Acceptance, effects, and tolerability in the vaccination process against SARS-CoV-2 among cancer patients in Bosnia and Herzegovina: A single-center cross-sectional study

Authors

  • Timur Cerić Clinic of Oncology, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0001-5478-8057
  • Emir Sokolović Clinic of Oncology, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Anes Pašić Clinic of Oncology, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Emina Borovac-Gurda Clinic of Oncology, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Velda Smajlbegović Clinic of Oncology, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Berisa Hasanbegović Clinic of Oncology, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Emina Bičakčić Filipović Clinic of Oncology, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Elma Kapisazović Clinic of Oncology, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Selma Sokolović Clinic of Oncology, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • Semir Bešlija Clinic of Oncology, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina

DOI:

https://doi.org/10.17305/bjbms.2021.7134

Keywords:

COVID-19, vaccination, cancer patients, acceptance

Abstract

The SARS-CoV-2 pandemic has been the main public health issue since the end of 2019. The vaccination campaign in Bosnia and Herzegovina started in April 2021, with several vaccines available. Our study aimed to evaluate the acceptance, effects, and tolerability of vaccines against SARS-COV-2 among cancer patients. We conducted a cross-sectional, observational study between 22 October and 30 November 2021, at the Clinic of Oncology, Clinical Center University of Sarajevo. Patients were enrolled during their regular visit to the Clinic of Oncology by agreeing to completean individual paper questionnaire. The study included 1063 patients with malignant diseases, of whom 681 (64.1%) were adequately vaccinated patients. In the study population, 76.9% of patients reported that they did not experience any side effects due to vaccination, while only 0.5% had side effects, causing a delay in their treatment. Among adequately vaccinated patients, there were 40 patients (3.8%) who were infected with SARS-CoV-2 after the second or booster dose of the vaccine. Five patients (0.5%) were hospitalized due to COVID-19 after being adequately vaccinated. The findings of our study suggest that cancer patients have a higher acceptance of vaccines against SARS-CoV-2 than the general population in Bosnia and Herzegovina. Vaccination side effects are tolerable and do not cause major delays in specific cancer treatment. The protective effects of COVID-19 vaccines in the cancer patients presented in our study are comparable to available results of similar studies, which included the general population.

Downloads

Download data is not yet available.
Acceptance, effects, and tolerability in the vaccination process against SARS-CoV-2 among cancer patients in Bosnia and Herzegovina: a single-center cross-sectional study

Downloads

Additional Files

Published

2022-04-08 — Updated on 2022-09-16

How to Cite

1.
Cerić T, Sokolović E, Pašić A, Borovac-Gurda E, Smajlbegović V, Hasanbegović B, Bičakčić Filipović E, Kapisazović E, Sokolović S, Bešlija S. Acceptance, effects, and tolerability in the vaccination process against SARS-CoV-2 among cancer patients in Bosnia and Herzegovina: A single-center cross-sectional study. Biomol Biomed [Internet]. 2022Sep.16 [cited 2023Jun.2];22(5):833-42. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/7134

Issue

Section

New and Emerging Medical Entities

INTRODUCTION

The SARS-CoV-2 pandemic has been the main public health issue since the end of 2019. Caused by the acute respiratory syndrome coronavirus-2 (SARS-CoV-2), COVID-19 can present with a diapason of cases – ranging from asymptomatic to severe, the most severe including respiratory distress, pneumonia, and even death [1].

As of December 4, 2021, 267,865,289 confirmed cases of COVID-19, including 5,285,888 deaths (1.97% of confirmed cases), have been reported worldwide to WHO [2].

The emergence of this pandemic drastically influenced the care of oncology patients worldwide, as well as in Bosnia and Herzegovina [3]. Given that COVID-19 is transmitted mainly by person-to-person contact, public health orders were issued in order to minimize person-to-person interaction [4, 5]. The first non-pharmaceutical interventions, colloquially known as lockdowns (stay-at-home orders, quarantines, and police curfews), had been implemented in order to reduce the spread of SARS-CoV-2 starting in China, then across multiple countries [6]. Studies so far have shown that the measures implemented played a significant role in effectively controlling the spread of the COVID-19 pandemic [7].

A single-center study in Southern Bosnia and Herzegovina, published by Arapović et al. [8], showed that the prompt introduction of restrictive socio-epidemiological measures resulted in better control of the pandemic in comparison with some higher-income countries (e.g., France, Italy, and Spain) during the first several months of the pandemic.

A study published by Goletic et al. [9] pointed out the importance of travel-associated disease introduction events. Through the molecular analysis of swab samples from different regions in Bosnia and Herzegovina, they pointed out the possible significance of independent travel modes and their impact on the increased incidence of COVID-19 cases as well as the importance of these findings in modifying the socio-epidemiological measures that are to be implemented.

