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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0007">Introduction</span><p id="para0006" class="elsevierStylePara elsevierViewall">Ivermectin is a medication of the avermectin family of compounds that is FDA-approved to treat parasite infections&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> A preliminary <span class="elsevierStyleItalic">in vitro</span> study on the effect of ivermectin against SARS-CoV-2&#44;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> caused a huge increase in its over-the-counter use&#44; despite the lack of evidence of clinical efficacy&#46; Ivermectin has a controversial immunomodulatory effect in animal models&#44; either increasing antibody production and white-blood-cell count or decreasing antibody levels in a dose dependent response&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a></p><p id="para0007" class="elsevierStylePara elsevierViewall">Seroconversion rates and durability of specific antibodies in SARS-CoV-2 infection are not completely understood&#46; Impaired production of antibodies against COVID-19 can affect disease severity&#44; and likelihood of reinfection&#46;<a class="elsevierStyleCrossRefs" href="#bib0004"><span class="elsevierStyleSup">4&#8211;6</span></a> Understanding the immune response in COVID-19 patients is essential for its treatment and prevention&#46;</p><p id="para0008" class="elsevierStylePara elsevierViewall">This study investigates the effects of self-prescribed use of different ivermectin doses on rates of seroconversion for SARS-CoV-2 in health care workers &#40;HCW&#41; diagnosed with COVID-19&#44; and the ability of HCW&#180; peripheral blood mononuclear cells &#40;PBMCs&#41; to present an <span class="elsevierStyleItalic">in vitro</span>-induced IgG antibodies &#40;IVIAP&#41; positive test&#44; as well as to produce Th1&#47;Th2 cytokines&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Methods</span><p id="para0009" class="elsevierStylePara elsevierViewall">In this cross-sectional study we included HCW diagnosed with COVID-19 from May to July 2020 at Professor Edgard Santos University Hospital&#44; in Salvador-Brazil&#46; SARS-CoV-2 infection was confirmed by RT-PCR test &#40;Charit&#233;-Berlin protocol&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> This study was approved by the Institutional Research Ethics Committee &#40;No&#46; 4&#46;042&#46;620&#41;&#46;</p><p id="para0010" class="elsevierStylePara elsevierViewall">After signing the informed consent form&#44; participants donated 10 ml of blood to perform laboratory tests and filled out a questionnaire on demographics&#44; clinical characteristics&#44; medications and ivermectin dosages used during disease&#46; We stratified HCW by use of ivermectin &#40;no use&#47;single dose vs multiple doses&#41;&#46; Each dose corresponds to one 6 mg pill of ivermectin&#46;</p><p id="para0011" class="elsevierStylePara elsevierViewall">Samples were screened using a commercially available <span class="elsevierStyleItalic">in vitro</span> immunoassay &#40;2019-nCoV IgG kit&#44; SNIBE diagnostics&#44; Shenzhen&#44; China&#41; to detect SARS-CoV-2-specific immunoglobulins against full-length spike and nucleocapsid proteins&#46; A result greater than or equal to 1&#46;00&#160;AU&#47;mL was considered reactive&#46; Next&#44; a cPass Neutralization Antibody Detection kit &#40;Genscript&#44; Leiden&#44; the Netherlands&#41; was used to detect circulating neutralizing antibodies against SARS-CoV-2 that block the interaction between the receptor binding domain &#40;RBD&#41; of the viral spike glycoprotein with the ACE2 cell surface receptor&#46; A ratio greater than 20&#37; was considered positive&#44; according to manufacturer&#180;s instructions&#46;</p><p id="para0012" class="elsevierStylePara elsevierViewall">An <span class="elsevierStyleItalic">in vitro</span> Induced Antibody Production &#40;IVIAP&#41; test was used to identify the ability of HCW&#180;s PBMC in producing IgG specific antibodies against SARS-CoV-2&#44; and 11 different cytokines&#44; after stimulation with the peak spike protein&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> PBMCs were separated by a Ficoll-Hypaque gradient&#44; washed three times and adjusted to 2&#160;&#215;&#160;10<span class="elsevierStyleSup">5</span> cells&#47;100 uL&#47;well in RPMI 1640 medium containing 10&#37; fetal bovine serum&#46; PBMCs were cultured in an Anti-SARS-CoV-2 IgG ELISA microplate for 24 hours at 37&#176;C and 5&#37; CO2&#46; After 24 h&#44; levels of IL1 beta&#44; IL2&#44; IL4&#44; IL5&#44; IL6&#44; IL10&#44; IL12&#44; P70IL13&#44; TNF-alpha&#44; IFN-y and GM-CSF were measured in culture&#180;s supernatant &#40;Human Th1&#47;Th2 Magnetic Luminex Performance Assay 11-plex Fixed Panel Summary&#44; R&#38;D Systems&#44; Minneapolis&#44; MN&#44; USA&#41;&#46; Detection of IgG antibodies against SARS-CoV-2 was performed in the microplates used to culture the PBMCs&#46; Mean elapsed time between diagnosis of COVID-19 and study&#180;s tests was 109 days&#44; and was similar for both groups&#46;</p><p id="para0013" class="elsevierStylePara elsevierViewall">To calculate the sample size we estimated that 75&#37; of COVID-19 patients would have a positive IVIAP test&#44; and only 30&#37; of those using ivermectin would do so&#46; A total of 46 participants would provide 80&#37; power&#44; 95&#37; confidence intervals &#40;CI&#41; for the study&#46; Mann-Whitney rank test was used to compare medians of IgG antibody Index and cPASS versus IVIAP &#40;positive&#47;negative&#41; and use of Ivermectin &#40;1 &#8804; dose versus multiple doses&#41;&#46; Fisher exact text &#40;bicaudal&#41; was used to compare ivermectin use versus ELISA&#44; IVIAP&#44; cPASS &#40;less than 20&#37;&#44; as negative&#44; 20&#37; or more&#44; positive&#41; results&#46;</p></span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Results</span><p id="para0014" class="elsevierStylePara elsevierViewall">A total of 45 HCW were evaluated&#46; Mean time between COVID-19 diagnosis and laboratory testing was similar for IVIAP positive &#40;110&#46;7&#177;31&#46;8 days&#41; or negative HCW &#40;112&#160;&#177;&#160;65&#46;5 days&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;3&#41;&#46; The most used medications during acute disease were ivermectin&#44; azithromycin&#44; and oral corticosteroids&#46; Ivermectin was used by 19 HCW &#40;8 used a single dose&#44; 11 used multiple doses&#41;&#46; There was no significant difference in disease severity for HCW who used ivermectin compared to those who did not&#46; However&#44; abdominal pain&#44; diarrhea&#44; and taste perversion were more frequent in HCW that used multiple doses of ivermectin &#40;<a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia><p id="para0015" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0002"></elsevierMultimedia><p id="para0016" class="elsevierStylePara elsevierViewall">Seroconversion for SARS-CoV-2 was detected in 42&#47;45 &#40;93&#37;&#41; HCW&#46; SARS-CoV-2 antibodies were detected in 8&#47;10 &#40;80&#37;&#41; HCW that used multiple doses of ivermectin&#44; versus 33&#47;34 &#40;97&#37;&#41; of those that used &#8804; 1 dose &#40;<span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;1&#59; One patient in multiple doses group was not tested because of insufficient sample&#41;&#46; IVIAP test was