\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[T2A]{fontenc}
\usepackage[polish,ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{The effect of Hydroxychloroquine use due to rheumatic disease on the
risk of Covid-19 infection and its course}



\author[1]{Tanzer  Korkmaz}%
\author[1]{Aslı Şener}%
\author[2]{Vedat Gerdan}%
\author[3]{İlker Kızıloglu}%
\affil[1]{Affiliation not available}%
\affil[2]{Bakircay Universitesi}%
\affil[3]{Doctor Suat Seren Chest Diseases Training and Research Hospital}%


\vspace{-1em}



  
  \date{June 16, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Introduction COVID-19 virus continues to spread and die worldwide. Some
studies examining hydroxychloroquine as a prophylactic agent reported
that its efficiency and reliability have not been proven so that it must
not be used for prophylaxis other than clinical researches. However we
think that the results of this study we conducted in a local area will
contribute to the literature data. Methods The study was designed as
adult patients who were in follow-up taking HC due to their chronic
diseases were included. 384 patients who were taking hydroxychloroquine
regularly and 299 patients who were not taking hydroxychloroquine were
included. The primary outcome of this study is to detect a positive PCR
result in patients who received a PCR test and to determine the
incidence rate and its course of the disease among those who were taking
HC and those who were not taking hydroxychloroquine. Results The
majority of the patients (median age: 51.8- range 17-89) were women and
housewives. In the patient group using hydroxychloroquine, 22 patients
were tested for PCR and only 2 positive patients were found. Covid-19
was detected in 24 (8.02\%) of 65 (21.73\%) patients who underwent PCR
test at Control group (n = 299). PCR positivity was statistically lower
in the HK group (n = 2, 0.52\%, n = 24, 8.02\%, respectively, p =
0.0001). Conclusions Our study supported the fact that there is a lower
PCR positivity and symptoms are milder among patients who are using HC
regularly, as compared to those who are not using hydroxychloroquine.%
\end{abstract}%



\sloppy


The effect of Hydroxychloroquine use due to rheumatic disease on the
risk of Covid-19 infection and its course

Hydroxychloroquine in Covid-19 and its course

\textbf{Abstract}

Introduction

COVID-19 virus continues to spread and die worldwide. Some studies
examining hydroxychloroquine as a prophylactic agent reported that its
efficiency and reliability have not been proven so that it must not be
used for prophylaxis other than clinical researches. However we think
that the results of this study we conducted in a local area will
contribute to the literature data.

Methods

The study was designed as adult patients who were in follow-up taking HC
due to their chronic diseases were included. 384 patients who were
taking hydroxychloroquine regularly and 299 patients who were not taking
hydroxychloroquine were included.

The primary outcome of this study is to detect a positive PCR result in
patients who received a PCR test and to determine the incidence rate and
its course of the disease among those who were taking HC and those who
were not taking hydroxychloroquine.

Results

The majority of the patients (median age: 51.8- range 17-89) were women
and housewives. In the patient group using hydroxychloroquine, 22
patients were tested for PCR and only 2 positive patients were found.
Covid-19 was detected in 24 (8.02\%) of 65 (21.73\%) patients who
underwent PCR test at Control group (n = 299). PCR positivity was
statistically lower in the HK group (n = 2, 0.52\%, n = 24, 8.02\%,
respectively, p = 0.0001).

Conclusions

Our study supported the fact that there is a lower PCR positivity and
symptoms are milder among patients who are using HC regularly, as
compared to those who are not using hydroxychloroquine.

