Comparison of Incidence and Clinical Outcomes of COVID-19 among Healthcare Workers in the Pre- vaccination and Post-vaccination Periods: A Real-world Impact Study

Abstract

Aim: Real-life data on the effect of coronavirus disease-2019 (COVID-19) vaccination is limited. We aimed to compare the incidence of COVID-19 among healthcare workers (HCWs) in the pre-vaccination and post-vaccination periods during the COVID-19 pandemic and identify associated factors for COVID-19 development.
Methods: In this single-center and cross-sectional study, HCWs employed in a tertiary care hospital were included. Pre-vaccination (14 October, 2020 and 14 January, 2021) and post-vaccination periods (1 March, 2021 and 1 June, 2021) were compared. A subgroup analysis was performed on HCWs without a previous history of COVID-19. Additionally, univariate regression analysis of COVID-19 development in the post-vaccination period was performed.
Results: Of 2,922 HCWs, 2,096 (71.7%) were vaccinated. The incidence of COVID-19 was higher in the pre-vaccination period (16.3%) than in the post-vaccination (6.6%) (p<0.01). In the subgroup analysis, the incidence of COVID-19 was 16.6% in the pre-vaccination period and 8.1% in the post-vaccination period (p<0.01). Previous history of COVID-19 (p<0.01) and double-dose vaccination (p<0.01) were associated with a decreased risk of COVID-19 development.
Conclusion: This study demonstrates the real-life impact of COVID-19 vaccination in reducing disease development and preventing poor clinical outcomes in a setting where the vaccination rate among HCWs was fairly low.
Keywords: COVID-19, vaccination, incidence, healthcare workers

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©Copyright 2022 by The Medical Bulletin of
Istanbul Haseki Training and Research Hospital
The Medical Bulletin of Haseki published by Galenos Yayinevi.
DOI: 10.4274/haseki.galenos.2022.8505
Med Bull Haseki 2022;60:310-317
Original Article
Surme et al. COVID-19 Vaccination in Healtcare Workers
Comparison of Incidence and Clinical Outcomes of
COVID-19 among Healthcare Workers in the Pre-
vaccination and Post-vaccination Periods: A Real-world
Impact Study
Serkan Surme*,**, Betul Copur*, Osman Faruk Bayramlar***, Gulsah Tuncer*,
Yusuf Emre Ozdemir****, Filiz Pehlivanoglu*, Gonul Sengoz*
*University of Health Sciences Turkey, Istanbul Haseki Training and Research Hospital, Clinic of Infectious Diseases and Clinical
Microbiology, Istanbul, Turkey
**Istanbul University-Cerrahpasa, Institute of Graduate Studies, Department of Medical Microbiology, Institute of Graduate Studies,
Istanbul, Turkey
***Bakirkoy District Health Directorate, Clinic of Public Health, Istanbul, Turkey
****University of Health Sciences Turkey, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Clinic of Infectious Diseases and
Clinical Microbiology, Istanbul, Turkey
Introduction
The coronavirus diseases-2019 (COVID-19) pandemic
had a magnificent impact on global health, especially
on healthcare workers (HCWs). Researchers from Turkey
and all around the world made a great effort to better
understand the epidemiology, clinical features, risk factors,
and predictors of poor clinical outcomes, including the
need for hospital admission, intensive care unit (ICU)
transfer, and in-hospital death (1-3).
Nevertheless, treatment of and prevention against
COVID-19 are still under research (4,5). Vaccination is one
of the most effective methods of preventing infectious
Ad dress for Cor res pon den ce: Gulsah Tuncer,
University of Health Sciences Turkey, Istanbul Haseki Training and Research Hospital, Clinic of
Infectious Diseases and Clinical Microbiology, Istanbul, Turkey
Phone: +90 543 579 94 09 E-mail: gulsah_durak_51@hotmail.com ORCID: orcid.org/0000-0002-9841-9146
Received: 27.05.2022 Ac cep ted: 14.08.2022
Aim: Real-life data on the effect of coronavirus disease-2019 (COVID-19) vaccination is limited. We aimed to compare the incidence of
COVID-19 among healthcare workers (HCWs) in the pre-vaccination and post-vaccination periods during the COVID-19 pandemic and
identify associated factors for COVID-19 development.
