Coronavirus (46) NHS website on vitamins and minerals

Coronavirus (46) NHS website on vitamins and minerals
After reading the last two blog posts, you might be eager to start a balanced diet in order to strengthen your immune system. The NHS website on vitamins and minerals provides examples of food that can be easily found in UK supermarkets.¹ Here in this blog post, I would like to tabulate the information from the website to make it easier for you to have a look. The harmful effects if we have too much of the vitamins/minerals and the suggested maximum daily intake amount for an adult in the website are also included in the table.

As the daily intake requirement for the vitamins/minerals between adults and children, male and female are different, you might have an interest to have a look at the report from the Public Health of England on dietary recommendations for both children and adults before you plan for your diet.²

Table 1. Sources of vitamins and minerals

	Sources of Vitamin	Can it be stored in the body?	Effects if having too much
Vitamin A	cheese, eggs, oily fish such as trout, salmon, sardines, pilchards, fortified low-fat spreads milk and yoghurt, liver and liver products such as liver pâté	Yes	Having more than an average of 1.5 mg a day of vitamin A over many years may affect your bones, making them more likely to fracture when you're older..Having large amounts of vitamin A can harm your unborn baby.
Beta-carotene (Precursor of vitamin A)	Yellow, red and green (leafy) vegetables, such as spinach, carrots, sweet potatoes and red peppers, yellow fruit, such as mango, papaya and apricots	Yes	If you eat more beta-carotene, less is converted, and the rest is stored in fat reserves in the body. So too much beta-carotene can make you turn yellow, but will not kill you with hypervitaminosis.
Vitamin B1 (Thiamine)	Peas, some fresh fruits (such as bananas and oranges), nuts, wholegrain breads, some fortified breakfast cereals, liver	No	There's not enough evidence to know what the effects might be of taking high doses of thiamin supplements each day. Taking 100mg or less a day of thiamin supplements is unlikely to cause any harm.
Vitamin B2 (Riboflavin)	Milk, eggs, fortified breakfast cereals, mushrooms, plain yoghurt	No	There's not enough evidence to know what the effects might be of taking high doses of riboflavin supplements each day. Taking 40mg or less a day of riboflavin supplements is unlikely to cause any harm.
Vitamin B3 (Niacin: nicotinic acid and nicotinamide. )	Meat, fish, wheat flour, eggs	No	Taking high doses of nicotinic acid supplements can cause skin flushes. Taking high doses for a long time could lead to liver damage. Taking 17mg or less of nicotinic acid supplements a day, or 500mg or less of nicotinamide supplements a day, is unlikely to cause any harm.
Vitamin B5 (Pantothenic acid)	Chicken, beef, liver and kidney, eggs, mushrooms, avocado	No	If you take supplements, do not take too much as this might be harmful. Taking 200mg or less a day of pantothenic acid in supplements is unlikely to cause any harm.
Vitamin B6 (Pyridoxine)	Pork, poultry, such as chicken or turkey, some fish, peanuts, soya beans, wheatgerm, oats, bananas, milk, some fortified breakfast cereals. The bacteria that live naturally in your bowel are also able to make vitamin B6.	No	Taking 200mg or more a day of vitamin B6 can lead to a loss of feeling in the arms and legs known as peripheral neuropathy. This will usually improve once you stop taking the supplements. But in a few cases when people have taken large amounts of vitamin B6, particularly for more than a few months, the effect can be permanent.
Vitamin B7 (Biotin)	Biotin is also found in a wide range of foods, but only at very low levels. The bacteria that live naturally in your bowel are able to make biotin, so it's not clear if you need any additional biotin from the diet.	No	If you take biotin supplements, do not take too much as this might be harmful. Taking 0.9mg or less a day of biotin in supplements is unlikely to cause any harm.
Vitamin B9 (Folate or folic acid)	Broccoli, brussels sprouts, leafy green vegetables such as cabbage, kale, spring greens and spinach, peas, chickpeas and kidney beans, liver (but avoid this during pregnancy), breakfast cereals fortified with folic acid	No	Taking doses of folic acid higher than 1mg can mask the symptoms of vitamin B12 deficiency, which can eventually damage the nervous system Taking 1mg or less a day of folic acid supplements is unlikely to cause any harm.
Vitamin B12	Meat, fish, milk, cheese, eggs, some fortified breakfast cereals	No	There's not enough evidence to show what the effects may be of taking high doses of vitamin B12 supplements each day. Taking 2mg or less a day of vitamin B12 in supplements is unlikely to cause any harm.
Vitamin C (Ascorbic acid)	Citrus fruit, such as oranges and orange juice, peppers, strawberries, blackcurrants, broccoli, brussels sprouts, potatoes	No	Taking large amounts (more than 1,000mg per day) of vitamin C can cause stomach pain, diarrhoea, flatulence. These symptoms should disappear once you stop taking vitamin C supplements.
Vitamin D	The body creates vitamin D from direct sunlight on the skin when outdoors. Vitamin D is also found in a small number of foods. Sources include oily fish – such as salmon, sardines, herring and mackerel, red meat, liver, egg yolks, fortified foods – such as some fat spreads and breakfast cereals	Yes	Taking too many vitamin D supplements over a long period of time can cause too much calcium to build up in the body (hypercalcaemia). This can weaken the bones and damage the kidneys and the heart. If you choose to take vitamin D supplements, 10 micrograms a day will be enough for most adults.
