The fight against COVID-19 has not been an easy one. The entire world has been fighting this battle for almost 3 years now, and though we have made significant progress there is still so much more to be done. In tremendous efforts, scientists with the backing of pharmaceutical company power and technology have found new ways to fight this disease. We have even reached the state in which the virus is mutating and with that, some drugs that were effective against certain mutations are becoming obsolete in the treatment of newer variations. In the biggest leap yet, two companies have put forth by mouth treatments for COVID-19. These treatments may seem to be just more COVID-19 medications authorized by different governments, but they provide great attributes that previously authorized medication did not. Because these medications come in a tablet dosage form, they can be taken at home. They do not require a visit to an ambulatory or hospital site for treatment. Patients can walk into their local pharmacies, a place they are more than likely familiar with, and receive this treatment.
Molnupiravir is a small-molecule ribonuclease prodrug of N- hydroxycytidine. This drug has activity against the virus that causes COVID-19 and a strong barrier to the development of resistance. Mechanistically, the drug works by causing the viral polymerase to insert guanosine or adenosine during viral replication. This causes several errors throughout the viral genome causing the virus to eventually become non-infectious and leave it unable to properly replicate. In its phase 3 clinical trials, Molnupiravir met its pre-specified superiority criterion during its interim analysis on day 29, the final day of observation of patients on the medication. In the intention-to-treat population, participants receiving molnupiravir had a lower risk of hospitalization or death through day 29: 6.8% (48 of 709 participants). Regarding safety, the percentage of patients experiencing at least one adverse event was similar in the molnupiravir vs. placebo groups. Deaths that resulted from adverse events, which was deemed not to be related to the trail regimen, were reported less often in the molnupiravir group than placebo.
Many patients who suffer from COVID-19 do recover from acute infections. It is those patients whom the disease progresses that have an impact on health-systems, causing an increased risk of hospital overburden that are of concern. An interesting note of this trial is that only patients who were not vaccinated against COVID-19 were eligible to participate. This choice was reported by investigators as a need to focus on those more likely to need antiviral treatment. This is an especially important idea to consider when thinking about countries that do not have easy access to vaccines. Vaccines need to be transported and delivered under stringent temperature conditions. These conditions can be difficult to maintain when the vaccines need to be sent especially long distances. Though vaccines are the best way to remain safe from COVID-19, having an easily taken and easily transportable treatment for the virus is the next best thing.
1. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients [published online ahead of print, 2021 Dec 16]. N Engl J Med. 2021;NEJMoa2116044. doi:10.1056/NEJMoa2116044
2. Merck and Ridgeback's molnupiravir receives U.S. FDA emergency use authorization for the treatment of high-risk adults with mild to moderate COVID-19. Merck.com. https://www.merck.com/news/merck-and-ridgebacks-molnupiravir-receives-u-s-fda-emergency-use-authorization-for-the-treatment-of-high-risk-adults-with-mild-to-moderate-covid-19/#:~:text=Molnupiravir%20has%20not%20been%20approved,severe%20COVID%2D19%2C%20including%20hospitalization. Published December 23, 2021. Accessed February 1, 2022.
Casirivimab and Imdevimab vs. Omicron
Coronavirus-2019 (COVID-19), a disease that was unknown to the world less than three years ago has now claimed millions of lives. Governments across the world have scrambled to put up their best defenses against the disease, and still COVD-19 remains a constant fear in the hearts of many. With the introduction of the COVID-19 vaccine, one of the best defenses we have against the virus, many people are protected from catching the virus, and even if caught, symptoms are for the most part minor. Multiple drug companies have efficiently developed different types of treatments for those with the active disease that have proven to be successful in many patients, but with the constant mutation of the virus, some treatments are becoming less effective.
Casirivimab and imdevimab, a monoclonal antibody treatment produced by Regeneron Pharmaceuticals under the brand name REGEN-COV are one of the drug treatments produced in response to the need for treatment in patients with COVID-19. The cocktail was given Emergency Use Authorization by the FDA for use in the treatment of mild to moderate coronavirus disease in adult and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death. It is also indicated for post-exposure prophylaxis for the same patient age group that have a high risk of progression to severe COVID-19.