For oncology patients globally, the protective measures meant that diagnostic and surgical procedures were delayed, treatment plans were altered in order to minimize visits to the clinic, and routine follow-ups were postponed [8]. Many patients had to receive treatment in clinic, in larger hospitals, or in clinical centers, meaning greater exposure and higher risk for getting infected with SARS-CoV-2. Changes in the treatment regimen of these patients may lead to disease progression or even worse outcomes [9]. Every oncology center made a management strategy for the spread of COVID-19 in order to reduce the delay of treatment. The COVID-19 pandemic has shown a significant impact on cancer patient care worldwide. The ONCOCARE-COV study published by Brugel et al. [10] shows the dramatic impact the COVID-19 pandemic had on different levels of oncology patient care. A relative decrease in chemotherapy and radiotherapy treatment was observed, as well as a significant negative impact on screening, cancer diagnostics, and surgical treatment of oncology patients. Similar results can be found in other European countries, such as Belgium, the UK, Spain, as well as in the US [1116]. Due to limited healthcare personnel, a majority of systems were faced with during the pandemic, an international collaborative group recommended a prioritization plan to maximize health benefits, considering the patient, their disease, and its prognosis [1016]. During the period of March–May 2020 of the 8657 patients planned for the administration of therapy at the Clinic of Oncology, Sarajevo, therapy was postponed for 77 individuals due to a positive anamnesis or a high body temperature. Out of the 40 symptomatic patients tested, infection with SARS-CoV-2 was confirmed in two [10]. Susak et al. [17] published a single-center study in Konjic, Bosnia and Herzegovina demonstrating the correlation between symptoms and IgG seroconversion against SARS-CoV-2 one year after the infection, with patients having positive IgG serology one year after contact. Symptoms of high fever and headache can be possible indicators of a better immune response as they have shown correlation with IgG levels. The study has also shown a significant increase in antibody titers of vaccinated participants one year after the infection which could possibly point to better protection against reinfection.

Oncology patients on active treatment were quickly considered as a potentially vulnerable population, especially individuals with risk factors, such as therapy-related immunosuppression, co-morbidities, age, etc. [11]. Conducted studies clearly showed that patients that go in for in-patient or out-patient treatment have an increased risk of COVID infection, patients were concerned about the risk of infection with COVID-19 when coming to the hospital, and some showed reluctance to proceed with treatment [12, 18]. Thus, leading oncology societies recommend that cancer patients on active treatment, those starting treatment and those that have been treated in the past six months, be prioritized for vaccination [19].

Protective behavior is crucial to managing a pandemic and effective immunization could bear the most promise for resolving the health issue of COVID-19 pandemic [13]. During 2020, several vaccines were being developed in multiple countries, and by the end of the year, results of the Phase III trial had been published which resulted in the approval of the vaccines against COVID-19 [1418].

Vaccination against COVID-19 commenced at the beginning of 2021, worldwide. The Strategic Advisory Group of Experts on Immunization (SAGE) issued a framework for the prioritization of COVID-19 vaccination considering cancer patients a high priority population, a plan that was also implemented in our country [19, 20]. Vaccination campaign in Bosnia and Herzegovina started in April 2021 with several vaccines available: SinoPharm (BBIBO), SinoVac (CoronaVac), ChAdOx1 nCoV-19 (Oxford/AstraZeneca), and later on, BNT162b2 (Pfizer/BioNTech). It must be noted that a significant number of individuals were vaccinated outside of the country before the vaccination campaign had started in Bosnia and Herzegovina.

Up until December 9, 2021, a total of 8,158,815,265 vaccine doses have been administered, as reported to WHO [20]. Data for Bosnia and Herzegovina show a total of 280,469 confirmed cases of COVID-19 have been reported, out of which 12,882 resulted in death. Up until November 4, 2021, a total of 1,553,874 vaccine doses have been administered; 833,233 individuals have been vaccinated with at least one dose; and 720,631 individuals are fully vaccinated [21].

According to the Institute for Public Health of the Federation of Bosnia and Herzegovina, in the period from 3rd March to 5th December, a total of 995,646 persons were vaccinated, out of which 525,844 with at least one dose, 461,597 with two doses administered, and 8205 people received the third dose [22].

According to the current data, several studies have been conducted to assess the cancer population’s attitude toward COVID-19 immunization. Several cross-sectional surveys have been conducted in order to better understand the acceptance of the SARS-CoV-2 vaccination of patients with malignant diseases. Most studies have shown that the majority of patients are willing to get vaccinated [2326].

The aim of our study is to evaluate the acceptance, effects, and tolerability of vaccines against the SARS-CoV-2 virus among cancer patients. We conducted a cross-sectional, observational study between October 22, 2021 and November 30, 2021 at the Clinic of Oncology, Clinical Center University of Sarajevo.

MATERIALS AND METHODS

We conducted a cross-sectional, observational study between October 22, 2021 and November 30, 2021 at the Clinic of Oncology, Clinical Center University of Sarajevo. The study included 1063 patients with malignant disease that have been visiting inpatient or outpatient departments of our clinic for treatment, follow-up, and consultations. They were enrolled during their regular visit to the Clinic of Oncology by agreeing to fill in an individual paper questionnaire on personal demographic information (initials, age, gender, and area of living), information on the previous COVID-19 infection, anti SARS-CoV-2 vaccination acceptance, vaccinational status, side effects of SARS-CoV-2 vaccination, and eventual delay of oncologic treatment caused by vaccines side effects. During the scheduled appointment, the attending physician filled in information about the diagnosis, presence of metastatic disease, and modality of the therapy into the questionnaire. Vaccinated patients in our study received one of the following vaccines against SARS-CoV-2: BNT162b2 (Pfizer/BioNtech); ChAdOx1 nCoV-19 (Oxford/AstraZeneca); SinoPharm (BBIBO); and CoronaVac (SinoVac).

