COVID-19 medical therapy: Difference between revisions
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'''For COVID-19 frequently asked inpatient questions, click [[COVID-19 frequently asked inpatient questions|here]]'''<br>'''For COVID-19 frequently asked outpatient questions, click [[COVID-19 frequently asked outpatient questions|here]]'''<br> | '''For COVID-19 frequently asked inpatient questions, click [[COVID-19 frequently asked inpatient questions|here]]'''<br>'''For COVID-19 frequently asked outpatient questions, click [[COVID-19 frequently asked outpatient questions|here]]'''<br> | ||
__NOTOC__{{COVID-19}} | __NOTOC__{{COVID-19}} | ||
{{CMG}}; {{AE}} {{Sara.Zand}}, {{HK}}, {{Sab}} | {{CMG}}; {{AE}} {{Sara.Zand}}, {{HK}},{{Sab}} | ||
==Overview== | ==Overview== | ||
[[COVID-19]] is an inflammatory [[hypercytokinemia]] disease. The aim of therapy is prevention of [[viral replication]] and controlling the [[inflammatory]] process | [[COVID-19]] is an inflammatory [[hypercytokinemia]] disease. The aim of therapy is prevention of [[viral replication]] and controlling the [[inflammatory]] process.<br /> | ||
== Antiviral Agents == | == Antiviral Agents == | ||
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*[[Remdesivir]] is a [[prodrug]] and inhibits viral [[RNA polymerase]] when intracellularly metabolized to an [[ATP analog|ATP analog.]] | *[[Remdesivir]] is a [[prodrug]] and inhibits viral [[RNA polymerase]] when intracellularly metabolized to an [[ATP analog|ATP analog.]] | ||
*[[Remdesivir]] has been effective on [[MERS|MERS-COV]],[[EBOLA]], [[SARS-COV1]]. | *[[Remdesivir]] has been effective on [[MERS|MERS-COV]],[[EBOLA]], [[SARS-COV1]]. | ||
* Effects of [[remdesivir]] in [[COVID-19]] include : | * Effects of [[remdesivir]] in [[COVID-19]] include : | ||
# Significant reduction in viral load in [[bronchoaleolar lavage]] | # Significant reduction in viral load in [[bronchoaleolar lavage]] | ||
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*[[Remdesivir]] Indicates only for [[in-hospital]] setting in Severe [[COVID-19]] disease. | *[[Remdesivir]] Indicates only for [[in-hospital]] setting in Severe [[COVID-19]] disease. | ||
*The recommended dose of [[remdesivir]] in [[COVID-19]] is: | *The recommended dose of [[remdesivir]] in [[COVID-19]] is: | ||
** Adult dosing (wt > 40 kg): 200 mg IV loading dose on day 1, then 100 mg IV daily maintenance dose | ** Adult dosing (wt > 40 kg): 200 mg IV loading dose on day 1, then 100 mg IV daily maintenance dose | ||
*** Infuse each dose over 30-120 min | *** Infuse each dose over 30-120 min | ||
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=== Hydroxychloroquine and Chloroquine === | === Hydroxychloroquine and Chloroquine === | ||
*[[Hydroxychloroquine]] has been effective in [[graft versus host disease]] ,[[lupus erythematosus]], [[rheumatoid arthritis]], and [[malaria]] | *[[Hydroxychloroquine]] has been effective in [[graft versus host disease]] ,[[lupus erythematosus]], [[rheumatoid arthritis]], and [[malaria]] | ||
*In the begining of COVID-19 pandemic ,[[hydroxychloroquine]] was used due to inhibition of the entry of [[SARS-COV-2]] and prevention of the fusion of viral [[spike protein]] to ACE2 receptor and reduction of cytokine storm. | *In the begining of COVID-19 pandemic ,[[hydroxychloroquine]] was used due to inhibition of the entry of [[SARS-COV-2]] and prevention of the fusion of viral [[spike protein]] to ACE2 receptor and reduction of cytokine storm. | ||
*Intracellular uptake of [[hydroxychloroquine]] was enhanced with combination with Zinc. | *Intracellular uptake of [[hydroxychloroquine]] was enhanced with combination with Zinc. | ||
*[[Hydroxychloroquine]] has cardiac side effects due to QT prolongation effect. | *[[Hydroxychloroquine]] has cardiac side effects due to QT prolongation effect. | ||
*Efficacy of [[remdesivir]] is reduced in combination with [[Hydroxychroroquine|hydroxychroroquine.]] | *Efficacy of [[remdesivir]] is reduced in combination with [[Hydroxychroroquine|hydroxychroroquine.]] | ||
*Due to cardiac side effects, recently [[FDA]] dissapproved the emergency use authorization of [[hydroxychloroquine]] if clinical trials are unavailable. | *Due to cardiac side effects, recently [[FDA]] dissapproved the emergency use authorization of [[hydroxychloroquine]] if clinical trials are unavailable. | ||
*[[Hydroxychloroquine]] foe early treatment of adults with mild [[COVID-19]] does not improve outcomes in modest sized unblinded randomized controlled trial. | |||
=== Lopinavir-Ritonavir or kalerta === | === Lopinavir-Ritonavir or kalerta === | ||
