The COVID-19 pandemic (the Pandemic) has swept through the whole world for over half a year. There seems no sign of slowing down. Traditionally, infection problems are dealt with by experts who clarify the cause of the disease and the pathological involvements, work out the effective treatment protocol, then organise a public health program on prevention. Unfortunately, with regard to this current devastating Pandemic, up to today there is yet consensus on the use of therapy: anti-flu, anti-HIV, antimalarial and steroidal classics have all been tried. New drugs, of course, have been on the list. The diverse views of clinical scientists have invited populist politicians to join in the fray. They make unsubstantiated comments indiscriminately. With regard to clinical involvements: those chronically ill and elderlies are expected to be more vulnerable. Nevertheless, with further spread of the Pandemic, a much broader age range, from neonates, children to the young and healthy, could all be victims.

Progress in the world has never been advanced equally, whether a place is considered developed or otherwise would normally be judged by its economic status. Advanced economy has done better in life expectancy, infection rate of diseases, etc. However, with this once in a century Pandemic, the unequal world regions appear to have become equal. The wealthy regions are affected as badly as the poor ones. The day-to-day world data related to the infection and mortality numbers, which shows that wealthy places such as the United States and some countries from Europe fare no better than underdeveloped countries, gives vivid illustrations of the mystery of this Pandemic.

Experts and Governments have in fact tried their best in their attempt to halt the viral spread: from closing borders, quarantining, lockdowns, viral testing, compulsory wearing of face-masks to social distancing etc. Whilst all those actions are useful to contain the spread of the virus, there is no surety that the virus could be curtailed. Even with all the public health measures in place, still, the world could only patiently wait for the aggressive viral activities to die down with time.

None of us could have experienced the 1918 Influenza Pandemic, which lasted more than two years; with 18 months of disastrous disturbances followed by scattered events extending to 1920⁽¹⁾. In the decades that followed, influenza epidemics on smaller scales have been common in the United States and Asia, particularly China. Such epidemics lasted a few months, then disappeared. Seventeen years ago, the Hong Kong experience of SARS has remained in the vivid memory of locals. It gave us just over 100 dark days of threatening uncertainty, then disappeared totally within half a year. If we compare today’s Pandemic with the worst period of the 1918 Influenza Pandemic, it might seem that the present experience is just as bad as then. The universally shared feeling of today is fear: fear among the medical professions, fear of health providers that facilities are drying up, fear from governments and economists that recession is upon us. When is the Pandemic going to end?

Governments the world over have been proclaiming that a vaccine is coming! There are over 120 institutes and pharmaceutical companies globally toiling for vaccine production day and night. Countries including China announced that their vaccines have passed the safety requirements and dosage tests, and are ready for clinical trials. Some countries already signed contracts with producers for the exclusive provision of the successful vaccine. China vowed that its production could be made available for the whole world. The announcements do have soothing effects against worries and fears. Apparently, the current hope for the control of the Pandemic lies in the vaccine.

Effective Vaccine

Indeed, vaccines have solved a lot of problems related to infections. Varicella vaccine has eliminated small pox. Children from birth to two years all receive vaccines for measles, tetanus, whooping cough, diphtheria and polio which have freed them from those infections ever since. The most remarkable example is the orally taken polio-vaccine which is simple to administer and effective ⁽²⁾.

All these successful vaccines convince us that vaccine is the solution for infections. Nevertheless, if we are aware of other sad examples, we might not be so optimistic. HIV infection experts have tried for some 40 years, no vaccine is yet available. Tuberculosis has gone through generations of vaccine and yet after 70 years, has not reached the efficacy expected. Influenza vaccine which is so familiar to us, only has efficacy ranging from 30-50%. More desperate examples include parasitic infections like malaria, schistosomiasis, etc, which are “vaccine resistant” ⁽³⁾.

Now that many vaccines for the Pandemic have passed initial safety and dosage tests but how about their efficacy? Whilst new vaccines may be available in the market in the months ahead, what about their effectiveness?

As a matter of fact, the standard requirements of an effective vaccine to control an infection has long been documented ⁽²⁾. The following table gives a brief summary:

Features of effective vaccines
Safe	Vaccine must not itself cause illness or death
Protective	Vaccine must protect against illness resulting from exposure to live pathogen
Gives sustained protection	Protection against illness must last for several years
Induces neutralising antibody	Some pathogens (such as poliovirus) infect cells that cannot be replaced (e.g., neurons). Neutralising antibody is essential to prevent infection of such cells
Induces protective T cells	Some pathogens, particularly intracellular, are more effectively dealt with by cell-mediated responses
Practical considerations	Low cost-per-dose, biological stability, ease of administration and few side-effects

We could follow the logic and workout useful ideas:

1. The vaccine must be proven safe i.e. not imposing any pathological harm, immediately after the vaccination and later in subsequent months. Short-term safety refers to three months and longer term could extend to more than 6-9 months. Some vaccines in the past had serious adverse effects after even longer periods.
2. The vaccine is meant for a specific target organism i.e. COVID-19, and the immunological achievement must be related to COVID-19 control, not general response. To demonstrate this, the vaccine has to be tested amongst high-risked group or people at early stage of contagion in infectious areas. Presumably, most research institutions have yet to reach this stage of testing or they are still in preparation to do so.
3. The vaccine must provide long-term protection, not “one-shot effect”.
4. In response to the vaccine, the recipient must be proven to develop antibodies specific to COVID-19.
5. The vaccination should result in the promotion of favourable cellular and serological responses (T cells related) for sustained effects. Currently, researchers may be confident in the said results in control setting but have yet obtained clinical trial evidence.

