Introduction
Throughout human history, infectious diseases have been the leading cause of death, especially during pandemics (1). As expected, the COVID-19 pandemic had a major impact on humanity. Vaccination has been shown to reduce morbidity and mortality, particularly among vulnerable populations; cancer patients are one of the most vulnerable groups both due to the disease itself and more frequent hospital presentations. They also have an increased risk of developing severe complications and even die due to the infection (2).
Cancer patients have a higher risk of mortality as compared to non-cancer patients. Consequently, mortality rates were high among patients with active cancer who developed COVID-19 during the first wave of the pandemic. In the United Kingdom, mortality in hospitalized cancer patients with COVID-19 was 40.5% vs. 28.5% for non-cancer patients (HR 1.62; p <0.001) (3), while in the German LEOSS registry, COVID-19-related mortality in cancer patients was 22.5% vs. 14% for non-cancer patients (p <0.001) (4).
Vaccination campaigns were launched less than a year after the pandemic outbreak. In studies, the vaccine demonstrated more than 90% efficacy in the general population (5). Cancer patients were shown to have a variable, higher risk of developing COVID-19, and were considered a target population for vaccination (6). Therefore, COVID-19 prevention is crucial for cancer patients, with vaccination being the most effective method to achieve this goal.
Vaccines have always been surrounded by controversy and polarized the wide public into two opposing camps: those in favor of vaccination and those against it. The most common reasons for vaccination refusal include negative opinions about the need of vaccination, fear of side effects and fear of needles (7,8). Although the infection caused by SARS-CoV-2 spread around the world, in Romania a large part of the population denied the very existence of the disease, the need of vaccination and the use of prevention methods such as wearing a mask or social distancing (9). Immediately after the beginning of the pandemic, major research centers focused on the discovery of a vaccine. The relatively brief time interval needed for the development of vaccines raised suspicions among the general population, while doubts about the long-term side effects, effectiveness and safety of the vaccine were the main concerns of cancer patients (10). Furthermore, the use of non-scientific sources of information led to misconceptions about vaccination (11).
The main purpose of our study was to assess the acceptance of the COVID-19 vaccine among cancer patients undergoing immunosuppressive therapy from 12 oncology centers in Western and Northwestern Romania by means of administration of an adapted questionnaire and to understand which factors are associated with COVID-19 vaccine acceptance.
Since according to GLOBOCAN 2020(12), there were approximately 260,000 cancer patients in Romania, we calculated a statistically representative sample for this population of 384 respondents by sample size determination test. Normality analyses were performed and the results and statistical tests were adjusted accordingly. This means at least 384 measurements/surveys were needed to have a confidence level of 95% that the real value is within +/- 5% of the measured/surveyed value.
To the best of our knowledge, no study has been performed to date to investigate the perception regarding COVID-19 vaccination among cancer patients considering their reason for acceptance, educational level and source of information. In our opinion, such an assessment is of extreme importance in this specific group of patients, therefore we conducted this pilot study in Romania.
Discussion
COVID-19 vaccination hesitancy rates vary in the general population worldwide (13). This attitude towards COVID-19 vaccines among cancer patients was reported in other papers as well (14,15,16). According to the findings of this study, the Romanian cancer patients also need more comprehensible information regarding this issue.
In Romania, the first dose of COVID-19 vaccine was administered on December 27, 2020 and all eligible individuals were encouraged to get vaccinated, cancer patients in particular. The European Society for Medical Oncology (ESMO) issued a statement recommending vaccination in cancer patients, monitoring of side effects and specific patient education. The European Medicines Agency (EMA)-approved RNA vaccines are safe and have no contraindications in patients with active cancer or in immunocompromised patients (17).
The study we conducted to investigate the attitudes of cancer patients regarding the COVID-19 vaccination, one year from the start of the vaccination campaign, was based on 932 analyzed patients: 58.05% were vaccinated and 41.95% not vaccinated. These results are comparable to data from the general population of Romania, where the rate of vaccination amounts to only 41.44% of the total population (18). Of the total number of patients enrolled in the study, 31.54% had a history of COVID-19 infection and 55.44% of these patients wanted to receive the vaccine. This finding is comparable to the data from a study published in Vaccines in 2022 regarding the general population of Romania, where 33% of participants had a history of SARS-CoV-2 infection with different degrees of severity (9).
As far as the influenza vaccination is concerned, 41.20% of the total number of patients analyzed in our study received such a vaccine, a higher rate as compared to the findings of another study conducted in the Romanian cancer population published in ESMO Open in 2021, before the start of SARS-CoV-2 vaccination campaign, where only 15.9% of patients had been vaccinated against influenza the previous year (19). Higher rates of influenza vaccination may be a useful by-product of the COVID-19 vaccination campaigns.
In Romania, 4 types of COVID-19 vaccine were available, all approved for use in cancer patients as well. Vaccinated cancer patients preferred Pfizer-BioNTech (72%), followed by Johnson & Johnson (14%). This finding is consistent with the general population, with a significantly higher number of Pfizer vaccines administered daily as compared to other vaccines (18). The drivers for this preference for Pfizer may be that it is EMA approved and shown to be 95% safe and effective in people 16 years of age and older (20).