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* To date (08/07/2020), there is no proven efficacy of [[lopinavir]]-[[ritonavir]] for [[COVID-19]] management | * To date (08/07/2020), there is no proven efficacy of [[lopinavir]]-[[ritonavir]] for [[COVID-19]] management | ||
*Lopinavir-Ritonavir Inhibits the activity of the HIV-1 protease. | *Lopinavir-Ritonavir Inhibits the activity of the HIV-1 protease. | ||
* In an open-label randomized controlled trial, the comparison between patients with [[COVID-19]] received either lopinavir-ritonavir 400/100 mg, orally twice daily plus standard of care or standard care alone showed no benefit of administration of [[lopinavir-ritonavir]] | * In an open-label randomized controlled trial, the comparison between patients with [[COVID-19]] received either lopinavir-ritonavir 400/100 mg, orally twice daily plus standard of care or standard care alone showed no benefit of administration of [[lopinavir-ritonavir]] | ||
* Only one study in Korea in the initial phase of outbreak accepted using this combination. | * Only one study in Korea in the initial phase of outbreak accepted using this combination. | ||
* Side effects: [[Diarrhea]], [[nausea]], [[asthenia]] | * Side effects: [[Diarrhea]], [[nausea]], [[asthenia]] | ||
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*To date (08/07/2020), there is no proven efficacy of umifenovir for [[COVID-19]] management | *To date (08/07/2020), there is no proven efficacy of umifenovir for [[COVID-19]] management | ||
*[[Umifenovir]] has been used in treatment of [[Ebola]] virus, [[human herpesvirus 8 (HHV-8)]], [[hepatitis C virus]] ([[HCV)]], and [[Tacaribe arenavirus]], [[influenza A,B]] | *[[Umifenovir]] has been used in treatment of [[Ebola]] virus, [[human herpesvirus 8 (HHV-8)]], [[hepatitis C virus]] ([[HCV)]], and [[Tacaribe arenavirus]], [[influenza A,B]] | ||
* Mechanism of action: inhibition of the virus fusion to the cell membrane and hydrogen binding to [[membrance phospholipids]]. | * Mechanism of action: inhibition of the virus fusion to the cell membrane and hydrogen binding to [[membrance phospholipids]]. | ||
* In a retrospective cohort study showed improvement in chest ct scan of COVID-19 patients received a combination of umifenovir and lopinavir-ritonavir. | * In a retrospective cohort study showed improvement in chest ct scan of COVID-19 patients received a combination of umifenovir and lopinavir-ritonavir. | ||
* In prospective study, [[umifenovir]] had inferior outcomes in clinical recovery rate and relief of fever and [[cough]] compared with [[favipiravir]] | * In prospective study, [[umifenovir]] had inferior outcomes in clinical recovery rate and relief of fever and [[cough]] compared with [[favipiravir]] | ||
* Safety and efficacy in COVID-19 is under investigation in china with two randomized open trials. | * Safety and efficacy in COVID-19 is under investigation in china with two randomized open trials. | ||
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*To date (08/07/2020), there is no proven efficacy of [[Favipiravir covid-19|favipiravir]] for [[COVID-19]] management | *To date (08/07/2020), there is no proven efficacy of [[Favipiravir covid-19|favipiravir]] for [[COVID-19]] management | ||
*[[Favipiravir]] has been used in 2014 in Japan for the treatment of influenza resistant to [[neuraminidase inhibitors]] and has been used in the treatment of infectious diseases caused by RNA viruses such as influenza, [[Ebola]], and norovirus | *[[Favipiravir]] has been used in 2014 in Japan for the treatment of influenza resistant to [[neuraminidase inhibitors]] and has been used in the treatment of infectious diseases caused by RNA viruses such as influenza, [[Ebola]], and norovirus '''''' | ||
* Mechanism of action: after entering the infected cells and being phosphorylated, inhibits viral [[RNA replication]]. | * Mechanism of action: after entering the infected cells and being phosphorylated, inhibits viral [[RNA replication]]. | ||
*[[SARS-CoV-2]] is an enveloped, positive-sense, single-strand RNA virus and studies showed the efficacy of favipiravir on [[SARS-COV-2.]] | *[[SARS-CoV-2]] is an enveloped, positive-sense, single-strand RNA virus and studies showed the efficacy of favipiravir on [[SARS-COV-2.]] | ||
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*To date (08/07/2020), there is no proven efficacy of [[oseltamivir]] for [[COVID-19]] management | *To date (08/07/2020), there is no proven efficacy of [[oseltamivir]] for [[COVID-19]] management | ||
