COVID-19 medical therapy

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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

  1. Significant reduction in viral load in bronchoaleolar lavage
  2. Inhibition of SARS-COV-2 replication in nasal and bronchial airway epithelial cells.
  • Remdesivir is indicated in the treatment of all hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19 , regardless of the severity of disease according to FDA emergency use authorization.
  • The recommended dose of remdesivir in COVID-19 is::[2]
    • 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
  • Contraindications of remdesivir include :
  1. Severe renal impairment (eGFR <30 ml/min)
  2. Severe hepatic dysfunction or alanin transferase (ALT)ᐳ 5-times upper limit

Interferon-1

Atazanavir

Hydroxychloroquine and Chloroquine

Lopinavir-Ritonavir or kalerta

  • 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.[8]
  • Only one study in Korea in the initial phase of outbreak accepted using this combination.[9]
  • Side effects: Diarrhea, nausea, asthenia

Umifenovir (Arbidol)

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.[14] [15]
  • 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. [13]
  • Two randomized and nonrandomized controlled trials are evaluating the safety and efficacy of favipiravir for treatment of COVID-19 disease.

Oseltamivir (Tamiflu)

Supportive Agents

Azithromycin

  • Azithromycin has been effective in the treatment of Zika and Ebola viruses and prevented severe respiratory tract infection.[19]
  • 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.[20]
  • A trial in france reported  %100 viral clearance in nasopharengeal swap after recieving hydroxychloroquine with azithromycin.[20]
  • Data about benefits of azithromycin in COVID-19 disease is still inadequate and needs further evaluation.

Vitamin C (Ascorbic Acid)

  1. Maturation of T lymphocytes and NK( natural killer) cells that are involved in the immune response to viral agents.
  2. Inhibition of reactive oxygen species (ROS) production
  3. 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.[22]

Corticosteroids

  • Meta-analysis of multiple trials confirmed lower 28-day all-cause mortality with systemic corticosteroid in critically ill patients with COVID-19.[23]


Methylprednisolone

  1. Controlled of hypercytokinemia
  2. Anti-inflammatory effect in superimposed infection in COVID-19
  3. Increased blood pressure when it is low
  4. Decreased risk of death in ARDS related COVID-19[26]

Dexamethasone

  1. Decreased days of intubation
  2. Decreased mortality


Niclosamide and Ivermectin

  • Mechanism of action is the Inhibition of binding of coronavirus onto the cells.[28]

Convalescent Plasma

  • Convalescent Plasma is Transfusion of plasma loaded with antibodies after improvement from COVID-19.
  • Serious side effects were not reported.[32]
  • There is no randomized trial data to assess the efficacy of convalescent plasma in COVID-19.

Anticoagulation

  • 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. [34]

Ibuprofen

Tucilizumab (Actemra)

  • Tocilizumab is a monoclonal antibody that binds to IL-6 receptor on the cells and prevents inflammatory response.[37]
  • Study in Wuhan showed significant clinical improvement in severe COVID-19 patients.[38]
  • Tucilizumab is indicated in COVID-19 patients with the following criteria:[39]
  1. Hypoxia
  2. Lung infiltration on CXR
  3. High inflammatory markers(CRP>3g/dl,ferritin>400ng/dl
  4. Clinical deterioration
  • Contraindications of tocilizumab 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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