Treatments For Covid-19

The world remains in turmoil over SARS-CoV-2. But, ground-breaking progress in global vaccination has been made in India through Covishield and Covaxin.

Multiple scientific advances in the 21st century have given us a lifeline in nature’s arms race. The world, however, remains in turmoil over SARS-CoV-2, which is continuing to plague even our largest economies, with India being no exception. Ground-breaking progress in global vaccination has been made in India through Covishield and Covaxin. Despite this progress, the country now has the highest per-day rate of positive cases in the world. Furthermore, it is unlikely that vaccines will reach most of the population necessary to stop the spread of the virus. Another major problem in India is for the critically ill with Covid-19, who require mechanical ventilation, as ventilators and trained operators are in short supply in India’s overtaxed hospital system. Beyond this, the mortality rate with invasive mechanical ventilation is at 70%. Both grim facts highlight the overwhelming need to avoid invasive mechanical ventilation. What can India do to combat this? The answer lies within a diversified approach to target treatment of Covid-19 rather than solely addressing infection prevention.

WHAT TOOLS DO WE HAVE TO TREAT COVID-19?
The repurposing of previously used drugs is of great value to patients within our suffocating healthcare systems. Remdesivir, an antiviral treatment previously used for SARS and MERS, has been applied to Covid-19 patients. The efficacy of remdesivir’s five- to ten-day treatment course in hospitalized Covid-19 patients has been globally debated by leading international health care organizations and scientists. The drug demonstrated improvement in recovery in a randomized, double-blind clinical trial versus a placebo group. The US Food and Drug Administration granted the drug emergency use authorization in October 2020 for Covid-19 patients requiring hospitalization. Marketed as Veklury™, remdesivir has recently been approved in India. Manufacture and distributions have been significantly accelerated by scaling up batch sizes, contracting local manufacturers, and adding production facilities. The opportunity exists to curb the damage of SARS-CoV-2 if the region is willing to adapt its current practices to the rapidly changing needs.

Dexamethasone, an inexpensive corticosteroid, is an older drug that has been found most beneficial in hospitalized patients who require invasive mechanical ventilation. Yet, when given too early in Covid-19, for example, when supplemental oxygen is not required, dexamethasone may be detrimental. Dexamethasone may also be inappropriate for use in patients that have co-morbidities such as obesity and diabetes. Dexamethasone has been used to reduce cellular immune responses and treat patients with acute respiratory distress syndrome (ARDS). It is now repurposed to combat severe symptoms of Covid-19 and is one tool in the Covid-19 treatment armamentarium.

With the crisis pushing us to innovate, we are learning about newer drugs that can fight the virus’ effects. One such promising medication is lenzilumab, a drug created by Humanigen, based in the United States. Lenzilumab targets the initiation of “cytokine storm,” the hyper inflammation consequent to SARS-Cov-2 infection that leads to critical illness in many patients. In the LIVE-AIR phase 3 clinical trial, lenzilumab improved the likelihood of survival and/or ventilation by 54%, over and above remdesivir and dexamethasone, in newly hospitalized Covid-19 patients, who required supplemental oxygen but had not yet progressed to invasive mechanical ventilation. The effect of this one-day treatment was most beneficial in patients who were less than 85 years old and had a biomarker of early hyperinflammatory response; in which lenzilumab improved the likelihood of survival and/or ventilation by nearly three-fold.
Other innovative treatments include tocilizumab (Regeneron) and otilimab (Glaxo Smith Kline). Tocilizumab works on a downstream mediator in the cytokine storm. The open-label RECOVERY study showed that tocilizumab improved survival and other clinical outcomes in hospitalized Covid-19 patients who required respiratory support. However, results from other trials are conflicting, including one that found no benefit in clinical status or survival. Otilimab, like lenzilumab, also targets the early steps in cytokine storm. Otilimab failed to achieve its primary endpoint in a clinical trial, but an exploratory analysis found that it provided benefit in hospitalized, ventilated Covid-19 patients who were over 70 years of age—an effect that is being explored in an additional clinical trial.