The antibody cocktail is made up of two non-competing human IgG1 antibodies that neutralize the COVID-19 virus by targeting its spike protein. The “cocktail” was created versus just one antibody treatment, because of the company’s recent experience with resistance when a single antibody was used to treat another respiratory disease. In the beginning trials, phases 1 and 2, the cocktail reduced the viral load in patients and subsequently reduced hospital visits. In the phase 3 trials, the researchers found that COVID-19 related hospitalization from any cause occurred in 18 of 1355 patients (1.3%) and 62 of 1341 (4.6%) in patients receiving placebo. The time to resolution of symptoms was 4 days shorter for patients receiving the antibodies than compared to placebo, 10 days vs. 14 days. The antibody cocktail remains under Emergency Use Authorization and has not yet been fully approved by the FDA.
Omicron is a newer variant of COVID-19 that is rendering some previous treatments against the virus less effective. Regeneron has confirmed in a statement that its antibody cocktail loses most of its effectiveness against individuals infected with the omicron variant. Another victim of the omicron variant is bamlanivimab, an antibody treatment produced by Eli Lilly. This single antibody treatment has also been proven to be less effective in the face of omicron. The only other antibody treatment on the market that shows effectiveness against the omicron variant is sotrovimab. The National Institute of Health has recommended that remdesivir, a drug that was not previously recommended to be used in the treatment of the virus, now be added as a treatment option for patients infected with omicron.
1. Weinreich DM, Sivapalasingam S, Norton T, et al. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2021;384(3):238-251. doi:10.1056/NEJMoa2035002
2. Kaplon H, Reichert JM. Antibodies to watch in 2021. MAbs. 2021;13(1):1860476. doi:10.1080/19420862.2020.1860476
3. Statement on therapies for high-risk, nonhospitalized patients. National Institutes of Health. https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-therapies-for-high-risk-nonhospitalized-patients/. Accessed January 21, 2022.
4. Regeneron evaluating Regen-Cov and next generation ... newsroom.regeneron.com. https://newsroom.regeneron.com/static-files/969bdb0b-53f5-46c7-94fb-7473ee7f5be3. Accessed January 21, 2022.
Throughout my work experience and research, I have noted there have been many medications that have been utilized off-label to treat COVID-19. COVID-19 is an ongoing pandemic that has infected over 106 million people and killed over 2.3 million people worldwide. In the United States alone, it has infected over 27 million and killed over 465 thousand people. Three examples of potential treatments are 1. Ivermectin- an antiparasitic that may be able to prevent hospitalizations in COVID-19 patients, 2. Famotidine- an H2-receptor antagonist (H2RA) that may be able to improve outcomes in hospitalized COVID-19 patients, and 3. Angiotensin-converting enzyme inhibitor (ACEI) and Angiotensin receptor blocker (ARB)- hypertension treatments that have been debated to either be harmful or beneficial in COVID-19 patients.
As mentioned before, There are many different medications with other clinical indications that are being utilized in the treatment of COVID-19. This includes hydroxychloroquine, dexamethasone, and ivermectin. It is important to note that although remdesivir is the only FDA-approved drug to treat COVID-19, remdesivir has only been shown to shorten the time until recovery in hospitalized patients. Currently, there are no therapeutic agents that have been FDA-approved to prevent hospitalizations in COVID-19 patients. However, there are currently studies being conducted to see if any therapeutic agent such as ivermectin can have this outcome, with the primary endpoint as the need for hospitalization in patients with COVID-19. Ivermectin is an anthelmintic (more specifically, a broad-spectrum antiparasitic) that’s commonly used to treat a variety of parasitic diseases including but not limited to onchocerciasis and strongyloidiasis. In relation to the treatment of COVID-19, its proposed mechanism of action is through the inhibition of the classical protein nuclear import pathway mediated by importin-alpha and beta1, thereby inhibiting the replication of SARS-CoV-2 and decreasing its viral load.
