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In the Time of COVID-19, ‘What’s the Harm’ Prescriptions Are Not Harmless

In the Time of COVID-19, ‘What’s the Harm’ Prescriptions Are Not Harmless

A scanning electron microscope image of SARS-CoV-2 (yellow) isolated from a patient, emerging from the surface of cells (blue/pink) cultured in the lab. Image: NIAID/Flickr, CC BY 2.0

Thousands are dying horrible deaths of COVID-19 every day in India. The heartbreaking stories of people gasping for oxygen, their relatives running from pillar to post to get a hospital bed, chasing after medicines and desperately calling for help on social media have been well documented.

Less appreciated are the stories of hundreds of thousands who, upon recognising symptoms suggestive of the disease and receiving the dreaded diagnosis, are running straight into the hands of predatory medical practitioners, who are exploiting this desperation to peddle unproven therapies and order unnecessary tests.

I became aware of this when family members, friends, colleagues and patients started calling me for advice. I would give the common-sense advice, which was largely reassurance, to take paracetamol, monitor oxygen saturation and get medical help locally. Soon, prescriptions started coming to my WhatsApp number and email inbox. They consisted of anywhere between six and 10 medicines and a series of investigations.

After talking to a few colleagues, I decided to check (where else but Twitter) if this was common. I am a modest Twitter user and have never seen my feed fill up so quickly with responses and retweets, all with similar stories.

Reliable data doesn’t exist – but of the almost 26.7 million cases of COVID-19 reported thus far in India, fewer than 10% have required hospitalisation. A vast majority of those with the disease have mild to moderate symptoms and get better without entering hospitals. And in most instances, they seek care from local medical practitioners.

A typical COVID-19 prescription in India (and according to reports from other parts of the world) consists of a mix of azithromycin, doxycycline, ivermectin, hydroxychloroquine, vitamin C, vitamin D, zinc and n-acetylcysteine, often along with inhaled budesonide or oral dexamethasone (both are corticosteroids). Other antibiotics, including ones typically given for serious infections seen in hospitalised patients, are added “just in case”.

Also read: Have You Tested Positive For COVID-19? This is What Happens Next.

The antiviral drug favipiravir, which is not recommended by any treatment guideline, was reported to have become the top-selling pharmaceutical product in India in April 2021. Drugs to prevent blood clotting, meant to be used in special situations such as those at high risk of developing clots, are frequently prescribed in outpatient settings. This is against the recommendations of most international expert panels.

Many doctors have printed out such prescriptions and handed them out or sent them over WhapsApp. Stories of medicine shortage have been plastered all over the media. While a lot of them are genuine, at least some are deliberately made up to foster demand. Many, including Bibek Debroy, have written quite knowledgeably about this.

A major source of harm with such ‘polypharmacy’ is the risk of adverse effects that arise due to the use of these drugs, both individually and as a result of interacting with each other inside the body.

The interaction could be direct, i.e. interfering with each other’s mechanism of action or disposal in the body, or indirect through their impact on the multiple biological processes that happen inside our tissues. Such data on drugs’ adverse effects is usually accumulated through careful study or by observation in real-world situations. The cocktail of drugs in use today has not been tried before in clinical practice. But how they interact with each other is unknown, much less their interaction with other drugs these patients may already be taking for unrelated conditions.

A pharmacist holds the anti-parasite drug ivermectin in Santa Cruz, Bolivia, May 19, 2020. Photo: Reuters/Rodrigo Urzagasti

Therefore, it is difficult to judge whether complications that might develop are a result of COVID-19, an adverse drug reaction or a new complication. There have been reports of patients improving from the disease and suddenly deteriorating. At a minimum, such events need to be documented along with their treatment details.

Indiscriminate drug use continues even inside the hospital. Much has been written about the high prevalence of fungal infections among COVID-19 patients. This is not a surprise given the indiscriminate use of high-dose steroids1, powerful antibiotics that suppress natural human antimicrobial flora. Together with a compromised immune system and breaches in the natural barriers, these forces create a perfect storm for fungal infections to take root.

