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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Oral Health</journal-id>
<journal-title-group>
<journal-title>Frontiers in Oral Health</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Oral Health</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">2673-4842</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/froh.2025.1633542</article-id>
<article-version article-version-type="Version of Record" vocab="NISO-RP-8-2008"/>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Research</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Xerostomia in survivors of severe COVID-19: findings from a Latin American cohort</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Escobar Villegas</surname><given-names>Paola Andrea</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name><surname>Cordoba-Melo</surname><given-names>Brayan Daniel</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
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<contrib contrib-type="author">
<name><surname>Arango-Ibanez</surname><given-names>Juan Pablo</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
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<contrib contrib-type="author">
<name><surname>Naranjo-Ramirez</surname><given-names>Maria Camila</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
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<contrib contrib-type="author">
<name><surname>Barbosa</surname><given-names>Mario Miguel</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author">
<name><surname>Casanova Rojas</surname><given-names>Andr&#x00E9;s Felipe</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author">
<name><surname>Mina S&#x00E1;nchez</surname><given-names>Andr&#x00E9;s Fernando</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="investigation" vocab-term-identifier="https://credit.niso.org/contributor-roles/investigation/">Investigation</role>
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<contrib contrib-type="author">
<name><surname>Herrera</surname><given-names>Cesar Jos&#x00E9;</given-names></name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1569984/overview" />
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<contrib contrib-type="author">
<name><surname>Quintana Da Silva</surname><given-names>Miguel &#x00C1;ngel</given-names></name>
<xref ref-type="aff" rid="aff5"><sup>5</sup></xref>
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<contrib contrib-type="author">
<name><surname>Buitrago Sandoval</surname><given-names>Andr&#x00E9;s Felipe</given-names></name>
<xref ref-type="aff" rid="aff6"><sup>6</sup></xref>
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<contrib contrib-type="author">
<name><surname>Coronel Gilio</surname><given-names>Mar&#x00ED;a Lorena</given-names></name>
<xref ref-type="aff" rid="aff7"><sup>7</sup></xref>
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<contrib contrib-type="author">
<name><surname>Chon Long</surname><given-names>Freddy Pow</given-names></name>
<xref ref-type="aff" rid="aff8"><sup>8</sup></xref>
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<contrib contrib-type="author">
<name><surname>C&#x00E1;rdenas Aldaz</surname><given-names>Liliana</given-names></name>
<xref ref-type="aff" rid="aff9"><sup>9</sup></xref>
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<contrib contrib-type="author" corresp="yes">
<name><surname>Gomez-Mesa</surname><given-names>Juan Esteban</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="aff" rid="aff10"><sup>10</sup></xref>
<xref ref-type="corresp" rid="cor1">&#x002A;</xref>
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<aff id="aff1"><label>1</label><institution>Colegio Odontol&#x00F3;gico, Instituci&#x00F3;n Universitaria Colegios de Colombia&#x2014;Unicoc</institution>, <city>Cali</city>, <country country="co">Colombia</country></aff>
<aff id="aff2"><label>2</label><institution>Centro de Investigaciones Cl&#x00ED;nicas, Fundaci&#x00F3;n Valle del Lili</institution>, <city>Cali</city>, <country country="co">Colombia</country></aff>
<aff id="aff3"><label>3</label><institution>Departamento de Cardiolog&#x00ED;a, Fundaci&#x00F3;n Valle del Lili</institution>, <city>Cali</city>, <country country="co">Colombia</country></aff>
<aff id="aff4"><label>4</label><institution>Departamento de Cardiolog&#x00ED;a, Centros de Diagn&#x00F3;stico y Medicina Avanzada y de Conferencias M&#x00E9;dicas y Telemedicina (CEDIMAT)</institution>, <city>Santo Domingo</city>, <country>Rep&#x00FA;blica Dominicana</country></aff>
<aff id="aff5"><label>5</label><institution>Departamento de Cardiolog&#x00ED;a, Instituto Cardiovascular Sanatorio MIGONE</institution>, <city>Asunci&#x00F3;n</city>, <country country="py">Paraguay</country></aff>
<aff id="aff6"><label>6</label><institution>Departamento de Cardiolog&#x00ED;a, Fundaci&#x00F3;n Santa Fe</institution>, <city>Bogot&#x00E1;</city>, <country country="co">Colombia</country></aff>
<aff id="aff7"><label>7</label><institution>Departamento de Cardiolog&#x00ED;a, Instituto de Cardiolog&#x00ED;a J. F. Cabral</institution>, <city>Corrientes</city>, <country country="ar">Argentina</country></aff>
<aff id="aff8"><label>8</label><institution>Departamento de Cardiolog&#x00ED;a, Hospital Luis Vernaza</institution>, <city>Guayaquil</city>, <country country="ec">Ecuador</country></aff>
<aff id="aff9"><label>9</label><institution>Departamento de Cardiolog&#x00ED;a, Hospital Eugenio Espejo</institution>, <city>Quito</city>, <country country="ec">Ecuador</country></aff>
<aff id="aff10"><label>10</label><institution>Facultad de Ciencias de la Salud, Universidad Icesi</institution>, <city>Cali</city>, <country country="co">Colombia</country></aff>
<author-notes>
<corresp id="cor1"><label>&#x002A;</label><bold>Correspondence:</bold> Juan Esteban Gomez-Mesa <email xlink:href="mailto:juan.gomez.me@fvl.org.co">juan.gomez.me@fvl.org.co</email></corresp>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2025-10-07"><day>07</day><month>10</month><year>2025</year></pub-date>
<pub-date publication-format="electronic" date-type="collection"><year>2025</year></pub-date>
<volume>6</volume><elocation-id>1633542</elocation-id>
<history>
<date date-type="received"><day>22</day><month>05</month><year>2025</year></date>
<date date-type="accepted"><day>22</day><month>09</month><year>2025</year></date>
</history>
<permissions>
