Covid-19: India's Top Doctors On How To Treat It

What Happens When There Is No Known Treatment Available?

Recall the last time you had fever and cough and visited a doctor. It was probably a ten- or fifteen-minute interaction, during which the doctor would have advised you to take rest and drink plenty of water. The doctor may also have prescribed a few pills (not necessarily an antibiotic) to reduce the symptoms.

It is also possible that if you had an illness which may have been spread by coughing and sneezing, the doctor would have advised you to cover your mouth while coughing. No matter which part of the country (or world) you are in, it is likely that you would be provided a similar course of treatment, with minor variations. A standardized approach is how medical science functions and it is backed by current evidence on how best to manage such a clinical situation.

In the early couple of months of 2020, when the COVID-19 pandemic was spreading across the world, there was limited consensus on the range of symptoms. We knew little else than that the infection was respiratory and could be severe. Laboratory tests were quickly developed but there was limited availability of the testing services. There was no proven effective treatment.

'Empirical Treatment' as the Best Strategy

What therapeutic approach is followed when a new disease appears and there is no known treatment? The first thought is to treat the symptoms; second, to follow an empirical approach, in other words, what is considered logical and appropriate, applying scientific principles. Most COVID-19 patients suffered from fever and cough, and the symptoms were mild. From a clinical perspective, they were put under close medical watch, given medicines to reduce fever, and treated for any change in clinical condition. From a public health perspective, the experiences being reported from Wuhan had already revealed the need for isolation.

A small proportion of COVID-19 cases had difficulty in breathing (or breathlessness). In such cases, usually due to pneumonia or micro-clots in the vessels of the lungs, the oxygen saturation in the blood of the person would start to decline, at times quite suddenly. In these cases, the oxygen saturation needed to be closely monitored. It should be 95 per cent or higher. If the oxygen saturation fell below 95 per cent, it was a sign that close observation and supplemental oxygen might be required. Such patients were classified as moderate cases. At least initially in China, patients with breathing difficulty were put on ventilators quickly, but within a couple of months doctors realized that early invasive ventilation was not required. For those with SARS-CoV-2 infection, it was discovered that simple oxygen could indeed be life-saving. It was thus crucially important for healthcare centres treating COVID-19 to have an adequate supply of oxygen. Since the oxygen saturation of affected individuals needed to be regularly monitored, the need for the wider use of pulse oximeters was identified. If the saturation did not improve with oxygen given through a mask or with a cannula or a plastic tube, high-flow nasal oxygen (HFNO) therapy or a non-invasive ventilation (NIV) approach was used at healthcare facilities. Only two to three out of every ten patients who developed symptoms would reach this stage.

Apart from these observations, it was recognized that making patients lie in the prone position-on their bellies-could improve their oxygen saturation levels. This method, termed 'proning', had been used in the past in the ICU for patients on mechanical ventilators who were not maintaining adequate saturation; it had been found to be effective in clinical trials. However, before COVID-19, 'proning' was not done with conscious patients. This process came to be known as 'conscious proning' and many patients whose oxygen was low were asked to lie on their side and on their belly. This allows the base of the lungs, especially the lung on the posterior side to expand more freely and take in more oxygen and thereby improve oxygen saturation. This benefitted many individuals and helped avoid the need for ventilators either partly or entirely.

Though more studies are needed to ascertain exactly how many this approach has benefitted, and how it works, it is considered potentially useful and is now routinely used in most hospitals.

While these measures work in a large proportion of the cases, there are a few whose health condition continues to deteriorate. Such cases are classified as severe and need to be admitted to specialized health facilities or hospitals where there is provision for ICUs and ventilators. Not all these patients necessarily need ICUs and ventilators, but keeping them in such equipped facilities when admitted reduces the delay in transferring them to places with these facilities in case their condition worsens. Those admitted in the ICU are observed and monitored closely. Their vital parameters such as blood pressure, heart rate, breathing rate and urine output are monitored. A proportion of those in the ICU need to be put on assisted or mechanical ventilation. In such cases, the person's lungs are not functioning well: they are either not able to help in gas exchange (take in oxygen into the blood and expel carbon dioxide) or not able to suck air into the lungs due to fatigue in the breathing muscles (respiratory failure). The machines which help the breathing process in such a scenario are called ventilators. When an individual is on a ventilator, the machine essentially breathes for him/her, pushing in oxygen and removing carbon dioxide at a set rate and volume. Ventilators are complex devices as they have to push oxygen carefully into the unhealthy and fragile lung, making sure that they do not cause more damage, a complication called ventilator-induced lung injury (VILI).

These devices need constant adjustment as the patient's needs change depending on how the disease evolves with time. This device is an essential tool for severe respiratory illnesses. Patients in severe respiratory distress may need to have a ventilator breathe for them until their lungs heal. 

However, the ICU is just a well-equipped hospital setup for intensive monitoring and management. Ventilators are machines which support treatment until the patient recovers the ability to breathe. Therefore, essentially, treatment for COVID-19 has been centred on providing good supportive care. None of these is specific treatment for the disease itself. To facilitate recovery from diseases, the virus needs to be cleared from the body of the affected person. Moreover, the effects caused by the viral infection, such as an increased clotting mechanism or a hyper-inflammatory response, need to be reversed. Recovery or return to health, therefore, involves reversal of all clinical conditions triggered by the virus.

In any infectious disease, in order to prevent it from progressing to the severe stage, first the cause of the infection needs to be addressed and then the body's response to the infection. The primary focus is on stopping the multiplication of the virus. However, since the SARS-CoV-2 virus was not known earlier, how could any specific drug have been developed? When the pandemic emerged, we did not have a medicine available.

Give Me Any Therapy, Urgently!

In the early period of the pandemic, especially in March-April 2020, in a few countries, nearly one in every ten to twenty patients (or 5 to 10 per cent of total identified cases) had died. This was a high mortality rate. A treatment was urgently needed.

There are standard procedures for research on drugs and therapies and for making these available for use. There is a process that is to be followed before a doctor can prescribe a medicine.

First, a potential biochemical or biologic molecule is identified. The initial in-vitro ('in glass', meaning, in a laboratory) studies are done, which are followed by preclinical trials on animals, which can look either for toxic side effects or for treatment in a model of the disease. Once the molecule is found to be non-toxic and effective on animal models, clinical trials on humans are started. Once all phases of the clinical trials are conducted as per the protocol agreed on, and if the drug is found to be safe and effective, it is submitted to the regulatory authorities for a review. After a thorough review, if it meets the criteria of quality, safety and efficacy for licensing, the drug is approved. It is after this process of testing and approval that production is started and a drug becomes available for prescription and sale. Needless to say, drug research takes years, with no one being certain about the final outcome. (Nearly similar steps are followed for vaccine research and development). Many molecules which show potential in preclinical trials fail in clinical trials due to lack of significant efficacy or unacceptable side effects.

(Published with permission of Penguin Random House India from 'Till We Win: India's Fight Against The Covid-19 Pandemic' by Dr. Chandrakant Lahariya, Dr. Gagandeep Kang and Dr. Randeep Guleria. Order your copy here.)

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