WHAT CAN BE DONE?
To date, more than 20 million confirmed cases of coronavirus are reported in India, with an exponential increase in cases over the past month. More than 222,408 people have died, but survivors, funeral directors, and scientists say the actual numbers of infections and deaths in India may be many times more than the reported figures. Therapies, which are quick and easy to administer, can help countries struggling to contain SARS-CoV-2. A new urgency to investigate alternative treatments for Covid-19 is imperative, as this pandemic is suspected of remaining present for several years.
Lessons are to be learned from the case of Hepatitis C. While vaccines for Hepatitis A and B are available and frequently used, the Hepatitis C virus constantly mutates and has escaped the development of an effective vaccine. However, Hepatitis C treatment has been successfully developed. So why should approaches to Covid-19 be different?

WHAT IS THERE TO OVERCOME?
A big consideration for our political leaders is the size of the problem. India’s mammoth population is its biggest resource and one of its greatest challenges. The vaccination process is slow and tedious. With our limited understanding of the virus, it will not be long before we see newer mutations arise, which would require boosters to mediate. Once vaccinated, populations will require following up and, given the geographical challenges, will push back recovery many years.
Another significant challenge the country faces is the daily mortality figures. Symptoms of Covid have an uncanny resemblance to that of many common tropical diseases. It is not the system’s failure but the success of a virus that has been baffling epidemiologists at every corner. Our reality may be far worse than what we perceive it to be. Unaccounted deaths from people dying at home, on the way to hospitals, and the streets remain unaccounted in the national statistics as many are untested for Covid due to test shortages. If there is a drug accessible at local pharmacies, it can reduce these unaccounted deaths—these precious lives.

THE WAY FORWARD
Locking down India for Covid-19 is an untenable answer, as this approach previously almost collapsed the economy. Therefore, prevention and treatments are required and need to be delivered to hospitals and the populace. Inefficiencies in the logistical process of drug and oxygen manufacture and distribution should be at the top of the government’s plan.
It is time to reform the Drugs and Cosmetics Act of 1940 and Rules 1945. Covid-19 drugs, especially those showing efficacy in phase 3 of trials, under reliable international health authorities, should be given conditional approval in India immediately by the Drug Controller General of India (DCGI). Data needs to be collected as done with the NIH in the US and NHS in the UK, and drug efficacy and side effects reported publicly. Manufacturers such as Regeneron, Humanigen, Pfizer, and GSK should be encouraged to produce in India for the local population. We should end this over-reliance on vaccines and focus on treatments. Such open-minded approval processes will decrease dependency on a single solution, give our system more breathing room and drive down prices for life-saving medications.
The biggest democracy in the world needs just as many options when the matter is of saving its own citizens’ lives.

Prof (Dr) Joseph M. Chalil is an Adjunct Professor & Chair of the Complex Health Systems advisory board at Nova Southeastern University’s School of Business; Chairman of the Indo-American Press Club, and The Universal News Network publisher. He recently published a best seller book, “Beyond the Covid-19 Pandemic: Envisioning a Better World by Transforming the Future of Healthcare”.

Let this be the Last Medical Oxygen Crisis in India

The problem is not a shortage of medical oxygen but the supply chain of delivering it to the patient bedside in a hospital. A routine site at all major Indian hospitals is the large oxygen cylinders delivering oxygen to patients at the bedside, says Dr. Joseph Chalil.

International media is filled with headlines such as “Indian COVID-19 Patients Die as Ventilators Run Out of Oxygen” and showing images of people with empty oxygen cylinders crowding refilling facilities in Uttar Pradesh for their relatives in hospitals. The last such news was from Pakistan in December 2020 when six COVID-19 patients died in Khyber teaching hospital in Peshawar.

India has a daily production capacity of at least 7,100 tons of oxygen, including for industrial use, which appears to be more than enough to meet current demand. The problem is not a shortage of medical oxygen but the supply chain of delivering it to the patient bedside in a hospital. A routine site at all major Indian hospitals is the large oxygen cylinders delivering oxygen to patients at the bedside. Yet this is something you never see in a western hospital. All American hospitals have central piping, which delivers oxygen to the patient bedside from a Pressure Swing Adsorption (PSA) Oxygen Plant attached to each hospital. This is one of the building permit requirements for a new hospital in the USA. Medical oxygen can easily be manufactured from surrounding air.