Based on the above analysis, positive reports on vaccines still lack substantiation. More work will need to be done to obtain solid data and evidence.

Another question is on the method of delivery of vaccine. If it could be administered orally, this will be the simplest method. Nevertheless, there are many hurdles to overcome to produce an oral vaccine, in particular, if we need to conceive a new vaccine quickly.

Innate Defense

So far, our discussion has been focusing on the target-orientated way of immunological defense against the invading COVID-19, i.e. the vaccine, which once is proven successful, will provide quick and effective prevention against COVID-19. At the same time, should we not also be concerned in case the vaccine fails?

Actually, our immune system is responsible to combat invading organisms, and under normal circumstances, without unusual virulent invasions, the system works well. It is this general immunological strength of infection resistance that keeps us from being infected. Succumbing to the panic caused by the Pandemic, we are all putting our hope in a miracle vaccine. Nevertheless, we should, at the same time, be prepared to raise our immunological strength in case that hope is dashed. Whilst we may not be able to have a targeted approach, could we not enhancing our non-targeted general immunological strength to fight the invading COVID-19? It is not uncommon to find one member contracted the infection whilst other family members staying healthy. The healthy members must have more efficient immunological strength. Is this not evidence that there is extra defense strength innate with those healthy members?

From the time any pathogen attack takes place, our general immunological defense through production of nasal mucus, phlegm will increase our antibodies, giving time for our body to produce more T cells, ready for a long battle. This innate defense is not imaginary but part of all human faculty and has been widely reported. Those who win the battle will come out with hardly any symptoms and those who lose will fall ill.

Can this innate immunological defense be stimulated and strengthened? Documented reports about desirable ways of boosting innate immunological defense are plentiful. Whilst relying on innate defense is not as compelling as vaccines, its effect in maintaining one’s health is just as important. Otherwise, the human race could not have been sustained. The “Herd Immunological Defense” theory as a way to control a rapidly spreading epidemic – allow the vulnerable to get infected widely, so that those with extra immune-defensive strength would help stabilizing the spread – might rely on the same argument.

Beyond Vaccination

Allopathic therapy today relies heavily (nearly solely) on target-orientated treatment. General supportive measures tend to be ignored. Vaccine is a “bullet shot”, considered the most appropriate method. Boosting the existing innate immune defense ability falls under general support, hence considered unimportant. Between 2017 and 2019, before the advancement of COVID-19, Harvard scholars provided ample clinical and public health data, together with verification from laboratory research: that vitamin D could be recommended for the prevention of respiratory tract infection, that is, it boosts the existing innate immune defense ability to fight pathogens. Cold, humid Northern countries in the world do have more respiratory infections in winter and spring when sunlight, which helps the natural production of vitamin D, is deficient. Laboratory studies have worked out the molecular details of how vitamin D helps the immunological defense with essential support. ⁽⁴⁾

This insight from Harvard gave us a lot of encouragement. It supports the holistic approach of boosting immunological defense. Sadly, when COVID-19 started its attack, all attention shifted to target treatment, and currently, on vaccine. Harvard experts’ advice was thus cast aside.

Traditional Chinese Medicine and Immuno-defense

Traditional medicines, such as Traditional Chinese Medicine (TCM), have recorded a lot of immunological research over time. Such well-documented research has caught some attention in the public sphere. It is an opportune time for us to contribute towards battling the Pandemic through our work on this front. For example, making use of herbal medicine with known therapeutic and immunological properties, augmented with vitamin D, to demonstrate the synergy effect of enhanced innate defense.

Over the years, we have paid attention to immunological properties of TCM. TCM advocates holistic balance and harmonisation for all therapeutic designs. To ensure a healthy body, whilst treatment could have some specific target, in the treatment protocol, a balanced support to all functional organs is advocated. Using the current language of immunology, the balanced harmony could be an immunological state of neither over-activity nor underactivity. Indeed, over-activity leads to allergy and autoimmune diseases while underactivity undermines normal physiological functions and invites pathological changes. In deciding on our research direction, this simple but logical immunological line of thinking has much been adopted.