*[[Oseltamivir]] has been approved for the treatment of [[influenza]] A,B viruses and inhibits [[neuraminidase glygoprotein]] which is essential for replication of [[influenza A and B]] viruses | *[[Oseltamivir]] has been approved for the treatment of [[influenza]] A,B viruses and inhibits [[neuraminidase glygoprotein]] which is essential for replication of [[influenza A and B]] viruses | ||
* The study in wohan showed no positive outcomes were observed in [[COVID-19]] patients after recieving [[osetamivir]] | * The study in wohan showed no positive outcomes were observed in [[COVID-19]] patients after recieving [[osetamivir]] | ||
* A clinical trial is investigating the efficacy of combination between [[Oseltamivir]] with [[chloroquine]] and [[favipiravir]] . | * A clinical trial is investigating the efficacy of combination between [[Oseltamivir]] with [[chloroquine]] and [[favipiravir]] . | ||
== Supportive Agents == | == Supportive Agents == | ||
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*To date (08/07/2020), there is no proven efficacy of [[azithromycin]] for [[COVID-19]] management | *To date (08/07/2020), there is no proven efficacy of [[azithromycin]] for [[COVID-19]] management | ||
*[[Azithromycin]] has been effective in the treatment of [[Zika]] and [[Ebola]] viruses and prevented severe respiratory tract infection | *[[Azithromycin]] has been effective in the treatment of [[Zika]] and [[Ebola]] viruses and prevented severe respiratory tract infection | ||
* Mechanism of action is binding to [[50S subunit]] of the [[bacteria ribosom]],then inhibition of translation of [[mRNA]]. | * Mechanism of action is binding to [[50S subunit]] of the [[bacteria ribosom]],then inhibition of translation of [[mRNA]]. | ||
* Effects of [[azithromycin]] in treatment of viral respiratory tract infection include:1. antibacterial coverage 2.immunomodulatory and anti-inflammatory effects. | * Effects of [[azithromycin]] in treatment of viral respiratory tract infection include:1. antibacterial coverage 2.immunomodulatory and anti-inflammatory effects. | ||
* Many trials in [[COVID-19]] patients showed the effectiveness of [[azithromycin]] combined with [[hydroxychloroquine]]. | * Many trials in [[COVID-19]] patients showed the effectiveness of [[azithromycin]] combined with [[hydroxychloroquine]]. | ||
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* To date (08/07/2020), there is no proven efficacy of [[vitamin C]] for [[COVID-19]] management | * To date (08/07/2020), there is no proven efficacy of [[vitamin C]] for [[COVID-19]] management | ||
* Effects of [[Vitamin C]] in viral agents include''': | * Effects of [[Vitamin C]] in viral agents include''':''' | ||
# Maturation of [[T lymphocytes]] and [[NK]]( [[natural killer]]) cells which are involved in the immune response to viral agents. | # Maturation of [[T lymphocytes]] and [[NK]]( [[natural killer]]) cells which are involved in the immune response to viral agents. | ||
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# Remodulation of the [[cytokine]] network in systemic inflammatory syndrome. | # Remodulation of the [[cytokine]] network in systemic inflammatory syndrome. | ||
* Study in [[COVID-19]] patients in china showed administration of high dose IV,[[Vitamin C]] (1500mg per day) in moderate and severe cases was correlated with improvement in [[oxygenation indexes]] and recovery . | * Study in [[COVID-19]] patients in china showed administration of high dose IV,[[Vitamin C]] (1500mg per day) in moderate and severe cases was correlated with improvement in [[oxygenation indexes]] and recovery . | ||
===[[Corticosteroids]]=== | ===[[Corticosteroids]]=== | ||
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==== Methylprednisolone ==== | ==== Methylprednisolone ==== | ||
* Effects of low doses of [[methylprednisolone]] in [[COVID-19]] include: | * Effects of low doses of [[methylprednisolone]] in [[COVID-19]] include: | ||
# Controlled of [[hypercytokinemia]] | # Controlled of [[hypercytokinemia]] | ||
# Anti-inflammatory effect in superimposed infection in [[COVID-19]] | # Anti-inflammatory effect in superimposed infection in [[COVID-19]] | ||
# Increased blood pressure when it is low | # Increased blood pressure when it is low | ||
# Decreased risk of death in [[ARDS]] related [[COVID-19]] | # Decreased risk of death in [[ARDS]] related [[COVID-19]] | ||
==== Dexamethasone ==== | ==== Dexamethasone ==== | ||
* The recommended [[dose]] of [[dexamethasone]] for [[COVID-19]] is 6 mg IV once daily or po x 10 days<ref name="urlSanford Guide" /> | * The recommended [[dose]] of [[dexamethasone]] for [[COVID-19]] is 6 mg IV once daily or po x 10 days<ref name="urlSanford Guide" /> | ||