\textbf{KeyWord:} hydroxychloroquine, SARS-CoV-2, Covid-19, prophylaxis,
pandemic

\selectlanguage{polish}\textbf{İntroduction}\selectlanguage{english}

According to Chinese authorities, Severe Acute Respiratory
Syndrome-Coronavirus-2 (SARS-CoV-2) (COV\selectlanguage{polish}İ\selectlanguage{english}D-19), which is a member of the
Coronavirus family, has spread rapidly from China to the rest of the
world and stopped the life, leaving its mark on the future after 2020.
The covid-19 virus that is extracted from patients with pneumonia at
Wuhan is an enveloped single-stranded RNA beta-coronavirus. The genomic
sequence of Covid-19 shares 79.5\% sequence identity to other
coronaviruses that cause Severe Acute Respiratory Syndrome (SARS-CoV).
The COVID-19 virus permeates to human alveolar epithelium cells by
binding its spike S protein to angiotensin converting enzyme 2 (ACE2)
receptor.\textsuperscript{1} The number of cases continues to increase
since the COVID-19 virus is rapidly transmitted from human to human. The
most important property of this virus whose source has not yet clear is
the fact that it can rapidly transmit from human to human through
droplets and contact. Thus, it has affected large amounts of people in a
short time. This was declared by World Health Organization as a pandemic
and emergency. Globally, as of 7 January 2021, there have been
85.509.194 confirmed cases of COVID-19, including 1.868.622 deaths,
reported to WHO.\textsuperscript{2} The infection is still uncontrolled
in many countries and continues to show its effect. Its course is not
yet sufficiently predicted. To reduce the load of Covid-19, effective
vaccines and non-pharmacological intervention strategies such as
personal, regional, and global isolation or quarantine and full-scale
lockdown are adopted. It has a wide clinical spectrum ranging from
asymptomatic patients to those with mild symptoms or those requiring
hospitalization and even intensive care unit support and may result in
death. The majority of Covid-19 patients who are admitted to the
intensive care unit have comorbid diseases so they have more
hospitalization complications. Therefore, effective treatment can
improve the prognosis.\textsuperscript{3} The studies for the treatment
of the worldwide spreading Covid-19 virus are in progress. The
multi-centered clinical studies in China showed that Chloroquine
phosphate, which is a medication primarily used to treat malaria but
commonly used for rheumatic diseases, has an apparent efficacy and
acceptable reliability for Covid-19-related
pneumonia.\textsuperscript{4} Chloroquine is used to treat and prevent
Malaria, and an anti-inflammatory agent in the treatment of rheumatoid
arthritis, lupus erythematosus, and porphyria cutanea tarda. The studies
also revealed that it shows a potential wide-spectrum antiviral activity
enhancing the endosomal pH needed for virus and cell fusion and
intervening with glycosylation of the cellular receptors of
SARS-CoV.\textsuperscript{5-7} The antiviral and anti-inflammatory
activity of hydroxychloroquine (HC) can demonstrate its strong
efficiency to treat patients with COVID-19 pneumonia. It was emphasized
that there are different opinions about the use of HC among countries,
but this should be supported by further studies. Some studies reported
that there is no enough information on this subject and recommended the
controlled use of HC, while some studies reported that it should be used
in the treatment protocols.\textsuperscript{4,8} Some studies reported
that none of the agents are effective to prevent Covid-19. Some studies
examining HC as a prophylactic agent reported that its efficiency and
reliability have not been proven so that it must not be used for
prophylaxis other than clinical researches. However, the results of
ongoing studies on prophylaxis (NCT04308668, NCT04303507, NCT04318015,
NCT04318444) will enlighten the discussions on this subject. Our study
aims to examine the effects of hydroxychloroquine (HC) on the frequency
and course of Covid-19 in patients who were administered with HC for
their chronic diseases.\textsuperscript{9} Considering these findings in
the current scientific literature, which were mostly contrary to the
potential anti-viral effects of these compounds, we think that the
results of this study we conducted in a local area will contribute to
the literature data.

\textbf{Method:}

\emph{\textbf{Setting and data source}}

The study was designed as an observational, retrospective questionnaire
study in which adult patients who were in follow-up in the Department of
Rheumatology and taking HC due to their chronic diseases were included.
All the patients who were in follow-up in the Department of Rheumatology
in our hospital between March and April 2020 were scanned via the
``hospital digital registration system''. Among them, 384 patients who
were taking HC regularly were included in the study. 299 patients who
were not taking HC were included in the control group. The study
protocol was reviewed and approved by I\selectlanguage{english}zmir Bakircay University Ethics
Board. The study protocol conforms to the ethical guidelines of the 1975
Declaration of Helsinki as reflected in a priori approval by the
institution's human research committee. Written informed consent was not
necessary because no patient data has been included in the manuscript.
And the patients are phoned and their verbal consents were obtained.

