What medications and treatments are currently being used in combat against COVID-19, and how effective are they?
Top in Trends: COVID Treatment
Coronavirus disease has been spreading across the world by leaps and bounds. Yet no perfect cure was found till date except for some drugs which are approved for emergency and conditional use by different regulatory bodies.
At these times, one should be aware of the current treatments and should be able to follow the updated guidelines to help protect themselves and their families in order to defeat COVID-19.
After the overhyped HCQ (Hydroxychloroquine) was revoked for its emergency use for COVID treatment by FDA, the need for being vigilant and updated has become quite obvious to cut off unnecessary use of medications and side effects associated with them.
Let’s have an overview of the drugs that are currently in use in the treatment of COVID 19.
1. Remdesivir:
Remdesivir is an antiviral used for the treatment of Ebola and has already been repurposed for the treatment of Covid19. It is originally developed by the American company Gilead Sciences. As part of the continuing Solidarity Trials of the World Health Organisation, Remdesivir obtained a US Food and Drug Administration (USFDA) Emergency Usage Authorisation on May 1.
- It is a Hospital-only, Injectable drug.
- Indian companies allowed by DCGI to launch drug under license from Gilead Hetero Pharma — Covifor / Rs5400/100 mg vial Cipla — Cepremi / Rs4000/vial Mylan — Yet to be launched
Mechanism of Action:
Remdesivir is designed to obstruct the viral replication of SARS-CoV-2. It is the stage when the virus creates copies of itself, followed endlessly by the copies creating copies of themselves.
Coronaviruses are RNA viruses, and at the replication stage, the key viral protein at play is an enzyme called RNA-dependent RNA polymerase (RdRp). Remdesivir mimics a part of the viral RNA, and it inserts itself into the RNA strand during the replication stage. When attached, the drug prevents any further copying, leaving the RNA strand incomplete and unable to produce critical viral parts.
2.Favipiravir:
Recently, an oral antiviral drug approved for use in influenza patients in Japan has been approved for emergency use by the regulator in India for patients with mild to moderate conditions. Glenmark, a company based in Mumbai, conducted Indian clinical trials and launched the drug for Rs 103/- per tablet. Glenmark cut the prices down to Rs 75/- per tablet within one month of the launch. Several Indian manufacturers, including Dr. Reddy ‘s Laboratories at Hyderabad, are in a state of fray to launch this drug. A pack of 34 tablets of Glenmark’s FabiFlu brand now costs Rs 2,550.
Favipiravir has shown clinical improvement of up to 88 percent in mild to moderate Covid-19 cases, as stated in an official statement.
- The drug is not approved in the EU or US.
- Contraindications: Cannot be given to patients with severe renal complications, hepatic impairment, pregnant and lactating women.
Mechanism of Action:
Since the novel coronavirus is an RNA virus, studies have shown that Favipiravir gets activated inside the cells and then gets incorporated into the viral RNA. It restricts the multiplication of the virus in the body of the host once it gets inside a host cell, reducing viral load.
3. Steroids (Dexamethasone, Methylprednisolone):
Indian clinical management protocol takes advantage of steroids such as dexamethasone. This cheap steroid (Rs 3 or so for a 10-tablet strip and Rs 10 for a 4-mg injection) was found to be effective in treating patients. According to the World Health Organization (WHO), “in the United Kingdom’s national clinical trial ‘Recovery’ it has been tested in hospitalized patients with Covid-19 and has been found to benefit critically ill patients.” According to preliminary results, the procedure has been shown to reduce mortality by about one-third for patients on ventilators, and mortality has been reduced by about one-fifth for patients needing only oxygen. Dexamethasone falls under a broader class of drugs called corticosteroids, and for its powerful anti-inflammatory properties is an often-used steroid. It is administered for various conditions, such as allergies, disorders in the immune system, and even arthritis.
Methylprednisolone is another steroid that Indian doctor’s use to treat moderate to severe cases of Covid-19. It is also a corticosteroid, and a 40 mg injection cost around Rs 50.
Mechanism of Action:
Steroid drugs reduce inflammation, which sometimes develops in Covid-19 patients as the immune system overreacts to fight the infection. The UK-based RECOVERY trial results have shown dexamethasone reduces death by up to a third in Covid-19 patients on ventilator support, and by a fifth in patients receiving only oxygen.
Dexamethasone is categorized under corticosteroids, which closely mimic cortisol, the hormone naturally produced by the adrenal glands in humans.
4.Monoclonal Antibodies:
Tocilizumab:
This Roche drug, marketed by Cipla in India, is used in hospitals for the treatment of COVID-19 severe patients, especially those with a cytokine release syndrome. This functions to reduce the inflammation that happens when an abnormal response in a patient’s immune system has occurred. The medication is pricey, valued about 40,500 Rs for a dosage of 400 mg (commonly prescribed), 20,200 Rs for 200 mg, and 8,112 Rs for an 80 mg dose.
