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<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Med.</journal-id>
<journal-title>Frontiers in Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Med.</abbrev-journal-title>
<issn pub-type="epub">2296-858X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fmed.2025.1533009</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Medicine</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Does long COVID in people living with HIV resemble the functional phenotype of non-HIV individuals who had moderate or severe acute COVID-19? A retrospective cross-sectional study</article-title>
</title-group>
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<name><surname>Rezende</surname> <given-names>Anna Gabriela</given-names></name>
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<name><surname>Valente</surname> <given-names>Jefferson</given-names></name>
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<name><surname>Goulart</surname> <given-names>C&#x000E1;ssia da Luz</given-names></name>
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<name><surname>Facioli</surname> <given-names>Fernanda</given-names></name>
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<name><surname>Maia</surname> <given-names>Bernardo</given-names></name>
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<name><surname>Mwangi</surname> <given-names>Victor Irungu</given-names></name>
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<contrib contrib-type="author">
<name><surname>Bonilla</surname> <given-names>Hector</given-names></name>
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<name><surname>Franssen</surname> <given-names>Frits M. E.</given-names></name>
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<name><surname>Amaral</surname> <given-names>Camila Miriam Suemi Sato Barros do</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff6"><sup>6</sup></xref>
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<name><surname>Motta</surname> <given-names>Tha&#x000ED;s Jord&#x000E3;o Perez Sant&#x00027;Anna</given-names></name>
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<name><surname>Alexandre</surname> <given-names>Marcia</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff7"><sup>7</sup></xref>
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<contrib contrib-type="author">
<name><surname>Ferreira</surname> <given-names>Luiz Carlos de Lima</given-names></name>
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<name><surname>Cipriano Junior</surname> <given-names>Gerson</given-names></name>
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<name><surname>Ar&#x000EA;as</surname> <given-names>Guilherme Peixoto Tinoco</given-names></name>
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<contrib contrib-type="author" corresp="yes" equal-contrib="yes">
<name><surname>Almeida-Val</surname> <given-names>Fernando</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff7"><sup>7</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x0002A;</sup></xref>
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<aff id="aff1"><sup>1</sup><institution>Universidade Federal do Amazonas</institution>, <addr-line>Manaus</addr-line>, <country>Brazil</country></aff>
<aff id="aff2"><sup>2</sup><institution>Universidade do Estado do Amazonas</institution>, <addr-line>Manaus</addr-line>, <country>Brazil</country></aff>
<aff id="aff3"><sup>3</sup><institution>Universidade de Bras&#x000ED;lia</institution>, <addr-line>Bras&#x000ED;lia</addr-line>, <country>Brazil</country></aff>
<aff id="aff4"><sup>4</sup><institution>Stanford University</institution>, <addr-line>Stanford, CA</addr-line>, <country>United States</country></aff>
<aff id="aff5"><sup>5</sup><institution>Maastricht University Medical Center</institution>, <addr-line>Maastricht</addr-line>, <country>Netherlands</country></aff>
<aff id="aff6"><sup>6</sup><institution>Hospital e Pronto Socorro 28 de Agosto</institution>, <addr-line>Manaus</addr-line>, <country>Brazil</country></aff>
<aff id="aff7"><sup>7</sup><institution>Funda&#x000E7;&#x000E3;o de Medicina Tropical Dr. Heitor Vieira Dourado</institution>, <addr-line>Manaus</addr-line>, <country>Brazil</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Pei-Hui Wang, Shandong University, China</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Tope Oyelade, University College London, United Kingdom</p>
<p>Jacques L. Tamuzi, Stellenbosch University, South Africa</p></fn>
<corresp id="c001">&#x0002A;Correspondence: Fernando Almeida-Val <email>ffaval&#x00040;gmail.com</email></corresp>
<fn fn-type="equal" id="fn001"><p>&#x02020;These authors have contributed equally to this work</p></fn></author-notes>
<pub-date pub-type="epub">
<day>25</day>
<month>04</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>12</volume>
<elocation-id>1533009</elocation-id>
<history>
<date date-type="received">
<day>28</day>
<month>11</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>07</day>
<month>04</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2025 Rezende, Valente, Goulart, Facioli, Maia, Mwangi, Bonilla, Franssen, Amaral, Motta, Alexandre, Ferreira, Cipriano Junior, Ar&#x000EA;as and Almeida-Val.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Rezende, Valente, Goulart, Facioli, Maia, Mwangi, Bonilla, Franssen, Amaral, Motta, Alexandre, Ferreira, Cipriano Junior, Ar&#x000EA;as and Almeida-Val</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license>
</permissions>
<abstract>
<sec>
<title>Introduction</title>
<p>It has been postulated that individuals with long COVID have reduced exercise capacity, just as people living with HIV (PLWH), although having even lower exercise capacity. The extent to which long COVID in PLWH resembles long COVID in individuals who presented different COVID-19 phenotypes is unknown, so we aimed to determine if the long COVID profile in PLWH resembled the symptoms experienced by individuals with long COVID following mild/moderate or severe acute COVID-19, 2 years after the initial disease.</p>
</sec>
<sec>
<title>Material and methods</title>
<p>A pulmonary function test and a 6-min walk test (6MWT) were performed on adult individuals with PACS (Post-Acute COVID Syndrome) in 3 groups: COVID-19&#x0002B;PLWH (plwHCOV), mild/moderate COVID-19 (mmCOV); severe COVID-19 (seCOV).</p>
</sec>
<sec>
<title>Results</title>
