who completed the scheduled vaccination. Other researchers have also described the importance of incentives for frontline workers [14, 26], and this study confirmed that incentives can provide an inducement for vaccination. Judicious employment of incentives is required, taking into account the fatigue that people might have felt since the pandemic began, and their hope of returning to “normalcy” in the context of the pandemic.

This study has several limitations. Due to the inherent limitation of a survey-based study, we could not conduct a direct comparison between the responders to the first and second surveys. However, it is reasonable to assume that the responders are a representative sample of the hospital staff with a response rate of > 70%. Second, the factors that influenced the participants who made early decisions regarding vaccination, as well as those who refused to receive the first dose of the vaccine, could not be determined in this study. This study focused on individuals who were likely to be affected by news on TTS adverse events and highlighted measures to improve second dose uptake amid heightened alerts for vaccine side effects. In order to take measures to improve overall vaccination rates in other settings, reasons for outright refusal of ChAdOx1 nCov-19 vaccination need to be investigated. Lastly, our results should be interpreted with caution because the surveys were conducted at a single centre; hence, the findings might not be generalisable. Further study is warranted to evaluate the effects of interventions to promote COVID-19 vaccination in other settings.

Conclusions

This is the first study showing the effect of a hospital-wide campaign to promote COVID-19 vaccination among HCWs. For successful campaigning, it is necessary to plan tailored intervention strategies considering the characteristics of HCWs. A hospital-wide campaign based on a survey of HCWs (emphasising the importance of vaccination, providing accurate information about vaccines, sending reminders for vaccination using email, and reducing concerns about adverse events through a specialised clinic team for HCWs) contributed to improve COVID-19 vaccination coverage. Our findings need to be emphasized when scaling up vaccination coverage for the general population.

Supporting information

S1 Appendix. The questionnaire used in the study.

(DOCX)

Click here for additional data file.^{(37KB, docx)}

S2 Appendix. Raw datasets used in the analysis.

(XLSX)

Click here for additional data file.^{(210.9KB, XLSX)}

Acknowledgments

We thank the hospital staff at Yongin Severance Hospital. We thank Medical Illustration & Design, part of the Medical Research Support Services of Yonsei University College of Medicine, for all artistic support related to this work.

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

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PLoS One. doi: 10.1371/journal.pone.0258236.r001

Decision Letter 0

Etsuro Ito

20 Aug 2021

PONE-D-21-22598

Effect of a hospital-wide campaign on the COVID-19 vaccination uptake among healthcare workers

PLOS ONE

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Reviewer #1: Review Report

Manuscript Number: PONE-D-21-22598

Title: Effect of a hospital-wide campaign on the COVID-19 vaccination uptake among healthcare workers

Background:

This study focusses on the vaccine hesitancy of hospital workers in Republic of Korean context. It shows that hospital-wide campaign to motivate health workers to get vaccinated – lowered vaccine hesitancy among health workers in getting the second dose.

Comments:

While I enjoyed reading the paper, I have some major reservations.

First, I am not sure about the novelty of the study. It is well known that ‘directed campaign’ and ‘generating awareness on vaccination’, encourage people to get vaccinated. Such campaign is also seen as an important means to mitigate the adverse affect of vaccine misinformation. Therefore, while I acknowledge that this might be the first study on hospital workers on vaccine hesitancy, the results are not surprising. I would suggest the authors to focus more on the contribution of the study/ paper. In other words, what is the incremental leaning from this study? In this context, I would like to highlight that it should be easier to convince hospital workers (compared to general public) about the benefits of vaccination and lower their vaccine hesitancy.

Second, I have concerns about the survey design. As mentioned in the study, 1,171 (60.3%) of the total hospital workers (1,851) received vaccination during the period of 8 to 19 March, 2021. The survey (of this study) focusses on 1,171 health workers who received the first dose of vaccination. To me, it is more important to focus on the health workers who did not want to get vaccinated (even the first dose). Because, those who got the first dose, know that without the second dose their vaccine will not be effective. Therefore, it is easier to manage the vaccine hesitancy challenge of this group. But the real challenge lies with the unvaccinated health workers (36.7% of total health workers!). I would suggest the authors to focus on this group as well – and explore what is the cause of vaccine hesitancy for this group (who did not even want to get the first dose).