Ethical statement

Ethical approval was obtained from the Hospital Ethics Committee at the Clinical Center University of Sarajevo (number 1178/21). Participation in the study was voluntary. Participants were assured of the anonymity and confidentiality of their responses. Refusals were not documented. Patients received no financial compensation. The questionnaire was approved by the institutional ethics committee.

Statistical analysis

IBM SPSS Statistics v. 23.0 was used for the statistical analysis. We defined the descriptive measures, including absolute value and percentages. The Chi-square test of independence was used to evaluate the relationship of categorical variables between adequately vaccinated and inadequately vaccinated patients. The Chi-square test of independence was used to evaluate the presence of side effects and the type of administered vaccine. Post-hoc Chi-square testing was performed to analyze adjusted residuals and to identify cells with statistically significant z-scores in cross tabulation. P < 0.05 was an indicator of significance.

RESULTS

Our study included 1063 patients who were treated or examined at the Clinic of Oncology, Clinical Centre University of Sarajevo during October and November 2021.

The mean age of all patients included in our study was 61.9 (SD = 11.5) years old and the study population consisted of 65.7% of female patients and 34.3% of male patients.

The characteristics of the study population are presented in Table 1.

TABLE 1: Characteristics of patients included in the study
Characteristics All patients n (%) Adequately vaccinated n (%) Not adequately vaccinated n (%) P value
Number of patients 1063 681 (64.1) 382 (35.9)
Gender Male Female 365 (34.3) 698 (65.7) 255 (69.9) 426 (61.0) 110 (30.1) 272 (39.0) P = 0.004
Age group (years) P <0.001
18–24 6 2 (33.3) 4 (66.7)
25–49 131 74 (56.5) 57 (43.5)
50–59 257 130 (50.6) 127 (49.4)
60–69 380 264 (69.5) 116 (30.5)
70–79 243 173 (71.2) 70 (28.8)
>80 46 38 (82.6) 8 (17.4)
Primary tumor P <0.001
Breast cancer 395 (37.2) 251 (63.5) 144 (36.5)
Gastrointestinal cancer 236 (22.2) 132 (55.9) 104 (44.1)
Genitourinary cancer 203 (19.1) 157 (77.3) 46 (22.7)
Lung cancer 58 (5.5) 43 (74.1) 15 (25.9)
Gynecological cancer 111 (10.4) 61 (55.0) 50 (45.0)
Other 59 (5.6) 36 (61.0) 23 (39.0)
Cancer treatment phase P=0.005
Active treatment 895 (84.2) 557 (62.2) 338 (37.8)
Follow up 168 (15.8) 124 (74.3) 44 (25.7)
Canton P <0.001
Sarajevo Canton 787 (74.0) 542 (68.9) 245(31.1)
Central Bosnia Canton 184 (17.3) 93 (50.5) 91 (49.5)
Una-Sana Canton 18 (1.7) 6 (33.3) 12 (66.7)
Herzegovina-Neretva Canton 10 (0.9) 4 (40.0) 6 (60.0)
Bosnian-Podrinje Canton 42 (4.0) 22 (52.4) 20 (47.6)
Zenica-Doboj Canton 22 (2.1) 14 (63.6) 8 (38.9)
Metastatic disease Yes No 403 (37.9) 660 (62.1) 235 (58.5) 445 (67.4) 168 (41.5) 215 (32.6) P = 0.003

Frequency distribution difference between patient characteristics and their vaccination status was analyzed by Chi-square test, P < 0.05 was considered statistically significant

In our study population, there were 339 (31.9%) unvaccinated patients and 43 (4.0%) patients who were vaccinated with the first dose of a vaccine. These patients were classified as inadequately vaccinated patients in further analysis. Patients who were classified as adequately vaccinated were those who received the second dose of a SARS-CoV-2 vaccine (63.9% of patients) or a booster dose (3rd dose) of the vaccine (0.2% of patients). The frequency distribution difference of vaccinated patients across cantons (areas of living) was statistically significant (P < 0.001). The highest percentage of vaccinated patients was in the Sarajevo Canton (68.9%), whereas the lowest percentage was in the Una-Sana Canton (33.3%).

The most commonly applied vaccine was BNT162b2 (Pfizer/BioNtech) to 53% of the patients, whereas 23.3% patients were vaccinated with ChAdOx1 nCoV-19 (Oxford/AstraZeneca) vaccine, 20.7% with the SinoPharm (BBIBO) vaccine, and 3% chose the CoronaVac (SinoVac) vaccine.

SARS-CoV-2 infection prior to filling out the questionnaire was reported by 261 (26.5%) patients.

BNT162b2 was the most commonly administered vaccine in almost all age groups except in patients over 80 years where the most common vaccine was ChAdOx1 nCoV-19 (Figure 1).

FIGURE 1: Frequency of different types of administered vaccines in different age groups of patients.