<p>Sixty three individuals were included: plwHCOV (<italic>n</italic> = 12), mmCOV (<italic>n</italic> = 33) and seCOV (<italic>n</italic> = 18). Across all groups, males were predominant. BMI was 25 &#x000B1; 3, 28 &#x000B1; 4, and 32 &#x000B1; 7 kg/m<sup>2</sup> in plwHCOV, mmCOV, and seCOV, respectively (<italic>p</italic> = 0.003). The plwHCOV walked 545 m (&#x000B1;93) at the 6MWT, which was comparable to the mmCOV group (555 m &#x000B1; 63) but significantly higher than the seCOV group (435 m &#x000B1; 84) (<italic>p</italic> &#x0003C; 0.0001). The plwHCOV group had worse forced expiratory volume in 1st second (FEV<sub>1</sub>%, 80 &#x000B1; 12) (<italic>p</italic> &#x0003C; 0.0001), forced vital capacity (FVC%, 83 &#x000B1; 11) (<italic>p</italic> = 0.002) and FEV<sub>1</sub>/FVC (0.80 &#x000B1; 0.1, <italic>p</italic> = 0.004) when compared to the seCOV group. Interestingly, PLWH had comparable 6MWT, FEV<sub>1</sub>, FVC, and FEV<sub>1</sub>/FVC results as mmCOV.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>Our results indicate that even 2 years post-COVID-19 infection, PLWH exhibits significantly decreased spirometry compared to the seCOV group. Despite this lung function impairment, their functional capacity was similar to individuals with PACS following mild/moderate COVID-19.</p>
</sec></abstract>
<kwd-group>
<kwd>HIV</kwd>
<kwd>long Covid</kwd>
<kwd>functional capacity</kwd>
<kwd>pulmonary function</kwd>
<kwd>COVID-19</kwd>
</kwd-group>
<counts>
<fig-count count="2"/>
<table-count count="2"/>
<equation-count count="0"/>
<ref-count count="71"/>
<page-count count="10"/>
<word-count count="6968"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Pulmonary Medicine</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="s1">
<title>Introduction</title>
<p>COVID-19 and HIV/AIDS are among the most impactful viral diseases of global concern in recent history (<xref ref-type="bibr" rid="B1">1</xref>), both of which are known to affect functional and respiratory capacity (<xref ref-type="bibr" rid="B2">2</xref>, <xref ref-type="bibr" rid="B3">3</xref>). While most patients recover from acute COVID-19, &#x0007E;1 in 10 develop long COVID symptoms that can persist for months (<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B5">5</xref>). More than 200 symptoms and conditions, such as postural orthostatic tachycardia syndrome (PoTS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), have been associated with long COVID (<xref ref-type="bibr" rid="B6">6</xref>). Definitions vary across agencies: the CDC/NIH considers symptoms lasting 4 or more weeks (<xref ref-type="bibr" rid="B7">7</xref>), WHO/NICE defines it as symptoms persisting for at least 2 months after 3 months from infection (<xref ref-type="bibr" rid="B8">8</xref>), and the RECOVER initiative extends this window to 6 months (<xref ref-type="bibr" rid="B6">6</xref>).</p>
<p>Although most long COVID studies focus on prevalence and symptom description in the general population (<xref ref-type="bibr" rid="B6">6</xref>, <xref ref-type="bibr" rid="B9">9</xref>&#x02013;<xref ref-type="bibr" rid="B12">12</xref>), fewer have investigated its long-term functional consequences, mainly using objective measures (<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B14">14</xref>). Reduced exercise capacity has been postulated as a hallmark of long COVID (<xref ref-type="bibr" rid="B13">13</xref>), yet little is known about how this manifests in specific vulnerable groups.</p>
<p>Globally, nearly 39 million people live with HIV, with rising numbers in Latin America (<xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B16">16</xref>). Advances in antiretroviral therapy (ART) have reduced morbidity and mortality (<xref ref-type="bibr" rid="B17">17</xref>), but people living with HIV (PLWH) increasingly face challenges such as chronic disease, reduced quality of life, and functional decline linked to viral persistence, frailty, and systemic deterioration (<xref ref-type="bibr" rid="B18">18</xref>, <xref ref-type="bibr" rid="B19">19</xref>). Recent evidence suggests that PLWH are at increased risk of developing long COVID, regardless of ART status, CD4 count, or viral load (<xref ref-type="bibr" rid="B20">20</xref>, <xref ref-type="bibr" rid="B21">21</xref>). A recent systematic review and meta-analysis further confirmed that HIV infection is associated with a higher likelihood of developing long COVID, with common symptoms including fatigue, cough, and asthenia, and evidence of impaired lung function and immune dysregulation in this population (<xref ref-type="bibr" rid="B21">21</xref>).</p>
<p>Despite this elevated risk, the functional profile of PLWH with long COVID remains poorly understood, particularly in comparison to individuals without HIV who experienced different severities of acute COVID-19. Most available studies rely on subjective self-reports, highlighting the need for studies that use objective assessments. Therefore, the present study aims to evaluate the functional profile of PLWH with long COVID in comparison to individuals with long COVID who had mild/moderate or severe acute COVID-19, more than 2 years after initial infection.</p>
</sec>
<sec sec-type="methods" id="s2">
<title>Methods</title>
<sec>
<title>Study design and setting</title>
<p>This retrospective cross-sectional study involved 63 individuals of both sexes, over 18 years old, and residents of Manaus. It was conducted at the Federal University of Amazonas (UFAM) in Manaus, Brazil. All individuals had the first confirmed SARS-CoV-2 infection before the vaccine roll-out in Manaus, which started in January 2021.</p>
</sec>
<sec>
<title>Eligibility criteria and study groups</title>
<p>People living with HIV, who had an undetectable viral load (&#x0003C;40 cells/ml), with at least 6 months of adherence to antiretroviral therapy (ART), who had mild/moderate COVID-19 in 2020, and with no history of respiratory or neurological diseases comprised the plwHCOV group, totaling 12 individuals. The comparative groups of people not living with HIV were mmCOV (mild/moderate COVID-19, a total of 33 individuals) and seCOV (severe COVID-19, a total of 18 individuals). The severity of COVID-19 was defined by the provisional clinical guidance of the World Health Organization (WHO) (<xref ref-type="bibr" rid="B22">22</xref>). Overall, clinically unstable individuals presenting musculoskeletal, neurological, or respiratory disorders that affected the performance of functional tests were excluded. All subjects had no current or chronic lung disease or health conditions that would interfere with functional and respiratory assessments. The long COVID-19 definition followed the WHO classification (<xref ref-type="bibr" rid="B22">22</xref>) and HIV infection was defined as a positive confirmatory molecular test.</p>
</sec>
<sec>
<title>Measurements</title>