positive in 24&#47;45 &#40;53&#37;&#41; HCW&#44; all of them in &#8804; 1 dose group &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#41;&#46; In addition&#44; HCW in multiple dose ivermectin group had significantly lower antibodies levels than those in &#8804; 1 dose group &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;009&#41;&#46; Neutralizing antibodies against SARS-CoV-2 were detected in 39 &#40;91&#37;&#41; participants &#40;97&#37; in 1 &#8804; dose vs&#46; 70&#37; in &#62;1 dose groups&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;03&#41;&#46; cPass values were also significantly higher for patients with an IVIAP positive test than for those with a negative result &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#41;&#46; Serological results are summarized in <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>&#46; There was no difference in cytokines production across groups&#46; SARS-CoV-2 viral load did not differ among HCW who used &#8804; 1 dose &#40;CT&#58; 31&#46;1&#160;&#177;&#160;4&#46;7&#41; or multiple doses of ivermectin &#40;CT&#160;&#61;&#160;29&#46;8&#160;&#177;&#160;4&#46;7&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;37&#41;&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Discussion</span><p id="para0017" class="elsevierStylePara elsevierViewall">We showed that self-prescribed&#44; multiple doses ivermectin use was significantly associated with lower frequency and levels of neutralizing antibodies against SARS-CoV-2&#46; In addition&#44; PBMCs of most individuals who used multiple doses of ivermectin&#44; failed to produce SARS-CoV-2 IgG antibodies when exposed to the recombinant protein S1 in a dose-dependent fashion&#46;</p><p id="para0018" class="elsevierStylePara elsevierViewall">Ivermectin is a macrocyclic lactone that has direct action on PAK-1&#44; interfering in phosphorylation events&#44; essential for a large number of cellular processes&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> Immunosuppressants derived from macrocyclic lactones &#40;like Everolimus and Sirolimus&#41;&#44; act in the Mtor activation domain&#44; resulting in inhibition of antigen-induced T lymphocyte activation and proliferation&#44; as well as cytokine blockage&#44; also inhibiting antibody production&#46; High doses of ivermectin could induce such effects and interfere with antigen recognition and immune memory formation&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a></p><p id="para0019" class="elsevierStylePara elsevierViewall">Ivermectin was able to inhibit replication of several RNA viruses &#40;including SARS-CoV-2&#41; in <span class="elsevierStyleItalic">in vitro</span> studies&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> However&#44; the inhibitory capacity &#40;IC 50&#41; of ivermectin only occurs in extremely high concentrations&#44; 50&#8211;100 times that detected in plasma of an adult weighing 70&#160;kg after a single dose of 200&#160;&#956;g&#47;kg&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> Co-administration of ivermectin and azithromycin promotes an increase of 31&#37; in maximum concentration &#40;Cmax&#41; and 27&#37; in the maximum time &#40;Tmax&#41; of stay in the AUC of ivermectin&#46;<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a> In our study&#44; we found that among 25&#47;45 &#40;55&#46;5&#37;&#41; patients who presented a negative IVIAP test&#44; 14 &#40;56&#37;&#41; of them used ivermectin&#44; 12 &#40;86&#37;&#41; for three or more days&#44; often in association with azithromycin&#46;</p><p id="para0020" class="elsevierStylePara elsevierViewall">Our findings demonstrate that use of multiple doses of ivermectin in COVID-19 patients was significantly associated with lower frequency&#47;lower levels of neutralizing antibodies and reduced production of SARS-CoV-2 antibodies by stimulated PBMCs&#46; No effect was observed on Th1&#47;Th1 cytokines production by stimulated cells&#44; suggesting the effect could be associated with interference on B cells activation or immune memory formation&#46;</p><p id="para0021" class="elsevierStylePara elsevierViewall">The lack of evaluation of specific cellular population involved in immune response to SARS-CoV-2&#44; and the relatively small sample size limit the reach of our conclusions&#46; Nevertheless&#44; our results strongly suggest that ivermectin use can interfere in the specific immune response to SARS-CoV-2 infection&#44; affecting memory cells and the production of antibodies against that virus&#46; Further studies are needed to understand how this effect is promoted by ivermectin use&#44; and what are the consequences for post-infection immunity&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">Funding</span><p id="para0022" class="elsevierStylePara elsevierViewall">The study was not associated with any research grant or other funding support&#46;</p></span></span>"
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          "titulo" => "Acknowledgments"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2021-05-19"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Background</span><p id="spara005" class="elsevierStyleSimplePara elsevierViewall">Over-the-counter use of ivermectin amongst other drugs as SARS-CoV-2 treatment has been increasingly common&#44; despite the lack of evidence on its clinical efficacy&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Objective</span><p id="spara006" class="elsevierStyleSimplePara elsevierViewall">To evaluate the effect of ivermectin use on production of antibodies against SARS-CoV-2 in health care workers &#40;HCW&#41; diagnosed with COVID-19 and of Th1&#47;Th2 cytokines by stimulated peripheral blood mononuclear cells of the same cohort &#40;PBMCs&#41;&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Methods</span><p id="spara007" class="elsevierStyleSimplePara elsevierViewall">This cross-sectional study evaluated seroconversion and neutralizing antibodies production in HCW at Complexo Hospitalar Universit&#225;rio Professor Edgard Santos &#40;Salvador&#44; Brazil&#41;&#44; diagnosed with COVID-19 from May to July&#44; 2020&#44; as well as <span class="elsevierStyleItalic">in vitro</span> production of antibody against SARS-CoV-2 and Th1&#47;Th2 cytokines&#46; Analyses were performed between December 2020 and February 2021&#46; Participants were stratified according to the use of ivermectin &#40;&#8804; 1 dose vs&#46; multiple doses&#41; for treatment of COVID-19&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Results</span><p id="spara008" class="elsevierStyleSimplePara elsevierViewall">45 HCW were included &#40;62&#37; women&#41;&#46; Mean age was 39 years&#44; and disease severity was similar across groups&#46; Neutralizing antibodies were detected less frequently in multiple doses &#40;70&#37;&#41; vs&#46; &#8804; 1 dose &#40;97&#37;&#41; groups&#44; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;02&#41;&#46; PBMCs of patients in multiple doses group also were less likely to produce antibodies against SARS-CoV-2 following <span class="elsevierStyleItalic">in vitro</span> stimulation with purified spike protein in comparison with patients in &#8804; 1 dose group &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#41;&#46; PBMC&#180;s production of Th1&#47;Th2 cytokines levels was similar across groups&#46; Abdominal pain &#40;15&#37; vs 46&#37;&#44; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;04&#41;&#44; diarrhea &#40;21&#37; vs&#46; 55&#37;&#44; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;05&#41; and taste perversion &#40;0&#37; vs&#46; 18&#37;&#44; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;05&#41; were more frequently reported by participants that used multiple doses of ivermectin&#46;</p></span> <span id="abss0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0006">Conclusions</span><p id="spara009" class="elsevierStyleSimplePara elsevierViewall">Although there was no evidence for differential disease severity upon ivermectin use for treatment of COVID-19 it was associated with more gastro-intestinal side-effects and impairment of anti-SARS-CoV2 antibodies production&#44; in a dose dependent manner&#46; This potentially impacts the effectiveness of immune response and the risk of reinfection and warrants additional studies for clarifying the mechanisms and consequences of such immunomodulatory effects&#46;</p></span>"
