The story so far: Globally unknown till under 200-days ago, the virus SARS-CoV-2, has today, according to the World Health Organization (WHO), caused the world’s largest pandemic. Over half-a-million people are under lockdown, over six lakh are infected and nearly 29,000 dead globally. In India, the numbers stand at a shade below 1,000 cases and 24 deaths (as on March 28, 9 p.m.). The number of cases is growing despite the unprecedented measures put in place by the Central and State governments. With the rise in cases, India has now joined the world in the search for drugs to treat COVID-19. Earlier this week, India approved the use of the anti-malarial drug, hydroxychloroquine, as a preventive medication for people at high risk, such as health workers and immediate contacts of a person who has tested positive for COVID-19.
What is causing death in COVID-19 patients?
In India, COVID-19 deaths have been seen in mostly the elderly population with other health issues including diabetes. Emerging data from China and Italy show that COVID-19 patients have severe blood-clotting disorders that lead to respiratory failure and death. Vaccination has been ruled out as an immediate solution, with WHO noting that even if the process is fast-tracked, a vaccine would take over 18 months to be ready for use. The discovery and licensed use of a drug comes with a long-gestation period.
Hence, WHO and other health agencies are re-looking the efficacy of known therapies and drugs this time to treat COVID-19.
Dr. Raman R. Gangakhedkar, Head of Epidemiology and Communicable diseases at the Indian Council of Medical Research (ICMR), said India, like the rest of the world, does not have the luxury of time to look for new treatment or vaccines right now, “though five vaccines have gone into animal toxicity tests. Our best bet right now is looking at re-purposed drugs”.
With this in mind, WHO Director-General, Dr. Tedros Adhanom Ghebreyesus, recently announced the launch of ‘Solidarity’, a giant multinational trial for testing therapies that researchers have suggested may be effective against COVID-19.
He said, “It is launched to generate robust, high quality evidence as fast as possible.” India, on Friday, aligned with the study after having so far stayed away due to its small sample size, according to the ICMR. WHO said, “This is now is an all-out, coordinated push to collect robust scientific data from across the world.”
What are the drugs being considered?
WHO is looking at some of what doctors and researchers believe are the most promising therapies including a combination of two HIV drugs, lopinavir and ritonavir (used in India also for an Italian patient in Rajasthan), anti-malaria medications, chloroquine and hydroxychloroquine, and an experimental antiviral compound called remdesivir.
As for hydroxychloroquine, a senior Health Ministry official clarified this by saying: “This drug has been brought in at an experimental level and the general public has been cautioned that it is not for use without a doctor’s prescription. To counter any shortage of the drug supplies we have banned the export of the finished drug and its component ingredients.”
A small study conducted in France found it led to a significant reduction in viral load in COVID-19 patients.
What does the research say so far?
The drug, remdesivir, developed to treat Ebola and related viruses, is being tested to find out whether it can be used on COVID-19 patients. Says WHO in research material it has released: “It works by shutting down the viral replication. This was first tested in a COVID-19 patient diagnosed in the United States, when his condition started worsening, according to a case report in the New England Journal of Medicine . The condition of the patient improved.”
The international health community has maintained that of the drugs in the Solidarity trial, remdesivir has the best potential — the drug shows that it can be used in high doses without causing toxicities.
What about anti-malaria drugs?
Chloroquine and hydroxychloroquine are decades-old anti-malarial drugs. Hydroxychloroquine is being looked at in India and the ICMR has said that it is currently studying the drug action in the Indian population with respect to COVID-19. After being left out from the ‘Solidarity trial’ previously, the two drugs were brought back for consideration when some countries showed interest in its potential.
A study on 20 COVID-19 patients in France who were given hydroxychloroquine showed a significant reduced viral load in nasal swabs. Hydroxychloroquine, in particular, is known to have a variety of side-effects, and can in some cases harm the heart. “People with heart conditions are at higher risk of severe COVID-19,” warns cardiologist Dr. Naresh Trehan, who heads Medanta Hospital.
The combination drug, ritonavir/lopinavir, was introduced two decades ago to treat HIV infections. Doctors in Wuhan, China, gave 199 patients two pills of lopinavir/ritonavir twice a day plus standard care, or standard care alone.
There was no significant difference between the groups as per reports submitted on March 15. Says Dr. K.K. Aggarwal, former head of the Indian Medical Association, “Although the drug is generally safe it may interact with drugs usually given to severely ill patients, and doctors have warned it could cause significant liver damage.”
He added that another combination under testing is interferon-beta, which WHO has cautioned might be risky.
Says Dr. Aggarwal, “15% of COVID-19 needs hospitalised care and of these 5% need ICU care. Now with time running out rapidly for the entire world, re-purposed drugs are being aimed at to contain the problem, reducing hospital load, freeing critical hospital beds and allowing people to swiftly return to normal work. Agencies are also looking at unapproved drugs that have performed well in animal studies with the other two deadly coronaviruses, which cause Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).”
Is plasma therapy a possibility?
The world health community is also looking at plasma or antibody therapy for COVID-19 with China using it recently on its patients. WHO had recommended its use against Ebola, and issued protocols for its use to treat MERS but its clear-cut benefit to treat COVID-19 cases is still under investigation.
The novel coronavirus hails from a family on which work has already been done worldwide after SARS and MERS. Says Dr. Gangakhedkar, “This really helps in research in the sense that we don’t have to start from scratch. This is vital in our hunt for drugs to contain this virus.”
Why is the lockdown necessary?
Lav Agarwal, Joint Secretary, Union Health Ministry, says, “The lockdown will give us time delay, maybe push back any surge towards community transmission of COVID-19. It is also helping us to re-draw our strategy to cope with this very strong and infectious virus. India has asked all State governments to be prepared in terms of manpower, hospital facilities and care for patients.”
India is now readying its health infrastructure to cope with a virus that has tested the most resilient health-care systems in the world, bringing them to their knees. According to Prof Balram Bhargava, Director-General, ICMR, “This is a crisis like no other and we will have to work together as a nation and an international community. Globally, the problem is being tackled with great urgency. The way out is to find a sustainable solution quickly.”