<p>Patient clinical data, including age, sex, weight, and height (used to calculate the body mass index, BMI), details on past medical history, comorbidities, persistent symptoms, smoking habits, vital signs, severity of respiratory fatigue by the mMRC (Modified Medical Research Council) dyspnea scale (<xref ref-type="bibr" rid="B23">23</xref>) and medication usage were collected to characterize the groups.</p>
<sec>
<title>Pulmonary function and respiratory muscle strength (RMS)</title>
<p>Spirometry (Cosmed<sup>&#x000AE;</sup>, Italy) was performed for lung function and was interpreted according to the <italic>American Thoracic Society (ATS)</italic> and <italic>European Respiratory Society (ERS)</italic> standards. We measured the forced expiratory volume in 1st second (FEV<sub>1</sub>) and the forced vital capacity (FVC). The predicted values were calculated according to the ERS equation (<xref ref-type="bibr" rid="B24">24</xref>). The FEV<sub>1</sub> (L, %), FVC (L, %), and FEV<sub>1</sub>/FVC (%) were recorded (<xref ref-type="bibr" rid="B25">25</xref>). Percent-predicted values were determined as per the proposed recommendations by Alberto et al. (<xref ref-type="bibr" rid="B26">26</xref>). Maximum inspiratory pressure (MIP) was obtained after the individual expired to residual volume and performed a maximal effort inspiration against a closed valve, during which the pressure was measured. For the maximum expiratory pressure (MEP) assessment, patients underwent an inspiration to total lung capacity, followed by a maximal effort expiration against a closed valve for 2 s, after which the valve was opened (<xref ref-type="bibr" rid="B24">24</xref>).</p>
</sec>
<sec>
<title>Functional capacity</title>
<p>This was determined using the 6-min walk test (6MWT), during which participants received standardized verbal encouragement and instructions to walk the maximum distance possible within 6 min along a flat corridor measuring 30 m in length. At the beginning and end of the tests, vital signs are measured for hemodynamic monitoring: Systolic and diastolic blood pressure (SBP and DBP), heart rate (HR), peripheral oxygen saturation (SpO2), and perception of dyspnea (BORG Scale). The test followed the guidelines set by the <italic>American Thoracic Society</italic> (<xref ref-type="bibr" rid="B27">27</xref>). All groups underwent spirometry and 6MWT tests (<xref ref-type="bibr" rid="B28">28</xref>).</p>
</sec>
<sec>
<title>Quality of life - SF-36</title>
<p>The Short Form Health Survey (SF-36) questionnaire was used to assess the Quality of life among individuals living with HIV. This assessment was conducted at an exploratory level, recognizing the challenges related to stigma and social neglect within the PLWH population. The SF-36 evaluates eight quality-of-life domains, which are categorized into physical (functioning, role limitations-physical, pain, general health) and mental health (vitality, social functioning, role limitations-emotional, and emotional/mental health). Scoring was as outlined by Hays et al. (<xref ref-type="bibr" rid="B29">29</xref>). Item scores were converted to a scale ranging from 0 to 100 points, where 0 indicated the poorest perception of health, and 100 reflects the best perception of health. Averaging individual items within the subscale and physical composite and mental health determined the domain scores.</p>
</sec>
</sec>
<sec>
<title>Ethical aspects</title>
<p>The Federal University of Amazonas Institutional Review Board approved this study (CAAE 44971221.7.0000.5020). This adhered to the principles outlined in the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonization. Eligible before enrollment. They were allowed sufficient time to thoroughly review and sign an informed consent form (ICF).</p>
</sec>
<sec>
<title>Statistical analysis</title>
<p>The Shapiro-Wilk and Levene&#x00027;s tests assessed data normality and homogeneity, respectively. The results were presented as mean &#x000B1; standard deviation, median, and interquartile range, or percentage values. The Chi-square test and ANOVA one-way test <italic>post hoc</italic> Tukey test were used for group characteristic analyses. Pearson&#x00027;s correlation determined the correlation coefficient between variables, considering indices from 0.1&#x02013;0.3, 0.4&#x02013;0.6, and 0.7&#x02013;0.9 with weak, moderate, and strong associations, respectively (<xref ref-type="bibr" rid="B30">30</xref>). A <italic>p</italic>-value &#x0003C; 0.05 was considered statistically significant. The SPSS software version 23.0 (IBM, Chicago, USA) was used for calculations, and GraphPad Prism software version 8.0 (GraphPad, California, USA) was used for creating the images. The sample size was calculated using G<sup>&#x0002A;</sup>Power 3.1 software for a Pearson correlation analysis, assuming a moderate effect size (<italic>r</italic> = 0.5), a significance level of &#x003B1; = 0.05, and a statistical power (1&#x02013;&#x003B2;) of 0.80. Based on these parameters, the minimum required sample size was estimated at 29 participants. The actual number of participants included in each subgroup provided slightly higher statistical power (&#x0007E;86%), reducing the likelihood of a type II error.</p>
</sec>
</sec>
<sec sec-type="results" id="s3">
<title>Results</title>
<sec>
<title>Population characteristics for the plwHCOV group</title>
<p>Participants from the plwHCOV group were predominantly male, above 40 years of age, living with HIV for at least 12 months, and adherent to ART. For a detailed individual description of this group, please see <xref ref-type="table" rid="T1">Table 1</xref>. Clinical, functional, and lung function characteristics of individuals are detailed in <xref ref-type="table" rid="T2">Table 2</xref>. The most frequent comorbidity in the plwHCOV group was hypertension, while the most reported medication used daily was Losartan. All participants denied engaging in harmful habits and addictions, as described in <xref ref-type="table" rid="T1">Table 1</xref>. The FEV<sub>1</sub> was 2.6 &#x000B1; 0.7 L, FEV<sub>1</sub> predicted 80 &#x000B1; 12%, FVC 3.3 &#x000B1; 0.9 L, FVC predicted 83 &#x000B1; 11%, FEV1/FVC 0.80 &#x000B1; 0.1 L/s, MIP 92 &#x000B1; 39 cmH2O, MEP 105 &#x000B1; 33 cmH<sub>2</sub>O. The SF-36 mean total score was 51.9 &#x000B1; 29.4. Details of the quality-of-life assessment are also available in <xref ref-type="table" rid="T1">Table 1</xref>.</p>
<table-wrap position="float" id="T1">
<label>Table 1</label>
<caption><p>Sociodemographic, HIV status and quality of life characteristics of the PLWHCOV group.</p></caption>
<table frame="box" rules="all">
<thead>
<tr style="background-color:#919498;color:#ffffff">
