Summary of COVID-19 Medications

The past year has seen tremendous changes due to the coronavirus 2019 (COVID-19) pandemic across multiple levels. While behavioral changes and social isolation helped with limiting the spread of the disease, certain medications were studied and have been shown to be of benefit in COVID-19 patients. In this article, we summarize some of these medications, the mechanism of action and add references to the major studies supporting them.

1-Glucocorticoids — Steroids are recommended for severely ill patients with COVID-19 who are on supplemental oxygen or ventilatory support [1,2].

2-Baricitinib is a selective JAK1 and JAK2 inhibitor used for the treatment of rheumatoid arthritis, and has been used in COVID-19 patients on the basis that it disrupts the activation of downstream signaling molecules and proinflammatory mediators[ 3].

3- Tocilizumab  — Markedly elevated inflammatory markers (including interleukin [IL]-6) are associated with critical and severe COVID-19, and blocking these it may prevent disease progression. Tocilizumab is a recombinant humanized monoclonal antibody that competitively inhibits the binding of interleukin-6 (IL-6) to its receptor (IL-6R) [4].

4Favipiravir is an RNA polymerase inhibitor available in some Asian countries for the treatment of influenza and mild COVID-19, and it is being evaluated in clinical trials for the treatment of COVID-19 in the United States and elsewhere [5].

5-Remdesivir — is an adenosine triphosphate analogue, which stops replication of the virus. It was first described in the literature in 2016 as a potential treatment for Ebola. The FDA granted full approval as a COVID-19 treatment on October 22, 2020, for hospitalized children ≥12 years and adults with COVID-19, regardless of disease severity [6]. 

6Hydroxychloroquine/chloroquine is not recommended in hospitalized patients given the lack of clear benefit and potential for toxicity. There is also for QTc prolongation and arrhythmias with the use of this medication [7].

7Monoclonal antibody therapy –In the United States, the following monoclonal antibody therapies are available for patients with mild to moderate infection in the outpatient setting [8,9]:

Bamlanivimab-etesevimab
Casirivimab-imdevimab
Sotrovimab

8Interferons – Interferon beta has been reported in the literature to inhibit COVID-19 replication in vitro. Defects in type 1 interferon production (which include interferon beta), have been associated with severe COVID-19 infections. However, clinical data so far do not support a clear benefit of interferon beta for severe COVID-19 [10].

9- IL-1 inhibitors – Interleukin-1 (IL-1) is a pro-inflammatory cytokine that has been associated with severe COVID-19, and several observational studies have suggested that IL-1 inhibitors, for example, Anakinra, is associated with reduced COVID-19-associated mortality [11].

10- Colchicine – Although there are some data demonstrating a benefit from Colchicine in mild to moderate COVID-19, the benefit is modest without a reduction in mortality, and adverse effects are common [12].

This is a brief summary of some of these medications. A registry of international clinical trials can be found at covid-trials.org.

A special thank you to my sister, Rawan Ya’acoub, a clinical pharmacist and an assistant professor at the University of Jordan in Amman, Jordan.

References

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[6] Antinori S, Cossu MV, Ridolfo AL, Rech R, Bonazzetti C, Pagani G, Gubertini G, Coen M, Magni C, Castelli A, Borghi B, Colombo R, Giorgi R, Angeli E, Mileto D, Milazzo L, Vimercati S, Pellicciotta M, Corbellino M, Torre A, Rusconi S, Oreni L, Gismondo MR, Giacomelli A, Meroni L, Rizzardini G, Galli M. Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status. Pharmacol Res. 2020 Aug;158:104899. doi: 10.1016/j.phrs.2020.104899. Epub 2020 May 11. PMID: 32407959; PMCID: PMC7212963.

[7] Rochwerg B, Siemieniuk RA, Agoritsas T, Lamontagne F, Askie L, Lytvyn L, Agarwal A, Leo YS, Macdonald H, Zeng L, Amin W, Burhan E, Bausch FJ, Calfee CS, Cecconi M, Chanda D, Du B, Geduld H, Gee P, Harley N, Hashimi M, Hunt B, Kabra SK, Kanda S, Kawano-Dourado L, Kim YJ, Kissoon N, Kwizera A, Mahaka I, Manai H, Mino G, Nsutebu E, Pshenichnaya N, Qadir N, Sabzwari S, Sarin R, Shankar-Hari M, Sharland M, Shen Y, Ranganathan SS, Souza JP, Stegemann M, De Sutter A, Ugarte S, Venkatapuram S, Dat VQ, Vuyiseka D, Wijewickrama A, Maguire B, Zeraatkar D, Bartoszko JJ, Ge L, Brignardello-Petersen R, Owen A, Guyatt G, Diaz J, Jacobs M, Vandvik PO. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. doi: 10.1136/bmj.m3379. Update in: BMJ. 2020 Nov 19;371:m4475. Update in: BMJ. 2021 Mar 31;372:n860. PMID: 32887691.

[8] Chen P, Nirula A, Heller B, Gottlieb RL, Boscia J, Morris J, Huhn G, Cardona J, Mocherla B, Stosor V, Shawa I, Adams AC, Van Naarden J, Custer KL, Shen L, Durante M, Oakley G, Schade AE, Sabo J, Patel DR, Klekotka P, Skovronsky DM; BLAZE-1 Investigators. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):229-237. doi: 10.1056/NEJMoa2029849. Epub 2020 Oct 28. PMID: 33113295; PMCID: PMC7646625.

[9] Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Musser BJ, Soo Y, Rofail D, Im J, Perry C, Pan C, Hosain R, Mahmood A, Davis JD, Turner KC, Hooper AT, Hamilton JD, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Kohli A, Sachdeva Y, Graber X, Kowal B, DiCioccio T, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD; Trial Investigators. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):238-251. doi: 10.1056/NEJMoa2035002. Epub 2020 Dec 17. PMID: 33332778; PMCID: PMC7781102.

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[11] Huet T, Beaussier H, Voisin O, Jouveshomme S, Dauriat G, Lazareth I, Sacco E, Naccache JM, Bézie Y, Laplanche S, Le Berre A, Le Pavec J, Salmeron S, Emmerich J, Mourad JJ, Chatellier G, Hayem G. Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatol. 2020 Jul;2(7):e393-e400. doi: 10.1016/S2665-9913(20)30164-8. Epub 2020 May 29. PMID: 32835245; PMCID: PMC7259909.

[12] Deftereos SG, Giannopoulos G, Vrachatis DA, Siasos GD, Giotaki SG, Gargalianos P, Metallidis S, Sianos G, Baltagiannis S, Panagopoulos P, Dolianitis K, Randou E, Syrigos K, Kotanidou A, Koulouris NG, Milionis H, Sipsas N, Gogos C, Tsoukalas G, Olympios CD, Tsagalou E, Migdalis I, Gerakari S, Angelidis C, Alexopoulos D, Davlouros P, Hahalis G, Kanonidis I, Katritsis D, Kolettis T, Manolis AS, Michalis L, Naka KK, Pyrgakis VN, Toutouzas KP, Triposkiadis F, Tsioufis K, Vavouranakis E, Martinèz-Dolz L, Reimers B, Stefanini GG, Cleman M, Goudevenos J, Tsiodras S, Tousoulis D, Iliodromitis E, Mehran R, Dangas G, Stefanadis C; GRECCO-19 investigators. Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e2013136. doi: 10.1001/jamanetworkopen.2020.13136. PMID: 32579195; PMCID: PMC7315286.

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