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Original Article
Efficacy and safety of hydroxychloroquine in healthcare professionals with mild SARS-CoV-2 infection: Prospective, non-randomized trial
Eficacia y seguridad de hidroxicloroquina en profesionales sanitarios con infección leve por SARS-CoV-2: Estudio prospectivo y no aleatorio
Antonia Agustia,b, Elena Guillena,b, Alfonso Ayorac, Andres Antond,e, Cristina Aguileraa,b, Xavier Vidala,b, Cristina Andresd,e, Manuel Alonsoc, Meritxell Espugac, Juliana Esperalbad,e, Mª Queralt Gorgasb,f, Benito Almiranteg,h, Esteban Riberag,h,
Corresponding author
eriberap@gmail.com

Corresponding author.
a Clinical Pharmacology Service, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Barcelona, Spain
b Departament de Farmacologia, Terapèutica I Toxicologia, Universitat Autònoma de Barcelona, Bellaterra, Spain
c Occupational Health Service, Vall d’Hebron Hospital Universitari, Barcelona, Spain
d Respiratory Viruses Unit, Microbiology Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Barcelona, Spain
e Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Spain
f Clinical Pharmacy Service, Vall d’Hebron Hospital Universitari, Barcelona, Spain
g Infectious Diseases Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Barcelona, Spain
h Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain
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and in healthcare personnel particularly&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Hydroxychloroquine &#40;HCQ&#41; has been worldwide used as anti-malarial and autoimmune disease drug&#44; with an acceptable safety profile&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1&#44;2</span></a> It has some antiviral properties as well as immunomodulatory effects&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a> a potent in vitro activity against SARS-CoV-2&#44;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">2&#8211;4</span></a> and the pharmacokinetic profile seems favorable to treat COVID-19&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">2&#44;4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Evidence from few small observational and controlled studies on the benefits and harms of using HCQ to treat COVID-19 is weak and conflicting&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> Some studies have reported promising results with HCQ&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">5&#8211;8</span></a> Other studies have shown no benefit of HCQ&#44; particularly in patients with severe or critical COVID-19 illness&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">9&#8211;12</span></a> Most of these studies included hospitalized patients usually of greater age&#44; with many comorbidities and moderate or severe disease&#46; Moreover&#44; the end-points were mortality reduction and HCQ was usually associated with other antiviral drugs&#44; with or without azithromycin&#46; Therefore&#44; the role of HCQ was difficult to fully elucidate&#46; There is also a growing concern about the risk of prolonged QT intervals when combining HCQ with azithromycin&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">13&#8211;15</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Recently&#44; the results of two randomized studies in non-hospitalized patients have been reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">16&#44;17</span></a> In both studies&#44; treatment with HCQ did not substantially reduce symptom severity&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The main objective of our study was to assess whether treatment with HCQ alone reduces the time to negative PCR&#44; and the symptoms of healthcare personnel with mild illness by COVID-19&#44; who did not require initial hospitalization&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study setting&#44; design and participants</span><p id="par0030" class="elsevierStylePara elsevierViewall">This is a prospective&#44; non-randomized&#44; single center study&#44; conducted at the Vall d&#8217;Hebron Hospital&#46; This is a 1&#46;100-beds public&#44; university&#44; tertiary hospital in Barcelona&#44; with a total of 6&#46;731 healthcare workers&#46; At the peak of the pandemic&#44; about 650 beds were occupied by COVID-19 patients and by April 30th&#44; 2020&#44; 5&#46;435 patients had been diagnosed of SARS-CoV-2 infection&#44; 2&#46;236 patients with moderate-severe disease had been hospitalized&#44; 335 in critical care unit&#44; and 285 died&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Healthcare workers from Vall d&#8217;Hebron Hospital with symptoms compatible with COVID-19 were sent to Occupational Risks Prevention Unit for medical evaluation and to collect pooled nasal and pharyngeal swabs for PCR assay&#46; Patients were eligible for the study if they had PCR confirmed SARS-CoV-2 infection with mild symptoms &#40;eg&#44; fever&#44; acute cough&#44; sore throat&#44; fatigue&#44; headache&#44; muscle pain&#44; sudden gustatory or olfactory loss&#44; but no dyspnea&#41;&#44; that allowed confinement at home&#46; Recruitment started on April 7 and ended on May 6&#44; 2020&#46; We included all eligible healthcare professionals diagnosed during this period that gave their consent to participate in the study&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Treatment&#44; procedures and assessment</span><p id="par0040" class="elsevierStylePara elsevierViewall">Patients were divided into two groups&#58; treatment group &#40;patients who accepted the HCQ treatment&#41; and control group &#40;patients with contraindications to HCQ<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">18</span></a> or who rejected treatment&#41;&#46; Patients in the treatment group were given HCQ at baseline for five days&#44; with a loading dose of 400<span class="elsevierStyleHsp" style=""></span>mg q12<span class="elsevierStyleHsp" style=""></span>h the first day&#44; followed by 200<span class="elsevierStyleHsp" style=""></span>mg q12<span class="elsevierStyleHsp" style=""></span>h the remaining four days&#44; as suggested by Yao et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a> In both groups symptomatic treatments were given as needed&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The start of follow-up &#40;baseline&#41; for each patient was