Third, based on the univariate and multivariate analysis, the study has identified a few factors that contribute to vaccine hesitancy (female workers, younger workers…). However, no compelling arguments are presented by the authors as to why these factors lead to a higher level of vaccine hesitancy. As the general management literature suggests, female workers are more rule abiding, more compassionate and care more about society. It is not clear why female workers would be more hesitant. Similarly, it is not clear why younger workers would be more hesitant (may be, they have lower covid risk?). These points are important – because the hospital wide campaign should be linked to such factors.

Fourth, (somewhat linked to my previous point), there is no link discussed between the hospital wide campaign and the factors contributing to vaccine hesitancy. It looks like that any general campaign could work. This view questions the relevance of this study.

Reviewer #2: The authors report on a study on hesitancy to get vaccinated with the AstraZeneca vaccine among healthcare workers (HCW) in Yonin Severence Hospital in South Korea. HCW participated in online surveys after the first vaccine dose and were interviewed about vaccine hesitancy to receive a second doses. After the survey, a hospital-wide information campaign was launched to promote compliance with the second dose. After the second dose a second online survey was conducted among HCW to investigate the reasons for compliance with the second dose.

The topic is definitely relevant in the context of vaccination hesitancy, particularly in the context of the ongoing discussion of mandatory vaccines. Naturally, such studies have their limitations. The manuscript is well written and easy to understand. I think it has merit and should be published. However, I have a number of comments and suggestions that should definitely be addressed. I believe my comments can be easily addressed.

Kristan Schneider

Comments:

General comments:

1. Reasons to get vaccinated change rapidly throughout the pandemic. While some people did not want to get vaccinated immediately, their concerns naturally diminished over time, as more people were already vaccinated, aggressive variants are spreading, and incentives to get vaccinated are being implemented. This should be discussed a bit more.

2. Throughout the ms, the vaccine is called ChAdOx1 nCoV-19. It should be mentioned that it Is called also AZD 1222 or the AstraZeneca vaccine. I believe this will improve accessibility to a broader audience.

3. It should be discussed that the campaign can presumably not be scaled up to the full extend. It might work well in hospitals, but running such information campaigns in the general population is different, particularly point (4). However, some parts of the campaign are scalable. In so far this study gives insights in what could be done in the general population to promote the vaccine. I think the ms would profit from a broader discussion.

Major comments:

1. I have major concerns regarding the statistical analyses. Looking at the numbers in Table 1, I did not believe the p-vales reported. Hence, I ran some tests in R and obtained totally different p-values (which seem plausible to me). For instance, smoking: I ran the following R-code:

Fishers exact test:

fisher.test(matrix(c(79,540,14,204),ncol=2,nrow=2))

and obtained a p-value of 0.01171

Chi-square test with Yates correction:

chisq.test(matrix(c(79,540,14,204),ncol=2,nrow=2))

p-value: 0.01483

Chi-square test without Yates correction:

chisq.test(matrix(c(79,540,14,204),ncol=2,nrow=2),correct = FALSE)

p-value: 0.01042

The reported p-value was <0.001

It is similar for all other variables I checked. The p-values reported just do not seem plausible to me, and I obtained different p-values for all variables I checked.

I believe it is necessary to revise the table and the main text accordingly.

2. Table 1: Please be more specific on the statistical test. In all 2x2 tables a fisher’s exact should be performed. If a chi-square test is performed, it is unclear whether the Yates correction was applied (with this sample size I would not do it as it tends to over-correct).

3. Page 12: It needs to be specified more clearly what models were run. I suppose the univariate analyses means a logistic regression just with an intercept and this variable. With the multivariate analysis on the other hand all variables were forced into the logistic model.

I have objections against both. By the univariate analyses, a lot of models are fit, all of them presumably with a poor fit. However, since there is just one covariate and the intercept, the estimated regression coefficient will always appear significantly different form 0. This is actually seen by the small p-values. By the multivariate analysis, the model tends to overfit. After correction for multiple testing hardly any odd ratio is significantly different from 1.