Methods: In this single-center and cross-sectional study, HCWs employed in a tertiary care hospital were included. Pre-vaccination (14
October, 2020 and 14 January, 2021) and post-vaccination periods (1 March, 2021 and 1 June, 2021) were compared. A subgroup
analysis was performed on HCWs without a previous history of COVID-19. Additionally, univariate regression analysis of COVID-19
development in the post-vaccination period was performed.
Results: Of 2,922 HCWs, 2,096 (71.7%) were vaccinated. The incidence of COVID-19 was higher in the pre-vaccination period (16.3%)
than in the post-vaccination (6.6%) (p<0.01). In the subgroup analysis, the incidence of COVID-19 was 16.6% in the pre-vaccination
period and 8.1% in the post-vaccination period (p<0.01). Previous history of COVID-19 (p<0.01) and double-dose vaccination (p<0.01)
were associated with a decreased risk of COVID-19 development.
Conclusion: This study demonstrates the real-life impact of COVID-19 vaccination in reducing disease development and preventing
poor clinical outcomes in a setting where the vaccination rate among HCWs was fairly low.
Keywords: COVID-19, vaccination, incidence, healthcare workers
Abs tract

Surme et al. COVID-19 Vaccination in Healtcare Workers
311
diseases and the poor clinical outcomes that accompany
them. Also, there is evidence that CoronaVac, which is an
inactivated whole-virion severe acute respiratory syndrome-
coronavirus-2 (SARS-CoV-2) vaccine, is safe and effective
against COVID-19 (6). A randomized clinical efficacy trial
has demonstrated that COVID-19 vaccination decreased
the risk of COVID-19 development and COVID-19 related
poor outcomes (7). However, there are a limited number
of vaccine studies on the real-life experiences of preventing
COVID-19 development, related hospitalization, and
mortality among HCWs.
Therefore, we compared the incidence and clinical
outcomes of COVID-19 among HCWs in the pre-
vaccination and post-vaccination periods during the
COVID-19 pandemic. Additionally, factors affecting the
development of COVID-19 in the post-vaccination period
were analyzed.
Materials and Methods
Compliance with Ethical Standards
All procedures performed in this study were in
accordance with the ethical standards of the Declaration
of Helsinki. This study was approved by the University
of Health Sciences Turkey, Istanbul Haseki Training and
Research Hospital Clinical Research Ethics Committee
(approval number: 96-2022, date: 11.05.2022) and the
Advisory Board on Coronavirus Research of the Republic
of Turkey Ministry of Health Written informed consent
was waived because of the retrospective nature of this
study.
Study Design
In this single-center and cross-sectional study, HCWs
employed in a tertiary care hospital were enrolled.
Demographic features, clinical characteristics, and
outcomes of HCWs with COVID-19 were recorded via
data-sheets from follow-up forms. The vaccination status
of all HCWs was collected via the hospital electronic
medical record system.
The pre-vaccination period was defined as the 3-month
period before the first vaccination was started (between
October 14, 2020 and January 14, 2021). The post-
vaccination period was defined as the 3-month period from
15 days after the second dose of vaccination (between 1
March, 2021 and 1 June, 2021).
The primary outcome was the development of
COVID-19. The secondary outcome was a composite
endpoint including hospital admission, ICU transfer, and
in-hospital death. To detect the differences in the primary
and secondary outcomes between the two periods, pre-
vaccinated and post-vaccinated periods were compared.
Additionally, a subgroup analysis was performed on HCWs
without a previous history of COVID-19. The incidence
rates of COVID-19 in the community and in HCWs in our
study group were compared. Community-related data were
obtained from the Republic of Turkey Ministry of Health’s
Coronavirus Information Platform (8). Prior to November
25, 2020, data were determined by proportioning patient
data based on the symptomatic COVID-19 incidence rate.
Moreover, HCWs with and without COVID-19 in the post-
vaccination periods were compared to identify protective
factors for developing COVID-19.
Statistical Analysis
Categorical parameters were represented as
frequencies (n) and percentages (%), whereas quantitative
parameters were represented as median and interquartile
ranges. The chi-square test or Fisher’s exact test were
used to compare categorical data. The Kolmogorov-
Smirnov test was used for normal distribution analysis.
