Therapeutic Management of COVID-19 Patients: A systematic review
Identifieur interne : 001938 ( Pmc/Corpus ); précédent : 001937; suivant : 001939Therapeutic Management of COVID-19 Patients: A systematic review
Auteurs : Mansour Tobaiqy ; Mohammed Qashqary ; Shrooq Al-Dahery ; Alaa Mujallad ; Almonther Abdullah Hershan ; Mohammad Azhar Kamal ; Nawal HelmiSource :
- Infection Prevention in Practice [ 2590-0889 ] ; 2020.
Abstract
SARS-CoV-2 is the causative agent of COVID-19; that has been declared a global pandemic by the WHO in 2020. The COVID-19 treatment guidelines vary in each country, and yet there is no approved therapeutic for COVID-19.
this review aimed to report any evidence of therapeutics used for the management of COVID-19 patients in clinical practice since the emergence of the virus.
A systematic review protocol was developed based on PRISMA Statement. Articles for review were selected from electronic databases (Embase, Medline and Google Scholar). Readily accessible peer-reviewed, full articles in English published from December 1st , 2019 to March 26th , 2020 were included. The search terms included combinations of: COVID, SARS-COV-2, glucocorticoids, convalescent plasma, antiviral and antibacterial. There were no restrictions on the type of study design eligible for inclusion.
As of March 26th, 2020, of the initial manuscripts identified (n=449); forty-one studies were included. These consisted of clinical trials (n=3), case reports (n=7), case series (n=10), retrospective (n=11) and prospective (n=10) observational studies. Thirty-six studies were conducted in China (88%).
The most commonly reported medicine in this systematic review was corticosteroids (n=25), followed by Lopinavir (n=21) and Oseltamivir (n=16).
This is the first systematic review to date related to the therapeutics used in COVID-19 patients. Only 41 research articles on COVID-19 and therapeutics were found eligible to be included, most conducted in China. Corticosteroid therapy was found to be the most studied medicine in the literature.
Url:
DOI: 10.1016/j.infpip.2020.100061
PubMed: NONE
PubMed Central: 7162768
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Therapeutic Management of COVID-19 Patients: A systematic review</title><author><name sortKey="Tobaiqy, Mansour" sort="Tobaiqy, Mansour" uniqKey="Tobaiqy M" first="Mansour" last="Tobaiqy">Mansour Tobaiqy</name><affiliation><nlm:aff id="aff1">Department of Pharmacology, College of Medicine, University of Jeddah, Jeddah, Kingdom of Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Qashqary, Mohammed" sort="Qashqary, Mohammed" uniqKey="Qashqary M" first="Mohammed" last="Qashqary">Mohammed Qashqary</name><affiliation><nlm:aff id="aff2">Department of Family Medicine, College of Medicine, University of Jeddah</nlm:aff></affiliation></author><author><name sortKey="Al Dahery, Shrooq" sort="Al Dahery, Shrooq" uniqKey="Al Dahery S" first="Shrooq" last="Al-Dahery">Shrooq Al-Dahery</name><affiliation><nlm:aff id="aff3">Department of Applied Radiologic Technology, College of Applied Medical Sciences, University of Jeddah</nlm:aff></affiliation></author><author><name sortKey="Mujallad, Alaa" sort="Mujallad, Alaa" uniqKey="Mujallad A" first="Alaa" last="Mujallad">Alaa Mujallad</name><affiliation><nlm:aff id="aff4">Department of Nursing, College of Applied Medical Sciences, University of Jeddah</nlm:aff></affiliation></author><author><name sortKey="Hershan, Almonther Abdullah" sort="Hershan, Almonther Abdullah" uniqKey="Hershan A" first="Almonther Abdullah" last="Hershan">Almonther Abdullah Hershan</name><affiliation><nlm:aff id="aff5">Department of Medical Microbiology and Parasitology, College of Medicine, University of Jeddah</nlm:aff></affiliation></author><author><name sortKey="Kamal, Mohammad Azhar" sort="Kamal, Mohammad Azhar" uniqKey="Kamal M" first="Mohammad Azhar" last="Kamal">Mohammad Azhar Kamal</name><affiliation><nlm:aff id="aff6">Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">Centre for Science and Medical Research (UJC-SMR), University of Jeddah, Jeddah, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Helmi, Nawal" sort="Helmi, Nawal" uniqKey="Helmi N" first="Nawal" last="Helmi">Nawal Helmi</name><affiliation><nlm:aff id="aff6">Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia</nlm:aff></affiliation><affiliation><nlm:aff id="aff8">Department of Medical Laboratory Technology, College of Applied Medical Sciences, University of Jeddah</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmc">7162768</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162768</idno><idno type="RBID">PMC:7162768</idno><idno type="doi">10.1016/j.infpip.2020.100061</idno><idno type="pmid">NONE</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">001938</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001938</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Therapeutic Management of COVID-19 Patients: A systematic review</title><author><name sortKey="Tobaiqy, Mansour" sort="Tobaiqy, Mansour" uniqKey="Tobaiqy M" first="Mansour" last="Tobaiqy">Mansour Tobaiqy</name><affiliation><nlm:aff id="aff1">Department of Pharmacology, College of Medicine, University of Jeddah, Jeddah, Kingdom of Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Qashqary, Mohammed" sort="Qashqary, Mohammed" uniqKey="Qashqary M" first="Mohammed" last="Qashqary">Mohammed Qashqary</name><affiliation><nlm:aff id="aff2">Department of Family Medicine, College of Medicine, University of Jeddah</nlm:aff></affiliation></author><author><name sortKey="Al Dahery, Shrooq" sort="Al Dahery, Shrooq" uniqKey="Al Dahery S" first="Shrooq" last="Al-Dahery">Shrooq Al-Dahery</name><affiliation><nlm:aff id="aff3">Department of Applied Radiologic Technology, College of Applied Medical Sciences, University of Jeddah</nlm:aff></affiliation></author><author><name sortKey="Mujallad, Alaa" sort="Mujallad, Alaa" uniqKey="Mujallad A" first="Alaa" last="Mujallad">Alaa Mujallad</name><affiliation><nlm:aff id="aff4">Department of Nursing, College of Applied Medical Sciences, University of Jeddah</nlm:aff></affiliation></author><author><name sortKey="Hershan, Almonther Abdullah" sort="Hershan, Almonther Abdullah" uniqKey="Hershan A" first="Almonther Abdullah" last="Hershan">Almonther Abdullah Hershan</name><affiliation><nlm:aff id="aff5">Department of Medical Microbiology and Parasitology, College of Medicine, University of Jeddah</nlm:aff></affiliation></author><author><name sortKey="Kamal, Mohammad Azhar" sort="Kamal, Mohammad Azhar" uniqKey="Kamal M" first="Mohammad Azhar" last="Kamal">Mohammad Azhar Kamal</name><affiliation><nlm:aff id="aff6">Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">Centre for Science and Medical Research (UJC-SMR), University of Jeddah, Jeddah, Saudi Arabia</nlm:aff></affiliation></author><author><name sortKey="Helmi, Nawal" sort="Helmi, Nawal" uniqKey="Helmi N" first="Nawal" last="Helmi">Nawal Helmi</name><affiliation><nlm:aff id="aff6">Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia</nlm:aff></affiliation><affiliation><nlm:aff id="aff8">Department of Medical Laboratory Technology, College of Applied Medical Sciences, University of Jeddah</nlm:aff></affiliation></author></analytic><series><title level="j">Infection Prevention in Practice</title><idno type="ISSN">2590-0889</idno><idno type="eISSN">2590-0889</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>SARS-CoV-2 is the causative agent of COVID-19; that has been declared a global pandemic by the WHO in 2020. The COVID-19 treatment guidelines vary in each country, and yet there is no approved therapeutic for COVID-19.</p></sec><sec><title>Aims of the study</title><p>this review aimed to report any evidence of therapeutics used for the management of COVID-19 patients in clinical practice since the emergence of the virus.</p></sec><sec><title>Methods</title><p>A systematic review protocol was developed based on PRISMA Statement. Articles for review were selected from electronic databases (Embase, Medline and Google Scholar). Readily accessible peer-reviewed, full articles in English published from December 1<sup>st</sup> , 2019 to March 26<sup>th</sup> , 2020 were included. The search terms included combinations of: COVID, SARS-COV-2, glucocorticoids, convalescent plasma, antiviral and antibacterial. There were no restrictions on the type of study design eligible for inclusion.</p></sec><sec><title>Results</title><p>As of March 26<sup>th</sup>, 2020, of the initial manuscripts identified (n=449); forty-one studies were included. These consisted of clinical trials (n=3), case reports (n=7), case series (n=10), retrospective (n=11) and prospective (n=10) observational studies. Thirty-six studies were conducted in China (88%).</p><p>The most commonly reported medicine in this systematic review was corticosteroids (n=25), followed by Lopinavir (n=21) and Oseltamivir (n=16).</p></sec><sec><title>Conclusions</title><p>This is the first systematic review to date related to the therapeutics used in COVID-19 patients. Only 41 research articles on COVID-19 and therapeutics were found eligible to be included, most conducted in China. 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<front><journal-meta><journal-title-group><journal-title>Infection Prevention in Practice</journal-title></journal-title-group><issn pub-type="ppub">2590-0889</issn><issn pub-type="epub">2590-0889</issn><publisher><publisher-name>Published by Elsevier Ltd on behalf of The Healthcare Infection Society.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmc">7162768</article-id><article-id pub-id-type="publisher-id">S2590-0889(20)30025-1</article-id><article-id pub-id-type="doi">10.1016/j.infpip.2020.100061</article-id><article-id pub-id-type="publisher-id">100061</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Therapeutic Management of COVID-19 Patients: A systematic review</article-title></title-group><contrib-group><contrib contrib-type="author" id="au1"><name><surname>Tobaiqy</surname><given-names>Mansour</given-names></name><email>mtobaiqy@uj.edu.sa</email><xref rid="aff1" ref-type="aff">1</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib><contrib contrib-type="author" id="au2"><name><surname>Qashqary</surname><given-names>Mohammed</given-names></name><xref rid="aff2" ref-type="aff">2</xref></contrib><contrib contrib-type="author" id="au3"><name><surname>Al-Dahery</surname><given-names>Shrooq</given-names></name><xref rid="aff3" ref-type="aff">3</xref></contrib><contrib contrib-type="author" id="au4"><name><surname>Mujallad</surname><given-names>Alaa</given-names></name><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author" id="au5"><name><surname>Hershan</surname><given-names>Almonther Abdullah</given-names></name><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author" id="au6"><name><surname>Kamal</surname><given-names>Mohammad Azhar</given-names></name><xref rid="aff6" ref-type="aff">6</xref><xref rid="aff7" ref-type="aff">7</xref></contrib><contrib contrib-type="author" id="au7"><name><surname>Helmi</surname><given-names>Nawal</given-names></name><xref rid="aff6" ref-type="aff">6</xref><xref rid="aff8" ref-type="aff">8</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Department of Pharmacology, College of Medicine, University of Jeddah, Jeddah, Kingdom of Saudi Arabia</aff><aff id="aff2"><label>2</label>Department of Family Medicine, College of Medicine, University of Jeddah</aff><aff id="aff3"><label>3</label>Department of Applied Radiologic Technology, College of Applied Medical Sciences, University of Jeddah</aff><aff id="aff4"><label>4</label>Department of Nursing, College of Applied Medical Sciences, University of Jeddah</aff><aff id="aff5"><label>5</label>Department of Medical Microbiology and Parasitology, College of Medicine, University of Jeddah</aff><aff id="aff6"><label>6</label>Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia</aff><aff id="aff7"><label>7</label>Centre for Science and Medical Research (UJC-SMR), University of Jeddah, Jeddah, Saudi Arabia</aff><aff id="aff8"><label>8</label>Department of Medical Laboratory Technology, College of Applied Medical Sciences, University of Jeddah</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding Author. Department of Pharmacology, College of Medicine, University of Jeddah, Jeddah, Kingdom of Saudi Arabia. P.O. Box 45311 Jeddah 21512. <email>mtobaiqy@uj.edu.sa</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>17</day><month>4</month><year>2020</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="epub"><day>17</day><month>4</month><year>2020</year></pub-date><elocation-id>100061</elocation-id><history><date date-type="received"><day>3</day><month>4</month><year>2020</year></date><date date-type="accepted"><day>10</day><month>4</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 Published by Elsevier Ltd on behalf of The Healthcare Infection Society.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder></copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract id="abs0010"><sec><title>Background</title><p>SARS-CoV-2 is the causative agent of COVID-19; that has been declared a global pandemic by the WHO in 2020. The COVID-19 treatment guidelines vary in each country, and yet there is no approved therapeutic for COVID-19.</p></sec><sec><title>Aims of the study</title><p>this review aimed to report any evidence of therapeutics used for the management of COVID-19 patients in clinical practice since the emergence of the virus.</p></sec><sec><title>Methods</title><p>A systematic review protocol was developed based on PRISMA Statement. Articles for review were selected from electronic databases (Embase, Medline and Google Scholar). Readily accessible peer-reviewed, full articles in English published from December 1<sup>st</sup> , 2019 to March 26<sup>th</sup> , 2020 were included. The search terms included combinations of: COVID, SARS-COV-2, glucocorticoids, convalescent plasma, antiviral and antibacterial. There were no restrictions on the type of study design eligible for inclusion.