when they were contacted by a researcher Clinical Pharmacologist and accepted to participate in the study&#44; between 0 and 2 days after PCR confirmed SARS-CoV-2 infection&#46; All patients were followed up from baseline to day 28&#46; Patients were confined at home and received an informed consent&#46; Three telephonic interviews were performed at baseline and at days 14 and 28 to collect demographic and clinical data&#44; and possible side effects of HCQ treatment&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Samples and PCR assay</span><p id="par0050" class="elsevierStylePara elsevierViewall">Clinical specimens for RT-PCR assay from each patient were obtained initially for diagnosis and according to the study protocol on days 7&#44; 10&#44; 14&#44; 21 and 28 for patients who continued to test positive &#40;&#177;2 days&#41;&#46; Viral RNA was extracted from pooled nasal and oropharyngeal swabs and they were processed at the Respiratory Viruses Unit of the Microbiology Department&#46; The diagnosis of COVID-19 was initially performed by two commercial RT-PCR-based assays&#44; Allplex&#8482; 2019-nCoV &#40;Seegene&#44; Korea&#41; and Cobas&#174; SARS-CoV-2 &#40;Roche Diagnostics&#44; USA&#41; tests&#46; In addition&#44; to evaluate viral dynamics&#44; an in-house RT-PCR assay using the primer&#47;probe set targeting the nucleocapsid protein &#40;N1&#41; and the human RNase P &#40;housekeeping gene&#41; from the CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel was also carried out&#46; High-moderate viral load were defined as those with a cycle threshold &#40;Ct&#41; value for N1<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>35&#46; The Ct values of the viral target were normalized to a housekeeping gene based on the &#916;Ct method &#40;Ct<span class="elsevierStyleInf">sample</span><span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>Ct<span class="elsevierStyleInf">housekeeping gene</span>&#41; in order to minimize the variations due to the non-standardized collection of a heterogenous specimen&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The primary outcome for this trial was the proportion of patients in which the first control PCR at day 7 &#40;&#177;2&#41; was negative&#46; Secondary objectives included&#58; time to negative conversion of PCR&#44; proportion of patients and probability of negative PCR conversion at 14&#44; 21 and 28 days&#44; dynamics of &#916;Ct&#44; duration of clinical symptoms&#44; and progression to pneumonia&#44; hospitalization or death&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Considering an approximate ratio of 3&#58;2 of patients accepting to be treated with HCQ vs&#46; control patients&#44; 75&#8211;84 treated patients and 49&#8211;53 control patients achieve a minimum power of 80&#37; to detect a difference of 25&#37; in the main variable between both groups&#46; For continuous variables&#44; description of the sample has been made with the median and quartiles&#44; and comparisons between groups with the Wilcoxon-Mann-Whitney test&#46; For categorical variables&#44; frequency and percentage for description&#44; and chi-square test for comparisons&#46; In addition&#44; 95&#37; confidence interval has also been calculated for the percentage differences&#46; To compare the time to the negative status of the PCR tests&#44; a Kaplan&#8211;Meier analysis was used with the log-rank test&#46; Probabilities of reaching the outcome at predefined time points &#40;7&#44; 10&#44; 14&#44; 21&#44; and 28 days&#41; were also compared&#46; Finally&#44; a polynomial regression has been adjusted to explore the evolution of &#916;Ct as a function of time for each group&#46; The p value for statistical significance has been set at 0&#46;05 and all tests have been considered bilateral&#46; The analyses have been carried out with the SAS&#174; 9&#46;4 &#40;SAS Institute Inc&#46;&#44; Cary&#44; NC&#44; USA&#41; and R 4&#46;0&#46;2 &#40;R Core Team&#44; <a href="http://www.r-project.org/">http&#58;&#47;&#47;www&#46;R-project&#46;org</a>&#41; programs&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Patients and baseline characteristics</span><p id="par0065" class="elsevierStylePara elsevierViewall">Of 176 healthcare workers with PCR confirmed SARS-CoV-2 infection from 7 April to 6 May of 2020&#44; 34 were not included in the study&#44; mainly because they refused study participation&#46; Characteristics of patients not included in the study were similar to those of included patients&#46; Of the remaining 142&#44; 87 received HCQ treatment&#44; and 55 were included in the control group&#44; being the main reason treatment refusal &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the baseline demographic and clinical characteristics of patients in both groups&#46; The median age of patients was 37 years and 75&#37; were female&#46; The median body mass index was 24&#46; Patients in both groups had few comorbidities&#59; being arterial hypertension&#44; dyslipidemia and asthma the most common&#46; There were more medical doctors in the treatment group &#40;25&#37;&#41; and more nurses in the control group &#40;52&#37;&#41;&#46; The median interval between symptoms onset and inclusion to the study was 5 days&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Evolution of viral load</span><p id="par0075" class="elsevierStylePara elsevierViewall">The percentage of patients with a negative viral load for SARS-CoV-2 in their nasopharyngeal swap samples was numerically higher in the treatment group than in control group in the different sampling PCRs&#58; day 7&#44; 25&#46;6&#37; vs&#46; 14&#46;3&#37; &#40;primary outcome&#41;&#59; day 10&#44; 43&#46;5&#37; vs&#46; 36&#37;&#59; day 15&#44; 61&#46;2&#37; vs&#46; 47&#46;1&#37;&#44; day 22&#44; 80&#37; vs 71&#46;2&#37;&#46; However&#44; no differences were statistically significant &#40;<a class="elsevierStyleCrossRef" href="#sec0085">Table S1&#44; Supplementary data</a>&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Most patients had a high&#47;moderate SARS-CoV-2 viral load &#40;PCR N1 Ct<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>35&#41; at baseline&#44; with an early viral clearance in both groups&#46; Differences between both groups were lower than 10&#37; and not significant &#40;<a class="elsevierStyleCrossRef" href="#sec0085">Table