Subcutaneous administration of interferon beta-1a for COVID-19: A non-controlled prospective trial.
Identifieur interne : 001395 ( Main/Corpus ); précédent : 001394; suivant : 001396Subcutaneous administration of interferon beta-1a for COVID-19: A non-controlled prospective trial.
Auteurs : Farzaneh Dastan ; Seyed Alireza Nadji ; Ali Saffaei ; Majid Marjani ; Afshin Moniri ; Hamidreza Jamaati ; Seyed Mohammadreza Hashemian ; Parvaneh Baghaei ; Atefeh Abedini ; Mohammad Varahram ; Sahar Yousefian ; Payam TabarsiSource :
- International immunopharmacology [ 1878-1705 ] ; 2020.
English descriptors
- KwdEn :
- Adolescent (MeSH), Adult (MeSH), Aged (MeSH), Aged, 80 and over (MeSH), Antiviral Agents (administration & dosage), Antiviral Agents (pharmacology), Antiviral Agents (therapeutic use), Betacoronavirus (drug effects), COVID-19 (MeSH), Coronavirus Infections (diagnostic imaging), Coronavirus Infections (drug therapy), Drug Combinations (MeSH), Drug Therapy, Combination (MeSH), Female (MeSH), Humans (MeSH), Hydroxychloroquine (administration & dosage), Hydroxychloroquine (therapeutic use), Injections, Subcutaneous (MeSH), Interferon beta-1a (administration & dosage), Interferon beta-1a (pharmacology), Interferon beta-1a (therapeutic use), Lopinavir (administration & dosage), Lopinavir (therapeutic use), Lung (diagnostic imaging), Male (MeSH), Middle Aged (MeSH), Pandemics (MeSH), Pneumonia, Viral (diagnostic imaging), Pneumonia, Viral (drug therapy), Prospective Studies (MeSH), Ritonavir (administration & dosage), Ritonavir (therapeutic use), SARS-CoV-2 (MeSH), Tomography, X-Ray Computed (MeSH), Treatment Outcome (MeSH), Young Adult (MeSH).
- MESH :
- chemical , administration & dosage : Antiviral Agents, Hydroxychloroquine, Interferon beta-1a, Lopinavir, Ritonavir.
- chemical , pharmacology : Antiviral Agents, Interferon beta-1a.
- chemical , therapeutic use : Antiviral Agents, Hydroxychloroquine, Interferon beta-1a, Lopinavir, Ritonavir.
- diagnostic imaging : Coronavirus Infections, Lung, Pneumonia, Viral.
- drug effects : Betacoronavirus.
- drug therapy : Coronavirus Infections, Pneumonia, Viral.
- Adolescent, Adult, Aged, Aged, 80 and over, COVID-19, Drug Combinations, Drug Therapy, Combination, Female, Humans, Injections, Subcutaneous, Male, Middle Aged, Pandemics, Prospective Studies, SARS-CoV-2, Tomography, X-Ray Computed, Treatment Outcome, Young Adult.
Abstract
BACKGROUND
Recently, a new coronavirus spreads rapidly throughout the countries and resulted in a worldwide epidemic. Interferons have direct antiviral and immunomodulatory effects. Antiviral effects may include inhibition of viral replication, protein synthesis, virus maturation, or virus release from infected cells. Previous studies have shown that some coronaviruses are susceptible to interferons. The aim of this study was to evaluate the therapeutic effects of IFN-β-1a administration in COVID-19.
METHODS
In this prospective non-controlled trial, 20 patients included. They received IFN-β-1a at a dose of 44 µg subcutaneously every other day up to 10 days. All patients received conventional therapy including Hydroxychloroquine, and lopinavir/ritonavir. Demographic data, clinical symptoms, virological clearance, and imaging findings recorded during the study.
RESULTS
The mean age of the patients was 58.55 ± 13.43 years. Fever resolved in all patients during first seven days. Although other symptoms decreased gradually. Virological clearance results showed a significant decrease within 10 days. Imaging studies showed significant recovery after 14-day period in all patients. The mean time of hospitalization was 16.8 ± 3.4 days. There were no deaths or significant adverse drug reactions in the 14-day period.
CONCLUSIONS
Our findings support the use of IFN-β-1a in combination with hydroxychloroquine and lopinavir/ritonavir in the management of COVID-19.
CLINICAL TRIAL REGISTRATION NUMBER
IRCT20151227025726N12.
