Covid-19 treatment: A lowdown on possible cure and drugs being used

India is using HCQ as a prophylactic (or preventive) for frontline medical workers, police, etc
It has been more than six months since the first Covid-19 infection was reported. Now, even as the SARS-CoV2 pandemic has left over half a million people dead, there is still no cure against the virus that causes Covid-19. As such, antiobiotics do not help with viral infections, but some old anti-viral drugs have been repurposed to treat Covid-19 patients. Researchers worldwide are testing various possible treatments that would help patients recover faster from the disease.

According to the Mayo Clinic, an American non-profit academic medical centre, supportive care is aimed at relieving the symptoms and might include pain relievers (ibuprofen or acetaminophen), cough syrup or medication, rest, and fluid intake. It says that there is no evidence that ibuprofen or other non-steroidal anti-inflmmatory drugs (NSAIDs) need to be avoided.

The US Food and Drug Administration (FDA) granted emergency-use authorisation for antiviral drug remdesivir (developed by Gilead, originally for Ebola) to treat severe Covid-19 patients. Several corticosteroids like dexamethasone have also been recommended for use, apart from supplemental oxygen or mechanical ventilation.

Immunosupressant drugs, too, are being tried to treat Covid-19 patients with abnormal immune response against the virus. Doctors have also prescribed drugs like Roche's Tocilizumab, used typically for rheumatoid arthritis (a painful condition where a patient's own immune system attacks their joints). The immune system of patients with Covid-19 often goes into an overdrive and produces an excess of immune-signalling molecules called cytokines. This cytokine release syndrome, popularly called the 'cytokine storm', leads to hyper inflammation. This, in turn, exacerbates breathing difficulties and might lead to acute respiratory distress syndrome (ARDS). Drugs like Tocilizumab and Interferon alfa-2b (used to treat Hepatitis B & C) help suppress the immune system response by blocking certain receptors called interleukin-6 (IL6). Interferon alfa-2b is under clinical trial for Covid-19 treatment now.

Let’s take a look at the common drugs that are being used in India for treating Covid-19 patients. These are all 'off-label' uses of drugs or approved for 'emergency use', as none of these is a proven treatment for the disease. Some are undergoing trials, too.

Hydroxycholoroquine (HCQ)

India is using HCQ as a prophylactic (or preventive) for frontline medical workers, police, etc. It is also approved as a treatment in mild cases with some caveats (not to be used on people with retinopathy, cardiac rhythm disorders, and kids below 15 years of age). After US President Donald Trump touted this drug as a magical medicine for Covid-19, several global trials like the WHO Solidarity trial and UK's Recovery trial have not found conclusive evidence to suggest proven benefits of HCQ. A strip of 15 tablets of HCQ (200 mg tablets) costs around Rs 100 or it is roughly priced at Rs 6 per tablet. Ipca and Zydus Cadila are the major producers.

Favipiravir

Oral antiviral drug approved for use in Japan for influenza patients recently got the regulator's approval in India for emergency use on patients with mild to moderate conditions. Mumbai-based Glenmark conducted clinical trials for India and launched the drug for Rs 103 per tablet. Within a month of the launch, Glenmark slashed the prices to Rs 75 per tablet. Several Indian players, including Hyderabad's Dr Reddy's Laboratories, are in fray to launch this drug. A pack of 34 tablets now costs Rs 2,550 for Glenmark's brand FabiFlu. Further price crash is expected.

How does this drug work? Researchers have suggested that favipiravir gets incorporated into the viral RNA which induces mutations to the RNA and eventually causes reduction in viral load. The drug may be binding itself to certain areas of the viral RNA polymerase (enzyme) and it stops the enzyme from doing its work (that is, making new RNA). Basically, it can help stop the virus from making more copies of itself inside the patient’s body. The drug cannot be used for patients with renal or hepatic (liver) conditions.

Remdesivir

Developed by US-based Gilead Sciences for Ebola, this drug has been approved in India for hospital use. It is an injectable drug, and two companies have launched it so far – Hetero's Covifor (Rs 5,400 per dose) and Cipla's Cipremi (Rs 4,000 per dose). Others like Zydus Cadila, Mylan and Dr Reddy's are also expected to launch this drug, after which the prices might come down further. Clinical trials have shown that remdesivir helps shorten the recovery time and in turn the hospital stay. It, however, does not reduce mortality.