In our study population, 76.9% of patients reported that they did not experience any side effects of vaccination, whereas only 0.5% of patients had a delay in their treatment due to side effects of vaccination. The most commonly reported side effect was local pain at the site of vaccine injection and it was reported in 12.3% of patients. Beside local pain, fever was reported in 5.5% of patients, myalgia in 5.0% of patients, fatigue in 4.1% of patients, bone pain in 2.9% of patients, and 1% of patients complained about having nausea or vomiting after vaccination. Table 2 presents the most common side effects reported by the type of vaccine administered. In the post-hoc Chi-square testing, using values of adjusted residuals (z-scores) in cross tabulation, we have identified that side effects of vaccination were most commonly reported in patients vaccinated with ChAdOx1 nCoV-19 vaccine (z-score = 2.1; P = 0.03) and that patients without side effects of vaccination were most commonly vaccinated with SinoPharm vaccine (z-score = 3.8; P < 0.001). Local pain was the most commonly reported side effect – 12.3% of patients and it was most commonly present in patients vaccinated by the BNT162b2 vaccine (z-score = 3.8; P < 0.001). ChAdOx1 nCoV-19 vaccine was the most commonly administered vaccine in patients who reported fever as a side effect of vaccination against SARS-CoV-2 (z-score = 3.8; P < 0.001).

TABLE 2: Side effects of specific types of vaccines administered to study subjects
Side effects Types of vaccines P value
ChAdOx1 nCoV-19 n (%) BNT162b2n (%) SinoPharm (%) CoronaVacn (%)
Side effects Yes No 49 (28.8) 120 (71.2) 100 (26) 285 (74) 17 (11.3) 133 (88.7) 2 (9.5) 19 (90.5) <0.001
Local pain No Yes 153 (90.5) 16 (9.5) 321 (83.4) 64 (16.6) 141 (94) 9 (6) 21 (100) 0 (0) 0.001
Bone pain No Yes 165 (97.6) 4 (2.4) 372 (96.6) 13 (3.4) 148 (98.7) 2 (1.3) 19 (90.5) 2 (9.5) 0.167
Fever No Yes 150 (88.8) 19 (11.2) 368 (95.6) 17 (4.4) 146 (97.3) 4 (2.7) 21 (100) 0 (0) 0.002
Myalgia No Yes 160 (94.7) 9 (5.3) 363 (94.3) 22 (5.7) 145 (96.7) 5 (3.3) 21 (100) 0 (0) 0.485
Fatigue No Yes 159 (94.1) 10 (5.9) 373 (96.9) 12 (3.1) 144 (96) 6 (4) 19 (90.5) 2 (9.5) 0.272
Nausea/vomiting No Yes 169 (100) 0 (0) 378 (98.2) 7 (1.8) 150 (100) 0 (0) 21 (100) 0 (0) 0.1

Frequency distribution difference between specific side effects and type of administered vaccine was analyzed by Chi-square test, P < 0.05 was considered statistically significant *Cells with bold numbers had statistically significant z-scores in post-hoc Chi-square testing

Beside side effects reported in Table 2, three patients reported headache as side effect of vaccination, two of them were vaccinated with the BNT162b2 vaccine and one with the ChAdOx1 nCoV-19 vaccine. No serious adverse events of SARS-CoV-2 vaccines were reported by the patients.

Among adequately vaccinated patients, there were 40 patients (3.8%) who were infected with SARS-CoV-2 after the second or booster dose of the vaccine. The mean number of months of SARS-CoV-2 infection after being adequately vaccinated was 3.35 (SD = 1.77). Five patients (0.5%) were hospitalized because of COVID-19 after being adequately vaccinated.

The type of vaccine administered was not significantly related with patients who were infected with SARS-CoV-2 or hospitalized due to COVID-19 after full vaccination.

The presence of metastatic disease did not have a statistically significant relation with being infected with SARS-CoV-2 or hospitalized due to COVID-19 after adequate vaccination.

DISCUSSION

The first cases of COVID-19 in Bosnia and Herzegovina were reported at the beginning of March 2020.The vaccine campaign in Bosnia and Herzegovina had started later than in other European countries, probably due to the late arrival of the vaccines to our country [27]. In order to minimize the risk of COVID-19 infection and severe complications in this vulnerable population, cancer patients were prioritized as a group and encouraged to get vaccinated by the on-going campaign for vaccination via media outlets along with recommendations from their oncologists. Variations in the vaccination rate of population among different geographical areas could be attributed to the different quality and intensity of the implementation of vaccination campaigns against the SARS-CoV-2 virus by local experts.

Several studies reporting on the safety and efficacy of COVID vaccines amongst the cancer patient population have been published. Yasin et al. published a multicenter cohort study showing that cancer patients have significantly lower seropositivity rates compared to non-cancer patients (85.2% and 97.5%, respectively) when vaccinated with the CoronaVac vaccine. These findings were not surprising, considering that the cancer patients are immunosupressed, which therefore has a negative effect on the immune response. The study also confirmed the safety and efficacy of applying the CoronaVac in cancer patients [28]. Ariamanesh et al. found a 86.9% seropositivity rate in cancer patients vaccinated with the Sinopharm inactivated vaccine (BBIBP), also finding that low seropositivity rates are mostly found in elderly cancer patients, those on active treatment, and patients with haematologic malignant diseases [29]. Massarweh et al. found that 90% of patients receiving systemic anticancer treatment had an adequate immune response, but also significantly lower antibody titers compared to a healthy control group after receiving the BNT162b2 vaccine. The lowest antibody titers observed were in patients receiving chemotherapy in combination with immunotherapy [30].