<th valign="top" align="left"><bold>ID</bold></th>
<th valign="top" align="left"><bold>Sex/Age</bold></th>
<th valign="top" align="center"><bold>BMI</bold></th>
<th valign="top" align="center"><bold>Years with HIV</bold></th>
<th valign="top" align="center"><bold>CD4 levels</bold></th>
<th valign="top" align="left"><bold>Comorbidities</bold></th>
<th valign="top" align="center" colspan="9"><bold>Quality of life (SF-36 questionnaire)</bold></th>
</tr>
<tr style="background-color:#919498;color:#ffffff">
<th/>
<th/>
<th/>
<th/>
<th/>
<th/>
<th valign="top" align="center"><bold>Physical function</bold></th>
<th valign="top" align="center"><bold>Role physical</bold></th>
<th valign="top" align="center"><bold>Role emotional</bold></th>
<th valign="top" align="center"><bold>Vitality</bold></th>
<th valign="top" align="center"><bold>Mental health</bold></th>
<th valign="top" align="center"><bold>Social function</bold></th>
<th valign="top" align="center"><bold>Bodily pain</bold></th>
<th valign="top" align="center"><bold>General health</bold></th>
<th valign="top" align="center"><bold>Total score</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">1</td>
<td valign="top" align="left">M/48</td>
<td valign="top" align="center">26.8</td>
<td valign="top" align="center">9y</td>
<td valign="top" align="center">603</td>
<td valign="top" align="left">Hypertension</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">60</td>
<td valign="top" align="center">68</td>
<td valign="top" align="center">87.5</td>
<td valign="top" align="center">57.5</td>
<td valign="top" align="center">65</td>
<td valign="top" align="center">62.7</td>
</tr> <tr>
<td valign="top" align="center">2</td>
<td valign="top" align="left">F/51</td>
<td valign="top" align="center">24.6</td>
<td valign="top" align="center">12y</td>
<td valign="top" align="center">678</td>
<td valign="top" align="left">Hypertension</td>
<td valign="top" align="center">35</td>
<td valign="top" align="center">25</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">76</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">45</td>
<td valign="top" align="center">30</td>
<td valign="top" align="center">38.8</td>
</tr> <tr>
<td valign="top" align="center">3</td>
<td valign="top" align="left">F/46</td>
<td valign="top" align="center">24.2</td>
<td valign="top" align="center">23y</td>
<td valign="top" align="center">772</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">35</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">15</td>
<td valign="top" align="center">20</td>
<td valign="top" align="center">25</td>
<td valign="top" align="center">35</td>
<td valign="top" align="center">35</td>
<td valign="top" align="center">20.6</td>
</tr> <tr>
<td valign="top" align="center">4</td>
<td valign="top" align="left">F/53</td>
<td valign="top" align="center">18.9</td>
<td valign="top" align="center">12y</td>
<td valign="top" align="center">602</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">55</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">4</td>
<td valign="top" align="center">37.5</td>
<td valign="top" align="center">22.5</td>
<td valign="top" align="center">40</td>
<td valign="top" align="center">20.5</td>
</tr> <tr>
<td valign="top" align="center">5</td>
<td valign="top" align="left">F/51</td>
<td valign="top" align="center">28.7</td>
<td valign="top" align="center">8y</td>
<td valign="top" align="center">1,012</td>
<td valign="top" align="left">Depression</td>
<td valign="top" align="center">15</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">55</td>
<td valign="top" align="center">48</td>
<td valign="top" align="center">25</td>
<td valign="top" align="center">10</td>
<td valign="top" align="center">10</td>
<td valign="top" align="center">20.3</td>
</tr> <tr>
<td valign="top" align="center">6</td>
<td valign="top" align="left">M/35</td>
<td valign="top" align="center">25.9</td>
<td valign="top" align="center">1y</td>
<td valign="top" align="center">771</td>
<td valign="top" align="left">Rheumatoid arthritis</td>
<td valign="top" align="center">40</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">25</td>
<td valign="top" align="center">40</td>
<td valign="top" align="center">12.5</td>
<td valign="top" align="center">22.5</td>
<td valign="top" align="center">30</td>
<td valign="top" align="center">21.2</td>
</tr> <tr>
<td valign="top" align="center">7</td>
<td valign="top" align="left">M/26</td>
<td valign="top" align="center">24.2</td>
<td valign="top" align="center">2y</td>
<td valign="top" align="center">542</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">75</td>
<td valign="top" align="center">84</td>
<td valign="top" align="center">87.5</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">60</td>
<td valign="top" align="center">88.3</td>
</tr> <tr>
<td valign="top" align="center">8</td>
<td valign="top" align="left">M/44</td>
<td valign="top" align="center">28.4</td>
<td valign="top" align="center">7y</td>
<td valign="top" align="center">481</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">90</td>
<td valign="top" align="center">76</td>
<td valign="top" align="center">25</td>
<td valign="top" align="center">57.5</td>
<td valign="top" align="center">75</td>
<td valign="top" align="center">77.9</td>
</tr> <tr>
<td valign="top" align="center">9</td>
<td valign="top" align="left">M/31</td>
<td valign="top" align="center">24.1</td>
<td valign="top" align="center">7y</td>
<td valign="top" align="center">1,107</td>
<td valign="top" align="left">Anxiety</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">50</td>
<td valign="top" align="center">52</td>
<td valign="top" align="center">75</td>
<td valign="top" align="center">90</td>
<td valign="top" align="center">75</td>
<td valign="top" align="center">67.7</td>
</tr> <tr>
<td valign="top" align="center">10</td>
<td valign="top" align="left">M/40</td>
<td valign="top" align="center">23.3</td>
<td valign="top" align="center">8y</td>
<td valign="top" align="center">676</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">85</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">15</td>
<td valign="top" align="center">40</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">45</td>
<td valign="top" align="center">55</td>
<td valign="top" align="center">30</td>
</tr> <tr>
<td valign="top" align="center">11</td>
<td valign="top" align="left">M/36</td>
<td valign="top" align="center">28.3</td>
<td valign="top" align="center">7y</td>
<td valign="top" align="center">637</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">55</td>
<td valign="top" align="center">72</td>
<td valign="top" align="center">75</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">55</td>
