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| ==Background==
| | #REDIRECT[[COVID-19#Management_by_Patient_Category]] |
| *As of December 2020, there is currently only a single FDA-approved therapeutic for the treatment
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| **However, there are many therapeutics that have been considered for therapy and available for off-label use and through FDA Emergency-Use-Authorization.
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| ==Evidence Supported Acute Therapies==
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| {{COVID Dex}}
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| {{COVID Remdesivir}}
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| ==Investigational Therapies==
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| ''NIH panel does not recommend initiation of any investigational therapies outside of a clinical trial<ref>https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/</ref>''
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| ===[[Antivirals]]===
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| ===Chloroquine or Hydroxychloroquine With or Without Azithromycin===
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| *FDA cautions '''against''' use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems<ref>https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or</ref>
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| *NIH panel recommends '''against''' the use of chloroquine or hydroxychloroquine with or without azithromycin for the treatment of COVID-19 in hospitalized patients.<ref>https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/</ref>
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| *In nonhospitalized patients, the Panel recommends '''against''' the use of chloroquine or hydroxychloroquine with or without azithromycin for the treatment of COVID-19, except in a clinical trial.<ref>https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/</ref>
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| *NIH panel recommends '''against''' the use of high-dose chloroquine (600 mg twice daily for 10 days) for the treatment of COVID-19.<ref>https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/</ref>
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| ===Lopinavir/Ritonavir and Other HIV Protease Inhibitors===
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| *NIH Panel recommends '''against''' using lopinavir/ritonavir (AI) or other HIV protease inhibitors to treat COVID-19, except in a clinical trial.<ref>https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/</ref>
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| *Known in the U.S as Kaletra, this HIV medication has been widely used in China to treat COVID patients.<ref>https://www.reuters.com/article/us-health-coronavirus-china-wuhan-hospit/key-china-coronavirus-hospital-says-hiv-drug-beneficial-to-patients-idUSKCN21R1LX</ref>.
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| *An RCT with 199 confirmed COVID-19 positive patients concluded that there was no benefit to treating hospitalized patients with [[Lopinavir]]/[[Ritonavir]] versus supportive care.<ref>Cao, B., Wang, Y., Wen, D., Liu, W., Wang, J., Fan, G., ... & Li, X. (2020). A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. New England Journal of Medicine.</ref>
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| *<b>Dose:</b> 400/100mg BID x 10 days. <ref>https://www.massgeneral.org/assets/MGH/pdf/news/coronavirus/mass-general-COVID-19-treatment-guidance.pdf</ref>
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| ===Ivermectin===
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| *NIH Panel recommends '''against''' the use of ivermectin for the treatment of COVID-19, except in a clinical trial.<ref>https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/</ref>
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| ====[[Oseltamivir]]====
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| *Coronaviruses do not utilize neuraminidase for the budding stage of reproduction and therefore no activity is expected.
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| *Several small trials have not shown any benefit in patients with COVID-19. <ref>Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. E-pub Date: aheadofprint February 2020.
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| DOI # 10.1001/jama.2020.1585 . https://www.ncbi.nlm.nih.gov/pubmed/32031570 </ref>
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| ====[[Baloxavir marboxil]]====
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| *Several clinical trials are underway however there is '''no evidence''' at this time for the efficacy of [[Baloxavir marboxil]] in treating COVID-19
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| ====[[Favipiravir]]====
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| *A small, open label, non-randomized trial in China has shown promising results and has not been peer reviewed.<ref>https://www.jwatch.org/na51293/2020/04/09/favipiravir-potential-antiviral-covid-19</ref>
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| *A small prospective, open label study conducted in China has shown promise in symptom reduction for moderately ill patients with COVID-19 and has not yet been peer reviewed <ref>https://www.medrxiv.org/content/10.1101/2020.03.17.20037432v3</ref>
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| ====[[Ribavirin]]====
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| *Has been used in patients with [[MERS]] with inconclusive results.<ref>Arabi YM, et al. Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter
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| Observational Study. Clin Infect Dis. 2019 Jun 25. https://www.ncbi.nlm.nih.gov/pubmed/31925415.</ref>
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| *Small trials in China and North America have failed to establish a therapeutic benefit of Ribavirin. <ref>Devaux CA1, Rolain JM2, Colson P2, Raoult D2. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?. Int J Antimicrob Agents. 2020 Mar 12:105938. doi: 10.1016/j.ijantimicag.2020.105938.</ref>
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| ====[[Azithromycin]]====
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| *Macrolide antibiotic with purported anti-inflammatory effects in certain respiratory conditions such as [[COPD]].