Study population

We used the data of patients who were in follow-up in the Department of
Rheumatology. The patients who were continuing to take HC in this period
were assigned as the experimental group, while those who were not taking
HC were assigned as the control group. The patients who applied to the
Rheumatology Department but were not diagnosed with rheumatic disease
were excluded. The patients are phoned and their verbal consents were
obtained. The consents were obtained verbally since it was not
appropriate for the patients to come to the hospital in terms of
contamination risk in the Covid-19 pandemic process. It was emphasized
that their data will not be shared in any way. The information on their
demographical characteristics (age, gender, occupation), primary
diseases, other medications than HC they used, the dose of HC they
received, whether they had Covid-19, whether they were administered with
PCR test as a potential case, if so the results of the test (From the
individual's self-declaration or central result system referred to as
''PHMS'' Public Health Management System), whether people who they were
living together or those with whom they had close contact were diagnosed
with Covid-19 and received Covid-19 treatment, were recorded.
Information on the course of disease (follow-up at home,
hospitalization, intensive care unit, exitus) was collected from the
hospital registration system or the patients themselves.

Main outcomes and measures

The primary outcome is to detect a positive PCR result in patients who
received a PCR test and to determine the incidence rate of the disease
among those who were taking HC and those who were not taking HC.

Statistical analysis

The statistical analysis was performed using SPSS 22 (SPSS Inc.,
Chicago, IL) software program. The demographic data were analyzed based
on the means and standard deviation and the Chi-square test was used for
group comparisons. Continuous data were expressed as mean \selectlanguage{ngerman}± standard
deviation and categorical parameters were computed as percentages, where
appropriate. If p\textless{}0.05, then the result was considered
statistically significant.

\textbf{Results}

The patients who were taking HC agents due to rheumatic disease and
those in the control group were examined (Figure 1). It was seen that
the majority of patients were female and housewives (Figure 2, Table 1).
The median age was 51.8 years (from 17 to 89) and the majority of them
were in the 50-60 age band (Figure 3). It was found that 56 (14.6\%)
patients had comorbidity (14.6\%), while 34 (8.9\%) had diabetes and 9
(2.3\%) had hypertension (2.3\%). All the patients were taking HC
1x1/day or 2x1/day. Thirty-two (8.33\%) patients who were included in
the study could not be reached by phone. Based on the phone calls, the
number of patients who were in close contact with Covid-19 patients was
15 (3.9\%). The number of the patients who underwent Covid-19
examination for any reason was found to be 5.72\%(22/384). Only 2
(0.52\%) patients under our observation were diagnosed with Covid-19.
Both of them were mild cases and without hospitalization. When we
examined 299 patients who were under follow-up because of their
rheumatic diseases but were not taking HC, PCR positivity was detected
in 24 (8.02\%) of 65 (21.73\%) patients who received a PCR test. It was
also found that two patients who were not using HC died due to Covid-19.
When we compared the PCR positivity rate between the patients who were
taking HC (n=2) and those who were not using HC (n=24), we found that
the PCR positivity was statistically lower in the HC group (Respectively
n=2 0.52\%, n=24 8.02\%, p=0.0001).

One of the Covid-19 patients was a 42-year-old teacher and the other was
a 48-year-old housewife. Both of them had connective tissue disease. The
phone calls with the patients revealed that the teacher patient has not
worked during the pandemic period but her husband contacted other
patients (for about 1 hour) when their daughter got sick. Then first her
husband and then she was diagnosed with Covid-19 (PCR and thorax CT
positive). She healed at home with mild myalgia and fever which lasted
for few days. The other patient who was a housewife had no contact with
a confirmed Covid-19 patient. But her husband was a plumber and had a
plumbery. She had an irritable cough and her thorax CT was compatible
with viral pneumonia but healed at home without any complication.