S2&#44; Supplementary data</a>&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Kaplan-Meier curves of time to negative conversion of SARS-CoV-2 PCR from nasopharyngeal swaps showed no significant differences between both groups &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The median time of negative PCR conversion was 15 days &#40;95&#37; CI&#44; 11&#8211;18&#41; in treatment group and 22 days &#40;95&#37;CI&#44; 14&#8211;24&#41; in the control group&#46; The maximum and only significant difference in the probability of negative conversion was 18&#46;7&#37; &#40;95&#37;CI 2&#46;0 to 35&#46;4&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;034&#41; at day 21 &#40;<a class="elsevierStyleCrossRef" href="#sec0085">Table S3&#44; Supplementary data</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a> shows the evolution of normalized viral load values during follow-up in both groups&#44; fitted by second-degree polynomial curves&#46; The &#916;Ct &#40;Ct sample<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>Ct reference&#41; was similar in both groups at baseline and during follow-up&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Evolution of symptoms</span><p id="par0095" class="elsevierStylePara elsevierViewall">The most common symptoms were headache&#44; muscle pain&#44; fatigue&#44; smell and taste disorders&#44; fever&#44; nasal congestion and cough&#46; Smell and taste disorders and diarrhea appeared in a higher proportion of patients during follow-up and smell and taste disorders&#44; fatigue and cough persisted in more patients at finalization of the study period &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Symptoms with a longer duration were smell and taste disorders&#44; fatigue&#44; nasal congestion and cough &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; The duration of sore throat was significantly longer in patients without treatment in comparison to the treatment group&#44; but the number of patients with this symptom was low in both groups&#46; The duration of smell and taste disorders and cough was also longer in patients without HCQ treatment&#44; but the difference was not significant&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">In our study&#44; 2 patients &#40;2&#46;3&#37;&#41; in the HCQ group and 4 patients &#40;7&#46;3&#37;&#41; in the control group developed pneumonia &#40;OR 0&#46;30&#44; 95&#37;CI&#44; 0&#46;05&#8211;1&#46;70&#41;&#46; No patients required admission to the Intensive Care Unit or died&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Side effects with HCQ treatment</span><p id="par0105" class="elsevierStylePara elsevierViewall">During follow-up&#44; 44&#47;87 &#40;50&#46;6&#37;&#41; patients in the treatment group reported 64 possible side effects associated with HCQ treatment &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; Diarrhea was the most common side effect&#44; reported in 30 &#40;34&#46;5&#37;&#41; patients&#44; in 25 of them diarrhea appeared after starting HCQ and in 5 diarrhea worsened&#46; It was mostly mild&#44; but in two cases led to treatment withdrawal&#46; Side effects had not resolved at the end of the study period in only three patients&#59; including a case of skin hyperpigmentation and another case of ocular photosensitivity&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">In our study&#44; a comprehensive analysis of the evolution of nasopharyngeal SARS-CoV-2 viral load and follow-up of symptoms until 28 days postinclusion in the study was performed&#46; Five day treatment with HCQ in healthcare professionals with mild SARS-CoV-2 infection did not significantly reduce time to negative PCR-test&#46; Differences in the percentages of patients with negative PCR at days 7&#44; 10&#44; 14 and 28 were not statistically significant&#46; The only marginally significant difference in the probability of negative conversion of PCR was observed at day 21&#44; but it was a secondary variable of the study&#46; Furthermore&#44; there were no differences in the evolution of the amount of viral load during follow-up in both groups&#46; In addition&#44; duration of some symptoms tended to be shorter in those patients treated with HCQ&#44; but the difference was not statistically significant&#46; A considerable proportion &#40;approximately 50&#37;&#41; of the patients treated with HCQ had side effects possibly associated to its use&#44; mainly diarrhea&#44; although mild in most cases&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Patients included in our study were young&#44; predominantly female and with few comorbidities&#44; similar to those of the trials by Skipper et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a> and by Mitj&#224; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> As a difference&#44; all of our patients were healthcare professionals&#46; The percentages of nurses &#40;&#8764;60&#37;&#41; and medical doctors &#40;&#8764;20&#37;&#41; are in accordance with the distribution of COVID-19 infected healthcare professional during the pandemia in our hospital&#46; A higher percentage of medical doctors received treatment with HCQ&#44; mainly because a higher percentage of nurses rejected treatment with HCQ&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">We found few differences in the evolution of patients in both groups&#46; These negative results have been confirmed in the study by Mitj&#224; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> They did not find differences in the mean reduction of viral RNA load in the nasopharyngeal swaps at days 3 and 7 after initiation of treatment&#46; Nevertheless&#44; in our study&#44; a longer follow-up of the evolution of nasopharyngeal viral loads was obtained&#46; The maximum difference in the percentage of patients with a negative PCR-test between groups was observed at 21 days&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Headache&#44; smell and taste disorders&#44; muscle pain&#44; cough and fatigue were in general the most frequently reported symptoms during the study&#44; and smell and taste disorders and diarrhea were those that appeared with a higher frequency during follow-up&#46; However&#44; in most cases HCQ could be the cause of diarrhea when it appeared after treatment initiation&#46; Smell and taste disorders&#44; fatigue