In response to the Covid-19 pandemic

There have been serious mistakes made by some politicians and their followers. Despite this, many scientists, nurses, physicians and other healthcare workers have been remarkably successful in developing, manufacturing and delivering safe and effective vaccines and treatments for Covid-19. They are using the principles of systems thinking, Total Quality Leadership (TQL) and Total Quality Manufacturing (TQM). The goals of this article are to describe these principles and show how they are being used to save hundreds of millions of lives.

Systems thinking, TQL and TQM

Systems thinking has been defined in many ways, but this is my favorite:

Systems thinking is a set of synergistic analytic skills used to improve the capability of identifying and understanding systems, predicting their behaviors, and devising modifications to them in order to produce desired effects. These skills work together as a system¹.

Fritjof Capra described how it is important in modern physics and biology^2,3. He and Pier Luigi Luisi further showed how it is important in mathematics, biology and medicine⁴. In systems thinking, a holistic approach is used to look for interactions and hidden connections between objects in a whole unit^3,4. The whole is more than the sum of its interacting parts. Some interactions are synergistic and others are inhibitory. Pier Luigi Luisi also described the difference between systems thinking and reductionism in this journal⁵. The roots of systems thinking are found in traditional medicine, in which humans were thought to be a part of nature, not separate from it and should not be in conflict with it⁴. Systems thinkers realize that life depends on properly balanced ecosystems. The human body is an ecosystem that contains not just eukaryotic cells (human cells), but also bacteria and archaea (prokaryotic cells), as well as viruses, fungi, yeasts and protozoa⁶. A healthy gut microbiome fed with sufficient dietary fiber can help support our immune system and act as your personal oncologist to help prevent cancer. Non-digestible carbohydrates in dietary fiber are fermented by healthy bacteria in the gut to produce short chain fatty acids (butyric and propionic acids) that induce the differentiation of important immune cells that help to control inflammation⁶.

Life is not due to survival of the fittest, but survival of the most cooperative. The organization called One Health recognizes that the health and well-being of humans, animals, and the environment are tightly interconnected⁷. Shortly before the emergence of the Covid-19 pandemic, they encouraged collaborative, cross-disciplinary approaches when responding to emerging and resurging diseases. They also urged including studying the health of wildlife to help predict, prevent and mitigate global diseases. Another organization called the Global Initiative on Sharing All Influenza Data (GISAID) has used this interdisciplinary approach to study influenza for years and more recently, the Covid-19 pandemic. They have a database that has over 767,000 genomic sequences of the SARS-CoV-2 virus that causes Covid-19⁸. It also tracks variants and reports on new developments.

So, there is a deep ecology, in which humans are viewed as just one of many equally important parts of the global ecosystem. Systems thinkers realize that we continuously evolve in harmony with other organisms in our ecosystems and environment. Properly organized networks are essential for life and help make us human. We are complex, self-regenerating, autopoietic organisms, whose bodies are ecosystems living in larger ecosystems. Life is sustained by a network of production processes, in which the function of almost every component is to participate in the production or transformation of itself and the other components in the network^3,4. So, network theory and systems thinking have emerged as guiding principles in biology and medicine⁹. Total Quality, Evidence-Based Medicine uses more than just science and technology. It also uses teamwork, compassion and solidarity.

Systems thinking is also used in TQL and TQM

Systems thinking has been integrated into TQM for decades¹⁰. Basically, TQL and TQM demand that we listen to the voice of the customer or patient and respond appropriately. The same is true for people who want to make friends and influence people¹¹. It is essential for survival in an increasingly polluted and infected environment. The health and productivity of humanity require using a holistic approach. Traditional operating methods must be continuously evaluated and replaced when they become dysfunctional or unnecessary. In evolution, the ancestors of cetaceans (whales and dolphins) replaced their legs with fins as they evolved into creatures that spent their entire lives in water. Moreover, the same principles of TQM are used by our bodies to maintain good health and to prevent diseases. Just as businesses listen to the voices of customers and communicate with them, cells within our bodies communicate with each other. The first rule of communication is ‘know your audience’. So, we have an immune system that needs to distinguish between self and non-self. The cells in a healthy, properly balanced immune system will only attack viruses and deadly organisms that are non-self, while leaving alone the essential human cells that it recognizes as self. In autoimmune diseases and fatal reactions to Covid-19 this balance is lost as the body kills itself. So, proper health requires a balance of all the systems, viruses and cells in the body.