An appropriate approach is to do a model selection based on the AIC criterium (in R function stepAIC – you specify the minimal model which is just and the maximum model). It will return the optimal model based on the AIC. The p-values of the z-tests for the regression coefficients that remain in the model should then be corrected for multiple testing by the Holm-method (I do not recommend the Hochberg method in this case).

In any case the model fit needs to be reported in terms of AIC and Null-Deviance and Deviance. The logistic regression is only justified if the model properly fits.

4. Introduction/Methods (L90-97): other reasons for vaccine hesitancy could have been the fact that the former “South African” variant spread and the AstraZeneca is not properly protecting from that variant. Another reason for hesitancy for the second dose might have been, that at this time it was reported that a longer vaccination schedule would improve the vaccine’s effectiveness. This should be discussed.

Minor comments:

L81: vaccine coverage rate: what is the vaccine coverage rate? Is it really a rate (with unit 1/time) or is it the percentage of vaccinated individuals in a certain group?

L81: I am confused about the 1.19%. This cannot be the percentage in the hospital where 63.3% got vaccinated. Is the 1.19% a figure for all of Korea? Also, it is important to report accessibility of the vaccine in this context. Vaccine distribution was characterized by bottlenecks in February and March this year.

L83: What is the completion rate? Is it the fraction of vaccinated individuals that complete the vaccination schedule? Again this would not be a rate (it is a dimensionless quantity, rates have unit 1/time).

L125-129: the statistical methods should be described in more detail, particularly whether the Yates correction was used with the chi-square tests, or what routines were run. Was it proc glm in SAS or glm() in R? etc.

Trivial comments:

L138: study -> the study

P12L6: sSARS -> SARS

**********

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2021 Oct 1;16(10):e0258236. doi: 10.1371/journal.pone.0258236.r002

Author response to Decision Letter 0

13 Sep 2021

To the reviewers

Thank you for your detailed evaluation of our article. We have corrected the text based on your recommendations. Corrections are shown in red and our responses to your comments are provided below.

Reviewer #1

While I enjoyed reading the paper, I have some major reservations.

1. First, I am not sure about the novelty of the study. It is well known that ‘directed campaign’ and ‘generating awareness on vaccination’, encourage people to get vaccinated. Such campaign is also seen as an important means to mitigate the adverse affect of vaccine misinformation. Therefore, while I acknowledge that this might be the first study on hospital workers on vaccine hesitancy, the results are not surprising. I would suggest the authors to focus more on the contribution of the study/ paper. In other words, what is the incremental leaning from this study? In this context, I would like to highlight that it should be easier to convince hospital workers (compared to general public) about the benefits of vaccination and lower their vaccine hesitancy.

Response: Thank you for your opinion. We revised our article to put an emphasis on the fact that our survey was conducted in the context of raised concerns for adverse events of the vaccine and to highlight the role of our campaign providing immediate medical services to promote vaccine uptake. Furthermore, we decided to include additional discussion regarding the implication of our research for the general population. We revised our script as follows:

In the Discussion section on page 19, lines 220-244:

“The second survey revealed that 76.7% of participants had decided to accept the second dose of the vaccine before the campaign began. Previous reports on HCWs in France also suggested a similar percentage of vaccine acceptance. In contrast to the general population [1], stronger intentions to receive vaccination have already been established among HCWs regardless of their job type. Responsibility as HCWs and high risk of exposure to COVID-19 might contribute to a favourable attitude towards the vaccine. This reflects the social consensus formed among HCWs confronting an unprecedented pandemic. Therefore, the HCWs of this study might be easily convinced of the necessity of vaccination and lower vaccine hesitancy.