Itolizumab:
Psoriasis (skin condition) drug from Biocon is also an injectable medication for use in hospitals. Biocon released the drug in 2013 to treat plaque psoriasis, under the brand name Alzumab. It is priced at Rs 7,950 per vial, and most Covid-19 patients will require four vials, so the total therapy cost comes to Rs 32,000 (some patients may need two extra vials). The drug is authorized by the Drug Controller General of India (DCGI) on July 11 for restricted emergency use to treat cases of moderate to extreme coronavirus disease
The drug works by controlling the immune system which helps to slow the release of cytokines causing inflammation. This functions best when given to patients before hyper activating the immune system.
5. Plasma therapy:
Convalescent plasma therapy or CPT requires transfusing one healed patient’s blood plasma into another. The treatment was used earlier for many diseases, but its efficacy for Covid-19 is still under study. The therapy is intended for patients with low levels of oxygen saturation, or those suffering from a cytokine storm. Under the ICMR protocol, those at risk of cytokine storm, severe breathlessness with massive pneumonia, are given a choice.
In this experimental treatment, blood plasma from patients recovering from Covid-19 infection is extracted and transfused into a person who is currently ill. This gives the recipient a ‘borrowed immunity’ as the antibodies are passed on to the sick person by a recovered individual. It makes them fight back against the pathogen. This therapy was used in 2003 in SARS1 and in 2012 in MERS too. There is no fixed rate for this — although some donors give their plasma free of cost, others charge up to any amount from Rs 20,000 (for 300 ml of plasma). For some States, plasma banks have already been developed for this.
Mechanism of action:
Convalescent plasma therapy seeks to make use of the antibodies developed in the recovered patient against the coronavirus. It boosts the received individual’s fight against the virus.
6.Heparin:
A popular anticoagulant medication (that reduces the formation of blood clots in the body), this is used in the treatment of Covid-19 patients. The SARS-CoV-2 virus works to bind to human cells and begin infection by using its spike protein. Heparin can bind to surface spike protein, which can potentially block the infection, according to recent findings. Researchers at the US-based Rensselaer Polytechnic Institute said heparin could neutralize SARS-CoV-2 effectively. Heparin can serve as a decoy to prevent the virus from infecting human cells according to findings published in Antiviral Research. It may also be administered as a nasal spray or nebulizer to the body.
To date, low-molecular-weight heparin has also been used to reduce the patients’ risk of forming clots. If people are hospitalized and confined to beds, clots can form in the veins of legs, etc. It can cause stroke, myocardial infarction (commonly known as a heart attack), pulmonary embolism, etc. if the clot is dislodged. Heparin serves an anti-coagulant. Heparin is also a low-cost product, and the country’s pricing regulator recently approved a 50 percent hike in this vital product ‘s price (until December), as the raw material prices increased. The National Pharmaceutical Pricing Authority (NPPA) used its emergency powers to allow companies to increase the price of heparin, which now has a price limit of 1,000 International Units Per Millilitre (IU / ml) of Rs 24.39 per ml injection, and 5,000 IU / ml of Rs 60.54 per ml injection. Prices of imported raw materials from China have shot up 211 percent compared to the 2018 base year.
8.Doxycycline:
Doxycycline is a broad-spectrum antimicrobial targeting the synthesis and ribosomes of bacterial proteins. Many reviews discussed doxycycline’s antiviral role on dengue virus (DNV) viruses, vesicular stomatitis virus (VSV), and chikungunya virus (CHIKV). Doxycycline can achieve its antiviral action through many mechanisms; interference with viral adsorption as in DNV and CHIKV or Replication Inhibition as in can inhibit DNV and CHIKV proteases; these proteases are closely associated with the process of replication of SARS-CoV-2 in the cleavage of viral polyproteins.
Doxycycline also has an anti-inflammatory effect which is accomplished by modulating interleukin expression 6 and 8, and TNF-alpha. For mice exposed to intratracheal lipopolysaccharide, it also blocks the migration of neutrophils into the lungs. Based on previous data, doxycycline could be beneficial for SARS-CoV2 management by inhibiting viral replication and improving the outcome of the disease through its anti-inflammatory effect.
A recent study found that doxycycline has an anti-SARS-CoV2 in-vitro effect. They can inhibit the concentration-dependent replication of SARS-CoV2. The doxycycline EC50 against SARS-CoV-2 indicates a weak-moderate antiviral effect so that COVID-19 can not be used as a monotherapy. For better results, it is advisable to add hydroxychloroquine to doxycycline. Coxiella burnetii is a known treatment for this combined regimen. It has a good safety profile; thus, it may be a suitable substitute for COVID-19 for azithromycin and hydroxychloroquine, which can cause cardiovascular mortality due to synergistic effects on QT duration.
In addition, doxycycline is a potent antimicrobial with both anti-inflammatory and antiviral activities. The combined hydroxychloroquine therapy could be a safe and effective COVID-19 treatment.
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References:
Covid-19 treatment: A lowdown on possible cure and drugs being used
COVID-19 treatment update: Here is a list of all drugs used in India; their pros and cons
Doxycycline: a new treatment option for COVID-19
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