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. On February 09, 2021 FDA approved emergency use authorization of monoclonal antibodies including bamlanivimab and etesevimab for mild to moderate covid-19 patients who are high risk for progression of disease ( age > 65years, medical comorbidities).

Current Treatment

Corticosteroids

Dexamethasone

  1. Decreased days of intubation
  2. Decreased mortality

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[6]

Inhaled corticosteroids

Inhaled corticosteroids (budesonide) may improve recovery time and reducing hospital admission or death in high risk covid-19 patients in the community. [7].

Experimental Treatments

Remdesivir

  • Significant reduction in viral load in bronchoaleolar lavage
  • Inhibition of SARS-COV-2 replication in nasal and bronchial airway epithelial cells.
  • Remdesivir is approved by FDA on 22 October 2020 for all hospitalized adult and pediatric older than 12 years of age and weighing at least 40 kg (88 pounds).
  • Remdesivir was effective in shortening the time of recovery about 32% and survival benefit in adult hospitalized covid-19 patients according to ACTT-1 trial.[8]
  • In a Phase 3 open label randomized trial, No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID19,who were symptomatic for more than 7 days, and required oxygen support.(doi:10.1016/S1473-3099)
  • The combination of Remdesivir and Baricitinib reduced recovery time in hospitalized covid-19 patients according to ACTT-2 trial.
  • Safety and efficacy of the combination of Remdesivir and interferon b-1a is under investigation according to ACTT-3 trial.
  • 5-day course of remdesivir in hospitalized patients with moderate Covid-19 had better clinical status compared with standard care at 11 days after starting the treatment.[9]
  • Remdesivir indicates 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 (EUA) issued on 1 May 2020.
  1. Severe renal impairment (eGFR <30 ml/min)
  2. Severe hepatic dysfunction or alanin transferase (ALT)ᐳ 5-times upper limit

Favipiravir (Avigan)

Atazanavir

Umifenovir (Arbidol)


Clofazimine

Lopinavir-Ritonavir or kalerta

  • Lopinavir-Ritonavir Inhibits the activity of the HIV-1 protease.
  • In the Recovery Trial kaletra was not effective in reducing of mortality, duration of hospitalization or prevention of ventilation.[22]
  • 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.[23]
  • Only one study in Korea in the initial phase of outbreak accepted using this combination.[24]
  • Side effects: Diarrhea, nausea, asthenia

Niclosamide and Ivermectin

  • Mechanism of action is the Inhibition of binding of coronavirus onto the cells.[25]

Supportive Agents

Tocilizumab (Actemra)


  1. Hypoxia
  2. Lung infiltration on CXR
  3. High inflammatory markers (CRP>3g/dl, ferritin>400ng/dl
  4. Clinical deterioration
  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

Bamlanivimab,Etesevimab

Casirivimab, Imdevimab

Sotrovimab


Interferon-1

Azithromycin

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.[41]


Convalescent Plasma

Anticoagulation

In COVID-19 hypercoagulable state induces micro-macro-vascular thrombosis.


  • 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. [48]

Ibuprofen

Failed therapies

Hydroxychloroquine and Chloroquine

References

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