</p></sec><sec><title>Results</title><p>As of March 26<sup>th</sup>, 2020, of the initial manuscripts identified (n=449); forty-one studies were included. These consisted of clinical trials (n=3), case reports (n=7), case series (n=10), retrospective (n=11) and prospective (n=10) observational studies. Thirty-six studies were conducted in China (88%).</p><p>The most commonly reported medicine in this systematic review was corticosteroids (n=25), followed by Lopinavir (n=21) and Oseltamivir (n=16).</p></sec><sec><title>Conclusions</title><p>This is the first systematic review to date related to the therapeutics used in COVID-19 patients. Only 41 research articles on COVID-19 and therapeutics were found eligible to be included, most conducted in China. Corticosteroid therapy was found to be the most studied medicine in the literature.</p></sec></abstract><kwd-group id="kwrds0010"><title>Key word</title><kwd>SARS-CoV-2</kwd><kwd>COVID-19</kwd><kwd>Hydroxychloroquine</kwd><kwd>Arbidol hydrochloride</kwd><kwd>Corticosteroids</kwd><kwd>Convalescent Plasma Therapy</kwd></kwd-group></article-meta></front><body><sec id="sec1"><title>Introduction</title><p id="p0010">Severe acute respiratory syndrome coronavirus SARS-CoV-2 is the <ext-link ext-link-type="uri" xlink:href="https://en.wikipedia.org/wiki/Cause_(medicine)" id="intref0010">cause</ext-link> of <ext-link ext-link-type="uri" xlink:href="https://en.wikipedia.org/wiki/2019%E2%80%9320_coronavirus_pandemic" id="intref0015">the</ext-link><ext-link ext-link-type="uri" xlink:href="https://en.wikipedia.org/wiki/Coronavirus_disease_2019" id="intref0020">coronavirus disease 2019</ext-link> (COVID-19) that has been declared a global pandemic by the World Health Organization (WHO) in 2020. SARS-CoV-2 was discovered in December 2019, in Wuhan City (the capital of Hubei province), China. The origin of the virus is unknown, but initially newly diagnosed cases were linked to the Huanan Seafood Wholesale Market where people can buy wild animals, such as bats <sup>(</sup><xref rid="bib1" ref-type="bibr"><sup>1</sup></xref><sup>)</sup>. SARS-CoV-2 has phylogenetic similarity to SARS-CoV and MERS- CoV. The virus was identified as a novel enveloped RNA betacoronavirus that has been named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) <sup>(</sup><xref rid="bib2" ref-type="bibr"><sup>2</sup></xref><sup>)</sup>.</p><p id="p0015">One of the characteristics of COVID-19 is that it is highly contagious; many countries were affected, including China and 164 other countries in less than three months. Despite China reaching 81,151 confirmed cases with 3,242 deaths, the country reported only one new domestic case as of March 18<sup>th</sup>, 2020. As of that date, the total worldwide confirmed cases are 193,475 with 7,864 deaths (WHO). Although protective measures have been implemented in China (such as isolation from confirmed and suspected cases) to reduce the spread of the virus, the need for effective treatment is imperative to stop the outbreak and reduce the morbidity and mortality of COVID-19<sup>(</sup><xref rid="bib1" ref-type="bibr"><sup>1</sup></xref><sup>)</sup>.</p><p id="p0020">Since onset of the outbreak, researchers have proposed many agents that could have efficacy against COVID-19. Different antiviral agents were included in the latest guidelines from the National Health Commission (NHC) including Interferon, Lopinavir/Ritonavir, Chloroquine Phosphate, Ribavirin, and Arbidol<sup>(</sup><xref rid="bib3" ref-type="bibr"><sup>3</sup></xref><sup>)</sup>. Angiotensin receptor blockers, such as Losartan, are another suggestion to treat COVID-19<sup>(</sup><xref rid="bib4" ref-type="bibr"><sup>4</sup></xref><sup>)</sup>.</p><p id="p0025">COVID-19 treatment guidelines vary in each country. The WHO guidelines are very general, to manage only the symptoms and advise to be cautious with paediatric patients, pregnant, and patients with underlying co-morbidities. There is no approved treatment for COVID-19; the care advised is to give supportive management according to each patient’s need; Such as antipyretics for fever and oxygen therapy for patients with respiratory distress. Moreover, WHO recommendations for severe cases are to give empiric antimicrobial therapy and implement mechanical ventilation depending on the patient’s clinical condition. Some of the Asian guidelines were not easy to interpret because they are not yet translated to English, such as the Japanese guidelines. The treatment protocols across countries are similar. They are using Hydroxychloroquine, Chloroquine phosphate, Remedesivir, and Lopinavir/Ritonavir<sup>(</sup><xref rid="bib5" ref-type="bibr">5</xref>, <xref rid="bib6" ref-type="bibr">6</xref>, <xref rid="bib7" ref-type="bibr">7</xref><sup>)</sup>. There are slight differences between some countries treatment guidelines which will be represented in the <xref rid="tbl1" ref-type="table">Table 1</xref><sup>(</sup><xref rid="bib8" ref-type="bibr">8</xref>, <xref rid="bib9" ref-type="bibr">9</xref>, <xref rid="bib10" ref-type="bibr">10</xref>, <xref rid="bib11" ref-type="bibr">11</xref><sup>)</sup>.<table-wrap position="float" id="tbl1"><label>Table 1</label><caption><p>Comparison between the Treatment Guidelines for COVID-19 in Saudi Arabia, USA, Europe, and Egypt</p></caption><alt-text id="alttext0015">Table 1</alt-text><table frame="hsides" rules="groups"><thead><tr><th></th><th>Ministry of Health<break></break>M.O. H<break></break>Saudi Arabia</th><th>USA<break></break>Massachusetts General Hospital</th><th>Europe<break></break>Ireland</th><th>Egypt</th></tr></thead><tbody><tr><td><bold>Mild to moderate disease</bold></td><td><list list-type="simple" id="ulist0015"><list-item id="u0020"><p id="p0185">-Hydroxychloroquine</p></list-item><list-item id="u0025"><p id="p0190">-Chloroquine</p></list-item><list-item id="u0030"><p id="p0195">-chloroquine phosphate</p></list-item></list></td><td><list list-type="simple" id="ulist0020"><list-item id="u0035"><p id="p0200">-Clinical trial of Remdesivir</p></list-item></list></td><td rowspan="2"><list list-type="simple" id="ulist0025"><list-item id="u0040"><label>-</label><p id="p0205">Chloroquine (oral)</p></list-item><list-item id="u0045"><label>-</label><p id="p0210">Hydroxychloroquine (oral)</p></list-item><list-item id="u0050"><label>-</label><p id="p0215">Lopinavir/ritonavir (oral)</p></list-item><list-item id="u0055"><label>-</label><p id="p0220">Remdesivir (intravenous)</p></list-item></list></td><td><list list-type="simple" id="ulist0030"><list-item id="u0060"><label>-</label><p id="p0225">Oseltamivir</p></list-item><list-item id="u0065"><label>-</label><p id="p0230">Hydroxy Chloroquine</p></list-item><list-item id="u0070"><label>-</label><p id="p0235">Chloroquine phosphate</p></list-item></list></td></tr><tr><td><bold>Severe COVID-19</bold></td><td><list list-type="simple" id="ulist0035"><list-item id="u0075"><label>-</label><p id="p0240">Hydroxychloroquine</p></list-item><list-item id="u0080"><label>-</label><p id="p0245">Chloroquine</p></list-item><list-item id="u0085"><label>-</label><p id="p0250">Chloroquine phosphate</p></list-item><list-item id="u0090"><label>-</label><p id="p0255">Combination therapy (Lopinavir/Ritonavir)</p></list-item></list></td><td><list list-type="simple" id="ulist0040"><list-item id="u0095"><label>-</label><p id="p0260">Hydroxychloroquine</p></list-item><list-item id="u0100"><label>-</label><p id="p0265">Chloroquine</p></list-item><list-item id="u0105"><label>-</label><p id="p0270">Lopinavir/ritonavir darunavir/cobicistat</p></list-item></list></td><td><list list-type="simple" id="ulist0045"><list-item id="u0110"><label>-</label><p id="p0275">Oseltamivir</p></list-item><list-item id="u0115"><label>-</label><p id="p0280">Hydroxychloroquine</p></list-item><list-item id="u0120"><label>-</label><p id="p0285">Chloroquine phosphate</p></list-item><list-item id="u0125"><label>-</label><p id="p0290">Lopinavir/Ritonavir</p></list-item><list-item id="u0130"><label>-</label><p id="p0295">Serum ferritin, D- Dimer</p></list-item></list></td></tr><tr><td><bold>Critical</bold></td><td><list list-type="simple" id="ulist0050"><list-item id="u0135"><label>-</label><p id="p0300">Combination therapy (Lopinavir/Ritonavir)</p></list-item><list-item id="u0140"><label>-</label><p id="p0305">hydroxychloroquine</p></list-item><list-item id="u0145"><label>-</label><p id="p0310">remdesivir</p></list-item></list></td><td><list list-type="simple" id="ulist0055"><list-item id="u0150"><label>-</label><p id="p0315">With ID approval, Interferon beta B1 (Betaseron)</p></list-item></list></td><td></td><td><list list-type="simple" id="ulist0060"><list-item id="u0155"><label>-</label><p id="p0320">Antibiotics</p></list-item><list-item id="u0160"><label>-</label><p id="p0325">Oseltamivir</p></list-item><list-item id="u0165"><label>-</label><p id="p0330">Hydroxy Chloroquine (or _Chloroquine phosphate)</p></list-item><list-item id="u0170"><label>-</label><p id="p0335">Azithromycin (Hydrocortisone (anticoagulants if</p></list-item><list-item id="u0175"><label>-</label><p id="p0340">D-Dimer</p></list-item><list-item id="u0180"><p id="p0345">Invasive</p></list-item></list></td></tr></tbody></table></table-wrap></p><p id="p0030">In light of limited and scarce evidence around therapeutics for COVID-19 in the literature, this review aims to retrospectively evaluate the therapeutic management that was given to COVID-19 patients since the emergence of the virus.</p></sec><sec id="sec2"><title>Methods</title><p id="p0035">A systematic review protocol was developed based on PRISMA-P and the PRISMA statement. Articles for review were selected from electronic databases (Embase, Medline and Google Scholar). Readily accessible peer-reviewed, full articles in English, published from December 1<sup>st</sup>, 2019 to March 26<sup>th</sup>, 2020 were included. The search terms included combinations of: COVID-19, SARS-COV-2, Glucocorticoids, Chloroquine, convalescent plasma, antiviral, antibacterial, Oseltamivir, Hydroxychloroquine, Chloroquine phosphate and monoclonal antibodies. There were no restrictions on the type of study design eligible for inclusion; however, these were likely to be quantitative and RCT studies. The focus of the review was therapeutics for use of the management of COVID-19 patients. Primary outcomes were:<list list-type="simple" id="ulist0010"><list-item id="u0010"><p id="p0040">(1)the evidence of therapeutics used for the management of COVID-19 patients in clinical practice, irrespective of patient characteristics, setting and outcome measures to discuss the most common reported medicines in this review.</p></list-item><list-item id="u0015"><p id="p0045">(2)the clinical outcome of the therapeutic treatment (recovery, mortality) in COVID-19 patients. The secondary outcome was adverse events associated with the treatment.</p></list-item></list></p><p id="p0050">Duplicate articles were removed. Titles were independently screened by both reviewers with abstracts followed by full articles reviewed where any doubt remained. Inclusions and exclusions were recorded following PRISMA guidelines presented in the form of a PRISMA flow diagram and detailed reasons recorded for exclusion. Critical appraisal checklists appropriate to each study design were applied and checked by a second team member. Any bias or quality issues identified were considered prior to a quantitative meta-analysis and meta-narrative. CASP appraisal checklist tools were used for quality assessments. A data extraction tool was designed to capture focus of interest, population, geographical location, methodology, specific mention of therapeutic treatment and adverse events, key findings and further research. Ethical approval was not required for this review of existing peer reviewed literature.</p></sec><sec id="sec3"><title>Results</title><p id="p0055">As of March 26<sup>th</sup>, 2020, the initial manuscripts identified 449 articles. Inclusions and exclusions are reported following PRISMA guidelines presented in the form of a PRISMA flow diagram (<xref rid="fig1" ref-type="fig">Figure 1</xref>) with reasons for exclusion recorded (<xref rid="tbl2" ref-type="table">Table 2</xref>) as follows: duplicates removed (n=213), 28 records were excluded of which 18 were excluded due to language (9 Chinese, 2 Dutch, 1 Vietnamese, 1Spanish, 1 Italian, 1 Russian, 1 Portuguese, 1 Iranian and 1 German). Ten articles were excluded for other reasons, including incomplete and irrelevant articles.<fig id="fig1"><label>Figure1</label><caption><p>PRISMA Flow Diagram reporting search results</p></caption><alt-text id="alttext0010">Figure1</alt-text><graphic xlink:href="gr1"></graphic></fig><table-wrap position="float" id="tbl2"><label>Table 2</label><caption><p>List of excluded papers and reasons for exclusion:</p></caption><alt-text id="alttext0020">Table 2</alt-text><table frame="hsides" rules="groups"><thead><tr><th>No.#</th><th>Authors</th><th>Title</th><th>Covid-19<break></break>Yes / No</th><th>Reason for Exclusion</th></tr></thead><tbody><tr><td>1</td><td>Chughtai A. et al, 2020</td><td>Policies on the use of respiratory protection for hospital health workers to protect from coronavirus disease (covid-19).</td><td>Yes</td><td>No details on therapeutics/commentary</td></tr><tr><td>2</td><td>Gurwitz D. 2020</td><td>Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics</td><td>Yes</td><td>Commentary</td></tr><tr><td>3</td><td>Wang M., et al, 2020</td><td>Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro</td><td>Yes</td><td>Commentary</td></tr><tr><td>4</td><td>Colson P., et al, 2020</td><td>Chloroquine and hydroxychloroquine as available weapons to fight COVID-19</td><td>Yes</td><td>Commentary</td></tr><tr><td>5</td><td>Liu Y., Chen H., Tang K., Guo Y., 2020</td><td>Clinical manifestations and outcome of SARS-CoV-2 infection during pregnancy</td><td>Yes</td><td>No details on therapeutics/commentary</td></tr><tr><td>6</td><td>Baron S., et al., 2020</td><td>Teicoplanin: an alternative drug for the treatment of coronavirus COVID-19?