Is Covid-19 treatment based on trial and error?

As the number of COVID-19 cases in India soar, so does information (and misinformation) about the treatment protocols, adding to the strain, confusion and feeling of helplessness among patients and caregivers.

There are many contradicting views. Questions have been raised about combinations of repurposed and experimental medicines recommended by healthcare practitioners as a one-size-fits-all solution.

Researchers, medical practitioners, and citizens have been debating if the over-prescription of drugs is responsible for the rising health complications among COVID-19 patients.
Top-notch doctors address the many issues people are raising on the pros and cons of various treatment options.

Remdesivir — to use or not?
Drugs such as Chloroquine, Remdesivir, Favipiravir and other experimental drugs, which were used to treat COVID-19 around the globe, have subsequently been found to be of no or limited use.

Though the WHO has issued a conditional recommendation against the use of Remdesivir in COVID-19 patients, the ICMR in its recent guidelines continues to endorse it as an ‘off label drug' in the management of moderate to severe cases of COVID-19 infection within 10 days of onset of symptoms, points out Dr. Viswesvaran Balasubramanian, Senior Interventional Pulmonologist and Sleep Medicine Specialist, Yashoda Hospitals.

Dr Nageshwar Reddy presents a different view. “There is a lot of confusion about the use of Remedesivir, and world scientific literature is divided. The Ministry of Health in India did not recommend it. But unfortunately, if you look at the studies, there are a lot of flaws,” he says. According to Dr. Reddy, “in all the studies, Remdesivir was used at a later stage of disease, when the patient was already very sick, either on ventilation or oxygen.” He however cites a study published in the New England Journal of Medicine, saying that “it shows that if Remdesivir is used within seven days of the start of the disease, then it is effective in reducing mortality.”

Steroids — When and how much?
Unmerited use of steroids is leading to uncontrolled sugar levels in patients, and it is also thought to facilitate the rapid growth of the deadly Black Fungus. Though many patients may require steroids, the dosage and duration of use need reconsideration, especially among diabetic patients, experts feel.

Dr Reddy feels a common major mistake is taking steroids from the first day of diagnosis itself. “Steroids could worsen the infection if given too early,” he warns. “The virus starts multiplying in the body, but the body feels relaxed due to steroids (hampering the ability to fight back), and from the second week, the disease turns serious, patients require ventilator support, and then, even increasing the dose of steroids will not work,” he says. An Oxford University study has found that steroids like Dexamethasone, when used in a dose of 6 ml gm in the second week — when the cytokine storm occurs — can decrease the need for ventilator support and also bring down mortality rates. “The trial clearly mentions use of steroids in the second week, and only for those who require oxygen,” says Dr Reddy.

“There are controversies regarding drugs like Tocilizumab and immunosuppressants too,” Dr Reddy points out. In his view, Baricitinib a drug usually used in the treatment of arthritis and is now being used increasingly to treat COVID-19 patients, “acts like a steroid without the side-effects of steroids.” He adds that “earlier, it was extremely expensive, costing around '3,000 per tablet, but now Indian companies are making it for around '30 to '40 a tablet.”

Evolving Remedies

A look at COVID-19 treatment modules
It’s been over a year since COVID-19 was declared a pandemic, but the world is still trying to find ways to conquer it. The second wave has been more destructive than the first one. Many lives have been lost.
The disease is new, the virus itself seems to be evolving, and so is the knowledge about it, and consequently, the best ways of handling it can only be arrived at by a process of trial, and possibly, error.

Researchers, medical practitioners, and citizens have been debating if the over-prescription of drugs is responsible for the rising health complications among COVID-19 patients.

An overall look at the situation indicates that doctors are prescribing up to a dozen medicines for even mild cases of COVID-19; antibiotics like azithromycin and doxycycline are being commonly advised despite significant clinical trials having found no evidence of their efficacy; the World Health Organization (WHO) has cautioned that there is no evidence to suggest that the antiviral drug Remdesivir is useful in treating hospitalised COVID-19 patients; Plasma therapy has been dropped as a treatment for the disease after a Government panel found it ‘ineffective’; and drugs that have proven benefits in managing the infection are often prescribed at inappropriate clinical stages of the disease – for instance, steroids like dexamethasone and methylprednisolone benefit only patients with moderate to severe COVID-19, but many doctors prescribe them for patients with mild infections.