<copyright-statement>&#x00A9; 2025 Escobar Villegas, Cordoba-Melo, Arango-Ibanez, Naranjo-Ramirez, Barbosa, Casanova Rojas, Mina S&#x00E1;nchez, Herrera, Quintana Da Silva, Buitrago Sandoval, Coronel Gilio, Chon Long, C&#x00E1;rdenas Aldaz and Gomez-Mesa.</copyright-statement>
<copyright-year>2025</copyright-year><copyright-holder>Escobar Villegas, Cordoba-Melo, Arango-Ibanez, Naranjo-Ramirez, Barbosa, Casanova Rojas, Mina S&#x00E1;nchez, Herrera, Quintana Da Silva, Buitrago Sandoval, Coronel Gilio, Chon Long, C&#x00E1;rdenas Aldaz and Gomez-Mesa</copyright-holder><license><ali:license_ref start_date="2025-10-07">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
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</permissions>
<abstract><sec><title>Objectives</title>
<p>SARS-CoV-2 primary affects the respiratory tract; however, evidence suggests the oral cavity can be involved in severe COVID-19 survivors. This study investigates factors associated with xerostomia in severe COVID-19 survivors from a Latin American cohort.</p>
</sec><sec><title>Materials and methods</title>
<p>A prospective multicenter study from the Latin American Registry of Cardiovascular Disease and COVID-19, analyzed data on 272 severe COVID-19 patients from 7 institutions in 5 countries (Colombia, Dominican Republic, Ecuador, Argentina, and Paraguay). Long-term follow-up assessed demographics characteristics, comorbidities, lifestyle, cardiovascular complications, and oral health. Logistic regression in R software identified factors associated with xerostomia.</p>
</sec><sec><title>Results</title>
<p>Xerostomia was reported in 20.6&#x0025; of patients. Among affected individuals, 53.6&#x0025; were female, while women represented 35.6&#x0025; of those without the condition. In the overall cohort, the most common comorbidities were overweight/obesity (57.0&#x0025;), hypertension (55.9&#x0025;), and dyslipidemia (32.0&#x0025;). Patients with xerostomia had higher rates of dyslipidemia (48.2&#x0025; vs. 27.8&#x0025;) and asthma/COPD (16.1&#x0025; vs. 4.2&#x0025;) compared to the group without xerostomia. In multivariable logistic regression, asthma/COPD (aOR: 5.14; 95&#x0025; CI: 1.76&#x2013;15.7), palpitations (aOR: 2.47; 95&#x0025; CI: 1.04&#x2013;5.94), and chest pain (aOR: 3.74; 95&#x0025; CI: 1.67&#x2013;8.43) were independently associated with xerostomia. Conversely, male sex was associated with lower odds of reporting xerostomia (aOR: 0.47; 95&#x0025; CI: 0.24&#x2013;0.89).</p>
</sec><sec><title>Conclusion</title>
<p>These findings underscore the need for clinicians to actively assess oral health symptoms such as xerostomia in post-COVID care, particularly in patients with cardiopulmonary comorbidities and persistent systemic symptoms.</p>
</sec>
</abstract>
<kwd-group>
<kwd>long COVID</kwd>
<kwd>xerostomia</kwd>
<kwd>COVID-19 sequelae</kwd>
<kwd>dry mouth</kwd>
<kwd>mouth dryness</kwd>
</kwd-group><funding-group>
<funding-statement>The author(s) declare that financial support was received for the research and/or publication of this article. This study was funded through a general research grant from Tecnoquimicas S.A to Centro de Investigaciones Cl&#x00ED;nicas at Fundaci&#x00F3;n Valle del Lili (TQ-2021-1756). The results and conclusions are those by the authors and do not necessarily represent the view of either institution.</funding-statement>
</funding-group>
<counts>
<fig-count count="2"/>
<table-count count="3"/><equation-count count="0"/><ref-count count="21"/><page-count count="8"/><word-count count="45784"/></counts><custom-meta-group><custom-meta><meta-name>section-at-acceptance</meta-name><meta-value>Cardiometabolic Health</meta-value></custom-meta></custom-meta-group>
</article-meta>
</front>
<body><sec id="s1" sec-type="intro"><label>1</label><title>Introduction</title>
<p>Xerostomia (dry mouth) is common and can substantially impair quality of life, causing difficulty swallowing, reduced taste, cough, and voice changes (<xref ref-type="bibr" rid="B1">1</xref>). In the general population, medication use is the leading cause: more than 400 prescription and over-the-counter drugs are associated with reduced salivary flow and xerostomia (e.g., antihypertensives, antidepressants, anticholinergics, diuretics, opioids, nonsteroidal anti-inflammatory drugs, antihistamines) (<xref ref-type="bibr" rid="B2">2</xref>&#x2013;<xref ref-type="bibr" rid="B5">5</xref>). Less commonly, xerostomia arises from systemic conditions such as Sj&#x00F6;gren&#x0027;s syndrome, connective tissue diseases, diabetes mellitus, chronic kidney disease, and autoimmune disorders, as well as infections like human immunodeficiency virus and cytomegalovirus (<xref ref-type="bibr" rid="B2">2</xref>, <xref ref-type="bibr" rid="B6">6</xref>).</p>
<p>While the primary manifestation of SARS-CoV-2 infection in humans is in the respiratory tract, it raises the question of whether this virus, like other infections, can affect the oral cavity. It has been demonstrated that salivary glands are a potential target for COVID-19 infection due to the documented expression of the ACE2/transmembrane serine protease 2 receptor in the epithelial cells of salivary glands (<xref ref-type="bibr" rid="B7">7</xref>, <xref ref-type="bibr" rid="B8">8</xref>). Emerging evidence suggests that the oral cavity is a potential target of COVID-19, with persistent alterations observed in a majority of survivors well beyond their clinical recovery. Individuals who have recovered from COVID-19 have reported various clinical conditions in the upper airway, including xerostomia, increased thirst, and persistent dry cough, which endure for an extended post-COVID period and can be defined as long COVID or post COVID-19 syndrome (<xref ref-type="bibr" rid="B9">9</xref>).</p>
<p>Evaluating long-term oral complications in COVID-19 patients is crucial due to the wide variability in prevalence depending on the study and methodology employed. A literature review included seven studies on xerostomia, involving a total of 654 COVID-19 survivors from Italy, Turkey, China, India, Israel, and Colombia. Reported prevalence ranged from 2&#x0025; to 40&#x0025; with follow-up of 28&#x2013;230 days; the review did not distinguish by hospitalization status or disease severity (<xref ref-type="bibr" rid="B10">10</xref>).</p>