According to WHO, up to November 2021, a total of 720,631 individuals were fully vaccinated, whereas 882,641 people were vaccinated with at least one dose in Bosnia and Herzegovina [28].

According to the data from the Institute for Public Health of the Federation of Bosnia and Herzegovina, in the period from March 3, 2021 to January 16, 2022, only 28.20% of the population has been fully vaccinated, whereas 7.47% received a booster dose [29]. Marijanović et al. showed that most cancer patients (62.2%) had hesitancy toward immunization with COVID-19 vaccines through their cross-sectional study conducted at the Clinic of Oncology, Mostar, Bosnia and Herzegovina [30]. Although we had a small sample of patients from this area of Bosnia and Herzegovina, our results are compatible since 40% of patients from the Herzegovina-Neretva Canton were adequately vaccinated. However, we should mention that this study was conducted during February 2021, when data on the safety of vaccination in cancer patients were limited.

A French cross-sectional study has shown that 53.7% of oncology patients, on active treatment or active surveillance, were likely to be vaccinated, whereas 29.7% considered themselves not ready yet [24].

Similar results have been documented in a Portuguese study by de Sousa et al., where a majority of cancer patients (84%) on immunosuppressive therapy had the intention to be vaccinated, as well as a Lebanese study where 55% of the patients had shown willingness for COVID-19 vaccination [23, 31].

A cross-sectional study carried out in Serbia has shown that 41.72% of cancer patients were vaccinated, whereas 17.67% wanted to be vaccinated as soon as possible. More than half of the patients not wanting vaccination stated that they wish to be vaccinated after their cancer treatment, which may point to a fear of the possibility of delaying active cancer treatment due to possible side effects [26].

However, data from our study show that 64.1% of patients were adequately vaccinated and these results outweigh the first data on vaccination hesitancy amongst cancer patients. In the majority of studies conducted, the main reasons for patients unwilling to get vaccinated lie in the uncertainty of the possible side effects or that vaccines may impact cancer treatment efficacy and outcomes, suggesting that these may be the reasons that in our study patients who were on follow-up were significantly more vaccinated compared to patients on active treatment (74.3% and 62.2%, respectively) [32].

When divided by the area of living, the highest percentage of vaccinated patients was in the Sarajevo Canton (68.9%). According to the Institute for Public Health of Canton Sarajevo in the period between March 2021 and January 2022, 50.1% of the Sarajevo Canton population has been fully vaccinated with a SARS-CoV-2 vaccine [33]. Comparing these two results, we can conclude that the encouragement and recommendation of oncologists at local clinics for vaccination against SARS-CoV-2 were fruitful and successful since the percentage of vaccinated cancer patients from Canton Sarajevo is higher than in the general population. The lowest percentage of vaccinated patients was in the Una-Sana Canton (33.3%). The difference in the percentage of vaccinated patients could be caused by the fact that the Sarajevo Canton has a much wider urban zone, and thus greater exposure of the population to vaccination campaigns conducted, among other things, through health institutions and various media.

As with most studies published to this day, data show that there is a significant correlation between age and vaccine acceptance [34]. We note that the majority of patients vaccinated were 50 years old and above, whereas only 33.3% patients between 18 and 24 years old were adequately vaccinated, which may imply that the older part of the population consider themselves to have a greater benefit from vaccination and decreased risk of COVID complications.

In our study, 53% of patients received BNT162b2 (Pfizer/BioNtech), whereas in the neighboring Serbia it was reported that the majority of cancer patients received the SinoPharm (BBIBO) vaccine [26].

Since cancer patients were not included in the clinical trials of the vaccine, limited data about vaccine tolerability are available for this part of population [35].

Meta-analysis on the safety of COVID vaccines in cancer patients suggested that vaccination appeared to be generally very safe, with mostly mild and moderate adverse effects reported. None of the included studies have described serious adverse events [36].

In our study population, 76.9% of patients reported that they did not have any side effects of vaccination, whereas only 0.5% of patients had a delay in their treatment caused by the side effects of vaccination.

The most common side effect was local pain at the injection site, reported in 12.3% of patients, out of whom the majority received the BNT162b2 vaccine.

Our study results correspond to the other results where the incidence of side effects in patients receiving the SinoPharm vaccine was lowest compared to other types of vaccines [26]. Reports of fever were the highest amongst patients receiving the ChAdOx1 nCOV-19 vaccine [11.2%] and it was significantly higher compared to other vaccines.

Tenforde et al. presented that vaccine effectiveness was significantly reduced for patients with immunocompromising conditions (59.2%) compared to individuals without an immunocompromising condition (91.3%) and that when restricted to immunocompromised patients with an active solid organ or hematologic malignancy or solid organ transplant, vaccine effectiveness was 51.2%. In this study, the authors also reported that 20% of patients who developed COVID-19 symptoms after being vaccinated were patients with active solid organ or hematologic malignancy. In the group of patients who developed COVID-19 infection after being adequately vaccinated, the median time between the final vaccine dose and symptom onset was 44 days [37]. In our study, only 3.8% of patients were infected with SARS-CoV-2 after the second or booster dose of the vaccine and the mean number of months of SARS-CoV-2 infection after being adequately vaccinated was 3.35 months (SD = 1.77).