Monoclonal antibody therapy – Proven efficacy
“Many things are clear now. The therapy scientifically proven to be most effective is the use of monoclonal antibodies within seven days of disease onset. This is used only for mild and moderate cases of COVID-19, and prevents these cases from turning severe. It is found effective even on patients above 65 years and those who have diabetes, or kidney and cardiac problems,” says Dr D Nageshwar Reddy, Chairman of the Asian Institute of Gastroenterology and AIG Hospitals.

2-DG — A GAME-CHANGER?
Lately, 2-DG, a drug developed by India’s Defence Research and Development Organisation (DRDO), has been in the news as a possible saviour in COVID-19 infections.

Talking about the process of endorsement, Dr G. Satheesh Reddy, DRDO, chief, says “Phase-2 trials were done on 110 patients from May 2020 to Oct 2020. Safety was very well established and verified by an independent DSM Board. Efficacy was found to be very highly significant in Phase-2. Based on these highly encouraging results, DCGI gave permission for Phase-3 trial. Phase-3 trials were done on 220 patients from November 2020 to May 2021 in 27 hospitals throughout the country. DCGI has given Emergency Use Authorisation for its use as adjunct therapy in moderate to severe covid patients.”

Sudhir Chandna, Chief Scientist INMAS and Additional Director DRDO, explains that “the primary efficacy endpoint analysis has shown that 42% of patients treated with 2-DG plus standard care were able to be free of oxygen dependence, as compared to 31% patients in standard care.” He adds that patients with controlled diabetes were among those enrolled in the trial of the prescribed dose (45 mg/kg twice a day), and the drug was found to be safe in these patients too. “Uncontrolled diabetics were excluded from the trials, and the drug is not recommended for them,” he cautions.
Giving his views on this treatment option, Dr Nageshwar Reddy says, “2-DG is potentially a good drug in patients who require oxygen. It is an old drug used for cancer patients, where the cells divide rapidly.”

PLASMA — NO LONGER AN OPTION
Talking of Plasma therapy, Dr. Viswesvaran Balasubramanian notes that despite clinical trials suggesting no significant benefit in this intervention, it was initially recommended by the Indian Council for Medical Research (ICMR) for ‘off label' use. “However, this was changed following evidence generated from international trials, including some information indicating the possibility that plasma played a role in facilitating new mutations of the virus.”

TIMING AND TREATMENT
Meanwhile, Dr Shankara Chetty, a General Practitioner in South Africa who qualified as a doctor in India, believes that COVID-19 is allergic in nature. He has advised his community to record the first day of the appearance of symptoms like fever, headache, cold, dry cough, body aches etc., and note the eighth day, when the symptoms should get better. However, instead of getting better, if the patient develops breathlessness on that day, he/she should be immediately treated with steroids and anti-histamines under the guidance of a qualified doctor, according to Dr. Chetty. He claims that none of the 4,000 COVID patients he has treated using this guideline needed hospitalisation, oxygen support or a ventilator.
Meanwhile, based on evolving data from clinical trials conducted both in India and abroad and with the introduction of new regimen like the antibody cocktail for mild to moderate COVID-19 pneumonia in India, we may expect to see further changes in the treatment modules.
 

Fungal infection — A fallout of treatment?
Incidence of Mucormycosis or Black Fungus has been linked to the treatment protocol adopted for the disease.

Dr Kasu Prasad Reddy, Chief Surgeon, Founder & Mentor MaxiVision Eye Hospitals Group, explains that “Black Fungus is said to be secondary to severe reduction of immunity. The general feeling is that the reason for this declared epidemic of Black Fungus could be the use of industrial oxygen, unsterile humidification while giving oxygen, bad diabetes control, normal and abnormal usage of steroids, and last but not the least, self-prescription by patients and unqualified persons.” He adds that “in reality it is very difficult to pinpoint one or the other reason as the exact cause of Black Fungus infection.”