<p>Further research is needed to clarify the long-term impact of SARS-CoV-2 infection on oral health, as current evidence is scarce and heterogeneous. Important gaps remain regarding the relative contribution of viral effects, systemic inflammation, neurological mechanisms, and treatments such as antibiotics to the development of xerostomia and other oral manifestations (<xref ref-type="bibr" rid="B11">11</xref>). Addressing these uncertainties requires studies that document the occurrence of xerostomia and explore its associations in well-defined patient populations.</p>
</sec>
<sec id="s2"><label>2</label><title>Objective</title>
<p>To describe the occurrence and associations of xerostomia in a cohort of Latin American survivors of severe COVID-19.</p>
</sec>
<sec id="s3" sec-type="methods"><label>3</label><title>Methods</title>
<sec id="s3a"><label>3.1</label><title>Study design and participants</title>
<p>A prospective cohort study was conducted using data from the CARDIO COVID 19&#x2013;20 Registry (Registro Latinoamericano de Enfermedad Cardiovascular y COVID-19) and its long-term extension, the CARDIO COVID 20&#x2013;21 registry. The CARDIO COVID 19&#x2013;20 registry was an observational, multicenter, ambispective, and hospital-based registry of patients with confirmed COVID-19 infection who required in-hospital treatment in Latin America, while the CARDIO COVID 20&#x2013;21 registry prospectively followed a subset of these patients after discharge<bold>.</bold> The CARDIO COVID 19&#x2013;20 registry enrolled patients over 18 years old hospitalized for more than 24&#x2005;h with confirmed SARS-CoV-2 infection v&#x00ED;a RT-PCR following World Health Organization (WHO) guidelines. The study was conducted across 44 hospitals in 14 Latin American countries, including Argentina, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Mexico, Panama, Paraguay, Peru, and Venezuela (<xref ref-type="bibr" rid="B12">12</xref>).</p>
<p>Between June 2020 and June 2021, a total of 3,260 patients were enrolled in the CARDIO COVID 19&#x2013;20 registry. Of these, 869 (26.7&#x0025;) died during hospitalization and 417 (12.8&#x0025;) were excluded because they did not fulfill severity criteria, leaving 1,974 (60.5&#x0025;) patients classified as severe COVID-19. This population served as the source for long-term follow-up in the CARDIO COVID 20&#x2013;21 registry.</p>
<p>The criteria for a severe COVID-19 episode were defined as having at least one of the following: high risk of venous thromboembolism (elevated D-dimer: 1219 patients, 61.8&#x0025;), the necessity for intensive care unit (ICU) admission (896 patients, 45.4&#x0025;), cardiovascular complications during hospitalization (such as arrhythmia, arterial or venous embolism, coronary events, and heart failure: 406 patients, 20.6&#x0025;), or myocardial injury (elevated troponin levels above the 99th percentile: 302 patients, 15.3&#x0025;).</p>
<p>At 30-day follow-up, 318 unreachable patients and 37 deaths left 1619 (49.7&#x0025;) severe COVID-19 patients for long-term follow-up. Only seven of 44 institutions (Colombia, Dominican Republic, Ecuador, Argentina, and Paraguay) joined the second registry (CARDIO COVID 20&#x2013;21), excluding 1105 patients. Of the remaining 514 patients, 242 were lost, leaving a final cohort of 272 patients.</p>
<p>Among the 272 severe COVID-19 patients included in the long-term follow-up, 39.3&#x0025; (107/272) met one severity criterion, 35.7&#x0025; (97/272) met two, 24.3&#x0025; (66/272) met three, and 0.7&#x0025; (2/272) met all four. Within these strata, xerostomia was present in 23.4&#x0025; (25/107), 20.6&#x0025; (20/97), 15.2&#x0025; (10/66), and 50.0&#x0025; (1/2), respectively.</p>
<p>Follow-up visits occurred at a median of 25 months post-discharge, in person (192 patients) or via telephone (80 patients). Under physician supervision, self-reported symptoms and medical histories and assessments for anxiety, depression, stress, quality of life, and cognitive impairment were collected. <xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref> summarizes the patient selection and exclusion process, providing the study&#x0027;s design and participant flow. Oral health symptoms were assessed using a standardized, physician-supervised, self-report questionnaire. For xerostomia, patients were directly asked: &#x201C;Have you experienced a persistent dry mouth or lack of saliva over the past month?&#x201D; The full set of questions and guidance for healthcare professionals is available in the <xref ref-type="sec" rid="s13">Supplementary Table S1</xref>.</p>
<fig id="F1" position="float"><label>Figure&#x00A0;1</label>
<caption><p>Patient selection flowchart.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="froh-06-1633542-g001.tif"><alt-text content-type="machine-generated">Patient selection flowchart study. Step 1: 3,260 patients from 44 institutions in 14 countries from the CARDIO COVID 19-20. Step 2: 1,974 patients. Step 3: 1,619 patients with 30-day follow-up; 318 not located, 37 deceased. Step 4: 514 patients. Step 5: 272 patients with 25-month follow-up; 242 not located. A total of 869 patients died and 417 did not meet severe criteria. CARDIO COVID 19-20 involved 7 institutions from 5 countries.</alt-text>
</graphic>
</fig>
<p>Both the CARDIO COVID 19&#x2013;20 and CARDIO COVID 20&#x2013;21 registries were coordinated by the Inter-American Council of Heart Failure and Pulmonary Hypertension (CIFACAH) of the Inter-American Society of Cardiology (IASC) with operational support from the Clinical Research Center at Fundaci&#x00F3;n Valle del Lili (FVL) in Cali, Colombia. All patients provided written informed consent, and data was securely stored and accessed only by the principal investigators. The study received ethical approval from the Academic Committee of the IASC and the Institutional Review Board (IRB) of Fundaci&#x00F3;n Valle de Lili (2021.1756), following the ethical principles of the 1975 Declaration of Helsinki.</p>
</sec>
<sec id="s3b"><label>3.2</label><title>Statistical analysis</title>