* Effects of [[Dexamethasone|dexamethason]] in [[ARDS]] related [[COVID-19]] include: | * Effects of [[Dexamethasone|dexamethason]] in [[ARDS]] related [[COVID-19]] include: <ref name="pmid32043983">{{cite journal |vauthors=Russell CD, Millar JE, Baillie JK |title=Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury |journal=Lancet |volume=395 |issue=10223 |pages=473–475 |date=February 2020 |pmid=32043983 |pmc=7134694 |doi=10.1016/S0140-6736(20)30317-2 |url=}}</ref> | ||
# Decreased days of [[intubation]] | # Decreased days of [[intubation]] | ||
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* To date (08/07/2020), there is no proven efficacy of [[niclosamide]] and [[ivermectin]] for [[COVID-19]] management | * To date (08/07/2020), there is no proven efficacy of [[niclosamide]] and [[ivermectin]] for [[COVID-19]] management | ||
*Mechanism of action is Inhibition of binding of [[Coronavirus, SARS associated|coronavirus]] onto the cells. | *Mechanism of action is Inhibition of binding of [[Coronavirus, SARS associated|coronavirus]] onto the cells. | ||
*[[Niclosamid]] inhibits replication of [[MERS-COV]] AND [[SARS-COV-2|SARS-COV-2.]] | *[[Niclosamid]] inhibits replication of [[MERS-COV]] AND [[SARS-COV-2|SARS-COV-2.]] | ||
*[[Ivermectin]] inhibits viral replication in dengue virus, [[flavivirus]],[[influenza]]. <ref name="pmid31852899">{{cite journal |vauthors=Gassen NC, Niemeyer D, Muth D, Corman VM, Martinelli S, Gassen A, Hafner K, Papies J, Mösbauer K, Zellner A, Zannas AS, Herrmann A, Holsboer F, Brack-Werner R, Boshart M, Müller-Myhsok B, Drosten C, Müller MA, Rein T |title=SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection |journal=Nat Commun |volume=10 |issue=1 |pages=5770 |date=December 2019 |pmid=31852899 |pmc=6920372 |doi=10.1038/s41467-019-13659-4 |url=}}</ref> | *[[Ivermectin]] inhibits viral replication in dengue virus, [[flavivirus]],[[influenza]]. <ref name="pmid31852899">{{cite journal |vauthors=Gassen NC, Niemeyer D, Muth D, Corman VM, Martinelli S, Gassen A, Hafner K, Papies J, Mösbauer K, Zellner A, Zannas AS, Herrmann A, Holsboer F, Brack-Werner R, Boshart M, Müller-Myhsok B, Drosten C, Müller MA, Rein T |title=SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection |journal=Nat Commun |volume=10 |issue=1 |pages=5770 |date=December 2019 |pmid=31852899 |pmc=6920372 |doi=10.1038/s41467-019-13659-4 |url=}}</ref> | ||
* FDA approved Ivermectin for treatment of SARS-COV-2. Study showed [[Ivermectin]] inhibited [[SARS-COV-2]] replication up to 5000 fold at 48 h in vitro. | * FDA approved Ivermectin for treatment of SARS-COV-2. Study showed [[Ivermectin]] inhibited [[SARS-COV-2]] replication up to 5000 fold at 48 h in vitro. | ||
=== Convalescent Plasma === | === Convalescent Plasma === | ||
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*Convalescent Plasma is Transfusion of plasma loaded with antibodies after improvement from [[COVID-19]]. | *Convalescent Plasma is Transfusion of plasma loaded with antibodies after improvement from [[COVID-19]]. | ||
* Studies in Taiwan and South Korea showed clinical benefits in severe cases of [[SARS-COV]] and [[MERS]] | * Studies in Taiwan and South Korea showed clinical benefits in severe cases of [[SARS-COV]] and [[MERS]] | ||
* Pilot study in [[COVID19]] showed symptoms improvement including [[fever]], [[cough]], [[tightness of breath]],[[chest pain]]. | * Pilot study in [[COVID19]] showed symptoms improvement including [[fever]], [[cough]], [[tightness of breath]],[[chest pain]]. | ||
* Serious side effects were not reported.<ref name="pmid32253318">{{cite journal |vauthors=Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, Zhou M, Chen L, Meng S, Hu Y, Peng C, Yuan M, Huang J, Wang Z, Yu J, Gao X, Wang D, Yu X, Li L, Zhang J, Wu X, Li B, Xu Y, Chen W, Peng Y, Hu Y, Lin L, Liu X, Huang S, Zhou Z, Zhang L, Wang Y, Zhang Z, Deng K, Xia Z, Gong Q, Zhang W, Zheng X, Liu Y, Yang H, Zhou D, Yu D, Hou J, Shi Z, Chen S, Chen Z, Zhang X, Yang X |title=Effectiveness of convalescent plasma therapy in severe COVID-19 patients |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=117 |issue=17 |pages=9490–9496 |date=April 2020 |pmid=32253318 |pmc=7196837 |doi=10.1073/pnas.2004168117 |url=}}</ref> | * Serious side effects were not reported.<ref name="pmid32253318">{{cite journal |vauthors=Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, Zhou M, Chen L, Meng S, Hu Y, Peng C, Yuan M, Huang J, Wang Z, Yu J, Gao X, Wang D, Yu X, Li L, Zhang J, Wu X, Li B, Xu Y, Chen W, Peng Y, Hu Y, Lin L, Liu X, Huang S, Zhou Z, Zhang L, Wang Y, Zhang Z, Deng K, Xia Z, Gong Q, Zhang W, Zheng X, Liu Y, Yang H, Zhou D, Yu D, Hou J, Shi Z, Chen S, Chen Z, Zhang X, Yang X |title=Effectiveness of convalescent plasma therapy in severe COVID-19 patients |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=117 |issue=17 |pages=9490–9496 |date=April 2020 |pmid=32253318 |pmc=7196837 |doi=10.1073/pnas.2004168117 |url=}}</ref> | ||
