Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : February | Volume : 16 | Issue : 2 | Page : OC18 - OC23 Full Version

Implementing a Fever Clinic for Managing COVID-19 Patients using Hydroxychloroquine Protocol- An Experience from a Primary Healthcare Centre in Riyadh, Saudi Arabia


Published: February 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/52890.16009
Azzam F Al Otaibi, Ayla M Tourkmani, Abuobieda Khogali, Ibrahim H Al Khashan ,Attiat Yousef, Alaa Abdelaziz, Abdulrahman N Alreshaed, Maher A AlSakkak

1. Consultant Medical Doctor, Department of Family Medicine, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. 2. Consultant Clinical Pharmacist and Clinical Researcher, Department of Family and Community Medicine, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. 3. Registrar Medical Doctor, Department of Preventive Medicine, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. 4. Medical Student, College of Medicine, Imam Muhammad ibn Saud Islamic University, Riyadh, Saudi Arabia. 5. Registrar Medical Doctor, Department of Family Medicine, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. 6. Senior Registrar Medical Doctor, Department of Family Medicine, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. 7. Consultant Medical Doctor, Department of Family Medicine, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. 8. Consultant Medical Doctor, Department of Family Medicine, Prince Sultan Military Medical City, Riyadh, Saudi Arab

Correspondence Address :
Ayla M Tourkmani,
Consultant Clinical Pharmacist and Clinical Researcher, Department of Family Medicine,
Prince Sultan Military Medical City, Riyadh-11159, Saudi Arabia.
E-mail: aylatourkmani@gmail.com

Abstract

Introduction: During the initial weeks of the COVID-19 pandemic, there was limited information and evidence about therapeutic interventions for management of COVID-19 infections. Consequently, fever clinics were established in Saudi Arabia to provide supportive treatment for all COVID-19 patients as specialised clinics. During the early months of 2020, Hydroxychloroquine (HCQ) was being used as part of the Saudi Ministry of Health (MoH) protocol for management of COVID-19 infections.

Aim: To report the experience with implementing fever clinic utilising the HCQ-based protocol for adults with mild and moderate symptoms of COVID-19, and provide further evidence regarding the efficacy and safety of HCQ.

Materials and Methods: A prospective observational study was conducted in one of the primary healthcare centres in Saudi Arabia. All patients with suspected or confirmed COVID-19 who visited the fever clinic and met the eligibility criteria of starting HCQ based protocol were included in the study. Beside supportive treatment, the intervention dose of HCQ was 400 mg twice a day for one day followed by 200 mg twice a day for another four days. Statistical Package for Social Sciences (SPSS) version 22 was used for data analyses.

Results: A total of 108 patients with mean age of 36 years with Standard Deviation (SD) of 9.3 were included in the study. The mean Body Mass Index (BMI) was 27.1 (SD 4.9). In addition, 73.1% of the patients were males and 25% were smokers. The study findings showed that the fever clinic was effective in managing the symptoms of COVID-19 and treating the patients regardless of the use or completion of HCQ. In particular, on day 6, cough improved in >85% of the patients and fever was resolved in >83% of patients. However, there were no statistically significant differences among the patients who received/completed HCQ and those who did not start or complete the protocol in terms of negative conversion based on the Nasopharyngeal (NP) swab real time Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) by day 14, and resolution/improvement of symptoms on day 6 (p>0.05).

Conclusion: This study documented the experience of implementing a fever clinic to manage the suspected and confirmed COVID-19 patients with mild to moderate symptoms during the initial phase of the pandemic in Saudi Arabia. The study findings revealed that the concept of fever clinics was useful for managing suspected and confirmed cases. At the same time, there were no additional benefits of HCQ compared to the supportive treatment in this study.

Keywords

Coronavirus disease-2019, Cough, Pandemic, Symptoms

The COVID-19 infections are increasing rapidly throughout the world and this novel virus has crossed the frontiers (1),(2). The infected individuals from COVID-19 can develop flu or pneumonia-like symptoms and in severe cases, it can lead to multi-organ failure (3). This highly contagious disease spreads from one individual by body secretions such as saliva or nasal droplets and it can also pass from human to the next by coming in contact with the infected individual or by touching the infected areas (4),(5). The virus started its journey in one of the provinces of China, named Wuhan, at the end of 2019 and spread with great speed through China and the rest of the world (6). Overall, a peak in the number of cases was usually followed by a decline when timely control measures were taken (7). Despite the effective and timely measures, almost all of the developed and developing countries have faced substantial morbidity and mortality from this unanticipated pandemic (8),(9).

