COVID-19 medical therapy: Difference between revisions

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Revision as of 15:04, 10 July 2020

For COVID-19 frequently asked inpatient questions, click here
For COVID-19 frequently asked outpatient questions, click here

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

Treatment of coronavirus infection includes supportive measures and symptomatic management. No specific treatment is available. Given the emergence of the cases during the influenza season, all patients presenting with COVID-19 were given oral and intravenous antibiotics and Oseltamivir (75 mg twice daily via oral route) empirically. Corticosteroids (methylprednisolone 40 - 120 mg/day) were given as a combined regimen if severe community-acquired pneumonia was diagnosed. Oxygen support (e.g., via nasal cannula and invasive mechanical ventilation) was given to patients indicated by the severity of hypoxemia.

Medical Therap

antiviral agents

Remdesivir (initially named GS-5734) is a prodrug and inhibits viral RNA polymerase when intracellularly metabolized to an ATP analogue

It has been effective on MERS-COV,EBOLA, SARS-COV1.(1)

Results in SARS-COV2:

significant reduction in viral load in bronchoaleolar lavage
inhibition of SARS-COV replication in nasal and bronchial airway epithelial cells.

Indicated only for inhospital setting for adults and children with
laboratory confirmed COVID-19 disease
severe COVID-19 disease.

severe COVID-19 disease defined as:

SO2ᐸ%94 on room air,
need to supplement oxygen,
mechanical ventilation,
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

It has been effective in graft versus host disease lupus erythematosus, rheumatoid arthritis, and malaria

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)
recovery of lymphopnea due to anti-inflamatory effect
The US FDA has issued emergency authorization for the use of chloroquine and ydroxychloroquine for the treatment of COVID-19
intracellular uptake, was enhanced with combination with Zinc
high doses of chloroquine 600 mg twice daily for 10 days or total dose of 12 g may be related to cardiac risks.

Lopinavir-Ritonavir or kalerta

Inhibit the activity of the HIV-1 protease
there is no benefit in adminstration 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 DOI: 10.1056/NEJMoa2001282
Only one study in korea in the initial phase of outbreak accepted using this combination PMID: 32056407
side effects: Diarrhea, nausea, asthenia

Umifenovir (Arbidol)

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
In retrospective cohort study showed improvement in chest ct scan of COVID-19 patients recieved 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)

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 and inhibits 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 non randomized controlled trials are evaluating safety and efficacy of favipiravir for treatment of COVID-19 disease.

Oseltamivir (Tamiflu)

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

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 effivacy of combination between Oseltamivir with chloroquine and favipiravir . PMID: 32256547