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*In COVID-19 hypercoagulable state induces micro-macro-vascular [[thrombosis]]. | *In COVID-19 hypercoagulable state induces micro-macro-vascular [[thrombosis]]. | ||
* Predictors of poor outcome in COVID-19 include: Disseminated intravascular [[Coagulopathy|coagulation]] , high level of [[D-dimer]]. | * Predictors of poor outcome in COVID-19 include: Disseminated intravascular [[Coagulopathy|coagulation]] , high level of [[D-dimer]]. | ||
*[[Mortality]] with [[anticoagulant therapy]] was decreased in COVID-19. | *[[Mortality]] with [[anticoagulant therapy]] was decreased in COVID-19. | ||
* Efficacy of [[heparin]] in [[COVID-19]] includes : 1.anti inflammatory properties,2. prevention of viral attachment via changing in [[covid 19]] spike protein | * Efficacy of [[heparin]] in [[COVID-19]] includes : 1.anti inflammatory properties,2. prevention of viral attachment via changing in [[covid 19]] spike protein 3.anticoagulation effect. | ||
*<nowiki/>Efficacy of [[low molecular weight hepari]]<nowiki/>n in [[COVID-19]] includes: | *<nowiki/>Efficacy of [[low molecular weight hepari]]<nowiki/>n in [[COVID-19]] includes: | ||
*<nowiki/>1.Reduction in level of [[IL-6]] and [[cytokin|cytok]][[cytokin|i]]<nowiki/>[[cytokin|ne storm]]. | *<nowiki/>1.Reduction in level of [[IL-6]] and [[cytokin|cytok]][[cytokin|i]]<nowiki/>[[cytokin|ne storm]]. | ||
*<nowiki/>2.[[Anticoagulation]] effect. | *<nowiki/>2.[[Anticoagulation]] effect. | ||
*Prophy<nowiki/>lactic anticoagulant therapy is n<nowiki/>ecessary for all hospitalized [[COVID-19]] patients. | *Prophy<nowiki/>lactic anticoagulant therapy is n<nowiki/>ecessary for all hospitalized [[COVID-19]] patients. | ||
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*[[Ibuprofen]] is an anti-inflammatory drug [[(NSAID)]] and blocks the renin-angiotensin pathway. | *[[Ibuprofen]] is an anti-inflammatory drug [[(NSAID)]] and blocks the renin-angiotensin pathway. | ||
*[[Ibuprofen]] is Activator of ACE2 receptor. | *[[Ibuprofen]] is Activator of ACE2 receptor. | ||
* There is No strong evidence between intake of NSAID and worsening [[COVID-19.]] | * There is No strong evidence between intake of NSAID and worsening [[COVID-19.]] | ||
*[[Ibuprofen]] approved by [[Food and Drug Administration|FDA]] for treatment of [[COVID-19]]. | *[[Ibuprofen]] approved by [[Food and Drug Administration|FDA]] for treatment of [[COVID-19]]. | ||
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=== '''[[Tucilizumab]] (Actemra)''' === | === '''[[Tucilizumab]] (Actemra)''' === | ||
* Tucilizumab is a monocolonal antibody that binds to [[IL-6 receptor]] on the cells and prevents inflammatory response. | * Tucilizumab is a monocolonal antibody that binds to [[IL-6 receptor]] on the cells and prevents inflammatory response. | ||
* Tucilizumab has been used for treatment of [[RA]] and [[juvenile ideopathic artheritis]]. | * Tucilizumab has been used for treatment of [[RA]] and [[juvenile ideopathic artheritis]]. | ||
* Study in wohan showed significant clinical improvement in severe [[COVID-19]] patients. | * Study in wohan showed significant clinical improvement in severe [[COVID-19]] patients. | ||
* Tucilizumab is indicated in [[COVID-19]] patients with the following criteria: | * Tucilizumab is indicated in [[COVID-19]] patients with the following criteria: | ||
#[[Hypoxia]] | #[[Hypoxia]] | ||
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==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
<references /> |
Revision as of 16:04, 9 August 2020
For COVID-19 frequently asked inpatient questions, click here
For COVID-19 frequently asked outpatient questions, click here
COVID-19 Microchapters |
Diagnosis |
---|
Treatment |
Case Studies |
COVID-19 medical therapy On the Web |
American Roentgen Ray Society Images of COVID-19 medical therapy |
Risk calculators and risk factors for COVID-19 medical therapy |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Zand, M.D.[2], Syed Hassan A. Kazmi BSc, MD [3],Sabawoon Mirwais, M.B.B.S, M.D.[4]
Overview
COVID-19 is an inflammatory hypercytokinemia disease. The aim of therapy is prevention of viral replication and controlling the inflammatory process.