Authentic information and dedicating resources to managing potential adverse events are important motivators for vaccination. Previous reports have revealed that misinformation often leads to vaccine hesitancy, which prompts the need for education of the public. The importance of education targeting HCWs has been emphasized in studies of other vaccines. We strived to correct misinformation related to ChAdOx1 nCov-19 vaccine through education. Several opportunities were provided to HCWs to be educated during a hospital-wide campaign. Such campaigns should be tailored to meet the needs of the public to address the ongoing challenge: For example, cases of TTS were reported among persons who had received the ChAdOx1 nCov-19 vaccine, after which many HCWs who had been vaccinated with first dose expressed concerns about vaccination with the second dose. Therefore, our campaign focused on addressing concerns related to TTS. In addition to providing accurate information about TTS, we developed a specialized clinical team so that HCWs can receive medical consultation promptly whenever they complained of any symptoms after the second dose. Most responders said that the hospital campaign was a major determinant in their decision to accept the second dose of vaccination. Although it was not determined which component of the campaign had the greatest effects on resolving the hesitancy for the second dose, we believe that education and a specialized clinical team for HCWs played a major role in addressing vaccine hesitancy. Our findings provide insight for the direction of national policies to improve vaccine coverage in the general population, especially among young adults who agonize over vaccination due to an imbalance in the associated risks and benefits of vaccination [2]. Further study evaluating the effects of tailored campaign on vaccine uptake in the general population is warranted.”

2. Second, I have concerns about the survey design. As mentioned in the study, 1,171 (60.3%) of the total hospital workers (1,851) received vaccination during the period of 8 to 19 March, 2021. The survey (of this study) focusses on 1,171 health workers who received the first dose of vaccination. To me, it is more important to focus on the health workers who did not want to get vaccinated (even the first dose). Because, those who got the first dose, know that without the second dose their vaccine will not be effective. Therefore, it is easier to manage the vaccine hesitancy challenge of this group. But the real challenge lies with the unvaccinated health workers (36.7% of total health workers!). I would suggest the authors to focus on this group as well – and explore what is the cause of vaccine hesitancy for this group (who did not even want to get the first dose).

Response: We totally agree with your opinion. It is important to explore causes of vaccine refusal for the first dose, but we couldn’t pay attention to them. Instead, we focused on hesitancy for the second dose and highlighted measures to improve second dose uptake because concerns for a second dose peaked among HCWs who received the first dose with reports of unexpected severe adverse events (TTS) associated with ChAdOx1 nCov-19. Therefore, taking that into account, we expounded on your comments as a limitation as follows:

In the Discussion section on page 20, lines 253-259

“Second, the factors that influenced the participants who made early decisions regarding vaccination, as well as those who refused to receive the first dose of the vaccine, could not be determined in this study. This study focused on individuals who were likely to be affected by news on TTS adverse events and highlighted measures to improve second dose uptake amid heightened alerts for vaccine side effects. In order to take measures to improve overall vaccination rates in other settings, reasons for outright refusal of ChAdOx1 nCov-19 vaccination need to be investigated.”

3. Third, based on the univariate and multivariate analysis, the study has identified a few factors that contribute to vaccine hesitancy (female workers, younger workers…). However, no compelling arguments are presented by the authors as to why these factors lead to a higher level of vaccine hesitancy. As the general management literature suggests, female workers are more rule abiding, more compassionate and care more about society. It is not clear why female workers would be more hesitant. Similarly, it is not clear why younger workers would be more hesitant (may be, they have lower covid risk?). These points are important – because the hospital wide campaign should be linked to such factors.

Response: Thank you for pointing this out. We agree with you and included the following explanations:

In the Discussion section on page 18, lines 210-214:

“Vaccination rate drops when the perceived side effects of a vaccine outweigh the disease severity. We demonstrated that female sex and young age were risk factors associated with hesitancy to receive the second dose of ChAdOx1 nCov-19 vaccine in univariate analysis. Since initial reports have shown that life-threatening TTS has occurred mainly in young-aged women, persons with one of these factors would likely be hesitant to get vaccinated with a second dose [3]. “

4. Fourth, (somewhat linked to my previous point), there is no link discussed between the hospital wide campaign and the factors contributing to vaccine hesitancy. It looks like that any general campaign could work. This view questions the relevance of this study.