</td><td>Yes</td><td>Commentary</td></tr><tr><td>7</td><td>Mitja O., & Clotet B., 2020</td><td>Use of antiviral drugs to reduce COVID-19 transmission</td><td>Yes</td><td>Commentary</td></tr><tr><td>8</td><td>Colson P., Rolain JM., & Raoult D., 2020</td><td>Chloroquine for the 2019 novel coronavirus SARS-CoV-2</td><td>Yes</td><td>Commentary</td></tr><tr><td>9</td><td>Morse J., et al, 2020</td><td>Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV</td><td>Yes</td><td>Commentary</td></tr><tr><td>10</td><td>Thevarajan I. et al., 2020</td><td>Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19</td><td>Yes</td><td>Commentary</td></tr><tr><td>11</td><td>Elfiky A., 2020</td><td>Anti-HCV, nucleotide inhibitors, repurposing against COVID-19</td><td>Yes</td><td>Commentary</td></tr><tr><td>12</td><td>Ung C., 2020</td><td>Community pharmacist in public health emergencies: Quick to action against the coronavirus 2019-nCoV outbreak</td><td>Yes</td><td>Commentary</td></tr><tr><td>13</td><td>Gupta R., 2020</td><td>Clinical considerations for patients with diabetes in times of COVID-19 epidemic</td><td>Yes</td><td>Commentary</td></tr><tr><td>14</td><td>Dong L., Hu S., and Gao J., 2020</td><td>Discovering drugs to treat coronavirus disease 2019 (COVID-19)</td><td>Yes</td><td>Commentary</td></tr><tr><td>15</td><td>Zhang C., Shi L., and Wang FS., 2020</td><td>Liver injury in COVID-19: management and challenges</td><td>Yes</td><td>Commentary</td></tr><tr><td>16</td><td>Cunningham A., Goh H., and Koh D., 2020</td><td>Treatment of COVID-19: old tricks for new challenges</td><td>Yes</td><td>Commentary</td></tr><tr><td>17</td><td>Ko WC., et al., 2020</td><td>Arguments in favour of remdesivir for treating SARS-CoV-2 infections</td><td>Yes</td><td>Commentary</td></tr><tr><td>18</td><td>Arabi Y., Murthy S., and Webb S., 2020</td><td>COVID-19: a novel coronavirus and a novel challenge for critical care</td><td>Yes</td><td>Commentary</td></tr><tr><td>19</td><td>Wang J., and Shi Y., 2020</td><td>Managing neonates with respiratory failure due to SARS-CoV-2</td><td>Yes</td><td>Commentary</td></tr><tr><td>20</td><td>Stebbing J., et al., 2020</td><td>COVID-19: combining antiviral and anti-in ammatory treatments</td><td>Yes</td><td>Commentary</td></tr><tr><td>21</td><td>Touret F., and Lamballerie X., 2020</td><td>Of chloroquine and COVID-19</td><td>Yes</td><td>Commentary</td></tr><tr><td>22</td><td>Porcheddu R., et al., 2020</td><td>Similarity in Case Fatality Rates (CFR) of COVID-19/SARS-COV-2 in Italy and China</td><td>Yes</td><td>No therapeutic data/commentary</td></tr><tr><td>23</td><td>Zhang J., et al 2020</td><td>Therapeutic and triage strategies for 2019 novel coronavirus disease in fever clinics</td><td>Yes</td><td>Commentary</td></tr><tr><td>24</td><td>Baden L., and Rubin E. 2020</td><td>Covid-19 — The Search for Effective Therapy</td><td>Yes</td><td>Commentary</td></tr><tr><td>25</td><td>Baud D., et al. 2020</td><td>COVID-19 in pregnant women</td><td>Yes</td><td>No therapeutic data/commentary</td></tr><tr><td>26</td><td>Ortega J., et al., 2020</td><td>Unrevealing sequence and structural features of novel coronavirus using in silico approaches: the main protease as molecular target</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>27</td><td>Ma Y., et al. 2020</td><td>2019 novel coronavirus disease in hemodialysis (HD) patients: Report from one HD center in Wuhan, China</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>28</td><td>Columbus C, Brust K., and Arroliga A., 2020</td><td>2019 novel coronavirus: an emerging global threat</td><td>Yes</td><td>Commentary</td></tr><tr><td>29</td><td>Barry M., Amri M., and Memish. 2020</td><td>COVID-19 in the Shadows of MERS-CoV in the Kingdom of Saudi Arabia</td><td>Yes</td><td>Commentary</td></tr><tr><td>30</td><td>Wang M., et al., 2020</td><td>A precision medicine approach to managing 2019 novel coronavirus pneumonia</td><td>Yes</td><td>No therapeutic data/commentary</td></tr><tr><td>31</td><td>Singhal T., 2020</td><td>A Review of Coronavirus Disease-2019 (COVID-19)</td><td>Yes</td><td>Review article</td></tr><tr><td>32</td><td>Li Q., et al. 2020</td><td>A simple laboratory parameter facilitates early identification of COVID-19 patients</td><td>Yes</td><td>Retrospective case-negative control study</td></tr><tr><td>33</td><td>Guo W., et al. 2020</td><td>A Survey for COVID-19 among HIV/AIDS Patients in Two Districts of Wuhan, China</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>34</td><td>Gao J., Tian Z., and Yang X. 2020</td><td>Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies</td><td>Yes</td><td>Commentary</td></tr><tr><td>35</td><td>Deng L., et al. 2020</td><td>Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study</td><td>Yes</td><td>Retrospective control study</td></tr><tr><td>36</td><td>Murthy S., Gomersall C., and Fowler R. 2020</td><td>Care for Critically Ill Patients With COVID-19</td><td>Yes</td><td>Commentary</td></tr><tr><td>37</td><td>Deng SQ., and Peng HJ. 2020</td><td>Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China</td><td>Yes</td><td>Review</td></tr><tr><td>38</td><td>Wang Z., et al. 2020</td><td>Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>39</td><td>Xiong Y., et al. 2020</td><td>Clinical and High-Resolution CT Features of the COVID-19 Infection: Comparison of the Initial and Follow-up Changes</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>40</td><td>Chen G., et al. 2020</td><td>Clinical and immunologic features in severe and moderate forms of Coronavirus Disease 2019</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>41</td><td>Chen H., et al. 2020</td><td>Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>42</td><td>Hong H., et al. 2020</td><td>Clinical characteristics of novel coronavirus disease 2019 (COVID-19) in newborns, infants and children</td><td>Yes</td><td>Perspectives / No therapeutic data</td></tr><tr><td>43</td><td>Ye G., et al. 2020</td><td>Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>44</td><td>Anderson D., et al. 2020</td><td>Clinical management of suspected or confirmed COVID-19 disease</td><td>Yes</td><td>Review</td></tr><tr><td>45</td><td>Zhang T., et al. 2020</td><td>Clinical trials for the treatment of coronavirus disease 2019 (COVID-19): A rapid response to urgent need</td><td>Yes</td><td>Commentary</td></tr><tr><td>46</td><td>Chen L., et al. 2020</td><td>Convalescent plasma as a potential therapy for COVID-19</td><td>Yes</td><td>Commentary</td></tr><tr><td>47</td><td>Yang P., et al. 2020</td><td>Corona Virus Disease 2019, a growing threat to children?</td><td>Yes</td><td>Commentary / No therapeutic data</td></tr><tr><td>48</td><td>Kooraki S., et al. 2020</td><td>Coronavirus (COVID-19) Outbreak:<break></break>What the Department of Radiology<break></break>Should Know</td><td>Yes</td><td>Commentary / No therapeutic data</td></tr><tr><td>49</td><td>Rasmussen S., et al., 2020</td><td>Coronavirus Disease 2019 (COVID-19) and Pregnancy: What obstetricians need to know</td><td>Yes</td><td>Commentary / No therapeutic data</td></tr><tr><td>50</td><td>Liu W., et al. 2020</td><td>Coronavirus disease 2019 (COVID-19) during pregnancy: a case series</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>51</td><td>Mclntosh K., Hirsch M., and Bloom. 2020</td><td>Coronavirus disease 2019 (COVID-19)</td><td>Yes</td><td>Review</td></tr><tr><td>52</td><td>He F., and Li W. 2020</td><td>Coronavirus Disease 2019 (COVID-19): What we know?</td><td>Yes</td><td>Review</td></tr><tr><td>53</td><td>Xiong TY., et al. 2020</td><td>Coronaviruses and the cardiovascular system: acute and long-term implications</td><td>Yes</td><td>Commentary</td></tr><tr><td>54</td><td>Gong J., et al. 2020</td><td>Correlation Analysis Between Disease Severity and Inflammation-related Parameters in Patients with COVID-19 Pneumonia</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>55</td><td>Dong Y., et al. 2020</td><td>Epidemiological Characteristics of 2143 Pediatric Patients With 2019 Coronavirus Disease in China</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>56</td><td>Shereen M., et al. 2020</td><td>COVID-19 infection: origin, transmission, and characteristics of human coronaviruses</td><td>Yes</td><td>Review</td></tr><tr><td>57</td><td>Rio C., and Malani P. 2020</td><td>COVID-19—New Insights on a Rapidly Changing Epidemic</td><td>Yes</td><td>Review</td></tr><tr><td>58</td><td>Yi Y., et al., 2020</td><td>COVID-19: what has been learned and to be learned about the novel coronavirus disease</td><td>Yes</td><td>Review</td></tr><tr><td>59</td><td>Rezaeetalab F., et al. 2020</td><td>COVID-19: A New Virus as a Potential Rapidly Spreading in the Worldwide</td><td>Yes</td><td>Review</td></tr><tr><td>60</td><td>Shaker M., et al. 2020</td><td>COVID-19: Pandemic Contingency Planning for the Allergy and Immunology Clinic</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>61</td><td>Aslam S., and Mehra M. 2020</td><td>COVID-19: Yet Another Coronavirus Challenge in Transplantation</td><td>Yes</td><td>Commentary</td></tr><tr><td>62</td><td>Padmanabhan S. 2020</td><td>Potential dual therapeutic approach against SARS-CoV-2/COVID-19 with Nitazoxanide and Hydroxychloroquine</td><td>Yes</td><td>Commentary</td></tr><tr><td>63</td><td>Hick J., et al, 2020</td><td>Duty to Plan: Health Care, Crisis Standards of Care, and Novel Coronavirus SARS-CoV-2</td><td>Yes</td><td>Discussion</td></tr><tr><td>64</td><td>Yang P., et al. 2020</td><td>Epidemiological and clinical features of COVID-19 patients with and without pneumonia in Beijing, China</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>65</td><td>Khan N. 2020</td><td>Epidemiology of corona virus in the world and its effects on the China economy</td><td>Yes</td><td>Review</td></tr><tr><td>66</td><td>Hoehl S., et al. 2020</td><td>Evidence of SARS-CoV-2 Infection in Returning Travelers from Wuhan, China</td><td>Yes</td><td>Commentary</td></tr><tr><td>67</td><td>Yang Y., et al. 2020</td><td>Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome</td><td>Yes</td><td>Review</td></tr><tr><td>68</td><td>Cascella M., et al. 2020</td><td>Features, Evaluation and Treatment Coronavirus (COVID-19)</td><td>Yes</td><td>Review</td></tr><tr><td>69</td><td>Erol A. 2020</td><td>High-dose intravenous vitamin C treatment for COVID-19 (a mechanistic approach)</td><td>Yes</td><td>Review</td></tr><tr><td>70</td><td>Liu F., et al. 2020</td><td>Highly ACE2 Expression in Pancreas May Cause Pancreas Damage After SARS-CoV-2 Infection</td><td>Yes</td><td>Commentary</td></tr><tr><td>71</td><td>Zhang B. et al. 2020</td><td>Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>72</td><td>Mao R., et al. 2020</td><td>Implications of COVID-19 for patients with pre-existing digestive diseases</td><td>Yes</td><td>Commentary</td></tr><tr><td>73</td><td>Ferguson N. et al. 2020</td><td>Impact of non-pharmaceutical interventions (NPIs) to reduce COVID- 19 mortality and healthcare demand</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>74</td><td>Qiu H., et al. 2020</td><td>Intensive care during the coronavirus epidemic</td><td>Yes</td><td>Commentary</td></tr><tr><td>75</td><td>Poon L. et al. 2020</td><td>ISUOG Interim Guidance on 2019 novel coronavirus infection during pregnancy and puerperium: information for healthcare professionals</td><td>Yes</td><td>Review</td></tr><tr><td>76</td><td>Khan S., et al. 2020</td><td>The emergence of a novel coronavirus (SARS-CoV-2), their biology and therapeutic options</td><td>Yes</td><td>Discussion</td></tr><tr><td>77</td><td>Sun Q., et al. 2020</td><td>Lower mortality of COVID-19 by early recognition and intervention: experience from Jiangsu Province</td><td>Yes</td><td>Commentary</td></tr><tr><td>78</td><td>Guzzi P., et al. 2020</td><td>Master Regulator Analysis of the SARS-CoV-2/Human interactome</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>79</td><td>Memish Z. et al. 2020</td><td>Middle East respiratory syndrome</td><td>No</td><td>Review</td></tr><tr><td>80</td><td>Nicastri E., 2020</td><td>National Institute for the Infectious Diseases<break></break>“L. Spallanzani”, IRCCS. Recommendations for COVID-19 clinical management</td><td>Yes</td><td>Commentary</td></tr><tr><td>81</td><td>Li X., et al. 2020</td><td>Network bioinformatics analysis provides insight into drug repurposing for COVID-2019</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>82</td><td>Xiong R., et al. 2020</td><td>Novel and potent inhibitors targeting DHODH, a rate-limiting enzymein de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>83</td><td>Rezabakhsh A., Ala A., and Khodaei S. 2020</td><td>Novel Coronavirus (COVID-19): A New Emerging Pandemic Threat</td><td>Yes</td><td>Survey/ No therapeutic data</td></tr><tr><td>84</td><td>Ai JW., et al. 2020</td><td>Optimizing diagnostic strategy for novel coronavirus pneumonia, a multi-center study in Eastern China</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>85</td><td>Qiu R., et al. 2020</td><td>Outcome reporting from protocols of clinical trials of Coronavirus Disease 2019 (COVID-19): a review</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>86</td><td>Bajema K., et al. 2020</td><td>Persons Evaluated for 2019 Novel Coronavirus — United States, January 2020</td><td>Yes</td><td>Commentary</td></tr><tr><td>87</td><td>Shanmugaraj B., et al. 2020</td><td>Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19)</td><td>Yes</td><td>Review</td></tr><tr><td>88</td><td>Zhou G., and Zhao Q., 2020</td><td>Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2</td><td>Yes</td><td>Review</td></tr><tr><td>89</td><td>Hoffmann M., et al. 2020</td><td>SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>90</td><td>Zhang L., and Liu Y. 2020</td><td>Potential interventions for novel coronavirus in China: A systematic review</td><td>Yes</td><td>Review</td></tr><tr><td>91</td><td>Vasylyeva