Antiviral Agents
Remdesivir
- Remdesivir is a prodrug and inhibits viral RNA polymerase when intracellularly metabolized to an ATP analog.
- Remdesivir has been effective on MERS-COV,EBOLA, SARS-COV1.
- Effects of remdesivir in COVID-19 include :
- Significant reduction in viral load in bronchoaleolar lavage
- Inhibition of SARS-COV-2 replication in nasal and bronchial airway epithelial cells.
- Remdesivir Indicates only for in-hospital setting in Severe COVID-19 disease.
- The recommended dose of remdesivir in COVID-19 is:
- Adult dosing (wt > 40 kg): 200 mg IV loading dose on day 1, then 100 mg IV daily maintenance dose
- Infuse each dose over 30-120 min
- 5 day course if not on ventilation/ECMO. If no clinical improvement at 5 days, extend to 10 days
- 10 day course for patients on mechanical ventilation/ECMO
- Pediatric dosing (wt 3.5 - 40 kg): 5 mg/kg loading dose on day 1, then 2.5 mg/kg maintenance dose
- 5 day course if not on ventilation/ECMO. If no clinical improvement at 5 days, extend to 10 days
- 10 day course for patients on mechanical ventilation/ECMO
- Adult dosing (wt > 40 kg): 200 mg IV loading dose on day 1, then 100 mg IV daily maintenance dose
- Contraindications of remdesivir include :
- Severe renal impairment (eGFR <30 ml/min)
- Severe hepatic dysfunction or alanin transferase (ALT)ᐳ 5-times upper limit
Hydroxychloroquine and Chloroquine
- Hydroxychloroquine has been effective in graft versus host disease ,lupus erythematosus, rheumatoid arthritis, and malaria
- In the begining of COVID-19 pandemic ,hydroxychloroquine was used due to inhibition of the entry of SARS-COV-2 and prevention of the fusion of viral spike protein to ACE2 receptor and reduction of cytokine storm.
- Intracellular uptake of hydroxychloroquine was enhanced with combination with Zinc.
- Hydroxychloroquine has cardiac side effects due to QT prolongation effect.
- Efficacy of remdesivir is reduced in combination with hydroxychroroquine.
- Due to cardiac side effects, recently FDA dissapproved the emergency use authorization of hydroxychloroquine if clinical trials are unavailable.
- Hydroxychloroquine foe early treatment of adults with mild COVID-19 does not improve outcomes in modest sized unblinded randomized controlled trial.
- To date (08/07/2020), there is no proven efficacy of lopinavir-ritonavir for COVID-19 management
- Lopinavir-Ritonavir Inhibits the activity of the HIV-1 protease.
- In an open-label randomized controlled trial, the comparison between patients with COVID-19 received either lopinavir-ritonavir 400/100 mg, orally twice daily plus standard of care or standard care alone showed no benefit of administration of lopinavir-ritonavir
- Only one study in Korea in the initial phase of outbreak accepted using this combination.
- Side effects: Diarrhea, nausea, asthenia
Umifenovir (Arbidol)
- To date (08/07/2020), there is no proven efficacy of umifenovir for COVID-19 management
- Umifenovir has been used in treatment of Ebola virus, human herpesvirus 8 (HHV-8), hepatitis C virus (HCV), and Tacaribe arenavirus, influenza A,B
- Mechanism of action: inhibition of the virus fusion to the cell membrane and hydrogen binding to membrance phospholipids.
- In a retrospective cohort study showed improvement in chest ct scan of COVID-19 patients received a combination of umifenovir and lopinavir-ritonavir.