Vitamin E	Plant oils – such as rapeseed (vegetable oil), sunflower, soya, corn and olive oil; nuts and seeds; wheatgerm-found in cereals and cereal product	Yes	There is not enough evidence to know what the effects might be of taking high doses of vitamin E supplements each day. Taking 540mg (800 IU) or less a day of vitamin E supplements is unlikely to cause any harm.
Vitamin K	Green leafy vegetables such as broccoli and spinach, vegetable oils, cereal grains. Small amounts can also be found in meat and dairy foods.	n.a	There's not enough evidence to know what the effects might be of taking high doses of vitamin K supplements each day. Adults need approximately 1 microgram a day of vitamin K for each kilogram of their body weight.
Calcium	Milk, cheese and other dairy foods, green leafy vegetables such as curly kale, okra but not spinach (spinach does contain high levels of calcium but the body cannot digest it all), soya drinks with added calcium, bread and anything made with fortified flour, fish where you eat the bones such as sardines and pilchards	n.a.	Taking high doses of calcium (more than 1,500mg a day) could lead to stomach pain and diarrhoea. Adults aged 19 to 64 need 700mg of calcium a day.
Chromium	Meat, nuts, cereal grains	n.a.	There's not enough evidence to know what the effects might be of taking high doses of chromium each day. Having 10mg or less a day of chromium from food and supplements is unlikely to cause any harm.
Copper	Nuts, shellfish, offal	n.a.	Taking high doses of copper could cause stomach pain, sickness, diarrhoea, damage to the liver and kidneys (if taken for a long time). Having 10mg or less a day of copper supplements is unlikely to cause any harm.
Iodine	Sea fish, shellfish, plant foods such as cereals and grains (the levels vary depending on the amount of iodine in the soil where the plants are grown)	n.a.	Taking high doses of iodine for long periods of time could change the way your thyroid gland works. This can lead to a wide range of different symptoms, such as weight gain. However, taking 0.5mg or less a day of iodine supplements is unlikely to cause any harm.
Iron	Liver (but avoid this during pregnancy); red meat; beans such as red kidney beans, edamame beans and chickpeas; nuts; dried fruit such as dried apricots; fortified breakfast cereals; soy bean flour	n.a.	Side effects of taking high doses (over 20mg) of iron include: constipation, feeling sick, being sick, stomach pain. Very high doses of iron can be fatal, particularly if taken by children. Taking 17mg or less a day of iron supplements is unlikely to cause any harm. But continue taking a higher dose if advised to by a GP.
Manganese	Bread, nuts, breakfast cereals (especially wholegrain), green vegetables such as peas	n.a.	Taking high doses of manganese for long periods of time might cause muscle pain, nerve damage and other symptoms, such as fatigue and depression. For most people, taking 4mg or less of manganese supplements a day is unlikely to cause any harm. For older people, who may be more sensitive to manganese, taking 0.5mg or less of manganese supplements a day is unlikely to cause any harm.
Molybdenum	Molybdenum is found in a wide variety of foods. Foods that grow above ground tend to be higher in molybdenum than foods that grow below the ground, such as potatoes or carrots.	n.a.	There's some evidence to suggest taking molybdenum supplements might cause joint pain.
Phosphorus	Red meat, dairy foods, fish, poultry, bread, brown rice, oats	n.a.	Taking high doses of phosphorus supplements for a short time can cause diarrhoea or stomach pain. Taking high doses for a long time can reduce the amount of calcium in the body, which means bones are more likely to fracture. Taking 250mg or less a day of phosphorus supplements on top of the phosphorous you get from your diet is unlikely to cause any harm.
Potassium	Bananas, some vegetables such as broccoli, parsnips and brussels sprouts, beans and pulses, nuts and seeds, fish, beef, chicken, turkey	n.a.	Taking too much potassium can cause stomach pain, feeling sick and diarrhoea. Taking 3,700mg or less of potassium supplements a day is unlikely to have obvious harmful effects. But older people may be more at risk of harm from potassium because their kidneys may be less able to remove potassium from the blood.
Selenium	Brazil nuts, fish, meat, eggs	n.a.	Too much selenium causes selenosis, a condition that, in its mildest form, can lead to loss of hair and nails. Taking 350μg or less a day of selenium supplements is unlikely to cause any harm.
Sodium chloride (salt)	Ready meals, meat products such as bacon, some breakfast cereals, cheese, tinned vegetables with added salt, some bread, savoury snacks	n.a.	Having too much salt is linked to high blood pressure, which raises your risk of serious problems like strokes and heart attacks. You should have no more than 6g of salt (around 1 teaspoon) a day.
Zinc	Meat, shellfish, dairy foods such as cheese, bread, cereal products such as wheatgerm	n.a.	Taking high doses of zinc reduces the amount of copper the body can absorb. This can lead to anaemia and weakening of the bones. Do not take more than 25mg of zinc supplements a day unless advised to by a doctor.