<p>Categorical variables were evaluated by assessing their frequency and percentage, whereas continous variables were studied by analyzing their median with interquartile range [interquartile range (IQR)]. Cross-tabulations with Chi-square or Fisher&#x0027;s exact tests were used to compare proportions between groups. The Kruskal&#x2013;Wallis and Mann&#x2013;Whitney U tests were used to compare continuous variables between groups. Logistic regression analyses, both univariate and multivariate, were performed to examine the contribution of specific variables to the development of xerostomia. Variables with a <italic>P</italic> value &#x003C;0.05 in the univariate analysis, as well as those reported in the literature as potential covariates or considered clinically significant, were included in the multivariate analysis. All analyses were performed using R statistical software (version 4.02). The REDCap (Research Electronic Data Capture) electronic database system was used to collect data from the medical records.</p>
</sec>
</sec>
<sec id="s4" sec-type="results"><label>4</label><title>Results</title>
<p><xref ref-type="table" rid="T1">Table&#x00A0;1</xref> summarizes the baseline characteristics of the study population. Overall, the median age was 58 years, without differences between patients with and without xerostomia. A higher proportion of women reported xerostomia than men (53.6&#x0025; vs. 35.6&#x0025;; <italic>P</italic>&#x2009;&#x003D;&#x2009;0.021). Dyslipidemia (48.2&#x0025; vs. 27.8&#x0025;; <italic>P</italic>&#x2009;&#x003D;&#x2009;0.006) and asthma/COPD (16.1&#x0025; vs. 4.2&#x0025;; <italic>P</italic>&#x2009;&#x003D;&#x2009;0.004) were also significantly more frequent in the xerostomia group, whereas the remaining comorbidities and pharmacological treatments showed comparable distributions.</p>
<table-wrap id="T1" position="float"><label>Table&#x00A0;1</label>
<caption><p>Xerostomia by demographic and clinical characteristics.</p></caption>
<table>
<thead>
<tr>
<th valign="top" align="left">Characteristic</th>
<th valign="top" align="center">Overall (<italic>N</italic>&#x2009;&#x003D;&#x2009;272)<xref ref-type="table-fn" rid="TF3"><sup>a</sup></xref></th>
<th valign="top" align="center">Xerostomia: Yes (<italic>n</italic>&#x2009;&#x003D;&#x2009;56)<xref ref-type="table-fn" rid="TF3"><sup>a</sup></xref></th>
<th valign="top" align="center">Xerostomia: No (<italic>n</italic>&#x2009;&#x003D;&#x2009;216)<xref ref-type="table-fn" rid="TF3"><sup>a</sup></xref></th>
<th valign="top" align="center"><italic>P</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Age, median (IQR)</td>
<td valign="top" align="center">58 (48&#x2013;69)</td>
<td valign="top" align="center">57 (47&#x2013;63)</td>
<td valign="top" align="center">58 (48&#x2013;69)</td>
<td valign="top" align="center">0.4<xref ref-type="table-fn" rid="TF4"><sup>b</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left" colspan="5" style="background-color:#7e8080">Sex</td>
</tr>
<tr>
<td valign="top" align="left">Male</td>
<td valign="top" align="center">165 (60.7)</td>
<td valign="top" align="center">26 (46.4)</td>
<td valign="top" align="center">139 (64.4)</td>
<td valign="top" align="center"><bold>0</bold><bold>.</bold><bold>021</bold><xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Female</td>
<td valign="top" align="center">107 (39.3)</td>
<td valign="top" align="center">30 (53.6)</td>
<td valign="top" align="center">77 (35.6)</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left" colspan="5" style="background-color:#7e8080">Comorbidities</td>
</tr>
<tr>
<td valign="top" align="left">Overweight/Obesity</td>
<td valign="top" align="center">155 (57.0)</td>
<td valign="top" align="center">35 (62.5)</td>
<td valign="top" align="center">120 (55.6)</td>
<td valign="top" align="center">0.4<xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Hypertension</td>
<td valign="top" align="center">152 (55.9)</td>
<td valign="top" align="center">33 (58.9)</td>
<td valign="top" align="center">120 (55.6)</td>
<td valign="top" align="center">0.8<xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Dyslipidemia</td>
<td valign="top" align="center">87 (32.0)</td>
<td valign="top" align="center">27 (48.2)</td>
<td valign="top" align="center">60 (27.8)</td>
<td valign="top" align="center"><bold>0</bold>.<bold>006</bold><xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Diabetes mellitus</td>
<td valign="top" align="center">79 (29.0)</td>
<td valign="top" align="center">22 (39.3)</td>
<td valign="top" align="center">57 (26.4)</td>
<td valign="top" align="center">0.069<xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">CKD</td>
<td valign="top" align="center">39 (14.3)</td>
<td valign="top" align="center">9 (16.1)</td>
<td valign="top" align="center">30 (13.9)</td>
<td valign="top" align="center">0.6<xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Asthma/COPD</td>
<td valign="top" align="center">18 (6.6)</td>
<td valign="top" align="center">9 (16.1)</td>
<td valign="top" align="center">9 (4.2)</td>
<td valign="top" align="center"><bold>0</bold>.<bold>004</bold><xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left" colspan="5" style="background-color:#7e8080">Pharmacological therapy</td>
</tr>
<tr>
<td valign="top" align="left">ARBs</td>
<td valign="top" align="center">83 (30.5)</td>
<td valign="top" align="center">23 (41.1)</td>
<td valign="top" align="center">60 (27.8)</td>
<td valign="top" align="center">0.072<xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Statins</td>
<td valign="top" align="center">68 (25.0)</td>
<td valign="top" align="center">15 (27.0)</td>
<td valign="top" align="center">53 (24.5)</td>
<td valign="top" align="center">0.7<xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Hypoglycemic agents</td>
<td valign="top" align="center">45 (16.5)</td>
<td valign="top" align="center">11 (19.6)</td>
<td valign="top" align="center">34 (15.7)</td>
<td valign="top" align="center">0.6<xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">CCBs</td>
<td valign="top" align="center">40 (14.7)</td>
<td valign="top" align="center">9 (16.1)</td>
<td valign="top" align="center">31 (14.4)</td>
<td valign="top" align="center">0.8<xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">BB</td>
<td valign="top" align="center">36 (13.2)</td>
<td valign="top" align="center">9 (16.1)</td>
<td valign="top" align="center">27 (12.5)</td>
<td valign="top" align="center">0.5<xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Diuretics</td>
<td valign="top" align="center">36 (13.2)</td>
<td valign="top" align="center">10 (17.9)</td>
<td valign="top" align="center">26 (12.0)</td>
<td valign="top" align="center">0.3<xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">ACE inhibitors</td>
<td valign="top" align="center">27 (9.9)</td>
<td valign="top" align="center">5 (8.9)</td>
<td valign="top" align="center">22 (10.2)</td>