Famotidine is an H2 receptor antagonist (H2RA) that is FDA-approved as an antihistamine or antacid. More specifically, famotidine is indicated for the treatment of ulcers, gastroesophageal reflux disease (GERD), the causes of excess stomach acid, and heartburn as well. Clinical studies were in progress to determine if the use of famotidine is associated with improved clinical outcomes in hospitalized COVID-19 patients in addition to the efficacy of famotidine in improvement of outcomes in hospitalized COVID-19 patients. These studies were conducted to see if famotidine, a H2RA, can inhibit the SARS-CoV-2 genome, specifically the 3-chymotrypsin-like protease which processes proteins essential for viral replication. Famotidine has been demonstrated to inhibit HIV viral replication in vitro which was the purpose of this trial. This study effectively demonstrated that the use of famotidine was associated with a reduced risk of clinical deterioration leading to intubation or death.
Nearly half of adults in the United States (108 million, or 45%) have hypertension as defined as a systolic blood pressure ≥ 130 mm Hg or a diastolic blood pressure ≥ 80 mm Hg or are taking medication for hypertension. Only about 1 in 4 adults (24%) with hypertension have their condition under control. The use of an ACEI or an ARB is considered first-line treatment in conjunction with a calcium-channel blocker (CCB) for treating hypertension. Currently, there is controversy surrounding the use of ACEIs and ARBs, two of the most commonly used antihypertensive classes that may increase ACE2 expression. Angiotensin-converting enzyme 2 (ACE2) has been implicated in facilitating the SARS-CoV-2 host cell entry and potentially contributing to the SARS-CoV-2 infection and severity. However, there is also evidence suggesting that ACE2 overexpression can protect from SARS coronavirus-induced lung injury. With contrasting evidence, it remains unclear whether ACEIs or ARBs are beneficial or harmful in patients with COVID-19. With more and more potential treatments of COVID-19 coming out, we must be cognizant and vigilant in what may work and what won’t.
COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). https://coronavirus.jhu.edu/map.html
King, C., Tessier, T., et al. (2020, August 31). Inhibition of Human Adenovirus Replication by the Importin α/β1 Nuclear Import Inhibitor Ivermectin. American Society for Microbiology- Journal of Virology. https://jvi.asm.org/content/94/18/e00710-20.long
Freedberg, D., Conigliaro, J., et al. (2020, September 1). Famotidine Use Is Associated With Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study. Gastroenterology. 2020; 159 (3): 1129-1131. https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0016508520347065?scrollTo=%23tblS1
Samimagham, H., Azad, M., et al. (2020, October 13). The Efficacy of Famotidine in improvement of outcomes in Hospitalized COVID-19 Patients: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020; 21: 848. https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-020-04773-6
The Food & Drug Administration (FDA) allowed for REGEN-COV (casirivimab and imdevimab) to be available for Emergency Use Authorization (EUA) on November 21, 2020. Regeneron Pharmaceuticals Inc is the pharmaceutical company responsible for development of the investigational monoclonal treatment REGEN-COV. The EUA is allowed by a Secretary of Health and Human Service (HHS) declaration to justify the emergency usage of drugs and biological products for the SARS-CoV-2 virus. The EUA was approved for REGEN-COV due to the known and potential benefits of the product used to diagnose, treat, or prevent COVID-19 symptoms. The benefits outweigh the potential risks, as well as no other appropriate alternatives are available. However, the FDA may also choose to revoke the EUA for REGEN-COV which will no longer allow its usage.
REGEN-COV is an investigational medication indicated for the treatment of mild to moderate symptoms of COVID-19 in non-hospitalized adolescents (12 years+) and adults, who weigh at least 40 kg (88 Ibs) and at risk of developing severe symptoms/risk of being hospitalized. REGEN-COV consists of casirivimab and imdevimab which are both investigational medicines, which are both administered through a single intravenous infusion. It is usually administered as a single dose and the duration of infusion is usually 20 to 50 minutes. REGEN-COV is also available as a subcutaneous injection, one dose involves four subcutaneous injections in separate locations over the body given simultaneously. Side effects due to intravenous injection involves bruising of the skin, pain, soreness, swelling and infection at the injection site. Patients may develop an allergic reaction to REGEN-COV during or after receiving the infusion, and must notify their physician right away. Signs and symptoms of allergic reaction include nausea, fever, chills, low/high blood pressure, chest pain, face/lips/throat swelling, skin rash and dizziness. Severe side effects which require immediate medical attention include fever, difficulty breathing, and rapid or slowed heart rate.