By now, you might have an idea what you would like to have in your meals. However, before you start the next meal, you can think about preparing it by yourself: buy fresh and unprocessed foods, add less salt and sugar, and use moderate amounts of oil for cooking. This way, you can get the most value of vitamins/minerals from the meal. Last but not least, don’t forget to drink enough water and exercise regularly.³



References
1. Vitamins and minerals. NHS. https://www.nhs.uk/conditions/vitamins-and-minerals/
2. Government dietary recommendations. Government recommendations for energy and nutrients for males and females aged 1 – 18 years and 19+ years. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/618167/government_dietary_recommendations.pdf
3. Nutrition advice for adults during the COVID-19 outbreak. WHO. http://www.emro.who.int/nutrition/news/nutrition-advice-for-adults-during-the-covid-19-outbreak.html

Coronavirus (45) Nutrients help to combat COVID-19 (cont'd)

Coronavirus (45) Nutrients help to combat COVID-19 (cont’d)
In addition to the vitamins mentioned in my last blog post, minerals such as iron, zinc, selenium and copper are also essential for good immunity. They are required in smaller quantities and are therefore called trace minerals. Let us have a look at the same two review articles^1,2 used in the last blog post, on how different trace minerals can protect ourselves from infectious diseases.

Copper
Copper itself is an antimicrobe. Copper supports neutrophil, monocyte and macrophage function and natural killer cell activity.

People on a low copper diet have decreased lymphocyte proliferation and decreased production of IL-2, which is important for immune response. Children with Menke’s syndrome, a rare congenital disease with no circulating copper-carrying protein caeruloplasmin, show immune impairments and have increased bacterial infections and pneumonia. Analysis of studies on Chinese children showed that those with recurrent respiratory tract infection were more likely to have low levels of copper in their hair.¹

Iron
Iron is a trace mineral that we should be careful about the amount we take in. Iron is required for both host and pathogen. Iron deficiency can impair host immunity, while iron overload can cause oxidative stress to propagate harmful viral mutations.²