Remdesivir works by faking out genetic building blocks and thus interrupting the viral replication. This stops the virus from making copies of itself, reducing the viral load.

Tocilizumab

This Roche drug, marketed by Cipla in India, is used in hospitals to treat severe Covid-19 patients, especially those experiencing a cytokine release syndrome. It works to reduce the inflammation that happens when a patient's immune system reacts abnormally. The drug is expensive, priced around Rs 40,500 for a 400 mg dose (commonly prescribed), Rs 20,200 for 200 mg, and Rs 8,112 for an 80 mg dose.  

Itolizumab

Biocon's psoriasis (skin condition) drug is also an injectable for hospital use. The drug was launched by Biocon in 2013 under the brand name Alzumab to treat plaque psoriasis. It is priced at Rs 7,950 per vial and most Covid-19 patients would need four vials, so the total cost of therapy comes to Rs 32,000 (some patients may need two additional vials). The drug was approved on July 11 by the Drug Controller General of India (DCGI) for restricted emergency use for treating moderate to severe coronavirus disease cases

The drug works by regulating the immune system which helps slow down the release of inflammation-causing cytokines. It works best when given to patients before the immune system is hyper-activated.

Steroids

Indian clinical management protocol has use of steroids like Dexamethasone. This inexpensive steroid (Rs 3 or so for a strip of 10 tablets and Rs 10 for a 4 mg injection) has been found to be effective in treating patients. According to the World Health Organization (WHO), "it was tested in hospitalised patients with Covid-19 in the United Kingdom’s national clinical trial ‘Recovery’ and was found to have benefits for critically ill patients". WHO further said, according to preliminary findings, the treatment was shown to reduce mortality by about a third for patients on ventilators, and mortality was cut by about a fifth for patients requiring only oxygen. Dexamethasone falls under a broader class of drugs called corticosteroids and is an oft-used steroid for its powerful anti-inflammatory properties. It is administered for various conditions like allergies, immune system disorders, even arthritis.

Methylprennisolone is another steroid being used by Indian doctors to handle moderate to severe Covid-19 cases. It is also a corticosteroid and costs around Rs 50 for a 40 mg injection.

Heparin

A common anti-coagulant drug (that reduce blood clots from forming in the body), this is used in treating Covid-19 patients. The SARS-CoV-2 virus works by using its spike protein to attach to human cells and begin infection. According to recent findings, heparin can bind with the surface spike protein and can potentially block the infection. Researchers at Rensselaer Polytechnic Institute in the US have said heparin could effectively neutralise SARS-CoV-2. According to findings published in Antiviral Research, heparin may act as a decoy to prevent the virus from infecting human cells. It can be delivered into the body as a nasal spray or nebulizer, too.

So far, low-molecular-weight heparin has also been used to reduce the risk of developing clots in patients. Clots can develop in veins of legs, etc, when people are hospitalised and confined to beds. If the clot is dislodged, it can cause stroke, myocardial infarction (commonly understood as heart attack), pulmonary embolism, etc. Heparin is an anti-coagulant. Heparin is also a low-cost drug and the country's pricing regulator recently allowed a 50 per cent hike in the price of this essential drug (till December), as the prices of the raw material went up. The National Pharmaceutical Pricing Authority (NPPA) used its emergency powers to allow companies to raise the price of heparin, which now has a price ceiling of 1,000 International Units Per Millilitre (IU/ml) of heparin injection at Rs 24.39 per ml, and 5,000 IU/ml of injection at Rs 60.54 per ml. Prices of raw materials imported from China have shot up by 211 per cent compared with base year of 2018.

Convalescent plasma therapy

In this experimental therapy, blood plasma from patients who have recovered from Covid-19 infection is collected and transfused into a currently sick person. It gives the receiver a 'borrowed immunity' as the antibodies that a recovered person has are passed on to the sick person. This helps them fight the pathogen. This therapy was used in SARS1 in 2003 and also in MERS in 2012. There is no fixed rate for this – while some donors give their plasma free of cost, some charge from Rs 20,000 (for 300 ml of plasma) to any amount. Plasma banks for this have already been set up in some states.

Table: https://infogram.com/coronavirus-cure-1hxj48ynorgq2vg?live 



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