Covid-19 resurgence

While New Zealand has been one of the most successful countries in the world at not letting Covid-19 (SARS-CoV-2) become a rampant infection throughout its communities, the global impact of this pandemic remains extremely high.  Given how difficult an elimination strategy has been to execute, and the economic consequences of lockdowns, many countries are now in the process of developing and implementing policies that are based upon learning to live with rather than eliminate it.

The last 18 months have seen a whirlwind of change as this clever virus has caused so many deaths and disrupted so many lives. Over the next year or two we will undoubtedly continue to see further new developments, including the emergence of new variants and increased rates of vaccination, but also further increases in our understanding about how to best deal with the virus in different scenarios.

Recent experiences of our cousins over the ditch in Australia, highlight just how easy it is to tilt from living life largely as we used to, to being back in lockdown, as the more infectious delta variant runs through communities. New South Wales has just recorded 163 cases in the last 24 hours, its highest number of new cases since the latest outbreak began. Other nearby countries such as Fiji, are presently faring much worse, with 918 new cases and 15 more deaths confirmed in the 24 hours to 22^nd July.

Apart from being more infectious, studies suggest the delta variant can also produce a much higher viral load within the respiratory system than the original strain of the virus. This combination of a higher viral load and more efficient transmission, makes this variant particularly worrisome.

While vaccination rates are increasing, supply shortfalls and differing levels of prophylactic efficacy, are concerns. Additionally, the duration of immune memory and thus protective immunity after contracting a Covid-19 infection, or after vaccination, are still unknowns that will take years to gather reliable data on⁽¹⁾. All of this and more, highlights just how challenging the battle against this virus is, and that its impact on our lives will continue for a long time yet.

Developing Immunity:

New Zealand modelling has estimated that to ensure herd immunity, an overall vaccination rate of around 83 percent using the Pfizer vaccine will be required. With the more contagious delta variant however, a vaccination rate of 97%, is likely to be needed⁽²⁾.

Discussing the pros and cons of vaccination is not the purpose of this article. But what now seems clear, is that achieving these levels of vaccination in our population, is very unlikely to happen.  While most New Zealanders will probably opt for vaccination particularly as the global situation remains dire, I cant see more than 70% of the population being vaccinated anytime soon. The conclusion now being reached by epidemiologists and microbiologists is that in addition to relying heavily on vaccination, we’ll probably need to maintain and add a mix of other measures in order to achieve an acceptable level of population immunity. Ongoing border restrictions, mask wearing, social distancing and the need for differing levels of lockdown in the coming months or more, seems unavoidable. In addition to such measures, a focus on individual immunity and treatment interventions should an infection arise, is also important.

Plants have enormous potential to help optimise immunity in humans, and a healthy vegetable and fruit rich diet, is linked with favourable influences on the gut microbiome and immune function. Their complex phytochemistry including diverse polyphenolic molecules and fibre, and vitamins such as vitamin C, contribute to the healthy functioning of these bodily defence systems.

The use of herbal medicines or supplementation of the diet with immune enhancing herbs and spices for at least 14 days during periods of community outbreaks, is a recommendable component of a Covid-19 management strategy. Culinary herbs and spices such as ginger, blackseed and holy basil show potential as antiviral agents and immunity enhancers against viral infections, while others such as horseradish, cinnamon thyme, oregano and garlic, may be useful to help prevent or treat secondary bacterial infections that can contribute to patients becoming seriously unwell⁽³⁾.

Variations in death rates from Covid-19 in different countries, may in fact partly relate to differences in diet. Associations have been suggested between several countries with low Covid-19 death rates, and traditional diets which incorporate large quantities of certain spices, or fermented vegetables (such as cassava in Africa, cabbage and other cruciferous vegetables in Germany and Korea)^{(4, 5)}.  

Echinacea (Purple coneflower) is one of the most promising immune enhancers from both a traditional as well as evidence-based perspective, and has pronounced anti-inflammatory and immunomodulatory effects. Its immunomodulatory mode of action, whereby it enhances the immune system when taken in the absence of infection, but may reduce excessive and possibly damaging inflammation (the ‘cytokine storm’) during a viral infection, is of particular interest. These properties suggest both a useful prophylactic effect of Echinacea against unwanted viruses, but also a potential usefulness during upper respiratory tract viral infections^(6).

While a Cochrane review found Vitamin C supplementation of at least 200mg per day to be associated with a 7.7% reduction in the duration of colds in adults⁽⁷⁾, a recent clinical trial which investigated the effects of 8 grams a day of vitamin C or its combination with zinc on recovery from Covid-19 infection, was stopped early due to disappointing results⁽⁸⁾. The methodology of this trial and rationale for its early termination, has however been challenged⁽⁹⁾.

Vitamin D deficiency has been revealed as a significant risk factor for acute respiratory distress syndrome, heart failure and sepsis, as well as in critically ill Covid-19 patients^{(10, 11)}.  Apart from addressing any deficiency as a prophylactic measure, supplementation and restoration to normal range of vitamin D in patients with Covid-19, has been reported to reduce inflammation and improve their immunologic state during antiviral drug treatment^{(12, 13)}.

