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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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| ===[[Dexamethasone]]===
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| *Dosage: 6mg Qday
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| **Dexamethasone improves 28d mortality compared to placebo in patients requiring IMV (NNT = 8.5) and those patients requiring oxygen therapy (NNT = 29).
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| **There was no benefit to patients not requiring oxygenation support and potentially harm
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| ====[[Remdesivir]]====
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| *Previously used to treat Ebola<ref>Auwaerter. Johns Hopkins Antibiotic guide. Coronavirus COVID-19. April 8 2020</ref> this medication inhibits viral RNA polymerase and has shown some promisinng invitro activity against [[SARS-CoV-2]].
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| *A recent small study among 53 patients with severe symptoms from COVID-19 were given [[Remdesivir]] for compassionate use. 68% percent of patients showed some clinical improvement.<ref>Grein, J., Ohmagari, N.,...Oda, R (2020). Compassionate Use of Remdesivir for Patients with Severe COVID-19. New England Journal of Medicine.</ref>
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| *A large NIH funded trial is currently underway to assess the efficacy of this medication <ref>https://clinicaltrials.gov/ct2/show/NCT04280705</ref>
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| *Consider using in hospitalized patients with severe symptoms and significant Oxygen requirements
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| *As of November 2020, WHO recommends against the use of remdesivir in COVID-19 patients, regardless of disease severity<ref>https://www.who.int/news-room/feature-stories/detail/who-recommends-against-the-use-of-remdesivir-in-covid-19-patients</ref>
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| *Contact Gilead directly for use: compassionateaccess@gilead.com
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| *<b>Dose:</b> 200mg IV one time. Then 100mg IV once daily for 10 days. <ref>https://www.massgeneral.org/assets/MGH/pdf/news/coronavirus/mass-general-COVID-19-treatment-guidance.pdf</ref>
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| *'''[[Remdesivir]] (IV)'''
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| **Consider for severely hypoxemic (Mechanical vent, high PEEP, FiO2 requirements >40%,).
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| ** Contact Gilead directly for use: compassionateaccess@gilead.com
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| ** Background: novel antiviral nucleotide analog. Initially developed for Ebola and Marburg (has since been found to show activity against other single stranded RNA viruses such as RSV, Lassa fever virus, Nipah virus and the coronaviruses including MERS and SARS)
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| *** 3 clinical trials across country (one is NIH adaptive trial)
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| *** 2 other trials are investigational open-label trials testing different dosages for moderate or severely hospitalized patients
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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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