<td valign="top" align="center">82.1</td>
</tr> <tr>
<td valign="top" align="center">12</td>
<td valign="top" align="left">M/42</td>
<td valign="top" align="center">23.8</td>
<td valign="top" align="center">7y</td>
<td valign="top" align="center">1,090</td>
<td valign="top" align="left">No</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">66.6</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">84</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">100</td>
<td valign="top" align="center">95</td>
<td valign="top" align="center">93.2</td>
</tr> <tr>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">72 &#x000B1; 33<sup>&#x0002A;</sup></td>
<td valign="top" align="center">52 &#x000B1; 50<sup>&#x0002A;</sup></td>
<td valign="top" align="center">38 &#x000B1; 48<sup>&#x0002A;</sup></td>
<td valign="top" align="center">45 &#x000B1; 33<sup>&#x0002A;</sup></td>
<td valign="top" align="center">55 &#x000B1; 25<sup>&#x0002A;</sup></td>
<td valign="top" align="center">45 &#x000B1; 36<sup>&#x0002A;</sup></td>
<td valign="top" align="center">57 &#x000B1; 33<sup>&#x0002A;</sup></td>
<td valign="top" align="center">52 &#x000B1; 23<sup>&#x0002A;</sup></td>
<td valign="top" align="center">51.9 &#x000B1; 29.4<sup>&#x0002A;</sup></td>
</tr></tbody>
</table>
<table-wrap-foot>
<p>M, Male; F, Female; BMI, Body Mass Index in kg/m<sup>2</sup>; Y, years; CD4 in cells/mm3; ART, Antiretroviral Therapy; DTG, Dolutegravir; 3TC, Lamivudine; TDF, Tenofovir; EFZ, Efavirenz; DRV, Darunavir; RTV, Ritonavir; <sup>&#x0002A;</sup>Mean score of each domain, Mean &#x000B1; SD.</p>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="T2">
<label>Table 2</label>
<caption><p>Clinical, functional, and lung function characteristics of individuals with COVID.</p></caption>
<table frame="box" rules="all">
<thead>
<tr style="background-color:#919498;color:#ffffff">
<th valign="top" align="left"><bold>Variables</bold></th>
<th valign="top" align="center"><bold>plwHCOV (<italic>n =</italic> 12)</bold></th>
<th valign="top" align="center"><bold>mmCOV (<italic>n =</italic> 33)</bold></th>
<th valign="top" align="center"><bold>seCOV (<italic>n =</italic> 18)</bold></th>
<th valign="top" align="center"><bold><italic>P</italic> value</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left"><bold>Age (years)</bold></td>
<td valign="top" align="center">42 &#x000B1; 8</td>
<td valign="top" align="center">42 &#x000B1; 13</td>
<td valign="top" align="center">46 &#x000B1; 7</td>
<td valign="top" align="center">0.437</td>
</tr> <tr style="background-color:#dee1e1">
<td valign="top" align="left" colspan="5">Sex, <italic>n</italic> (%)</td>
</tr> <tr>
<td valign="top" align="left">Male</td>
<td valign="top" align="center">8 (67)</td>
<td valign="top" align="center">19 (58)</td>
<td valign="top" align="center">14 (78)</td>
<td valign="top" align="center"><bold>0.028</bold></td>
</tr> <tr>
<td valign="top" align="left">Female</td>
<td valign="top" align="center">4 (33)</td>
<td valign="top" align="center">14 (42)</td>
<td valign="top" align="center">4 (22)</td>
<td/>
</tr> <tr>
<td valign="top" align="left"><bold>BMI, kg/m</bold><sup><bold>2</bold></sup></td>
<td valign="top" align="center">25 &#x000B1; 3<sup>&#x0002A;</sup></td>
<td valign="top" align="center">28 &#x000B1; 4<sup>&#x00023;</sup></td>
<td valign="top" align="center">32 &#x000B1; 7</td>
<td valign="top" align="center"><bold>0.003</bold></td>
</tr> <tr style="background-color:#dee1e1">
<td valign="top" align="left" colspan="5">mMRC score</td>
</tr> <tr>
<td valign="top" align="left">0</td>
<td valign="top" align="center">2 (17)</td>
<td valign="top" align="center">18 (55)</td>
<td valign="top" align="center">4 (22)</td>
<td valign="top" align="center"><bold>&#x0003C;0.0001</bold></td>
</tr> <tr>
<td valign="top" align="left">I</td>
<td valign="top" align="center">4 (33)</td>
<td valign="top" align="center">14 (42)</td>
<td valign="top" align="center">8 (44)</td>
<td/>
</tr> <tr>
<td valign="top" align="left">II</td>
<td valign="top" align="center">6 (50)</td>
<td valign="top" align="center">1 (3)</td>
<td valign="top" align="center">6 (33)</td>
<td/>
</tr> <tr style="background-color:#dee1e1">
<td valign="top" align="left" colspan="5">6MWT</td>
</tr> <tr>
<td valign="top" align="left">Walking distance (m)</td>
<td valign="top" align="center">545 &#x000B1; 93<sup>&#x0002A;</sup></td>
<td valign="top" align="center">555 &#x000B1; 63<sup>&#x00023;</sup></td>
<td valign="top" align="center">453 &#x000B1; 84</td>
<td valign="top" align="center"><bold>&#x0003C;0.0001</bold></td>
</tr> <tr>
<td valign="top" align="left">% predicted of 6MWT</td>
<td valign="top" align="center">81 &#x000B1; 28<sup>&#x0002A;</sup></td>
<td valign="top" align="center">100 &#x000B1; 14<sup>&#x00023;</sup></td>
<td valign="top" align="center">79 &#x000B1; 18</td>
<td valign="top" align="center"><bold>&#x0003C;0.0001</bold></td>
</tr> <tr style="background-color:#dee1e1">
<td valign="top" align="left" colspan="5">Hemodynamic variables of the 6MWT</td>
</tr> <tr>
<td valign="top" align="left">Initial SBP (mmHg)</td>
<td valign="top" align="center">118 &#x000B1; 9</td>
<td valign="top" align="center">111 &#x000B1; 15<sup>&#x00023;</sup></td>
<td valign="top" align="center">106 &#x000B1; 45</td>
<td valign="top" align="center">0.459</td>
</tr> <tr>
<td valign="top" align="left">Initial DBP (mmHg)</td>
<td valign="top" align="center">79 &#x000B1; 7</td>
<td valign="top" align="center">78 &#x000B1; 10</td>
<td valign="top" align="center">76 &#x000B1; 34</td>
<td valign="top" align="center">0.938</td>
</tr> <tr>
<td valign="top" align="left">Final SBP (mmHg)</td>
<td valign="top" align="center">129 &#x000B1; 17<sup>&#x0002A;</sup></td>
<td valign="top" align="center">123 &#x000B1; 18<sup>&#x00023;</sup></td>
<td valign="top" align="center">100 &#x000B1; 50</td>
<td valign="top" align="center"><bold>0.022</bold></td>
</tr> <tr>
<td valign="top" align="left">Final DBP (mmHg)</td>
<td valign="top" align="center">85 &#x000B1; 10</td>
<td valign="top" align="center">78 &#x000B1; 9</td>
<td valign="top" align="center">68 &#x000B1; 32</td>
<td valign="top" align="center">0.058</td>
</tr> <tr>
<td valign="top" align="left">Initial HR (bpm)</td>
<td valign="top" align="center">74 &#x000B1; 8</td>
<td valign="top" align="center">81 &#x000B1; 12</td>
<td valign="top" align="center">73 &#x000B1; 19</td>
<td valign="top" align="center">0.101</td>
</tr> <tr>
<td valign="top" align="left">Final HR (bpm)</td>
<td valign="top" align="center">83 &#x000B1; 7 <sup>a&#x0002A;</sup></td>
<td valign="top" align="center">127 &#x000B1; 22<sup>&#x00023;</sup></td>