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          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">&#40;A-D&#41; &#8211; Index of IgG antibodies against SARS-CoV-2 and Neutralization values according to IVIAP results and to ivermectin use&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0002"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Ivermectin use</th></tr><tr title="table-row"><a name="en0003"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&#8804; 1 dose <span class="elsevierStyleItalic">N</span>&#160;&#61;&#160;34 &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tb1fn1"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tb1fn2"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tb1fn3"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0005"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Multiple doses <span class="elsevierStyleItalic">N</span>&#160;&#61;&#160;11 &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0006"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Total <span class="elsevierStyleItalic">N</span>&#160;&#61;&#160;45 &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0007"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Female sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21 &#40;61&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0009"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7 &#40;63&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">28 &#40;62&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0011"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Median age &#40;IQI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">39&#46;0 &#40;36&#8211;43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0013"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">39 &#40;35&#8211;58&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">39 &#40;36&#8211;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0015"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Disease presentation Severe Moderate Asymptomatic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0019"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11 &#40;32&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0021"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 &#40;31&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0023"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0025"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;45&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17 &#40;37&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0027"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11 &#40;32&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0029"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 &#40;31&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0031"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Ageusia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19 &#40;55&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;45&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">24 &#40;53&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0035"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Anorexia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;14&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7 &#40;15&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0039"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21 &#40;61&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">9 &#40;81&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">30 &#40;66&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0043"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Diarrhea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7 &#40;20&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6 &#40;54&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13 &#40;28&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0047"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Abdominal pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;14&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;45&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10 &#40;22&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0051"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Throat pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0055"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Chest pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;14&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8 &#40;17&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0059"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Fatigue&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0061"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;45&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17 &#40;37&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0063"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0065"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13 &#40;28&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0067"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Myalgia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0069"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;45&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17 &#40;37&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0071"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Nausea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8 &#40;23&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;36&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;26&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0075"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Odynophagia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;5&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;4&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0079"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Anosmia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21 &#40;61&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0081"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6 &#40;54&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">27 &#40;60&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0083"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Dyspnea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11 &#40;32&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0085"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;36&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0087"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Muscle Weakness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;8&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0091"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Paresis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;8&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0093"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0095"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Dizziness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6 &#40;17&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8 &#40;17&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0099"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Cough&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11 &#40;32&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0101"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0102"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 &#40;31&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0103"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Arthralgia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0104"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;8&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0105"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0106"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;8&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0107"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Dysgeusia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0108"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0109"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0110"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;4&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0111"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Azithromycin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0112"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13 &#40;38&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0113"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">9 &#40;81&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0114"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">22 &#40;48&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0115"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Corticosteroid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0116"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10 &#40;29&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;36&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0118"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 &#40;31&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0119"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Other medication&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0120"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10 &#40;30&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0121"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;45&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 &#40;34&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Clinical and demographic characteristics of health care workers diagnosed with COVID-19&#44; by ivermectin use&#46;</p>"
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                  \t\t\t\t ; entry_with_role_colgroup " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Ivermectin use</th></tr><tr title="table-row"><a name="en0125"></a><th class="td" title="\n
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                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8804; 1 dose Median &#40;IQR&#41;</th><a name="en0127"></a><th class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Multiple doses Median &#40;IQR&#41;</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0128"></a><td class="td-with-role" title="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="" valign="top">1&#46;0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&#40;1&#46;0&#8211;29&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">IL - 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0139"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#40;1&#46;3&#8211;3&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">IL - 6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0149"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&#40;1&#8211;447&#46;32&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&#40;1&#8211;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">IL - 10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0154"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;2495&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#40;0&#46;069&#8211;0&#46;922&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;873&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0157"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#40;0&#46;146&#8211;1&#46;24&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0158"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">IL - 12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0159"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;0275&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&#40;0&#46;022&#8211;0&#46;034&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">0&#46;032&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&#40;0&#46;022&#8211;0&#46;043&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">IL - 13&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0168"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">TNF-&#945;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">495&#46;19&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">519&#46;14&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#40;154&#46;79&#8211;10&#44;000&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0173"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">IFN- y&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">26&#46;394&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0178"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">GM-CSF&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&#40;0&#46;0&#8211;0&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">0&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&#40;0&#46;1&#8211;0&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                        "tituloSerie" => "Antiviral Res"
                        "fecha" => "2020"
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                            5 => "W&#46; Ng Chie"
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                        "tituloSerie" => "Vet Immunol Immunopathol"
                        "fecha" => "1995"
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                    0 => array:2 [
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Brief Communication
Self-prescribed Ivermectin use is associated with a lower rate of seroconversion in health care workers diagnosed with COVID, in a dose-dependent response
Célia Pedrosoa, Sara Vaza, Eduardo Martins Nettoa, Daniele Souzaa, Felice Demincoa, Rafaela Mayorala, Eliana Menezesa, Ana Patricia Amancio da Cunhaa, Andres Moreira-Sotob, Jan Felix Drexlerb,c, Carlos Britesa,
Corresponding author
crbrites@gmail.com

Corresponding author.
