COVID-19 medical therapy: Difference between revisions

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==Overview==
==Overview==
[[COVID-19]] is an inflammatory hypercytokinemia disease. The aim of therapy is inhibition of replication of viruse and controlling the inflammatory process. <br />
[[COVID-19]] is an inflammatory hypercytokinemia disease. The aim of therapy is the inhibition of the replication of the virus and controlling the inflammatory process. <br />


== antiviral agents[edit | edit source] ==
== antiviral agents[edit | edit source] ==
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=== Remdesivir[edit | edit source] ===
=== Remdesivir[edit | edit source] ===


*[[Remdesivir]] is a prodrug and inhibits viral [[RNA polymerase]] when intracellularly metabolized to an [[ATP analogue]].
*[[Remdesivir]] is a prodrug and inhibits viral [[RNA polymerase]] when intracellularly metabolized to an [[ATP analog]].


* It has been effective on [[MERS|MERS-COV]],[[EBOLA]], [[SARS-COV1]]. '''PMID:''' '''28124907'''
* It has been effective on [[MERS|MERS-COV]],[[EBOLA]], [[SARS-COV1]].<ref name="pmid28124907">{{cite journal |vauthors=Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L, Neville S, Carra E, Lew W, Ross B, Wang Q, Wolfe L, Jordan R, Soloveva V, Knox J, Perry J, Perron M, Stray KM, Barauskas O, Feng JY, Xu Y, Lee G, Rheingold AL, Ray AS, Bannister R, Strickley R, Swaminathan S, Lee WA, Bavari S, Cihlar T, Lo MK, Warren TK, Mackman RL |title=Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses |journal=J. Med. Chem. |volume=60 |issue=5 |pages=1648–1661 |date=March 2017 |pmid=28124907 |pmc=7202039 |doi=10.1021/acs.jmedchem.6b01594 |url=}}</ref>
 
* Effects in [[SARS-COV2]]:<ref name="GreinOhmagari2020">{{cite journal|last1=Grein|first1=Jonathan|last2=Ohmagari|first2=Norio|last3=Shin|first3=Daniel|last4=Diaz|first4=George|last5=Asperges|first5=Erika|last6=Castagna|first6=Antonella|last7=Feldt|first7=Torsten|last8=Green|first8=Gary|last9=Green|first9=Margaret L.|last10=Lescure|first10=François-Xavier|last11=Nicastri|first11=Emanuele|last12=Oda|first12=Rentaro|last13=Yo|first13=Kikuo|last14=Quiros-Roldan|first14=Eugenia|last15=Studemeister|first15=Alex|last16=Redinski|first16=John|last17=Ahmed|first17=Seema|last18=Bernett|first18=Jorge|last19=Chelliah|first19=Daniel|last20=Chen|first20=Danny|last21=Chihara|first21=Shingo|last22=Cohen|first22=Stuart H.|last23=Cunningham|first23=Jennifer|last24=D’Arminio Monforte|first24=Antonella|last25=Ismail|first25=Saad|last26=Kato|first26=Hideaki|last27=Lapadula|first27=Giuseppe|last28=L’Her|first28=Erwan|last29=Maeno|first29=Toshitaka|last30=Majumder|first30=Sumit|last31=Massari|first31=Marco|last32=Mora-Rillo|first32=Marta|last33=Mutoh|first33=Yoshikazu|last34=Nguyen|first34=Duc|last35=Verweij|first35=Ewa|last36=Zoufaly|first36=Alexander|last37=Osinusi|first37=Anu O.|last38=DeZure|first38=Adam|last39=Zhao|first39=Yang|last40=Zhong|first40=Lijie|last41=Chokkalingam|first41=Anand|last42=Elboudwarej|first42=Emon|last43=Telep|first43=Laura|last44=Timbs|first44=Leighann|last45=Henne|first45=Ilana|last46=Sellers|first46=Scott|last47=Cao|first47=Huyen|last48=Tan|first48=Susanna K.|last49=Winterbourne|first49=Lucinda|last50=Desai|first50=Polly|last51=Mera|first51=Robertino|last52=Gaggar|first52=Anuj|last53=Myers|first53=Robert P.|last54=Brainard|first54=Diana M.|last55=Childs|first55=Richard|last56=Flanigan|first56=Timothy|title=Compassionate Use of Remdesivir for Patients with Severe Covid-19|journal=New England Journal of Medicine|volume=382|issue=24|year=2020|pages=2327–2336|issn=0028-4793|doi=10.1056/NEJMoa2007016}}</ref>


