COVID-19 medical therapy

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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] Sara Zand, 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

Contraindications of remdesivir include :


Hydroxychloroquine and Chloroquine

Lopinavir-Ritonavir or kalerta

  • Lopinavir-Ritonavir Inhibits 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, 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[4]
  • Only one study in Korea in the initial phase of outbreak accepted using this combination.[5]
  • Side effects: Diarrhea, nausea, asthenia

Umifenovir (Arbidol)

  • Mechanism of action: inhibition of the virus fusion to the cell membrane and hydrogen binding to membrance phospholipids.[7]
  • In a retrospective cohort study showed improvement in chest ct scan of COVID-19 patients received a combination of umifenovir and lopinavir-ritonavir.[8]
  • In prospective study, umifenovir had inferior outcomes in clinical recovery rate and relief of fever and cough compared with favipiravir[9]
  • Safety and efficacy in COVID-19 is under investigation in china with two randomized open trials.

Favipiravir (Avigan)

  • 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 [10] [11]
  • 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 [9]
  • Two randomized and nonrandomized controlled trials are evaluating the safety and efficacy of favipiravir for treatment of COVID-19 disease.

Oseltamivir (Tamiflu)

  • The study in wohan showed no positive outcomes were observed in COVID-19 patients after recieving osetamivir[13]

Supportive Agents

Azithromycin

  • Azithromycin has been effective in the treatment of Zika and Ebola viruses and prevented severe respiratory tract infection[15]
  • 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. [16]
  • A trial in france reported  %100 viral clearance in nasopharengeal swap after recieving hydroxychloroquine with azithromycin [16]
  • Data about benefits of azithromycin in COVID-19 disease is still inadequate and needs further evaluation.

Vitamin C (Ascorbic Acid)

Effects of Vitamin C in viral agents include:[17]

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 .[18]

Corticosteroids

  1. Effects of Low doses of methylprednisolone in COVID-19 include:[19][20]
  • Increased blood pressure when it is low

2.Effects of dexamethason in ARDS related COVID-19 include:[22] [20]


3.Due to suppression of immune system, the role of corticosteroid in COVID-19 would be evaluated by further investigation.

Niclosamide and Ivermectin

  • Mechanism of action is Inhibition of binding of coronavirus onto the cells.[23]

Convalescent Plasma

  • Convalescent Plasma is Transfusion of plasma loaded with antibodies after improvement from COVID-19.
  • Serious side effects were not reported.[27]

Anticoagulation

  • Efficacy of heparin in COVID-19 includes  : 1.anti inflammatory properties,2. prevention of viral attachment via changing in covid 19 spike protein [29]3.anticoagulation effect.

Ibuprofen



Tucilizumab (Actemra)

  • Tucilizumab is a monocolonal antibody that binds to IL-6 receptor on the cells and prevents inflammatory response.[32]
  • Study in wohan showed significant clinical improvement in severe COVID-19 patients.[33]
  • Tucilizumab is indicated in COVID-19 patients with the following criteria:[34]


  1. Hypoxia
  2. Lung infiltration on CXR
  3. High inflammatory markers(CRP>3g/dl,ferritin>400ng/dl
  4. Clinical deterioration
  • Contraindications of tucilizumab include as followings:
  1. Confirmed bacterial or fungal infection
  2. Platelet count<100000/cc
  3. Neutrophil count<2000/cc
  4. Alanin aminotrasferase or aspartat aminotransferase >5times upper limit normal

References

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