and cough persisted longer during the study period and although the median time duration of smell and taste disorders and cough tended to be shorter with HCQ treatment&#44; the differences between groups were not statistically significant&#46; In the study by Skipper et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a> no differences in the evolution of symptoms between the treatment and placebo groups were found either&#46; In this study&#44; change in overall symptoms severity was the main variable&#44; but information on symptom severity was only obtained until day 14&#46; In our study&#44; very few patients were diagnosed with pneumonia during follow-up in both groups and none required admission at the intensive care unit or died&#46; In the study by Mitj&#224; et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> the clinical outcome of risk of hospitalization was similar in both arm groups and no patient required mechanical ventilation no deaths were reported during the study&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Several reasons have to be taken into consideration when explaining why a drug that has shown promising data in vitro against SARS-CoV2 has obtained disappointing results in clinical studies&#46; Firstly&#44; it has been suggested that the disparity between laboratory and clinical data may be due at least in part to the complex pharmacokinetics of 4-aminoquinolines&#44; making it difficult to extrapolate concentrations in culture media to doses in humans&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">19</span></a> Secondly&#44; the variability of the doses and duration of HCQ treatment between studies has been high&#44; and the effect of different loading and maintenance doses or the duration of treatments on clinical outcomes has not been properly addressed in the studies&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a> However&#44; negative results in several studies using different posology have already been published&#44; and therefore&#44; this could mean that in fact dose variability between studies is not the key&#46; Finally&#44; the Ct cut-off level used to report PCR-test as positive or negative has also been variable between studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">6&#44;9</span></a> In our laboratory&#44; the routine cut-off level &#62;40 is reported as PCR-negative&#44; but when a cut-off of 35 was tested for this study the proportion of negative results was higher&#46; However&#44; differences between both groups were not significant for both cut-offs&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">An argument often used to justify the use of HCQ was its safety and the broad experience in its use to treat certain rheumatic diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">2&#44;19</span></a> However&#44; concerns arose when in several studies a prolongation of QT interval and in some cases potential lethal arrhythmias were documented&#44; especially in patients treated with concomitant azithromycin&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">12&#8211;14</span></a> In our study more than half of the patients treated with HCQ had side effects&#44; however the severity was mostly mild&#44; being diarrhea and gastrointestinal discomfort the most common&#46; No electrocardiogram monitoring was performed during the study&#44; but no patients reported possible cardiac side effects&#46; It should be noted that our patients were younger and with less comorbidity than those included in the studies where the concerns on the cardiac side effects of HCQ in combination with azithromycin emerged&#46; In addition&#44; in our study patients with contraindications to HCQ were excluded from treatment&#46; In the studies of Mitj&#224; et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">17</span></a> and Skipper et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">16</span></a> with similar populations and the same or slightly higher doses of HCQ than in our study&#44; the proportion of participants with adverse events was even higher than in our study&#44; but also with only mild side effects&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Our study has several limitations&#46; Firstly&#44; it was not a randomized study therefore we cannot rule out a possible influence of factors that could drive the preferences of patients when they decided to accept or reject treatment&#46; Secondly&#44; the study was powered to detect a difference of 25&#37; in the percentage of negative PCR-test at 7 days post-inclusion&#46; It is possible that the expected difference has been oversized and that in fact the real difference is lower&#46; However&#44; our results are in accordance with those of some recently published clinical trials in patients with similar characteristics&#46; One of the main strengths of our study is that all professional healthcare workers with SARS-CoV2 infection during the study period were detected and asked for participation&#46; In addition&#44; all the included patients had a confirmed COVID19 infection by a positive PCR-test in the nasopharyngeal swap&#46; Furthermore&#44; a comprehensive follow-up of participants was carried out during the study in order to fulfill the scheduled PCR-tests and obtain the information on symptom evolution and side effects to treatment&#46; Finally&#44; information on the evolution of viral RNA load was provided at several time-points during the study and for a longer period of time than in other recently published studies with also more extensive information on the evolution of symptoms&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In conclusion&#44; our study failed to show a substantial benefit of HCQ in viral dynamics and in resolution of clinical symptoms&#46; Treatment with HCQ was associated with a numerically higher percentage of negative PCR-tests at some points during follow-up in comparison with the non-treatment group&#44; and a shorter duration of some symptoms was also seen with HCQ&#44; but differences were only marginally significant and not clinically relevant&#46; Adverse events possibly associated with HCQ appeared in about 50&#37; of patients&#44; but were mild&#46; These negative results are in accordance with those reported in recently published randomized clinical trials