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| *A small French study with 20 patients showed benefit in reducing symptoms and viral carriage when combined with [[Hydroxychloroquine]]. <ref>Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020:105949. [PMID: 32205204] doi:10.1016/j.ijantimicag.2020.105949 </ref>
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| *Recommended if there is concern for bacterial superinfection<ref>https://www.massgeneral.org/assets/MGH/pdf/news/coronavirus/mass-general-COVID-19-treatment-guidance.pdf</ref>
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| *'''Dosage:''' 500mg x 1 day. Then 250mg x 4 days.
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| ===Immunomodulators===
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| ====[[Interferon]]====
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| *Typically used in combination with ribavirin, interferons have been studied for patients with other coronaviruses, with mixed results. Their adverse effect profiles are also generally unfavorable.
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| ===[[Tocilizumab]]===
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| *FDA approved Interleukin-6 (IL-6) monoclonal antibody receptor antagonist used to treat rheumatoid arthritis and cytokine release storm syndrome.
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| *Multiple anecdotal reports and cases showing marked improvement in oxygenation and clinical outcome after drug administration.<ref>Xu X et al. Effective Treatment of Severe COVID-19 Patients with Tocilizumab. Unpublished study. 2020) https://www.ser.es/wp-content/uploads/2020/03/TCZ-and-COVID-19.pdf</ref> <ref> Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA. Published online April 13, 2020. doi:10.1001/jama.2020.6019 </ref>
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| *FDA approved randomized double-blinded clinical trial under way to evaluate its safety and efficacy. <ref> “Roche Initiates Phase III Clinical Trial of Actemra/RoActemra in Hospitalised Patients with Severe COVID-19 Pneumonia.” Roche, www.roche.com/media/releases/med-cor-2020-03-19.htm.</ref>
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| *'''Dosage:''' Typically 8 mg/kg single dose, though some reports suggest giving repeated dosages in critically ill patients. <ref> Luo, Pan. “Tocilizumab Treatment in COVID-19: A Single Center Experience.” Journal of Medical Virology, 2020, doi:10.1002/jmv.25801.</ref>
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| ===[[Convalescent Plasma]]===
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| *Prior studies with convalescent plasma involving SARS, H1N1, and Ebola have had proven benefit in critically ill patients. <ref>Chen, Long et al. “Convalescent plasma as a potential therapy for COVID-19.” The Lancet. Infectious diseases vol. 20,4 (2020): 398-400. doi:10.1016/S1473-3099(20)30141-9 </ref>
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| *Involves obtaining plasma/antibodies from patients who have recovered from COVID-19 and injecting them into critically ill patients.
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| *Shown to have possible clinical improvement in patients with severe ARDS and COVID-19. <ref> “Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. Published online March 27, 2020. doi:10.1001/jama.2020.4783” </ref>
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| ===[[Anticoagulation]]===
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| *Anticoagulation may be associated with lower mortality due to COVID-19 associated vascular thromboemboli resulting in increased dead space ventilation. <ref>Tang et al. J Thromb Haemost 2020 Mar 27. PMID: 32220112 </ref>
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| *Do not give anticoagulation to patients who have a high risk of bleeding as judged by the treating physician.
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| *Before starting anticoagulation, check cbc, pt/ptt, d-dimer. Hold anticoagulation if platelet count <50,000 or INR >1.5.
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| *In admitted patients with moderate or severe COVID-19:
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| *High risk: No definitive criteria, but clinician should use a combination of respiratory distress, o2 requirement, elevated d-dimer, creatinine, and crp in making determination.
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| ====Dosing====
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| *ICU: Heparin drip per PE protocol (goal PTT 70 - 110) or Enoxaparin SC 1mg/kg BID.
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| *High risk admitted patients:
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| **CrCl > 50: [[Enoxaparin]] SC 1m/kg BID
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| **CrCl <50:
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| ***On renal replacement Therapy: [[Apixaban]] 5mg PO BID or heparin drip PE protocol.
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| ***Not on renal replacement Therapy: [[Apixaban]] 5mg PO BID or Adjusted Dose Enoxaparin.
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| *Not high risk:
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| **[[Apixaban]] 2.5-5.0mg PO BID or Enoxaparin SC 40mg QD.
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| ===Other experimental agents===
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| *[[IVIG]]
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| {{COVID contraindicated therapies}}
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| ==[[COVID-19 vaccines]]==
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| See:
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| *[[COVID-19 Vaccine (Moderna)]]
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| *[[COVID-19 Vaccine (Pfizer-BioNTech)]]
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| ==See Also==
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| {{Special:Prefixindex/COVID-19 |hideredirects=1}}
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| ==External Links==
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| *https://www.covid19treatmentguidelines.nih.gov/
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| ==References==
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| [[Category:COVID-19]]
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