Iron deficiency has harmful effects on immune function, including impairment of: 1. the ability to generate reactive oxygen species for the killing of harmful microorganisms; 2. bacterial killing; 3. natural killer cell activity; 4. T lymphocyte proliferation, and 5. production of T helper 1 cytokines. These in turn increase susceptibility to infection.¹

On the other hand, infections caused by organisms that spend part of their life-cycle intracellularly may actually be enhanced by iron. In the children living in tropical regions, iron at doses above a particular threshold has been associated with increased risk of malaria and other infections, including pneumonia. Thus, iron intervention in malaria-endemic areas is not advised.¹ Moreover, a study giving iron (50 mg on each of 4 days a week) to iron-deficient schoolchildren in South Africa increased the risk of respiratory infections.¹

In general, the harmful consequences of iron overdoses on infections include: 1. Impairment of immune function; 2. Excess iron favours damaging inflammation; 3. Helping the growth of pathogens that require iron.

Selenium
Selenium deficiency adversely affects several components of both innate* and acquired immunity,** and increases susceptibility to infections.¹

It is of concern to find that dietary selenium deficiency induces rapid mutation of benign variants of RNA viruses to virulence. Deficiency in selenium can cause oxidative stress in the host, and can alter a viral genome so that a normally benign or mildly pathogenic virus can become highly virulent.² Selenium could assist a group of enzymes that, in concert with vitamin E, work to prevent the formation of free radicals and prevent oxidative damage to cells and tissues.

It was reported that combination of selenium with ginseng stem-leaf saponins could induce immune response to a live bivalent infectious bronchitis coronavirus vaccine in chickens.² Therefore, the review article written by Zhang et al suggests that selenium supplementation could be an effective choice for the treatment of novel variants of COVID-19.²

You may wonder how much selenium we need to maintain the normal function of our immunity. It was found that selenium supplementation with 100 to 300 µg/day could improve various aspects of immune function in humans including in the elderly. Selenium supplementation of 50 or 100 µg/day in adults in the UK with low selenium status improved some aspects of their immune response to a poliovirus vaccine.¹

Zinc
Zinc has an important role in maintaining and developing immune cells of both the innate* and adaptive immune system.***

Especially you may find it interesting that zinc seems to play an important role in antiviral defence. It was found to inhibit the RNA polymerase required by RNA viruses to replicate. Moreover, zinc supports proliferation of CD8+ cytotoxic T lymphocytes, key cells in antiviral defence. These findings suggest that zinc might play a key role in host defence against the RNA virus SARS-CoV-2 that cause COVID-19.¹ In fact, the combination of zinc and pyrithione at low concentrations inhibits the replication of SARS coronavirus.²

Zinc deficiency has a marked impact on bone marrow by decreasing the number of immune precursor cells. Therefore, zinc is important in maintaining T and B lymphocyte numbers. Moreover, antibody production is decreased in zinc deficiency. Zinc deficiency also impairs many aspects of innate immunity, including phagocytosis and natural killer cell activity. Patients with the zinc malabsorption syndrome, acrodermatitis enteropathica, display severe immune impairments and increased susceptibility to bacterial, viral and fungal infections.¹

Correcting zinc deficiency lowers the likelihood of respiratory and skin infections. Recent reviews and analysis of trials with zinc reported shorter durations of common cold in adults, reduced incidence and prevalence of pneumonia in children, and reduced mortality when given to adults with severe pneumonia.¹

Conclusion
After reading the two blog posts on the different nutrients and their importance in fighting against infection, we understand we should have a balanced diet in order to maintain our immune system to prevent respiratory diseases such as COVID-19. No single nutrient should be left out in order to attain the optimum condition of our immune system for health.

As new pathogens responsible for influenza continually emerge, and outbreaks of new variants of the SARS-CoV-2 virus are highly possible, it is especially necessary to have a dietary regimen that includes all the nutrients in order to reduce the adverse effects from new or mutating pathogens.