\textbf{Discussion}

Severe acute respiratory syndrome (SARS) is caused by a newly discovered
coronavirus (Covid-19). No effective prophylactic or post-exposure
therapy is currently available.\textsuperscript{10} Some
disease-modifying agents commonly used to treat patients with rheumatic
diseases/autoimmune disorders, such as HC and colchicine, are explored
as potential treatments for COVID-19. However, their prophylactic roles
are still not certain.\textsuperscript{11} Hydroxychloroquine was first
approved for medical use in the USA in 1955.\textsuperscript{1} The
studies showed that these molecules inhibit viral DNA and RNA polymerase
enzymes and also inhibit viral protein glycosylation and viral
proliferation. The virus binds to target cells by angiotensin-converting
enzyme 2 (ACE2). HC was preferred in SARS treatment because it can
inhibit the terminal glycosylation of ACE2 and modify cytokine release.
It was thought that it can be used in Covid-19
treatment.\textsuperscript{6} It was observed that in clinical use, HC
prevented the progress of virus-related pneumonia. In March 2020
hydroxychloroquine (HC) was reported to have a positive effect in a
Covid-19 treatment open-label non-randomized clinical trial. In this
study, hydroxychloroquine and azithromycin were used to prevent
bacterial infection, and no treatment was applied to the negative
control group. 20 of 36 patients were administered with azithromycin and
600 mg/day HC. A significant decrease in viral load was found on day 6,
as compared with the control group.\textsuperscript{12} However,
Rosendaal reported that there were great methodological deficits in this
study and the results did not support the results on the efficiency of
hydroxychloroquine in Covid-19.\textsuperscript{13} Similarly, Goldman
et al. stated in their comment that randomized controlled studies are
needed for the data to be significant.\textsuperscript{14} The
difference of our study from the study by Gautret et all. is that our
study was not an intervention and treatment study and it was only an
observational study for patients with HC use history. Currently, there
is still no suggestion to use antiviral agents as prophylaxis for
Covid-19 but many studies are in progress to evaluate the effects of
treatment as well as prophylaxis.\textsuperscript{9} We hope that the
results of the ongoing studies will give us more insight into
prophylaxis and help with prophylaxis agents, which will reduce the
rapid spread of the disease. Another study reviewed all available
resources to overview the potential role of HC in preventing the spread
of COVID-19 and to determine a reasonable schedule for its use as
prophylaxis. It was stated that there were very limited clinical data on
the prophylactic role of HC. It was reported that HC is used for
prophylaxis because it showed reductions of exacerbation of pneumonia,
duration of symptoms, and delay of viral clearance, all in the absence
of severe side effects. As a result, they said that further information
can be obtained only by wide prospective randomized
studies.\textsuperscript{15} We hope that our data and a meta-analysis
of the results of similar observational studies and ongoing randomized
studies serve to justify the large-scale use of prophylactic HC.
Although research on the use of HC in the control of COVID-19 is still
preliminary, the potential use of these drugs is supported by factors
such as their usability in the treatment of rheumatic and infectious
diseases such as malaria, low cost and history of use. Furthermore, HC
is increasingly preferred because it is a less toxic derivative of CQ
and showed better results in inhibiting the proliferation of
SARS-CoV-2.\textsuperscript{16} The review study by Preira reported that
a meta-analysis was conducted to investigate the effects of using CQ and
HC in 16,679 patients with rheumatic disease, but their effects on
cardiomyopathy and neuropathy were not confirmed. In the systematic
literature review, he examined cardiac complications associated with CQ
and HC and noted that cardiac disorders related to CQ or HC were rare,
but a prolonged administration resulted in serious adverse effects. He
emphasized that there is no evidence on the preventive effect of HC on
Covid-19 and suggested that sharing HC use information will lead to
healthier results.\textsuperscript{16} Our main purpose was to determine
whether HC can be used or not, instead of reaching a conclusion. We aim
to share our data that will likely to contribute studies with larger
participation.