Among the most significant challenges early in the COVID-19 Pandemic was the shortage of essential supplies like personal protective equipment (PPE) and ventilators. These products are tied to supply chains that stretch worldwide, and the Pandemic highlighted their fragility and susceptibility to significant disruptions. As China, a leading global exporter, dealt with the Pandemic in its early days, it was forced to shut down manufacturing, leaving the rest of the world scrambling to address its rapidly shifting supply needs.

Prime Minister Narendra Modi has also given a call for self-reliance – an ‘Aatmanirbhar Bharat’ where he talks of integrating India with the world moving away from isolation but from a position of internal strength. The aim is to make India and its citizens independent and self-reliant in all senses. Mr. Modi further outlined five pillars of Aatma Nirbhar Bharat – Economy, Infrastructure, System, Vibrant Demography, and Demand. India demonstrated its ability to go from producing zero PPE kits pre- COVID to producing millions of kits and exporting them today as a result of the COVID-19 Pandemic. Let us also make our hospitals self-reliant in Medical Oxygen production.

A vision for the future of health-conscious manufacturing

A supply chain that depends on domestic manufacturing is part of our strategic healthcare plan for the future. In the book *Beyond the COVID-19 Pandemic*, we outline a 33-33-33 Buy Local Policy, which involves increased purchases of local products while allowing purchasers flexibility to tap into the global marketplace. In the plan, healthcare systems would be required to buy 33% of their products locally within their region, 33% of their products within the country, and 33% from outside. This policy aims to create a flexible supply chain that could be ramped up to deal with emergencies.

Self-reliance has always been an Indian (The Swadeshi Movement) virtue and the key to India’s success and development. Suppose one supply chain is cut off due to war, natural disaster, or bioterrorism; there are other options to maintain and sustain supply chains. This will also ensure that the dependency on one particular source for anything essential is minimized. Domestic manufacturing is vital for job creation and a strong economy, and it’s also essential for national security.

AirSep Corporation of New York has installed PSA Medical Oxygen Systems in more than 4,500 hospitals in nearly 50 countries worldwide, including several hospitals in India, to meet their central pipeline and other oxygen needs. These generators and plants operate automatically to supply patient, surgical, and critical care units in medical facilities, military field hospitals, on-site emergency preparedness centers, and disaster-relief efforts. There are several other manufacturers with similar technologies.

Supply chain policy does not have to be an all-or-nothing proposition. That is to say, we should neither import everything nor should we import nothing. Currently, however, we are too reliant on imports in some areas, which hurt us during the early days of this Pandemic. More steps must be taken to create reserves of supplies and manufacturing capacity, similar to the U.S. strategic oil reserves or the Indian strategic food reserves.

India should invest in mobile containerized, turnkey packaged oxygen systems that are ideal for locations where a compressed air supply is limited or unavailable. These units can be truck mounted and moved to areas of shortage or pandemic hot spots. Containerized units can also be used for military applications as well. The oxygen generator within a containerized unit produces oxygen from an air compressor that is included in the package. These rugged systems can perform in extreme temperatures, high humidity conditions, and at high elevations.

Let this be the Last Medical Oxygen Crisis in India. Let us not scramble our resources; purchasing compressed liquid oxygen from Russia or China, which at best is a temporary fix but will arrive too late for our patients’ bedside in Delhi. Let us retrofit our hospitals with central oxygen piping
and support installing hospital oxygen plants and backup systems. Domestic production policies of all medical supplies will lead to job creation and positively impact the environment, reducing the distance oxygen and other supplies must travel from manufacturer to end-user. Local production is also a necessary part of national defense in a world where bioterrorism is an ever-present possibility—the military, for its part, has demonstrated the importance of not centralizing any aspect of its supply chain to one region or country.

India can lead the way globally by building supply chains that incorporate local manufacturing that can be ramped up to address critical needs. This goal recognizes that global supply chains can be broken, and alternatives need to be in place. When countries take these lessons and models to heart and use them to craft policy, their citizens can benefit from a common-sense approach that empowers us to mitigate challenges—everything from a natural disaster or political upheaval to a once-in-a-100-year pandemic.

(Prof. (Dr.) Joseph M. Chalil is an Adjunct Professor & Chair of the Complex Health Systems advisory board at Nova Southeastern University’s School of Business; Chairman of the Indo-American Press Club, and The Universal News Network publisher. He recently published a Best Seller Book – “Beyond the COVID-19 Pandemic: Envisioning a Better World by Transforming the Future of Healthcare.”)