Olfactory and taste disorders in COVID-19: a cross-sectional study in primary health care

SUMMARY OBJECTIVE: The objective of this study was to describe the occurrence of self-reported olfactory and taste disorders in non-hospitalized Brazilian adults who presented severe acute respiratory syndrome-related coronavirus 2 infection symptoms and attended primary health care. METHODS: This cross-sectional study was based on a routine standardized diagnostic screening questionnaire applied in a Brazilian primary care facility. The olfactory and taste disorder occurrence was compared between severe acute respiratory syndrome-related coronavirus 2-positive and severe acute respiratory syndrome-related coronavirus 2-negative cases and described by age and sex. RESULTS: Severe acute respiratory syndrome-related coronavirus 2-positive patients had a higher proportion of self-reported olfactory and taste disorders, as compared with severe acute respiratory syndrome-negative (50.7%, vs. 20.6%, p<0.0001). Of all individuals with self-reported olfactory and taste disorder cases, 69% presented both olfactory and taste impairments, 13% olfactory only, and 17% taste only. In severe acute respiratory syndrome-related coronavirus 2-positive cases, the frequency of olfactory and taste disorders was significantly higher among females as compared with males (71% vs. 34%). Additionally, people with olfactory and taste disorders were significantly younger in the severe acute respiratory syndrome-related coronavirus 2-positive group. CONCLUSION: Self-reported olfactory and taste disorders are highly common among non-hospitalized severe acute respiratory syndrome-related coronavirus 2-positive Brazilian people who attended the Family Health Care Unit. The co-occurrence of both self-reported olfactory and taste disorders was more frequent than self-reported olfactory or taste disorders alone.


INTRODUCTION
Early diagnosis of viral infection caused by SARS-CoV-2 is essential for the management of associated illness, referred to as COVID-19 1 .The clinical manifestation of this disease varies broadly from mild, flu-like conditions to life-threatening acute respiratory syndrome.Thus, the understanding of the predictive value of symptoms caused by SARS-CoV-2 infection is important for timely diagnosis and effective health care.
Brazil was among the countries that were most affected by the COVID-19 pandemic.In 2020-2021, the country registered one of the highest numbers of cases and deaths in the world 12 .The limited access to virus testing during this period led to national health care systems relying on the isolation of mild cases who presented flu-like manifestations, including olfactory and taste symptoms.Nevertheless, less is known about the prevalence of OTDs among COVID-19 patients during the pandemic in Brazil regarding its regional differences, seroprevalence, health care settings, and other characteristics.Furthermore, only a few studies reported non-hospitalized OTD cases among COVID-19 patients who were enrolled via telemedicine 13 or by online surveys 14 .In Brazil, primary health care as a part of the universal public Health Care System (Sistema Único de Saúde (SUS)) plays a key role in the implementation of certain policies for improving population health and promotion of health equity.While research supports Olfactory and taste disorders in COVID-19 the practical issues related to community health and its demands, it can contribute to the development of certain primary care preventive policies toward disease's consequences or future outbreaks 15 .
Therefore, this study aimed to investigate the occurrence of OTDs among patients presenting with COVID-19 in a Brazilian primary care facility in the period between March and December 2021.We compare the frequency of OTDs between confirmed SARS-CoV-2-positive and -negative cases and describe the occurrence of OTDs by age and gender.

Study design and settings
This is a cross-sectional study that used a standardized diagnostic questionnaire.The study was conducted in a Family Health Care Unit (Unidade de Saúde da Família -USF), in Joao Pessoa city city of Paraiba state, Brazil.
We initially included all adult people, ≥18 years old, who presented in a study setting with symptoms of acute respiratory infection (ARI) in the period between March 1, 2021, and December 31, 2021.During this period of pandemic, any individual with ARI symptoms was considered a suspect of SARS-CoV-2 infection 16 .Figure 1 presents a flowchart of selection and inclusion into the analysis.
All patients suspected of COVID-19 and who were presented at the Family Health Care Unit routinely received a standardized diagnostic questionnaire.The diagnostic questionnaire was part of a routine diagnostic procedure conducted by the outpatient clinic research team at the time of pandemic (2020-2021).The questionnaire asked respondents about the presence of active symptoms, including self-assessment of the patients' current smell and taste function.Demographic data (e.g., age and sex), date of onset, list of the preexisting conditions, and date of SARS-CoV-2 test if performed were collected.
For the analysis, 763 patients who had an RT-PCR test for SARS-CoV-2 infection were included.
We estimated and compared the frequency of self-reported OTDs among SARS-CoV-2-positive and SARS-CoV-2-negative patients, overall and by age and sex.OTDs were grouped as having reported: (i) olfactory, defined as reduction/change or loss of smell (hyposmia/anosmia), (ii) taste (hypogeusia/ageusia), defined as reduction or loss of taste, and (iii) both OTDs.

Statistical methods
Descriptive analyses were performed for continuous and categorical variables.The sample was described by study groups, i.e., SARS-CoV-2-positive and SARS-CoV-2-negative. Patients' demographic characteristics and frequency of OTDs were compared using the chi-square test and independent-samples t-test.

RESULTS
The characteristics of 763 participants included in the study groups are presented in Table 1.From this sample, 300 individuals tested positive for SARS-CoV-2, and 463 tested negative.The mean age was 41.6 (range 18-89) years in the SARS-CoV-2-positive group and 37.9 (range 18-80) years in the negative group (p<0.0001).We observed a higher proportion (56.3%) of men in the SARS-CoV-2-positive group as compared with the negative group (46.7%) (p<0.0001).
The overall frequency of OTDs in SARS-CoV-2-positive participants was higher in females (71.8%) as compared with males (34.3%) (Table 2).In contrast, there was no difference in the occurrence of OTDs by sex in the SARS-CoV-2-negative group.People with OTDs were significantly younger in the SARS-CoV-2-positive group.However, in the SARS-CoV-2negative group, age was not related to OTDs.

DISCUSSION
The occurrence of OTDs in COVID-19 patients, isolated or combined, varies dramatically across populations [8][9][10] .However, the knowledge of OTD occurrence among COVID-19 patients in Brazil regarding its regional differences and characteristics of patients who attended on the ambulatory level during the pandemic is still limited, especially in the family health care units.Our results support previous findings that olfactory and gustatory dysfunctions are both prevalent in patients with mild COVID-19 infection and that they typically present as a combined disorder 8,9,17 .The underlying mechanism of COVID-related OTDs remains a topic of investigation: the contribution of local inflammation caused by the virus and its to olfaction epithelium via the angiotensin-converting enzyme-2 (ACE-2) 18 , central olfaction pathway, interconnection of retro-nasal olfaction to taste perception, and direct damage of taste function caused by the presence of virus 9 are some of the most cited evidence.
Regarding sex distribution, the higher occurrence of olfactory and taste symptoms among females was reported previously 8,19 , yet the potential sex differences in the development of symptoms remain unclear 20 .
Olfactory and taste impairments were found to be highly common among adults with positive SARS-CoV-2 infection and they are generally younger than those who tested negative.Data based on Table 1.Characteristics of patients and frequency of olfactory and taste disorders on initial presentation at a primary care clinic, by the severe acute respiratory syndrome-related coronavirus 2 test status.

Figure 1 .
Figure 1.Flowchart of study sample selection.

Table 2 .
Frequency of olfactory and taste disorders by sex and age among severe acute respiratory syndrome-related coronavirus 2-positive and -negative patients.