In a data analysis conducted in Israel, all COVID-19 cases were screened
and it was found that 36 patients were using HC regularly and only three
(0.23\%) patients were COVID-19 positive.\textsuperscript{11} In our
study, 384 patients who were using HC were screened and it was found
that 2 (0.52\%) of 22 patients who were examined were Covid-19 positive,
and 24 (8.02\%) of 65 patients who were not using HC and examined were
Covid-19 positive. In the study by Boulware et al., randomly selected
821 asymptomatic Covid-19 patients were administered with placebo and HC
after the exposure. They reported that there was no difference between
the two groups and no serious adverse effect was
seen.\textsuperscript{17} Rajasingham et al. did not find a significant
decrease in the incidence of Covid-19 based on the prophylaxis results
of 1483 health professionals before the HC exposure (400 mg HC twice a
week and 400 mg HC and placebo twice a week).\textsuperscript{18} Abella
et al. conducted a randomized, double-blind, placebo-controlled study on
a population of health professionals but early stopped the study since
they predicted that there would be no significant difference. However,
they did not report any serious side
effects.\textsuperscript{19}Although there are no many studies
suggesting the use of HC for prophylaxis, more reliable data will be
obtained if all researchers shared their data and the results of
randomized controlled studies are provided. It seems that; Covid-19 will
continue to be a threat to the world.

\textbf{Conclusion}

Our study supported the fact that there is a lower PCR positivity and
symptoms are milder among patients who are using HC regularly, as
compared to those who are not using HC. Whether prior exposure
prophylaxis is effective in populations at high risk is a separate
question and studies are continuing and will continue. If our results
are reproduced in other ongoing studies, our results will be verified.

\textbf{Limitations}

We do not know the rate of patients who are using HC regularly among all
suspected Covid-19 cases. We examined only the HC patients in an
isolated area. The lack of precisely recorded comorbidities in our all
data directed us to only the patients who were registered and using HC
regularly. Another limitation was the lack of data of patients who could
not be reached by phone and of those in the control group. Another
limitation was the fact that the contact histories of patients were
evaluated only based on the self-declaration. It is difficult to
determine who contacted Covid-19 patients, which doesn't make much sense
today.

\textbf{Author contributions:} All the authors contributed
intellectually and directly to the preparation of this article, and read
and approved the current version of the article for publication.

Conflicting interests: The Author(s) declare(s) that there is no
conflict of interest.

\textbf{References}

1. Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese Medicine
in the Treatment of Patients Infected with 2019-New Coronavirus
(SARS-CoV-2): A Review and Perspective. International journal of
biological sciences 2020;16(10):1708-1717.

2. Dashboard WCDC-: https://covid19.who.int. Data last updated:
2021/1/7, 10:18am CET 2021.

3. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features
of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet
2020; 395(10223):497-506.

4. Gao J TZ, Yang X. Breakthrough: Chloroquine phosphate has shown
apparent efficacy in treatment of COVID-19 associated pneumonia in
clinical studies. BioScience Trends /Advance Publication 2020;14(1):
72-73. doi.org/10.5582/bst.2020.01047.

5. Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of
chloroquine on viral infections: an old drug against today's diseases?
Lancet Infect Dis 2003; 3(11):722-727.

6. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and
chloroquine effectively inhibit the recently emerged novel coronavirus
(2019-nCoV) in vitro. Cell Res 2020;30(3):269-271.

7. Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. In Vitro
Antiviral Activity and Projection of Optimized Dosing Design of
Hydroxychloroquine for the Treatment of Severe Acute Respiratory
Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis
2020;71(15):732-739. doi: 10.1093/cid/ciaa237.

8. Infectious Diseases Society of America Guidelines on the Treatment
and Management of Patients with COVID-19.
https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
(Accessed on April 13, 2020).

9. Agrawal S GAD, Gupta N. Emerging prophylaxis strategies against
COVID-19. Monaldi Archives for Chest Disease 2020; 90:1289.

10. Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek
TG, et al. Chloroquine is a potent inhibitor of SARS coronavirus
infection and spread. Virology Journal 2005; \textbf{2} (1):69.

11. Gendelman O, Amital H, Bragazzi NL, Watad A, Chodick G. Continuous
hydroxychloroquine or colchicine therapy does not prevent infection with
SARS-CoV-2: Insights from a large healthcare database analysis.
Autoimmun Rev 2020; 19(7):102566-102566.

12. Gautret P LJ, Parola P, Hoang T, Meddeb L, Mailhe M, Doudier B, et
al. Hydroxychloroquine and azithromycin as a treatment of COVID-19:
results of an open- label non-randomized clinical trial. Int J
Antimicrob Agents 2020;56(1):105949. doi:
10.1016/j.ijantimicag.2020.105949.

13. Rosendaal FR. Review of: ''Hydroxychloroquine and azithromycin as a
treatment of COVID-19: results of an open-label non-randomized clinical
trial Gautret et al. Int J Antimicrob Agents 2020;56(1):106063.
doi:10.1016/j.ijantimicag.2020.105949.

14. Goldman JD, Diaz G, Urba WJ. Use of hydroxychloroquine in
combination with azithromycin for patients with COVID-19 is not
supported by recent literature. Int J Antimicrob Agents 2021;
57(1):106174.

15. Monti M, Vertogen B, Masini C, Donati C, Lilli C, Zingaretti C, et
al. Hydroxychloroquine as Prophylaxis for COVID-19: A Review. Frontiers
in pharmacology 2020;11:605185-605185.

16. Pereira BB. Challenges and cares to promote rational use of
chloroquine and hydroxychloroquine in the management of coronavirus
disease 2019 (COVID-19) pandemic: a timely review. J Toxicol Environ
Health B Crit Rev 2020;23(4):177-181.

17. Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM,
Okafor EC, et al. A Randomized Trial of Hydroxychloroquine as
Postexposure Prophylaxis for Covid-19. New England Journal of Medicine
2020;383(6):517-525.

18. Rajasingham R, Bangdiwala AS, Nicol MR, Skipper CP, Pastick KA,
Axelrod ML, Pullen MF, Nascene AA, Williams DA, Engen NW et al:
Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease
2019 (COVID-19) in Healthcare Workers: A Randomized Trial. Clinical
Infectious Diseases 2020; ciaa1571. doi.org/10.1093/cid/ciaa1571.

19. Abella BS, Jolkovsky EL, Biney BT, Uspal JE, Hyman MC, Frank I,
Hensley SE, Gill S, Vogl DT, Maillard I et al: Efficacy and Safety of
Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis
Among Health Care Workers: A Randomized Clinical Trial. JAMA Internal
Medicine 2021;181(2):195-202. doi:10.1001/jamainternmed.2020.6319

Figure 1. Working flow chart

Figure 2. Gender distribution of patients using hydroxychloroquine

Figure 3. Distribution of patients using hydroxychloroquine by age
groups

Table1. Occupational distribution of patients\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\textbf{Occupation} & \textbf{n} & \textbf{\%}\tabularnewline
Housewife & 233 & 60.7\tabularnewline
Retired & 47 & 12.2\tabularnewline
Officer* & 24 & 6.3\tabularnewline
Self-employment & 34 & 8.9\tabularnewline
Student & 3 & 0.8\tabularnewline
Worker & 30 & 7.8\tabularnewline
Missing & 13 & 3.4\tabularnewline
\textbf{Total} & 384 & 100.0\tabularnewline
\bottomrule
\end{longtable}

* Civil servants include 9 healthcare workers (4 nurses, one doctor, 4
others) and 5 teachers)\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}

\textbf{Hosted file}

\verb`Table1.docx`  available at \url{https://authorea.com/users/417382/articles/524514-the-effect-of-hydroxychloroquine-use-due-to-rheumatic-disease-on-the-risk-of-covid-19-infection-and-its-course}

\selectlanguage{english}
\FloatBarrier
\end{document}