<td valign="top" align="center">84 &#x000B1; 34</td>
<td valign="top" align="center"><bold>&#x0003C;0.0001</bold></td>
</tr> <tr>
<td valign="top" align="left">Initial SpO<sub>2</sub> (%)</td>
<td valign="top" align="center">96 &#x000B1; 1</td>
<td valign="top" align="center">96 &#x000B1; 4<sup>&#x00023;</sup></td>
<td valign="top" align="center">92 &#x000B1; 23</td>
<td valign="top" align="center">0.560</td>
</tr> <tr>
<td valign="top" align="left">Final SpO<sub>2</sub> (%)</td>
<td valign="top" align="center">97 &#x000B1; 1</td>
<td valign="top" align="center">97 &#x000B1; 1</td>
<td valign="top" align="center">81 &#x000B1; 37</td>
<td valign="top" align="center"><bold>0.026</bold></td>
</tr> <tr>
<td valign="top" align="left">Initial BORG dyspnea</td>
<td valign="top" align="center">1.5 &#x000B1; 1</td>
<td valign="top" align="center">0.9 &#x000B1; 0.9<sup>&#x00023;</sup></td>
<td valign="top" align="center">1.9 &#x000B1; 1.8</td>
<td valign="top" align="center"><bold>0.049</bold></td>
</tr> <tr>
<td valign="top" align="left">Final BORG dyspnea</td>
<td valign="top" align="center">3 &#x000B1; 1</td>
<td valign="top" align="center">2.5 &#x000B1; 1.4</td>
<td valign="top" align="center">3.0 &#x000B1; 1.9</td>
<td valign="top" align="center">0.616</td>
</tr> <tr style="background-color:#dee1e1">
<td valign="top" align="left" colspan="5">Spirometry</td>
</tr> <tr>
<td valign="top" align="left">FEV<sub>1</sub>, L/s</td>
<td valign="top" align="center">2.6 &#x000B1; 0.7<sup>a</sup></td>
<td valign="top" align="center">3.1 &#x000B1; 0.7<sup>&#x00023;</sup></td>
<td valign="top" align="center">2.6 &#x000B1; 0.6</td>
<td valign="top" align="center"><bold>0.038</bold></td>
</tr> <tr>
<td valign="top" align="left">FEV<sub>1</sub>, %</td>
<td valign="top" align="center">80 &#x000B1; 12<sup>a&#x0002A;</sup></td>
<td valign="top" align="center">98 &#x000B1; 10<sup>&#x00023;</sup></td>
<td valign="top" align="center">94 &#x000B1; 14</td>
<td valign="top" align="center">&#x0003C;0.0001</td>
</tr> <tr>
<td valign="top" align="left">FVC, L/s</td>
<td valign="top" align="center">3.3 &#x000B1; 0.9</td>
<td valign="top" align="center">3.8 &#x000B1; 0.9</td>
<td valign="top" align="center">3.2 &#x000B1; 0.6</td>
<td valign="top" align="center">0.076</td>
</tr> <tr>
<td valign="top" align="left">FVC, %</td>
<td valign="top" align="center">83 &#x000B1; 11<sup>a&#x0002A;</sup></td>
<td valign="top" align="center">98 &#x000B1; 10</td>
<td valign="top" align="center">94 &#x000B1; 14</td>
<td valign="top" align="center"><bold>0.002</bold></td>
</tr> <tr>
<td valign="top" align="left">FEV<sub>1</sub>/FVC, L/s</td>
<td valign="top" align="center">0.80 &#x000B1; 0.1<sup>&#x0002A;</sup></td>
<td valign="top" align="center">0.87 &#x000B1; 0.1</td>
<td valign="top" align="center">0.94 &#x000B1; 0.1</td>
<td valign="top" align="center"><bold>0.004</bold></td>
</tr> <tr style="background-color:#dee1e1">
<td valign="top" align="left" colspan="5">Respiratory muscle strength</td>
</tr> <tr>
<td valign="top" align="left">MIP (cmH<sub>2</sub>O)</td>
<td valign="top" align="center">92 &#x000B1; 39</td>
<td valign="top" align="center">100 &#x000B1; 36</td>
<td valign="top" align="center">88 &#x000B1; 30</td>
<td valign="top" align="center">0.509</td>
</tr> <tr>
<td valign="top" align="left">Inspiratory muscle weakness</td>
<td valign="top" align="center"><bold>2 (16)</bold></td>
<td valign="top" align="center">6 (18)</td>
<td valign="top" align="center">2 (11)</td>
<td valign="top" align="center">0.800</td>
</tr> <tr>
<td valign="top" align="left">MEP (cmH<sub>2</sub>O)</td>
<td valign="top" align="center">105 &#x000B1; 33</td>
<td valign="top" align="center">122 &#x000B1; 47</td>
<td valign="top" align="center">95 &#x000B1; 40</td>
<td valign="top" align="center">0.095</td>
</tr> <tr>
<td valign="top" align="left"><bold>HIV time (years)</bold></td>
<td valign="top" align="center">8 &#x000B1; 5</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">&#x02013;</td>
<td valign="top" align="center">&#x02013;</td>
</tr></tbody>
</table>
<table-wrap-foot>
<fn id="TN1"><p>plwHCOV, HIV&#x0002B;COVID-19; mmCOV, mild/moderate COVID-19; seCOV, severe COVID-19.</p></fn>
<fn id="TN2"><p><sup>&#x0002A;</sup>p &#x0003C; 0.05 plwHCOV vs. seCOV; <sup>&#x00023;</sup>p &#x0003C; 0.05 seCOVvs mmCOV; <sup>a</sup>p &#x0003C; 0.05 plwHCOV vs mmCOV. BMI, Body mass index; mMRC, modified-Medical research council;</p></fn>
<fn id="TN3"><p>6MWT, 6-min walk test; SBP, Systolic blood pressure; DBP, Diastolic blood pressure; SpO2, O2 saturation; BORG, Scale for dyspnea/fatigue;</p></fn>
<fn id="TN4"><p>FEV, Forced expiratory volume; FVC, Forced vital capacity; MIP, Maximum inspiratory pressure; MEP, Maximum expiratory pressure.</p></fn>
<fn id="TN5"><p>Bold values indicate statistical significance.</p></fn>
</table-wrap-foot>
</table-wrap>
<p>In the plwHCOV group, we found strong correlations (<xref ref-type="fig" rid="F1">Figure 1</xref>) between D6MWT and MEP (<italic>r</italic> = 0.700, <italic>p</italic> = 0.016) and a moderate correlation between SF-36 total score and MEP (cmH<sub>2</sub>O) (<italic>r</italic> = 0.633, <italic>p</italic> = 0.027), demonstrating that respiratory muscle strength directly affects the functional capacity and quality of life.</p>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption><p><bold>(A)</bold> Distance Walked in the 6-Minute Walk Test (D6MWT). <bold>(B)</bold> Maximum Expiratory Pressure (MEP).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fmed-12-1533009-g0001.tif"/>
</fig>
</sec>
<sec>
<title>Population characteristics for the mmCOV and seCOV groups</title>
<p>The mmCOV group had an average age of 42 years and a more balanced gender distribution (58% were male). The mean BMI was 28 kg/m<sup>2</sup>. This group had the best functional performance, covering the longest distance in the 6MWT (555 &#x000B1; 63 m), reaching 100% of the predicted value. FEV1 (98%) and FVC (98%) were the highest among the groups, indicating better lung function. In the seCOV group, the average age was 46 years, with a male predominance (78%) and the highest BMI (32 kg/m<sup>2</sup>). Functional capacity was the most impaired, with the shortest 6MWT distance (453 &#x000B1; 84 m, 79% predicted). Lung function was observed with an FEV1 of 94% and FVC of 94%, along with the highest FEV1/FVC ratio (0.94).</p>
</sec>
<sec>
<title>Functional assessment outcomes</title>