Taking REGEN-COV may interfere with the body’s immune response upon receiving the SARS-COV-2 vaccine, as well as increase the risk of developing a future infection. REGEN-COV has not been studied well enough in pregnant/lactating mothers and the risk of taking this medication outweighs the benefits of treatment. Veklury (remdesivir) an antiviral drug, and Bamlanivimab/etesevimab monoclonal antibodies, were also given EUAs by the FDA. Veklury was the first COVID-19 treatment to become available in the US on October 22, 2020 and is indicated for the treatment of patients with COVID-19 needing hospitalization. The mechanism of action of Veklury involves inhibiting the replication of SARS-CoV-2, the virus responsible for COVID-19. Bamlanivimab/etesevimab was approved on February 25, 2021 and is indicated for treatment of pediatric patients (12+, >40 kg) and adults with mild to moderate COVID-19 symptoms who have positive SARS-CoV-2 viral results and are high at risk for severe COVID-19 symptoms/hospitalization.
Food & Drug Administration. Regeneron EUA Patient Fact Sheet. https://www.fda.gov/media/145612/download. Published 2021 June 3. Accessed 2021 June 14.
U.S. Department of Health and Human Services, Public Health Emergency. REGEN-COV: Outpatient Monoclonal Antibody Treatment for COVID-19 Made Available under Emergency Use Authorization. https://www.phe.gov/emergency/events/COVID19/investigation-MCM/cas_imd/Pages/default.aspx. Reviewed 2021 May 26. Accessed 2021 June 14.
U.S. Department of Health and Human Services, Public Health Emergency. Veklury (remdesivir): ASPR’s Portfolio of COVID-19 Medical Countermeasures Made Available as a Licensed Product. https://www.phe.gov/emergency/events/COVID19/investigation-MCM/Pages/Veklury.aspx. Reviewed 2020 November 16. Accessed 2021 June 14.
U.S. Department of Health and Human Services, Public Health Emergency. Bamlanivimab/etesevimab: Outpatient Monoclonal Antibody Treatment for COVID-19 Made Available under Emergency Use Authorization. https://www.phe.gov/emergency/events/COVID19/investigation-MCM/Bamlanivimab-etesevimab/Pages/default.aspx. Reviewed 2021 June 01. Accessed 2021 June 14.
With the emergence of COVID-19 into society, many different medications are being used to treat the disease as it is fairly new and there is no established process to cure the disease. Tocilizumab, known as Actemra, is one of them. Actemra is an immunosuppressive medication used in cytokine release syndrome, giant cell arteritis (GCA), polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis and rheumatoid arthritis (RA). It is available both in IV and SQ injection, but procurement of IV Actemra in the United States is difficult. It works in the body by antagonizing the interleukin-6 (IL-6) receptor that is an inflammatory cytokine that has systemic effects on the body. Inhibition of these type of IL-6 receptors by Actemra leads to a reduction in cytokine and acute phase reactant production caused in many autoimmune diseases like the arthritis it is sometimes used to treat. Patients should be mindful that since this is an immunosuppressive drug, their susceptibility for infection is greater and patients are immunocompromised on this therapy with a number of patients developing TB (tuberculosis) when started on this medication. Some more medication side effects of Actemra include increase in cholesterol and triglyceride, increased risk of bleeding, weight change, high or low blood pressure, confusion and allergic reaction. All these should be taken into consideration before starting a patient on this medication. For COVID-19, there is no formal treatment guideline to treat the infection. Therefore, many health care providers have sought out various treatments like Actemra. Actemra is used to treat cytokine release syndrome and that is an apparent outcome in severe COVID-19 causing very high fever. With severe COVID-19 and fever, patients experience respiratory failure, multi organ failure and higher levels of inflammatory modulators such as interleukin-6 (IL-6). When cytokines like IL-6 are released uncontrollably, systemic inflammation and rapid progression of the disease is evident. Actemra stops this uncontrolled release, specifically on IL-6 receptors. A small study in China that was a prospective multicenter randomized controlled study with 11 patients with a fever due to COVID-19 showed progressive decrease in symptoms after Actemra administration. This urged health care providers to use Actemra as a viable option. Testing began on Actemra in the United States as a result of the small studies in China. However, as of October 2020, both the National Institute of Health’s (NIH) COVID-19 guidelines and the Infectious Diseases Society of America’s COVID-19’s guideline recommended against the use of anti-IL-6 receptor monoclonal antibodies for the treatment of COVID-19, except in clinical trial. This includes the use of Actemra in patients with severe COVID-19. This recommendation is because preliminary, unpublished data from randomized, controlled trials failed to demonstrate the efficacy of tocilizumab in patients with COVID-19. For Actemra, in the COVACTA trial, 450 adults hospitalized with COVID-19 related pneumonia were randomized to receive Actemra or placebo. The trial failed to meet primary endpoint or secondary endpoints. Differences amongst the Actemra and placebo groups were not statistically significant, showing the treatment was not as effective as we had hoped it would be.