The Independent sample t-test was applied for normally
distributed variables, while the Mann-Whitney U test was
performed for variables without normal distribution. A
univariate regression analysis for developing COVID-19
was performed. A p-value less than 0.05 was considered
significant. Odds ratios (OR) with 95% confidence intervals
(CI) were determined. The analyses were performed using
IBM SPSS-21 (Statistical Package for Social Sciences, IL,
USA).
Results
A total of 2922 HCWs were enrolled in this study.
Of these, 1,179 (40.3%) were males. The mean age
was 33.3±9.5 years. Overall, the vaccination rate in the
study group during the first 3 months of the vaccination
program was 71.7%. The single-dose and double-dose
vaccination rates were 22.9% (n=668) and 48.9%
(n=1428), respectively. Demographic characteristics of
HCWs according to vaccination status are represented in
Table 1.
Of 2,922 HCWs, 476 (16.3%) had COVID-19 in the pre-
vaccination period, whereas 193 (6.6%) had COVID-19 in
the post-vaccination period (p<0.01). Clinical deterioration
as a secondary outcome occurred in 22 (0.8%) HCWs
in the pre-vaccination period, whereas 11 (0.4%) HCWs
had poor clinical outcomes in the post-vaccination period
(p=0.06) (Table 2).
In the subgroup analysis, after excluding HCWs with
a previous history of COVID-19 in the last 3 months, the
incidence of COVID-19 was 16.6% in the pre-vaccination
period and 8.1% in the post-vaccination period (p<0.01)
(Table 3).
The weekly and cumulative incidence rates showed
the positive impact of the COVID-19 vaccination program
in preventing COVID-19 development among HCWs in

Surme et al. COVID-19 Vaccination in Healtcare Workers
312
our study group. While the concurrent lockdown might
have influenced our results, these same trends did not
occur either during the previous lockdown among HCWs
in our hospital or during the current lockdown at the
community level. The weekly incidence rates of COVID-19
in the community and HCWs in our study group are
demonstrated in Figure 1. The cumulative incidence rates
of COVID-19 in the community and HCWs in our study
group are demonstrated in Figure 2.
When we evaluated the factors affecting the
development of COVID-19 in the post-vaccination period,
previous history of COVID-19 (OR: 0.01, CI: 0.00-0.17,
Table 1. Demographic characteristics of healthcare workers according to the vaccination status in the first 3-month period
Parameters Total
(n=2,922) Unvaccinated (n=826) Single-dose vaccinated
(n=668)
Double-dose
vaccinated
(n=1,428)
Age (mean ± SD) 33.3±9.5 33.5±10.1 32.3±9.0 33.6±9.4
Sex
Male, n (%) 1,179 (40.3) 338 (40.9) 271 (40.6) 570 (39.9)
Female, n (%) 1,743 (59.7) 488 (59.1) 397 (59.4) 858 (60.1)
Comorbid diseases, n (%) 758 (25.9) 176 (21.3) 154 (23.1) 428 (30.0)
HT, n (%) 442 (15.1) 101 (12.2) 92 (13.8) 249 (17.4)
DM, n (%) 270 (9.2) 65 (7.9) 49 (7.3) 156 (10.9)
CAD, n (%) 137 (4.7) 34 (4.1) 27 (4.0) 76 (5.3)
Asthma/COPD, n (%) 32 (1.1) 5 (0.6) 8 (1.2) 19 (1.3)
Pre-vaccination COVID-19 history, n (%) 534 (83.7) 326 (63.7) 47 (94.9) 161 (90.1)
Pre-vaccination COVID-19 history (last 3
months), n (%) 58 (2.0) 26 (3.1) 13 (1.9) 19 (1.3)
Pre-vaccination COVID-19 history before the last
3-month, n (%) 476 (16.3) 300 (36.3) 34 (5.1) 142 (9.9)
HT: Hypertension, DM: Diabetes mellitus, CAD: Chronic artery disease, COPD: Chronic obstructive pulmonary disease, SD: Standard deviation, COVID-19: Coronavirus
disease-2019
Table 2. Comparison of pre-vaccination and post-vaccination periods in terms of COVID-19 development and the clinical deterioration
Parameters
Pre-vaccination period
(n=2922)
Post-vaccination period
(n=2922)
n (%) n (%) p-value
COVID-19
Yes 476 (16.3) 193 (6.6) <0.01*
No 2,446 (83.7) 2,729 (93.4)
COVID-related hospitalization
Yes 22 (0.8) 11 (0.4) 0.06*
No 2,900 (99.2) 2,911 (99.6)
Need for ICU admission
Yes 1 (0.03) 1 (0.03) 1.00†
No 2,921 (99.97) 2,921 (99.97)
In-hospital death
Yes 0 (0) 1 (0.03) 0.09†
No 2,922 (100) 2,921 (99.97)
Composite end-pointa
Yes 22 (0.8) 11 (0.4) 0.06*
No 2,920 (99.2) 2,911 (99.6)
a: Composite end-point includes COVID-19 related hospitalization, need for ICU admission, and in-hospital death, *: Chi-square test, †: Fisher’s exact test. Bold values
represent statistical significance at the level of p<0.05. The incidence of COVID-19 was significantly higher in the pre-vaccination period (16.3%) than in the post-vaccination
period (6.6%).
