COVID-19 incidence, severity, medication use, and vaccination among dentists: survey during the second wave in Brazil

Abstract Objective This cross-sectional study with dentists in Brazil assessed the COVID-19 incidence and severity, its vaccination status, and the level of confidence in vaccines in May 2021 (COVID-19 second wave). The medications used to prevent or treat COVID-19, including controversial substances (vitamin D, ivermectin, zinc, and chloroquine), were analyzed. Methodology Dentists were recruited by email and responded to a pretested questionnaire until May 31, 2021. Bivariate and multivariate regression analyses were performed (α=0.05). Prevalence ratios were calculated for the association between professional characteristics and two outcomes: SARS-CoV-2 infection and use of controversial substances. Results In total, 1,907 responses were received (return rate of 21.2%). One third of dentists reported intermediate levels of confidence in the safety and efficacy of COVID-19 vaccines, but 96% had received at least one vaccine dose, mainly CoronaVac. The effect of the pandemic on dental practice was classified as lower/much lower, in comparison with the first wave, by 46% of participants. Moreover, 27% of dentists had already tested positive for SARS-CoV-2 and about 50% had relatives or friends who had been hospitalized or died from COVID-19. At least one medication was used by 59% of participants and 43% used two or more substances. Vitamin D (41%), ivermectin (35%), and zinc (29%) were the most frequent substances. More experienced dentists (≥21 years of professional experience) were 42% more likely to use controversial substances than less experienced dentists. The prevalence of use of controversial substances was 30% higher among dentists with residency or advanced training, such as postgraduate degrees, in comparison with participants holding MSc or PhD degrees. Participants with low confidence in vaccines were 2.1 times more likely to use controversial substances than participants with a very high confidence. Conclusion The results of this study show the high severity of the COVID-19 pandemic in Brazil and raised questions about the use of scientific evidence by dentists in their decision to use controversial substances.


Introduction
The COVID-19 pandemic imposed significant challenges to dentistry worldwide. [1][2][3] Dental practice during the pandemic was associated with negative feelings among dentists, who presented high anxiety levels and fear of exposure to SARS-CoV-2 and infection at work. [3][4][5] A study during the first wave in Brazil showed that regional COVID-19 incidence and mortality rates were associated with fear of SARS-CoV-2 infection in dental offices. 3 Since the beginning of the pandemic, the Brazilian government has been criticized for being hostile to scientific evidence and unable to stop the spread of SARS-CoV-2. 6,7 Until June 2022, COVID-19 caused more than 666,000 deaths in Brazil, which is one of the highest global mortality rates (about 313 deaths per 100,000 inhabitants). 8 Amid an epidemiological crisis, a topic that has received great attention worldwide is the use of ineffective or controversial substances to prevent or treat  This issue was the subject of investigational hearings in the Brazilian Senate, including the off-label use of hydroxychloroquine and ivermectin, among others. A recent article showed that a small set of poorly designed studies on medications played a significant role in misinformation during the COVID-19 first wave in Brazil, 13 when vaccines were still not available. In this turbulent scenario of uncertainty about the future of the pandemic combined with fear and high risk of exposure to SARS-CoV-2 in dental offices, dentists could be inclined to selfmedicate or use substances without proven efficacy against COVID-19. At the same time, hesitation about accepting vaccination has been an issue worldwide 14,15 and the level of confidence in COVID-19 vaccines could be associated with the use of unproved medications.
A recent study performed in Italy showed that 18% of participating dentists were hesitant about COVID-19 vaccines 16 whereas another study showed that the willingness to receive a COVID-19 vaccine was higher in South America than in the USA and Russia. 15 This study aimed to assess the COVID-19 incidence and severity among dentists in Brazil, as well as the use of medications to prevent or treat COVID- 19 first wave. 3 The study protocol was approved by the institutional review board (Protocol No. 4.015.536) and all research methods were in accordance with the Declaration of Helsinki. This study mainly aimed to address the effect of COVID-19 on dental practice and its associated aspects, including COVID-19 incidence, severity, medication use, and vaccination among dentists. A questionnaire which was developed and pretested in previous studies was used. 3 in three discrete rounds of revision.
The questionnaire was created on SurveyMonkey (Momentive Inc., San Mateo, CA, USA). Its first section presented the title and objective of the study and informed that the invitation was extended only to dentists. This section provided the informed consent form, which explained that the participation was voluntary and unpaid and showed the potential risks and benefits of the study. Moreover, it assured that all responses would be anonymous and confidential.
Multiple participations from a same respondent were not allowed by the surveying system, which also protected the questionnaire from unauthorized access. Each question was presented to participants only after they responded to the previous question, showing that there were no discrete screens. The and COVID-19 vaccination, prevalence, severity, and medication (n=6). The items were not randomized and no adaptive questioning methods were used. All responses could be revised using back buttons at any time before submitting the completed form. In order to reduce bias related to response errors (units), the options "I'd rather not say," "I don't know how to answer it," and "Does not apply to me" were available in all close-ended questions.
Sample selection, participant recruitment, and survey administration A total of 24,392 registered dentists were invited to participate by an email sent via SurveyMonkey (convenience sampling). The list was provided by the Brazilian Ministry of Health in 2020 and did not include all dentists registered in Brazil, but professionals from all Brazilian states working in public and/or private dental networks. This list was used as it was receivedno selection was carried out. It also included dentists who participated in the first study in May 2020. 3 In previous studies, these sources promoted sample variability and corresponded to the general population of registered dentists in Brazil. 3,17 The email was a brief invitation with the study objective, the average response time (5 min), and the notification of the university conducting the study. The questionnaire was tested for its possibility to be well read on different computers, tablets, and mobile phones. The first emails were sent on May 13, 2021. Reminder emails were sent seven and 11 days after to reduce nonresponse bias. Considering a number of about 350,000 dentists in Brazil, 1,530 responses would be necessary to ensure a 95% confidence interval and 2.5% margin of error. Responses were collected until May 31, 2021.

