Part 54--Re-examining Existing Medications and Developing New Drugs For COVID-19

Natural ways to boost one’s immunity:

There are several natural ways to boost one’s immune system to combat bacterial and viral illnesses. These include but not limited to, managing stress, engaged in meditation (in own house), adequate sleep and physical activity, exposing the skin to direct sunlight between 9.30 AM and noon to generate vitamin D, and consuming a balanced diet rich in micronutrients. Being healthier, and be mentally and physically stronger, and developing resilience through positive thinking and attitude, and meditation are helpful works in combination.

As of now, there are no approved or effective antiviral medications or vaccines available for COVID-19. In the previous article on coronavirus, the author wrote on 5th if January 2020 suggested some options, including the use of an anti-malarial agent, chloroquine. A time-tested and familiar agent that had been used for more than half a century. There is no reason why this agent should not be approved immediately by all drug-regulatory bodies. A recent in vitro study also reported that the combination of chloroquine and remdesivir (an antiviral agent) is effective in the control of COVID-19 infection. 

In mid-March, the FDA has approved the use of this drug on clinical trials to evaluate its efficacy against COVID-19. That is not good enough; while clinical trials are ongoing, physicians should be allowed to prescribe chloroquine at their discretion, without liability. In this regard, I am glad that President of the United States over-ruled the bureaucratic objections of the FDA and let physicians use existing agents to treat persons with COVID-19, including chloroquine and others.

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While no antiviral or immunomodulatory therapies for COVID-19 yet to have proven effective, a majority of severely ill patients described are (ad should) receiving various potential targeted therapies—such as neuraminidase inhibitors, anti-viral therapies, chloroquine, and corticosteroids. A small minority of patients have been enrolled in clinical trials with combination antiviral therapy.

While mortality among all infected otherwise healthy people is in the range of 0.2% to 3%, those who are requiring intensive care therapy, mortality is between, 4% to 15%. This is in part due to a combination of advance age, multiple comorbidities, and weak immune systems. Those who become critically ill with cardio-pulmonary complications in the Hubei Province case series from China, a wider mortality range was reported, between, 22% to 62%. With severer illnesses, patients develop progressive hypoxia together with multi-organ dysfunction leading to death. 

A smaller number of persons with high viral loads and compromised immune system, requiring the care in intensive care units (ICUs) with assisted ventilation facilities. In the absence of a proven and approved medications, current treatment focuses on supportive therapy and keeping affected persons comfortable and airways open allowing oxygenation of the blood; lack of exogen-hypoxia, is the final cause of death. Provision of assisted ventilation, when needed is helpful. However, the lack of oxygenation is due to insufficient surviving pneumocytes (lung cells). 

Below a critical mass of these pulmonary pneumocytes, even providing the best care with a higher concentration of oxygen and assisted ventilation are unlikely to rescue them from death. In these patients, the rate of death (apoptosis) of pneumocytes are far exceeded the rate of generation of new lung cells, a negative vicious cycle. Those who have adequate immunity to suppress the exponential viral growth and an adequate number of functional pneumocytes to transfer of oxygen across the lung membrane into the blood-stream, will survive. These conditions would allow patients, time to gain natural recovery through their own immunity to overcome COVID-19. 

It is possible that enhancing the internal defense system by taking oral lactoferrin, preferably the enteric-coated version prior to a meal to enhance its absorption, also will help to improve the immune system. However, no clinical trial data are currently available. Preliminary data in animal models suggest that broad-spectrum antivirals, such as an RNA polymerase inhibitor, remdesivir, and lopinavir/ritonavir, and interferon-b might be effective against COVID-19 (found effective against MERS-CoV). Table 1 illustrates some of the anti-viral agents that are currently under investigation.

Table 1: Anti-viral agents that are currently in clinical trials against COVID-19

Name ---Mode of action

1. Remdesivir: Block RNA-dependent polymerase activity

2. Chloroquine: Block viral entry into endosomes

3 Oseltamivir: Block neuraminidase

4 Ritonavir or lopinavir: Protease inhibitors

5. Tocilizumab: Block generation of interleukin 6, to curtail inflammation

6 Sparing use of corticosteroids; Block T-cells, inflammatory cytokines, and reduce general inflammation

None of the agents mentioned in above, have yet proved efficacious or been approved by regulatory agencies as a treatment for COVID-19.  Yet the desperate times needs out-of-the-box actions, including the use of experimental drug to save lives, outside clinical research protocols. Therefore, the medications mentioned in the table 1 should be made available to physicians at the minimum to be used in ICU facilities, if a physician believes that it is the right action to save the lives of their patients. 

Other effective options include the use of anti-COVID-19 antibodies in extremely ill patients, as in ICU set-ups. Those who have COVID-19 and overcame and in the convalescing phase can donate their blood to administer to severely ill patients with COVID-19. Similarly, genetically engineered antibodies (e.g., humanized monoclonal antibodies) using the rapid, novel technologies, can also effectively use to neutralize COVID-19 viruses in the circulation.

An effective vaccine while preventing the disease, the new anti-COVID-19 anti-viral drugs will add to the armamentaria of physicians to help patients recover quickly. These are likely to be available by the end of 2020. However, by that time the spread of the virus is likely to have subsided. Until these new drugs and vaccines become available, one should not allow patents to die because of bureaucratic regulatory blocks.  

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Professor Sunil J. Wimalawansa, MD, Ph.D., MBA, DSc, is a physician-scientist, educator, social entrepreneur, and process consultant. He is a philanthropist with experience in long-term strategic planning and cost-effective investment and interventions globally for preventing non-communicable diseases [recent charitable work]. The author has no conflicts of interest and received no funding for this work.