Modern medicine and science now realize that the human body is an ecosystem with a deep ecology. Human eukaryotic cells are just one component of the ecosystem. This is similar to the concept in TQM in which all associates are important to the organization. In modern biology, we are changing the way we think about what it is to be human. That is, the viruses, Bacteria, Archaea and other microorganisms in us help make us healthy humans. As in TQM, there is an extensive communication network among different microbes and between microbes and human (eukaryotic) cells. However, TQM in industry is often involved in manufacturing tools and machines. They don’t make themselves. They are made by people. In contrast, living systems are not machines. We make ourselves in a process called autopoiesis (self-making). We make ourselves and we team with other people and organizations made by humans to improve all aspects of our healthcare. So, in biology, TQM means Total Quality Making, not Total Quality Manufacturing.

The principles of TQM are used by an extensive networking system in many governments. For example, the FDA’s Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) are developing a more systematic approach for incorporating the “Patient’s Voice” into drug development. In addition, physicians are distinguishing between care that concentrates on the patient’s disease and care that looks at the whole patient. Healthcare that is focused on the individual looks for changing interrelationships over time. It also views episodes in illness as being part of experiences with health that occur throughout the course of one’s life. It considers diseases to be interrelated as well affecting the evolution of one’s health problems. Moreover, organs and systems in the body are thought to be interrelated. In reductionist thinking, when a seemingly complex problem occurs (like a disease), it could be solved once the single root cause was identified. This is especially popular in politics, in which the root cause is assigned to the opposition party. The goal is to fix the blame – not the problem. Sadly, people who follow the preaching of Donald Trump and believe his lies try to blame the Covid-19 pandemic on the Chinese, as if that would help find ways to prevent or cure it. They ignore the fact that the SARS-CoV-2 virus that causes Covid-19 could have appeared before December, 2020 in the USA, but we wouldn’t have recognized it. The Chinese and other Asian scientists and doctors had previous experience with the first SARS virus, so they were able to recognize it. Moreover, systems thinkers realize that the Covid-19 pandemic did not have a single root cause. The SARS-CoV-2 virus did not start the pandemic by itself. It emerged because of human encroachment on previously untouched environments and the widespread demand for meat. Scientists, environmentalists and public health workers predicted the emergence of more pandemics and are predicting more¹².

An essential part of TQL and TQM is to eliminate management by fear. Before TQM, if a union worker on an assembly line made a mistake that could produce a faulty product, he or she would try to hide the mistake and fix the blame – not the problem. That way, they could keep their job, even though the manufacturing system suffered. Moreover, union workers were often told that they were being paid to work and obey orders – and not to think. If a problem occurred in production, the engineer or manager in charge was supposed to stop production and fix the problem. In TQM, all workers are considered to be managers. If a person caused a problem or saw a problem occur, he or she would be required to stop production. Often, the person who caused the problem is the one who is most capable of solving the problem. Fear causes problems and lets them grow undetected. If a country is afraid that the USA will attack them with nuclear weapons if they identify a new deadly virus, they won’t tell the world about it and the virus will spread. The Chinese did tell the world about the SARS-CoV-2 virus and the Covid-19 disease. They also showed the world that testing, contact tracing and quarantines can stop the spread of the virus and disease. They also led the world in developing and manufacturing a safe and effective vaccine¹³.

It should be added that science rejects dogma and that people saying that something can’t be done are often being passed by people doing it. Sadly, some people just can’t believe that vaccines could be safe if they were developed so fast. Others have natural disbelief of new technologies. So, some people (including some pharmacists and physicians) are telling people that they should not take the vaccines that are based on the new mRNA technology¹⁴. This is false. Fortunately, over 100 million people worldwide have been fully vaccinated. Over 98 million doses have been given to 19.3% of the population in the USA, as of 11 March¹⁵. Most of them were either from Pfizer or Moderna. Both are based on mRNA technology. Over 2.2 million jabs are being given each day.