Data analysis
To reduce non-response error, the partial completion of questionnaires was not allowed (completion proportion=100%). In some questions, responses were restricted to a specific population-only dentists assisting patients when the study was performed, for example. The responses "I'd rather not say," "I don't know how to answer it," and "Does not apply to me" were considered missing data. No strategies for weighting items, propensity scores, or sensitivity analysis were used. In analyses using data from the question on medication use, vitamin D, ivermectin, zinc, and chloroquine/hydroxychloroquine were considered controversial substances. Descriptive statistics were used to identify variable frequencies and distributions with respective 95% confidence intervals (CI). Bivariate and multivariate Poisson regression analyses were performed and prevalence ratios (PR) were estimate for the association between professional characteristics and two COVID-19-

Results
Of the 24,392 emails sent to dentists, 1,347 bounced (loss of 5.5%) and 9,010 were opened (unique visitors), as registered by the surveying system (view proportion=36.9%). A return rate of 21.2% was calculated from the opened emails and 1,907 valid responses were received from all 26 Brazilian states and the Federal District.

Sample characteristics
The length of work experience and levels of postgraduate education varied among participants (

COVID-19 incidence, severity, and medication use
In total, 27% of dentists had already tested positive for SARS-CoV-2 by May 2021 and most of them were asymptomatic or had mild symptoms (88%).
Moreover, 49.8% had relatives or friends who had been hospitalized or died from COVID-19. Regarding medication use, 58.9% of participants used at least one of the seven controversial substances listed in Table 1 to prevent or treat COVID-19. Vitamin D was the most common (41%), followed by ivermectin (35%), zinc (29%), and azithromycin (27%). The use of chloroquine or hydroxychloroquine was not prevalent (4%). A total of 74.7% of participants who tested positive for SARS-CoV-2 used at least one of Continued from previous page CI: confidence interval. *Varies from total n due to missing data in different questions. **More than one answer was possible. ***Prescription medication.
J Appl Oral Sci.
2022;30:e20220016 6/11 these substances whereas the frequency of this use among dentists who tested negative was 52.4%. In total, 42.7% of dentists used two or more substances.

The most frequent combination was vitamin D and zinc
combined or not with ivermectin. were 26% more likely to be infected than professionals with MSc or PhD degrees. The level of confidence in COVID-19 vaccines was not associated with a history of infection. Participants who reported no fear of being infected at work were 48% more likely to be infected with COVID-19 than those who reported high fear.

