INTRODUCTION

Healthcare workers (HCWs) take an active role in the diagnosis, treatment, and monitoring stages of coronavirus disease-2019 (COVID-19). During the pandemic process, HCWs need extra care in vaccination from other occupational groups because they carry the risk of being infected, getting the disease, transmission, and even dying. The number of HCWs who have been diagnosed with this disease and lost their lives due to COVID-19 is increasing day by day worldwide (1). Rapid and safe protection of HCWs with vaccination is one of the most important elements in the control of an epidemic (2). Vaccination against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in Turkey started for HCWs as a prioritized group, on January 14, 2021. Afterward, the risk groups were expanded and community vaccination was initiated (3). SARS-CoV-2 vaccines (COVID-19 vaccines) are considered the most promising approach to ending the pandemic. CoronaVac^® (Sinovac, China), inactivated SARS-CoV-2 vaccine, in which the vast majority of HCWs are vaccinated in our country, is well-tolerated and induced an anti-body response in phase 1 and 2 studies (4).

We determined COVID-19 immunity among HCWs and their opinions on COVID-19 vaccines. We also assessed the seropositivity rates after CoronaVac^® vaccination in the study group and the surveillance of the COVID-19 was performed among those for 6 months.

METHODS

Design and Setting

The study was approved by the University of Health Sciences Turkey, Bakırköy Dr. Sadi Konuk Training and Research Hospital Clinical Research Ethics Committee (decision no: 2021-03-14, date: 01.02.2021). This study is a prospective observational study, conducted to obtain the anti-body levels for SARS-CoV-2 before the CoronaVac^® (Sinovac, China) vaccination of the people who are working as HCWs in the pediatric emergency room (PER) and pediatric intensive care unit (PICU) in Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey. The participants, including physicians, nurses, and other medical staff, were enrolled in the study between 1 and 14 January 2021. Participants were informed about all the steps of the study. Being a worker in the PER, PICU, and being 18 years and older were inclusion criteria. HCWs who had consent and were eligible for the study were included in the study. HCWs who had not worked in PICU and PER, or who did not give a written informed consent form were excluded. One hundred and sixty-eight HCWs were working in these departments and 127 HCWs were eligible to join the study (Figure 1).

In the first step, all participants completed a brief survey, and a blood sample was obtained to detect the anti-body levels against SARS-CoV-2. Survey data; included demographics, medical history, profession, experience in the profession, COVID-19 history, dates, and results of COVID-19 Polymerase Chain Reaction tests, and family diagnosis of COVID-19. Additionally, all participants were questioned about their intentions regarding COVID-19 vaccinations. HCWs who volunteered to be vaccinated were vaccinated with CoronaVac^® (Sinovac, China) vaccine.

In the second step of the study, those who had CoronaVac^®, anti-body titers were checked two more times: 1 month after 1^st and the 2^nd doses of vaccination. After all, vaccinations, the information about possible side effects was given and one week after each vaccination, appointments (by phone or face-to-face interview) were planned.

As strict infection control measures, HCWs were monitored for COVID-19 in pediatric department. In the last step of the study, COVID-19 surveillance was performed on all participants for 6 months (Figure 1).

Serum Samples

Approximately 10 mL of venous blood was collected from the subjects included in the study. Serum was separated by centrifugation at 5,000 rpm for five minutes within two hours after blood collection. The serum samples were tested for anti-SARS-CoV-2 anti-bodies on the same day. Increased serum samples were stored in Eppendorf tubes at -20 °C as 1.5 mL aliquots. The same procedure was repeated 28 days after the 1^st vaccine and 28 days after the 2^nd vaccine in the vaccinated participants. The study flowchart is given in Figure 1.

Serological Tests

All tests were performed at the Department of Laboratory Medicine, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul, Turkey. Blood samples were processed and stored, as noted previously. Total anti-bodies against SARS-CoV-2 were detected using the Elecsys^® anti-SARS-CoV-2 immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) on a Cobas e801 analyzer. A cut-off index >1 is positive.

In the case of positivity, a second test with Elecsys^® anti-SARS-CoV-2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) on a Cobas e801 analyzer for anti-bodies was performed to confirm the results. A cut-off index >0.8 is positive. Anti-body levels were performed using the Elecsys^® anti-SARS-CoV-2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) after the 1^st and 2^nd vaccinations of the vaccinated participants.