ICU: Intensive care unit, COVID-19: Coronavirus disease-2019

Surme et al. COVID-19 Vaccination in Healtcare Workers
313
p<0.01) and double-dose vaccination against COVID-19
(OR: 0.37, CI: 0.27-0.52, p<0.01) as well as comorbid
diseases, including diabetes mellitus (OR: 0.30, CI: 0.13-
0.68, p=0.01) and chronic artery disease (OR: 0.31, CI:
0.10-0.97, p=0.03) were associated with a decreased risk
of the disease development (Table 4).
Discussion
In this study, we presented a detailed analysis of
vaccination profiles in 2,922 HCWs employed in a
tertiary care teaching hospital, which is one of the
pandemic epicenters in Istanbul, Turkey, and compared
pre-vaccination and post-vaccination periods in terms of
Table 3. Subgroup analysis of pre-vaccination and post-vaccination periods in terms of COVID-19 development and the clinical
deterioration after exluding healthcare workers with previous history of COVID-19
Parameters Pre-vaccination period (n=2,864) Post-vaccination period (n=2,370)
n (%) n (%) p-value
COVID-19
Yes 476 (16.6) 193 (8.1) <0.01*
No 2,388 (83.4) 2,177 (91.9)
COVID-19 related hospitalization
Yes 22 (0.8) 11 (0.5) 0.17*
No 2,842 (99.2) 2,359 (99.5)
Need for ICU admission
Yes 1 (0.03) 1 (0.04) 1.00†
No 2,863 (99.97) 2,369 (99.6)
In-hospital death
Yes 0 (0) 1 (0.04) 0.45†
No 2,864 (100) 2,369 (99.6)
Composite end-point*
Yes 22 (0.8) 11 (0.5) 0.17*
No 2,842 (99.2) 2,359 (99.5)
*: Composite end-point includes COVID-19 related hospitalization, need for ICU admission, and in-hospital death, *: Chi-square test, †: Fisher’s Exact test. Bold values
represent statistical significance at the level of p<0.05. In the subgroup analysis after excluding HCWs with a previous history of COVID-19 in the last 3 months, the
incidence of COVID-19 was significantly higher in the pre-vaccination period (16.6%) than in the post-vaccination period (8.1%).
ICU: Intensive care unit, COVID-19: Coronavirus disease-2019, HCW: Healthcore workers
Figure 1. The cumulative incidence rates of COVID-19 in the community and HCWs
COVID-19: Coronavirus disease-2019, HCW: Healthcare workers

Surme et al. COVID-19 Vaccination in Healtcare Workers
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the incidence and clinical outcomes of COVID-19. We
analyzed the early impact (first 3 months) of the COVID-19
vaccination among HCWs. Therefore, the effect of
COVID-19 vaccination on the risk of infection and clinical
deterioration among HCWs was determined. Additionally,
protective factors for the risk of COVID-19 development in
the post-vaccination period were identified.