Since COVID-19 poses a severe threat to global health, therefore, there is an urgent need to cure symptomatic patients and to limit the transmission in the community and to reduce the morbidity and mortality associated with COVID-19 (10),(11). Consequently, many countries including Saudi Arabia established fever clinics to manage suspected cases of COVID-19 infections. These clinics serve all individuals who show COVID-19 symptoms such as fever, sore throat, muscle pain, shortness of breath, loss of taste or smell. The fever clinics receive patients at any time, without appointments for appropriate management of COVID-19 infections (12). In addition to this benefit, the clinics help to reduce the potential of further infections as the patients will be treated in separate clinics under strict infection control and precautionary measures rather than mixing with other patients in emergency department and ordinary medical clinics.

However, numerous drugs have been given to the patients of COVID-19 due to their well-known antiviral pharmacological actions hoping for potential effectiveness against COVID-19 infections (13),(14). The absence of a proven therapy for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has encouraged clinicians to use drugs that have been found effective for other medical conditions (15). For example, HCQ is being widely prescribed by physicians for COVID-19 patients on the basis of the results from some observational evidence (including a preprint) at the early months of the pandemic (16),(17),(18). Chloroquine or HCQ have been used as they have shown beneficial results
in-vitro and have also been used in the past for diseases similar to COVID-19 (13),(14),(19).

It has been postulated that that drugs such as HCQ suppresses the SARS-CoV-2 replication by hindering the production of pro-inflammatory cytokines thus blocking the inflammatory cascade that causes acute respiratory distress syndrome (20). However, some of the observational studies initially suggested positive results of HCQ, while others have shown lack of effectiveness of this drug (21),(22). Therefore, the investigators aimed to report experience from the fever clinic established during the early phases of the pandemic with assessment of the patients’ outcomes receiving the HCQ, besides supportive treatment in adults with mild and moderate symptoms of Coronavirus Disease-2019. This could help in providing further guidance especially during uncertain times of pandemics.

Material and Methods

A prospective observational study was conducted at the fever clinic of Wazarat Healthcare Centre (WHC) in Family and Community Medicine Department, which is a primary healthcare centre of Prince Sultan Military Medical City (PSMMC) in Riyadh, Saudi Arabia and it was accredited by Joint Commission International (JCI). The fever clinic was established during COVID-19 pandemic in Saudi Arabia and was established mainly to manage and follow-up stable suspected and confirmed COVID-19 mild and moderate cases attending the primary healthcare centre. The research ethics committee-Prince Sultan Military Medical City (PSMMC) approved the protocol of the study (HP-01-R097).

All patients attending the fever clinic with suspected or confirmed COVID-19, between 14th June 2020 to 3rd August 2020 who met the eligibility criteria of starting HCQ were included in the study. Patients were informed about the study and its objectives with all relevant information. Consequently, the patients who provided an informed consent were included in the study. In addition, they were informed about their right to withdraw from the study at any time.

Inclusion criteria: The eligibility of the patients for HCQ based protocol included patients’ between 18 years to 65 years of age.

Exclusion criteria: Severely ill patients with heart block, and arrhythmias; severe liver disease; pregnancy or lactation; retinopathy, and other retinal diseases; allergy to sulfa drug and patients with G6PD deficiency were excluded from the study.

Clinical Protocol of the Fever Clinic and HCQ for Treatment

The fever clinic protocol for management of suspected and confirmed COVID-19 cases are summarised in (Table/Fig 1). The protocol of HCQ was formed to manage and follow-up for stable and confirmed mild to moderate COVID-19 cases who attended primary healthcare centre for this purpose. This was adapted from approved Saudi MoH protocol at that time during the initial phase of the pandemic (23). As per the Saudi MoH protocol, HCQ was considered for all patients visiting the fever clinic aged ≥18 years, presenting with documented temperature of >38°C within the last 24 hours and suffered atleast from runny nose, sore throat, cough, shortness of breath, headache, and/or myalgia. In addition to the history taking and physical examination, NP swab and other laboratory investigations such as electrolyte, haemoglobin level, white blood cells, D-Dimer, serum creatinine were done before starting the treatment. The patients were re-evaluated when the first swab PCR result was out.