@@ Line 7: / Line 7: @@
 ==Overview==
 Treatment of coronavirus [[infection]] includes supportive measures and [[Symptomatic treatment|symptomatic management]]. No specific treatment is available. Given the emergence of the cases during the [[influenza]] season, all [[Patient|patients]] presenting with COVID-19 were given [[oral]] and [[intravenous]] [[antibiotics]] and [[Oseltamivir]] (75 mg twice daily via oral route) empirically. [[Corticosteroids]] ([[methylprednisolone]] 40 - 120 mg/day) were given as a combined regimen if severe [[community-acquired pneumonia]] was [[Diagnosis|diagnosed]]. Oxygen support (e.g., via nasal cannula and invasive mechanical ventilation) was given to [[Patient|patients]] indicated by the severity of [[hypoxemia]].
-==Medical Therapy==
+==Medical Therap==
-Treatment of coronavirus [[infection]] includes supportive measures and [[Symptomatic treatment|symptomatic management]], including:<ref>{{Cite web|url=https://www.cdc.gov/coronavirus/2019-ncov/about/prevention-treatment.html|title=|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
-* Taking [[pain]] and [[fever]] medications ([[aspirin]] should not be given to children).
-* Using a room humidifier or taking a hot shower to help ease [[sore throat]] and [[cough]].
-* Drinking plenty of liquids, staying home and taking rest.
-:*'''Severe acute respiratory distress syndrome- coronavirus'''<ref>{{cite book | last = Gilbert | first = David | title = The Sanford guide to antimicrobial therapy 2014 | publisher = Antimicrobial Therapy | location = Sperryville, Va | year = 2014 | isbn = 978-1930808782 }}</ref><ref name="pmid16968120">{{cite journal| author=Stockman LJ, Bellamy R, Garner P| title=SARS: systematic review of treatment effects. | journal=PLoS Med | year= 2006 | volume= 3 | issue= 9 | pages= e343 | pmid=16968120 | doi=10.1371/journal.pmed.0030343 | pmc=PMC1564166 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16968120  }} </ref><ref name="pmid15766649">{{cite journal| author=Groneberg DA, Poutanen SM, Low DE, Lode H, Welte T, Zabel P| title=Treatment and vaccines for severe acute respiratory syndrome. | journal=Lancet Infect Dis | year= 2005 | volume= 5 | issue= 3 | pages= 147-55 | pmid=15766649 | doi=10.1016/S1473-3099(05)01307-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15766649  }} </ref>
+==antiviral agents==
-:*Preferred regimen: Supportive therapy
-:*Note: New therapies were studied for SARS during the last outbreaks which concluded:
+*Remdesivir (initially named GS-5734) is a prodrug and inhibits viral RNA polymerase when intracellularly metabolized to an ATP analogue
-::* [[Ribavirin]] ineffective and probably harmful due to hemolytic anemia
-::* [[Lopinavir]] {{plus}} [[Ritonavir]] is still controversial and need further investigation
+*It has been effective on MERS-COV,EBOLA, SARS-COV1.(1)
-::* Interferon has no benefit and its studies are inconclusive
-::* [[Corticosteroids]] increases the risk of fungal infections, some studies showed a higher incidence of psychosis, diabetes, avascular necrosis and osteoporosis
+*Results in SARS-COV2:
-::* Inhaled [[Nitric oxide]] potent mediator of airway inflammation, it has improved oxygenation in some studies
+#significant reduction in viral load in bronchoaleolar lavage
+#inhibition of SARS-COV replication in nasal and bronchial airway epithelial cells.
+*Indicated only for inhospital setting for adults and children with
+* laboratory confirmed  COVID-19 disease
+*severe COVID-19 disease.
+severe COVID-19 disease defined as:
+#SO2ᐸ%94 on room air,
+#need to supplement oxygen,
+#mechanical ventilation,
+#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===
+<br />
+* It has been effective in  graft versus host disease lupus erythematosus, rheumatoid arthritis, and malaria
+*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)
+*recovery of lymphopnea due to anti-inflamatory effect
+*The US FDA has issued emergency authorization for the use of chloroquine and ydroxychloroquine for the treatment of COVID-19
+*intracellular uptake, was enhanced with combination with Zinc
+* high doses of chloroquine 600 mg twice daily for 10 days or total dose of 12 g may be related to cardiac risks.
+<br />
+===Lopinavir-Ritonavir or kalerta===
+*Inhibit the activity of the HIV-1 protease
+*there is no benefit in adminstration 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    DOI:  10.1056/NEJMoa2001282
+*Only one study in korea in the initial phase of outbreak accepted using this combination           PMID:            '''32056407'''
+*side effects: Diarrhea, nausea, asthenia
+===Umifenovir (Arbidol)===
+*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'''
+*In retrospective cohort study showed  improvement in chest ct scan of  COVID-19 patients recieved 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.
+<br />
+===Favipiravir (Avigan)===
+*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 and  inhibits 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 non randomized controlled trials are evaluating safety and efficacy of  favipiravir for treatment of COVID-19  disease.