In a phase-3 efficacy trial, the efficacy of CoronaVac
against SARS-CoV-2 infection was 50.7% (9). One
retrospective study including HCWs in Brazil demonstrated
Table 4. Univariate regression analysis for COVID-19 development in the post-vaccination period
Parameters Presence Absence OR CI p-value
n % n %
Sex
Male 68 5.8 1,111 94.2 0.79 0.58-1.07 0.13
Female 125 7.2 1,618 92.8
Comorbidity Yes 38 5.0 720 95.0 0.68 0.48-0.99 0.04
No 155 7.2 2,009 92.8
DM Yes 6 2.2 264 97.8 0.30 0.13-0.68 0.01
No 187 7.1 2,465 92.9
HT Yes 23 5.2 419 94.8 0.75 0.48-1.17 0.20
No 170 6.9 2,310 93.1
COPD Yes 2 6.3 30 93.8 0.94 0.22-3.97 0.94
No 191 6.6 2,699 93.4
CAD Yes 3 2.2 134 97.8 0.31 0.10-0.97 0.03
No 190 6.8 2,595 93.2
Double-dose vaccination Yes 53 3.7 1,375 96.3 0.37 0.27-0.52 <0.01
No 140 9.4 1,354 90.6
Previous history of COVID-19 Yes 0 0.0 534 100.0 0.01 0.00-0.17
<0.01
No 193 8.1 2,195 91.9
Bold values represent statistical significance at the level of p<0.05. Previous history of COVID-19 and double-dose vaccination against COVID-19 as well as comorbid diseases
including diabetes mellitus and chronic artery disease were associated with decreased risk of the disease development.
HT: Hypertension, DM: Diabetes mellitus, CAD: Chronic artery disease, COPD: Chronic obstructive pulmonary disease, COVID-19: Coronavirus disease-2019, OR: Odds ratio,
Cl: Confidence interval
Figure 2. The weekly incidence rates of COVID-19 in the community and HCWs
COVID-19: Coronavirus disease-2019, HCW: Healthcare workers

Surme et al. COVID-19 Vaccination in Healtcare Workers
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that while vaccination with CoronaVac was associated with
a 0.5-fold decreased risk, the adjusted effectiveness was
36.8% of the double-dose vaccination against COVID-19
(10). Rovida et al. (11) showed that unvaccinated patients
were transferred to the ICU more frequently (29.2%) than
vaccinated patients (3.7%) among HCWs. In a community-
based observational study, the efficacy of booster doses
with various vaccines against the development of
symptomatic COVID-19 was between 78.8% and 96.5%
(12). In a recent impact-study conducted in Turkey,
mortality was observed less frequently in patients who
had COVID-19 in the post-vaccination period compared to
those with COVID-19 in the pre-vaccination period (13). In
a retrospective study in Denmark, the risk of hospitalization
and mortality rate were significantly lower in vaccinated
patients with solid organ transplants than in unvaccinated
patients (14). In an Italian study, vaccinated patients
had a less severe disease than unvaccinated patients,
although vaccinated patients were older and had higher
comorbidities (15). At the same time, McNamara et al.
(16) demonstrated that vaccination programs decreased
the risk of COVID-19 development, visits to emergency
departments, and hospitalization among older adults.
Jara et al. (17) reported that the adjusted vaccine
effectiveness was 65.9% for COVID-19 development,
87.5% for COVID-19 related hospitalization, 90.3% for
preventing ICU admission, and 86.3% for preventing
death. A retrospective real-life Turkish study that included
HCWs found waning immunity in HCWs vaccinated
with CoronaVac and the researchers reported that the
unadjusted and adjusted effectiveness for preventing
COVID-19 development was 47% and 39%, respectively
(18). In our study, the incidence of COVID-19 was lower
in the post-vaccination period compared to the pre-
vaccination period. Moreover, COVID-19 vaccination and
previous history of COVID-19 were found as protective
factors for the disease’s development. Additionally, HCWs
with comorbid diseases had COVID-19 less frequently. This
could be due to the high compliance of the HCWs with
comorbid diseases. In this study, poor clinical outcomes
occurred less frequently in the post-vaccination period
compared to the pre-vaccination period.