* Effects in [[SARS-COV2]]:
'''DOI: ''10.1056''/''NEJMoa2007016'''''


# Significant reduction in viral load in [[bronchoaleolar lavage]].
# Significant reduction in viral load in [[bronchoaleolar lavage]].
# Inhibition of SARS-COV replication in [[nasal]] and [[bronchial]] airway epithelial cells.
# Inhibition of SARS-COV replication in [[nasal]] and [[bronchial]] airway epithelial cells.


* Indicated only for inhospital setting for adults and children that:
* Indicated only for in-hospital setting for adults and children that:
* Laboratory confirmed [[COVID-19]] disease
* Laboratory confirmed [[COVID-19]] disease
* Severe [[COVID-19]] disease.
* Severe [[COVID-19]] disease.
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* Mechanism of action: inhibit entry of [[SARS-COV-2]] and prevent fusion of viral [[spike protein]] to ACE2 receptor.
* Mechanism of action: inhibit entry of [[SARS-COV-2]] and prevent fusion of viral [[spike protein]] to ACE2 receptor.
* May more effective in the early stage of infection, before COVID-19 lessens [[ACE2]] expression and activity.
* May more effective in the early stage of infection, before COVID-19 lessens [[ACE2]] expression and activity.
* Reducing [[cytokine storm]] by anti -inflammatory effect on TH-17 related [[cytokine]]<nowiki/>s(IL-6,IL17,IL22) '''PMID''': '''32020029'''
* Reducing [[cytokine storm]] by anti -inflammatory effect on TH-17 related [[cytokine]]<nowiki/>s(IL-6,IL17,IL22)<ref name="pmid32020029">{{cite journal |vauthors=Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G |title=Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro |journal=Cell Res. |volume=30 |issue=3 |pages=269–271 |date=March 2020 |pmid=32020029 |pmc=7054408 |doi=10.1038/s41422-020-0282-0 |url=}}</ref>
* Recovery of [[lymphopnea]] due to anti-inflamatory effect
* Recovery of [[lymphopnea]] due to anti-inflamatory effect
* The US FDA has issued emergency authorization for the use of [[chloroquine]] and [[hydroxychloroquine]] for the treatment of COVID-19
* The US FDA has issued emergency authorization for the use of [[chloroquine]] and [[hydroxychloroquine]] for the treatment of COVID-19
* Intracellular uptake, was enhanced with combination with Zinc '''PMID:''' '''25271834'''
* Intracellular uptake, was enhanced with combination with Zinc<ref name="pmid25271834">{{cite journal |vauthors=Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding WQ |title=Chloroquine is a zinc ionophore |journal=PLoS ONE |volume=9 |issue=10 |pages=e109180 |date=2014 |pmid=25271834 |pmc=4182877 |doi=10.1371/journal.pone.0109180 |url=}}</ref>
* High doses of chloroquine 600 mg twice daily for 10 days or total dose of 12 g may be related to [[cardiac risks]].
* High doses of chloroquine 600 mg twice daily for 10 days or a total dose of 12 g may be related to [[cardiac risks]].


=== Lopinavir-Ritonavir or kalerta[edit | edit source] ===
=== Lopinavir-Ritonavir or kalerta[edit | edit source] ===