<td valign="top" align="center">&#x003E;0.9<xref ref-type="table-fn" rid="TF5"><sup>c</sup></xref></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TF1"><p>ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; BB, beta blockers; CCBs, calcium channel blockers; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease.</p></fn>
<fn id="TF2"><p>Bolded <italic>P</italic>-values indicate statistical significance.</p></fn>
<fn id="TF3"><label>a</label>
<p>Values are expressed as median (interquartile range) or <italic>n</italic> (&#x0025;).</p></fn>
<fn id="TF4"><label>b</label>
<p><italic>P</italic>-value from Wilcoxon rank sum test.</p></fn>
<fn id="TF5"><label>c</label>
<p><italic>P</italic>-value from Fisher&#x0027;s exact test.</p></fn>
</table-wrap-foot>
</table-wrap>
<p>Vital signs and anthropometry at the 25-month in-person evaluation (192/272 patients, 70.6&#x0025;) are shown in <xref ref-type="table" rid="T2">Table&#x00A0;2</xref>. In this subset, no statistically significant differences were observed between patients with and without xerostomia in respiratory rate, heart rate, systolic or diastolic blood pressure, oxygen saturation, or body mass index.</p>
<table-wrap id="T2" position="float"><label>Table&#x00A0;2</label>
<caption><p>Vital signs and anthropometry at 25-month follow-up (patients with face-to-face interview).</p></caption>
<table>
<thead>
<tr>
<th valign="top" align="left">Characteristic</th>
<th valign="top" align="center">Overall (<italic>N</italic>&#x2009;&#x003D;&#x2009;192)<xref ref-type="table-fn" rid="TF7"><sup>a</sup></xref></th>
<th valign="top" align="center">Xerostomia: Yes (<italic>n</italic>&#x2009;&#x003D;&#x2009;53)<xref ref-type="table-fn" rid="TF7"><sup>a</sup></xref></th>
<th valign="top" align="center">Xerostomia: No (<italic>n</italic>&#x2009;&#x003D;&#x2009;139)<xref ref-type="table-fn" rid="TF7"><sup>a</sup></xref></th>
<th valign="top" align="center"><italic>P</italic>-value<xref ref-type="table-fn" rid="TF8"><sup>b</sup></xref></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left" colspan="5" style="background-color:#7e8080">Vital signs</td>
</tr>
<tr>
<td valign="top" align="left">Respiratory rate<xref ref-type="table-fn" rid="TF9"><sup>c</sup></xref></td>
<td valign="top" align="center">17 (17, 18)</td>
<td valign="top" align="center">17 (17, 18)</td>
<td valign="top" align="center">17 (16, 18)</td>
<td valign="top" align="center">0.7831</td>
</tr>
<tr>
<td valign="top" align="left">Heart rate<xref ref-type="table-fn" rid="TF10"><sup>d</sup></xref></td>
<td valign="top" align="center">72 (66, 80)</td>
<td valign="top" align="center">72 (65, 78)</td>
<td valign="top" align="center">71 (66, 80)</td>
<td valign="top" align="center">0.5242</td>
</tr>
<tr>
<td valign="top" align="left">SBP<xref ref-type="table-fn" rid="TF11"><sup>e</sup></xref></td>
<td valign="top" align="center">126 (116, 138)</td>
<td valign="top" align="center">125 (113, 137)</td>
<td valign="top" align="center">127 (116.5, 138)</td>
<td valign="top" align="center">0.6513</td>
</tr>
<tr>
<td valign="top" align="left">DBP<xref ref-type="table-fn" rid="TF11"><sup>e</sup></xref></td>
<td valign="top" align="center">80 (70, 84)</td>
<td valign="top" align="center">80 (67, 85)</td>
<td valign="top" align="center">80 (71, 84)</td>
<td valign="top" align="center">0.8250</td>
</tr>
<tr>
<td valign="top" align="left">Oxygen saturation<xref ref-type="table-fn" rid="TF12"><sup>f</sup></xref></td>
<td valign="top" align="center">97 (96, 98)</td>
<td valign="top" align="center">97 (96, 98)</td>
<td valign="top" align="center">97 (95.5, 98)</td>
<td valign="top" align="center">0.5775</td>
</tr>
<tr>
<td valign="top" align="left" colspan="5" style="background-color:#7e8080">Anthropometry</td>
</tr>
<tr>
<td valign="top" align="left">BMI<xref ref-type="table-fn" rid="TF13"><sup>g</sup></xref></td>
<td valign="top" align="center">27.9 (25.1, 31.2)</td>
<td valign="top" align="center">27.2 (25.2, 31.5)</td>
<td valign="top" align="center">28.1 (24.95, 31.2)</td>
<td valign="top" align="center">0.8639</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TF6"><p>BMI, body mass index; bpm, beats per minute; DBP, diastolic blood pressure; rpm, respirations per minute; SBP, systolic blood pressure.</p></fn>
<fn id="TF7"><label>a</label>
<p>Values are expressed as median (interquartile range).</p></fn>
<fn id="TF8"><label>b</label>
<p><italic>P</italic>-value from Wilcoxon rank sum test.</p></fn>
<fn id="TF9"><label>c</label>
<p>Units: respirations per minute.</p></fn>
<fn id="TF10"><label>d</label>
<p>Units: beats per minute.</p></fn>
<fn id="TF11"><label>e</label>
<p>Units: millimeters of mercury.</p></fn>
<fn id="TF12"><label>f</label>
<p>Units: percentage.</p></fn>
<fn id="TF13"><label>g</label>
<p>Units: kilograms per square meter.</p></fn>
</table-wrap-foot>
</table-wrap>
<p>At the 25-month follow-up, functional status, oral manifestations, and systemic symptoms were assessed in the cohort (<italic>n</italic>&#x2009;&#x003D;&#x2009;272), as detailed in <xref ref-type="table" rid="T3">Table&#x00A0;3</xref>. Patients with xerostomia were less frequently classified as NYHA I than those without xerostomia (48.2&#x0025; vs. 69.0&#x0025;; <italic>P</italic>&#x2009;&#x003D;&#x2009;0.006), while classes II and III were more common in the xerostomia group. Dysphagia (30.4&#x0025; vs. 7.9&#x0025;; <italic>P</italic>&#x2009;&#x003C;&#x2009;0.001), salivary gland pain/swelling (7.1&#x0025; vs. 1.4&#x0025;; <italic>P</italic>&#x2009;&#x003D;&#x2009;0.035), and submandibular swelling (5.4&#x0025; vs. 0.5&#x0025;; <italic>P</italic>&#x2009;&#x003D;&#x2009;0.028) were also more frequent among patients with xerostomia, whereas other oral findings did not differ significantly. Systemic symptoms, including fatigue (75.0&#x0025; vs. 46.3&#x0025;; <italic>P</italic>&#x2009;&#x003C;&#x2009;0.001), myalgia/arthralgia (76.8&#x0025; vs. 31.9&#x0025;; <italic>P</italic>&#x2009;&#x003C;&#x2009;0.001), palpitations (50.0&#x0025; vs. 15.3&#x0025;; <italic>P</italic>&#x2009;&#x003C;&#x2009;0.001), and chest pain (51.8&#x0025; vs. 13.9&#x0025;; <italic>P</italic>&#x2009;&#x003C;&#x2009;0.001), were likewise more common in the xerostomia group, while dyspnea did not show a statistically significant difference (<italic>P</italic>&#x2009;&#x003D;&#x2009;0.056).</p>
<table-wrap id="T3" position="float"><label>Table&#x00A0;3</label>
<caption><p>Functional status, oral manifestations, and systemic symptoms at 25-month follow-up.</p></caption>