To get a better understanding of attitudes towards vaccination in our study, the vaccinated patients were asked about how they made their decision while non-vaccinated patients about their arguments against vaccination. The reasons in vaccinated patients were the following: 63.96% observed the physicians' recommendations, 56.56% reported fear of the side effects caused by the SARS-CoV-2 infection, 53.05% wanted to protect their loved ones and 46.58% wanted their life to return to normal as soon as possible. These rates mirror the findings from the study published in Vaccines in 2022, conducted on the general population of Romania which assessed how much Romanians trusted physicians and the Romanian medical system and showed that 65% had confidence in the recommendations made by Romanian physicians, but only 26% trusted the Romanian health system (7). This low percentage of confidence results from problems encountered by the health system in recent years such as lack of medicines, medical equipment and modern facilities, as well as deadly hospital fires (21,22).
We compared the reasons provided by non-vaccinated patients and 67.52% reported fear of vaccine-induced side effects, 28.13% did not consider the vaccine necessary and 20.46% did not trust the current scientific data about it. We asked them if they intended to get vaccinated and 50.38% promptly answered they were unwilling to get vaccinated, 20.97% considered getting vaccinated on completion of their oncological treatment, 18.93% expected more evidence of vaccine efficacy and 9.46% were willing to get vaccinated as soon as possible. This is how our results compare to the findings in French [53.7% reported the desire to get vaccinated, 29.7% considered they were not ready and 16.6% refused vaccination (14)], Portuguese [84% intended to get vaccinated, 16% had not yet decided or were reluctant (23)] and Serbian cancer patients, respectively [10% certainly rejected vaccination (24)].
The main reason the population continues to reject vaccination is the fear of side effects. Recent studies have begun to systematically examine the frequency and types of side effects (25,26). The authors highlight that the adverse events reported (cerebral thrombosis, Guillain-Barré syndrome, myocarditis, pericarditis) are not COVID-19 vaccination-specific side effects as compared with their background rate in the general population.
In our study, the most common side effect was pain at the injection site after the first and the second dose (for the Pfizer vaccine, 27.04 and 4.85%, respectively). Other side effects include fever, chills, headache, diarrhea, allergies, however all with significantly lower rates (around 1.28-2.81% for Pfizer). For other side effects, patients mentioned chest pain, dizziness, finger numbness, but rates were low (0.51%). We have comparative data from the study conducted in cancer patients in London by Monin et al reporting a lower rate of side effects in cancer patients compared to vaccinated healthy patients (46% vs. 62% and 29% vs. 69%) after the first and the second dose, respectively (27). A study published in The Breast which included breast and gynecologic cancer patients receiving active treatment in Germany found that the COVID-19 vaccines were well tolerated while undergoing systemic cancer therapy with no additional side effects reported as compared to the general population (28). The data provide solid evidence of the effectiveness of vaccinating patients while receiving active treatment.
In our study, we found a statistically significant association between the vaccination rate and both the place of residence and the level of education, as independent factors. These findings are comparable to those of the study published in Supportive Care in Cancer regarding patients in Portugal which showed that lower levels of education and rural residence are predictive factors of COVID-19 vaccination hesitancy (23).
Multiple sources of information regarding the COVID-19 infection and vaccines are used. As shown in Figs. 5 and 6, patients opted for different sources of information, depending on their level of education and area of residence. It is a known fact that mass-media often promote misinformation, channeling the opinions of different experts instead of official recommendations, which leads to increased uncertainty, anxiety and confusion in the general population and especially among cancer patients (29). The effects of ‘fake news’ were evident in the study conducted on the general population of Romania, where 47% of participants believed that a secret organization that controls the world wants to decrease the global population by means of vaccination (7,9). In February 2022 in Romania, only 44.62% of the total population of 19.29 million had received a COVID-19 vaccine (30).
Our study suggests that the information on vaccines needs to be tailored based on the patients' educational level. Also, public information campaigns designed on different levels of complexity may prove more efficient in Romania. Future research including a larger population with various subpopulations would provide further validation to our study. Also, this pilot study which highlights a correlation between the formal education level and the rate of vaccine acceptance gives a cue that public awareness-raising campaigns worldwide should be tailored to the patients' level of understanding.
The large number of cancer patients and the number of oncology centers included is the main strength of our study. The fact that it is the first study of this kind in Romania is the second. The first limitation of our study is the heterogeneity of participants and the lack of information on their medical background which made it impossible to demonstrate if the surveyed population is representative for the cancer patient population as a whole. Also, a better stratification of patients as well as an analysis of comorbidities would have helped to further clarify the patients' attitudes. Another limitation of our study is that the survey included non-standardized questions and that it was a multicenter study, leading to differences in terms of the health care providers-patient communication. However, to the best of our knowledge, there are no globally validated questionnaires to appropriately reflect our patients' characteristics and serve the objective of our study.
This study demonstrates that Romanian cancer patients are reluctant to receive the COVID-19 vaccines. In summary, their hesitancy is mainly influenced by the fear of side effects; mass-media (TV, radio) and social platforms play the main role as source of information among non-vaccinated patients, while for vaccinated patients the primary source of information is the recommendation by the oncologists or the general practitioners.
Although scientific evidence to support the efficacy and safety of vaccines exists, patients are prone to misinformation. The residence in rural areas and the lower level of education were identified as predictors of vaccination hesitancy.
Also, there is a need for specific vaccination-related education of the general population, especially in the rural areas, to improve the success of preventive measures and information campaigns implemented by health care authorities.