According to the report of the Institute for Public Health of Canton Sarajevo, 76% of hospitalized patients are unvaccinated, whereas only 24% of hospitalized patients have been fully vaccinated [33]. The Israeli study shows only 7.7% of patients hospitalized with COVID-19 were fully vaccinated with 7 or more days after the second dose of vaccine, pointing to vaccine effectiveness opposed to 71.8% of COVID-related hospitalizations where patients were not vaccinated [38]. In our study population, five patients (0.5%) were hospitalized because of COVID-19 after being adequately vaccinated and it represents 12.5% of patients who developed COVID-19 after being adequately vaccinated.

The limitation of our study was that it was conducted in a single center, although oncology patients from different geographical areas of Bosnia and Herzegovina are getting treated at our center. Also, the period between the initiation of the vaccine campaign in Bosnia and Herzegovina and initiation of our study was too short to fully assess the effects of vaccines regarding developing COVID-19 and frequency of hospitalizations caused by COVID-19 among vaccinated patients. Also, another limitation of our study was the method of patient enrolment in the study, since it was based on the voluntary filling out of the questionnaire during their regular visit at our clinic. We can assume that a certain number of patients with poor COVID-19 outcome did not show up for regular check-ups and therefore, were not a part of the analyzed study population.

CONCLUSION

The findings of our study suggest that cancer patients have a higher acceptance of vaccines against SARS-CoV-2 than the general population in Bosnia and Herzegovina. Vaccination side effects are tolerable and do not cause any major delay of specific cancer treatment. The protective effects of SARS-CoV-2 vaccines in the cancer patients presented in our study are comparable to available results of similar studies which included the general population.

In order to have more reliable conclusions about the efficacy and safety of the use of SARS-CoV-2 vaccines among cancer patients, it is necessary to conduct a number of studies of different designs that will have longer follow-up periods. However, at this point, we have enough available evidence to convincingly recommend SARS-CoV-2 vaccination to cancer patients.