O. 2020</td><td>Pregnancy and COVID-19: a brief review</td><td>Yes</td><td>Review</td></tr><tr><td>92</td><td>Alamri M., Qamar M., and Alqahtani S. 2020</td><td>Pharmacoinformatics and molecular dynamic simulation studies reveal potential inhibitors of SARS-CoV-2 main protease 3CL<sup>pro</sup></td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>93</td><td>Fisher d., and Heymann d. 2020</td><td>Q&A: The novel coronavirus outbreak causing COVID-19</td><td>Yes</td><td>Commentary</td></tr><tr><td>94</td><td>Goh K., et al. 2020</td><td>Rapid Progression to Acute Respiratory Distress Syndrome: Review of Current Understanding of Critical Illness from COVID-19 Infection</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>95</td><td>Chen X., et al. 2020</td><td>Restoration of leukomonocyte counts is associated with viral clearance in COVID-19 hospitalized patients</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>96</td><td>Bouadma L., et al. 2020</td><td>Severe SARS-CoV-2 infections: practical considerations and management strategy for intensivists</td><td>Yes</td><td>Review</td></tr><tr><td>97</td><td>Zhu R., et al. 2020</td><td>Systematic Review of the Registered Clinical Trials of Coronavirus Disease2019 (COVID-19)</td><td>Yes</td><td>Review</td></tr><tr><td>98</td><td>Yang Y. et al. 2020</td><td>The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China</td><td>Yes</td><td>Review</td></tr><tr><td>99</td><td>Li YS., Bai WZ., and Hashikawa T. 2020</td><td>The neuroinvasive potential of SARS CoV2 may play a role in the respiratory failure of COVID 19 patients</td><td>Yes</td><td>Review</td></tr><tr><td>100</td><td>Naicker S., et al. 2020</td><td>The Novel Coronavirus 2019 epidemic and kidneys</td><td>Yes</td><td>Review</td></tr><tr><td>101</td><td>Fang Y., Nie Y., and Penny. M., 2020</td><td>Transmission dynamics of the COVID 19 outbreak and effectiveness of government interventions: A data driven analysis</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>102</td><td>Sun P., et al. 2020</td><td>Understanding of COVID 19 based on current evidence</td><td>Yes</td><td>Review</td></tr><tr><td>103</td><td>Wang Y., et al. 2020</td><td>Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures</td><td>Yes</td><td>Review</td></tr><tr><td>104</td><td>Maoujoud O., Asserraji M., and Belarbi M. 2020</td><td>What nephrologist should know about COVID-19 outbreak?</td><td>Yes</td><td>Commentary</td></tr><tr><td>105</td><td>Cortegiani a., et al., 2020</td><td>A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19</td><td>Yes</td><td>Review</td></tr><tr><td>106</td><td>Ryu S., et al. 2020</td><td>An interim review of the epidemiological characteristics of 2019 novel coronavirus</td><td>Yes</td><td>Review</td></tr><tr><td>107</td><td>Yang N., and Shen HM. 2020</td><td>Targeting the Endocytic Pathway and Autophagy Process as A Novel Therapeutic Strategy In COVID-19</td><td>Yes</td><td>Review</td></tr><tr><td>108</td><td>Fan Y., et al. 2020</td><td>Bat Coronaviruses in China</td><td>Yes</td><td>Review</td></tr><tr><td>109</td><td>Russell C., Millar j., and Bailliek. 2020</td><td>Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury</td><td>Yes</td><td>Commentary</td></tr><tr><td>110</td><td>Liang B., et al 2020</td><td>Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells</td><td>Yes</td><td>No therapeutic data/commentary</td></tr><tr><td>111</td><td>Wu. X., et al. 2020</td><td>Co-infection with SARS-CoV-2 and Influenza A Virus in Patient with Pneumonia, China</td><td>Yes</td><td>Commentary</td></tr><tr><td>112</td><td>Martinez M., et al. 2020</td><td>Compounds with therapeutic potential against novel respiratory 2019 coronavirus</td><td>Yes</td><td>Commentary</td></tr><tr><td>113</td><td>Tang B., et al. 2020</td><td>Coronavirus Disease 2019 (COVID-19) Pneumonia in a Hemodialysis Patient</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>114</td><td>Chang L., Yan Y., and Wang L. 2020</td><td>Coronavirus Disease 2019: Coronaviruses and Blood Safety</td><td>Yes</td><td>Review</td></tr><tr><td>115</td><td>Walker L. 2020</td><td>COVID-19, Australia: Epidemiology Report 2</td><td>Yes</td><td>Commentary</td></tr><tr><td>116</td><td>Lu H., 2020</td><td>Drug treatment options for the 2019-new coronavirus (2019- nCoV)</td><td>Yes</td><td>Commentary</td></tr><tr><td>117</td><td>Hellewell J., et al. 2020</td><td>Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>118</td><td>Prompetchara E. Ketloy C., and Palaga T., 2020</td><td>Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic</td><td>Yes</td><td>Review</td></tr><tr><td>119</td><td>Ashour H., et al. 2020</td><td>Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks</td><td>Yes</td><td>Review</td></tr><tr><td>120</td><td>Zhou Y., et al. 2020</td><td>Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>121</td><td>Devaux C., et al. 2020</td><td>New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?</td><td>Yes</td><td>Review</td></tr><tr><td>122</td><td>Cauchi S., and Locht C. 2020</td><td>Non-specific Effects of Live Attenuated Pertussis Vaccine Against Heterologous Infectious and Inflammatory Diseases</td><td>Yes</td><td>Review</td></tr><tr><td>123</td><td>Chang YC., et al. 2020</td><td>Potential therapeutic agents for COVID-19 based on the analysis of protease and RNA polymerase docking</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>124</td><td>Pang J., et al. 2020</td><td>Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review</td><td>Yes</td><td>Review</td></tr><tr><td>125</td><td>Chen D., et al. 2020</td><td>Recurrence of positive SARS-CoV-2 RNA in COVID-19: A case report</td><td>Yes</td><td>Commentary</td></tr><tr><td>126</td><td>Liu C., et al. 2020</td><td>Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases</td><td>Yes</td><td>Review</td></tr><tr><td>127</td><td>Gralinski L., and Menachery V. 2020</td><td>Return of the Coronavirus: 2019-nCoV Return of the Coronavirus: 2019-nCoV</td><td>Yes</td><td>Commentary</td></tr><tr><td>128</td><td>Cao Q., et al. 2020</td><td>SARS-CoV-2 infection in children: Transmission dynamics and clinical characteristics</td><td>Yes</td><td>Commentary</td></tr><tr><td>129</td><td>Walls A., et al. 2020</td><td>Structure, Function, and Antigenicity of the SARS- CoV-2 Spike Glycoprotein</td><td>Yes</td><td>Commentary</td></tr><tr><td>130</td><td>Xu J., et al. 2020</td><td>Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV</td><td>Yes</td><td>Review</td></tr><tr><td>131</td><td>Garrett L. 2020</td><td>The art of medicine COVID-19: the medium is the message</td><td>Yes</td><td>Commentary</td></tr><tr><td>132</td><td>Habibzadeh P., and Stoneman E.</td><td>The Novel Coronavirus: A Bird's Eye View</td><td>Yes</td><td>Review</td></tr><tr><td>133</td><td>Wu D., et al. 2020</td><td>The SARS-CoV-2 Outbreak: What We Know</td><td>Yes</td><td>Review</td></tr><tr><td>134</td><td>Nezhad F., et al. 2020</td><td>Therapeutic approaches for COVID-19 based on the dynamics of interferon- mediated immune responses</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>135</td><td>Lu S. 2020</td><td>Timely development of vaccines against SARS- CoV-2</td><td>Yes</td><td>Commentary</td></tr><tr><td>136</td><td>Kim J., et al. 2020</td><td>Viral Load Kinetics of SARS-CoV-2 Infection in First Two Patients in Korea</td><td>Yes</td><td>Commentary</td></tr><tr><td>137</td><td>Sekhar T. 2020</td><td>Virtual screening bades prediction of potential drugs for COVID-19</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>138</td><td>Park W., et al. 2020</td><td>Virus Isolation from the First Patient with SARS-CoV-2 in Korea</td><td>Yes</td><td>Commentary</td></tr><tr><td>139</td><td>Lake M., 2020</td><td>What we know so far: COVID-19 current clinical knowledge and research</td><td>Yes</td><td>Review</td></tr><tr><td>140</td><td>Ralph R., et al. 2020</td><td>2019-nCoV (Wuhan virus), a novel Coronavirus: human-to-human transmission, travel-related cases, and vaccine rea</td><td>Yes</td><td>Review</td></tr><tr><td>141</td><td>Jin YH., 2020</td><td>A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)</td><td>Yes</td><td>Review</td></tr><tr><td>142</td><td>Liu R., et al. 2020</td><td>Association of Cardiovascular Manifestations with In-hospital Outcomes in Patients with COVID-19: A Hospital Staff Data</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>143</td><td>Lai CC., et al. 2020</td><td>Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths</td><td>Yes</td><td>Review</td></tr><tr><td>144</td><td>Bordi L., et al. 2020</td><td>Differential diagnosis of illness in patients under investigation for the novel coronavirus (SARS-CoV-2), Italy, February 2020</td><td>Yes</td><td>Commentary</td></tr><tr><td>145</td><td>Li T. 2020</td><td>Diagnosis and clinical management of severe acute respiratory syndrome Coronavirus 2 (SARS- CoV-2) infection: an operational recommendation of Peking Union Medical College Hospital (V2.0)</td><td>Yes</td><td>Review</td></tr><tr><td>146</td><td>Song P., and Karako T. 2020</td><td>COVID-19: Real-time dissemination of scientific information to fight a public health emergency of international concern</td><td>Yes</td><td>Commentary</td></tr><tr><td>147</td><td>Vankadari N., and Wilce J. 2020</td><td>Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26</td><td>Yes</td><td>Review</td></tr><tr><td>148</td><td>Hsih WH., et al. 2020</td><td>Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>149</td><td>Stoecklin S., et al. 2020</td><td>First cases of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>150</td><td>Chan J., et al. 2020</td><td>Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>151</td><td>Boulos M., and Geraghty E. 2020</td><td>Geographical tracking and mapping of coronavirus disease COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic and associated events around the world: how 21st century GIS technologies are supporting the global fight against outbreaks and epidemics</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>152</td><td>Zeng Q., et al. 2020</td><td>Mortality of COVID-19 is Associated with Cellular Immune Function Compared to Immune Function in Chinese Han Population</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>153</td><td>Ahmed S., et al. 2020</td><td>Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>154</td><td>Lai CC. et al. 2020</td><td>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges</td><td>Yes</td><td>Review</td></tr><tr><td>155</td><td>Alhazzani W., et al. 2020</td><td>Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19)</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>156</td><td>Guo YR., et al. 2020</td><td>The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status</td><td>Yes</td><td>Review</td></tr><tr><td>157</td><td>Yang Y., et al. 2020</td><td>Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective</td><td>Yes</td><td>Review</td></tr><tr><td>158</td><td>Liu X., et al. 2020</td><td>Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>159</td><td>WHO. 2020</td><td>Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected</td><td>Yes</td><td>Guidelines</td></tr><tr><td>160</td><td>Li Z., et al. 2020</td><td>Development and Clinical Application of a Rapid IgM-IgG Combined Antibody Test for SARS-CoV-2 Infection Diagnosis</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>161</td><td>Mao Y., et al. 2020</td><td>Clinical and pathological characteristics of 2019 novel coronavirus disease (COVID-19): a systematic reviews</td><td>Yes</td><td>Review</td></tr><tr><td>162</td><td>Cui P., et al. 2020</td><td>Clinical features and sexual transmission potential of SARS-CoV-2 infected female patients: a descriptive study in Wuhan, China</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>163</td><td>Saw Swee Hock School of Public Health, 2020</td><td>COVID-19 Science Report: Therapeutics</td><td>Yes</td><td>Report</td></tr><tr><td>164</td><td>Yao X., 2020</td><td>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)</td><td>Yes</td><td>Commentary</td></tr><tr><td>165</td><td>Pongpirul W., et al. 2020</td><td>Journey of a Thai Taxi Driver and Novel Coronavirus</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>166</td><td>Liu YC., et al. 2020</td><td>A Locally Transmitted Case of SARS-CoV-2 Infection in Taiwan</td><td>Yes</td><td>No therapeutic data</td></tr><tr><td>167</td><td>Velavan T., and Meyer C. 2020</td><td>The COVID-19 epidemic</td><td>Yes</td><td>Commentary</td></tr></tbody></table></table-wrap></p><p id="p0060">Consensus on final inclusion of studies (n=41) (negotiated without the need for a third reviewer) is presented in <xref rid="tbl3" ref-type="table">Table 3</xref>.<table-wrap position="float" id="tbl3"><label>Table 3</label><caption><p>Data extraction from included papers</p></caption><alt-text id="alttext0025">Table 3</alt-text><table frame="hsides" rules="groups"><thead><tr><th></th><th>Author/Title/DOI</th><th>Sample size</th><th>Age (mean)</th><th>Gender</th><th>Type of study</th><th>Therapeutic treatment</th><th>Type/number%</th><th>Outcomes (recovery/mortality)</th><th>Adverse events</th><th>Quality assessment (applicable/inapplicable)</th></tr></thead><tbody><tr><td><bold>1</bold></td><td>Cao B, Wang Y, Wen D, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1056/NEJMoa2001282" id="intref0095">https://doi.org/10.1056/NEJMoa2001282</ext-link></td><td>199</td><td>58 Y</td><td>120 M<break></break>79 F</td><td>Randomised Clinical Trial<break></break>RCT</td><td>Lopinavir & ritonavir</td><td>Lopinavir & ritonavir / 50%<break></break>Standard care / 50%</td><td><list list-type="simple" id="ulist0065"><list-item id="u0185"><label>-</label><p id="p0350">In hospitalized adult patients with severe COVID-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care.</p></list-item><list-item id="u0190"><label>-</label><p id="p0355">19 patients from whom received the intervention died.