An Update on Current Therapeutic Drugs Treating COVID-19.
Shannar A et al. 2020
Current treatments and repurposed therapeutics for COVID-19 reviewed and summarized here:
Remdesivir: Using a 10-day regimen (200 mg loading dose on day 1, followed by 100 mg once-daily maintenance doses for 9 days), some studies have shown a promising therapeutic effect. However, it is too early to conclude the direct antiviral effects of this agent on enhanced clearing of viral loads in the respiratory tract.
Chloroquine and hydroxychloroquine: There has been some evidence that these agents can reduce cytokine storm and inhibit SARS-CoV-2 infection in vitro. Trials are underway to evaluate the safety and efficacy of prophylactic hydroxychloroquine and treatment for COVID-19. The US FDA has issued emergency authorization for the use of chloroquine and hydroxychloroquine for the treatment of COVID-19. High doses of chloroquine (600 mg twice daily for 10 days or total dose of 12 g) may be associated with significant cardiac risks.There remains a lack of evidence regarding the safety and effectiveness of these agents in treating COVID-19.
Lopinavir-ritonavir: No benefit was observed when 400 mg/100 mg, orally twice daily plus standard of care was used in COVID-19 patients.However, in a single patient in South Korea, lopinavir-ritonavir significantly decreased coronavirus titers.
Umifenovir (Arbidol): Umifenovir shows in vitro activity against SARS-CoV-1 and SARS-CoV-2. Combination therapy of umifenovir and lopinavir-ritonavir showed increased negative conversion rate of SARS-CoV-2 and improved chest CT scan results. However, compared with favipiravir, umifenovir had an inferior outcome in clinical recovery rate and relief of fever and cough. Overall, conflicting evidence exists for umifenovir and is currently under investigation in multiple trials.
Favipiravir (Avigan): The randomized control trial (ChiCTR200030254) showed that favipiravir had superior recovery rate (71.43%) than umifenovir (55.86%) with the duration of fever and cough being significantly shorter in favipiravir group than in umifenovir group. As of mid-April 2020 there are 8 clinical trials in China and 2 in Japan examining the anti-SARS-CoV-2 potential of favipiravir.
Oseltamivir (Tamiflu): Although trials are still underway, no positive outcomes have been observed after receiving treatment with oseltamivir.
Azithromycin: Combination trials of hydroxychloroquine and azithromycin showed conflicting evidence in virologic cure rate.Thus, data presented to date are insufficient to evaluate possible clinical benefits of azithromycin in patients with COVID-19. Also, the additive cardiac toxicity of hydroxychloroquine and azithromycin must be considered.
Vitamin C: High-dose (1.5 mg/kg body weight) vitamin C is safe and has no major side effects as no contraindications have been found.
Corticosteroids: The suspected benefit of corticosteroids in patients with COVID-19 and ARDS remains to be determined. Thus, clinical utilization of corticosteroids should be considered on a case by case basis.
Nitric Oxide and Epoprostenol: In vitro evidence of antiviral activity against SARS-CoV suggested potential effectiveness against SARS-CoV-2. For inhaled nitric oxide (iNO): FDA granted emergency expanded access for its delivery system (INOpulse®) to be immediately used for the treatment of COVID-19. For inhaled epoprosten (iEPO): the most effective and safe dosage appears to be 20–30 ng/kg per minute in adults and 30 ng/kg per minute in pediatric patients. Additional studies are needed to evaluate the potential role of iEPO and iNO in the treatment of COVID-19 patient
Sirolimus: The exact utility of sirolimus in treating COVID-19 patients remains to be evaluated
Tocilizumab: Promising results were observed with tocilizumab treatment (20/21 severe or critical COVID-19 patients in China showed recovery at time of publication). Thus, a multicenter clinical trial (ChiCTR2000029765) is underway.
Sarilumab: Results of a phase 2/3 randomized double-blind placebo-controlled clinical trial planned by Regeneron Pharmaceuticals and Sanofi in partnership with Northwell Health’s Feinstein Institutes have yet to be made public
Anakinra: There are 5 approved clinical trials on anakinra, 2 of which include tocilizumab. Results from these trials have yet to be published.
Miscellaneous Agents and Therapies:
Angiotensin-Converting Enzyme 2 Receptor: Continued treatment with angiotensin-converting enzyme (ACE) inhibitors may be essential for the survival to attenuate the cardiac stress of advancing COVID-19.
Ibuprofen: There is no strong evidence suggesting a link between NSAIDs and worsening symptoms due to infection caused by SARS-CoV-2. The FDA considers ibuprofen and the likes as potentially promising agents.
Thiazolidinediones: Thiazolidinediones may have the potential to upregulate ACE2 receptor. There is a lack of clinical evidence in determining thiazolidinediones therapeutic efficacy against coronavirus infections.
Indomethacin: Viral RNA synthesis was found to be blocked in dogs infected with canine coronavirus CCoV following oral administration of the drug (1 mg/kg) suggesting probable efficacy against SARS-CoV-2.
Colchicine: In COVID-19 patients presenting with myopathies, colchicine has been shown to reduce inflammation in the cardiac myocytes. There are several ongoing studies investigating colchicine for cytokine storm (NCT04326790, NCT04322682, NCT04322565).
Niclosamide and Ivermectin: Efficacy of niclosamide in inhibiting MERS-CoV replication has been shown. Ivermectin has shown inhibition against SARS-CoV-2 in vitro. However, in vivo efficacy remains to be explored.
Nitazoxanide and Tizoxanide: Nitazoxanide was found to suppress pro-inflammatory cytokines in peripheral blood mononuclear cells (PBMCs) and IL-6 in vivo. However, the relevance of this information to COVID-19 is currently unknown.
Convalescent plasma: Limited data on COVID-19 patients from China illustrated clinical benefits of convalescent plasma. A pilot study reported no serious side effects and clinical improvement in terms of fever, cough, shortness of breath, and chest pain
Anticoagulation: Venous thromboembolism prophylaxis with either a low molecular weight or unfractionated heparin is reasonable to administer in hospitalized patients. Treatment doses of anticoagulants may be considered in patients with rapidly progressing respiratory deterioration or signs of thrombosis.
Traditional Chinese Medicine (TCM):
The top 10 most commonly used TCM herbal medicinal products to treat COVID-19 patients in China include: Astragalus membranaceus, Glycyrrhiza uralensis, Saposhnikoviae divaricata, Rhizoma Atractylodis Macrocephalae, Lonicerae Japonicae Flos, Fructus forsythia, Atractylodis Rhizoma, Radix platycodonis, Agastache rugosa, and Cyrtomium fortunei J. Sm
TCM products were used in COVID-19 patients with mild to severe symptoms and were shown to potentially prevent or block disease progression. However, the precise molecular mechanisms currently are unknown.
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