As the race for the novel coronavirus (SARS-CoV-2) vaccine continues, there is an ever-increasing need for therapeutic options to address patients currently battling infections. As of right now, supportive care is the standard treatment for COVID-19. Clinical trials are being carried out to evaluate potential therapies. Here is a brief overview of several treatment options, among them include antiviral, anti-inflammatory, and antibody-neutralizing medications, that are currently being evaluated.

Antiviral Therapies

Remdesivir

Remdesivir is an antiviral agent that was originally developed to treat Ebola and Marburg viruses. The mechanism of action of this drug is proposed to be premature termination of viral RNA Transcription¹. Previous studies demonstrated the effective activity of remdesivir against MERS-CoV and SARS-CoV-1, two closely related viruses to the novel coronavirus^2-4.  There has been widespread excitement for remdesivir after generating positive results in a double-blind, placebo-controlled, randomized trial⁵.

Remdesivir administered for 5 days may shorten the recovery times for hospitalized patients with lower respiratory tract infections. It is important to note that the impact of remdesivir has not been established.

Dexamethasone

In coronavirus patients requiring respiratory support with supplemental oxygen, dexamethasone (6 mg) administered for up to 10 days can potentially improve survival. Dosing quantities and duration of glucocorticoids has yet to be established as well.

Favipiravir

An inhibitor of viral RNA polymerase, favipiravir has shown activity against RNA viruses and was designed to treat neuraminidase-inhibitor-resistant influenza⁶.  This standalone therapy is showing promise in in-vitro models and clinical trials are underway.

Lopinavir-Ritonavir

This combined protease inhibitor had been used for HIV treatment and PEP, prior to its testing for COVID-19 therapeutic potential. Lopinavir has demonstrated in vitro activity against SARS-CoV-1^7-9. Ritonavir, a cytochrome P450 inhibitor, is then combined with lopinavir to raise the plasma concentration of lopinavir. In 2004, an open-label study was performed with lopinavir-ritonavir in conjunction with ribavirin to reduce acute respiratory distress syndrome (ARDS) or death when compared with standalone ribavirin therapy in SARS-CoV-1⁷. There is no clinical evidence to suggest lopinavir-ritonavir are beneficial as a standalone therapy.

Chloroquine and Hydroxychloroquine (with or without Azithromycin)

Chloroquine has been used as a treatment option and preventative therapeutic against malaria. Additionally, chloroquine and hydroxychloroquine have demonstrated efficacy as anti-inflammatory treatments for rheumatoid arthritis and lupus erythematosus. There is limited data on the mechanism of action for these therapies, however, it is likely that they interfere with viral-cell effusion^10-11. A single-arm study from France involving 20 patients (mild to moderate symptoms) were treated with hydroxychloroquine and showed reduced nasopharyngeal viral loads when compared to patients at another center¹². There have been zero randomized controlled trials performed.

Anti-Inflammatory Medications

Glucocorticoids

In attempts to address the devastating immune response COVID-19 initiates, known as a cytokine storm, medical professionals are relying on modulating the immune response to help increase positive health outcomes. In a retrospective cohort study, 84 participants with COVID-19 and ARDS demonstrated a reduced risk of mortality when that received methylprednisolone¹³. This suggests that patients with severe COVID-19 may find some benefit with corticosteroid therapy.

Interleukin-6 (IL-6) and Interleukin-1 (IL-1) Inhibitors

Tocilizumab and siltuximab are IL-6 inhibitors and are being considered in critically ill patients with ARDS and elevated IL-6 levels¹⁴.

Anakinra is an IL-1 inhibitor used to treat autoimmune conditions. A phase 3 trial showed promise of anakinra as a therapy to critical patients who suffered from sepsis and hyperinflammation¹⁵.

Neutralizing Antibodies

Convalescent Plasma

This therapy utilizes immunoglobulins from recovered patients. It has been demonstrated to show therapeutic potential in SARS, H1N1, and Ebola^16-21. Convalescent plasma has been shown to be safe in patients supported by mechanical ventilation. Extensive clinical trials are needed to explore its efficacy against COVID-19.

 

Author Notes

Chris Cicinelli is the Editor of Labcompare and American Laboratory. He can be reached at [email protected]

References

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