Response: Thank you for your comment. We believe that education targeting HCWs and a specialized clinical team for HCWs to respond promptly to any adverse events after vaccination have played a major role in addressing vaccine hesitancy, and we have already mentioned this in the Discussion section. We further emphasized the effects of these and revised our article as follows:

In the Discussion section on page 19, lines 227-244:

“Authentic information and dedicating resources to managing potential adverse events are important motivators for vaccination. Previous reports have revealed that misinformation often leads to vaccine hesitancy, which prompts the need for education of the public. The importance of education targeting HCWs has been emphasized in studies of other vaccines. We strived to correct misinformation related to ChAdOx1 nCov-19 vaccine through education. Several opportunities were provided to HCWs to be educated during a hospital-wide campaign. Such campaigns should be tailored to meet the needs of the public to address the ongoing challenge: For example, cases of TTS were reported among persons who had received the ChAdOx1 nCov-19 vaccine, after which many HCWs who had been vaccinated with first dose expressed concerns about vaccination with the second dose. Therefore, our campaign focused on addressing concerns related to TTS. In addition to providing accurate information about TTS, we developed a specialized clinical team so that HCWs can receive medical consultation promptly whenever they complained of any symptoms after the second dose. Most responders said that the hospital campaign was a major determinant in their decision to accept the second dose of vaccination. Although it was not determined which component of the campaign had the greatest effects on resolving the hesitancy for the second dose, we believe that education and a specialized clinical team for HCWs played a major role in addressing vaccine hesitancy. Our findings provide insight for the direction of national policies to improve vaccine coverage in the general population, especially among young adults who agonize over vaccination due to an imbalance in the associated risks and benefits of vaccination [2]. Further study evaluating the effects of tailored campaign on vaccine uptake in the general population is warranted.”

Reviewer #2:

The authors report on a study on hesitancy to get vaccinated with the AstraZeneca vaccine among healthcare workers (HCW) in Yonin Severence Hospital in South Korea. HCW participated in online surveys after the first vaccine dose and were interviewed about vaccine hesitancy to receive a second doses. After the survey, a hospital-wide information campaign was launched to promote compliance with the second dose. After the second dose a second online survey was conducted among HCW to investigate the reasons for compliance with the second dose.

General comments:

Response: Thank you for your detailed comment.

1. We agree to your opinion that concerns about vaccination would diminish naturally over time. Some of HCWs decided to get vaccinated with second dose regardless of our campaign, as shown in results of this study. However, our study highlights the effects of our campaign on responders who decided to receive a second dose after the hospital-wide campaign. Indeed, 57.1% of those responded that the hospital campaign was a major determinant in their decision to accept the second dose of vaccination.

2. We agree with your opinion regarding that vaccine incentives would have influenced on improving vaccine coverage. This has already been described in discussion section, on page 19, line 241.

3. Emergence of variants would likely to have influenced to get vaccinated with ChAdOx1 nCoV-19 due to reduced vaccine efficacy compared with mRNA vaccines manufactured by Pfizer or Moderna. However, it is difficult that variants could have influenced on vaccination with second dose in our study since variants were rarely observed in South Korea at the time this survey was conducted.

Response: We agree with your comment, so we added the official name of the vaccine, which is Oxford-AstraZeneca adenovirus-vectored vaccine, at its first appearance.

In the Introduction section on page 3, line 71:

“The Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19)”

Response: We agree with your comment, so, we supplemented our article by adding discussion for the implication for general population. We revised discussion accordingly.

In the discussion section page 19, line 220-244:

Authentic information and dedicating resources to managing potential adverse events are important motivators for vaccination. Previous reports have revealed that misinformation often leads to vaccine hesitancy, which prompts the need for education of the public. The importance of education targeting HCWs has been emphasized in studies of other vaccines. We strived to correct misinformation related to ChAdOx1 nCov-19 vaccine through education. Several opportunities were provided to HCWs to be educated during a hospital-wide campaign. Such campaigns should be tailored to meet the needs of the public to address the ongoing challenge: For example, cases of TTS were reported among persons who had received the ChAdOx1 nCov-19 vaccine, after which many HCWs who had been vaccinated with first dose expressed concerns about vaccination with the second dose. Therefore, our campaign focused on addressing concerns related to TTS. In addition to providing accurate information about TTS, we developed a specialized clinical team so that HCWs can receive medical consultation promptly whenever they complained of any symptoms after the second dose. Most responders said that the hospital campaign was a major determinant in their decision to accept the second dose of vaccination. Although it was not determined which component of the campaign had the greatest effects on resolving the hesitancy for the second dose, we believe that education and a specialized clinical team for HCWs played a major role in addressing vaccine hesitancy. Our findings provide insight for the direction of national policies to improve vaccine coverage in the general population, especially among young adults who agonize over vaccination due to an imbalance in the associated risks and benefits of vaccination [2]. Further study evaluating the effects of tailored campaign on vaccine uptake in the general population is warranted.”