<p>The functional assessments in this study were conducted on average 24 &#x000B1; 5 months after the initial acute COVID-19 in all groups, and all were done before the COVID-19 vaccination roll-out. The proportion of mMRC II scores across groups was 6 (50%), 1 (3%), and 6 (33%) in plwHCOV, mmCOV, and seCOV, respectively. The male sex was predominant across all groups. The plwHCOV group had worse forced expiratory volume in 1st second (FEV<sub>1</sub>%, 80 &#x000B1; 12) (<italic>p</italic> &#x0003C; 0.0001), forced vital capacity (FVC%, 83 &#x000B1; 11) (<italic>p</italic> = 0.002) and FEV<sub>1</sub>/FVC (0.80 &#x000B1; 0.1, <italic>p</italic> = 0.004) when compared to the seCOV group. Interestingly, the plwHCOV group responded similarly to the mmCOV group for the 6MWT, FEV<sub>1</sub>, FVC, and FEV1/FVC (<xref ref-type="table" rid="T2">Table 2</xref>).</p>
</sec>
<sec>
<title>Correlation analysis</title>
<p>We found a moderate correlation association between the walked distance in the 6MWT (6MWD) and FEV<sub>1</sub> (L) (<italic>r</italic> = 0.528, <italic>p</italic> &#x0003C; 0.001) and D6MWT and FVC (L) (<italic>r</italic> = 0.568, <italic>p</italic> &#x0003C; 0.001) (<xref ref-type="fig" rid="F2">Figure 2</xref>) in all three groups. All correlations were tested within the individual populations. For the groups without HIV, the correlation results were: seCOV (<italic>p</italic> = 0.001, <italic>r</italic> = 0.60) and mmCOV (<italic>p</italic> = 0.041, <italic>r</italic> = 0.61).</p>
<fig id="F2" position="float">
<label>Figure 2</label>
<caption><p><bold>(A)</bold> Forced Expiratory Volume in One Second (FEV1). <bold>(B)</bold> Forced Vital Capacity (FVC).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fmed-12-1533009-g0002.tif"/>
</fig>
</sec>
</sec>
<sec sec-type="discussion" id="s4">
<title>Discussion</title>
<p>This study showed a significant proportion of individuals living with HIV presenting significant functional and Quality of life deficits long after COVID-19 infection. Comparing the clinical profiles of long COVID between PLWH and individuals who did not live with HIV and had moderate and severe COVID-19, we observed that PLWH presented functional capacity parameters like moderate cases. At the same time, their lung function was worse than individuals who had had severe COVID-19. Furthermore, we observed correlations between respiratory parameters with D6MWT and Quality of life in the group of individuals living with HIV.</p>
<p>The majority of PLH individuals in this study were male and aged above 40 years, similar to other studies (<xref ref-type="bibr" rid="B31">31</xref>&#x02013;<xref ref-type="bibr" rid="B36">36</xref>). Here, individuals living with HIV demonstrated a 6MWT walked distance above the average of 400 m previously reported for this population (<xref ref-type="bibr" rid="B34">34</xref>). Studies assessing long COVID using the 6MWD outcome report values ranging from 400 to 500 m (<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B37">37</xref>&#x02013;<xref ref-type="bibr" rid="B40">40</xref>) The progression of long COVID-19 is associated with reduced exercise capacity and physical activity levels, which may exacerbate exercise intolerance and ultimately lead to a decline in functional capacity and the ability to perform activities of daily living (<xref ref-type="bibr" rid="B41">41</xref>). In this study, the plwHCOV and mmCOV groups showed greater 6MWT distances compared to the seCOV group. Previous studies have shown that severe acute COVID-19 is characterized by more intense symptoms, greater systemic involvement, and longer hospitalization and recovery periods; thus, worse post-illness conditions were expected (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B37">37</xref>, <xref ref-type="bibr" rid="B42">42</xref>&#x02013;<xref ref-type="bibr" rid="B45">45</xref>). For instance, researchers assessing functional deficiencies post-COVID-19 using the 6MWT in a Mexican population aged above 40 years found that individuals with moderate to severe disease walked shorter distances than those with mild cases, with this decline independently associated with breathing difficulties and respiratory function changes (<xref ref-type="bibr" rid="B46">46</xref>). The extent to which the overlap between long COVID and HIV, or the impact of hospitalization and invasive support during severe and critical acute COVID-19, contributes to functional capacity decline in these populations remains largely unknown and warrants further research.</p>
<p>The plwHCOV group also showed reduced lung function compared to the mmCOV group. Previous studies have demonstrated that PLWH may experience pulmonary deficits associated with both HIV itself and opportunistic respiratory conditions (<xref ref-type="bibr" rid="B47">47</xref>). In our sample, hypertension was the most frequent comorbidity among PLWH, and losartan was the most commonly used antihypertensive. Although some experimental and preclinical studies have suggested a potential protective effect of losartan against lung fibrosis and inflammation through TGF-&#x003B2; modulation and attenuation of AngII activity (<xref ref-type="bibr" rid="B48">48</xref>) these findings have not been supported by robust clinical evidence. A multicenter randomized controlled trial in hospitalized patients with COVID-19 showed that losartan did not improve oxygenation, severity of illness, or other clinical outcomes and even raised concerns about potential adverse effects on hemodynamics and renal function (<xref ref-type="bibr" rid="B49">49</xref>). Similarly, a large placebo-controlled trial evaluating losartan in patients with emphysema found no benefit in preventing disease progression or improving pulmonary function (<xref ref-type="bibr" rid="B50">50</xref>). Based on this high-quality evidence, it is unlikely that losartan biased pulmonary outcomes in our PLWH group; if anything, its use may have attenuated even poorer results. Importantly, participants in the mmCOV and seCOV groups did not report hypertension or use of losartan, which is shown in the results section to address potential treatment-related confounding.</p>
<p>We also observed a correlation between respiratory muscle strength and the distance walked among PLWH participants, suggesting that respiratory performance directly influences functional capacity, as previously described in the literature (<xref ref-type="bibr" rid="B2">2</xref>, <xref ref-type="bibr" rid="B51">51</xref>&#x02013;<xref ref-type="bibr" rid="B53">53</xref>). Collini (<xref ref-type="bibr" rid="B54">54</xref>) showed that PLWH on antiretroviral therapy experience faster pulmonary decline than HIV-negative individuals, driven largely by systemic inflammation (<xref ref-type="bibr" rid="B55">55</xref>&#x02013;<xref ref-type="bibr" rid="B58">58</xref>). This chronic inflammation, combined with the known respiratory consequences of COVID-19 (<xref ref-type="bibr" rid="B22">22</xref>, <xref ref-type="bibr" rid="B59">59</xref>&#x02013;<xref ref-type="bibr" rid="B61">61</xref>), may help explain the reduced lung function observed in the plwHCOV group. The relationship between pulmonary function and functional capacity is well established (<xref ref-type="bibr" rid="B38">38</xref>), and our findings reinforce this association, with significant correlations observed between spirometric values and 6MWD across all groups.</p>