and&#44; therefore do not support the use of HCQ in patients with mild COVID19 infection&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Ethics</span><p id="par0150" class="elsevierStylePara elsevierViewall">The study was conducted according to international ethical recommendations&#46; In accordance with the national directives in relation to post-authorization studies&#44; the study was approved by the Ethics Committee of Clinical Investigation of the Vall d&#8217;Hebron University Hospital &#40;Institutional Review Board &#8211; 03&#47;04&#47;2020&#41; and registered on the European Union electronic Register of Post-Authorization Studies &#40;EU PAS Register Number EUPAS34570&#41;&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Funding</span><p id="par0155" class="elsevierStylePara elsevierViewall">This trial had no financial support&#46; Laboratorios Rubi&#243; contributed to the study with the required doses of hydroxychloroquine &#40;Dolquine&#41;&#46; Laboratorios Rubi&#243; had no role in study design&#44; data collection and interpretation&#44; or the decision to submit the work for publication&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflict of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">All authors declare no conflict of interest&#46;</p></span></span>"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-09-01"
    "fechaAceptado" => "2020-10-29"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1830905"
          "palabras" => array:5 [
            0 => "SARS-CoV-2 infection"
            1 => "COVID-19"
            2 => "Hydroxychloroquine"
            3 => "Healthcare workers"
            4 => "Outpatients"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1830904"
          "palabras" => array:5 [
            0 => "Infecci&#243;n por SARS-CoV-2"
            1 => "COVID-19"
            2 => "Hidroxicloroquina"
            3 => "Trabajadores sanitarios"
            4 => "Pacientes externos"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To assess the efficacy and safety of hydroxychloroquine &#40;HCQ&#41; compared with no treatment in healthcare workers with mild SARS-CoV-2 infection&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Prospective&#44; non-randomized study&#46; All health professionals with confirmed COVID-19 between April 7 and May 6&#44; 2020&#44; non-requiring initial hospitalization were asked to participate&#46; Patients who accepted treatment were given HCQ for five days &#40;loading dose of 400<span class="elsevierStyleHsp" style=""></span>mg q12<span class="elsevierStyleHsp" style=""></span>h the first day followed by200<span class="elsevierStyleHsp" style=""></span>mg q12<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; Control group included patients with contraindications for HCQ or who rejected treatment&#46; Study outcomes were negative conversion and viral dynamics of SARS-CoV-2&#44; symptoms duration and disease progression&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Result</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Overall&#44; 142 patients were enrolled&#58; 87 in treatment group and 55 in control group&#46; The median age was 37 years and 75&#37; were female&#44; with few comorbidities&#46; There were no significant differences in time to negative conversion of PCR between both groups&#46; The only significant difference in the probability of negative conversion of PCR was observed at day 21 &#40;18&#46;7&#37;&#44; 95&#37;CI 2&#46;0&#8211;35&#46;4&#41;&#46; The decrease of SARS-CoV-2 viral load during follow-up was similar in both groups&#46; A non significant reduction in duration of some symptoms in HCQ group was observed&#46; Two patients with HCQ and 4 without treatment developed pneumonia&#46; No patients required admission to the Intensive Care Unit or died&#46; About 50&#37; of patients presented mild side effects of HCQ&#44; mainly diarrhea&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Our study failed to show a substantial benefit of HCQ in viral dynamics and in resolution of clinical symptoms in health care workers with mild COVID-19&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Result"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar la eficacia y seguridad de hidroxicloroquina &#40;HCQ&#41;&#44; en comparaci&#243;n con la ausencia de tratamiento en los profesionales sanitarios con infecci&#243;n leve por SARS-CoV-2&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo y no aleatorio&#46; Se solicit&#243; su participaci&#243;n a todos los profesionales sanitarios con diagn&#243;stico confirmado de COVID-19&#44; entre el 7 de abril y el 6 de mayo de 2020&#44; que no requirieron hospitalizaci&#243;n inicial&#46; Los pacientes que aceptaron el tratamiento recibieron HCQ durante cinco d&#237;as &#40;dosis de carga de 400 mg cada 12 h el primer d&#237;a&#44; y a continuaci&#243;n 200 mg cada 12 h&#41;&#46; El grupo control incluy&#243; pacientes con contraindicaciones de HCQ&#44; o que rechazaron el tratamiento&#46; Los resultados del estudio fueron conversi&#243;n negativa y din&#225;mica viral de SARS-CoV-2&#44; duraci&#243;n de los s&#237;ntomas y progresi&#243;n de la enfermedad&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En total se incluyeron 142 pacientes&#58; 87 en el grupo de tratamiento&#44; y 55 en el grupo control&#46; La edad media fue de 37 a&#241;os&#44; y el 75&#37; fueron mujeres&#44; con pocas comorbilidades&#46; No existieron diferencias significativas en cuanto al tiempo transcurrido hasta la conversi&#243;n negativa de la PCR entre ambos grupos&#46; La &#250;nica diferencia significativa en cuanto a la probabilidad de negativizaci&#243;n de la PCR se observ&#243; el d&#237;a 21 &#40;18&#44;7&#37;&#44; IC 95&#37; 2-35&#44;4&#41;&#46; El descenso de la carga viral de SARS-CoV-2 durante el seguimiento fue similar en ambos grupos&#46; Se observ&#243; una reducci&#243;n no significativa de la duraci&#243;n de algunos s&#237;ntomas en el grupo HCQ&#46; Dos pacientes con HCQ y cuatro sin tratamiento desarrollaron neumon&#237;a&#46; Ning&#250;n paciente requiri&#243; ingreso en la Unidad de Cuidados Intensivos&#44; ni hubo fallecidos&#46; Cerca del 50&#37; de los pacientes present&#243; efectos secundarios leves de HCQ&#44; principalmente diarrea&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nuestro estudio no reflej&#243; un beneficio sustancial de HCQ&#44; en cuanto a din&#225;mica viral y resoluci&#243;n de los s&#237;ntomas cl&#237;nicos en los profesionales sanitarios con infecci&#243;n leve por COVID-19&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivos"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "apendice" => array:1 [