Since the turn of the century, we have, in partnership with the Memorial Sloan Kettering Cancer Center of New York, explored medicinal plants that could immunologically counteract cancer growth. We found five promising herbs that deserved further explorations. It is known in TMC that increase in “Qi” will boost our immunity whilst blood stasis will do the opposite. The research findings, in general, support that theory. For instance, astragalus (Huang Qi) is known for its immunological property. Subsequently, we have researched on medicinal herbs that support treatment of allergic dermatitis and nasal sinusitis, using immunological platforms. The research is continuing.

Seventeen years ago, the Hong Kong SARS crisis gave us an opportunity to engage in viral infection prevention. We created an herbal formula, not for treatment, but prevention: i.e. for the boosting of natural immunological defense against SARS. We organised a clinical trial using the innovative herbal formula for two weeks. Over 2,000 hospital workers volunteered to participate. The subsequent analysis showed zero infection rate, compared with a 0.4% infection rate among those not taking the formula ⁽⁵⁾. The convincing results gave us a lot of encouragement to continue research on the preventive aspect of herbal products against virus infection.

The said formula consisted of two parts: part one was supportive of “Qi” and part two was a simple herbal combination advocated for mild symptoms (which to our mind, meant prevention of deterioration). “Qi” was an important ancient concept of balance and harmony which we took as prevention of deficiency in immunological defense.

Conclusion

Since the COVID-19 pandemic, reports from China again strongly recommended the use of complicated classical herbal formulae for hospital treatment. The overwhelming importance of hospital treatment has again diluted the importance of prevention. Moreover, the role of prevention is totally accorded to hopeful vaccines. This might be a suitable time, for the standard commonplace aspects of immunological defense be seriously studied and be included into the immediate future planning, not only for COVID-19 prevention but also for other respiratory infections. Even when the effective vaccine becomes a reality, those at risk of infection with or without the vaccination could still benefit. Accordingly, we have worked out research protocols for the study that we are pursuing in a number of published manuscripts. ^(6-10)

It is good to remember: as nasty viruses reach the respiratory gate, they would encounter the guarding sentinel, who only use standard shields and clubs to defend. Neither have they been armed with arrows with past knowledge nor promising bullets. Yet this well-trained, well-nourished and well-prepared sentinel still keeps the house secure and clean. The master is perturbed but well sustained. Our job is to strengthen this sentinel further through simple means inherited from tradition.

At the time of writing, COVID-19 has spread in Africa. President Rajoelina of Madagascar has, in fact, been promoting a herbal remedy for its anti-viral properties. Madagascar has close relationship with India, it may well be an Indian herbal medicine which may have properties to prevent infection. Africa and Asia may be separated by the ocean but we have similar ideas on prevention.

 

References

1. What Happened in China during the 1918 influenza pandemic. Cheng KF, Leung PC. International J. of Inflections Diseases (2009) 11, 360-364.
2. Immunological principles of vaccination. Ada GL. Lancet 1990, 335:523-526.
3. Immunology. Janeway CA. Garland Publisher USA p.579.
4. Study Confirms Vitamin D protects against Cold and Flu. Mc Greevvey S, Morrison (2017). Harvard Gazette Oct 2019.
5. Using herbal medicine as a means of prevention: Experience during the SARS crisis. Lau TF, Leung PC, Wong V. 2005. Am J Chin Med. Vol 33(3) 345-356.
6. What can we do for the Personal Protection against the CoVID-19 infection? Immuno-boostering Specific Supplement could be the Answer. Ben Chan, CK Wong, Ping Chung Leung. J Emerg Med Trauma Surg Care 2020, 2: 007.
7. What do we expect from Traditional Chinese Medicine in the COVID-19 Pandemic? Leung Ping-chung, Chan Chung-lap Ben, Wong Chun-kwok. Chinese Traditional Medicine Journal, 2020, Vol 3, Issue 1.
8. A Response to Massimo Bonucci’s Editorial: COVID-19 Outbreak: How to Use Current Knowledge to Better Treat. Ping-Chung L. EJMO DOI: 10.14744/ejmo.2020.46269.
9. Clinical Use of Chinese Medicine in the Current COVID-19 Crisis and Related Research Planning. Ping-Chung L, Chung-Lap Ben C, Chun-Kwok W. Clin Res Infect Dis (2020). 5(1): 1054.
10. Epidemic Diseases and Chinese Medicine - From Ancient to Current Time. Leung Ping-chung. Journal of Tropical Medicine and Infection Diseases 1: 001. 10.29011/JTMID-101.100001.

Professor Ping-Chung LEUNG

MBBS(HK), FRACS, FRCS (Edin), MS(HK), FHKCOS, FHKAM (Orthopaedic Surgery), DSc (CUHK)
Emeritus Professor of Orthopaedics & Traumatology, Faculty of Medicine of The Chinese University of Hong Kong
Director of Centre for Clinical Trials on Chinese Medicine of Institute of Chinese Medicine, The Chinese University of Hong Kong
Director of State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants (The Chinese University of Hong Kong)

September 2020