Tocilizumab, a monoclonal antibody which acts against interleukin‐6 (IL‐6), was originally developed to treat arthritis. With the recent trials and studies, however, Tocilizumab has been shown to be an alternative treatment for COVID‐19 patients with a risk of cytokine storms. IL‐6 is a cytokine that plays an important role in inflammatory reaction and immune response, and recent experiences in China suggests that IL‐6 is one of the most important cytokines involved in COVID‐19‐induced cytokine storms. For this reason, Tocilizumab is recommended in seriously ill patients with elevated IL‐6. Acute respiratory distress syndrome is the leading cause of death in COVID–19 patients and the extensive release of pro–inflammatory cytokines is suspected to contribute to poor outcomes in patients. These pro-inflammatory cytokines can lead to cytokine storms which then progress to cardiovascular collapse, multiple organ dysfunction, and death rapidly. As a result, identification, treatment, and prevention of the cytokine storms are of utmost importance for the patients. The first study had 15 patients who qualified to be in the study. Three out of the four critically ill patients who received only a single dose of Tocilizumab therapy ended up passing away and the C-reactive protein level in the other critically ill patient failed to return to normal range (nearly 20 times higher than normal) during the week‐long session. In the other 11 patients, C-reactive protein levels were in or near the normal range within 1 week. In addition, Tocilizumab also had a higher rate of improvement in the oxygen–support category when compared to control. Although the two studies reported a good response in patients with Tocilizumab, the number of cases reported and sample size is still small. In addition, the treatment duration is not enough to reach a final conclusion. As a result, a sufficient number of COVID‐19 patients are still needed in order to continue testing the efficacy of Tocilizumab against COVID-19.
Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol. 2020;92(7):814-818.
Kewan, T., Covut, F., Al–Jaghbeer, M., Rose, L., Gopalakrishna, K., & Akbik, B. (2020, June 20). Tocilizumab for treatment of patients with severe COVID–19: A retrospective cohort study. Retrieved July 25, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305505/
Tocilizumab, an immunosuppressive drug, is a humanized monoclonal antibody. It is an interleukin-6 receptor inhibitor that blocks IL-6 from binding so a complex and signal transduction doesn’t occur. IL-6 is a cytokine involved in inflammatory and immune responses. Tocilizumab was a drug developed to treat arthritis and juvenile idiopathic arthritis. Currently, there is no treatment for Coronavirus but it has been proposed to use tocilizumab to treat severe COVID-19 since it is used to treat cytokine release syndrome. Uncontrolled release of cytokines causes systemic inflammation and rapid progression of disease. Severe symptoms of COVID-19 include respiratory failure, multi-organ failure, and higher serum levels of multiple cytokines including IL-6. Several clinical trials have been initiated around the world using and evaluating tocilizumab as a treatment for Coronavirus. In a prospective multicenter randomized controlled study done in China, it was found that after treatment with tocilizumab with conventional therapy, 11 patients with persistent fever had a decrease in body temperature within 24 hours and their respiratory function improved (Zhang). In another small clinical study done after the severe COVID-19 patients were given tocilizumab, the fever went back to normal after a few days and symptoms improved including lymphocytes levels returning to normal and elevated C-reactive proteins decreasing (Zhang). Adverse effects of long term use of tocilizumab requires monitoring including serious infections like tuberculosis, gastrointestinal perforations, and hypertension. It should be noted that there is the risk of bias in these studies done such as a small sample size used. Chinese COVID-19 guidelines have already included tocilizumab as a treatment with the first recommended dose of 4-8 mg/kg diluted in 100 mL of 0.9% sodium chloride injection. However, there are limited studies done thus far so more studies need to be conducted to evaluate and support the use of tocilizumab in COVID-19.