Informed consent was taken from patients that were administered the medication. As per the protocol, HCQ was initiated and accounted as day 1 with 400 mg every 12 hours (for 1 day) followed with 200 mg every 12 hours for 4 days with zinc 60 mg OD. All patients with confirmed COVID-19 were enrolled in the study and who met the inclusion criteria for starting HCQ. Diagnosis and classification of COVID-19 was based on the criteria of the Saudi Arabia Ministry of Health Protocol, June 2020 (23). ECG was done at baseline and on day 3. If the QT Interval (QTc) was exceeding 470 ms during initial measurement on day 1, HCQ was not initiated. In day 3, if QTc exceeded 470 ms or increased more than 40 ms from baseline, HCQ was discontinued. Patients who showed clinical deterioration at day three, were referred to the hospital and continuous follow-up was done by the research team for outcomes.

The collected data included demographic and general patient information, vital signs, and Electrocardiogram (ECG) and if the QTc >470 ms, the HCQ was not be started. Chest X-ray was done when it was clinically indicated. Co-morbidities were assessed to improve safety during the use of HCQ. Safety outcome of the treatment protocol, including the percentages of patients who developed side-effects (ECG changes, GI symptoms, nausea and headache), and reasons for medication discontinuation was recorded. Results of laboratory tests done on day 1 were reviewed and repeated on day 3. ECG was repeated and QTc was measured, if it exceeded >470 ms or increased more than 40 ms compared to baseline, the medication was stopped immediately.

Patients’ Follow-up and Outcomes Monitoring

Clinical symptoms were re-evaluated after treatment administered and temperature was also recorded. On day 6 follow-up, alleviation of clinical symptoms were assessed in comparison to day 1. On the other hand, a second NP swab real time RT-PCR, was taken to assess negative conversion of coronavirus on day 14. According to the WHO guidelines, during the early phase of the pandemic, a positive result of (RT-PCR) based on a NP swab was considered as a confirmed case of COVID-19. Adherence to the prescribed dose of HCQ was assessed during the follow-up period. Flow chart of the study is shown in (Table/Fig 2) and demonstrates the response of participants on day 1, 3, 6 and 14. The outcomes for the fever clinic-based protocol included COVID-19 negativity test, which was measured at day 14 after using HCQ. Negative conversion of COVID-19 was based on atleast one laboratory report. The second outcome was resolution of symptoms.

Statistical Analysis

Continuous data were presented as means±SD and categorical data were presented as frequencies (n) and percentages (%). The level of p-value <0.05 was used for all analyses to indicate a statistical significance. Chi-square test and Fisher-exact test was used to compare the differences across categorical variables for HCQ usage. Statistical Package for the Social Science (SPSS) version 22 was used for data analyses.

Results

Socio-demographic and clinical characteristics of the patients: The mean age of the 108 patients was 36 years (SD 9.3) and mean BMI was 27.1 kg/m2 (SD 4.9). In addition, 73.1% of the patients were males and 25% were smokers (Table/Fig 3). Moreover, regarding clinical parameters of the patients, 4.6% of the patients were diabetic, 5.6% were hypertensive and none were suffering from other co-morbidities (congestive heart failure, recent myocardial infarction, active malignancy, immunosuppressive illness, G6PD deficiency, retinopathy). The mean systolic and diastolic pressure at the time of admission was 118.9 (SD 14) and 75.7 (SD 9.6), respectively. The mean heart rate was 101.12 (SD 18.2) and mean haemoglobin (gm/dL) was 14.2 (SD 1.69). The mean value for temperature was (37.59±0.89), and the mean value for D-Dimer was (1.38±2.20). All patients were febrile, and 79.6% had cough at the initial presentation. None of the patients had abnormal ECG including QTc interval prolongation.