*The innate immune system is the body’s first line of defense against germs. The innate immune system consists of 1. skin and mucous membranes that forms a physical barrier against germs; 2. immune system cells (defense cells) and proteins that are activated upon inflammation; 3. white blood cells (leukocytes) that kill bacteria or viruses, by phagocytosis, that enter the body; 4. natural killer cells specialized in identifying cells that are infected by a virus, and then destroy the cell surface using cell toxins.³
Since the innate immune system responds in the same way to all germs and foreign substances, it is also referred to as the "nonspecific" immune system. It acts very quickly: it makes sure that bacteria that have entered the skin through a small wound are detected and destroyed on the spot within a few hours. However, the innate immune system has only limited power to stop germs from spreading.³
**“Acquired immunity is a type of immunity that develops when a person’s immune system responds to a foreign substance or microorganism, or that occurs after a person receives antibodies from another source. The two types of acquired immunity are adaptive and passive. Adaptive immunity occurs in response to being infected with or vaccinated against a microorganism. The body makes an immune response, which can prevent future infection with the microorganism. Passive immunity occurs when a person receives antibodies to a disease or toxin rather than making them through his or her own immune system.” (from online NCI (National Cancer Institute) dictionary. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/acquired-immunity)
***The adaptive immune system takes over if the innate immune system is not able to destroy the germs. The adaptive immune system is made up of 1. T lymphocytes in the tissue between the body's cells; 2. B lymphocytes which are also found in the tissue between the body's cells; 3. antibodies in the blood and other bodily fluids.
The adaptive immune system specifically targets the type of germ that is causing the infection. It first identifies the germ, which makes it slower to respond than the innate immune system, and then it destroys it. It can "remember" germs, so the next time a known germ is encountered, the adaptive immune system can respond faster.



References
1. P.C. Calder. Nutrition, immunity and COVID-19. Review. BMJ Nutrition, Prevention & Health. 2020 May 20;3(1):74-92.
2. L. Zhang, and Y. Liu. Potential interventions for novel coronavirus in China: A systematic review. Journal of Medical Virology, 2020 May 92(5):479-490.
3. The innate and adaptive immune systems. InformedHealth.org. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. https://www.ncbi.nlm.nih.gov/books/NBK279396/

Coronavirus (44) Nutrients help to combat COVID-19

Coronavirus (44) Nutrients help to combat COVID-19
Since the outbreak of COVID-19 in the UK, which led to the first national lockdown in March 2020, the pandemic has already lasted for more than 15 months. During this period of time, many countries in the world experienced several waves of COVID-19 outbreaks, and quite a few major variants of the SARS-CoV-2 virus emerged. For the UK, the country has been attacked by the wild type, the variant from South Africa (Beta variant, B1.351), the variant from Kent (Alpha variant, B.1.1.7), and recently the variant that originated from India (Delta variant, B1.617.2).

The existing therapies and vaccines against COVID-19 were designed based on the SARS-CoV-2 virus first identified. The longer the virus spread among people, the higher the chances that the virus would mutate. The mutated variants that later become dominant are usually more virulent, and they are more resistant, to various degrees, to the existing therapies and vaccines. Unless we could produce a specific therapy or vaccine in time for an emerged variant, a good immune system, which is able to respond promptly and appropriately to different challenges, is very important to protect us against any SARS-CoV-2 variants.

Optimal nutritional status and lifestyle habits are essential to keeping our immune systems working properly. Here in this blog post, I would like to share with you findings from two review articles on how different nutrients can help us protect ourselves from infectious diseases.^1,2 This might give us an idea of what we could prepare for our meals in order to strengthen our health to combat coronavirus-related diseases.

Vitamin A
Vitamin A has been called an “anti-infective vitamin”. It is essential for body's defences against infection as it is important for normal differentiation of epithelial tissue.*^1,2 Lack of vitamin A is associated with increased susceptibility to respiratory infections, diarrhoea and severe measles.