Cortegiani A, Ippolito M, Greco M, et al. Rationale and Evidence on the use of Tocilizumab in COVID-19: A Systematic Review [published online ahead of print, 2020 Jul 20]. Pulmonology. 2020;doi:10.1016/j.pulmoe.2020.07.003
Zhang S, Li L, Shen A, Chen Y, Qi Z. Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia. Clin Drug Investig. 2020;40(6):511-518. doi:10.1007/s40261-020-00917-3
At work I noticed the antipsychotic use for ICU delirium associated with COVID-19 patients was a thing. This virus has been shown to destroy the respiratory tract and effect the CNS. These put patients at an extremely high-risk brain dysfunction in patients. Human isolation, extended time away from family members and loved ones, as well as other elements of care should all be considered as adding to delirium. In patients with COVID-19, delirium can be due to direct CNS invasion, CNS inflammatory mediators, a result of other organ system failure, and other treatments and environmental factors. This includes use of sedatives for prone positioning of the patient and the quarantining and isolation during their treatment. Antipsychotic agents are usually use for severe agitation because these patients are at risk of self-harm with few effective alternatives. Currently, no antipsychotic are approved by the US Food and Drug Administration for the management of delirium, meaning use is off-label. Based on limited evidence, haloperidol dosed between 0.5 to 1 mg is recommended. It should be used as needed with a maximum dose of 5 mg per day. Continuous or prophylactic use is not recommended. Haloperidol can be administered orally, intramuscularly, or intravenously. It should be noted that intravenous haloperidol has been associated with clinically significant QT prolongation, and COVID-19 patients may be at risk to other medications for the virus. The antipyschotic effects of haloperidol are due to the butyrophenone structure that non-selectively block postsynaptic dopaminergic D2 receptors within the brain.
One medication that has become extremely popular, although not used technically to treat COVID-19, is enoxaparin. Through my work experience, I have seen many pharmacists question the use of the treatment because doctors have been ordering treatment doses for DVT prophylaxis. The direct effects of COVID-19 and indirect effects of the infection including hypoxia and complications due to severe illness may put patients at risk to thrombotic events. The early reports suggest hemostatic abnormalities, including disseminated intravascular coagulation (DIC), are frequently occurring in COVID patients The severe inflammatory response associated with the illness may also lead to thrombotic events. Many of the patients who are becoming critically ill already have the usual risk factors for thrombotic events. The other major concerns are the treatments for COVID-19 that may have adverse drug interactions with antiplatelet agents and anticoagulants the fact that many of the patients are being heavily sedated for long periods of time. An elevated D-dimer level is a common finding in patients with COVID-19 and the suspicion for a VTE should be high in the case of typical DVT symptoms, hypoxemia disproportionate to known respiratory pathologies, or acute unexplained right ventricular dysfunction in these patients. The usual dose for enoxaparin as a treatment dose for a pulmonary embolism of DVT is 1 mg/kg every 12 hours or once daily if their CrCl is <30ml/min. As for prophylaxis, the usual dose is 40mg subcutaneously daily or 30mg daily if the patient’s CrCl is < 30ml/min. There have been no specific studies for this use, and the risk of bleeding vs. clotting must be evaluated by the doctors.
www.onlinejacc.org › early › j.jacc.2020.04.031.full.pdf
Thank you Joe for sharing this experience at your hospital, very helpful to get this information out there to fellow professionals.