- In prospective study, umifenovir had inferior outcomes in clinical recovery rate and relief of fever and cough compared with favipiravir
- Safety and efficacy in COVID-19 is under investigation in china with two randomized open trials.
Favipiravir (Avigan)
- To date (08/07/2020), there is no proven efficacy of favipiravir for COVID-19 management
- Favipiravir has been used in 2014 in Japan for the treatment of influenza resistant to neuraminidase inhibitors and has been used in the treatment of infectious diseases caused by RNA viruses such as influenza, Ebola, and norovirus '
- Mechanism of action: after entering the infected cells and being phosphorylated, inhibits viral RNA replication.
- SARS-CoV-2 is an enveloped, positive-sense, single-strand RNA virus and studies showed the efficacy of favipiravir on SARS-COV-2.
- A randomized control trial has shown that COVID-19 patients treated with favipiravir have superior recovery rate (71.43%) than that treated with umifenovir (55.86%), and the duration of fever and cough relief time are significantly shorter in favipiravir group than in umifenovir group [1]
- Two randomized and nonrandomized controlled trials are evaluating the safety and efficacy of favipiravir for treatment of COVID-19 disease.
Oseltamivir (Tamiflu)
- To date (08/07/2020), there is no proven efficacy of oseltamivir for COVID-19 management
- Oseltamivir has been approved for the treatment of influenza A,B viruses and inhibits neuraminidase glygoprotein which is essential for replication of influenza A and B viruses
- The study in wohan showed no positive outcomes were observed in COVID-19 patients after recieving osetamivir
- A clinical trial is investigating the efficacy of combination between Oseltamivir with chloroquine and favipiravir .
Supportive Agents
Azithromycin
- To date (08/07/2020), there is no proven efficacy of azithromycin for COVID-19 management
- Azithromycin has been effective in the treatment of Zika and Ebola viruses and prevented severe respiratory tract infection
- Mechanism of action is binding to 50S subunit of the bacteria ribosom,then inhibition of translation of mRNA.
- Effects of azithromycin in treatment of viral respiratory tract infection include:1. antibacterial coverage 2.immunomodulatory and anti-inflammatory effects.
- Many trials in COVID-19 patients showed the effectiveness of azithromycin combined with hydroxychloroquine.
- A trial in france reported %100 viral clearance in nasopharengeal swap after recieving hydroxychloroquine with azithromycin [2]
- Data about benefits of azithromycin in COVID-19 disease is still inadequate and needs further evaluation.
Vitamin C (Ascorbic Acid)
- To date (08/07/2020), there is no proven efficacy of vitamin C for COVID-19 management
- Effects of Vitamin C in viral agents include:
- Maturation of T lymphocytes and NK( natural killer) cells which are involved in the immune response to viral agents.
- Inhibition of reactive oxygen species (ROS) production
- Remodulation of the cytokine network in systemic inflammatory syndrome.
- Study in COVID-19 patients in china showed administration of high dose IV,Vitamin C (1500mg per day) in moderate and severe cases was correlated with improvement in oxygenation indexes and recovery .
Corticosteroids
- Corticosteroids are indicated only if patients are on supplemental oxygen or receiving mechanical ventilation[3]
- Due to suppression of immune system, the role of corticosteroid in COVID-19 would be evaluated by further investigation.
Methylprednisolone
- Effects of low doses of methylprednisolone in COVID-19 include:
- Controlled of hypercytokinemia
- Anti-inflammatory effect in superimposed infection in COVID-19
- Increased blood pressure when it is low
- Decreased risk of death in ARDS related COVID-19
Dexamethasone
- The recommended dose of dexamethasone for COVID-19 is 6 mg IV once daily or po x 10 days[3]
- Effects of dexamethason in ARDS related COVID-19 include: [4]
- Decreased days of intubation
- Decreased mortality
Niclosamide and Ivermectin
- To date (08/07/2020), there is no proven efficacy of niclosamide and ivermectin for COVID-19 management
- Mechanism of action is Inhibition of binding of coronavirus onto the cells.
- Niclosamid inhibits replication of MERS-COV AND SARS-COV-2.
- Ivermectin inhibits viral replication in dengue virus, flavivirus,influenza. [5]
- FDA approved Ivermectin for treatment of SARS-COV-2. Study showed Ivermectin inhibited SARS-COV-2 replication up to 5000 fold at 48 h in vitro.
Convalescent Plasma
- To date (08/07/2020), there is no proven efficacy of the use of convalescent plasma for COVID-19 management
- Convalescent Plasma is Transfusion of plasma loaded with antibodies after improvement from COVID-19.
- Studies in Taiwan and South Korea showed clinical benefits in severe cases of SARS-COV and MERS
- Pilot study in COVID19 showed symptoms improvement including fever, cough, tightness of breath,chest pain.