* Inhibit the activity of the HIV-1 protease.
* Inhibit the activity of the HIV-1 protease.
* There is no benefit in adminstration of lopinavir-ritonavir in [[COVID-19]]
* There is no benefit in the administration of lopinavir-ritonavir in [[COVID-19]]
* In an open-label randomized controlied trial comparision between patients with [[COVID-19]] recieved either lupinavir-ritonavir 400/100 mg, orally twice daily plus standard of care or standard care alone showed no benefit of adminstration of [[lopinavir-ritonavir]]
* In an open-label randomized controlled trial 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]]<ref name="CaoWang2020">{{cite journal|last1=Cao|first1=Bin|last2=Wang|first2=Yeming|last3=Wen|first3=Danning|last4=Liu|first4=Wen|last5=Wang|first5=Jingli|last6=Fan|first6=Guohui|last7=Ruan|first7=Lianguo|last8=Song|first8=Bin|last9=Cai|first9=Yanping|last10=Wei|first10=Ming|last11=Li|first11=Xingwang|last12=Xia|first12=Jiaan|last13=Chen|first13=Nanshan|last14=Xiang|first14=Jie|last15=Yu|first15=Ting|last16=Bai|first16=Tao|last17=Xie|first17=Xuelei|last18=Zhang|first18=Li|last19=Li|first19=Caihong|last20=Yuan|first20=Ye|last21=Chen|first21=Hua|last22=Li|first22=Huadong|last23=Huang|first23=Hanping|last24=Tu|first24=Shengjing|last25=Gong|first25=Fengyun|last26=Liu|first26=Ying|last27=Wei|first27=Yuan|last28=Dong|first28=Chongya|last29=Zhou|first29=Fei|last30=Gu|first30=Xiaoying|last31=Xu|first31=Jiuyang|last32=Liu|first32=Zhibo|last33=Zhang|first33=Yi|last34=Li|first34=Hui|last35=Shang|first35=Lianhan|last36=Wang|first36=Ke|last37=Li|first37=Kunxia|last38=Zhou|first38=Xia|last39=Dong|first39=Xuan|last40=Qu|first40=Zhaohui|last41=Lu|first41=Sixia|last42=Hu|first42=Xujuan|last43=Ruan|first43=Shunan|last44=Luo|first44=Shanshan|last45=Wu|first45=Jing|last46=Peng|first46=Lu|last47=Cheng|first47=Fang|last48=Pan|first48=Lihong|last49=Zou|first49=Jun|last50=Jia|first50=Chunmin|last51=Wang|first51=Juan|last52=Liu|first52=Xia|last53=Wang|first53=Shuzhen|last54=Wu|first54=Xudong|last55=Ge|first55=Qin|last56=He|first56=Jing|last57=Zhan|first57=Haiyan|last58=Qiu|first58=Fang|last59=Guo|first59=Li|last60=Huang|first60=Chaolin|last61=Jaki|first61=Thomas|last62=Hayden|first62=Frederick G.|last63=Horby|first63=Peter W.|last64=Zhang|first64=Dingyu|last65=Wang|first65=Chen|title=A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19|journal=New England Journal of Medicine|volume=382|issue=19|year=2020|pages=1787–1799|issn=0028-4793|doi=10.1056/NEJMoa2001282}}</ref>


* Only one study in korea in the initial phase of outbreak accepted using this combination PMID: '''32056407'''
* Only one study in Korea in the initial phase of outbreak accepted using this combination PMID: '''32056407'''
* Side effects: [[Diarrhea]], [[nausea]], [[asthenia]]
* Side effects: [[Diarrhea]], [[nausea]], [[asthenia]]


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* It has been used in treatment of Ebola virus, [[human herpesvirus 8 (HHV-8)]], [[hepatitis C virus]] ([[HCV)]], and [[Tacaribe arenavirus]], [[influenza A,B]]   PMID:'''26739045'''
* It has been used in treatment of Ebola virus, [[human herpesvirus 8 (HHV-8)]], [[hepatitis C virus]] ([[HCV)]], and [[Tacaribe arenavirus]], [[influenza A,B]]   PMID:'''26739045'''


* Mechanism of action: inhibit the fusion virus to cell membrance and hydrogen binding to [[membrance phospholipids]].PMID: '''20527735'''
* Mechanism of action: inhibit the fusion virus to the cell membrane and hydrogen binding to [[membrance phospholipids]].PMID: '''20527735'''
* In retrospective cohort study showed improvement in chest ct scan of COVID-19 patients recieved combination of umifenovir and lopinavir-ritonavir.PMID: '''32171872'''
* In a retrospective cohort study showed improvement in chest ct scan of COVID-19 patients received a combination of umifenovir and lopinavir-ritonavir.PMID: '''32171872'''
* In prospective study, [[umifenovir]] had inferior outcomes in clinical recovery rate and relief of fever and [[cough]] , compared with [[favipiravir]] <nowiki>https://doi.org/10.1101/2020.03.17.20037432</nowiki>
* In prospective study, [[umifenovir]] had inferior outcomes in clinical recovery rate and relief of fever and [[cough]] , compared with [[favipiravir]] <nowiki>https://doi.org/10.1101/2020.03.17.20037432</nowiki>
* 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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=== Favipiravir (Avigan)[edit | edit source] ===
=== Favipiravir (Avigan)[edit | edit source] ===