      0 => array:1 [
        "seccion" => array:1 [
          0 => array:4 [
            "apendice" => "<p id="par0175" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0085"
          ]
        ]
      ]
    ]
    "multimedia" => array:8 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1436
            "Ancho" => 2167
            "Tamanyo" => 269069
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flow diagram of trial participants&#46; &#42;Absolute contraindications included&#58; 2 patients with history of hypersensibility to hydroxichloroquine&#44; 3 patients with retinopathy&#44; 3 patients with psoriasis and 1 miastenia gravis&#46;&#42;&#42;Relative contraindications included&#58; 2 patients with right blockage of bundle branch and 1 atopic dermatitis&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1135
            "Ancho" => 1508
            "Tamanyo" => 80894
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Kaplan&#8211;Meier curves of time to negative conversion of PCR test in HCQ group and in control group&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1105
            "Ancho" => 1508
            "Tamanyo" => 110080
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Viral dynamics&#58; Normalized viral loads of the nasopharyngeal swab samples at different times of disease onset from patients treated with HCQ and patients without treatment&#44; estimated with the &#916; Ct method &#40;Ct<span class="elsevierStyleInf">N1</span> Ct<span class="elsevierStyleInf">human RNase P</span>&#41;&#46; Note that higher viral loads are inversely related to Ct values&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Data are <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41; unless otherwise stated&#46;</p>"
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            0 => array:2 [
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">37 &#40;27&#8211;47&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">38 &#40;28&#8211;48&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">31 &#40;25&#8211;47&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Sex female</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">107 &#40;75&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">63 &#40;72&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">44 &#40;80&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Body mass index&#44; median &#40;IQR&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">24&#46;3 &#40;20&#46;8&#8211;28&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">23&#46;4 &#40;21&#46;3&#8211;27&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Caucasian&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">130 &#40;92&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">79 &#40;91&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Latin American&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">9 &#40;6&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">6 &#40;6&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3 &#40;5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Arab&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3 &#40;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No comorbidity&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">104 &#40;73&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 &#40;78&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;65&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;6&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;4&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dyslipidemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;6&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;8&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;3&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Chronic respiratory disease &#40;including asthma&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;5&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;8&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Thyroid disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;4&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>History of malignancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;5&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Psoriasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Diabetes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Migraine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;2&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Other<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;4&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Profession</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Nurse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54 &#40;38&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 &#40;29&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28 &#40;51&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Assistant nurse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;25&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24 &#40;27&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;25&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Doctor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29 &#40;20&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;25&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;12&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ancillary staff&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;5&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;5&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Administrative staff&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;2&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;3&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Other<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;6&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;9&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Days of symptoms&#44; median &#40;IQR&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;3&#8211;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;3&#8211;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;4&#8211;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Patients with a known previous contact&#44; n</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Days from contact to PCR&#43;&#44; median &#40;IQR&#41;</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;7&#8211;13&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;7&#8211;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;11&#8211;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Other comorbidities group included&#58; 1 atopic dermatitis in the treatment group and 1 myasthenia gravis&#44; 1 rheumatic disease&#44; 1 glaucoma&#44; 1 vitreous detachment&#44; and 1 celiac disease in the control group&#46;</p>"