Clinical outcomes of the patients treated at the fever clinic using HCQ based protocol: The clinical outcomes of the patients in terms of effectiveness are presented in light of conversion of results of NP swab for COVID-19 by day 14, and improvement in symptoms by day 6 after using HCQ. The fever clinic was effective in managing the symptoms regardless of completion of HCQ. For example, on day 6, improvement of cough was achieved by more than 85% in all patients and fever was resolved in more than 83% of all patients. Regarding conversions of the results of the swab by day 14, no statistically significant difference existed between patients with confirmed COVID-19 who completed the course of HCQ and those who did not (p=0.34) (Table/Fig 4). Similarly, there was no statistically difference in the resolution of fever by day 6 between those completed HCQ and those discontinued or did not started it. More specifically, 16.2% patients who took HCQ had fever compared with 9.5% of those who did not take HCQ (p=0.35). Similarly, there was no statistically significant difference for patients who completed HCQ and those who did not complete or start HCQ in terms of improvement of cough (p=0.18) (Table/Fig 4).

Safety outcomes during the treatment at the fever clinic with HCQ based protocol: (Table/Fig 5) demonstrates the findings regarding safety of HCQ. Only 1.4% of those who took HCQ reported of having nausea compared to 16.7% patients who did not complete HCQ (p=0.69). Likewise, 9.5% of the patients using HCQ complained of headache as opposed to 9.1% of their counterparts, however, the results were not statistically significant (p=0.56). Furthermore, while 4.8% of the patients using HCQ complained of gastric upset, 4.1% of the patients who did not use or start HCQ with insignificant differences (p=0.64). None of the patients using HCQ showed abnormal findings on ECG including prolonged QTc interval or any other abnormal finding by day 3. While investigating the proportion of patients who discontinued HCQ, it was found that among the majority, 17.6% of the patients discontinued as advised by doctor other than the treating one, while 23.5% stopped on their own after negative results (Table/Fig 5).

Discussion

This study was conducted to report the experience of implementing a fever clinic to manage the suspected and confirmed COVID-19 patients during the initial phase of the pandemic in Saudi Arabia. During early 2020, the clinical protocol approved by Saudi MoH included managing the patients in fever clinics using HCQ, besides supportive treatment in adults with mild and moderate symptoms Coronavirus Disease-2019 (23). The study findings revealed that the concept of fever clinics was useful for managing suspected and confirmed cases. In particular, these clinics helped in providing better health services and ensured appropriate supportive management and close follow-up especially during the uncertain time of the pandemic where no effective treatment was proven or available. This is evident by the resolution of the symptoms for the vast majority of patients. At the same time, there were no additional benefits of HCQ compared to the supportive treatment in the study. More specifically, there was no statistically significant effect of HCQ in converting the NP swab from positive at the first visit to negative at the follow-up visits. Similarly, there was no significant additional improvement in alleviating symptoms such as fever and cough. The safety of HCQ was assessed by evaluating the symptoms such as nausea, headache, gastric upset and repeated ECG after giving HCQ to the patients. The findings showed that HCQ was tolerable by the patients with a very minimum reported side effects. Thus, HCQ was not found to be unsafe for the patients in this study especially when used as part of an approved protocol in mild to moderate COVID-19 patients based on clear eligibility criteria. These findings need to be interpreted in the sociocultural and demographic context of Saudi Arabia.

When compared with the existing literature, the findings of this study are consistent with the published studies elsewhere. For instance, similar to this study, Chen Z et al., (preprint) did not find any statistically significant difference for virological cure between intervention (HCQ) and control arm (24). Likewise, Mallat J et al., (preprint), conducted a comparative observational study using data collected from routine care from four French tertiary care centres providing care to patients with COVID-19. It did not support HCQ use in patients admitted to hospital with COVID-19 who required oxygen, as there was no effect of HCQ in patients with COVID-19 (25).