Also read: COVID-19 and Black Fungus: What Is Mucormycosis?

Unlike in the early days of the pandemic, when there was little empirical basis to guide patient management, we now know a lot about the disease. The evidence-base for diagnostics and therapeutics has grown thanks to many clinical trials.

We know that for the outcomes that matter to patients, doctors and health systems (such as risk of death, need for admission in hospital, mechanical ventilation, dialysis and other serious complications), ivermectin, hydroxychloroquine, vitamin C, vitamin D, zinc, convalescent plasma in any situation, and steroids and/or remdesevir in non-severe disease offer no real benefits.

Equally dubious is the role of other antibiotics, like doxycycline and azithromycin. The risk of developing a bacterial infection in individuals isolating at home and not otherwise immunosuppressed is really low. Still, these drugs are routinely prescribed, often under the guise of “but we have to do something” and “patients ask for it”.

Together with therapeutics, a full diagnostic work-up is ordered, even for asymptomatic patients or those with mild disease who are better off with home care. The list typically includes a complete blood count, blood sugar, HbA1c, kidney and liver function tests, and levels of D-dimer, interleukin-6, procalcitonin, C-reactive protein, lactate dehydrogenase and ferritin.

All of these investigations are conducted at private laboratories. COVID-19 test packages, offering varying combinations of these tests, have been widely advertised. It is worth pointing out that no evidence-based guidelines or expert recommendations advise the blanket use of these investigations in outpatient settings. The change in COVID-19 disease severity is entirely determined by clinical features and oxygen saturation.

Regardless, these tests are frequently repeated, and crucial therapeutic decisions are offered including remdesivir, monoclonal antibody cocktails and convalescent plasma – based on changes in laboratory markers. Many of these tests are indeed expected to be abnormal to varying degrees and their value in determining treatment options or predicting response to therapy is not supported by any proper study. While many practitioners claim to order these tests in good faith, it should not be forgotten that medical practitioners could get a cut from diagnostic laboratories.

The other overused test is high-resolution computerised tomographic (CT) scan. In the absence of easy access to diagnostic tests for COVID-19, a large number of doctors are relying on CT scans for diagnosis, repeating it on the pretext of patient-monitoring and using the scoring number to determine therapy.

While CT scans do have a limited role in diagnosis, especially when other tests are inconclusive, no guideline recommends repeating them or deciding therapy on the basis of radiological scores. When Randeep Guleria, himself a pulmonologist, warned against the potentially harmful effects of CT scans, the Indian Radiology and Imaging Association took vehement exception and picked on a small part of his statement without any consideration for the clear conflicts of interest their protests represented.

Colorised scanning electron micrograph of a VERO E6 cell (gray) exhibiting signs of death after infection with SARS-CoV-2 virus particles (yellow), which were isolated from a patient sample. Image: NIAID/Flickr, CC BY 2.0

Care that does not provide clinical benefit and is therefore ‘wasted’ is called low-value care. Recognising the toll it takes on patients and the health system, researchers in the US developed a list of such options that cost money in Medicare, the American federal health programme, with a view to curbing their use. Pointing out that such care can’t be beneficial but even harmful, Atul Gawande has called it “no-value care”.

In India, a vast majority of people pay for COVID-19 care out of their own pockets. In a country where one of the most important factors contributing to people descending into poverty is catastrophic healthcare expenditures, the economic toll of inappropriate COVID-19 care will only become clear later. When the cost is covered by the state, this wasteful spending means loss to the public exchequer. In the case of private insurance, the amount spent is no longer available for genuine medical care for other conditions should it be needed, especially for people with pre-existing health conditions, since insurance is usually capped.

Finally, an inability to either find or afford these drugs generates anxiety and potentially lifelong guilt among caregivers. So in the context of no benefit and multiple possible harms, this kind of care lies firmly in the harmful territory.