a Federal University of Bahia, Complexo Hospitalar Universitário Professor Edgard Santos, Laboratório de Pesquisa em Infectologia (LAPI), Bahia, BA, Brazil
b Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Institute of Virology, Berlin, Germany
c German Centre for Infection Research, Berlin, Germany
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          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">&#40;A-D&#41; &#8211; Index of IgG antibodies against SARS-CoV-2 and Neutralization values according to IVIAP results and to ivermectin use&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0007">Introduction</span><p id="para0006" class="elsevierStylePara elsevierViewall">Ivermectin is a medication of the avermectin family of compounds that is FDA-approved to treat parasite infections&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> A preliminary <span class="elsevierStyleItalic">in vitro</span> study on the effect of ivermectin against SARS-CoV-2&#44;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a> caused a huge increase in its over-the-counter use&#44; despite the lack of evidence of clinical efficacy&#46; Ivermectin has a controversial immunomodulatory effect in animal models&#44; either increasing antibody production and white-blood-cell count or decreasing antibody levels in a dose dependent response&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a></p><p id="para0007" class="elsevierStylePara elsevierViewall">Seroconversion rates and durability of specific antibodies in SARS-CoV-2 infection are not completely understood&#46; Impaired production of antibodies against COVID-19 can affect disease severity&#44; and likelihood of reinfection&#46;<a class="elsevierStyleCrossRefs" href="#bib0004"><span class="elsevierStyleSup">4&#8211;6</span></a> Understanding the immune response in COVID-19 patients is essential for its treatment and prevention&#46;</p><p id="para0008" class="elsevierStylePara elsevierViewall">This study investigates the effects of self-prescribed use of different ivermectin doses on rates of seroconversion for SARS-CoV-2 in health care workers &#40;HCW&#41; diagnosed with COVID-19&#44; and the ability of HCW&#180; peripheral blood mononuclear cells &#40;PBMCs&#41; to present an <span class="elsevierStyleItalic">in vitro</span>-induced IgG antibodies &#40;IVIAP&#41; positive test&#44; as well as to produce Th1&#47;Th2 cytokines&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Methods</span><p id="para0009" class="elsevierStylePara elsevierViewall">In this cross-sectional study we included HCW diagnosed with COVID-19 from May to July 2020 at Professor Edgard Santos University Hospital&#44; in Salvador-Brazil&#46; SARS-CoV-2 infection was confirmed by RT-PCR test &#40;Charit&#233;-Berlin protocol&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> This study was approved by the Institutional Research Ethics Committee &#40;No&#46; 4&#46;042&#46;620&#41;&#46;</p><p id="para0010" class="elsevierStylePara elsevierViewall">After signing the informed consent form&#44; participants donated 10 ml of blood to perform laboratory tests and filled out a questionnaire on demographics&#44; clinical characteristics&#44; medications and ivermectin dosages used during disease&#46; We stratified HCW by use of ivermectin &#40;no use&#47;single dose vs multiple doses&#41;&#46; Each dose corresponds to one 6 mg pill of ivermectin&#46;</p><p id="para0011" class="elsevierStylePara elsevierViewall">Samples were screened using a commercially available <span class="elsevierStyleItalic">in vitro</span> immunoassay &#40;2019-nCoV IgG kit&#44; SNIBE diagnostics&#44; Shenzhen&#44; China&#41; to detect SARS-CoV-2-specific immunoglobulins against full-length spike and nucleocapsid proteins&#46; A result greater than or equal to 1&#46;00&#160;AU&#47;mL was considered reactive&#46; Next&#44; a cPass Neutralization Antibody Detection kit &#40;Genscript&#44; Leiden&#44; the Netherlands&#41; was used to detect circulating neutralizing antibodies against SARS-CoV-2 that block the interaction between the receptor binding domain &#40;RBD&#41; of the viral spike glycoprotein with the ACE2 cell surface receptor&#46; A ratio greater than 20&#37; was considered positive&#44; according to manufacturer&#180;s instructions&#46;</p><p id="para0012" class="elsevierStylePara elsevierViewall">An <span class="elsevierStyleItalic">in vitro</span> Induced Antibody Production &#40;IVIAP&#41; test was used to identify the ability of HCW&#180;s PBMC in producing IgG specific antibodies against SARS-CoV-2&#44; and 11 different cytokines&#44; after stimulation with the peak spike protein&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> PBMCs were separated by a Ficoll-Hypaque gradient&#44; washed three times and adjusted to 2&#160;&#215;&#160;10<span class="elsevierStyleSup">5</span> cells&#47;100 uL&#47;well in RPMI 1640 medium containing 10&#37; fetal bovine serum&#46; PBMCs were cultured in an Anti-SARS-CoV-2 IgG ELISA microplate for 24 hours at 37&#176;C and 5&#37; CO2&#46; After 24 h&#44; levels of IL1 beta&#44; IL2&#44; IL4&#44; IL5&#44; IL6&#44; IL10&#44; IL12&#44; P70IL13&#44; TNF-alpha&#44; IFN-y and GM-CSF were measured in culture&#180;s supernatant &#40;Human Th1&#47;Th2 Magnetic Luminex Performance Assay 11-plex Fixed Panel Summary&#44; R&#38;D Systems&#44; Minneapolis&#44; MN&#44; USA&#41;&#46; Detection of IgG antibodies against SARS-CoV-2 was performed in the microplates used to culture the PBMCs&#46; Mean elapsed time between diagnosis of COVID-19 and study&#180;s tests was 109 days&#44; and was similar for both groups&#46;</p><p id="para0013" class="elsevierStylePara elsevierViewall">To calculate the sample size we estimated that 75&#37; of COVID-19 patients would have a positive IVIAP test&#44; and only 30&#37; of those using ivermectin would do so&#46; A total of 46 participants would provide 80&#37; power&#44; 95&#37; confidence intervals &#40;CI&#41; for the study&#46; Mann-Whitney rank test was used to compare medians of IgG antibody Index and cPASS versus IVIAP &#40;positive&#47;negative&#41; and use of Ivermectin &#40;1 &#8804; dose versus multiple doses&#41;&#46; Fisher exact text &#40;bicaudal&#41; was used to compare ivermectin use versus ELISA&#44; IVIAP&#44; cPASS &#40;less than 20&#37;&#44; as negative&#44; 20&#37; or more&#44; positive&#41; results&#46;</p></span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Results</span><p id="para0014" class="elsevierStylePara elsevierViewall">A total of 45 HCW were evaluated&#46; Mean time between COVID-19 diagnosis and laboratory testing was similar for IVIAP positive &#40;110&#46;7&#177;31&#46;8 days&#41; or negative HCW &#40;112&#160;&#177;&#160;65&#46;5 days&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;3&#41;&#46; The most used medications during acute disease were ivermectin&#44; azithromycin&#44; and oral corticosteroids&#46; Ivermectin was used by 19 HCW &#40;8 used a single dose&#44; 11 used multiple doses&#41;&#46; There was no significant difference in disease severity for HCW who used ivermectin compared to those who did not&#46; However&#44; abdominal pain&#44; diarrhea&#44; and taste perversion were more frequent in HCW that used multiple doses of ivermectin &#40;<a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia><p