* It 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 PMID: '''28769016 PMID: 31389664'''
* It 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 PMID: '''28769016 PMID: 31389664'''
* 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.]]
* 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 '''Doi.org/10.1101/2020.03.17.20037432'''
* 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 '''Doi.org/10.1101/2020.03.17.20037432'''
* Two randomized and non randomized controlled trials are evaluating safety and efficacy of favipiravir for treatment of [[COVID-19]] disease.
* Two randomized and nonrandomized controlled trials are evaluating the safety and efficacy of favipiravir for treatment of [[COVID-19]] disease.


=== Oseltamivir (Tamiflu)[edit | edit source] ===
=== Oseltamivir (Tamiflu)[edit | edit source] ===


* It has been approved for treatment of [[influenza]] A,B viruses and inhibits [[neuraminidase glygoprotein]] which is essential for replication of [[influenza A and B]] viruses PMID:'''11270942'''
* It 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 PMID:'''11270942'''


* The study in wohan showed no positive outcomes were observed in [[COVID-19]] patients after recieving [[osetamivir]] '''doi:10.1001/jama.2020.1585'''
* The study in wohan showed no positive outcomes were observed in [[COVID-19]] patients after recieving [[osetamivir]] '''doi:10.1001/jama.2020.1585'''
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=== azithromycin[edit | edit source] ===
=== azithromycin[edit | edit source] ===


* It has been effective in treatment of [[Zika]] and [[Ebola]] viruses and prevented severe respiratory tarct infection PMID: '''27911847'''
* It has been effective in the treatment of [[Zika]] and [[Ebola]] viruses and prevented severe respiratory tract infection PMID: '''27911847'''
* Mechanism of action is binding to [[50S subunit]] of the [[bacteria ribosom]],then inhibits traslation [[mRNA]].
* Mechanism of action is binding to [[50S subunit]] of the [[bacteria ribosom]],then inhibits traslation [[mRNA]].
* Effects of [[azithromycin]] in treatment of viral respiratory tract infection include:1. antibacterial coverage 2. mmunomodulatory and anti-inflammatory effects '''doi: 10.1016/j.ijantimicag.2020.105949.'''
* Effects of [[azithromycin]] in treatment of viral respiratory tract infection include:1. antibacterial coverage 2. mmunomodulatory and anti-inflammatory effects '''doi: 10.1016/j.ijantimicag.2020.105949.'''
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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 .'''PMID: 32328576'''
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 .'''PMID: 32328576'''


=== Corticosteroids[edit | edit source] ===
=== Corticosteroids[edit | edit source] ===
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* Controlling the hypercytocynemia
* Controlling the hypercytocynemia
* Anti inflammation which is caused by infection superimposed in COVID-19
* Anti-inflammation which is caused by infection superimposed in COVID-19


* Increase blood pressure when it is low
* Increase blood pressure when it is low
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* Decreased mortality
* Decreased mortality


* .Due to suppression in immunesystem, the role of corticosteroid in [[COVID-19]] would be evaluated by further investigation . '''PMID: 32043983'''
*.Due to suppression in immune system, the role of corticosteroid in [[COVID-19]] would be evaluated by further investigation. '''PMID: 32043983'''


=== Niclosamide and Ivermectin[edit | edit source] ===
=== Niclosamide and Ivermectin[edit | edit source] ===
Inhibition of binding of corona virus onto the cells '''PMID: 15215127'''
Inhibition of binding of coronavirus onto the cells '''PMID: 15215127'''


[[Niclosamid]] inhibits replication of [[MERS-COV]] AND [[SARS-COV-2]] '''PMID: 31852899'''
[[Niclosamid]] inhibits replication of [[MERS-COV]] AND [[SARS-COV-2]] '''PMID: 31852899'''
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* Efficacy of [[low molecular weight hepari]]<nowiki/>n in [[COVID-19]] includes: reduction in level of [[IL-6]] and [[cytokin]] storm. '''<nowiki>https://doi.org/10.1101/2020.03.28.20046144</nowiki>'''
* Efficacy of [[low molecular weight hepari]]<nowiki/>n in [[COVID-19]] includes: reduction in level of [[IL-6]] and [[cytokin]] storm. '''<nowiki>https://doi.org/10.1101/2020.03.28.20046144</nowiki>'''


