Investigational approaches — Covid-19

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Salient Points

This article focuses on the role various drugs play in the management of Covid-19 patients.

  1. Glucocorticosteroids – glucocorticoids should not be routinely administered in patients with COVID-19. It must be considered in asthma, COPD, Septic Shock, Adrenal Insufficiency.
  2. Chloroquine/ hydroxychloroquine – reported to inhibit SARS-CoV-2 in Vitro. Hydroxychloroquine appears to have more potent antiviral activity. Some adverse effects noted are QTc interval prolongation, cardiomyopathy, retinal Toxicity, Hydroxychloroquine – 800mg on day 1, followed by 400mg daily, Chloroquine – 1g on day 1, followed by 500mg daily.
  3. IL-6 pathway inhibitors – COVID-19 patients are described to have clinical features consistent with a cytokine release syndrome – elevated IL-6 levels. IL-6 Receptor Inhibitors like TOCILIZUMAB are described to have good outcomes.
  4. Convalescent plasma – administration of plasma from donors who had completely recovered from COVID-19 to 5 patients with severe COVID-19 on mechanical ventilation with persistent high viral titres in spite of investigational antiviral treatment.
  5. Lopinavir-ritonavir antiviral therapy – Appears to have little to no role in the treatment of SARS-Co-V2 infection.

Detailed Summary

  1. Glucocorticoids
  • According to the CDC and WHO – glucocorticoids should not be routinely administered in patients with COVID-19.
  • Indications for use
  • Asthma
  • COPD exacerbation
  • Refractory Septic Shock
  • Adrenal Insufficiency
  • SCCM provides a weak recommendation in favour of glucocorticoid use in COVID-19 patients with severe ARDS. (PaO2/FiO2 < 100mmHg)
  1. Hydroxychloroquine
  • Chloroquine and hydroxychloroquine – reported to inhibit SARS-CoV-2 in Vitro.
  • Hydroxychloroquine appears to have more potent antiviral activity.
  • NOTE – Limited data available and efficacy unknown
  • Effects of Drug Toxicity
  • QTc interval prolongation
  • Cardiomyopathy
  • Retinal Toxicity
  • ACOC recommends frequent QTc monitoring
  • Dosing (suggested by FDA)
  • Hydroxychloroquine – 800mg on day 1, followed by 400mg daily
  • Chloroquine – 1g on day 1, followed by 500mg daily
  • Both for 4 – 7 days depending on clinical response.
  • According to a non randomised study of 36 COVID-19 patients, the use of hydroxychloroquine was associated with a high rate of undetectable SARS-CoV-2 RNA on nasopharyngeal specimens at day 6 compared with no specific treatment.
  • According to an International Journal of Antimicrobial Agents – March 2020, the use of Azithromycin in combination with hydroxychloroquine was associated with more rapid decline in viral RNA.
  1. IL-6 pathway inhibitors
  • COVID-19 patients described to have clinical features consistent with a cytokine release syndrome – elevated IL-6 levels.
  • Some reports have described good outcomes with IL-6 Receptor Inhibitors – TOCILIZUMAB.
  • Note – No published Clinical data supporting its use.
  1. Convalescent Plasma
  • Convalescent plasma use for patients with Severe COVID-19.
  • According to a case series it describes administration of plasma from donors who had completely recovered from COVID-19 to 5 patients with severe COVID-19 on mechanical ventilation with persistent high viral titres in spite of investigational antiviral treatment.
  1. Lopinavir-ritonavir
  • Appears to have little to no role in the treatment of SARS-Co-V2 infection.
  • This combined with Protease Inhibitor (Used for HIV infection) has in vitro activity against the SARS-CoV virus.

Note – there was no difference in time till clinical improvement or mortality (28 Days) in a randomised trial of 199 patients with severe COVID-19 who were given lopinavir-ritonavir (400/100 mg) twice daily for 14 days in addition to standard care versus those who received standard care alone.

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