DOI: 10.1016/j.intimp.2020.106688
PubMed: 32544867
PubMed Central: PMC7275997
Links to Exploration step
pubmed:32544867Le document en format XML
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Electronic address: tabarsi@nritld.ac.ir.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32544867</idno><idno type="pmid">32544867</idno><idno type="doi">10.1016/j.intimp.2020.106688</idno><idno type="pmc">PMC7275997</idno><idno type="wicri:Area/Main/Corpus">001395</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001395</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Subcutaneous administration of interferon beta-1a for COVID-19: A non-controlled prospective trial.</title><author><name sortKey="Dastan, Farzaneh" sort="Dastan, Farzaneh" uniqKey="Dastan F" first="Farzaneh" last="Dastan">Farzaneh Dastan</name><affiliation><nlm:affiliation>Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</nlm:affiliation></affiliation></author><author><name sortKey="Nadji, Seyed Alireza" sort="Nadji, Seyed Alireza" uniqKey="Nadji S" first="Seyed Alireza" last="Nadji">Seyed Alireza Nadji</name><affiliation><nlm:affiliation>Virology Research Center, National Institutes of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.</nlm:affiliation></affiliation></author><author><name sortKey="Saffaei, Ali" sort="Saffaei, Ali" uniqKey="Saffaei A" first="Ali" last="Saffaei">Ali Saffaei</name><affiliation><nlm:affiliation>Student Research Committee, Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.</nlm:affiliation></affiliation></author><author><name sortKey="Marjani, Majid" sort="Marjani, Majid" uniqKey="Marjani M" first="Majid" last="Marjani">Majid Marjani</name><affiliation><nlm:affiliation>Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</nlm:affiliation></affiliation></author><author><name sortKey="Moniri, Afshin" sort="Moniri, Afshin" uniqKey="Moniri A" first="Afshin" last="Moniri">Afshin Moniri</name><affiliation><nlm:affiliation>Virology Research Center, National Institutes of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.</nlm:affiliation></affiliation></author><author><name sortKey="Jamaati, Hamidreza" sort="Jamaati, Hamidreza" uniqKey="Jamaati H" first="Hamidreza" last="Jamaati">Hamidreza Jamaati</name><affiliation><nlm:affiliation>Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</nlm:affiliation></affiliation></author><author><name sortKey="Hashemian, Seyed Mohammadreza" sort="Hashemian, Seyed Mohammadreza" uniqKey="Hashemian S" first="Seyed Mohammadreza" last="Hashemian">Seyed Mohammadreza Hashemian</name><affiliation><nlm:affiliation>Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</nlm:affiliation></affiliation></author><author><name sortKey="Baghaei, Parvaneh" sort="Baghaei, Parvaneh" uniqKey="Baghaei P" first="Parvaneh" last="Baghaei">Parvaneh Baghaei</name><affiliation><nlm:affiliation>Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</nlm:affiliation></affiliation></author><author><name sortKey="Abedini, Atefeh" sort="Abedini, Atefeh" uniqKey="Abedini A" first="Atefeh" last="Abedini">Atefeh Abedini</name><affiliation><nlm:affiliation>Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</nlm:affiliation></affiliation></author><author><name sortKey="Varahram, Mohammad" sort="Varahram, Mohammad" uniqKey="Varahram M" first="Mohammad" last="Varahram">Mohammad Varahram</name><affiliation><nlm:affiliation>Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Disease Shahid Beheshti University of Medical Sciences, Tehran, Iran.</nlm:affiliation></affiliation></author><author><name sortKey="Yousefian, Sahar" sort="Yousefian, Sahar" uniqKey="Yousefian S" first="Sahar" last="Yousefian">Sahar Yousefian</name><affiliation><nlm:affiliation>Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</nlm:affiliation></affiliation></author><author><name sortKey="Tabarsi, Payam" sort="Tabarsi, Payam" uniqKey="Tabarsi P" first="Payam" last="Tabarsi">Payam Tabarsi</name><affiliation><nlm:affiliation>Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: tabarsi@nritld.ac.ir.</nlm:affiliation></affiliation></author></analytic><series><title level="j">International immunopharmacology</title><idno type="eISSN">1878-1705</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent (MeSH)</term><term>Adult (MeSH)</term><term>Aged (MeSH)</term><term>Aged, 80 and over (MeSH)</term><term>Antiviral Agents (administration & dosage)</term><term>Antiviral Agents (pharmacology)</term><term>Antiviral Agents (therapeutic use)</term><term>Betacoronavirus (drug effects)</term><term>COVID-19 (MeSH)</term><term>Coronavirus Infections (diagnostic imaging)</term><term>Coronavirus Infections (drug therapy)</term><term>Drug Combinations (MeSH)</term><term>Drug Therapy, Combination (MeSH)</term><term>Female (MeSH)</term><term>Humans (MeSH)</term><term>Hydroxychloroquine (administration & dosage)</term><term>Hydroxychloroquine (therapeutic use)</term><term>Injections, Subcutaneous (MeSH)</term><term>Interferon beta-1a (administration & dosage)</term><term>Interferon beta-1a (pharmacology)</term><term>Interferon beta-1a (therapeutic use)</term><term>Lopinavir (administration & dosage)</term><term>Lopinavir (therapeutic use)</term><term>Lung (diagnostic imaging)</term><term>Male (MeSH)</term><term>Middle Aged (MeSH)</term><term>Pandemics (MeSH)</term><term>Pneumonia, Viral (diagnostic imaging)</term><term>Pneumonia, Viral (drug therapy)</term><term>Prospective Studies (MeSH)</term><term>Ritonavir (administration & dosage)</term><term>Ritonavir (therapeutic use)</term><term>SARS-CoV-2 (MeSH)</term><term>Tomography, X-Ray Computed (MeSH)</term><term>Treatment Outcome (MeSH)</term><term>Young Adult (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antiviral Agents</term><term>Hydroxychloroquine</term><term>Interferon beta-1a</term><term>Lopinavir</term><term>Ritonavir</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Interferon beta-1a</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term><term>Hydroxychloroquine</term><term>Interferon beta-1a</term><term>Lopinavir</term><term>Ritonavir</term></keywords><keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Coronavirus Infections</term><term>Lung</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Betacoronavirus</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>COVID-19</term><term>Drug Combinations</term><term>Drug Therapy, Combination</term><term>Female</term><term>Humans</term><term>Injections, Subcutaneous</term><term>Male</term><term>Middle Aged</term><term>Pandemics</term><term>Prospective Studies</term><term>SARS-CoV-2</term><term>Tomography, X-Ray Computed</term><term>Treatment Outcome</term><term>Young Adult</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>Recently, a new coronavirus spreads rapidly throughout the countries and resulted in a worldwide epidemic. Interferons have direct antiviral and immunomodulatory effects. Antiviral effects may include inhibition of viral replication, protein synthesis, virus maturation, or virus release from infected cells. Previous studies have shown that some coronaviruses are susceptible to interferons. The aim of this study was to evaluate the therapeutic effects of IFN-β-1a administration in COVID-19.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>In this prospective non-controlled trial, 20 patients included. They received IFN-β-1a at a dose of 44 µg subcutaneously every other day up to 10 days. All patients received conventional therapy including Hydroxychloroquine, and lopinavir/ritonavir. Demographic data, clinical symptoms, virological clearance, and imaging findings recorded during the study.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>The mean age of the patients was 58.55 ± 13.43 years. Fever resolved in all patients during first seven days. Although other symptoms decreased gradually. Virological clearance results showed a significant decrease within 10 days. Imaging studies showed significant recovery after 14-day period in all patients. The mean time of hospitalization was 16.8 ± 3.4 days. There were no deaths or significant adverse drug reactions in the 14-day period.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b></p><p>Our findings support the use of IFN-β-1a in combination with hydroxychloroquine and lopinavir/ritonavir in the management of COVID-19.</p></div><div type="abstract" xml:lang="en"><p><b>CLINICAL TRIAL REGISTRATION NUMBER</b></p><p>IRCT20151227025726N12.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32544867</PMID><DateCompleted><Year>2020</Year><Month>07</Month><Day>17</Day></DateCompleted><DateRevised><Year>2021</Year><Month>01</Month><Day>10</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1878-1705</ISSN><JournalIssue CitedMedium="Internet"><Volume>85</Volume><PubDate><Year>2020</Year><Month>Aug</Month></PubDate></JournalIssue><Title>International immunopharmacology</Title><ISOAbbreviation>Int Immunopharmacol</ISOAbbreviation></Journal><ArticleTitle>Subcutaneous administration of interferon beta-1a for COVID-19: A non-controlled prospective trial.</ArticleTitle><Pagination><MedlinePgn>106688</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S1567-5769(20)31289-3</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.intimp.2020.106688</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Recently, a new coronavirus spreads rapidly throughout the countries and resulted in a worldwide epidemic. Interferons have direct antiviral and immunomodulatory effects. Antiviral effects may include inhibition of viral replication, protein synthesis, virus maturation, or virus release from infected cells. Previous studies have shown that some coronaviruses are susceptible to interferons. The aim of this study was to evaluate the therapeutic effects of IFN-β-1a administration in COVID-19.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">In this prospective non-controlled trial, 20 patients included. They received IFN-β-1a at a dose of 44 µg subcutaneously every other day up to 10 days. All patients received conventional therapy including Hydroxychloroquine, and lopinavir/ritonavir. Demographic data, clinical symptoms, virological clearance, and imaging findings recorded during the study.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">The mean age of the patients was 58.55 ± 13.43 years. Fever resolved in all patients during first seven days. Although other symptoms decreased gradually. Virological clearance results showed a significant decrease within 10 days. Imaging studies showed significant recovery after 14-day period in all patients. The mean time of hospitalization was 16.8 ± 3.4 days. There were no deaths or significant adverse drug reactions in the 14-day period.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Our findings support the use of IFN-β-1a in combination with hydroxychloroquine and lopinavir/ritonavir in the management of COVID-19.</AbstractText><AbstractText Label="CLINICAL TRIAL REGISTRATION NUMBER" NlmCategory="BACKGROUND">IRCT20151227025726N12.</AbstractText><CopyrightInformation>Copyright © 2020 Elsevier B.V. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Dastan</LastName><ForeName>Farzaneh</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nadji</LastName><ForeName>Seyed Alireza</ForeName><Initials>SA</Initials><AffiliationInfo><Affiliation>Virology Research Center, National Institutes of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Saffaei</LastName><ForeName>Ali</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Student Research Committee, Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marjani</LastName><ForeName>Majid</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moniri</LastName><ForeName>Afshin</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Virology Research Center, National Institutes of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jamaati</LastName><ForeName>Hamidreza</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hashemian</LastName><ForeName>Seyed MohammadReza</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baghaei</LastName><ForeName>Parvaneh</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Abedini</LastName><ForeName>Atefeh</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Varahram</LastName><ForeName>Mohammad</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Disease Shahid Beheshti University of Medical Sciences, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yousefian</LastName><ForeName>Sahar</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tabarsi</LastName><ForeName>Payam</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: tabarsi@nritld.ac.ir.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016430">Clinical Trial</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>06</Month><Day>07</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Int Immunopharmacol</MedlineTA><NlmUniqueID>100965259</NlmUniqueID><ISSNLinking>1567-5769</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004338">Drug Combinations</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C558899">lopinavir-ritonavir drug combination</NameOfSubstance></Chemical><Chemical><RegistryNumber>2494G1JF75</RegistryNumber><NameOfSubstance UI="D061466">Lopinavir</NameOfSubstance></Chemical><Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber><NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>O3J8G9O825</RegistryNumber><NameOfSubstance UI="D019438">Ritonavir</NameOfSubstance></Chemical><Chemical><RegistryNumber>XRO4566Q4R</RegistryNumber><NameOfSubstance UI="D000068556">Interferon beta-1a</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Protocol" UI="C000705127">COVID-19 drug treatment</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="Y">Betacoronavirus</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004338" MajorTopicYN="N">Drug Combinations</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004359" MajorTopicYN="N">Drug Therapy, Combination</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007279" MajorTopicYN="N">Injections, Subcutaneous</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000068556" MajorTopicYN="N">Interferon beta-1a</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D061466" MajorTopicYN="N">Lopinavir</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008168" MajorTopicYN="N">Lung</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058873" MajorTopicYN="Y">Pandemics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011446" MajorTopicYN="N">Prospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019438" MajorTopicYN="N">Ritonavir</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="N">SARS-CoV-2</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014057" MajorTopicYN="N">Tomography, X-Ray Computed</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword><Keyword MajorTopicYN="N">Coronavirus</Keyword><Keyword MajorTopicYN="N">Interferon Beta-1a</Keyword><Keyword MajorTopicYN="N">Pulmonary infection</Keyword></KeywordList><CoiStatement>Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>04</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>05</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>06</Month><Day>05</Day></PubMedPubDate><PubMedPubDate 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