* Prophilactic anticoagulant therapy is necessary for hospitalized patients
* Prophylactic anticoagulant therapy is necessary for hospitalized patients
* In patients with rapid progressing respiratory distress and probability of thrombosis, treatment doses of anticoagulant is considered.
* In patients with rapidly progressing respiratory distress and the probability of thrombosis, treatment doses of anticoagulant is considered.


=== Ibuprofen[edit | edit source] ===
=== Ibuprofen[edit | edit source] ===


* nonsteroidal anti-inflammatory drug [[(NSAID)]] and block renin-angiotensin pathway
* nonsteroidal anti-inflammatory drug [[(NSAID)]] and block the renin-angiotensin pathway
* Anti-inflammatory effect
* Anti-inflammatory effect
* Activator of ACE2 receptor '''PMID: 16007097'''
* Activator of ACE2 receptor '''PMID: 16007097'''
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==References==
==References==
<references />
{{reflist|2}}

Revision as of 03:13, 11 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]Sabawoon Mirwais, M.B.B.S, M.D.[3]

Overview

COVID-19 is an inflammatory hypercytokinemia disease. The aim of therapy is the inhibition of the replication of the virus and controlling the inflammatory process.

antiviral agents[edit | edit source]

Remdesivir[edit | edit source]


  1. Significant reduction in viral load in bronchoaleolar lavage.
  2. Inhibition of SARS-COV replication in nasal and bronchial airway epithelial cells.
  • Indicated only for in-hospital setting for adults and children that:
  • Laboratory confirmed COVID-19 disease
  • Severe COVID-19 disease.

Severe COVID-19 disease defined as:

  1. SO2ᐸ%94 on room air,
  2. Need to supplement oxygen,
  3. Mechanical ventilation,
  4. extracorporeal membrane oxygenation (ECMO)
  • Contraindications:

Severe renal impairment (eGFR <30 ml/min)

Severe hepatic dysfunction or alanin transferase (ALT)ᐳ 5-times upper limit


Hydroxychloroquine and Chloroquine[edit | edit source]

  • Mechanism of action: inhibit entry of SARS-COV-2 and prevent fusion of viral spike protein to ACE2 receptor.
  • May more effective in the early stage of infection, before COVID-19 lessens ACE2 expression and activity.
  • Reducing cytokine storm by anti -inflammatory effect on TH-17 related cytokines(IL-6,IL17,IL22)[3]
  • Recovery of lymphopnea due to anti-inflamatory effect
  • The US FDA has issued emergency authorization for the use of chloroquine and hydroxychloroquine for the treatment of COVID-19
  • Intracellular uptake, was enhanced with combination with Zinc[4]
  • High doses of chloroquine 600 mg twice daily for 10 days or a total dose of 12 g may be related to cardiac risks.

Lopinavir-Ritonavir or kalerta[edit | edit source]

  • Inhibit the activity of the HIV-1 protease.
  • There is no benefit in the administration of lopinavir-ritonavir in COVID-19
  • In an open-label randomized controlled trial 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[5]
  • Only one study in Korea in the initial phase of outbreak accepted using this combination PMID: 32056407
  • Side effects: Diarrhea, nausea, asthenia

Umifenovir (Arbidol)[edit | edit source]

  • Mechanism of action: inhibit the fusion virus to the cell membrane and hydrogen binding to membrance phospholipids.PMID: 20527735
  • In a retrospective cohort study showed improvement in chest ct scan of COVID-19 patients received a combination of umifenovir and lopinavir-ritonavir.PMID: 32171872
  • In prospective study, umifenovir had inferior outcomes in clinical recovery rate and relief of fever and cough , compared with favipiravir https://doi.org/10.1101/2020.03.17.20037432
  • Safety and efficacy in COVID-19 is under investigation in china with two randomized open trials.