Vaccines

The Chinese vaccine called CoronaVac was shown to be safe and effective in phase 1/2 clinical trials. It uses an inactivated coronavirus that still produces the spike (S) protein¹⁶. The S protein is the antigen that activates one’s immune system after being vaccinated. The vaccine was developed by Wuhan Institute of Biological Products/Sinopharm, Beijing Institute of Biological Products, Sinopharm and Sinovac. It has expanded its annual production capacity to 2 billion doses and offered its inactivated vaccines to over 16 countries and regions. Sinovac announced results on its phase 3 trials in Brazil, Turkey and Indonesia¹⁷. After 14 days following vaccination with 2 doses of vaccine following a 0,14-day schedule, the efficacy rate against diseases caused by Covid -19 was 50.65% for all cases, 83.70% for cases requiring medical treatment, and 100.00% for hospitalized, severe, and fatal cases. The participants in this trial were all healthcare workers over the age of 18. Phase II clinical trials on seniors are ongoing. Still, Sinovac has started to vaccinate the elderly in Turkey and other countries. Meanwhile, the World Health Organization (WHO) sent a team to visit Sinovac's manufacturing plant in mid-February as a prerequisite to obtain WHO's pre-qualification. They provided very pertinent and significant suggestions on improving medical quality.

The Russian vaccine, Sputnik V is called Gam-Covid-Vac Lyo in ongoing clinical trials in the USA. It uses a genetically modified adenovirus to produce the S protein. It has been approved in over 50 countries, including Hungary, the Czech Republic and Slovakia¹⁸. Other members of the European Union (EU) want to buy it but are waiting for approval. Russia says it is ready to sell 50 million of the two-dose vaccine to Europe as soon as the EU gives its approval¹⁹. A recent partnership was made between the state-owned Russian Direct Investment Fund, which funded Sputnik’s development, and the Italian-Swiss firm Adienne Pharma & Biotech, which will accelerate vaccine production. Only about six percent of the 450 million people in the EU have received at least one dose of a vaccine, far behind America’s 18 percent and Britain is 30 percent. Serbia, the best performing European nation after Britain, has vaccinated 25 percent of its population. They are using a variety of vaccines — from Western companies as well Russia’s Sputnik and China’s CoronaVac. Serbia isn’t a member of the EU. In contrast, Sputnik is banned in Ukraine, where some people call it a “hybrid weapon” ¹⁹.

On 30 Dec., 2020 the UK Medicines and Healthcare products Regulatory Agency (MHRA) approved AstraZeneca-Oxford’s AZD1222, also known as ChAdOx1 nCoV-19 and COVISHIELD²⁰, followed by India on 3 Jan., 2021. Bangladesh, Argentina, the Dominican Republic, El Salvador, Mexico and Nepal have also approved it. It uses a genetically engineered adenovirus to produce the S protein. However, Denmark, Iceland and Norway have suspended its use while the EU’s medicines regulator investigates whether the shot could be linked to a number of reports of blood clots. The investigation is the latest trouble in Europe for British-Swedish company AstraZeneca, which has come under pressure to produce more vaccines after it fell tens of millions of doses short in deliveries to the EU. Italy banned the export of 250,000 doses of the vaccine to Australia last week in an effort to protect its national supplies. France said it would also consider banning exports, as concerns of vaccine nationalism rise. In addition, regulatory bodies in some member countries have been slow to recommend the vaccine for people over the age of 65, citing a lack of data. Regulatory bodies in several countries, including Germany and France, have since changed recommendations to include over 65 as data from post-market monitoring has shown that the AZD1222 vaccine is highly effective at preventing hospitalization in the elderly. France limits the shot to people under the age of 74.

On Feb., 27, 2021 the FDA issued emergency use authorization for Johnson & Johnson’s vaccine (JNJ-78436735) that uses an attenuated adenovirus, but it only requires one dose^21,22. A Phase 3 clinical trial (called ENSEMBLE) is being conducted in Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa and the USA²². Then, on 2 March, 2021, one of Johnson & Johnson’s biggest competitors in the past, Merck, formed a partnership to help produce the JNJ-78436735 vaccine²³. They are expanding their manufacturing capacity using funds provided by the Biomedical Advanced Research and Development Authority (BARDA) within the Department of Health and Human Services²⁴.