<table>
<thead>
<tr>
<th valign="top" align="left">Characteristic</th>
<th valign="top" align="center">Overall (<italic>N</italic>&#x2009;&#x003D;&#x2009;272)<xref ref-type="table-fn" rid="TF15"><sup>a</sup></xref></th>
<th valign="top" align="center">Xerostomia: Yes (<italic>n</italic>&#x2009;&#x003D;&#x2009;56)<xref ref-type="table-fn" rid="TF15"><sup>a</sup></xref></th>
<th valign="top" align="center">Xerostomia: No (<italic>n</italic>&#x2009;&#x003D;&#x2009;216)<xref ref-type="table-fn" rid="TF15"><sup>a</sup></xref></th>
<th valign="top" align="center"><italic>P</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left" colspan="5" style="background-color:#7e8080">NYHA functional class</td>
</tr>
<tr>
<td valign="top" align="left">Class I</td>
<td valign="top" align="center">176 (64.7&#x0025;)</td>
<td valign="top" align="center">27 (48.2&#x0025;)</td>
<td valign="top" align="center">149 (69.0&#x0025;)</td>
<td valign="top" align="center"><bold>0</bold><bold>.</bold><bold>006</bold><xref ref-type="table-fn" rid="TF16"><sup>b</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Class II</td>
<td valign="top" align="center">63 (23.2&#x0025;)</td>
<td valign="top" align="center">17 (30.4&#x0025;)</td>
<td valign="top" align="center">46 (21.3&#x0025;)</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Class III</td>
<td valign="top" align="center">31 (11.4&#x0025;)</td>
<td valign="top" align="center">12 (21.4&#x0025;)</td>
<td valign="top" align="center">19 (8.8&#x0025;)</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Class IV</td>
<td valign="top" align="center">2 (0.7&#x0025;)</td>
<td valign="top" align="center">0 (0&#x0025;)</td>
<td valign="top" align="center">2 (0.9&#x0025;)</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left" colspan="5" style="background-color:#7e8080">Oral manifestations</td>
</tr>
<tr>
<td valign="top" align="left">Dysphagia</td>
<td valign="top" align="center">34 (12.5&#x0025;)</td>
<td valign="top" align="center">17 (30.4&#x0025;)</td>
<td valign="top" align="center">17 (7.9&#x0025;)</td>
<td valign="top" align="center"><bold>&#x003C;0</bold>.<bold>001</bold><xref ref-type="table-fn" rid="TF17"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Oral ulcers<xref ref-type="table-fn" rid="TF18"><sup>d</sup></xref></td>
<td valign="top" align="center">11 (4.0&#x0025;)</td>
<td valign="top" align="center">4 (7.1&#x0025;)</td>
<td valign="top" align="center">7 (3.2&#x0025;)</td>
<td valign="top" align="center">0.2<xref ref-type="table-fn" rid="TF17"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Salivary gland pain/swelling<xref ref-type="table-fn" rid="TF19"><sup>e</sup></xref></td>
<td valign="top" align="center">7 (2.6&#x0025;)</td>
<td valign="top" align="center">4 (7.1&#x0025;)</td>
<td valign="top" align="center">3 (1.4&#x0025;)</td>
<td valign="top" align="center"><bold>0</bold>.<bold>035</bold><xref ref-type="table-fn" rid="TF17"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Gum bleedin<xref ref-type="table-fn" rid="TF21"><sup>g</sup></xref></td>
<td valign="top" align="center">6 (2.2&#x0025;)</td>
<td valign="top" align="center">2 (3.6&#x0025;)</td>
<td valign="top" align="center">4 (1.9&#x0025;)</td>
<td valign="top" align="center">0.6<xref ref-type="table-fn" rid="TF17"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Oral lesions<xref ref-type="table-fn" rid="TF20"><sup>f</sup></xref></td>
<td valign="top" align="center">4 (1.5&#x0025;)</td>
<td valign="top" align="center">1 (1.8&#x0025;)</td>
<td valign="top" align="center">3 (1.4&#x0025;)</td>
<td valign="top" align="center">&#x003E;0.9<xref ref-type="table-fn" rid="TF17"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Submandibular swelling<xref ref-type="table-fn" rid="TF21"><sup>g</sup></xref></td>
<td valign="top" align="center">4 (1.5&#x0025;)</td>
<td valign="top" align="center">3 (5.4&#x0025;)</td>
<td valign="top" align="center">1 (0.5&#x0025;)</td>
<td valign="top" align="center"><bold>0</bold>.<bold>028</bold><xref ref-type="table-fn" rid="TF17"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Burning mouth/tongue<xref ref-type="table-fn" rid="TF22"><sup>h</sup></xref></td>
<td valign="top" align="center">3 (1.1&#x0025;)</td>
<td valign="top" align="center">1 (1.8&#x0025;)</td>
<td valign="top" align="center">2 (0.9&#x0025;)</td>
<td valign="top" align="center">0.5<xref ref-type="table-fn" rid="TF17"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Tongue redness</td>
<td valign="top" align="center">3 (1.1&#x0025;)</td>
<td valign="top" align="center">2 (3.6&#x0025;)</td>
<td valign="top" align="center">1 (0.5&#x0025;)</td>
<td valign="top" align="center">0.11<xref ref-type="table-fn" rid="TF17"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left" colspan="5" style="background-color:#7e8080">Signs and symptoms</td>
</tr>
<tr>
<td valign="top" align="left">Fatigue</td>
<td valign="top" align="center">142 (52.2&#x0025;)</td>
<td valign="top" align="center">42 (75.0&#x0025;)</td>
<td valign="top" align="center">100 (46.3&#x0025;)</td>
<td valign="top" align="center"><bold>&#x003C;0</bold>.<bold>001</bold><xref ref-type="table-fn" rid="TF17"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Myalgia/arthralgia</td>
<td valign="top" align="center">112 (41.2&#x0025;)</td>
<td valign="top" align="center">43 (76.8&#x0025;)</td>
<td valign="top" align="center">69 (31.9&#x0025;)</td>
<td valign="top" align="center"><bold>&#x003C;0</bold>.<bold>001</bold><xref ref-type="table-fn" rid="TF17"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Dyspnea</td>
<td valign="top" align="center">68 (25.0&#x0025;)</td>
<td valign="top" align="center">20 (35.7&#x0025;)</td>
<td valign="top" align="center">48 (22.2&#x0025;)</td>
<td valign="top" align="center">0.056<xref ref-type="table-fn" rid="TF17"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Palpitations</td>
<td valign="top" align="center">61 (22.4&#x0025;)</td>
<td valign="top" align="center">28 (50.0&#x0025;)</td>
<td valign="top" align="center">33 (15.3&#x0025;)</td>
<td valign="top" align="center"><bold>&#x003C;0</bold>.<bold>001</bold><xref ref-type="table-fn" rid="TF17"><sup>c</sup></xref></td>
</tr>
<tr>
<td valign="top" align="left">Chest pain</td>
<td valign="top" align="center">59 (21.7&#x0025;)</td>
<td valign="top" align="center">29 (51.8&#x0025;)</td>
<td valign="top" align="center">30 (13.9&#x0025;)</td>
