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Article: Beneficial effect of combinational methylprednisolone and remdesivir in hamster model of SARS-CoV-2 infection

TitleBeneficial effect of combinational methylprednisolone and remdesivir in hamster model of SARS-CoV-2 infection
Authors
KeywordsCOVID-19
SARS-CoV-2
remdesivir
corticosteroid
combination therapy
Issue Date2021
PublisherTaylor & Francis, published in association with Shanghai Shangyixun Cultural Communication Company. The Journal's web site is located at https://www.tandfonline.com/toc/temi20/current
Citation
Emerging Microbes & Infections, 2021, v. 10 n. 1, p. 291-304 How to Cite?
AbstractEffective treatments for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Dexamethasone has been shown to confer survival benefits to certain groups of hospitalized patients, but whether glucocorticoids such as dexamethasone and methylprednisolone should be used together with antivirals to prevent a boost of SARS-CoV-2 replication remains to be determined. Here, we show the beneficial effect of methylprednisolone alone and in combination with remdesivir in the hamster model of SARS-CoV-2 infection. Treatment with methylprednisolone boosted RNA replication of SARS-CoV-2 but suppressed viral induction of proinflammatory cytokines in human monocyte-derived macrophages. Although methylprednisolone monotherapy alleviated body weight loss as well as nasal and pulmonary inflammation, viral loads increased and antibody response against the receptor-binding domain of spike protein attenuated. In contrast, a combination of methylprednisolone with remdesivir not only prevented body weight loss and inflammation, but also dampened viral protein expression and viral loads. In addition, the suppressive effect of methylprednisolone on antibody response was alleviated in the presence of remdesivir. Thus, combinational anti-inflammatory and antiviral therapy might be an effective, safer and more versatile treatment option for COVID-19. These data support testing of the efficacy of a combination of methylprednisolone and remdesivir for the treatment of COVID-19 in randomized controlled clinical trials.
Persistent Identifierhttp://hdl.handle.net/10722/297272
ISSN
2023 Impact Factor: 8.4
2023 SCImago Journal Rankings: 2.316
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYe, ZW-
dc.contributor.authorYuan, S-
dc.contributor.authorChan, JFW-
dc.contributor.authorZhang, AJ-
dc.contributor.authorYu, CY-
dc.contributor.authorONG, CP-
dc.contributor.authorYANG, D-
dc.contributor.authorChan, CCY-
dc.contributor.authorTang, K-
dc.contributor.authorCao, J-
dc.contributor.authorPoon, VKM-
dc.contributor.authorChan, CS-
dc.contributor.authorCai, JP-
dc.contributor.authorChu, H-
dc.contributor.authorYuen, KY-
dc.contributor.authorJin, D-
dc.date.accessioned2021-03-08T07:16:36Z-
dc.date.available2021-03-08T07:16:36Z-
dc.date.issued2021-
dc.identifier.citationEmerging Microbes & Infections, 2021, v. 10 n. 1, p. 291-304-
dc.identifier.issn2222-1751-
dc.identifier.urihttp://hdl.handle.net/10722/297272-
dc.description.abstractEffective treatments for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Dexamethasone has been shown to confer survival benefits to certain groups of hospitalized patients, but whether glucocorticoids such as dexamethasone and methylprednisolone should be used together with antivirals to prevent a boost of SARS-CoV-2 replication remains to be determined. Here, we show the beneficial effect of methylprednisolone alone and in combination with remdesivir in the hamster model of SARS-CoV-2 infection. Treatment with methylprednisolone boosted RNA replication of SARS-CoV-2 but suppressed viral induction of proinflammatory cytokines in human monocyte-derived macrophages. Although methylprednisolone monotherapy alleviated body weight loss as well as nasal and pulmonary inflammation, viral loads increased and antibody response against the receptor-binding domain of spike protein attenuated. In contrast, a combination of methylprednisolone with remdesivir not only prevented body weight loss and inflammation, but also dampened viral protein expression and viral loads. In addition, the suppressive effect of methylprednisolone on antibody response was alleviated in the presence of remdesivir. Thus, combinational anti-inflammatory and antiviral therapy might be an effective, safer and more versatile treatment option for COVID-19. These data support testing of the efficacy of a combination of methylprednisolone and remdesivir for the treatment of COVID-19 in randomized controlled clinical trials.-
dc.languageeng-
dc.publisherTaylor & Francis, published in association with Shanghai Shangyixun Cultural Communication Company. The Journal's web site is located at https://www.tandfonline.com/toc/temi20/current-
dc.relation.ispartofEmerging Microbes & Infections-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCOVID-19-
dc.subjectSARS-CoV-2-
dc.subjectremdesivir-
dc.subjectcorticosteroid-
dc.subjectcombination therapy-
dc.titleBeneficial effect of combinational methylprednisolone and remdesivir in hamster model of SARS-CoV-2 infection-
dc.typeArticle-
dc.identifier.emailYe, ZW: zwye@hku.hk-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailZhang, AJ: zhangajx@hkucc.hku.hk-
dc.identifier.emailTang, K: kmtang20@HKUCC-COM.hku.hk-
dc.identifier.emailPoon, VKM: vinpoon@hku.hk-
dc.identifier.emailChan, CS: cschan@hku.hk-
dc.identifier.emailCai, JP: caijuice@hku.hk-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailJin, D: dyjin@hku.hk-
dc.identifier.authorityYuan, S=rp02640-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityZhang, AJ=rp00413-
dc.identifier.authorityChu, H=rp02125-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityJin, D=rp00452-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1080/22221751.2021.1885998-
dc.identifier.pmid33538646-
dc.identifier.pmcidPMC7919885-
dc.identifier.scopuseid_2-s2.0-85101790573-
dc.identifier.hkuros321583-
dc.identifier.volume10-
dc.identifier.issue1-
dc.identifier.spage291-
dc.identifier.epage304-
dc.identifier.isiWOS:000624955700001-
dc.publisher.placeUnited Kingdom-

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