            ]
            1 => array:3 [
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              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Other profession group included&#58; 2 maintenance staff&#44; 2 physiotherapist&#44; 1 kitchen staff&#44; 1 cleaning staff&#44; 1 pharmaceutical and 1 speech therapist in the treatment group and 1 Pharmacy Technician in the control group&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0015"><span class="elsevierStyleItalic">p</span> values that reached level of significance included&#58; other comorbidities &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;032&#41;&#44; profession &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;043&#41; and median time from contact to PCR&#43; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;010&#41;&#46;</p>"
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            0 => array:2 [
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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"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Symptom&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">At baseline</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Appeared during follow-up</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Persisted at finalization of the study</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HCQ group&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>87&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HCQ group&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>87&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HCQ group&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>87&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HCQ group&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>87&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55&#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"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 &#40;78&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41 &#40;74&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60 &#40;69&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;69&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;9&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;8&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smell and taste disorders&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60 &#40;69&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;65&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47 &#40;54&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29 &#40;52&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;15&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;12&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;25&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22 &#40;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Muscle pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65 &#40;74&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35 &#40;64&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62 &#40;71&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33 &#40;60&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;3&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;3&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;8&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;12&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fatigue&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63 &#40;72&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33 &#40;60&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62 &#40;71&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32 &#40;58&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1 &#40;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12 &#40;13&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7 &#40;12&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">57 &#40;65&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">33 &#40;60&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">52 &#40;59&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;3&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nasal congestion&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">48 &#40;55&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">36 &#40;65&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">44 &#40;50&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8 &#40;9&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;7&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cough&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">65 &#40;74&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">34 &#40;62&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sore throat&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anorexia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">6 &#40;6&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Shortness of breath&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">23 &#40;26&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;3&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4 &#40;7&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diarrhea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">42 &#40;48&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12 &#40;21&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">25<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;27&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chest pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">9 &#40;10&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Eye discomfort&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="left" valign="\n