Favipiravir (Avigan)[edit | edit source]

  • It 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 PMID: 28769016 PMID: 31389664
  • 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 Doi.org/10.1101/2020.03.17.20037432
  • Two randomized and nonrandomized controlled trials are evaluating the safety and efficacy of favipiravir for treatment of COVID-19 disease.

Oseltamivir (Tamiflu)[edit | edit source]

  • The study in wohan showed no positive outcomes were observed in COVID-19 patients after recieving osetamivir doi:10.1001/jama.2020.1585
  • A clinical trial is investigating the efficacy of combination between Oseltamivir with chloroquine and favipiravir . PMID: 32256547

supportive agents[edit | edit source]

azithromycin[edit | edit source]

  • It has been effective in the treatment of Zika and Ebola viruses and prevented severe respiratory tract infection PMID: 27911847
  • Mechanism of action is binding to 50S subunit of the bacteria ribosom,then inhibits traslation mRNA.
  • Effects of azithromycin in treatment of viral respiratory tract infection include:1. antibacterial coverage 2. mmunomodulatory and anti-inflammatory effects doi: 10.1016/j.ijantimicag.2020.105949.
  • 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 hydroxychloroquin with azithromycin doi: 10.1016/j.ijantimicag.2020.105949.
  • Data about benefits of azithromycin in COVID-19 disease is still inadequate and needs further evaluation.

Vitamin C (Ascorbic Acid)[edit | edit source]

Effects in viral agents include:PMID: 29534432

  • 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 .PMID: 32328576

Corticosteroids[edit | edit source]

  1. Effects of Low doses of methylprednisolone in COVID-19 include: PMID: 30097460 PMID: 32043983
  • Controlling the hypercytocynemia
  • Anti-inflammation which is caused by infection superimposed in COVID-19
  • Increase blood pressure when it is low
  • Decreased risk of death in ARDS complicated COVID-19 PMID: 32167524
  • .Effects of dexamethason in ARDS complicated COVID-19 include: PMID: 32043986
  • Decreased ventilation days
  • Decreased mortality
  • .Due to suppression in immune system, the role of corticosteroid in COVID-19 would be evaluated by further investigation. PMID: 32043983

Niclosamide and Ivermectin[edit | edit source]

Inhibition of binding of coronavirus onto the cells PMID: 15215127

Niclosamid inhibits replication of MERS-COV AND SARS-COV-2 PMID: 31852899

Ivermectin inhibits viral replication in dengue virus, flavivirus,influenza PMID: 31852899

Study showed Ivermectin inhibited SARS-COV-2 up to 5000 fold at 48 h in vitro https://doi.org/10.1016/j.antiviral.2020.104787

Convalescent Plasma[edit | edit source]

  • Transfusion of plasma loaded with antibodies after improvement from COVID-19 PMID: 16940336
  • Serious side effects were not reported. PMID: 32253318

Anticoagulation[edit | edit source]

  • Efficacy of heparin in COVID-19 including  : 1.anti inflammatory properties,2. prevention of viral attachment via changing in spike protein https://doi.org/10.1101/2020.02.29.971093
  • Efficacy of low molecular weight heparin in COVID-19 includes: reduction in level of IL-6 and cytokin storm. https://doi.org/10.1101/2020.03.28.20046144
  • Prophylactic anticoagulant therapy is necessary for hospitalized patients
  • In patients with rapidly progressing respiratory distress and the probability of thrombosis, treatment doses of anticoagulant is considered.

Ibuprofen[edit | edit source]

  • nonsteroidal anti-inflammatory drug (NSAID) and block the renin-angiotensin pathway
  • Anti-inflammatory effect
  • Activator of ACE2 receptor PMID: 16007097
  • No strong evidence between intake of NSAID and worsening SARS-COV-2
  • Approved by FDA for treatment of COVID-19

Thiazolidinediones

  • It has been used against pulmonary disease induced by respiratory syncytial virus (RSV) or H1N1 influenza infection PMID: 17425601
  • Upregulation ACE2 receptor, which is identified as receptor for SARS-CoV-2 in host cell PMID: 32171062
  • No strong evidence for therapeutic efficacy against coronavirus infection