Addressing weight loss when obesity is an issue, is also advisable. A retrospective study in China reported that 88% of non-survivors of Covid-19 with cardiovascular disease had a body mass index (BMI) over 25, as opposed to 18% in the survivor group⁽¹⁴⁾. Similarly a study involving 124 hospitalised Covid-19 patients in France observed that patients with a BMI over 35 were 7 times more at risk of requiring invasive mechanical ventilation during their ICU stay than patients with a BMI less than 25^(15)..

Some recent findings:

Despite all the grim news of late, there’s actually been a fair amount of encouraging research undertaken over the past year into plant-derived medicines and their influences on this cunning virus. Much of this has taken place in countries where the pandemic’s impact has been severe, and in others where traditional and plant-based medicines have for many years now been a focus of government health policies and research funding.

Herbal medicines can work well when combined appropriately with drug and other conventional therapies, and this is also the case with Covid-19 patients. In China, incorporation of traditional Chinese herbal treatments into the management of patients with Covid-19 has achieved additional benefits to those seen through drug-based treatment alone^(16-20). Similar experiences have been reported through the use of traditional herbal medicines in India and other countries^(21-23).

Another example of this is propolis, the resinous substance that bees produce from plant pollens, to help protect their hives. Propolis is full of powerful phytochemicals including many with antiviral properties, and results from a clinical trial involving patients hospitalized with Covid-19 in Brazil, are encouraging. Propolis administration alongside the various conventional drugs and treatments given to seriously ill Covid-19 patients, lead to a much faster recovery time and halving of the median duration of hospital stay, from  12 to 6 days^{(24, 25)}. The extent of kidney damage was also reduced in patients given propolis.

Separate clinical trials are also planned or underway in Iran into the use of ginger⁽²⁶⁾ or pomegranate juice⁽²⁷⁾ alongside standard hospital treatment for Covid-19, which will measure both inflammatory markers and clinical outcomes. In Saudi Arabia a trial is underway into adjunctive use of the popular middle eastern spice blackseed (Nigella sativa, or black cumin)⁽²⁸⁾. Several Nigella components have shown promise in in vitro studies as anti-viral agents^(29-32).

Extracts of the medicinal fungus Ganoderma lucidum (Reishi), and the wild and culinary herbs Perilla frutescens (Perilla) and Mentha haplocalyx (Mint), have all recently been found to reduce the viral load in animal studies⁽³³⁾. Reishi exhibits antiviral activities also against herpes simplex, dengue fever, hepatitis B, and HIV ⁽³⁴⁾. A combination of Reishi with another medicinal mushroom Lions Mane (Hericium erinaceus), significantly reduced bacteraemia and increased the survival in mice with pneumococcal sepsis⁽³⁵⁾. As with many other medicinal herbs, these mushroom extracts may exhibit preventive or therapeutic effects against severe bronchial infections and lung inflammation, that feature in severe Covid-19 infections.

In India, the highly regarded immunomodulatory and anti-inflammatory medicinal herb Andrographis paniculata, is being further researched by local scientists. Synergy has been shown between andrographolide and its other phytochemicals, in effects on upper respiratory tract infections and the ability to significantly decrease the production of pro-inflammatory cytokines in viral infections⁽³⁶⁾. Andrographolide seems to bind with crucial proteins to block the TNF-induced NFkB1 signaling pathway which contributes to the cytokine storm in Covid-19 patients⁽³⁷⁾. It also seems to inhibit the main protease and other key targets of the virus responsible for replication, transcription and host cell recognition^{(38, 39)}.

Sumac is the name given to many different species of Rhus, medicinal flowering plants that are endemic in temperate and tropical regions, including China (Rhus chinensis), the Middle east, and North America. Traditional uses in multiple countries include for antiviral, antimicrobial, antibacterial, antioxidant, and wound-healing properties. Molecular docking and drug-likeness studies have revealed potential protease inhibitory properties for various polyphenolic constituents of Rhus chinensis⁽⁴⁰⁾. Other Sumac extracts also exhibit organ-protective properties of relevance to Covid-19 pathology, and may also be useful during infections⁽⁴¹⁾.

In South America, the highly regarded medicinal tree Cats Claw (Uncaria tomentosa), has also been reported to contain compounds which inhibit the virus’s main protease^{(42, 43)}. A hydroethanolic extract of its stem bark, also inhibited the virus⁽⁴⁴⁾.

Desperate times lead to desperate measures however, and in some instances there have been exaggerated claims of efficacy with little evidence basis, for the use of particular plant medicines in treating symptoms of Covid-19 infection.

What is evident from the many studies either completed or underway in numerous countries of the world, is that planning and funding for research into specific locally available plants and dietary interventions, seems to be paying dividends. In most cases, targeted investigations into relevant traditional and historical uses of some highly regarded local species, including the application of molecular docking and other modern research technologies, combined with the incorporation of learnings to date about how this virus replicates and causes harm, is proving to be a worthwhile approach.

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