COVID-19 medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]Sabawoon Mirwais, M.B.B.S, M.D.[3]
Overview
Treatment of coronavirus infection includes supportive measures and symptomatic management. No specific treatment is available. Given the emergence of the cases during the influenza season, all patients presenting with COVID-19 were given oral and intravenous antibiotics and Oseltamivir (75 mg twice daily via oral route) empirically. Corticosteroids (methylprednisolone 40 - 120 mg/day) were given as a combined regimen if severe community-acquired pneumonia was diagnosed. Oxygen support (e.g., via nasal cannula and invasive mechanical ventilation) was given to patients indicated by the severity of hypoxemia.
Medical Therap
antiviral agents
- Remdesivir (initially named GS-5734) is a prodrug and inhibits viral RNA polymerase when intracellularly metabolized to an ATP analogue
- It has been effective on MERS-COV,EBOLA, SARS-COV1.(1)
- Results in SARS-COV2:
- significant reduction in viral load in bronchoaleolar lavage
- inhibition of SARS-COV replication in nasal and bronchial airway epithelial cells.
- Indicated only for inhospital setting for adults and children with
- laboratory confirmed COVID-19 disease
- severe COVID-19 disease.
severe COVID-19 disease defined as:
- SO2ᐸ%94 on room air,
- need to supplement oxygen,
- mechanical ventilation,
- extracorporeal membrane oxygenation (ECMO)
- Contraindications:
severe renal impairment (eGFR <30 ml/min)
severe hepatic dysfunction or alanin transferase (ALT)ᐳ 5-times upper limit
Hydroxychloroquine and Chloroquine
- It has been effective in graft versus host disease lupus erythematosus, rheumatoid arthritis, and malaria
- Mechanism of action: inhibit entry of SARS-COV-2 and prevent fusion of viral spike protein to ACE2 receptor.
- may more effective in the early stage of infection, before COVID-19 lessens ACE2 expression and activity.
- reducing cytokine storm by anti -inflammatory effect on TH-17 related cytokines(IL-6,IL17,IL22)
- recovery of lymphopnea due to anti-inflamatory effect
- The US FDA has issued emergency authorization for the use of chloroquine and ydroxychloroquine for the treatment of COVID-19
- intracellular uptake, was enhanced with combination with Zinc
- high doses of chloroquine 600 mg twice daily for 10 days or total dose of 12 g may be related to cardiac risks.
- Inhibit the activity of the HIV-1 protease
- there is no benefit in adminstration of lopinavir-ritonavir in COVID-19
- In an open-label randomized controlied trial comparision between patients with COVID-19 recieved either lupinavir-ritonavir 400/100 mg, orally twice daily plus standard of care or standard care alone showed no benefit of adminstration of lopinavir-ritonavir DOI: 10.1056/NEJMoa2001282
- Only one study in korea in the initial phase of outbreak accepted using this combination PMID: 32056407
- side effects: Diarrhea, nausea, asthenia
Umifenovir (Arbidol)
- It has been used in treatment of Ebola virus, human herpesvirus 8 (HHV-8), hepatitis C virus (HCV), and Tacaribe arenavirus, influenza A,B PMID:26739045
- mechanism of action: inhibit the fusion virus to cell membrance and hydrogen binding to membrance phospholipids.PMID: 20527735
- In retrospective cohort study showed improvement in chest ct scan of COVID-19 patients recieved combination of umifenovir and lopinavir-ritonavir.PMID: 32171872
- In prospective study, umifenovir had inferior outcomes in clinical recovery rate and relief of fever and cough , compared with favipiravir https://doi.org/10.1101/2020.03.17.20037432
- safety and efficacy in COVID-19 is under investigation in china with two randomized open trials.
Favipiravir (Avigan)
- It 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 PMID: 28769016 PMID: 31389664
- Mechanism of action: after entering the infected cells and being phosphorylated and inhibits 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 Doi.org/10.1101/2020.03.17.20037432
- two randomized and non randomized controlled trials are evaluating safety and efficacy of favipiravir for treatment of COVID-19 disease.
Oseltamivir (Tamiflu)
- It has been approved for treatment of influenza A,B viruses and inhibits neuraminidase glygoprotein which is essential for replication of influenza A and B viruses PMID:11270942
- The study in wohan showed no positive outcomes were observed in COVID-19 patients after recieving osetamivir doi:10.1001/jama.2020.1585
- A clinical trial is investigating the effivacy of combination between Oseltamivir with chloroquine and favipiravir . PMID: 32256547