<p>Studies have reported that PLWH has lower-than-expected perceptions of Quality of life due to multifactorial factors (<xref ref-type="bibr" rid="B62">62</xref>&#x02013;<xref ref-type="bibr" rid="B65">65</xref>); among them, non-use or irregular use of ART was indicative of worse perceptions of Quality of life (<xref ref-type="bibr" rid="B66">66</xref>&#x02013;<xref ref-type="bibr" rid="B68">68</xref>). In this study, although the individuals were all on regular ART, their perceptions of Quality of life in the SF-36 questionnaire were below that established in the literature (<xref ref-type="bibr" rid="B69">69</xref>). They significantly correlated with the individuals&#x00027; expiratory muscle strength. Previous studies evaluating respiratory muscle strength in PLWH indicated the influence of respiratory parameters on the general condition of individuals, in addition to the relationship between adequate respiratory muscle strength and Quality of life in other health contexts already established in the literature (<xref ref-type="bibr" rid="B19">19</xref>, <xref ref-type="bibr" rid="B70">70</xref>, <xref ref-type="bibr" rid="B71">71</xref>).</p>
<p>Finally, although BMI differed significantly across groups&#x02014;with higher values in the seCOV group&#x02014;the spirometry outcomes were expressed as predicted percentages adjusted for age, sex, and height, which minimizes the influence of body composition on interpretation. Moreover, the group with the lowest BMI (plwHCOV) exhibited the most reduced spirometric parameters, suggesting that BMI alone was not the primary factor influencing pulmonary function in this cohort. Nonetheless, we acknowledge that excess body weight may contribute to a restrictive ventilatory pattern in some individuals, particularly within the seCOV group, and this potential influence cannot be entirely excluded.</p>
<p>Our study has some limitations. Due to its cross-sectional design, the study cannot establish causal relationships between the observed outcomes and prior COVID-19 or long COVID. It is therefore unclear whether the reduced functional or respiratory measures observed, particularly in individuals with long COVID, were pre-existing or developed as a consequence of the infection. Additionally, no pre-COVID-19 data on lung function or functional capacity were available for comparison. The relatively small sample size and the fact that this was a single-center study may also limit the generalizability of the findings. Participants were heterogeneous in terms of BMI, which may have influenced the respiratory outcomes. The plwHCOV group was particularly limited in size due to challenges in recruiting individuals living with HIV, many of whom expressed concerns about confidentiality&#x02014;an issue often driven by persistent social stigma. These concerns also motivated the inclusion of quality of life assessments in this group.</p>
</sec>
<sec sec-type="conclusions" id="s5">
<title>Conclusion</title>
<p>People living with HIV/AIDS showed worse lung function compared to individuals without HIV but had severe COVID-19, yet showed similar results in 6MWT, FEV<sub>1</sub>, FVC, and FEV<sub>1</sub>/FVC as those with moderate/mild COVID-19. Our findings highlight persistent deficits in lung function among PLWH even after more than 2 years post-COVID-19 infection, significantly impacting their functional capacity and Quality of life. Targeted interventions involving cardiorespiratory and motor rehabilitation are essential for PLWH experiencing long COVID. Further comprehensive studies are needed to comprehend the contribution of HIV to functional deterioration in long COVID cases.</p>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="s6">
<title>Data availability statement</title>
<p>The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.</p>
</sec>
<sec sec-type="ethics-statement" id="s7">
<title>Ethics statement</title>
<p>The studies involving humans were approved by Federal University of Amazonas Institutional Review Board approved this study (CAAE 44971221.7.0000.5020). 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 sec-type="author-contributions" id="s8">
<title>Author contributions</title>
<p>AR: Conceptualization, Investigation, Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. JV: Investigation, Supervision, Visualization, Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. CG: Methodology, Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. FeF: Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. BM: Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. VM: Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. HB: Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. FrF: Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. CA: Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. TM: Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. MA: Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. LF: Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. GC: Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. GA: Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. FA-V: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing.</p>
</sec>
<sec sec-type="funding-information" id="s9">
<title>Funding</title>
<p>The author(s) declare that financial support was received for the research and/or publication of this article. The study was supported by CAPES (PROCAD Amazonia 88887.200582/2018-00) and CNPq (CNPq/MCTI/CT n&#x000B0;53/2022 and CNPq/MCTI/FNDCT n&#x000B0;18/2021). FA-V received a post-doctoral fellowship from CAPES, Brazil (PROCAD-AM 88887.321243/2019-00). AR, JV, and CA were supported by CNPq technological development grants (CNPq/MCTI/CT n&#x000B0;53/2022).</p>
</sec>
<sec sec-type="COI-statement" id="conf1">
<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 sec-type="ai-statement" id="s10">
<title>Generative AI statement</title>
<p>The author(s) declare that no Gen AI was used in the creation of this manuscript.</p>
</sec>
<sec sec-type="disclaimer" id="s11">
<title>Publisher&#x00027;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>
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