<td valign="top" align="center"><bold>&#x003C;0</bold>.<bold>001</bold><xref ref-type="table-fn" rid="TF17"><sup>c</sup></xref></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TF14"><p>Bolded <italic>P</italic>-values indicate statistical significance.</p></fn>
<fn id="TF15"><label>a</label>
<p>Values are expressed as <italic>n</italic> (&#x0025;).</p></fn>
<fn id="TF16"><label>b</label>
<p><italic>P</italic>-values from Fisher&#x0027;s exact test with simulated <italic>p</italic>-value (2,000 replicates), used for NYHA functional class (ordinal variable with 4 categories).</p></fn>
<fn id="TF17"><label>c</label>
<p><italic>P</italic>-values from Fisher&#x0027;s exact test (categorical dichotomous variables).</p></fn>
<fn id="TF18"><label>d</label>
<p>Oral ulcers: lesions inside the mouth.</p></fn>
<fn id="TF19"><label>e</label>
<p>Salivary gland pain/swelling: pain or swelling in the salivary glands (in front of the ear or cheek).</p></fn>
<fn id="TF20"><label>f</label>
<p>Oral lesions: spots or lesions on the lips or inside the mouth.</p></fn>
<fn id="TF21"><label>g</label>
<p>Submandibular swelling: swelling under the jaw.</p></fn>
<fn id="TF22"><label>h</label>
<p>Burning mouth/tongue: burning sensation in the mouth or tongue.</p></fn>
</table-wrap-foot>
</table-wrap>
<p><xref ref-type="fig" rid="F2">Figure&#x00A0;2</xref> summarizes the univariable and multivariable logistic regression analyses for factors associated with xerostomia. In the adjusted model, male sex was associated with lower odds of xerostomia (<italic>aOR</italic>: 0.47; 95&#x0025; CI: 0.24&#x2013;0.89; <italic>P</italic>&#x2009;&#x003D;&#x2009;0.021), while asthma/COPD was associated with higher odds (<italic>aOR</italic>: 5.14; 95&#x0025; CI: 1.76&#x2013;15.7; <italic>P</italic>&#x2009;&#x003D;&#x2009;0.003). Among symptoms, palpitations (<italic>aOR</italic>: 2.47; 95&#x0025; CI: 1.04&#x2013;5.94; <italic>P</italic>&#x2009;&#x003D;&#x2009;0.041) and chest pain (<italic>aOR</italic>: 3.74; 95&#x0025; CI: 1.67&#x2013;8.43; <italic>P</italic>&#x2009;&#x003D;&#x2009;0.001) remained significantly associated with xerostomia. Dyslipidemia, diabetes, age, dyspnea, and fatigue did not show significant associations after adjustment, although dyspnea and fatigue were significant in univariable analyses.</p>
<fig id="F2" position="float"><label>Figure&#x00A0;2</label>
<caption><p>Summary of logistic regression models for xerostomia.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="froh-06-1633542-g002.tif"><alt-text content-type="machine-generated">Forest plot showing crude (blue) and adjusted (red) odds ratios with 95&#x0025; confidence intervals for variables including asthma/COPD, dyslipidemia, age, gender, diabetes mellitus, dyspnea, palpitations, fatigue, and chest pain. Odds ratio values with confidence intervals are displayed on a log scale for each variable.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s5" sec-type="discussion"><label>5</label><title>Discussion</title>
<p>This study analyzed 272 survivors of severe COVID-19 from five Latin American countries and found that xerostomia persisted in approximately one-fifth of patients after more than two years of follow-up. The condition was more frequent in women and independently associated with asthma/COPD, palpitations, and chest pain, underscoring its multifactorial nature.</p>
<p>Strengths of this study include its multicenter design across different countries, the use of in-person assessments in most participants, and a follow-up period exceeding two years, which is longer than most published cohorts. These aspects enhance representativeness and external validity. Nonetheless, several limitations must be acknowledged. The retrospective design may introduce selection bias, xerostomia was self-reported without objective validation, baseline oral health status was not available, and the analysis of medications was not sufficiently detailed to establish their contribution. These elements restrict causal interpretation and should be considered when attempting to generalise from the findings.</p>
<p>Our findings are consistent with previous studies reporting a high burden of comorbidities among severe COVID-19 survivors (<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B14">14</xref>). Compared to prior cohorts, the prevalence of xerostomia in our population (20.6&#x0025;) was lower than in studies from Italy (30&#x0025;) and Colombia (26&#x0025;) (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B15">15</xref>), likely reflecting differences in follow-up duration and patient selection. Similar heterogeneity has been documented, with reported prevalences ranging from 2&#x0025; to 40&#x0025; depending on study design and methodology (<xref ref-type="bibr" rid="B10">10</xref>). Importantly, the association with asthma/COPD persisted beyond two years, extending prior evidence from shorter follow-up studies and suggesting that underlying respiratory disease and its treatments remain important determinants (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B16">16</xref>).</p>
<p>Other oral manifestations were also less frequent than in international reports. Dysphagia occurred in 12.5&#x0025; of patients, lower than the pooled prevalence reported in systematic reviews (<xref ref-type="bibr" rid="B17">17</xref>, <xref ref-type="bibr" rid="B18">18</xref>). Similarly, oral ulcers were uncommon in our cohort compared to previous literature (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B19">19</xref>). These differences likely arise from variability in populations studied, the tools used to capture oral symptoms, and the timing of follow-up. Together, these observations underscore the need for standardized methods to assess oral sequelae in COVID-19 survivors.</p>
<p>Pharmacological therapies may further contribute to xerostomia. More than 400 prescription and over-the-counter medications are recognized causes of reduced salivary flow and dry mouth in the general population (e.g., antihypertensives, antidepressants, anticholinergics, diuretics, opioids, nonsteroidal anti-inflammatory drugs, antihistamines) (<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B5">5</xref>). Several drug classes commonly prescribed in COVID-19 survivors, including ACE inhibitors, beta blockers, calcium channel blockers, diuretics, and ARBs, have been specifically linked to salivary dysfunction (<xref ref-type="bibr" rid="B20">20</xref>, <xref ref-type="bibr" rid="B21">21</xref>). In our cohort, ARBs were more frequent among patients with xerostomia, although without statistical significance. This highlights the challenge of disentangling the contributions of pharmacotherapy, comorbid conditions, and COVID-19 sequelae to the persistence of oral dryness.</p>