Similarly, the study conducted by Boulware DR et al., revealed that HCQ did not have additional benefits in alleviating the symptoms associated with COVID-19 when initiated within 4 days, thus, illustrating compatible results with this study (26). Moreover, findings from another study conducted on patients with mild to moderate COVID-19 disease were similar to findings of this study. More specifically, the results showed that HCQ was associated with a slower viral clearance at day 14 in COVID-19 patients with mild to moderate disease, and with no marked in improvement of inflammatory markers or lymphopenia rate (27). Lastly, findings from a recently conducted systematic review ant meta-analysis revealed that there was no difference in virologic cure, safety or alleviation of symptoms of COVID-19 disease in patients with and without HCQ (28).

Regarding safety of HCQ, it was found in the current study that around more than a quarter of the patients discontinued the treatment on physician’s advice and similar proportion stopped medication after having negative results for the swab. When comparing the findings with other studies in literature in terms of safety, the findings are almost similar. For instance, the study conducted by Chen J et al., revealed that 26.7% of the HCQ group and 20% of the participants in the control group complained of diarrhoea and altered liver function (29). Similarly, the study by Chen Z et al., demonstrated that two patients in the HCQ arm showed mild adverse reactions such as rash, and headache (24). Gautret P et al., showed that one patient discontinued treatment on day 3 because of nausea (17). Similarly, Boulware DR et al., noticed more side effects with HCQ than with the control group, however, no serious adverse reactions were noticed in their study (26). Additionally, a cross-sectional study conducted in Saudi Arabia to assess the safety of HCQ-based protocol, showed that 8.8% of patients discontinued the treatment because of the development of side effects, mainly cardiovascular adverse events (2.5%), followed by Gastrointestinal (GI) symptoms (2.4%) (30). The results, coupled with the literature finding, provide the guidance that the use of HCQ needs to be based on strict eligibility criteria with appropriate monitoring and patient counseling.

The findings from this study and their comparison with other studies illustrate that there is no solid evidence to use HCQ among COVID-19 patients to reduce the morbidity and mortality. Also, HCQ need to be used cautiously in such patients. The differences and conflict of results in literature about efficacy and safety of HCQ in literature especially at the initial phase of the pandemic could be due to several reasons such as dosage of HCQ, time duration of HCQ, differences in the outcomes measured by different studies, severity of the COVID-19 patients, and also the sample size and method of assigning HCQ to the COVID-19 patients. Another possible reason could be differences in the eligibility criteria between the studies.

This is one of the first study in Saudi Arabia to document the experience of fever clinics established in the initial months of the COVID-19 pandemic with comments on the safety and efficacy of HCQ in Saudi population. Secondly, the investigators measured the viral load using standard PCR techniques and they also evaluated patients for main symptoms, collected their necessary labs to have the data on important variables.

Limitation(s)

Firstly, the patients were not randomised to receive HCQ and any other treatment, therefore, could not control for unknown confounders. Secondly, the sample size was small, therefore, they might have missed the true effect of HCQ in the population, if there was any. Thirdly, the patients were not followed beyond 14 days and there is likelihood that HCQ might show its effects later. Also, the study did not consider side effects that may have developed later, as the study period was relatively short. Lastly, this study was conducted in a single primary centre therefore the findings might not be generalisable to other settings in Saudi Arabia or neighboring countries. Furthermore, viral load or cycle threshold (Ct) values from RT-PCR, as a proxy for the likelihood of clearance of the virus, was not done.

Conclusion

This study documented the experience of implementing a fever clinic to manage the suspected and confirmed COVID-19 patients with mild to moderate symptoms during the initial phase of the pandemic in Saudi Arabia. The study findings revealed that the concept of fever clinics were useful for managing suspected and confirmed cases. In particular, these clinics helped in providing better health services and ensured appropriate supportive management and close follow-up especially during the uncertain time of the pandemic where no effective treatment was proven or available. This is evident by the resolution of the symptoms for the vast majority of patients. At the same time, there were no additional benefits of HCQ compared to the supportive treatment in this study.

Acknowledgement

Heartfelt thanks to Dr. Abeer Mohammed Al Baadani, infectious disease consultant.

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DOI and Others

DOI: 10.7860/JCDR/2022/52890.16009

Date of Submission: Oct 15, 2021
Date of Peer Review: Dec 04, 2021
Date of Acceptance: Jan 06, 2022
Date of Publishing: Feb 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Oct 17, 2021
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• iThenticate Software: Jan 19, 2022 (15%)

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