REFERENCES

  1. , , (). Coronavirus disease 2019 (COVID-19): a clinical update.. Front Med.. https://doi.org/10.1007/s11684-020-0767-8
  2. (). . World Health Organization. WHO Coronavirus (COVID-19) Dashboard.. Accessed 4 December, 2021. Available from: https://covid19.who.int/table
  3. , , , , , (). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.. Lancet.. https://doi.org/10.1016/S0140-6736(20)30211-7
  4. (). . How COVID-19 Spreads. Centers for Disease Control and Prevention.. Updated July 14, 2021. Accessed 4 December, 2021. Available from: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html
  5. (). . CDC (2020b) Social distancing. CDC, Atlanta, GA, USA.. Available from: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html
  6. (). Non-pharmaceutical interventions during the COVID-19 pandemic: a review.. Phys Rep. https://doi.org/10.1016/j.physrep.2021.02.001
  7. , (). The efficacy of lockdown against COVID-19: a cross-country panel analysis.. Appl Health Econ Health Policy. https://doi.org/10.1007/s40258-020-00596-3PMID: 32495067PMCID: PMC7268966
  8. , (). The first two months of the COVID-19 pandemic in Bosnia and Herzegovina: single-center experience.. Bosn J Basic Med Sci.. Published 2020 Aug 3https://doi.org/10.17305/bjbms.2020.4838
  9. , , , , , (). Phylogenetic pattern of SARS-CoV-2 from COVID-19 patients from Bosnia and Herzegovina: lessons learned to optimize future molecular and epidemiological approaches.. Bosn J Basic Med Sci.. Published 2021 Aug 1https://doi.org/10.17305/bjbms.2020.5381
  10. , , , , , (). Dramatic changes in oncology care pathways during the COVID-19 pandemic: the French ONCOCARE-COV study.. Oncologist. https://doi.org/10.1002/onco.13578
  11. , , , , (). The impact of the COVID-19 pandemic and the associated Belgian governmental measures on cancer screening, surgical pathology and cytopathology.. Pathobiology. https://doi.org/10.1159/000509546Epub 2020 Jul 7PMID: 32634799PMCID: PMC7445376
  12. , , , , , (). Fewer cancer diagnoses during the COVID-19 epidemic in the Netherlands.. Lancet Oncol. https://doi.org/10.1016/S1470-2045(20)30265-5
  13. , , , (). Cancer diagnostic rates during the 2020 ‘lockdown’, due to COVID-19 pandemic, compared with the 2018–2019: an audit study from cellular pathology.. J Clin Pathol. https://doi.org/10.1136/jclinpath-2020-206833
  14. (). Covid-19: urgent cancer referrals fall by 60%, showing “brutal” impact of pandemic.. BMJ. https://doi.org/10.1136/bmj.m2386
  15. , , (). Impact of the COVID-19 outbreak on cancer patient flow and management: experience from a large university hospital in Spain.. ESMO Open. https://doi.org/10.1136/esmoopen-2020-000828
  16. , (). Flattening the curve in oncologic surgery: impact of COVID-19 on surgery at tertiary care cancer center.. J Surg Oncol. https://doi.org/10.1002/jso.26056[Epub ahead of print]
  17. , , , , (). Sustained seroprevalence of SARS-CoV-2 antibodies one year after infection: one of the first COVID-19 cluster cases in Bosnia and Herzegovina.. Bosn J Basic Med Sci. Published 2022 Feb 1https://doi.org/10.17305/bjbms.2021.6340
  18. , , (). Are all patients with cancer at heightened risk for severe Coronavirus disease 2019 (COVID-19)?. Clin Infect Dis. https://doi.org/10.1093/cid/ciaa1079
  19. (). . National Comprehensive Cancer Network. Recommendations of the NCCN COVID-19 vaccination advisory committee.. Available from: www.nccn.org/docs/default-source/covid-19/2021_covid-19_vaccination_guidance:v3-0.pdf?sfvrsn=b483da2b_60
  20. , , , , , (). Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study.. Future Oncol (London, England). https://doi.org/10.2217/fon-2021-1248PMID: 35081732PMCID: PMC8793921
  21. , , , , , (). Immunogenicity and safety of the inactivated SARS-CoV-2 Vaccine (BBIBP-CorV) in patients with malignancy.. Cancer Invest. https://doi.org/10.1080/07357907.2021.1992420
  22. , , , , , (). Evaluation of seropositivity following BNT162b2 messenger RNA vaccination for SARS-CoV-2 in patients undergoing treatment for cancer.. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2021.2155
  23. , , , , , (). Oncology patients’ perceptions of and experiences with COVID-19.. Support Care Cancer. https://doi.org/10.1007/s00520-020-05684-7
  24. , , , , , (). Prognostic impact of missed chemotherapy doses during chemoradiation therapy for non-small cell lung cancer.. Am J Clin Oncol. https://doi.org/10.1097/COC.0000000000000293
  25. (). Managing an oncology clinic during the COVID-19 pandemic-how we did it in Sarajevo?. Memo. https://doi.org/10.1007/s12254-020-00643-8
  26. , , , , , (). Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study [published correction appears in Lancet. 2020 Sep 12;396(10253):758].. Lancet. https://doi.org/10.1016/S0140-6736(20)31187-9
  27. , , , , , (). Perspectives, fears and expectations of patients with gynaecological cancers during the COVID-19 pandemic: a Pan-European study of the European Network of Gynaecological Cancer Advocacy Groups (ENGAGe).. Cancer Med. https://doi.org/10.1002/cam4.3605
  28. , (). Demographic and attitudinal determinants of protective behaviours during a pandemic: a review.. Br J Health Psychol. https://doi.org/10.1348/135910710X485826
  29. , , , , , (). An mRNA vaccine against SARS-CoV-2 – Preliminary report.. N Engl J Med. https://doi.org/10.1056/NEJMoa2022483
  30. , , , , , (). Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults [published correction appears in Nature. 2021 Feb;590(7844):E26].. Nature. https://doi.org/10.1038/s41586-020-2639-4
  31. (). . Spikevax (previously COVID-19 Vaccine Moderna). European Medicines Agency.. Accessed 3 December, 2021.Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/spikevax
  32. (). . Comirnaty. European Medicines Agency.. Accessed 3 December, 2021. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/comirnaty∖#authorisation-details-section
  33. (). . Vaxzevria (previously COVID-19 Vaccine AstraZeneca). European Medicines Agency.. Accessed 3 December, 2021. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/vaxzevria-previously-covid-19-vaccine-astrazeneca∖#authorisation-details-section
  34. (). . WHO SAGE values framework for the allocation and prioritization of COVID-19 vaccination, 14 September 2020. World Health Organization.. Accessed 3 December, 2021. Available from: https://apps.who.int/iris/handle/10665/334299
  35. (). . Preporuke Stručnog savjetodavnog tijela za imunizaciju o prioritetnim skupinama za cijepljenje protiv COVID-19. Institute for Public Health of Federation of Bosnia and Herzegovina.. Accessed 5 December, 2021. Available from: https://www.zzjzfbih.ba/wp-content/uploads/2021/04/Preporuke-Stru∖%C4∖%8Dnog-savjetodavnog-tijela-za-imunizaciju-o-prioritetnim-skupinama-za-cijepljenje-protiv-COVID.pdf
  36. (). . WHO Coronavirus (COVID-19) Dashboard. World Health Organization.. Accessed 5 December, 2021. Available from: https://covid19.who.int/
  37. (). . Vakcinacija protiv COVID-19 u Federaciji Bosne i Hercegovine. Institute for Public Health Federation of Bosnia and Herzegovina.. Accessed 7 December, 2021. Available from: https://www.zzjzfbih.ba/wp-content/uploads/2021/12/Izvje∖%C5∖%A1taj-o-provedenoj-vakcinaciji-protiv-COVID-19-u-Federaciji-BiH-49.-sedmica.pdf
  38. , , , , , (). Perceptions of the COVID-19 vaccine among patients with cancer: a single-institution survey.. Future Oncol. https://doi.org/10.2217/fon-2021-0265
  39. , , , , , (). Acceptance of SARS-CoV-2 vaccination among French patients with cancer: a cross-sectional survey.. Ann Oncol. https://doi.org/10.1016/j.annonc.2021.01.066
  40. , , , , , (). COVID-19 vaccination: the VOICE for patients with cancer.. Nat Med. https://doi.org/10.1038/s41591-021-01240-w
  41. , , , , , (). COVID-19 vaccines and cancer patients: acceptance, attitudes and safety.. J BUON.
  42. (). . Informacije o cjepivu. Institute for Public Health Federation of Bosnia and Herzegovina.. Accessed 19 January, 2022. Available from: https://www.zzjzfbih.ba/informacije-o-cjepivu/
  43. (). . WHO Dashboard.. Accessed 20 January, 2022. Available from: https://covid19.who.int/region/euro/country/ba
  44. (). . Vakcinacija protiv COVID-19 u Federaciji Bosne i Hercegovine. Institute for Public Health Federation of Bosnia and Herzegovina.. Accessed 23 January, 2022. Available from: https://www.zzjzfbih.ba/wp-content/uploads/2022/01/Izvje∖%C5∖%A1taj-o-provedenoj-vakcinaciji-protiv-COVID-19-u-Federaciji-BiH-2.-sedmica.pdf
  45. , , , (). Acceptance of COVID-19 vaccination and its associated factors among cancer patients attending the Oncology Clinic of University Clinical Hospital, Mostar, Bosnia and Herzegovina: a cross-sectional study.. Med Sci Monit. Published 2021 Nov 13.https://doi.org/10.12659/MSM.932788
  46. , , , , , (). 1598P acceptance of SARS-CoV-2 vaccination among patients with cancer undergoing immunosuppressive therapy: Portuguese study.. Ann Oncol. https://doi.org/10.1016/j.annonc.2021.08.1591
  47. , , , , , (). The first report on coronavirus disease 2019 (COVID-19) vaccine refusal by patients with solid cancer in Italy: early data from a single-institute survey.. Eur J Cancer. https://doi.org/10.1016/j.ejca.2021.05.006
  48. , , , (). Report on vaccination in Canton Sarajevo in the period of March 08th 2021 to January 16th 2022.. Institute for Public Health of Canton Sarajevo.. Accessed 20 January, 2022. Available from: https://zzjzks.ba/wp-content/uploads/2022/01/BILTEN-VAKCINACIJE-02-u-22.pdf
  49. , , , , , (). COVID-19 vaccine hesitancy and acceptance among individuals with cancer, autoimmune diseases, or other serious comorbid conditions: cross-sectional, Internet-based survey.. JMIR Public Health Surveill. Published 2022 Jan 5https://doi.org/10.2196/29872
  50. , , , , , (). COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials [published correction appears in Nat Rev Clin Oncol. 2021 Mar 23;:].. Nat Rev Clin Oncol. https://doi.org/10.1038/s41571-021-00487-z
  51. , , (). COVID-19 vaccines in cancer patients. seropositivity and safety. Systematic review and meta-analysis.. Vaccines (Basel). Published 2021 Sep 20https://doi.org/10.3390/vaccines9091048
  52. , , , , , (). Effectiveness of SARS-CoV-2 mRNA vaccines for preventing COVID-19 hospitalizations in the United States [published online ahead of print, 2021 Aug 6].. Clin Infect Dis. https://doi.org/10.1093/cid/ciab687
  53. , , , , , (). Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data [published correction appears in Lancet. 2021 Jul 17;398(10296):212].. Lancet. https://doi.org/10.1016/S0140-6736(21)00947-8