In a study that included HCWs in India, the vaccine
effectiveness against COVID-19 development was about
44% and 89% for partially and fully vaccinated HCWs,
respectively. Haas et al. (19) demonstrated that the
incidence of COVID-19 and related poor outcomes declined
with the increased vaccination rate. In a study from the
United States, they detected a significant decline (about
50%) in the daily COVID-19 cases in the 21-25 day post-
period after the initial doses of vaccination (20). Another
study comparing the pre- and post-vaccination periods
in the United States found that as the vaccination rate
increased, COVID-19 and related-poor clinical outcomes
decreased. Additionally, the researchers revealed that
older adults had the highest vaccination rate and a greater
decline (up to 66%) was observed in the older adults (21).
In the study by De Faria et al. (22), the effectiveness two
weeks after the second dose of CoronaVac among HCWs
was 50.7%. Toniasso et al. (23) reported that the incidence
of COVID-19 decreased by 65% in people with a previous
history of COVID-19 in the post-vaccination period.
Shoukat et al. (24) reported a 30% decline in
COVID-19 cases, a 51% decline in hospitalizations, and a
48% decline in deaths compared with the expected rates
between pre-vaccination and post-vaccination periods,
although single and double-dose vaccination rates among
adults were 64% and 69%, respectively. In a cohort that
comprised more than 90% fully vaccinated older adults,
the vaccine effectiveness for vaccinated people with no
known prior COVID-19 was 81.8% (25). Cavanaugh et
al. (26) reported that in a nursing facility, approximately
90% of residents and 52% of HCWs were fully vaccinated
and vaccine protection rates for COVID-19 development,
hospitalization, and death were 66%, 94%, and 94%,
respectively. Additionally, they revealed that the vaccination
effectiveness for developing COVID-19 among HCWs was
76%. As a result, studies conducted with different types of
vaccines, study protocols including study populations and
time frame, viral dynamics including SARS-CoV-2 variants,
and COVID-19 measures such as lockdown applications,
have different results in preventing COVID-19 and related
poor outcomes. However, most studies have confirmed
either the efficacy, effectiveness, or positive impact of
COVID-19 vaccines.
Study Limitations
Our study had some limitations. First, this study was
conducted retrospectively in a single center. Second, given
the study design, measuring the efficacy or effectiveness
of COVID-19 vaccination could not be possible. We
evaluated pre-vaccination and post-vaccination periods
and could compare the two periods. Comparing two
different periods does not reflect either vaccine efficacy
nor vaccine effectiveness. However, this study allowed us
to measure the impact of COVID-19 vaccination among
HCWs in the real world setting. Third, different pandemic
dynamics, such as viral mutations, lockdown applications,
and community compliance with COVID-19 measures,
may influence the impact of COVID-19 vaccination.
However, this study had several strengths. First, we could
closely evaluate the possible cases with active surveillance
since the study population was comprised of HCWs in our
pandemic hospital. Second, we could measure several
possible confounding variables, including age, sex, and

Surme et al. COVID-19 Vaccination in Healtcare Workers
316
comorbid conditions. These variables were not found as
significant covariates for each outcome in our study setting
comprising HCWs. Third, to mitigate the possible effect of
the prior SARS-CoV-2 infection on cases, we performed
subgroup analysis after excluding HCWs with a previous
history of COVID-19 infection in the last 3 months.
Conclusion
This study demonstrates the real-life impact of
vaccination against COVID-19 in both reducing disease
development and preventing poor clinical outcomes
in a setting where the vaccination rate among HCWs is
fairly low. Additionally, previous history of COVID-19 and
COVID-19 vaccination were detected as protective factors
for the disease’s development.
Ethics
Ethics Committee Approval: This study was approved
by the University of Health Sciences Turkey, Istanbul Haseki
Training and Research Hospital Clinical Research Ethics
Committee (approval number: 96-2022, date: 11.05.2022)
Informed Consent: Written informed consent was
waived because of the retrospective nature of this study.
Peer-review: Externally peer-reviewed.
Authorship Contributions
Concept: S.S., B.C., Design: S.S., B.C., O.F.B., Y.E.O.
Data Collection or Processing: B.C., G.T., Analysis or
Interpretation: S.S., B.C., O.F.B., G.T., Y.E.O., F.P., G.S.,
Literature Search: S.S., B.C., Y.E.O., Writing: S.S, B.C., O.F.B.,
G.T., Y.E.O.
Conflict of Interest: No conflict of interest was
declared by the authors.
Financial Disclosure: The present study has no
financial support.
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