Statistical Analysis

All statistical analyses were performed using IBM SPSS for Windows version 20.0 (IBM Corp., Armonk, NY, USA). Kolmogorov-Smirnov tests were used to test the normality of data distribution. Continuous variables were expressed as mean ± standard deviation, median (25^th-75^th percentiles), and categorical variables were expressed as counts (percentages). Differences between groups were tested with the Mann-Whitney U test for numerical variables that did not have a normal distribution also Pearson’s, Yates chi-square Fisher Exact and Monte Carlo chi-square analyses were used for categorical variables. P<0.05 was considered statistically significant for significance.

RESULTS

A total of 127 HCWs were enrolled in the study (Figure 1). In all, 104 (81.9%) of these responders were women, and 23 (18.1%) were men. The median age of HCWs was 29 years [Interquartile range (IQR): 27-34 years] and the median professional experience was 4 years (IQR: 3-7 years). Participants included 61 (48%) physicians, 49 (38.6%) nurses, 12 (9.4%) cleaning staff, and 5 (3.9%) secretaries. For health status, 26 (20.5%) of them reported having comorbidities, 22 (17.3) continually used medications and 36 (28.3%) of them reported tobacco usage. The median body mass index of HCWs was 23 kg/m² (IQR: 20.8-25.3 23 kg/m²). In all, 8 (6.2%) of them had obesity, 3 (2.3%) of them had morbid obesity, and 28 (22%) of them were overweight (Table 1). In terms of transportation, 59 (46.5%) HCWs used public transportation whereas 51 (40.2%) used private cars, and 17 (13.4%) came to the hospital by walking. Only 3 (2.4%) participants had a history of traveling to abroad. The median number of people living in the same house with HCWs was 2 (IQR: 2-4) (Table 1).

Previous COVID-19 history was detected among 43 (33.8%) participants. The history and seropositivity rates are given in Table 2. Among healthcare workers, physicians were the most affected group (n=18, 41.8%), followed by nurses (n=13, 27.6%). Of those who had COVID-19 history, 33 (76.7%) HCWs were the index cases in their houses. Anti-body levels were tested as positive in 4 (4.8%) of 84 participants who had no positive history of COVID-19. In all study groups, the CoronaVac^® acceptance rate was 59.8%. The distribution of vaccination rates among different serologic groups is given in Table 2.

The participants who refused vaccinations were questioned. The distribution of their reasons is given in Table 1. Fifteen (29.4%) HCWs expressed they already had the disease, 22 (43.1%) thought the vaccine was ineffective, and 5 (9.8%) of them expressed that they had concerns about its side effects. Three (5.8%) HCWs had doubts about allergic reactions, and 6 (11.8%) women refused to get the vaccine because they were pregnant or breastfeeding.

The side effects seen in individuals who were vaccinated were as follows: pain at the injection site (n=21, 27.6%), myalgia (n=12, 15.7%), fatigue (n=12, 15.7%), headache (n=4, 5.2%) and fever (n=3, 3.9%). No life-threatening side effects or allergic reactions were observed. COVID-19 anti-body positivity rate was 80.2% among all participants 28 days later than the administration of the first vaccine. This rate exceeded 100% after the administration of the second CoronaVac^® vaccine. The distribution of seropositivity rates is given in Table 2. During the 6-month follow-up period, 7 (13.7%) unvaccinated HCWs had COVID-19 infections. One of them had a history of previous COVID-19 infection. Only 1 (1.3%) HCW had COVID-19 after 2 doses of CoronaVac^® when we investigated that case, she was working as a chief physician in PICU for longer hours than usual due to overload.

DISCUSSION

In this study, we report the incidence of contracting COVID-19 infection, the attitudes, and seropositivity rates of HCWs for CoronaVac^® in a pediatric department.

The rate of COVID-19 infections in HCWs is higher than that results in the general population (5,6). During the first 10 months of the pandemic, more than 30% of the HCWs who participated in our study had COVID-19 infection. In our study, among 127 participants, 43 (33.8%) of them had a positive history of SARS-CoV-2, and 4 (3.1%) of them had anti-body-positivity had a negative history of SARS-CoV-2 to the disease, some people can have the infection without any symptoms, but still they might spread it (7). Thus, the vaccination of HCW is essential in the control of the infection measures through the population (2).