A

SUPPLEMENTAL DATA

Questionnaire S1

PLEASE ANSWER THE FOLLOWING QUESTIONS:

  1. Patient initials

  2. Age of patient (years)

  3. Gender M F

  4. Are you currently receiving oncology therapy? YES NO

  5. Have you had COVID-19 before vaccination? YES NO

  6. Vaccination status a) Vaccinated – III doses b) Vaccinated – II doses c) Vaccinated – I dose d) Unvaccinated

  7. Date of the administration of the first dose of vaccine?

  8. Type of vaccine: a) BNT162b2 (Pfizer/BioNtech) b) ChAdOx1 nCoV-19 (Oxford/AstraZeneca)

    c) SinoPharm (BBIBO) d) CoronaVac (SinoVac)

  9. Side effects of vaccine: a) without any side effects b) local pain c) fever

    d) muscle pain e) bone pain f) fatigue g) nausea and vomiting

    h) other symptoms (please describe)

  10. Have you had COVID-19 after vaccination? YES NO

  11. (If answer is YES please specify exact date of positive PCR SARS-CoV-2 test )

  12. Have you been in the hospital due to COVID-19 infection after vaccination against SARS-CoV-2?

    YES NO

  13. Whether your oncology therapy has been delayed due to the side effects of the vaccine against SARS-CoV-2?

    YES NO

  14. Canton of living? a) Sarajevo b) SBK c) USK d) HNK e) BPK f) ZDK g) ZHK

TO BE COMPLETED BY A DOCTOR WHO PERFORMS AN EXAMINATION

  1. Patient diagnosis

  2. Metastatic disease? YES NO

  3. Setting of therapy A) Adjuvant B) Neoadjuvant C) Metastatic milieu

  4. Modality of therapy A) Chemotherapy B) Target therapy C) Hormonal therapy

    D) Immunotherapy E) Radiotherapy