Major comments:

Fishers exact test:

fisher.test(matrix(c(79,540,14,204),ncol=2,nrow=2))

and obtained a p-value of 0.01171

Chi-square test with Yates correction:

chisq.test(matrix(c(79,540,14,204),ncol=2,nrow=2))

p-value: 0.01483

Chi-square test without Yates correction:

chisq.test(matrix(c(79,540,14,204),ncol=2,nrow=2),correct = FALSE)

p-value: 0.01042

The reported p-value was <0.001

It is similar for all other variables I checked. The p-values reported just do not seem plausible to me, and I obtained different p-values for all variables I checked.

I believe it is necessary to revise the table and the main text accordingly.

Response: Thank you for your comment. To make sure we had analyzed the data correctly, we double checked the result about smoking status using SAS. We reproduced p-value 0.0104, which was exactly the same figure as you had calculated with Chi-square test without Yates using program R. The results were also the same with the other two methods, Chi-square with Yates correction and Fishers exact test. We presented p-value by rounding it up to the decimal point 0.01. The result makes no difference whether you use Yates correction or not. I am afraid that you confused the number with that of the above. We present our results below.

Capture of the Table1 ‘Smoking’

Response: According to a study by Ronald Fisher (1922), a Chi-squared test (or better yet, a G-test) can be used when the sample size is big. However, it only provides approximation because the distribution of the samples that is calculated is an approximation which is equal to the theoretical Chi-squared distribution. The approximation is invalid when the sample sizes are small or data are unequally distributed across the table, resulting in low counts on the cells predicated on a null hypothesis (the expected counts). The usual rule of thumb is that chi-squared test is not suitable when the expected values in any of the cells of a contingency table are below 5, or below 10 when there is only one degree of freedom [3]. In our study, we annotated with lower case ‘a’ when Fisher’s exact test is required. We present the results below.

Capture of the Table 1 ‘Others’ and annotation

In any case the model fit needs to be reported in terms of AIC and Null-Deviance and Deviance. The logistic regression is only justified if the model properly fits.

Response: We appreciate your comment. Here are our answers. First of all, the purpose of the second analysis was to figure out the factors that leads to hesitancy. We carried out logistic regression analysis as described in “Statistical analysis” section, confirming the significance of each variable with univariate analysis. With the variables of p-value 0.05 or below by global test as well as the ones with clinical relevance, we performed multivariate analysis. Validity of the variables was confirmed by statistical variable selection method. Generally, researchers use Akaike Information Criterion (AIC) or Bayesian Information Criterion (BIC) to find the fittest model among various ones the methods present. Furthermore, AIC and BIC is useful to prevent reckless addition of variables for the purpose of gaining fitness. In this sense, we assume using them to check the adjusted effect of the variables is inappropriate.

Response: Thank you for your comments. It is true that the efficacy of the ChAdOx1 nCov-19 vaccine against variants is lower than that of mRNA vaccine. However, at the time this survey was conducted, variants were rare in South Korea and were observed in only a few foreign entrants from overseas. Therefore, I think that the emergence of variants is less likely to influence hesitancy for second dose. Also, since the schedule of second dose was set to 11-12 weeks after the first vaccine (recommended longest time to be extended) in our institution, it is difficult for HCWs to hesitant to second dose to improve the efficacy of vaccine.

Minor comments:

1. L81: vaccine coverage rate: what is the vaccine coverage rate? Is it really a rate (with unit 1/time) or is it the percentage of vaccinated individuals in a certain group?

Response: Thank you for your detailed comment. We decided to use ‘ratio’ instead of ‘rate’. We changed our article as follows.

In the Introduction section on page 3, line 84-85:

“As of 22 March, 2021, the vaccine coverage ratio among eligible Korean population was only 1.57%, largely due to constraints on vaccine supply and delivery around the world at that time [4].”