- Serious side effects were not reported.[6]
Anticoagulation
- In COVID-19 hypercoagulable state induces micro-macro-vascular thrombosis.
- Predictors of poor outcome in COVID-19 include: Disseminated intravascular coagulation , high level of D-dimer.
- Mortality with anticoagulant therapy was decreased in COVID-19.
- Efficacy of heparin in COVID-19 includes : 1.anti inflammatory properties,2. prevention of viral attachment via changing in covid 19 spike protein 3.anticoagulation effect.
- Efficacy of low molecular weight heparin in COVID-19 includes:
- 1.Reduction in level of IL-6 and cytokine storm.
- 2.Anticoagulation effect.
- Prophylactic anticoagulant therapy is necessary for all hospitalized COVID-19 patients.
- In patients with rapidly progressing respiratory distress and the probability of thrombosis, treatment doses of anticoagulant is considered.
Ibuprofen
- Ibuprofen is an anti-inflammatory drug (NSAID) and blocks the renin-angiotensin pathway.
- Ibuprofen is Activator of ACE2 receptor.
- There is No strong evidence between intake of NSAID and worsening COVID-19.
- Ibuprofen approved by FDA for treatment of COVID-19.
Tucilizumab (Actemra)
- Tucilizumab is a monocolonal antibody that binds to IL-6 receptor on the cells and prevents inflammatory response.
- Tucilizumab has been used for treatment of RA and juvenile ideopathic artheritis.
- Study in wohan showed significant clinical improvement in severe COVID-19 patients.
- Tucilizumab is indicated in COVID-19 patients with the following criteria:
- Hypoxia
- Lung infiltration on CXR
- High inflammatory markers(CRP>3g/dl,ferritin>400ng/dl
- Clinical deterioration
- Contraindications of tucilizumab include as followings:
- Confirmed bacterial or fungal infection
- Platelet count<100000/cc
- Neutrophil count<2000/cc
- Alanin aminotrasferase or aspartat aminotransferase >5times upper limit normal
References
- ↑ Chen, Chang; Zhang, Yi; Huang, Jianying; Yin, Ping; Cheng, Zhenshun; Wu, Jianyuan; Chen, Song; Zhang, Yongxi; Chen, Bo; Lu, Mengxin; Luo, Yongwen; Ju, Lingao; Zhang, Jingyi; Wang, Xinghuan (2020). doi:10.1101/2020.03.17.20037432. Missing or empty
|title=
(help) - ↑ Gautret, Philippe; Lagier, Jean-Christophe; Parola, Philippe; Hoang, Van Thuan; Meddeb, Line; Mailhe, Morgane; Doudier, Barbara; Courjon, Johan; Giordanengo, Valérie; Vieira, Vera Esteves; Dupont, Hervé Tissot; Honoré, Stéphane; Colson, Philippe; Chabrière, Eric; La Scola, Bernard; Rolain, Jean-Marc; Brouqui, Philippe; Raoult, Didier (2020). "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial". International Journal of Antimicrobial Agents: 105949. doi:10.1016/j.ijantimicag.2020.105949. ISSN 0924-8579.
- ↑ 3.0 3.1
- ↑ Russell CD, Millar JE, Baillie JK (February 2020). "Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury". Lancet. 395 (10223): 473–475. doi:10.1016/S0140-6736(20)30317-2. PMC 7134694 Check
|pmc=
value (help). PMID 32043983 Check|pmid=
value (help). - ↑ Gassen NC, Niemeyer D, Muth D, Corman VM, Martinelli S, Gassen A, Hafner K, Papies J, Mösbauer K, Zellner A, Zannas AS, Herrmann A, Holsboer F, Brack-Werner R, Boshart M, Müller-Myhsok B, Drosten C, Müller MA, Rein T (December 2019). "SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection". Nat Commun. 10 (1): 5770. doi:10.1038/s41467-019-13659-4. PMC 6920372 Check
|pmc=
value (help). PMID 31852899. - ↑ Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, Zhou M, Chen L, Meng S, Hu Y, Peng C, Yuan M, Huang J, Wang Z, Yu J, Gao X, Wang D, Yu X, Li L, Zhang J, Wu X, Li B, Xu Y, Chen W, Peng Y, Hu Y, Lin L, Liu X, Huang S, Zhou Z, Zhang L, Wang Y, Zhang Z, Deng K, Xia Z, Gong Q, Zhang W, Zheng X, Liu Y, Yang H, Zhou D, Yu D, Hou J, Shi Z, Chen S, Chen Z, Zhang X, Yang X (April 2020). "Effectiveness of convalescent plasma therapy in severe COVID-19 patients". Proc. Natl. Acad. Sci. U.S.A. 117 (17): 9490–9496. doi:10.1073/pnas.2004168117. PMC 7196837 Check
|pmc=
value (help). PMID 32253318 Check|pmid=
value (help).