</p></list-item></list></td><td>14% of lopinavir–ritonavir developed gastrointestinal adverse events, including anorexia, nausea, abdominal discomfort, or diarrhea, as well as two serious adverse events, both acute gastritis.<break></break>Two recipients had self-limited skin eruptions.</td><td>The study addressed a focused issue.<break></break>Randomization done with intention to treat analysis.<break></break>The population who entered the study are properly accounted for its conclusion.<break></break>Blindness not done.<break></break>The 2 groups who enter the study were similar together and treated equally.<break></break>The primary outcome clearly specified.</td></tr><tr><td><bold>2</bold></td><td>Cao J, Hu X, Cheng W, Yu L, Tu W, Liu Q. Clinical features and short-term outcomes of 18 patients with corona virus disease 2019 in intensive care unit. Intensive Care Med. 2020:1-3. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1007/s00134-020-05987-7" id="intref0100">https://doi.org/10.1007/s00134-020-05987-7</ext-link></td><td>41</td><td>49 Y</td><td>30 M<break></break>11 F</td><td>Prospective</td><td>Antibiotics and oseltamivir (orally 75 mg twice daily)<break></break>Corticosteroid therapy was given as a combined regimen if severe community-acquired pneumonia was diagnosed by physicians at the designated hospital.</td><td>All patients were administered with empirical antibiotic treatment,<break></break>38 (93%) patients received antiviral therapy (oseltamivir).<break></break>9 (22%) patients were given systematic corticosteroids.</td><td><list list-type="simple" id="ulist0070"><list-item id="u0195"><label>-</label><p id="p0360">Antiviral: 12 ICU admission (92%)</p></list-item><list-item id="u0200"><label>-</label><p id="p0365">Antibiotics: 13 ICU admission (100%)</p></list-item><list-item id="u0205"><label>-</label><p id="p0370">Corticosteroids: 6 ICU admission (46%)</p></list-item></list></td><td>Not reported</td><td>Adverse events not reported.<break></break>Treatment given not specified.<break></break>Types of antibiotics given not mentioned.</td></tr><tr><td><bold>3</bold></td><td>Chen C, Huang J, Cheng Z, et al. Favipiravir versus Arbidol for COVID-19: A Randomized Clinical Trial. medRxiv. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.03.17.200" id="intref0105">https://doi.org/10.1101/2020.03.17.200</ext-link></td><td>236 adults</td><td>56 (25-86)</td><td>Favipiravir group<break></break>59 M<break></break>57 F<break></break>Arbidol group<break></break>51 M<break></break>69 F</td><td>Randomised Controlled Trial</td><td>Favipiravir Arbidol</td><td>Antiviral /116<break></break>Antiviral /120</td><td>71 Recovery</td><td>LFT abnormal,<break></break>Raised serum uric acid, Psychiatric symptom reactions, and Digestive tract reactions.</td><td>There is no effective antiviral drug was reported, and the drugs mentioned were based on in the sixth edition of the guidelines.</td></tr><tr><td><bold>4</bold></td><td>Chen C, Qi F, Shi K, et al. Thalidomide combined with low-dose glucocorticoid in the treatment of COVID-19 Pneumonia. 2020.</td><td>1</td><td>45 Y</td><td>F</td><td>Case report</td><td>A case report of a 45-year-old Covid_19 Pneumonia female patient was treated with thalidomide and low-dose glucocorticoid. She was first treated with oral administration of ofloxacin and oseltamivir, but the condition deteriorated. And then treated with lopinavir/ritonavir</td><td></td><td>Thalidomide inhibit cytokine surge and regulate immune functions, also it could be used to calm patients down to reduce oxygen consumption and relieve digestive symptoms in COVID-19 patients.</td><td>Not reported</td><td>Need randomized control trials to be done.</td></tr><tr><td><bold>5</bold></td><td>Chen J, Hu C, Chen L, et al. Clinical study of mesenchymal stem cell treating acute respiratory distress syndrome induced by epidemic Influenza A (H7N9) infection, a hint for COVID-19 treatment. Engineering. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.eng.2020.02.006" id="intref0110">https://doi.org/10.1016/j.eng.2020.02.006</ext-link></td><td>61</td><td>62 Y</td><td>Not mentioned</td><td>Open labelled clinical trail</td><td>Oseltamivir or peramivir according to the standard therapy, and antibiotics were given based on positive results from blood test.</td><td>Not mentioned</td><td>17.6% died in the experimental group while 54.5% died in the control group.</td><td>Not reported</td><td>With only 17 patients using MSC, cannot guarantee that every step was perfect during the phase with only a one-time clinical trial.<break></break>Some patients refused to attend, and some did not complete follow-up. Thus, they are still concerned about the long-term safety of MSC transplantation for treating H7N9-induced ARDS, despite the lack of side effects observed in this clinical trial.<break></break>The study done on H7N9 patients not COVID-19 patients.</td></tr><tr><td><bold>6</bold></td><td>Chen J, Fan H, Zhang L, et al. Retrospective Analysis of Clinical Features in 101 Death Cases with COVID-19. medRxiv. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.03.09.20033068" id="intref0115">https://doi.org/10.1101/2020.03.09.20033068</ext-link></td><td>101</td><td>65.46 Y</td><td>64 M<break></break>37 F</td><td>single centre and observational study (retrospective).</td><td><list list-type="simple" id="ulist0075"><list-item id="u0210"><label>-</label><p id="p0375">Antiviral drugs, including Oseltamivir, Ribavirin, Lopinavir, Ritonavir, Ganciclovir, or Interferon, etc.;</p></list-item></list>Glucocorticoids, intravenous immunoglobulins, and thymosin preparations<break></break>antibiotic treatment, including cephalosporins and quinolones & carbapenems, linezolid, tigecycline, etc.</td><td>61 (60.40%) patients were given antiviral drugs, 59 (58.42%), received glucocorticoids, 63.37% were given intravenous immunoglobulins, and 44.55% were treated with thymosin preparations. All patients received antibiotic treatment, 63(62.38%) were given restricted antibiotics, 23(22.78%) were administrated to antifungal drugs.</td><td>101 Death</td><td>Not reported</td><td>Only the critical death patients are included.<break></break>No comparison was made between the improvement groups.</td></tr><tr><td><bold>7</bold></td><td>Chen J, Qi T, Liu L, et al. Clinical progression of patients with COVID-19 in Shanghai, China. J Infect. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.jinf.2020.03.004" id="intref0120">https://doi.org/10.1016/j.jinf.2020.03.004</ext-link></td><td>249</td><td>51 Y</td><td>126 M<break></break>123 F</td><td>retrospective, single-centre study.</td><td>Antiviral drugs (e.g., lopinavir/ritonavir, arbidol) were used in small proportion of patients.<break></break>Corticosteroid was not used unless a panel discussion by experts considered necessary (e.g., ARDS).</td><td>Not mentioned</td><td>2 patients died (0.8%).<break></break>22 patients admitted to ICU (8.8%)<break></break>8 patients developed ARDS (3.2%)<break></break>215 patients discharged (86.3%).</td><td>Not reported</td><td>A small proportion the patients were still hospitalized at the time of manuscript submission. Therefore, clinical outcomes in these patients were not available and continued observations are still needed.<break></break>They did not test SARS-CoV-2 daily for everybody. Hence, the actual duration to viral clearance should be shorter than the estimated one.</td></tr><tr><td><bold>8</bold></td><td>Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet. 2020;395(10223):507-513. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/S0140-6736(20)30211-7" id="intref0125">https://doi.org/10.1016/S0140-6736(20)30211-7</ext-link></td><td>99</td><td>55.5 Y</td><td>67 M<break></break>32 F</td><td>retrospective, single Centre descriptive study.</td><td>Antibiotic: cephalosporins, quinolones, carbapenems, tigecycline against methicillin resistant <italic>Staphylococcus aureus</italic>, linezolid,<break></break>Antifungal<break></break>Antiviral treatment:<break></break>Oseltamivir – ganciclovir – lopinavir & ritonavir<break></break>Glucocorticoids: methylprednisolone sodium succinate, methylprednisolone, and dexamethasone<break></break>Immunoglobulin</td><td>Antibiotic treatment<break></break>70 (71%)<break></break>Antifungal treatment<break></break>15 (15%)<break></break>Antiviral treatment: (75 (76%) patients received antiviral treatment, including oseltamivir (75 mg every 12 h, orally), ganciclovir (0·25 g every 12 h, intravenously), and lopinavir and ritonavir tablets (500 mg twice daily, orally). The duration of antiviral treatment was 3–14 days).<break></break>Glucocorticoids<break></break>19 (19%)<break></break>Intravenous immunoglobulin therapy<break></break>27 (27%)</td><td>11 (11%) patients had died</td><td>Not reported or NA</td><td>Suspected but undiagnosed cases were ruled out in the analyses.<break></break>More detailed patient information, particularly regarding clinical outcomes, was unavailable at the time of analysis.</td></tr><tr><td><bold>9</bold></td><td>Chen X, Zheng F, Qing Y, et al. Epidemiological and clinical features of 291 cases with coronavirus disease 2019 in areas adjacent to Hubei, China: a double-center observational study. medRxiv. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.03.03.20030353" id="intref0130">https://doi.org/10.1101/2020.03.03.20030353</ext-link></td><td>291</td><td>46 Y</td><td>145 M<break></break>146 F</td><td>double-center observational study</td><td>antiviral therapy including lopinavir and ritonavir tablet<break></break>Recombinant human interferon α2b<break></break>Recombinant cytokine gene derived protein<break></break>Arbidol hydrochloride capsules<break></break>Chinese Medicine.</td><td>285 (97.9%) patients received antiviral therapy: lopinavir and ritonavir tablets (75.9%), recombinant human interferon α2b (45.4%), recombinant cytokine gene derived protein (18.9%) and arbidol hydrochloride capsules (17.2%).<break></break>281 (96.6%) patients were treated with Chinese Medicine.</td><td>2 (0.7%) patients have died</td><td>Not reported</td><td>Due to the limitations of the retrospective study, laboratory examinations were performed according to the clinical care needs of the patient, thus some patients’ laboratory exam results were uncompleted.<break></break>Given the short observation period nearly half of our patients were still receiving treatment in hospital at the end of the follow-up and they could not decide the mortality and prognosis of the whole case series.</td></tr><tr><td><bold>10</bold></td><td>Cui Y, Tian M, Huang D, et al. A 55-Day-Old Female Infant infected with COVID 19: presenting with pneumonia, liver injury, and heart damage. J Infect Dis. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1093/infdis/jiaa113" id="intref0135">https://doi.org/10.1093/infdis/jiaa113</ext-link></td><td>1</td><td>55 Day old female infant</td><td>NA</td><td>Case report</td><td>inhaled interferon α-1b (15μg, bid);<break></break>amoxicillin potassium clavulanate (30mg/kg, Q8H, ivgtt).</td><td>NA</td><td>NA</td><td>NA</td><td>Case report for infant patient.<break></break>Adverse events & outcomes not reported.</td></tr><tr><td><bold>11</bold></td><td>Du Y, Tu L, Zhu P, et al. Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan: A Retrospective Observational Study. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://ssrn.com/abstract=3546088" id="intref0140">https://ssrn.com/abstract=3546088</ext-link></td><td>191</td><td>56 Y</td><td>119 M<break></break>72 F</td><td>Retrospective, multicenter cohort study.</td><td>Antibiotics<break></break>Antivirals (lopinavir and ritonavir)<break></break>Corticosteroids<break></break>IV immunoglobulin</td><td>Antibiotics 181 (95%)<break></break>Antivirals (lopinavir and ritonavir) 41 (21%)<break></break>Corticosteroids 57 (30%)<break></break>IV immunoglobulin 46 (24%)</td><td>Patients received antibiotics 181 (95%), non-survivor 53 (98%), survivor 128 (93%) P. value 0·15.<break></break>Antiviral treatment<break></break>41 (21%), non-survivor 12 (22%), survivor 29 (21%), P. value 0·87<break></break>Corticosteroids 57 (30%) non-survivor 26 (48%) survivor 31 (23%), P. value 0·0005.<break></break>IVIG: 46 (24%)<break></break>Non-survivor 36 (67%) survivor 10 (7%) p value < 0.0001<break></break>54 died in hospital.</td><td>Not reported</td><td>Lack of effective antivirals, inadequate adherence to standard supportive therapy, and high-dose corticosteroid use might have also contributed to the poor clinical outcomes in some patients.</td></tr><tr><td><break></break><bold>12</bold></td><td>Gautret P, Lagier J, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020:105949. . doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.ijantimicag.2020.105949" id="intref0145">https://doi.org/10.1016/j.ijantimicag.2020.105949</ext-link></td><td>Treated 20<break></break>Control 16<break></break>Total 36</td><td>45.1</td><td>15 M other= 21</td><td>Open label non- randomized clinical trail.</td><td>Hydroxychloroquin<break></break>and azithromycin</td><td>hydroxychloroquine sulfate 200 mg,<break></break>3 times per day during 10 days</td><td>At day 6 post-inclusion, 100% of patients treated with hydroxychloroquine and azithromycin combination were virologicaly cured comparing with 57.1% in patients treated with hydroxychloroquine only, and 12.5% in the control group.</td><td>One patient stopped the treatment on day3 post-inclusion because of nausea.</td><td>Clinical follow-up and occurrence of side-effects were not discussed in the paper.</td></tr><tr><td><break></break><bold>13</bold></td><td>Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1056/NEJMoa2002032" id="intref0150">https://doi.org/10.1056/NEJMoa2002032</ext-link></td><td>1099</td><td>47.9</td><td>F= 41.1%<break></break>Other=</td><td>Retrospective observational study</td><td>Intravenous antibiotics<break></break>Oseltamivir<break></break>Antifungal<break></break>Systemic Glucocorticoids</td><td>637 patients (58%)<break></break>393 patients (35.8%)<break></break>31 patients (2.8%)<break></break>204 patients (18.6%)</td><td>5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Among the 173 patients with severe disease.