When a new vaccine is introduced, vaccine hesitancy may raise (8). Indeed, the World Health Organization has considered the concept of vaccine hesitancy as one of the top ten threats to global health (9). In this study, it was observed that nearly 40% HCWs were vaccine-hesitant. A review examined the HCWs’ vaccine perceptions, knowledge and vaccination practices in 34 countries. It was stated that HCW are vital advocates for patients and the public, but studies indicated a prevalence of provider hesitancy about inadequate knowledge, low vaccine confidence, and suboptimal uptake themselves (10). There are many studies that have compared vaccine acceptance in different populations. Vaccine acceptance rates differ between occupational groups. Physicians are the occupational group most likely to accept vaccination also nurses are less often vaccine acceptors than physicians (11,12). In a study, which was held online in France in February 2021, the acceptance of the COVID-19 vaccine was examined among HCWs. In the 1965 HCWs, 1436 (73.1%) declared vaccine acceptance, 453 (23.1%) had vaccine hesitations and 76 (3.9%) of them stated that they were against vaccination (13). In another study conducted in France, among 2,057 healthcare professionals (21% physicians, 24% pharmacists, 18% nurses, 10% assistant nurses, 27% other); 1,554 (76.9%) declared that they would have the COVID-19 vaccine. Nurses and assistant nurses were found to be less willing than doctors to accept the vaccine against COVID-19 (14). In Israel, 1,941 people participated in an online study to compare the attitudes between the general population and health workers against COVID-19 vaccines. It has been observed that healthcare personnel caring for COVID-19-positive patients and individuals who consider themselves at risk of illness are willing to vaccinate with COVID-19 whenever possible. In contrast, parents, nurses, and HCWs who did not encounter SARS-CoV-2 positive patients expressed higher levels of vaccine hesitancy (11). In our study, the incidence of COVID infection among physicians was 29.5%, while it was 37.9% among non-physician HCWs. Although all participants were involved in the care of SARS-CoV-2-positive children, the vaccination rate was 72.1% among doctors, and 48.5% among non-physician HCWs. Efforts are recommended to inform healthcare professionals about the benefits of COVID-19 vaccines to maintain high vaccination rates. It is essential to make HCW competent with in-service training on vaccine education and their own vaccine acceptance (10).

According to the phase 3 results of CoronaVac^® performed in Brazil, Chile, and Turkey, while no serious side effects were observed after vaccination, the most common side effects are fatigue, headache, myalgia, fever, chills, and pain at the injection site. It was reported that no life-threatening side effects were observed in the phase 2 data, all side effects were seen between 25 and 35% of the subjects in the groups, and the most common side effect was pain at the injection site (15-17). In our study, the most common side effect was pain at the injection site and no life-threatening side effects were observed. Since the protection of vaccines is due to the complex interaction of the innate humoral and cellular immune response, the anti-body response is considered an important indicator of the immune response, although it does not fully demonstrate the protection of the vaccine (18). In our study, the ability of CoronaVac^® to produce anti-bodies was found to be 100% at least 28 days after the second vaccine.

There are some limitations to our study. Though the study was conducted in a certain occupational group, the results cannot be generalized to the population and all socioeconomic strata of society. The side effects were based on the reports of individuals. The humoral (neutralizing anti-body) response of the vaccine was revealed with anti-body measurements; no information on cellular immunity was presented. Therefore, this study cannot provide sufficient evidence on the protection of individuals from COVID-19.

CONCLUSION

In conclusion, vaccination of HCWs who are dealing with COVID-19 patients is essential to protect themselves and the population around them. Vaccine hesitancy against COVID-19 is a barrier to ending the pandemic in communities. It is recommended to identify the groups where vaccine acceptance is low or hesitant and to take additional precautions for these groups.

ETHICS

Ethics Committee Approval: The study was approved by the University of Health Sciences Turkey, Bakırköy Dr. Sadi Konuk Training and Research Hospital Clinical Research Ethics Committee (decision no: 2021-03-14, date: 01.02.2021).

Informed Consent: Written informed consent to publication has been obtained from all participants.

Authorship Contributions

Surgical and Medical Practices: N.A., Concept: N.A., E.Ş., Design: N.A., E.Ş., Data Collection or Processing: N.A., M.E.M., Analysis or Interpretation: N.A., M.E.M., C.B., Literature Search: N.A., E.Ş., Writing: N.A., E.Ş.

Conflicts of Interest: The authors declared that they have no conflicts of interest.

Financial Disclosure: This study received financial support from Bakirköy Dr. Sadi Konuk Training and Research Hospital Education Committee.