+===Oseltamivir (Tamiflu)===
+*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'''
+*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 effivacy of combination between Oseltamivir with chloroquine and favipiravir . '''PMID: 32256547'''
-=== Management of COVID-19 ===
-* Recently, remdesivir has been shown to exhibit anti-viral activity against COVID-19. Remdesivir inhibits RNA-dependent RNA polymerase in the viral genome hence blocking its replication in the host.<ref name="pmid32094225">{{cite journal |vauthors=Gordon CJ, Tchesnokov EP, Feng JY, Porter DP, Götte M |title=The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus |journal=J. Biol. Chem. |volume=295 |issue=15 |pages=4773–4779 |date=April 2020 |pmid=32094225 |pmc=7152756 |doi=10.1074/jbc.AC120.013056 |url=}}</ref><ref name="pmid32275812">{{cite journal |vauthors=Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, Feldt T, Green G, Green ML, Lescure FX, Nicastri E, Oda R, Yo K, Quiros-Roldan E, Studemeister A, Redinski J, Ahmed S, Bernett J, Chelliah D, Chen D, Chihara S, Cohen SH, Cunningham J, D'Arminio Monforte A, Ismail S, Kato H, Lapadula G, L'Her E, Maeno T, Majumder S, Massari M, Mora-Rillo M, Mutoh Y, Nguyen D, Verweij E, Zoufaly A, Osinusi AO, DeZure A, Zhao Y, Zhong L, Chokkalingam A, Elboudwarej E, Telep L, Timbs L, Henne I, Sellers S, Cao H, Tan SK, Winterbourne L, Desai P, Mera R, Gaggar A, Myers RP, Brainard DM, Childs R, Flanigan T |title=Compassionate Use of Remdesivir for Patients with Severe Covid-19 |journal=N. Engl. J. Med. |volume= |issue= |pages= |date=April 2020 |pmid=32275812 |pmc=7169476 |doi=10.1056/NEJMoa2007016 |url=}}</ref><ref name="pmid32247927">{{cite journal |vauthors=Cao YC, Deng QX, Dai SX |title=Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence |journal=Travel Med Infect Dis |volume= |issue= |pages=101647 |date=April 2020 |pmid=32247927 |pmc=7151266 |doi=10.1016/j.tmaid.2020.101647 |url=}}</ref><ref name="urlRemdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial - The Lancet">{{cite web |url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext |title=Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial - The Lancet |format= |work= |accessdate=}}</ref>
-*Given the emergence of the cases during the [[influenza]] season, all [[Patient|patients]] presenting with COVID-19 were given [[oral]] and [[intravenous]] [[antibiotics]] and [[Oseltamivir]] (75 mg twice daily via oral route) empirically.<ref name="HuangWang2020">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|year=2020|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref>
-*[[Corticosteroids]] ([[methylprednisolone]] 40 - 120 mg/day) were given as a combined regimen if severe [[community-acquired pneumonia]] was [[Diagnosis|diagnosed]].
-*Oxygen support (e.g., via nasal cannula and invasive mechanical ventilation) was given to [[Patient|patients]] indicated by the severity of [[hypoxemia]].
-====Antimicrobials====
-* A a [https://www.nejm.org/doi/full/10.1056/NEJMoa2016638 randomized, double-blind, placebo-controlled trial] across the United States and parts of Canada testing [[hydroxychloroquine]] as postexposure [[prophylaxis]] found that after high-risk or moderate-risk exposure to Covid-19, [[hydroxychloroquine]] did not prevent [[illness]] compatible with Covid-19 or confirmed [[infection]] when used as postexposure [[prophylaxis]] within 4 days after exposure.<ref name="pmid32492293">{{cite journal |vauthors=Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM, Okafor EC, Skipper CP, Nascene AA, Nicol MR, Abassi M, Engen NW, Cheng MP, LaBar D, Lother SA, MacKenzie LJ, Drobot G, Marten N, Zarychanski R, Kelly LE, Schwartz IS, McDonald EG, Rajasingham R, Lee TC, Hullsiek KH |title=A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 |journal=N. Engl. J. Med. |volume= |issue= |pages= |date=June 2020 |pmid=32492293 |doi=10.1056/NEJMoa2016638 |url=}}</ref>
-====Passive Immunization====
-* Among patients receiving intensive care with [[mechanical ventilation]] for [[ARDS]], a preliminary report of a case series suggest better outcomes receiving convalescent plasma<ref name="pmid32219428">{{cite journal| author=Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J | display-authors=etal| title=Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. | journal=JAMA | year= 2020 | volume=  | issue=  | pages=  | pmid=32219428 | doi=10.1001/jama.2020.4783 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32219428  }} </ref> than a prior case series of 67 similar patients of whom 44 (65.7%) died<ref name="pmid32167524">{{cite journal| author=Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S | display-authors=etal| title=Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. | journal=JAMA Intern Med | year= 2020 | volume=  | issue=  | pages=  | pmid=32167524 | doi=10.1001/jamainternmed.2020.0994 | pmc=7070509 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32167524  }} </ref>.
 ==References==
-{{reflist|2}}