2. L81: I am confused about the 1.19%. This cannot be the percentage in the hospital where 63.3% got vaccinated. Is the 1.19% a figure for all of Korea? Also, it is important to report accessibility of the vaccine in this context. Vaccine distribution was characterized by bottlenecks in February and March this year.

Response: The number 1.19% was produced with vaccine eligible Korean population as denominator. We corrected the miscalculation and revised our article accordingly.

In the Introduction section on page 3, line 84-85:

“As of 22 March, 2021, the vaccine coverage ratio among eligible Korean population was only 1.57%, largely due to constraints on vaccine supply and delivery around the world at that time [4].”

3. L83: What is the completion rate? Is it the fraction of vaccinated individuals that complete the vaccination schedule? Again this would not be a rate (it is a dimensionless quantity, rates have unit 1/time).

Response: We appreciate your detailed comment. We changed it to ‘percentage of completion’.

4. L125-129: the statistical methods should be described in more detail, particularly whether the Yates correction was used with the chi-square tests, or what routines were run. Was it proc glm in SAS or glm() in R? etc.

Response: Generally, Yates correction is used only in 2 by 2 case. In this study, we performed Chi-square test or Fisher’s exact test for 2 by r case not only for 2 by 2 case. As a results, we did not consider Yates correction into account. However, we would like to inform you that we performed Chi-square test or Fisher’s exact test with precision. Furthermore, we used proc logstic and proc freq procedure of SAS and R to produce figure. We revised our article accordingly.

In the subsection ‘Statistical analysis’ in Method section on page 5, line 131-137:

“Categorical variables are presented as frequencies and percentages and were compared using the Chi-square test or Fisher’s exact test. Logistic regression was performed to identify predictive factors. With variables exhibiting significance in univariate analysis, as well as those with clinical relevance, we performed multivariate analysis. The validity of the variables was confirmed using the statistical variable selection method. All statistical analyses were performed using the R software version 4.0.2 (R Development Core Team, Vienna, Austria) and SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA). Two-sided p-values < 0.05 were considered statistically significant.”

Trivial comments:

L138: study -> the study

Response: thank you for pointing out our mistake. We corrected it.

P12L6: sSARS -> SARS

Response: thank you for pointing out our mistake. We corrected it.

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PLoS One. doi: 10.1371/journal.pone.0258236.r003

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Etsuro Ito

22 Sep 2021

Effect of a hospital-wide campaign on COVID-19 vaccination uptake among healthcare workers in the context of raised concerns for life-threatening side effects

PONE-D-21-22598R1

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PLoS One. doi: 10.1371/journal.pone.0258236.r004

Acceptance letter

Etsuro Ito

24 Sep 2021

PONE-D-21-22598R1

Effect of a hospital-wide campaign on COVID-19 vaccination uptake among healthcare workers in the context of raised concerns for life-threatening side effects

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Supplementary Materials

S1 Appendix. The questionnaire used in the study.

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Data Availability Statement

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PERMALINK

Effect of a hospital-wide campaign on COVID-19 vaccination uptake among healthcare workers in the context of raised concerns for life-threatening side effects

Min Hyung Kim

Nak-Hoon Son

Yoon Soo Park

Ju Hyun Lee

Da Ae Kim

Yong Chan Kim

Roles

Abstract

Background

Methods

Findings

Conclusion

Introduction

Methods

Study population and study design

Survey

Hospital-wide campaigns

Statistical analysis

Ethics statement

Results

Fig 1. Timeline of vaccination, survey, and the hospital-wide campaign.

Characteristics of healthcare workers who had received the first dose of the vaccine

Table 1. Characteristics of healthcare workers who had received the first dose of ChAdOx1 nCov-19 vaccine in the hospital.

Hesitancy regarding the second dose of the vaccine

Table 2. Factors associated with hesitancy to the second dose of ChAdOx1 nCov-19 vaccine (N = 187).

Effect of hospital-wide campaign

Fig 2. Responses to when the second dose recipients decided to get vaccinated and reasons why the respondents decided to receive the second dose after the hospital-wide campaign.

Discussion

Conclusions

Supporting information

Acknowledgments

Data Availability

Funding Statement

References

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Etsuro Ito

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Associated Data

Supplementary Materials

Data Availability Statement

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