References

  1. ↑ Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L, Neville S, Carra E, Lew W, Ross B, Wang Q, Wolfe L, Jordan R, Soloveva V, Knox J, Perry J, Perron M, Stray KM, Barauskas O, Feng JY, Xu Y, Lee G, Rheingold AL, Ray AS, Bannister R, Strickley R, Swaminathan S, Lee WA, Bavari S, Cihlar T, Lo MK, Warren TK, Mackman RL (March 2017). "Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses". J. Med. Chem. 60 (5): 1648–1661. doi:10.1021/acs.jmedchem.6b01594. PMC 7202039 Check |pmc= value (help). PMID 28124907.
  2. ↑ Grein, Jonathan; Ohmagari, Norio; Shin, Daniel; Diaz, George; Asperges, Erika; Castagna, Antonella; Feldt, Torsten; Green, Gary; Green, Margaret L.; Lescure, François-Xavier; Nicastri, Emanuele; Oda, Rentaro; Yo, Kikuo; Quiros-Roldan, Eugenia; Studemeister, Alex; Redinski, John; Ahmed, Seema; Bernett, Jorge; Chelliah, Daniel; Chen, Danny; Chihara, Shingo; Cohen, Stuart H.; Cunningham, Jennifer; D’Arminio Monforte, Antonella; Ismail, Saad; Kato, Hideaki; Lapadula, Giuseppe; L’Her, Erwan; Maeno, Toshitaka; Majumder, Sumit; Massari, Marco; Mora-Rillo, Marta; Mutoh, Yoshikazu; Nguyen, Duc; Verweij, Ewa; Zoufaly, Alexander; Osinusi, Anu O.; DeZure, Adam; Zhao, Yang; Zhong, Lijie; Chokkalingam, Anand; Elboudwarej, Emon; Telep, Laura; Timbs, Leighann; Henne, Ilana; Sellers, Scott; Cao, Huyen; Tan, Susanna K.; Winterbourne, Lucinda; Desai, Polly; Mera, Robertino; Gaggar, Anuj; Myers, Robert P.; Brainard, Diana M.; Childs, Richard; Flanigan, Timothy (2020). "Compassionate Use of Remdesivir for Patients with Severe Covid-19". New England Journal of Medicine. 382 (24): 2327–2336. doi:10.1056/NEJMoa2007016. ISSN 0028-4793.
  3. ↑ Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G (March 2020). "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro". Cell Res. 30 (3): 269–271. doi:10.1038/s41422-020-0282-0. PMC 7054408 Check |pmc= value (help). PMID 32020029 Check |pmid= value (help).
  4. ↑ Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding WQ (2014). "Chloroquine is a zinc ionophore". PLoS ONE. 9 (10): e109180. doi:10.1371/journal.pone.0109180. PMC 4182877. PMID 25271834.
  5. ↑ Cao, Bin; Wang, Yeming; Wen, Danning; Liu, Wen; Wang, Jingli; Fan, Guohui; Ruan, Lianguo; Song, Bin; Cai, Yanping; Wei, Ming; Li, Xingwang; Xia, Jiaan; Chen, Nanshan; Xiang, Jie; Yu, Ting; Bai, Tao; Xie, Xuelei; Zhang, Li; Li, Caihong; Yuan, Ye; Chen, Hua; Li, Huadong; Huang, Hanping; Tu, Shengjing; Gong, Fengyun; Liu, Ying; Wei, Yuan; Dong, Chongya; Zhou, Fei; Gu, Xiaoying; Xu, Jiuyang; Liu, Zhibo; Zhang, Yi; Li, Hui; Shang, Lianhan; Wang, Ke; Li, Kunxia; Zhou, Xia; Dong, Xuan; Qu, Zhaohui; Lu, Sixia; Hu, Xujuan; Ruan, Shunan; Luo, Shanshan; Wu, Jing; Peng, Lu; Cheng, Fang; Pan, Lihong; Zou, Jun; Jia, Chunmin; Wang, Juan; Liu, Xia; Wang, Shuzhen; Wu, Xudong; Ge, Qin; He, Jing; Zhan, Haiyan; Qiu, Fang; Guo, Li; Huang, Chaolin; Jaki, Thomas; Hayden, Frederick G.; Horby, Peter W.; Zhang, Dingyu; Wang, Chen (2020). "A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19". New England Journal of Medicine. 382 (19): 1787–1799. doi:10.1056/NEJMoa2001282. ISSN 0028-4793.
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