Sadly, the politics of Donald Trump’s Republican Party is still powerful. The Conference of Catholic Bishops in the USA released a statement expressing "moral concerns" over the Johnson & Johnson vaccine due to its use of cells that were taken from the tissue of aborted fetuses in the 1980s. This is in direct rebellion against Pope Francis, who received the vaccine in January and wrote the following²⁵:

It is morally acceptable to receive Covid-19 vaccines that have used cell lines from aborted fetuses in their research and production process and the morality of vaccination depends not only on the duty to protect one's own health but also on the duty to pursue the common good.

Vaccinating the elderly

A recent study showed that vaccinating the elderly saves not only the most lives but also the most years of life²⁶. The risk of death from Covid-19 increases with age - at a rate of about 11% per year. Without vaccinations, the number of people who would die of Covid-19 is so much higher in the oldest age groups than in younger groups that protecting the older groups actually saves more years of life, in total. So, vaccinating a 90-year-old in the United States would save twice as many years as vaccinating a 75-year-old, and six times as many as vaccinating a 50-year-old²⁶.

Covid-19 and children

The international community of scientists and healthcare workers is especially interested in protecting young children. Unfortunately, there is a possibility that a small proportion of young children who become infected with the virus can develop a severe heart disease similar to Kawasaki disease that can lead to cardiac aneurysms^13,27. There appeared to be a small outbreak in the city of Bergamo, Italy during the height of the outbreak of Covid-19 in that country. There was a report of ten cases of children developing the Kawasaki-like disease. At this time, we don’t know if the SARS-CoV-2 virus triggered the disease or is simply a new disease that has emerged with unknown causes. The disease is called pediatric inflammatory multisystem syndrome temporarily associated with SARS-CoV-2 (PIMS-TS)¹³. It is possible that it is mediated by antibodies or immune complexes since there was little evidence that the virus was replicating in these children.

More recently, a multisystem inflammatory syndrome (MIS) has been described in children with Covid-19²⁸. Still, infection with the SARS-CoV-2 virus in young children seldom leads to the most severe symptoms of Covid-19. However, there have been more reports of severe hyperinflammatory disorders developing 1–2 months after the acute infection with SARS-CoV-2. It is also called MIS-C. Most patients were treated successfully with relatively high dose steroids in combinations with intravenous immunoglobulins (IVIG) to override the effect of potentially deadly autoantibodies and to stimulate inhibitory Fc immune receptors. Some children were also given recombinant IL1RA (Interleukin 1RA, or anakinra) to the extreme inflammation. The researchers found that there is a particular cytokine profile associated with MIS-C, which differs from Kawasaki disease hyper inflammation and changes in response to immunomodulatory treatment. They also measured the binding of immunoglobulin G (IgG) to the S protein from SARS-CoV-2. They found that 3 out of 4 tested MIS-C patients had comparable levels of SARS-CoV-2 IgG antibodies to the S protein as the children with mild SARS-CoV-2 infection and no MIS-C. A possible explanation for why some children develop MIS-C is that prior immunity to other viruses could modulate their responses to SARS-CoV-2 infection and give rise to hyperinflammation either by antibody-mediated enhancement or other mechanisms. They found that the children in their study had IgG antibodies to common viruses such as respiratory syncytial virus (RSV) and rhinovirus as well as viruses of the herpesvirus family. The common cold coronaviruses are particularly interesting as possible modulators of immune responses to SARS-CoV-2 given their similarities. They found that IgG antibodies to the human coronavirus HKU1 were commonly observed in most children, as were antibodies to betacoronavirus 1, but the MIS-C patients were the only ones lacking antibodies to either of these common coronaviruses. The relevance of this difference remains to be determined. It could be due to the fact that the MIS-C patients are older than the other groups of children analyzed, or the lack of IgG antibodies to common coronaviruses modulates the immune response to SARS-CoV-2 infection and plays a role in the pathogenesis of MIS-C. They also found autoantibodies to proteins involved in immune cell signaling, and structural proteins in heart and blood vessels. This strongly suggests that there has been an autoimmune attack. The hypothesis that autoantibodies contribute to the pathology in MIS-C is supported by the efficacy of IVIG in MIS-C, a common approach to activate inhibitory Fc-receptors and prevent autoantibody-mediated pathology²⁸.