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                  \t\t\t\t">28 &#40;1&#8211;39&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;078&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Muscle pain&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\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Fever&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="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;1&#8211;39&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;871&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cough&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;1&#8211;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19 &#40;2&#8211;41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;084&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Sore throat&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">5 &#40;1&#8211;41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;2&#8211;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Anorexia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;3&#8211;36&#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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;3&#8211;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;775&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Shortness of breath&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">6 &#40;1&#8211;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;1&#8211;41&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#46;373&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diarrhea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">4 &#40;1&#8211;32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">5 &#40;1&#8211;36&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;579&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">Chest pain&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10 &#40;4&#8211;33&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13 &#40;3&#8211;41&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sputum production&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14 &#40;1&#8211;41&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">30 &#40;5&#8211;41&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;271&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Eye discomfort&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">33 &#40;7&#8211;44&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;052&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t">30 &#40;34&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9 &#40;10&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9 &#40;10&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Headache&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">5 &#40;5&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Nausea&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3 &#40;3&#46;4&#41;&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"><span class="elsevierStyleHsp" style=""></span>Fatigue&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 &#40;2&#46;3&#41;&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"><span class="elsevierStyleHsp" style=""></span>Skin eruption&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Eye photosensitivity&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Skin hyperpigmentation&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1 &#40;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Treatment discontinuation owing to adverse events</span><a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">44 patients reported 64 possible side effects associated with hydroxychloroquine treatment&#46; In some cases the involvement of covid-19 could not be excluded&#46;</p>"
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          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Summary of side effects in patients treated with hydroxychloroquine&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:20 [
            0 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current and future use of chloroquine and hydroxychloroquine in infectious&#44; immune&#44; neoplastic&#44; and neurological diseases&#58; a mini-review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46; Plantone"
                            1 => "T&#46; Koudriavtseva"
                          ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40261-018-0656-y"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Drug Investig"
                        "fecha" => "2018"
                        "volumen" => "38"
                        "paginaInicial" => "653"
                        "paginaFinal" => "671"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29737455"
                            "web" => "Medline"
                          ]
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            1 => array:3 [
              "identificador" => "bib0110"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hydroxychloroquine&#44; a less toxic derivative of chloroquine&#44; is effective in inhibiting SARS-CoV-2 infection in vitro"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Liu"
                            1 => "R&#46; Cao"
                            2 => "M&#46; Xu"
                            3 => "X&#46; Wang"
                            4 => "H&#46; Zhang"
                            5 => "H&#46; Hu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41421-020-0156-0"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cell Discov"
                        "fecha" => "2020"
                        "volumen" => "6"
                        "paginaInicial" => "16"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32194981"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
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            2 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "3"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Battling COVID-19&#58; using old weapons for a new enemy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "R&#46; Kumar"
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos