Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: A retrospective cohort study.
Identifieur interne : 000548 ( Main/Exploration ); précédent : 000547; suivant : 000549Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: A retrospective cohort study.
Auteurs : Andrea Giacomelli [Italie] ; Gabriele Pagani [Italie] ; Anna L. Ridolfo [Italie] ; Letizia Oreni [Italie] ; Federico Conti [Italie] ; Laura Pezzati [Italie] ; Lucia Bradanini [Italie] ; Giacomo Casalini [Italie] ; Cinzia Bassoli [Italie] ; Valentina Morena [Italie] ; Simone Passerini [Italie] ; Giuliano Rizzardini [Italie, Afrique du Sud] ; Chiara Cogliati [Italie] ; Elisa Ceriani [Italie] ; Riccardo Colombo [Italie] ; Stefano Rusconi [Italie] ; Cristina Gervasoni [Italie] ; Dario Cattaneo [Italie] ; Spinello Antinori [Italie] ; Massimo Galli [Italie]Source :
- Journal of medical virology [ 1096-9071 ] ; 2021.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen (MeSH), Antiviraux (usage thérapeutique), Association médicamenteuse (MeSH), Femelle (MeSH), Humains (MeSH), Hydroxychloroquine (usage thérapeutique), Italie (MeSH), Lopinavir (usage thérapeutique), Mâle (MeSH), Ritonavir (usage thérapeutique), Sujet âgé (MeSH), Études rétrospectives (MeSH).
- MESH :
- usage thérapeutique : Antiviraux, Hydroxychloroquine, Lopinavir, Ritonavir.
- Adulte d'âge moyen, Association médicamenteuse, Femelle, Humains, Italie, Mâle, Sujet âgé, Études rétrospectives.
- Wicri :
- geographic : Italie.
English descriptors
- KwdEn :
- Aged (MeSH), Antiviral Agents (therapeutic use), COVID-19 (drug therapy), Drug Combinations (MeSH), Female (MeSH), Humans (MeSH), Hydroxychloroquine (therapeutic use), Italy (MeSH), Lopinavir (therapeutic use), Male (MeSH), Middle Aged (MeSH), Retrospective Studies (MeSH), Ritonavir (therapeutic use), SARS-CoV-2 (drug effects).
- MESH :
- chemical , therapeutic use : Antiviral Agents, Hydroxychloroquine, Lopinavir, Ritonavir.
- geographic : Italy.
- drug effects : SARS-CoV-2.
- drug therapy : COVID-19.
- Aged, Drug Combinations, Female, Humans, Male, Middle Aged, Retrospective Studies.
Abstract
As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID-19 during the first wave of the epidemic in Lombardy, Italy. To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within 5 days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). This was a retrospective intent-to-treat analysis of the hospitalized patients who started LPV/r + HCQ between 21 February and 20 March 2020. The association between the timing of treatment and the probability of 30-day mortality was assessed using univariable and multivariable logistic models. The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray's test P = .213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30-day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50-4.19). Eight percent of the patients discontinued the treatment becausebecause of severe gastrointestinal disorders attributable to LPV/r. The timing of the start of LPV/r + HCQ treatment does not seem to affect the clinical course of hospitalized patients with COVID-19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID-19.
DOI: 10.1002/jmv.26407
PubMed: 32776534
PubMed Central: PMC7436522
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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Sud</country><wicri:regionArea>School of Clinical Medicine, Faculty of Health Science, University of the Witwatersrand, Johannesburg</wicri:regionArea><orgName type="university">Université du Witwatersrand</orgName><placeName><settlement type="city">Johannesbourg</settlement><region type="region" nuts="2">Gauteng</region></placeName></affiliation></author><author><name sortKey="Cogliati, Chiara" sort="Cogliati, Chiara" uniqKey="Cogliati C" first="Chiara" last="Cogliati">Chiara Cogliati</name><affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Luigi Sacco Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Luigi Sacco Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Ceriani, Elisa" sort="Ceriani, 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Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Rusconi, Stefano" sort="Rusconi, Stefano" uniqKey="Rusconi S" first="Stefano" last="Rusconi">Stefano Rusconi</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Gervasoni, Cristina" sort="Gervasoni, Cristina" uniqKey="Gervasoni C" first="Cristina" last="Gervasoni">Cristina Gervasoni</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Cattaneo, Dario" sort="Cattaneo, Dario" uniqKey="Cattaneo D" first="Dario" last="Cattaneo">Dario Cattaneo</name><affiliation wicri:level="3"><nlm:affiliation>Unit of Clinical Pharmacology, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Unit of Clinical Pharmacology, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Antinori, Spinello" sort="Antinori, Spinello" uniqKey="Antinori S" first="Spinello" last="Antinori">Spinello Antinori</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Galli, Massimo" sort="Galli, Massimo" uniqKey="Galli M" first="Massimo" last="Galli">Massimo Galli</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:32776534</idno><idno type="pmid">32776534</idno><idno type="doi">10.1002/jmv.26407</idno><idno type="pmc">PMC7436522</idno><idno type="wicri:Area/Main/Corpus">000F18</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000F18</idno><idno type="wicri:Area/Main/Curation">000F18</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000F18</idno><idno type="wicri:Area/Main/Exploration">000F18</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: A retrospective cohort study.</title><author><name sortKey="Giacomelli, Andrea" sort="Giacomelli, Andrea" uniqKey="Giacomelli A" first="Andrea" last="Giacomelli">Andrea Giacomelli</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Pagani, Gabriele" sort="Pagani, Gabriele" uniqKey="Pagani G" first="Gabriele" last="Pagani">Gabriele Pagani</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Ridolfo, Anna L" sort="Ridolfo, Anna L" uniqKey="Ridolfo A" first="Anna L" last="Ridolfo">Anna L. Ridolfo</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Oreni, Letizia" sort="Oreni, Letizia" uniqKey="Oreni L" first="Letizia" last="Oreni">Letizia Oreni</name><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Conti, Federico" sort="Conti, Federico" uniqKey="Conti F" first="Federico" last="Conti">Federico Conti</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Pezzati, Laura" sort="Pezzati, Laura" uniqKey="Pezzati L" first="Laura" last="Pezzati">Laura Pezzati</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Bradanini, Lucia" sort="Bradanini, Lucia" uniqKey="Bradanini L" first="Lucia" last="Bradanini">Lucia Bradanini</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Casalini, Giacomo" sort="Casalini, Giacomo" uniqKey="Casalini G" first="Giacomo" last="Casalini">Giacomo Casalini</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Bassoli, Cinzia" sort="Bassoli, Cinzia" uniqKey="Bassoli C" first="Cinzia" last="Bassoli">Cinzia Bassoli</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Morena, Valentina" sort="Morena, Valentina" uniqKey="Morena V" first="Valentina" last="Morena">Valentina Morena</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Passerini, Simone" sort="Passerini, Simone" uniqKey="Passerini S" first="Simone" last="Passerini">Simone Passerini</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Rizzardini, Giuliano" sort="Rizzardini, Giuliano" uniqKey="Rizzardini G" first="Giuliano" last="Rizzardini">Giuliano Rizzardini</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="4"><nlm:affiliation>School of Clinical Medicine, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa.</nlm:affiliation><country xml:lang="fr">Afrique du Sud</country><wicri:regionArea>School of Clinical Medicine, Faculty of Health Science, University of the Witwatersrand, Johannesburg</wicri:regionArea><orgName type="university">Université du Witwatersrand</orgName><placeName><settlement type="city">Johannesbourg</settlement><region type="region" nuts="2">Gauteng</region></placeName></affiliation></author><author><name sortKey="Cogliati, Chiara" sort="Cogliati, Chiara" uniqKey="Cogliati C" first="Chiara" last="Cogliati">Chiara Cogliati</name><affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Luigi Sacco Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Luigi Sacco Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Ceriani, Elisa" sort="Ceriani, Elisa" uniqKey="Ceriani E" first="Elisa" last="Ceriani">Elisa Ceriani</name><affiliation wicri:level="3"><nlm:affiliation>Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Luigi Sacco Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Luigi Sacco Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Colombo, Riccardo" sort="Colombo, Riccardo" uniqKey="Colombo R" first="Riccardo" last="Colombo">Riccardo Colombo</name><affiliation wicri:level="3"><nlm:affiliation>Department of Anesthesiology and Intensive Care, ASST Fatebenefratelli-Sacco, Luigi Sacco Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Anesthesiology and Intensive Care, ASST Fatebenefratelli-Sacco, Luigi Sacco Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Rusconi, Stefano" sort="Rusconi, Stefano" uniqKey="Rusconi S" first="Stefano" last="Rusconi">Stefano Rusconi</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Gervasoni, Cristina" sort="Gervasoni, Cristina" uniqKey="Gervasoni C" first="Cristina" last="Gervasoni">Cristina Gervasoni</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Cattaneo, Dario" sort="Cattaneo, Dario" uniqKey="Cattaneo D" first="Dario" last="Cattaneo">Dario Cattaneo</name><affiliation wicri:level="3"><nlm:affiliation>Unit of Clinical Pharmacology, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Unit of Clinical Pharmacology, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Antinori, Spinello" sort="Antinori, Spinello" uniqKey="Antinori S" first="Spinello" last="Antinori">Spinello Antinori</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Galli, Massimo" sort="Galli, Massimo" uniqKey="Galli M" first="Massimo" last="Galli">Massimo Galli</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan</wicri:regionArea><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author></analytic><series><title level="j">Journal of medical virology</title><idno type="eISSN">1096-9071</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged (MeSH)</term><term>Antiviral Agents (therapeutic use)</term><term>COVID-19 (drug therapy)</term><term>Drug Combinations (MeSH)</term><term>Female (MeSH)</term><term>Humans (MeSH)</term><term>Hydroxychloroquine (therapeutic use)</term><term>Italy (MeSH)</term><term>Lopinavir (therapeutic use)</term><term>Male (MeSH)</term><term>Middle Aged (MeSH)</term><term>Retrospective Studies (MeSH)</term><term>Ritonavir (therapeutic use)</term><term>SARS-CoV-2 (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen (MeSH)</term><term>Antiviraux (usage thérapeutique)</term><term>Association médicamenteuse (MeSH)</term><term>Femelle (MeSH)</term><term>Humains (MeSH)</term><term>Hydroxychloroquine (usage thérapeutique)</term><term>Italie (MeSH)</term><term>Lopinavir (usage thérapeutique)</term><term>Mâle (MeSH)</term><term>Ritonavir (usage thérapeutique)</term><term>Sujet âgé (MeSH)</term><term>Études rétrospectives (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term><term>Hydroxychloroquine</term><term>Lopinavir</term><term>Ritonavir</term></keywords><keywords scheme="MESH" type="geographic" xml:lang="en"><term>Italy</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS-CoV-2</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antiviraux</term><term>Hydroxychloroquine</term><term>Lopinavir</term><term>Ritonavir</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Drug Combinations</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Retrospective Studies</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Association médicamenteuse</term><term>Femelle</term><term>Humains</term><term>Italie</term><term>Mâle</term><term>Sujet âgé</term><term>Études rétrospectives</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Italie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID-19 during the first wave of the epidemic in Lombardy, Italy. To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within 5 days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). This was a retrospective intent-to-treat analysis of the hospitalized patients who started LPV/r + HCQ between 21 February and 20 March 2020. The association between the timing of treatment and the probability of 30-day mortality was assessed using univariable and multivariable logistic models. The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray's test P = .213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30-day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50-4.19). Eight percent of the patients discontinued the treatment becausebecause of severe gastrointestinal disorders attributable to LPV/r. The timing of the start of LPV/r + HCQ treatment does not seem to affect the clinical course of hospitalized patients with COVID-19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID-19.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32776534</PMID><DateCompleted><Year>2021</Year><Month>03</Month><Day>08</Day></DateCompleted><DateRevised><Year>2021</Year><Month>03</Month><Day>08</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1096-9071</ISSN><JournalIssue CitedMedium="Internet"><Volume>93</Volume><Issue>3</Issue><PubDate><Year>2021</Year><Month>03</Month></PubDate></JournalIssue><Title>Journal of medical virology</Title><ISOAbbreviation>J Med Virol</ISOAbbreviation></Journal><ArticleTitle>Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: A retrospective cohort study.</ArticleTitle><Pagination><MedlinePgn>1421-1427</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/jmv.26407</ELocationID><Abstract><AbstractText>As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID-19 during the first wave of the epidemic in Lombardy, Italy. To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within 5 days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). This was a retrospective intent-to-treat analysis of the hospitalized patients who started LPV/r + HCQ between 21 February and 20 March 2020. The association between the timing of treatment and the probability of 30-day mortality was assessed using univariable and multivariable logistic models. The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray's test P = .213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30-day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50-4.19). Eight percent of the patients discontinued the treatment becausebecause of severe gastrointestinal disorders attributable to LPV/r. The timing of the start of LPV/r + HCQ treatment does not seem to affect the clinical course of hospitalized patients with COVID-19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID-19.</AbstractText><CopyrightInformation>© 2020 Wiley Periodicals LLC.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Giacomelli</LastName><ForeName>Andrea</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0003-3685-4289</Identifier><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pagani</LastName><ForeName>Gabriele</ForeName><Initials>G</Initials><Identifier Source="ORCID">0000-0002-1668-7543</Identifier><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ridolfo</LastName><ForeName>Anna L</ForeName><Initials>AL</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oreni</LastName><ForeName>Letizia</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Conti</LastName><ForeName>Federico</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pezzati</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bradanini</LastName><ForeName>Lucia</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Casalini</LastName><ForeName>Giacomo</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bassoli</LastName><ForeName>Cinzia</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Morena</LastName><ForeName>Valentina</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Passerini</LastName><ForeName>Simone</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rizzardini</LastName><ForeName>Giuliano</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Clinical Medicine, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cogliati</LastName><ForeName>Chiara</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Luigi Sacco Hospital, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ceriani</LastName><ForeName>Elisa</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Luigi Sacco Hospital, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Colombo</LastName><ForeName>Riccardo</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Anesthesiology and Intensive Care, ASST Fatebenefratelli-Sacco, Luigi Sacco Hospital, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rusconi</LastName><ForeName>Stefano</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0002-0375-9990</Identifier><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gervasoni</LastName><ForeName>Cristina</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cattaneo</LastName><ForeName>Dario</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Unit of Clinical Pharmacology, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Antinori</LastName><ForeName>Spinello</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Galli</LastName><ForeName>Massimo</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan, Milan, Italy.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>09</Month><Day>28</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Med Virol</MedlineTA><NlmUniqueID>7705876</NlmUniqueID><ISSNLinking>0146-6615</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>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></ChemicalList><SupplMeshList><SupplMeshName Type="Protocol" UI="C000705127">COVID-19 drug treatment</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004338" MajorTopicYN="N">Drug Combinations</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="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007558" MajorTopicYN="N" Type="Geographic">Italy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D061466" MajorTopicYN="N">Lopinavir</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012189" MajorTopicYN="N">Retrospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019438" MajorTopicYN="N">Ritonavir</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="N">SARS-CoV-2</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">COVID-19</Keyword><Keyword MajorTopicYN="Y">antiviral treatment</Keyword><Keyword MajorTopicYN="Y">early</Keyword><Keyword MajorTopicYN="Y">hydroxychloroquine</Keyword><Keyword MajorTopicYN="Y">lopinavir</Keyword><Keyword MajorTopicYN="Y">mortality</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>06</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>08</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>8</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>3</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>8</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32776534</ArticleId><ArticleId IdType="doi">10.1002/jmv.26407</ArticleId><ArticleId IdType="pmc">PMC7436522</ArticleId></ArticleIdList><ReferenceList><Title>REFERENCES</Title><Reference><Citation>World Health Organization. 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Journal of Antimicrobial Chemotherapy. 2020. http://doi.org/10.1093/jac/dkaa190</Citation></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>Afrique du Sud</li><li>Italie</li></country><region><li>Gauteng</li><li>Lombardie</li></region><settlement><li>Johannesbourg</li><li>Milan</li></settlement><orgName><li>Université du Witwatersrand</li></orgName></list><tree><country name="Italie"><region name="Lombardie"><name sortKey="Giacomelli, Andrea" sort="Giacomelli, Andrea" uniqKey="Giacomelli A" first="Andrea" last="Giacomelli">Andrea Giacomelli</name></region><name sortKey="Antinori, Spinello" sort="Antinori, Spinello" uniqKey="Antinori S" first="Spinello" last="Antinori">Spinello Antinori</name><name sortKey="Antinori, Spinello" sort="Antinori, Spinello" uniqKey="Antinori S" first="Spinello" last="Antinori">Spinello Antinori</name><name sortKey="Bassoli, Cinzia" sort="Bassoli, Cinzia" uniqKey="Bassoli C" first="Cinzia" last="Bassoli">Cinzia Bassoli</name><name sortKey="Bassoli, Cinzia" sort="Bassoli, Cinzia" uniqKey="Bassoli C" first="Cinzia" last="Bassoli">Cinzia Bassoli</name><name sortKey="Bradanini, Lucia" sort="Bradanini, Lucia" uniqKey="Bradanini L" first="Lucia" last="Bradanini">Lucia Bradanini</name><name sortKey="Bradanini, Lucia" sort="Bradanini, Lucia" uniqKey="Bradanini L" first="Lucia" last="Bradanini">Lucia Bradanini</name><name sortKey="Casalini, Giacomo" sort="Casalini, Giacomo" uniqKey="Casalini G" first="Giacomo" last="Casalini">Giacomo Casalini</name><name sortKey="Casalini, Giacomo" sort="Casalini, Giacomo" uniqKey="Casalini G" first="Giacomo" last="Casalini">Giacomo Casalini</name><name sortKey="Cattaneo, Dario" sort="Cattaneo, Dario" uniqKey="Cattaneo D" first="Dario" last="Cattaneo">Dario Cattaneo</name><name sortKey="Ceriani, Elisa" sort="Ceriani, Elisa" uniqKey="Ceriani E" first="Elisa" last="Ceriani">Elisa Ceriani</name><name sortKey="Cogliati, Chiara" sort="Cogliati, Chiara" uniqKey="Cogliati C" first="Chiara" last="Cogliati">Chiara Cogliati</name><name sortKey="Colombo, Riccardo" sort="Colombo, Riccardo" uniqKey="Colombo R" first="Riccardo" last="Colombo">Riccardo Colombo</name><name sortKey="Conti, Federico" sort="Conti, Federico" uniqKey="Conti F" first="Federico" last="Conti">Federico Conti</name><name sortKey="Conti, Federico" sort="Conti, Federico" uniqKey="Conti F" first="Federico" last="Conti">Federico Conti</name><name sortKey="Galli, Massimo" sort="Galli, Massimo" uniqKey="Galli M" first="Massimo" last="Galli">Massimo Galli</name><name sortKey="Galli, Massimo" sort="Galli, Massimo" uniqKey="Galli M" first="Massimo" last="Galli">Massimo Galli</name><name sortKey="Gervasoni, Cristina" sort="Gervasoni, Cristina" uniqKey="Gervasoni C" first="Cristina" last="Gervasoni">Cristina Gervasoni</name><name sortKey="Giacomelli, Andrea" sort="Giacomelli, Andrea" uniqKey="Giacomelli A" first="Andrea" last="Giacomelli">Andrea Giacomelli</name><name sortKey="Morena, Valentina" sort="Morena, Valentina" uniqKey="Morena V" first="Valentina" last="Morena">Valentina Morena</name><name sortKey="Morena, Valentina" sort="Morena, Valentina" uniqKey="Morena V" first="Valentina" last="Morena">Valentina Morena</name><name sortKey="Oreni, Letizia" sort="Oreni, Letizia" uniqKey="Oreni L" first="Letizia" last="Oreni">Letizia Oreni</name><name sortKey="Pagani, Gabriele" sort="Pagani, Gabriele" uniqKey="Pagani G" first="Gabriele" last="Pagani">Gabriele Pagani</name><name sortKey="Pagani, Gabriele" sort="Pagani, Gabriele" uniqKey="Pagani G" first="Gabriele" last="Pagani">Gabriele Pagani</name><name sortKey="Passerini, Simone" sort="Passerini, Simone" uniqKey="Passerini S" first="Simone" last="Passerini">Simone Passerini</name><name sortKey="Pezzati, Laura" sort="Pezzati, Laura" uniqKey="Pezzati L" first="Laura" last="Pezzati">Laura Pezzati</name><name sortKey="Pezzati, Laura" sort="Pezzati, Laura" uniqKey="Pezzati L" first="Laura" last="Pezzati">Laura Pezzati</name><name sortKey="Ridolfo, Anna L" sort="Ridolfo, Anna L" uniqKey="Ridolfo A" first="Anna L" last="Ridolfo">Anna L. Ridolfo</name><name sortKey="Rizzardini, Giuliano" sort="Rizzardini, Giuliano" uniqKey="Rizzardini G" first="Giuliano" last="Rizzardini">Giuliano Rizzardini</name><name sortKey="Rusconi, Stefano" sort="Rusconi, Stefano" uniqKey="Rusconi S" first="Stefano" last="Rusconi">Stefano Rusconi</name><name sortKey="Rusconi, Stefano" sort="Rusconi, Stefano" uniqKey="Rusconi S" first="Stefano" last="Rusconi">Stefano Rusconi</name></country><country name="Afrique du Sud"><region name="Gauteng"><name sortKey="Rizzardini, Giuliano" sort="Rizzardini, Giuliano" uniqKey="Rizzardini G" first="Giuliano" last="Rizzardini">Giuliano Rizzardini</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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