Discussion
This study showed a high prevalence of COVID-19 among Brazilian dental professionals (27%) and a frequent occurrence of hospitalization and death from this disease among their relatives or friends during the second wave. Moreover, 59% of participants used one or more substances to prevent or treat COVID-19, including vitamin D, zinc, and ivermectin, which have limited evidence to support their clinical use against

COVID-19.
Studies conducted in several countries showed varying prevalence of COVID-19 among dentists: 1.1% in Brazil (May 2020), 3 9.1% in Belgium (July-Sept. 2020), 19    Dentists who reported no fear of being infected by the disease were more likely to be infected by  which raises questions about the influence of the more or less strict preventive measures adopted by them. Moreover, the high risk of SARS-CoV-2 infection in dental offices, along with the frequent occurrence of COVID-19 among dentists' relatives and friends, could be associated with high levels of psychosis and anxiety, 2,5  courses. We also found that more experienced dentists were more likely to use controversial substances than less experienced dentists, which could be associated with the higher risk of older adults of having severe cases of COVID-19. Participants with low confidence in COVID-19 vaccines were 2.1 times more likely to use controversial substances than participants with a high confidence in these vaccines. To the best of our knowledge, this is the first study to show this association.
Among many factors that may negatively interfere with evidence-based health practice in the pandemic context, there is the large number of low-quality studies reporting conflicting results for the treatment of COVID-19. This is associated with difficulties of implementing the best available evidence due to lack of time, knowledge, or skills to critically evaluate the literature. This means that controversial substances could be considered either effective or ineffective depending on the article selected and how it was interpreted. Regarding vitamin D, for instance, a systematic review suggested that its supplementation was associated with reduced intensive care unit (ICU) admission, the need for mechanical ventilation, and mortality. 32 Another systematic review showed that vitamin D did not reduce the risk of these clinical outcomes. 33 A meta-analysis showed that zinc reduced COVID-19 death rates 34 whereas a different metaanalysis showed that there is no evidence to support zinc supplementation in patients with  Karale et al. 36 (2021) stated that the treatment of COVID-19 with ivermectin may reduce the need for hospitalization, but a living network meta-analysis showed that it was highly uncertain whether ivermectin used as a preventive measure would reduce the risk of SARS-CoV-2 infection. 37 Another frequent problem is the presence of methodological issues across the primary studies. In all aforementioned systematic reviews, the authors highlighted that more randomized controlled trials with larger sample sizes and less risk of bias, imprecision, and/or heterogeneity were necessary. It seems that the topic of controversial substances to prevent or treat COVID-19 will still attract attention in the following years, as definitive conclusions will hardly be accepted universally. In the meantime, dentists are encouraged to rely on evidence with low risk of bias and good methodological quality or evidence-based guidelines, when available.
A positive finding of this study was the high rate of COVID-19 vaccination. In Brazil, health professionals were priorities for vaccination, followed by older adults, thus, dentists were vaccinated in the first stages of the immunization program with the first vaccines available in Brazil. This explains the high frequency of dentists who received CoronaVac, which was the first vaccine authorized for emergency use by the Brazilian Health Regulatory Agency in January 2021. have been available for use in Brazil and dentists throughout the country are eligible to take booster shots. Further studies could evaluate the acceptance of dental professionals to the new phases of  vaccination and the maintenance of other preventive measures to address whether the so-called "pandemic fatigue" may decrease their adherence to individual and collective risk reduction strategies. 40 This study had limitations and care should be taken when extrapolating its results. Participants were free either to accept or not the invitation to participate in the study, which may have led to self-selection bias, increasing the chances of dentists who were more concerned about the pandemic and perhaps more willing to use medications to participate. Moreover, we did not collect data on doses or frequency of use of substances, which may have varied greatly among participants. Self-reported SARS-CoV-2 infection was another limitation, as the diagnosis could be influenced by variations in quality and accuracy across molecular and serologic tests. Moreover, self-reported medication use may have been influenced by social-desirability bias, but the questionnaire was anonymous and thus this influence could be low. A strength of this study was that a large sample of dentists was recruited in a period when Brazil was struggling to deal with the pandemic. Further studies could address the use of controversial substances and the socioeconomical aspects involved.

Conclusion
This study with dentists during the COVID-19 second wave in Brazil showed a high incidence of this disease among dentists, a frequent occurrence of hospitalization and death from COVID-19 among their relatives or friends, and a very frequent use of controversial substances to prevent or treat COVID-19.