Remdesivir and COVID-19
Another drug that is being used in trials to treat COVID-19 is remdesivir. It is a nucleotide analog with broad spectrum anti-viral activity that is said to be active against other viruses similar to COVID-19. Its proposed mechanism of action involves the inhibition of RNA synthesis by targeting RNA dependent RNA polymerase and preventing the production of viral RNA. Gilead, the company responsible for manufacturing this medication, has initiated two phase 3 clinical studies in order to better understand the safety and efficacy of remdesivir in adults diagnosed with COVID-19. Enrollment in these trials began in March 2020 with a goal of 1,000 patients. The studies will look at both 5-day and 10-day dosing in patients with either moderate or severe coronavirus disease and will also compare remdesivir with and with out standard of care therapy. The primary outcome is the odds ratio for improvement on a 7-point ordinal scale on day 14 where “1” is death “4” is hospitalized and requiring low flow oxygen and “7” is not hospitalized.
A recent observational trial has explored the use of Ivermectin in COVID.
Ivermectin in COVID, this is the second time I cover this medication during this pandemic. Ivermectin, an FDA-approved "anti-parasitic previously shown to have broad-spectrum antiviral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 h post-infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h". Therefore, this medication warrants further investigation for possible benefits in humans.
While this article has not been peer review and the fact that this is not a randomized controlled trial, at least the authors went through the trouble of propensity matching some controls to help out with the outcomes.
Data on trial
international and multicenter
n=1408, 704 got the study drug
Drug: 150mcg/kg x 1 dose
The patients in the Ivermectin group seem sicker at baseline: more CAD (p=0.03), more COPD/asthma, African American race (which seems to be the most vulnerable group, more immunocompromised ( a trend).
Primary outcome: mortality
If on mechanical ventilation: Mortality 7.3% vs 21.3% (NNT=7.1)
Overall death rates: 1.4% vs. 8.5% (p<0.0001; NNT 14.1)
The disadvantage of this trial:
No notations on the subject's underlying organ dysfunction, adverse effects of the study drug.
No comment on the course of the illness of the subjects receiving the drug.
Also no percentages of subjects getting other therapies outside of being matched in the two groups.
Overall: The author concluded that Ivermectin was associated with a higher likelihood of survival. However, it is essential that the author recommends a randomized control trial to further confirm the possibility of this drug.
Another medication that is being to treat COVID-19 is Famotidine. Patients currently being treated at Northwell Health for COVID-19 are currently receiving Famotidine intravenously, at nine times the heartburn dose. In China, the patients had improved outcomes among patients with GERD, specifically with Famotidine and not with PPI. There was 2-3 fold protective association for Famotidine and death/intubation. The mechanism behind this improvement can be due to the binding of the drug to the catalytic site of the SAR papin-like protease(COv Ploro). This protease is involved in processing of viral polyprotein and contributes to biogenesis of virus replication complex.
The MATCH trial is a multi-site adaptive trial using hydroxychloroquine and famotidine. It is a blinded randomized trial with 1170 participants and the two intervention arms are :
hydroxychloroquine( + Intravenous Famotidine)
hydroxychloroquine + Placebo
Hydroxychloroquine sulfate 200mg tablets will be administered as per the current clinical protocol for COVID - 19; a loading dose of 400 mg BID on day 1, followed by 200 mg BID for 4 days, or a loading dose of 800 mg QD on day 1, followed by 400 mg QD for 4 days, as per site specific clinical protocol for COVID-19.
Famotidine Injection, 10mg/mL mixed with Normal Saline is given intravenously at 120mg (30% of 400 mg oral dose). The total daily dose proposed is 360mg/day famotidine IV for a maximum of 14 days, or hospital discharge, whichever comes first)
Anakinra and COVID-19
Kineret also known as anakinra is an immunosuppressive drug that is used to reduce pain and inflammation in conditions such as rheumatoid arthritis. It is an interleukin-1 (IL-1) receptor blocker and works by inhibiting the activity of IL-1 in the body. IL-1 is a group of proteins that stimulate inflammation in response to infections. COVID-19 patients who experience acute respiratory distress syndrome have widespread inflammation of the lungs. By using medications that target these inflammatory mediators, the idea is that we can help control symptoms and reduce the negative impact of the virus. There are currently no known published clinical trial evidence supporting efficacy or safety of anakinra in treating COVID-19. There are however a number of studies that are currently underway that compare treatment of anakinra with other interleukin inhibitors. It is also important to note that anakinra is approved only for subcutaneous administration in the U.S.
Hello Will, Thank you for sharing your experience with the the off-the-label use of
Kineret (anakinra) during this time of covid-19 pandemic.