A Shifting Perspective

Perhaps you have started to envision what life will be like in the coming weeks and months, as countries start to transition away from the ‘lockdown’ status that many, including the UK has undertaken. It may be that looking ahead leaves you cautiously optimistic, anxious and worried, frustrated or relieved when considering all the different elements of your work and home life.

Certainly, its somewhat of an unknown project for all of us and with that comes uncertainty. Most people feel unsettled by uncertainty and for obvious reasons.  Yet it also allows for opportunity and development, changes in patterns long enshrined in time constrained lives and perhaps a fresh consideration about what your priorities are going to be for the coming months and possibly years.

This global ‘pause’ brought about by the identification and global transmission of a novel infectious agent is unfamiliar to all of us, the rationale for the actions, the consequences of the actions and the reality of managing the actions are all changes no-one anticipated in December 2019. When the initial reports emerged of an epidemic in Wuhan, the capital of China’s Hubei province, policymakers had to make far-reaching decisions based on extremely limited information. Terrifying statistics presented from early pandemic modelling pushed governments into economic and societal lockdowns.

Since the pandemic began, scientists have published more than 8,000 papers with thousands more in preprint peer review on COVID-19 https://bit.ly/3bYGxK3 although many are unlikely to be of ‘gold standard’, the ones that are have been rigorously assessed. But despite this deluge, we have not seen a lot of huge plot twists. One of the most important, was the realisation that people can spread the virus before showing symptoms. But even that insight was slow to dawn. A flawed German study hinted at it in early February, but scientific opinion shifted only after many lines of evidence emerged, including case reports, models showing that most infections are undocumented, and studies indicating that viral levels peak as symptoms appear.

This is how science works. It is less the parade of decisive blockbuster discoveries (or conspiracy generated explanations) that the press often portrays, and more a slow, erratic stumble toward ever less uncertainty. Understanding oscillates at first but converges on an answer. That is the normal scientific process, but it looks jarring and slow to people who are not used to it.

COVID-19 had infected more than 3.8 million people as of May 8th, 2020, and is already the most deadly new pandemic since the emergence of AIDS nearly 40 years ago.

But some things are becoming clearer.

1. COVID-19 infection rates it seems are more common than was initially assumed. It also appears that many and possibly most of the people infected experience mild or no symptoms. Researchers in California checking antibodies (Preprint), which are adaptive immune defence agents released post infection also support the proposal that infection rates are higher than presumed. Whilst there are questions about how these specific data sets have been collected (as risks of false positives in the tests used are high) and analysed it appears that infection rates amongst the population may well be higher than expected, but in time we will have a more complete view.
2. The at-risk groups are becoming better stratified. As larger collected data sets from different settings and countries are analysed it appears that age, i.e. over 65 is one of the most dominant risk factors, followed by being male with comorbidities, especially cardiovascular and obesity, diabetes, immunosuppressive medications and cancer. Obesity can restrict ventilation by impeding diaphragm excursion, impair immune responses to viral infection, is pro-inflammatory, and induces diabetes and oxidant stress to adversely affect cardiovascular function regardless of age. Social and economic status and race are also turning out to be significant factors in both the UK and USA.
3. One of the underlying risk factors is the response/competence of the immune system (The ability of the immune system to respond appropriately to an antigenic stimulation and unleash an immune response ‘cascade’ and generate memory). Either it is too little, in the case of generating an active response to resisting an infectious state, or too late, and an overactive response is triggered in critical care management leading to the now well-known but poorly understood ‘cytokine storm’ and associated risks. SARS-Cov-2 is easily spread from person to person and this makes the support and regeneration of optimal self-defence through the current hygiene requirements, behavioural activities and immune competence equally important.
4. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B₆, B₁₂, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections including SARS-Cov-2 and therefore, an increase in disease burden.
5. The influence of the gastrointestinal tracts (preprint) bacterial composition and related immune capabilities and ACE2 receptors may contribute a predisposition to COVID-19 in healthy individuals. 60% of patients with COVID-19 report GI symptoms and tend to experience more severe disease responses.
6. Defeating COVID-19 as if it were a war time enemy is highly unlikely, rather like AIDS, TB, Malaria, Flu and other infectious diseases we will have to adapt and manage it. Changes in treatments, behaviour and lifestyle, as well as the extensive list of co-existing non-communicable diseases will also have a major impact on outcomes but remain within our control to change and resolve.

Focussing as governments are, on the development of a ‘magic silver bullet’ in a pharmaceutical (Remdesivir or Hydroxyquinoline for example) to solve COVID-19 along the lines of antibiotics for bacterial infections, is understandable, but a 100% successful outcome will be very unlikely with this and other viral agents. With over 40 years research on HIV, you would think that the science on this virus would be complete, but there remain many unknowns about HIV. Trying to pin down the coronavirus SARS-Cov-2 in just a few months and develop effective, safe pharmaceutical strategies including vaccination seems improbable, albeit desired.

Based on what we have learned, the clinical course of SARS-CoV-2 infection could be divided into three phases: viremia phase, acute phase (pneumonia phase) and severe or recovery phase. Patients with competent immune functions and without obvious concomitant risk factors may generate effective and adequate immune responses to suppress the virus in the first or second phase without immune over-reaction. In contrast, patients with immune dysfunction may have a higher risk of failing the initial phase and becoming the severe or critical type with higher mortality.

Returning to the shifting perspective concept, we should perhaps see the ‘virus’ related effects not because of an independent infectious agent, but as a medium through which society, health and resilience can be viewed. Our current and perhaps future lifestyle choices are influencing the impact of this and other infectious agents, positive economic, ecological, behavioural, lifestyle and nutritional changes to ensure immune resilience will diminish the risks and consequences of viral infection and also reverse many chronic diseases, are you ready to make those changes?

If you were to look at just one intervention…there is mounting evidence that vitamin D for example is a negative endocrine regulator of the renin-angiotensin system (RAS) (a prime site for the ACE2 receptors that SARS-Cov-2 uses to enter the cells), and that optimisation of vitamin D levels can lower RAS activity via transcriptional suppression of renin expression.

Since at this time of the year (spring), the lack of vitamin D in the population of the northern hemisphere and in the black, Asian and minority ethnic population is widely observed, it is likely that the role of RAS in COVID-19 disease is not negligible. Indeed, the world distribution of COVID-19 fatalities appears to overlap with that of the vitamin D lacking population. Not to mention that people lacking vitamin D have a weaker innate immune defence against SARS-CoV-2. Vitamin D supplementation at 2-5000iu a day for adults is a very low risk, immune resilience generating option worth exploring.