Clinical decision-making during a pandemic is complex, as the evidence related to disease spread and symptoms as well as effectiveness of therapeutic approaches evolves continuously. Different people have conflicting opinions and delivering care is challenging. The uptake of approved therapies is often much swifter – healthcare workers and patients tend to be willing to try anything that might, in their view, save lives.

The situation demands the need for independence, heavy reliance on evidence and clear and uniform guidance. With uncertainty in the picture, it falls on professional medical societies and health institutions to provide guidance that practitioners without little experience in managing these conditions can depend on. These guidelines should depend on evidence, and be derived from clinical trials that have evaluated both benefit and harm. We should rely on expert opinion only when such evidence is unavailable – and these opinions should be changed as soon as new evidence presents itself.

A number of guidelines have been developed by medical institutions and are shared on social media. They differ with each other in the specifics of recommendations, and are presented as flow charts with terms like “may be used”, which lends them a degree of credibility that is not supported by evidence. Further, they do not provide evidence of the balance of benefit and harm, narrate uncertainties or spell out possible challenges around implementation.

No professional society or eminent medical body in India has made any definitive statements against the use of non-evidence based therapies, leaving ‘experts’ to grab the stage. Members of the general public immediately come about these dubious recommendations on social media, seize upon them as god’s truth, and demand these ‘recommended’ agents be prescribed. This puts added pressure on the treating physicians.

The CDC’s office in Atlanta. Photo: James Gathany/CDC, public domain

India does not have an organisation like the UK National Institute for Health and Care Excellence or the US Centers for Disease Control and Preventive Services Task Force, which provide guidance and advice through evidence-based approaches. These institutions develop guidelines through independent committees that include professionals and also other stakeholders and lay members, through a consultative process.

In another era (before COVID-19), India’s Department of Health Research had started a process to develop standard treatment workflows for health conditions, to be covered under the National Insurance schemes.

It is paradoxical that the practice of unapproved and random therapies has no barrier – whereas the right thing would have been to conduct scientifically sound clinical trials to test the safety and efficacy of repurposed as well as new drugs in controlled research settings.

Also read: In India, Drugs for COVID Are Being Tested, Approved in Ways That Should Worry Us

The UK recognised this early, where academics rapidly developed pragmatic but sound trials that received the full-backing of regulatory agencies and funding bodies. Such trials were declared to be of urgent public health importance, paving the way for rapid recruitment in trials like the RECOVERY, which has generated important evidence that is guiding patient management worldwide.

The Indian Council of Medical Research signalled its intent by giving the freedom to hospitals and institutes to accept ethics committee clearance by one site, but this received little uptake. Testing new agents needs approval from the Central Drug Standards Control Organisation, but academics find it challenging to navigate its bureaucratic approach, despite the rules having a facilitatory clause to permit such academic trials and generate scientific evidence.

That a collapsing healthcare system forcing a large number of Indians into desperation and poverty is being seen as an opportunity to profiteer did not happen just over the last 15 months. It has been 70 years in the making, enabled by the absence of guardrails around responsible evidence-based and accountable medical practice, although it has become accentuated in the last few years. This tarnishes the stellar work being done by a large majority of healthcare providers, who have been rightly lauded as heroes of the pandemic.

There is an urgent need for a voice of sanity, for responsible medical practice and for a source of truth that clinicians and non-experts alike can go to for authentic, actionable information. Some have expressed hope that COVID-19 will catalyse reforms in India’s healthcare system. If the full impact of such reforms is to be realised, we need to keep beating the drum to institutionalise the practice of evidence-informed medical care and prescription reforms.

Vivekanand Jha is the executive director of the George Institute for Global Health India and Chair of Global Kidney Health at Imperial College, London.


  1. Many physicians have even been prescribing steroids early, to those who don’t need it, in higher doses and keeping it on for longer

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