</td><td>Not reported</td><td>The study did not include the drugs’ doses, frequency, and duration.</td></tr><tr><td><bold>14</bold></td><td>Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020. doi: <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1056/NEJMoa2001191" id="intref0155">https://doi.org/10.1056/NEJMoa2001191</ext-link></td><td>1</td><td>35</td><td>M</td><td>Case report</td><td>antipyretic therapy consisting of guaifenesin</td><td>650 mg<break></break>600 mg</td><td>Discharged with no symptoms</td><td>Not reported</td><td>It is only one case study and it does not represent the whole population.<break></break>It is a case report, we cannot assure the positive impact on the patient’s health is due to the medication that he has taken.<break></break>Need randomized control trials to be done.</td></tr><tr><td><bold>15</bold></td><td>. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020;395(10223):497-506. :<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/S0140-6736(20)30183-5" id="intref0160">https://doi.org/10.1016/S0140-6736(20)30183-5</ext-link></td><td>41</td><td>49</td><td>M= 30 (73%)<break></break>F= 11(27%)</td><td>Prospective collection and analysed data for pneumonia patients</td><td>Antiviral therapy 38 (93%)<break></break>Antibiotic therapy 41 (100%)<break></break>Corticosteroid 9 (22%)</td><td>Not mentioned</td><td>1 patient was admitted to ICU<break></break>6 patients died.</td><td>Not reported</td><td>Since the causative pathogen has just been identified, kinetics of viral load and antibody titres were not available at the time of the study.</td></tr><tr><td><bold>16</bold></td><td>Huang M, Yang Y, Shang F, et al. Early and Critical Care in Severe Patients with COVID-19 in Jiangsu Province, China: A Descriptive Study. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.21203/rs.3.rs-17397/v1" id="intref0165">https://doi.org/10.21203/rs.3.rs-17397/v1</ext-link></td><td>60 are severe cases</td><td>57</td><td>M= 58.3%<break></break>Other= 42.8%</td><td>multicentre retrospective cohort study was conducted to extract and analyse epidemiological, clinical, laboratory data and treatment of 60 severe cases</td><td>Antiviral therapy 60 (100%)<break></break>Abidor 50 (83.3)<break></break>Lopinavir and Ritonavir Tablets 41 (68.3)<break></break>Interferon 12 (20.0)<break></break>Ribavirin 7 (11.7)<break></break>Oseltamivir 2 (3.3)<break></break>fluoroquinolones (61.7%)</td><td>. 34 patients (56.7%) received intravenous glucocorticoid administration at doses ranging from 40 to 80 mg/d.<break></break>28 patients (46.7%) received immunoglobulin (IgG enriched) injections for a period of 5 to 9 days immunoregulation</td><td>50 patients had significantly improved,<break></break>2 patients had been discharged,<break></break>8 patients were still in serious conditions</td><td>4 patients who developed secondary infections were received glucocorticoids,</td><td>The study did not include most of the drugs’ doses, frequency, and duration.<break></break>In the study, the effect of glucocorticoids was not significant</td></tr><tr><td><bold>17</bold></td><td>. Huang Y, Zhou H, Yang R, Xu Y, Feng X, Gong P. Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China. medRxiv. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.02.27.20029009" id="intref0170">https://doi.org/10.1101/2020.02.27.20029009</ext-link></td><td>36</td><td>69.22</td><td>M= 25(69.44%)<break></break>F= 11(30.56%)</td><td>retrospective, single-centre study</td><td>Antibiotic treatment 36 (100%)<break></break>Antiviral treatment 35 (97.22%)<break></break>Glucocorticoids 25 (69.44%)</td><td>Not mentioned</td><td>All the patients died</td><td>All the patients died.</td><td>The study did not include the drugs doses, frequency, and duration)</td></tr><tr><td><bold>18</bold></td><td>. Jian-ya G. Clinical characteristics of 51 patients discharged from hospital with COVID-19 in Chongqing, China. medRxiv. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.02.20.20025536" id="intref0175">https://doi.org/10.1101/2020.02.20.20025536</ext-link></td><td>51</td><td>45</td><td>M=32(62.7%)<break></break>F=<break></break>19 (37.3%)</td><td>Retrospective, single-centre case series</td><td>Oseltamivir (po) 7(13.7)<break></break>Interferon (po) 51(100)<break></break>Kaletra (po) 51 (100)<break></break>Thymopentin (im) 48(94.1)<break></break>Traditional Chinese medicine decoction (po) 28(54.9)<break></break>Reduling(iv) 30(58.8)<break></break>Xuebijing（iv） 2(3.9)</td><td>Not mentioned</td><td>1 patient died with shock complications</td><td>6 patients had obvious appetite decline<break></break>.</td><td>The study did not include the drugs’ doses, frequency, and duration).</td></tr><tr><td><bold>19</bold></td><td>Liang B, Zhao Y, Zhang X, Lu J, Gu N. Clinical Characteristics of 457 Cases with Coronavirus Disease 2019. Available at SSRN 3543581. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.2139/ssrn.3543581" id="intref0180">https://doi.org/10.2139/ssrn.3543581</ext-link></td><td>457</td><td>It varies</td><td>M= 267 (58%)<break></break>Pregnant women= 9 (2%)</td><td>Systematic Review</td><td>Antiviral therapy 352(77%)<break></break>Antibacterial therapy<break></break>258(56%)<break></break>Glucocorticoids<break></break>130(28%)</td><td>Not mentioned</td><td>195 in improved and discharged</td><td>35 death</td><td>The study did not include the drugs’ doses, frequency, and duration)</td></tr><tr><td><bold>20</bold></td><td>Liao J, Fan S, Chen J, et al. Epidemiological and clinical characteristics of COVID-19 in adolescents and young adults. medRxiv. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.03.10.20032136" id="intref0185">https://doi.org/10.1101/2020.03.10.20032136</ext-link></td><td>46</td><td>Not mentioned because they were two groups</td><td>M= 17(53.1)<break></break>F = 15(46.9)</td><td>Retrospective<break></break>Case series data</td><td>Antiviral therapy 46 (100.0)<break></break>Antifungal treatment 5 (10.9) glucocorticoid therapy</td><td>Not mentioned</td><td>(78.3%) were discharged</td><td>Three patients developed acute kidney injury during treatment</td><td>At the end date of this study, nearly 20% of the patients still hospitalized.</td></tr><tr><td><bold>21</bold></td><td>Lim J, Jeon S, Shin H, et al. Case of the index patient who caused tertiary transmission of Coronavirus disease 2019 in Korea: the application of lopinavir/ritonavir for the treatment of COVID-19 pneumonia monitored by quantitative RT-PCR. J Korean Med Sci. 2020;35(6). doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3346/jkms.2020.35.e79" id="intref0190">https://doi.org/10.3346/jkms.2020.35.e79</ext-link></td><td>1</td><td>54</td><td>M</td><td>Case Report</td><td>Lopinavir ritonavir</td><td>200 mg<break></break>50 mg (2 tablets bid)</td><td>Reduced viral loads and improved clinical symptoms</td><td>The patient also complained of psychiatric symptoms such as depression, insomnia and suicidal thoughts after isolation</td><td>It is only one case and does not represent the whole population.<break></break>Need randomized control trials to be done.</td></tr><tr><td><bold>22</bold></td><td>. Liu F, Xu A, Zhang Y, et al. Patients of COVID-19 may benefit from sustained lopinavir-combined regimen and the increase of eosinophil may predict the outcome of COVID-19 progression. International Journal of Infectious Diseases. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.ijid.2020.03.013" id="intref0195">https://doi.org/10.1016/j.ijid.2020.03.013</ext-link></td><td>10</td><td>42</td><td>6 F<break></break>Other=4</td><td>retrospective observational single-center study</td><td>lopinavir, LPV,<break></break>interferon α2b atomization inhalation,</td><td>400 mg every twelve<break></break>5 million U twice daily hours</td><td>Eosinophil counts presented potentiality as predictor on the development process of COVID-19 in this study<break></break>Seven discharged<break></break>Three patients stopped lopinavir<break></break>Two of them deteriorated, one hospitalized longer than others who with sustained lopinavir using</td><td>Digestive adverse effect and hypokalemia</td><td>Small sample size</td></tr><tr><td><bold>23</bold></td><td>Liu J, Ouyang L, Guo P, et al. Epidemiological, Clinical Characteristics and Outcome of Medical Staff Infected with COVID-19 in Wuhan, China: A Retrospective Case Series Analysis. medRxiv. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.03.09.20033118" id="intref0200">https://doi.org/10.1101/2020.03.09.20033118</ext-link></td><td>64 medical staff</td><td>35 (29-43)</td><td>23 M<break></break>41 F</td><td>Single centre- Retrospective – observational study</td><td>Immune globulin<break></break>Thymosin<break></break>Corticosteroids</td><td>Antibody / 23<break></break>Hormone / 33<break></break>Steroid hormone / 7</td><td>34 discharged<break></break>30 hospitalised</td><td>Not reported</td><td>Preliminary insight into epidemiological features and clinical outcomes.<break></break>Single center.</td></tr><tr><td><bold>24</bold></td><td>Liu W, Zhang Q, Chen J, et al. Detection of Covid-19 in Children in Early January 2020 in Wuhan, China. N Engl J Med. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1056/NEJMc2003717" id="intref0205">https://doi.org/10.1056/NEJMc2003717</ext-link></td><td>6 children</td><td>3 (1-7)</td><td>2 M<break></break>4 F</td><td>Retrospective Case Series Analysis</td><td>Ribavirin.<break></break>Oseltamivir.<break></break>Glucocorticoiuds.<break></break>Intravenous immune globulin.</td><td>Antiviral /2<break></break>Antiviral /6<break></break>Steroid hormone /4<break></break>Antibody /1.</td><td>6 recovery</td><td>Not reported</td><td>Small sample size</td></tr><tr><td><bold>25</bold></td><td>Liu Y, Sun W, Li J, et al. Clinical features and progression of acute respiratory distress syndrome in coronavirus disease 2019. medRxiv. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.02.17.20024166" id="intref0210">https://doi.org/10.1101/2020.02.17.20024166</ext-link></td><td>109 patients</td><td>55</td><td>59 M<break></break>50 F</td><td>Retrospective Case Series Analysis</td><td>Glucocorticoid.<break></break>Intravenous immunoglobulin therapies</td><td>Steroid hormone /43<break></break>Antibody / 32<break></break>Antibiotics /105<break></break>Antivirus /105</td><td>31 deaths</td><td>Not reported</td><td>This study did not mention the names of the therapeutic treatment used among ARDS patients.</td></tr><tr><td><bold>26</bold></td><td>Lo IL, Lio CF, Cheong HH, et al. Evaluation of SARS-CoV-2 RNA shedding in clinical specimens and clinical characteristics of 10 patients with COVID-19 in Macau. Int J Biol Sci. 2020;16(10):1698-1707. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.7150/ijbs.45357" id="intref0215">https://doi.org/10.7150/ijbs.45357</ext-link></td><td>10 patients</td><td>54 (27-64)</td><td>3 M<break></break>1 teenager<break></break>6 others</td><td>Retrospective Case Series Analysis</td><td>Lopinavir<break></break>Ritonavir</td><td>Antiviral / 10</td><td>5 discharged<break></break>5 hospitalised</td><td>Not reported</td><td>Small sample size, so it is hard to draw a definite conclusion.<break></break>Single center.<break></break>Half of the enrolled patients are still hospitalized at the time of the submission of this paper. Therefore, there may have been bias regarding the prognosis of the patients.</td></tr><tr><td><bold>27</bold></td><td>Mo P, Xing Y, Xiao Y, et al. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China. Clinical Infectious Diseases. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1093/cid/ciaa270" id="intref0220">https://doi.org/10.1093/cid/ciaa270</ext-link></td><td>155 patients</td><td>54 (42-66)</td><td>86 M<break></break>69 others</td><td>Single-centre, Retrospective Case Series Analysis</td><td>Arbidol<break></break>lopinavir and ritonavir;<break></break>interferon inhalation<break></break>Immune enhancer</td><td>Antiviral /31<break></break>Antiviral /27<break></break>Antiviral /30<break></break>14</td><td>22 deaths</td><td>Not reported</td><td>Selection bias might occur for this retrospective study and a large-scale nationwide study was needed.</td></tr><tr><td><bold>28</bold></td><td>Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1001/jama.2020.1585" id="intref0225">https://doi.org/10.1001/jama.2020.1585</ext-link></td><td>138 patients</td><td>56 (42-68)</td><td>75 M<break></break>63 F</td><td>Retrospectiv, single-centre case series</td><td>Oseltamivir<break></break>Moxifloxcain<break></break>Ceftriaxone<break></break>Azithromycin<break></break>Glucocorticoid</td><td>Antiviral / 124<break></break>Antibacterial /89<break></break>Antibacterial /34<break></break>Antibacterial /25<break></break>Glucocorticoid therapy /62</td><td>47 discharged<break></break>6 deaths<break></break>85 hospitalized.</td><td>Not reported</td><td>Most patients are still hospitalized at the time of manuscript submission. Therefore, there may have been bias regarding the prognosis of the patients.</td></tr><tr><td><bold>29</bold></td><td>Wang Z, Yang B, Li Q, Wen L, Zhang R. Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China. Clinical Infectious Diseases. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1093/cid/ciaa272" id="intref0230">https://doi.org/10.1093/cid/ciaa272</ext-link></td><td>69 patients</td><td>42 (35-62)</td><td>32 M<break></break>37 F</td><td>Retrospective case series</td><td>-</td><td>Antiviral /66<break></break>Antibiotic /66<break></break>Antifungal drug /8<break></break>Corticosteroids /10<break></break>Arbidol /36</td><td>44 hospitalised<break></break>18 discharged<break></break>5 deaths</td><td>Not reported</td><td>The study did not include the drugs’ doses, frequency, and duration).</td></tr><tr><td><bold>30</bold></td><td>Wu C, Hu X, Song J, et al. Heart injury signs are associated with higher and earlier mortality in coronavirus disease 2019 (COVID-19). medRxiv. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.02.26.20028589" id="intref0235">https://doi.org/10.1101/2020.02.26.20028589</ext-link></td><td>188 patients</td><td>52</td><td>119 M<break></break>69 others</td><td>Retrospective cohort study</td><td>-</td><td>Antibiotics / 185<break></break>Antiviral /158<break></break>Corticosteroids /59</td><td>43 deaths<break></break>145 discharged<break></break>12 Hospitalised</td><td>Not reported</td><td>The study did not include the drugs’ doses, frequency, and duration)</td></tr><tr><td><bold>31</bold></td><td>Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265-269. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1038/s41586-020-2008-3" id="intref0240">https://doi.org/10.1038/s41586-020-2008-3</ext-link></td><td>1</td><td>41 years</td><td>M</td><td>Epidemiological investigations</td><td>Antiviral therapy<break></break>Antibiotic<break></break>Glucocorticoid<break></break>Oxygen therapy</td><td>Oseltamivir<break></break>Cefoselis<break></break>Not mentioned<break></break>Mechanical ventilation</td><td>recovered</td><td>Not reported</td><td>Applicable</td></tr><tr><td><bold>32</bold></td><td>Xu Y, Li Y, Zeng Q, et al. Clinical characteristics of SARS-CoV-2 pneumonia compared to controls in Chinese Han population. medRxiv. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.03.08.20031658" id="intref0245">https://doi.org/10.1101/2020.03.08.20031658</ext-link></td><td>Patients: 69<break></break>Normal: 14,117</td><td>57 years</td><td>Male: 50.7%<break></break>Female: 49.3%</td><td>Retrospectiv, multi-centre case series</td><td>Antiviral therapy<break></break>Antibiotic<break></break>Oxygen therapy</td><td>Oseltamivir 38 (55.1%) patients<break></break>Moxifloxacin, ceftriaxone, azithromycin, and tigecycline or linezolid<break></break>31 (44.9%) patients.<break></break>3 patients used mechanical ventilation;<break></break>2 patients used an invasive ventilator.</td><td>Discharged- 3<break></break>Recovered- 1<break></break>Died- 1</td><td>6 patients significantly increased in IL6 were also treated with methylprednisolone.</td><td>Applicable</td></tr><tr><td><bold>33</bold></td><td>Xu Y, Xu Z, Liu X, et al. Clinical findings in critical ill patients infected with SARS-Cov-2 in Guangdong Province, China: a multi-center, retrospective, observational study. medRxiv. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.03.03.20030668" id="intref0250">https://doi.org/10.1101/2020.03.03.20030668</ext-link></td><td>45</td><td>56.7 years</td><td>Male:<break></break>29 (64,4%)<break></break>Female:<break></break>16 (35.6%)</td><td>multi-centre, retrospective, observational study</td><td>Antiviral agents 45 (100) pateints<break></break>Antibacterial agents 45 (100)<break></break>Antifungal agents 19 (42.2)<break></break>Convalescent plasma 6 (13.3)<break></break>Glucocorticoids 21 (46.7)<break></break>Immunoglobulin 28 (62.2)<break></break>Albumin<break></break>35 (77.8)</td><td>Osehamivir ribavirin<break></break>Not mentioned<break></break>Not mentioned<break></break>Not mentioned<break></break>Not mentioned<break></break>Not mentioned<break></break>Not mentioned</td><td>ICU discharge 23 (51.1%)<break></break>Hospital discharge 11 (24.4%)<break></break>Death<break></break>1 (2.2%)</td><td>37 patients (82.2%) had developed acute respiratory distress syndrome, and 13 (28.9%) septic shock.<break></break>A total of 20 (44.4%) patients required intubation and 9 (20%) required extracorporeal membrane oxygenation.</td><td>At the time of study submission, half of the patients had not been discharged from ICU, it is hard to estimate either ICU stay, ventilation free day, the case fatality rate or the predictors of fatality.<break></break>The study did not include the drugs’ doses, frequency, and duration.</td></tr><tr><td><bold>34</bold></td><td>Xu XW, Wu XX, Jiang XG, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ. 2020;368:m606. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1136/bmj.m606" id="intref0255">https://doi.org/10.1136/bmj.m606</ext-link></td><td>62</td><td>41 years</td><td>Male: 35 (56%)<break></break>Female: 27 (44%)</td><td>Retrospective study</td><td>antiviral treatment<break></break>55 (89%)<break></break>Antibiotics<break></break>Corticosteroid & gamma globulin</td><td>INFa inhalation 8 (13%);<break></break>Lopinavir/Ritonavir 4 (6%);<break></break>Arbidol+interferon alpha inhalation 1(2%);<break></break>Lopinavir/ritonavir+interferon alpha inhalation 21(34%);<break></break>Arbidol+lopinavir/ritonavir 17(28%);<break></break>Arbidol+lopinavir/ritonavir+interferon alpha inhalation 4(6%)<break></break>28 (45%) pateints<break></break>16 (26%) pateints</td><td>No mortality</td><td>Not reported</td><td>At the time of study submission, most patients had not been discharged, so it is hard to estimate either the case fatality rate or the predictors of fatality.</td></tr><tr><td><bold>35</bold></td><td>Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/S2213-2600(20)30076-X" id="intref0260">https://doi.org/10.1016/S2213-2600(20)30076-X</ext-link></td><td>1</td><td>50</td><td>Male: 50 years old</td><td>Postmortem biopsies</td><td>Antiviral therapy<break></break>Antibiotics<break></break>Corticosteroid</td><td>Interferon alfa-2b atomisation<break></break>lopinavir plus ritonavir<break></break>Moxifloxacin<break></break>Methylprednisolone</td><td>Died due to cardiac arrest</td><td>Chest x-ray showed progressive infiltrate and diffuse gridding shadow in both lungs. Hypoxaemia and shortness of breath worsened & patient had sudden cardiac arrest.</td><td>It is only one case study and it does not represent the whole population.<break></break>The patient refused ventilator support in the intensive care unit repeatedly because he suffered from claustrophobia; therefore, he received high-flow nasal cannula.<break></break>Need randomized control trials to be done.</td></tr><tr><td><bold>36</bold></td><td>Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/S2213-2600(20)30079-5" id="intref0265">https://doi.org/10.1016/S2213-2600(20)30079-5</ext-link></td><td>52</td><td>59·7 years</td><td>Male: 35 (67%)<break></break>Female: 17 (33%)</td><td>Single-centre retrospective, observational study.</td><td>Vasoconstrictive agents<break></break>Antiviral agents<break></break>23 (44%)<break></break>Antibacterial agents<break></break>Glucocorticoids<break></break>Immunoglobulin</td><td>18 (35%)<break></break>Oseltamivir 18(35%) patients, ganciclovir 14 (27%),<break></break>lopinavir 7 (13·5%).<break></break>49 (94%)<break></break>30 (58%)<break></break>28 (54%)</td><td>32 (61·5%) patients had died.</td><td>Not reported</td><td>Due to the exploratory nature of the study, which was not driven by formal hypotheses, the sample size calculation was waived.<break></break>The researchers acknowledged that some specific information from the ICU was missing, such as mechanical ventilation settings.<break></break>The study did not include the drugs’ doses, frequency, and duration.</td></tr><tr><td><bold>37</bold></td><td>Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1001/jama.2020.3204" id="intref0270">https://doi.org/10.1001/jama.2020.3204</ext-link></td><td>18</td><td>47 years;</td><td>Male:<break></break>9(50%)<break></break>Female: 9(50%)</td><td>Descriptive case series</td><td>Antiretroviral drug<break></break>Antiviral therapy<break></break>Antibiotics</td><td>lopinavir-ritonavir<break></break>oseltamivir<break></break>not reported</td><td>No deaths</td><td>Not reported</td><td>Small sample size<break></break>The study did not include some of the drugs’ doses, frequency, and duration</td></tr><tr><td><bold>38</bold></td><td>Zhang B, Zhou X, Qiu Y, et al. Clinical characteristics of 82 death cases with COVID-19. medRxiv. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.02.26.20028191" id="intref0275">https://doi.org/10.1101/2020.02.26.20028191</ext-link></td><td>82</td><td>72.5 years</td><td>Male: (65.9%)</td><td>Death cases</td><td>Antiviral therapy<break></break>Antibiotics<break></break>Corticosteroids 29 (35.3%) patients</td><td>82 (100%)<break></break>82 (100%)<break></break>29 (35.3%)</td><td></td><td>Not reported</td><td>The study has been done in one setting. There is no information about the hospital’s capabilities from personnel or equipment because the mortality rate from this centre is a little higher than the other centres.<break></break>Traditional Chinese Medicine were given.<break></break>The study did not include the drugs’ doses, frequency, and duration.</td></tr><tr><td><bold>39</bold></td><td>Zhang G, Hu C, Luo L, et al. Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China. medRxiv. 2020. doi:<break></break><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.03.02.20030452" id="intref0280">https://doi.org/10.1101/2020.03.02.20030452</ext-link></td><td>221</td><td>55.0 years</td><td>Male: 108(48.9%)<break></break>Female: 113(51.1%)</td><td>Retrospective case study.</td><td>Antiviral treatment<break></break>196 (88.7%)<break></break>Antibiotic therapy<break></break>Corticosteroid therapy<break></break>115(52.0%)</td><td>Oseltamivir,<break></break>Arbidol hydrochloride,<break></break>α-interferon atomization inhalation,<break></break>Lopinavir/ritonavir)<break></break>Moxifloxacin hydrochloride;<break></break>Piperacillin sodium tazobactam sodium;<break></break>Cefoperazone sulbactam<break></break>Glucocorticoid 64 (49.6%) patients</td><td>12 (5.4%) Death</td><td>Not reported</td><td>The dose and duration of intravenous glucocorticoid treatment showed no difference in outcomes of symptomatic relief and death.<break></break>The study did not include the drugs’ doses, frequency, and duration.</td></tr><tr><td><bold>40</bold></td><td>Zhang G, Hu C, Luo L, et al. Clinical Features and Treatment of 221 Patients with COVID-19 in Wuhan, China. China (2/27/2020). 2020 doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.2139/ssrn.3546095" id="intref0285">https://doi.org/10.2139/ssrn.3546095</ext-link>.</td><td>221</td><td>Not mentioned</td><td>M=108<break></break>F=113</td><td>single center, retrospective case series study (Observational)</td><td>Antiviral therapy 196 (88.7%)<break></break>Glucocorticoid 115(52.0)</td><td>Not mentioned</td><td>A total of 42 (19.0%) patients had been discharged<break></break>12 (5.4%) patients died<break></break>44 (80%) of them received ICU care<break></break>23 of them transferred to the general wards<break></break>Mortality rate was 21.8%</td><td>Not reported</td><td></td></tr><tr><td><bold>41</bold></td><td>Zhang JC, Zhang X, Wu G, Yi J. The potential role of IL-6 in monitoring coronavirus disease 2019. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1101/2020.03.01.20029769" id="intref0290">https://doi.org/10.1101/2020.03.01.20029769</ext-link></td><td>80</td><td>53</td><td>F= 46(57.5%)<break></break>M=34(42.5%)</td><td>Data collection (Clinical data of COVID-19 patients diagnosed by laboratory test in our institution were collected). observation of clinical manifestation</td><td>Antibiotics 73 (91·25)<break></break>Oseltamivir 20 (25·00)<break></break>Ribavirin, ganciclovir or peramivir 47 (58·75)<break></break>Arbidol 49 (61·25)<break></break>Antifungal medications 10 (12·50)<break></break>Intravenous immunoglobin 36 (45·00)<break></break>Corticosteroids 29 (36·25)</td><td>Not mentioned</td><td>It is suggested that IL-6 may be used as a biomarker for disease monitoring in severe COVID-19 patients.</td><td>Not reported</td><td>The study did not include the drugs’ doses, frequency, and duration.<break></break>IL-6 and the pathogenesis of COVID-19 remains elusive.</td></tr><tr><td><bold>42</bold></td><td>Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020. doi:<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/S0140-6736(20)30566-3" id="intref0295">https://doi.org/10.1016/S0140-6736(20)30566-3</ext-link></td><td>191 patients</td><td>56·0 years</td><td>Male: 119 (62%)<break></break>Female: 72 (38%)</td><td>Retrospective cohort study</td><td>Antibiotics 181 (95%)<break></break>Antiviral treatment<break></break>41 (21%)<break></break>Corticosteroids 57 (30%)<break></break>Intravenous immunoglobin<break></break>46 (24%)</td><td>Lopinavir/ritonavir</td><td>137 were discharged and 54 died in hospital.</td><td>191 patients</td><td>There was no observation of shortening of viral shedding duration after lopinavir/ritonavir treatment in the current study.<break></break>The study did not include the drugs’ doses, frequency, and duration.</td></tr></tbody></table></table-wrap></p><p id="p0065">Forty-one studies were included, of which clinical trials (n=3), case reports (n=7), case series (n=10), retrospective (n=11) and prospective (n=10) observational studies. Thirty-six studies were conducted in China, and one in each of; Korea, USA, France, Singapore and Macau .</p><sec id="sec3.1"><title>Patient Characteristics</title><p id="p0070">Total number of patients reported in these studies were 8,806. The mean of age was 50.8 years in 39 studies; the age was not specified in other studies.</p></sec><sec id="sec3.2"><title>Reported therapeutics</title><p id="p0075">The most commonly reported therapeutic in this systematic review was the anti-inflammatory medication, Corticosteroid (n=25) with different names and product characteristics, (Corticosteroid n=21, Methylprednisolone n=3, Dexamethasone n=1). This was followed by the antiviral HIV medication Lopinavir (n=21), as combination Lopinavir/Ritonavir (n=18), alone (n=3), followed by the Oseltamivir (n=16) and Arbidol Hydrochloride (n=8).</p><p id="p0080">In terms of antibacterial medicines, Moxifloxacin (n=4) and Tigecycline were the most reported.</p><p id="p0085">Convalescent plasma therapy was reported in one multi center retrospective observational study of six patients.