id="para0015" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0002"></elsevierMultimedia><p id="para0016" class="elsevierStylePara elsevierViewall">Seroconversion for SARS-CoV-2 was detected in 42&#47;45 &#40;93&#37;&#41; HCW&#46; SARS-CoV-2 antibodies were detected in 8&#47;10 &#40;80&#37;&#41; HCW that used multiple doses of ivermectin&#44; versus 33&#47;34 &#40;97&#37;&#41; of those that used &#8804; 1 dose &#40;<span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;1&#59; One patient in multiple doses group was not tested because of insufficient sample&#41;&#46; IVIAP test was positive in 24&#47;45 &#40;53&#37;&#41; HCW&#44; all of them in &#8804; 1 dose group &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#41;&#46; In addition&#44; HCW in multiple dose ivermectin group had significantly lower antibodies levels than those in &#8804; 1 dose group &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;009&#41;&#46; Neutralizing antibodies against SARS-CoV-2 were detected in 39 &#40;91&#37;&#41; participants &#40;97&#37; in 1 &#8804; dose vs&#46; 70&#37; in &#62;1 dose groups&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;03&#41;&#46; cPass values were also significantly higher for patients with an IVIAP positive test than for those with a negative result &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#41;&#46; Serological results are summarized in <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>&#46; There was no difference in cytokines production across groups&#46; SARS-CoV-2 viral load did not differ among HCW who used &#8804; 1 dose &#40;CT&#58; 31&#46;1&#160;&#177;&#160;4&#46;7&#41; or multiple doses of ivermectin &#40;CT&#160;&#61;&#160;29&#46;8&#160;&#177;&#160;4&#46;7&#59; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;37&#41;&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Discussion</span><p id="para0017" class="elsevierStylePara elsevierViewall">We showed that self-prescribed&#44; multiple doses ivermectin use was significantly associated with lower frequency and levels of neutralizing antibodies against SARS-CoV-2&#46; In addition&#44; PBMCs of most individuals who used multiple doses of ivermectin&#44; failed to produce SARS-CoV-2 IgG antibodies when exposed to the recombinant protein S1 in a dose-dependent fashion&#46;</p><p id="para0018" class="elsevierStylePara elsevierViewall">Ivermectin is a macrocyclic lactone that has direct action on PAK-1&#44; interfering in phosphorylation events&#44; essential for a large number of cellular processes&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> Immunosuppressants derived from macrocyclic lactones &#40;like Everolimus and Sirolimus&#41;&#44; act in the Mtor activation domain&#44; resulting in inhibition of antigen-induced T lymphocyte activation and proliferation&#44; as well as cytokine blockage&#44; also inhibiting antibody production&#46; High doses of ivermectin could induce such effects and interfere with antigen recognition and immune memory formation&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a></p><p id="para0019" class="elsevierStylePara elsevierViewall">Ivermectin was able to inhibit replication of several RNA viruses &#40;including SARS-CoV-2&#41; in <span class="elsevierStyleItalic">in vitro</span> studies&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> However&#44; the inhibitory capacity &#40;IC 50&#41; of ivermectin only occurs in extremely high concentrations&#44; 50&#8211;100 times that detected in plasma of an adult weighing 70&#160;kg after a single dose of 200&#160;&#956;g&#47;kg&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> Co-administration of ivermectin and azithromycin promotes an increase of 31&#37; in maximum concentration &#40;Cmax&#41; and 27&#37; in the maximum time &#40;Tmax&#41; of stay in the AUC of ivermectin&#46;<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a> In our study&#44; we found that among 25&#47;45 &#40;55&#46;5&#37;&#41; patients who presented a negative IVIAP test&#44; 14 &#40;56&#37;&#41; of them used ivermectin&#44; 12 &#40;86&#37;&#41; for three or more days&#44; often in association with azithromycin&#46;</p><p id="para0020" class="elsevierStylePara elsevierViewall">Our findings demonstrate that use of multiple doses of ivermectin in COVID-19 patients was significantly associated with lower frequency&#47;lower levels of neutralizing antibodies and reduced production of SARS-CoV-2 antibodies by stimulated PBMCs&#46; No effect was observed on Th1&#47;Th1 cytokines production by stimulated cells&#44; suggesting the effect could be associated with interference on B cells activation or immune memory formation&#46;</p><p id="para0021" class="elsevierStylePara elsevierViewall">The lack of evaluation of specific cellular population involved in immune response to SARS-CoV-2&#44; and the relatively small sample size limit the reach of our conclusions&#46; Nevertheless&#44; our results strongly suggest that ivermectin use can interfere in the specific immune response to SARS-CoV-2 infection&#44; affecting memory cells and the production of antibodies against that virus&#46; Further studies are needed to understand how this effect is promoted by ivermectin use&#44; and what are the consequences for post-infection immunity&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">Funding</span><p id="para0022" class="elsevierStylePara elsevierViewall">The study was not associated with any research grant or other funding support&#46;</p></span></span>"
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        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Background</span><p id="spara005" class="elsevierStyleSimplePara elsevierViewall">Over-the-counter use of ivermectin amongst other drugs as SARS-CoV-2 treatment has been increasingly common&#44; despite the lack of evidence on its clinical efficacy&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Objective</span><p id="spara006" class="elsevierStyleSimplePara elsevierViewall">To evaluate the effect of ivermectin use on production of antibodies against SARS-CoV-2 in health care workers &#40;HCW&#41; diagnosed with COVID-19 and of Th1&#47;Th2 cytokines by stimulated peripheral blood mononuclear cells of the same cohort &#40;PBMCs&#41;&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Methods</span><p id="spara007" class="elsevierStyleSimplePara elsevierViewall">This cross-sectional study evaluated seroconversion and neutralizing antibodies production in HCW at Complexo Hospitalar Universit&#225;rio Professor Edgard Santos &#40;Salvador&#44; Brazil&#41;&#44; diagnosed with COVID-19 from May to July&#44; 2020&#44; as well as <span class="elsevierStyleItalic">in vitro</span> production of antibody against SARS-CoV-2 and Th1&#47;Th2 cytokines&#46; Analyses were performed between December 2020 and February 2021&#46; Participants were stratified according to the use of ivermectin &#40;&#8804; 1 dose vs&#46; multiple doses&#41; for treatment of COVID-19&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Results</span><p id="spara008" class="elsevierStyleSimplePara elsevierViewall">45 HCW were included &#40;62&#37; women&#41;&#46; Mean age was 39 years&#44; and disease severity was similar across groups&#46; Neutralizing antibodies were detected less frequently in multiple doses &#40;70&#37;&#41; vs&#46; &#8804; 1 dose &#40;97&#37;&#41; groups&#44; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;02&#41;&#46; PBMCs