<p>Taken together, these findings indicate that xerostomia in long COVID is multifactorial, likely resulting from interactions between systemic comorbidities, chronic pharmacological treatment, and potential sequelae of SARS-CoV-2 infection (<xref ref-type="bibr" rid="B7">7</xref>, <xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B20">20</xref>, <xref ref-type="bibr" rid="B21">21</xref>). Clinically, this emphasizes the importance of incorporating oral health assessment into long-term follow-up of COVID-19 survivors. Physicians and dental practitioners should recognize its impact on quality of life and consider multidisciplinary approaches (<xref ref-type="bibr" rid="B8">8</xref>, <xref ref-type="bibr" rid="B9">9</xref>). Future research should prioritize objective assessments of salivary function, detailed evaluation of medication exposures, and the identification of modifiable risk factors, with the goal of guiding preventive and therapeutic strategies.</p>
</sec>
<sec id="s6" sec-type="conclusions"><label>6</label><title>Conclusions</title>
<p>These findings underscore xerostomia as a relatively common symptom in survivors of severe COVID-19, highlighting the need for increased awareness among physicians and dental health practitioners to actively screen for and manage this condition during long-term follow-up. Given the association of xerostomia with systemic conditions such as asthma/COPD, dyslipidemia, and cardiovascular disease, a multidisciplinary approach may be essential in addressing its impact on patient well-being. Furthermore, our findings suggest that long-term evaluations are crucial to better understanding the persistence of oral symptoms in COVID-19 survivors and their potential underlying mechanisms. Future prospective studies should focus on identifying modifiable risk factors and evaluating the role of pharmacotherapy and inflammatory pathways in the development of xerostomia, ultimately guiding more effective preventive and therapeutic strategies.</p>
</sec>
</body>
<back>
<sec id="s7" sec-type="data-availability"><title>Data availability statement</title>
<p>The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.</p>
</sec>
<sec id="s8" sec-type="ethics-statement"><title>Ethics statement</title>
<p>The studies involving humans were approved by the Institutional Review Board (IRB) of Fundaci&#x00F3;n Valle de Lili (2021.1756). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.</p>
</sec>
<sec id="s9" sec-type="author-contributions"><title>Author contributions</title>
<p>PE: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. BC-M: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. JA-I: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. MN-R: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. MB: Conceptualization, Investigation, Supervision, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing, Data curation, Formal analysis, Methodology, Software, Visualization. AC: Investigation, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. AM: Investigation, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. CH: Investigation, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. MQ: Investigation, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. AB: Investigation, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. MC: Investigation, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. FC: Investigation, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. LC: Investigation, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. JG-M: Investigation, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing, Conceptualization, Data curation, Formal analysis, Methodology, Supervision.</p>
</sec>
<ack><title>Acknowledgments</title>
<p>We extend our gratitude to all individuals and institutions involved in the design and execution of the CARDIO COVID 21-21 study.</p>
</ack>
<sec id="s11" sec-type="COI-statement"><title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s12" sec-type="ai-statement"><title>Generative AI statement</title>
<p>The author(s) declare that no Generative AI was used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
</sec>
<sec id="s14" sec-type="disclaimer"><title>Publisher&#x0027;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec id="s13" sec-type="supplementary-material"><title>Supplementary material</title>
<p>The Supplementary Material for this article can be found online at: <ext-link ext-link-type="uri" xlink:href="https://www.frontiersin.org/articles/10.3389/froh.2025.1633542/full#supplementary-material">https://www.frontiersin.org/articles/10.3389/froh.2025.1633542/full&#x0023;supplementary-material</ext-link></p>
<supplementary-material xlink:href="Table1.docx" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document"/>
</sec>
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<fn-group>
<fn id="n1" fn-type="custom" custom-type="edited-by"><p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3136703/overview">Henk Brand</ext-link>, Vrije Universiteit Amsterdam and University of Amsterdam, Netherlands</p></fn>
<fn id="n2" fn-type="custom" custom-type="reviewed-by"><p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/442629/overview">William Murray Thomson</ext-link>, University of Otago, New Zealand</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3154926/overview">Amal Sindi</ext-link>, King Abdulaziz University, Saudi Arabia</p></fn>
<fn fn-type="abbr" id="abbrev1"><label>Abbreviations:</label><p>ACE2, angiotensin-converting enzyme 2; ICU, Intensive Care Unit; CIFACAH, Inter-American Council of Heart Failure and Pulmonary Hypertension; IASC, Inter-American Society of Cardiology; FVL, Fundaci&#x00F3;n Valle del Lili; IRB, institutional review board; IQR, interquartile range; ARBs, angiotensin receptor blockers; COPD, chronic obstructive pulmonary disease; NYHA&#x2014;New York Heart Association; REDCap, research electronic data capture; aOR, adjusted odds ratio; BB, beta blockers; CCBs, calcium channel blockers.</p></fn>
</fn-group>
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</article>