</p></sec><sec id="sec3.3"><title>The outcome of the treatment</title><p id="p0090">The outcome measures recorded vary between patients discharge and recovery, ongoing hospitalization, and mortality. Available data concerning this issue is shown in <xref rid="tbl3" ref-type="table">Table 3</xref>.</p></sec></sec><sec id="sec4"><title>Discussion</title><p id="p0095">This is the first up to date review related the therapeutics used in COVID-19 patients in a systematic manner. As of March 26th, 2020 (since the emergence of COVID-19) only 41 eligible research articles on COVID-19 and therapeutics were found to be included in the current systematic review<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref><sup>,</sup><xref rid="bib5" ref-type="bibr"><sup>5</sup></xref><sup>,</sup><xref rid="bib12" ref-type="bibr">12</xref>, <xref rid="bib13" ref-type="bibr">13</xref>, <xref rid="bib14" ref-type="bibr">14</xref>, <xref rid="bib15" ref-type="bibr">15</xref>, <xref rid="bib16" ref-type="bibr">16</xref>, <xref rid="bib17" ref-type="bibr">17</xref>, <xref rid="bib18" ref-type="bibr">18</xref>, <xref rid="bib19" ref-type="bibr">19</xref>, <xref rid="bib20" ref-type="bibr">20</xref>, <xref rid="bib21" ref-type="bibr">21</xref>, <xref rid="bib22" ref-type="bibr">22</xref>, <xref rid="bib23" ref-type="bibr">23</xref>, <xref rid="bib24" ref-type="bibr">24</xref>, <xref rid="bib25" ref-type="bibr">25</xref>, <xref rid="bib26" ref-type="bibr">26</xref>, <xref rid="bib27" ref-type="bibr">27</xref>, <xref rid="bib28" ref-type="bibr">28</xref>, <xref rid="bib29" ref-type="bibr">29</xref>, <xref rid="bib30" ref-type="bibr">30</xref>, <xref rid="bib31" ref-type="bibr">31</xref>, <xref rid="bib32" ref-type="bibr">32</xref>, <xref rid="bib33" ref-type="bibr">33</xref>, <xref rid="bib34" ref-type="bibr">34</xref>, <xref rid="bib35" ref-type="bibr">35</xref>, <xref rid="bib36" ref-type="bibr">36</xref>, <xref rid="bib37" ref-type="bibr">37</xref>, <xref rid="bib38" ref-type="bibr">38</xref>, <xref rid="bib39" ref-type="bibr">39</xref>, <xref rid="bib40" ref-type="bibr">40</xref>, <xref rid="bib41" ref-type="bibr">41</xref>, <xref rid="bib42" ref-type="bibr">42</xref>, <xref rid="bib43" ref-type="bibr">43</xref>, <xref rid="bib44" ref-type="bibr">44</xref>, <xref rid="bib45" ref-type="bibr">45</xref>, <xref rid="bib46" ref-type="bibr">46</xref>, <xref rid="bib47" ref-type="bibr">47</xref>, <xref rid="bib48" ref-type="bibr">48</xref>, <xref rid="bib49" ref-type="bibr">49</xref>. Only three were clinical trials; most were either case reports, case series or prospective and retrospective observational studies. Systemic Corticosteroid of different names and formulation was the most commonly reported, medication, followed by the antivirals Lopinavir , Oseltamivir and Arbidol hydrochloride. Convalescent plasma therapy was mentioned in one multi-center retrospective observational study and was administered to six patients.</p><p id="p0100">Although quality assessment was applied to the included research articles, there was insufficient evidence from the articles identified in this review to conduct a meta-analysis. Nor was a subgroup analysis (adults and children, different formulations, dosages and duration) appropriate.</p><p id="p0105">Most reported articles in this review are low quality; the design and outcome of the studies are incomplete or inconsistent, hence difficult to interpret the therapeutics in terms of efficacy and safety.</p><p id="p0110">Despite these limitations, this is the first systematic review linked the therapeutics used in COVID-19 patients. Furthermore, the review provided up-to-date insight on the current therapeutics’ guidelines for the management of COVID-19 patients; most of reported medicines in this review were already in place in the USA, Saudi Arabia, Europe, and Egypt (<xref rid="tbl1" ref-type="table">Table 1</xref>).</p><p id="p0115"><bold>Corticosteroids</bold> were the most commonly reported and used medicine in this review, however, they are not recommended in any of the mentioned guidelines. The World Health Organization (WHO) and the United States Centers for Disease Control and Prevention (CDC), in the absence of conclusive scientific evidence, recommended that Corticosteroids should not be routinely used in patients with COVID-19 for treatment of viral pneumonia or acute respiratory distress syndrome (ARDS) unless indicated for other conditions, such as asthma or chronic obstructive pulmonary disease (COPD) exacerbation, or septic shock<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref><sup>,</sup><xref rid="bib50" ref-type="bibr">50</xref>, <xref rid="bib51" ref-type="bibr">51</xref>. Careful use of Corticosteroids with low-to-moderate doses in short courses is advised. Hyperglycemia, hypernatremia and hypokalemia are the most common adverse effects associated with Corticosteroid use and should be routinely monitored<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref><sup>,</sup><xref rid="bib51" ref-type="bibr"><sup>51</sup></xref>.</p><p id="p0120"><bold>Lopinavir/Ritonavir</bold> is available as the brand name Kaletra and was the second most reported medicine in this review. In their RCT, Cao B et al reported negative outcomes of this HIV treatment for COVID-19 patients (<xref rid="tbl2" ref-type="table">Table 2</xref>) <xref rid="bib30" ref-type="bibr"><sup>30</sup></xref><sup>,</sup><xref rid="bib52" ref-type="bibr">52</xref>, <xref rid="bib53" ref-type="bibr">53</xref>, <xref rid="bib54" ref-type="bibr">54</xref>. No benefit was observed with Lopinavir/Ritonavir treatment beyond standard care in this study, 19 patients who received the intervention died. However, some limitations were observed in the study, including the lack of blinding. RCT NCT04252885 and SOLIDARITY trial are ongoing to determine the efficacy in Lopinavir/Ritonavir COVID-19 patients<sup>(</sup><xref rid="bib52" ref-type="bibr"><sup>52</sup></xref><sup>)</sup>.</p><p id="p0125"><bold>Oseltamivir</bold> was the third most reported therapeutic in this review, and sold under the brand name Tamiflu, it is used to treat influenza A and influenza B. Oseltamivir was recommended by WHO for people at high risk of infection for prevention of pandemic influenza. Guan W and colleagues in their retrospective observational study reported the use of Oseltamivir in 1,099 patients; however, the study was not able to provide any solid data on the effectiveness of Oseltamivir in the prevention or treatment of COVID-19 patients. Study limitations included incomplete documentation of patients’ data and recall bias<sup>(</sup><xref rid="bib55" ref-type="bibr">55</xref>, <xref rid="bib56" ref-type="bibr">56</xref><sup>)</sup>.</p><p id="p0130"><bold>Arbidol hydrochloride</bold> was the fourth most reported medicine in this review; it is a broad-spectrum inhibitor of influenza A and B virus, parainfluenza virus, and other viruses, including hepatitis C virus. It is used in Russia and <ext-link ext-link-type="uri" xlink:href="https://en.wikipedia.org/wiki/China" id="intref0025">China</ext-link>, yet not approved for use in other countries<sup>(</sup><xref rid="bib52" ref-type="bibr"><sup>52</sup></xref><sup>)</sup>. However, no conclusive evidence of its efficacy in COVID-19 was reported. In this review, it was reported together with Favipiravir, which was approved recently for treatment of novel influenza on February 15<sup>th</sup>, 2020 in China<sup>(</sup><xref rid="bib52" ref-type="bibr"><sup>52</sup></xref><sup>)</sup>.</p><p id="p0135"><bold>Chloroquine phosphate</bold> and <bold>Hydroxychloroquine</bold> were reported in this review and showed favorable outcomes in the recovery of COVID-19 patients<xref rid="bib6" ref-type="bibr">6</xref>, <xref rid="bib7" ref-type="bibr">7</xref><sup>,</sup><xref rid="bib57" ref-type="bibr">57</xref>, <xref rid="bib58" ref-type="bibr">58</xref>, <xref rid="bib59" ref-type="bibr">59</xref>, <xref rid="bib60" ref-type="bibr">60</xref>. The mechanism of action on viruses for these two medicines is likely the same effect. Chloroquine has been used for a long time to treat malaria and showed positive outcomes in patients. Furthermore, Hydroxychloroquine showed a significant effectiveness to kill intracellar pathogens such as <italic>Coxiella burnetii</italic>, the agent of Q fever<sup>(</sup><xref rid="bib22" ref-type="bibr"><sup>22</sup></xref><sup>)</sup>. The French open label, non- randomized clinical trial was promising and the first clinical trial of these medications in COVID-19 patients. The effect of Hydroxychloroquine was significant because it showed reduction in the viral load when it compared with the control group<sup>(</sup><xref rid="bib22" ref-type="bibr"><sup>22</sup></xref><sup>)</sup>. Moreover, the effect of Hydroxychloroquine was significantly more potent when Azithromycin was added to the patients according to their clinical need. However, clinical follow-up and occurrence of adverse effects were not discussed in the paper; further work should be done on these medicines with the aim of reducing the morbidity and mortality of COVID-19 <sup>(</sup><xref rid="bib57" ref-type="bibr">57</xref>, <xref rid="bib58" ref-type="bibr">58</xref>, <xref rid="bib59" ref-type="bibr">59</xref><sup>)</sup>. Although these two medicines have shown promising activity against SARSCoV-2, there is a risk of arrhythmia associated with their administration. Therefore caution is required for use at higher cumulative dosages. It is recommended that their use in suspected/confirmed COVID-19 is to be restricted to hospitalized patients. On March 30<sup>th</sup>, 2020 the U.S Food and Drug Administration (US FDA) has issued an emergency use authorization (EUA) for Chloroquine and Hydroxychloroquine to treat patients hospitalized with Covid-19 <sup>(</sup><xref rid="bib60" ref-type="bibr"><sup>60</sup></xref><sup>)</sup>.</p><p id="p0140"><bold>Convalescent plasma treatment</bold> was mentioned once in this review, in a multi-centre cohort research trial of 45 critically ill COVID-19 patients admitted to ICU in Wuhan. The findings showed that convalescent plasma was administered to six patients and no transfusion reactions occurred; however, the study could not provide adequate information about the efficacy of convalescent plasma, due to limited sample sizes and lack of randomized control group<sup>(</sup><xref rid="bib61" ref-type="bibr">61</xref>, <xref rid="bib62" ref-type="bibr">62</xref><sup>)</sup>.</p><p id="p0145">In fact, convalescent plasma therapy could be a promising method of treatment for COVID-19 patients. A very recent case series reported from China, showed that five critically ill patients with laboratory confirmed COVID-19 (who had ARDS) improved. After receiving plasma transfusion, their body temperature normalized within 3 days (in 4 of 5 patients), their viral loads became undetectable within 12 days and 3 of 5 patients were discharged from the hospital and were in stable condition at 37 days post transfusion<sup>(</sup><xref rid="bib63" ref-type="bibr"><sup>63</sup></xref><sup>)</sup>.</p><p id="p0150">On March 24<sup>th</sup>, 2020 the US FDA has approved convalescent plasma treatment for investigational use under the traditional Investigational New Drug Applications (IND) regulatory pathway, and for <bold>e</bold>ligible patients who have confirmed COVID-19 and severe or immediately life-threatening conditions such as respiratory failure, septic shock, and/or multiple organ dysfunction or failure<sup>(</sup><xref rid="bib64" ref-type="bibr">64</xref>, <xref rid="bib65" ref-type="bibr">65</xref><sup>)</sup>.</p><p id="p0155">Notably there are some potential risks and ethical issues associated with their use, including increased thrombotic event risk (0.04 to 14.9%), lack of high quality research in this particular area and the selection of donors with high neutralizing antibody titers<sup>(</sup><xref rid="bib65" ref-type="bibr"><sup>65</sup></xref><sup>)</sup>.</p></sec><sec id="sec5"><title>Conclusions</title><p id="p0160">This is the first up to date systematic review of therapeutics used in COVID-19 patients. Only 41 research articles on COVID-19 and therapeutics were found eligible to be included, most conducted in China, of which only three were clinical trials.</p><p id="p0165">The anti-inflammatory medication Corticosteroid was found to be the most mentioned and widely used medicine in these studies, despite the safety alert issued by WHO and CDC, followed by antiviral medication Lopinavir, Oseltamivir and Arbidol hydrochloride.</p><p id="p0170">Although further research is warranted as the amount of the evidence increases, this study presents the current picture of treatment modalities used for COVID-19. Efficacy and safety profiles of treatments for COVID-19 will need to be characterized in future studies.</p></sec><sec id="sec6"><title>Funding</title><p id="p0175">Nil received</p></sec><sec id="sec7"><title>Conflict of Interest</title><p id="p0180">Nil declared</p></sec></body><back><ref-list id="cebib0010"><title>References</title><ref id="bib1"><label>1</label><element-citation publication-type="journal" id="sref1"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>W.</given-names></name><name><surname>Cao</surname><given-names>Q.</given-names></name><name><surname>Qin</surname><given-names>L.</given-names></name><name><surname>Wang</surname><given-names>X.</given-names></name><name><surname>Cheng</surname><given-names>Z.</given-names></name><name><surname>Pan</surname><given-names>A.</given-names></name></person-group><article-title>Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19):A multi-center study in Wenzhou city, Zhejiang, China [published online ahead of print, 2020 Feb 26]</article-title><source>J Infect</source><year>2020</year><pub-id pub-id-type="doi">10.1016/j.jinf.2020.02.016</pub-id><comment>S0163-4453(20)30099-2</comment></element-citation></ref><ref id="bib2"><label>2</label><mixed-citation publication-type="other" id="sref2">Guan W, Ni Z, Hu Y, et al. 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