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
antiviral agents[edit | edit source]
Remdesivir[edit | edit source]
- Remdesivir 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] PMID: 28124907
- Effects in SARS-COV2:[2]
DOI: 10.1056/NEJMoa2007016
- 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 that:
- 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[edit | edit source]
- 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) PMID: 32020029
- 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 PMID: 25271834
- 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)[edit | edit source]
- 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)[edit | edit source]
- 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 ,inhibits viral 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)[edit | edit source]
- 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
supportive agents[edit | edit source]
azithromycin[edit | edit source]
- It has been effective in treatment of Zika and Ebola viruses and prevented severe respiratory tarct infection PMID: 27911847
- mechanism of action is binding to 50S subunit of the bacteria ribosom,then inhibits traslation mRNA.
- effects of azithromycin in treatment of viral respiratory tract infection include:1. antibacterial coverage 2. mmunomodulatory and anti-inflammatory effects doi: 10.1016/j.ijantimicag.2020.105949.
- Many trials in COVID-19 patients showed the effectiveness of azithromycin combined with hydroxychloroquine.
- A trial in france reported %100 viral clearance in nasopharengeal swap after recieving hydroxychloroquin with azithromycin doi: 10.1016/j.ijantimicag.2020.105949.
- data about benefits of azithromycin in COVID-19 disease is still inadequate and needs further evaluation.
Vitamin C (Ascorbic Acid)[edit | edit source]
Effects in viral agents include:PMID: 29534432
- maturation of T lymphocytes and NK( natural killer) cells which are involved in the immune response to viral agents
- inhibition of reactive oxygen species (ROS) production
- 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 .PMID: 32328576
Corticosteroids[edit | edit source]
- effects of Low doses of methylprednisolone in COVID-19 include: PMID: 30097460 PMID: 32043983
- controlling the hypercytocynemia
- anti inflammation which is caused by infection superimposed in COVID-19
- increase blood pressure when it is low
- decreased risk of death in ARDS complicated COVID-19 PMID: 32167524
- 2.Effects of dexamethason in ARDS complicated COVID-19 include: PMID: 32043986
- decreased ventilation days
- decreased mortality
- 3.Due to suppression in immunesystem, the role of corticosteroid in COVID-19 would be evaluated by further investigation . PMID: 32043983
Niclosamide and Ivermectin[edit | edit source]
Inhibition of binding of corona virus onto the cells PMID: 15215127
Niclosamid inhibits replication of MERS-COV AND SARS-COV-2 PMID: 31852899
Ivermectin inhibits viral replication in dengue virus, flavivirus,influenza PMID: 31852899
Study showed Ivermectin inhibited SARS-COV-2 up to 5000 fold at 48 h in vitro https://doi.org/10.1016/j.antiviral.2020.104787
Convalescent Plasma[edit | edit source]
- Transfusion of plasma loaded with antibodies after improvement from COVID-19 PMID: 16940336
- Studies in Taiwan and South Korea showed clinical benefits in severe cases of SARS-COV and MERS PMID: 16183666
- Pilot study in COVID19 showed symptoms improvement including fever, cough, tightness of breath,chest pain PMID: 32253318
- Serious side effects were not reported. PMID: 32253318
Anticoagulation[edit | edit source]
- In COVID-19 hypercoagulable state induces micro-macro-vascular thrombosis
- predictors of poor outcome in COVID-19 include: Disseminated intravascular coagulation , high level of D-dimer. PMID: 32073213
- mortality with anticoagulant therapy was decreased
- Efficacy of heparin in COVID-19 including : 1.anti inflammatory properties,2. prevention of viral attachment via changing in spike protein https://doi.org/10.1101/2020.02.29.971093
- Efficacy of low molecular weight heparin in COVID-19 includes: reduction in level of IL-6 and cytokin storm. https://doi.org/10.1101/2020.03.28.20046144
- Prophilactic anticoagulant therapy is necessary for hospitalized patients
- In patients with rapid progressing respiratory distress and probability of thrombosis, treatment doses of anticoagulant is considered.
Ibuprofen[edit | edit source]
- nonsteroidal anti-inflammatory drug (NSAID) and block renin-angiotensin pathway
- anti-inflammatory effect
- Activator of ACE2 receptor PMID: 16007097
- no strong evidence between intake of NSAID and worsening SARS-COV-2
- Approved by FDA for treatment of COVID-19
Thiazolidinediones
- It has been used against pulmonary disease induced by respiratory syncytial virus (RSV) or H1N1 influenza infection PMID: 17425601
- upregulation ACE2 receptor, which is identified as receptor for SARS-CoV-2 in host cell PMID: 32171062
- No strong evidence for therapeutic efficacy against coronavirus infection
References
- ↑ Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L, Neville S, Carra E, Lew W, Ross B, Wang Q, Wolfe L, Jordan R, Soloveva V, Knox J, Perry J, Perron M, Stray KM, Barauskas O, Feng JY, Xu Y, Lee G, Rheingold AL, Ray AS, Bannister R, Strickley R, Swaminathan S, Lee WA, Bavari S, Cihlar T, Lo MK, Warren TK, Mackman RL (March 2017). "Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses". J. Med. Chem. 60 (5): 1648–1661. doi:10.1021/acs.jmedchem.6b01594. PMC 7202039 Check
|pmc=value (help). PMID 28124907. - ↑ Grein, Jonathan; Ohmagari, Norio; Shin, Daniel; Diaz, George; Asperges, Erika; Castagna, Antonella; Feldt, Torsten; Green, Gary; Green, Margaret L.; Lescure, François-Xavier; Nicastri, Emanuele; Oda, Rentaro; Yo, Kikuo; Quiros-Roldan, Eugenia; Studemeister, Alex; Redinski, John; Ahmed, Seema; Bernett, Jorge; Chelliah, Daniel; Chen, Danny; Chihara, Shingo; Cohen, Stuart H.; Cunningham, Jennifer; D’Arminio Monforte, Antonella; Ismail, Saad; Kato, Hideaki; Lapadula, Giuseppe; L’Her, Erwan; Maeno, Toshitaka; Majumder, Sumit; Massari, Marco; Mora-Rillo, Marta; Mutoh, Yoshikazu; Nguyen, Duc; Verweij, Ewa; Zoufaly, Alexander; Osinusi, Anu O.; DeZure, Adam; Zhao, Yang; Zhong, Lijie; Chokkalingam, Anand; Elboudwarej, Emon; Telep, Laura; Timbs, Leighann; Henne, Ilana; Sellers, Scott; Cao, Huyen; Tan, Susanna K.; Winterbourne, Lucinda; Desai, Polly; Mera, Robertino; Gaggar, Anuj; Myers, Robert P.; Brainard, Diana M.; Childs, Richard; Flanigan, Timothy (2020). "Compassionate Use of Remdesivir for Patients with Severe Covid-19". New England Journal of Medicine. 382 (24): 2327–2336. doi:10.1056/NEJMoa2007016. ISSN 0028-4793.