of patients in multiple doses group also were less likely to produce antibodies against SARS-CoV-2 following <span class="elsevierStyleItalic">in vitro</span> stimulation with purified spike protein in comparison with patients in &#8804; 1 dose group &#40;<span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;001&#41;&#46; PBMC&#180;s production of Th1&#47;Th2 cytokines levels was similar across groups&#46; Abdominal pain &#40;15&#37; vs 46&#37;&#44; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;04&#41;&#44; diarrhea &#40;21&#37; vs&#46; 55&#37;&#44; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;05&#41; and taste perversion &#40;0&#37; vs&#46; 18&#37;&#44; <span class="elsevierStyleItalic">p</span>&#160;&#61;&#160;0&#46;05&#41; were more frequently reported by participants that used multiple doses of ivermectin&#46;</p></span> <span id="abss0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0006">Conclusions</span><p id="spara009" class="elsevierStyleSimplePara elsevierViewall">Although there was no evidence for differential disease severity upon ivermectin use for treatment of COVID-19 it was associated with more gastro-intestinal side-effects and impairment of anti-SARS-CoV2 antibodies production&#44; in a dose dependent manner&#46; This potentially impacts the effectiveness of immune response and the risk of reinfection and warrants additional studies for clarifying the mechanisms and consequences of such immunomodulatory effects&#46;</p></span>"
        "secciones" => array:5 [
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            "identificador" => "abss0001"
            "titulo" => "Background"
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          1 => array:2 [
            "identificador" => "abss0002"
            "titulo" => "Objective"
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          2 => array:2 [
            "identificador" => "abss0003"
            "titulo" => "Methods"
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          3 => array:2 [
            "identificador" => "abss0004"
            "titulo" => "Results"
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          4 => array:2 [
            "identificador" => "abss0005"
            "titulo" => "Conclusions"
          ]
        ]
      ]
    ]
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      0 => array:8 [
        "identificador" => "fig0001"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
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        "figura" => array:1 [
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            "identificador" => "alt0001"
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        "descripcion" => array:1 [
          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">&#40;A-D&#41; &#8211; Index of IgG antibodies against SARS-CoV-2 and Neutralization values according to IVIAP results and to ivermectin use&#46;</p>"
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      ]
      1 => array:8 [
        "identificador" => "tbl0001"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0002"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0002"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Ivermectin use</th></tr><tr title="table-row"><a name="en0003"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&#8804; 1 dose <span class="elsevierStyleItalic">N</span>&#160;&#61;&#160;34 &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tb1fn1"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tb1fn2"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tb1fn3"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0005"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Multiple doses <span class="elsevierStyleItalic">N</span>&#160;&#61;&#160;11 &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0006"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Total <span class="elsevierStyleItalic">N</span>&#160;&#61;&#160;45 &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0007"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Female sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21 &#40;61&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0009"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7 &#40;63&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">28 &#40;62&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0011"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Median age &#40;IQI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">39&#46;0 &#40;36&#8211;43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0013"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">39 &#40;35&#8211;58&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">39 &#40;36&#8211;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0015"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Disease presentation Severe Moderate Asymptomatic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0019"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11 &#40;32&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0021"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 &#40;31&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0023"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0025"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;45&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17 &#40;37&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0027"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11 &#40;32&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0029"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 &#40;31&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0031"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Ageusia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19 &#40;55&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;45&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">24 &#40;53&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0035"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Anorexia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;14&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7 &#40;15&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0039"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21 &#40;61&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">9 &#40;81&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">30 &#40;66&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0043"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Diarrhea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">7 &#40;20&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6 &#40;54&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13 &#40;28&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0047"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Abdominal pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;14&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;45&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10 &#40;22&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0051"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Throat pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0055"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Chest pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;14&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8 &#40;17&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0059"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Fatigue&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0061"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;45&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17 &#40;37&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0063"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0065"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13 &#40;28&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0067"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Myalgia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;35&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0069"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;45&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17 &#40;37&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0071"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Nausea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8 &#40;23&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;36&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12 &#40;26&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0075"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Odynophagia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;5&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;4&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0079"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Anosmia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21 &#40;61&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0081"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6 &#40;54&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">27 &#40;60&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0083"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Dyspnea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11 &#40;32&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0085"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;36&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0087"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Muscle Weakness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;8&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0091"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Paresis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;8&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0093"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;11&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0095"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Dizziness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6 &#40;17&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8 &#40;17&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0099"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Cough&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11 &#40;32&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0101"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;27&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0102"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 &#40;31&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0103"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Arthralgia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0104"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3 &#40;8&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0105"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0106"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;8&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0107"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Dysgeusia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0108"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0109"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0110"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">2 &#40;4&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0111"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Azithromycin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0112"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13 &#40;38&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0113"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">9 &#40;81&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0114"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">22 &#40;48&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0115"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Corticosteroid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0116"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10 &#40;29&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4 &#40;36&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0118"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">14 &#40;31&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0119"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Other medication&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0120"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10 &#40;30&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0121"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">5 &#40;45&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 &#40;34&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0123"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0124"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Ivermectin use</th></tr><tr title="table-row"><a name="en0125"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Cytokine &#40;pg&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0126"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8804; 1 dose Median &#40;IQR&#41;</th><a name="en0127"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Multiple doses Median &#40;IQR&#41;</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0128"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">IL1 &#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0129"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">3603&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0130"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#40;129&#46;3&#8211;7426&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0131"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#44;332&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0132"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#40;132&#46;1-<a class="elsevierStyleCrossRef" href="#tb2fn1">&#42;&#42;&#42;</a>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0133"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">IL - 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0134"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0135"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#40;1&#46;0&#8211;31&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0136"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0137"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#40;1&#46;0&#8211;29&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0138"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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Article information
ISSN: 14138670
Original language: English
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The Brazilian Journal of Infectious Diseases