Moreover, vitamin A is important for immune cell maturation and function: Vitamin A controls maturation of neutrophils, macrophages, natural killer cells, dendritic cells, and CD4+ T lymphocyte, which are involved in the killing of pathogens.¹

As we are undergoing a national vaccination program in the UK, it is also relevant to note that vitamin A deficiency can impair the body’s response to vaccination. Vitamin A’s metabolite, retinoic acid, is required for normal functioning of B lymphocytes, including antibody generation. An example from Indonesian children with vitamin A deficiency showed a higher antibody response to tetanus vaccination after providing them with vitamin A, suggesting that lack of vitamin A can impair the response to vaccination.¹

B group vitamins
B vitamins are water-soluble vitamins and work as part of coenzymes.² B vitamins are generally involved in intestinal immune regulation, thus contributing to gut barrier function.¹ Vitamins B6 and B12 and folate (Vitamin B9) all support the activity of natural killer cells and CD8+ cytotoxic T lymphocytes, effects which would be important in antiviral defence.¹ Lack of vitamin B6 deficiency causes thymus and spleen atrophy, low blood T lymphocyte numbers, and impaired lymphocyte proliferation and T lymphocyte-mediated immune responses,¹ while vitamin B12 deficiency decreases phagocytic** and bacterial killing capacity of neutrophils. In general, shortage of B vitamins weakens the host immune response.

Other B vitamins also has their special functions.1 Vitamin B2 (riboflavin) and UV light effectively reduced the amount of MERS-CoV in human plasma products.^2,3 Vitamin B3 (nicotinamide) could enhance the killing of Staphylococcus aureus (bacteria which often cause skin infections, pneumonia, heart valve infections, and bone infections). Moreover, lung injury during mechanical ventilation is usually seen in the severe cases of COVID-19 who need ventilators to get oxygen into body. Vitamin B3 treatment to these patients has a strong anti-inflammatory effect as it significantly inhibits neutrophil infiltration into the lungs.² Neutrophil infiltration in inflamed lung causes damage to the lung, and is a hallmark of Acute Respiratory Distress Syndrome in severe COVID-19 cases.

Vitamin C
Vitamin C is involved in collagen biosynthesis in connective tissues and is important for maintaining epithelial integrity (tissue in glands and linings).***^1,2

Its roles in immunity include leucocyte migration to sites of infection, phagocytosis** and bacterial killing, natural killer cell activity, T lymphocyte function (especially of CD8+ cytotoxic T lymphocytes) and antibody production1 (similar to the function of vitamin A).

Vitamin C supplementation has been shown to decrease the duration and severity of upper respiratory tract infections such as the common cold.¹ People deficient in vitamin C are susceptible to severe respiratory infections such as pneumonia.¹ This suggests that vitamin C might prevent the susceptibility to lower respiratory tract infections. Furthermore, vitamin C may also protect against infection caused by a coronavirus, as vitamin C increased the resistance of cultures of chick embryo tracheal organ to avian coronavirus infection.² As COVID-19 is related to lower respiratory tract infection, the Chinese researchers of a review article even suggest vitamin C could be one of the choices for COVID-19 treatment.²

Vitamin D
Vitamin D receptors are found in most immune cells. Vitamin D stimulates the maturation of many immune cells, and enhances epithelial integrity. Vitamin D also induces antimicrobial peptide synthesis in epithelial cells and macrophages, directly enhancing host defence.¹ Moreover, vitamin D increases phagocytosis, superoxide^# production and bacterial killing by innate immune cells.¹

A study from Taiwan found that people with vitamin D deficiency has lower antibody response, after vaccination with influenza A virus subtype H3N2 and B strain, than the group of people with normal vitamin D levels.¹ Studies using data from British and American populations suggested that vitamin D levels is inversely correlated with respiratory infection. This means the lower the vitamin D levels, the higher the risk of viral respiratory tract infection.¹

Vitamin D can be synthesized in our body with the help of sunlight. Summer is the time with sufficient sunlight, but over a year it is only a short time, so a high proportion of healthy adults in the UK are reported to have low levels of vitamin D. Moreover, the reduced outdoor journies due to the COVID-19 pandemic, further decreases the chance of people to absorb sunlight. Therefore, in addition to absorbing vitamin D from food, vitamin D deficient patients in the UK are usually prescribed vitamin D supplements by a GP. Meanwhile, a study in Japan found that supplementation of Japanese schoolchildren with vitamin D for 4 months during winter reduces the risk of influenza A by about 40%.¹

Vitamin E
Vitamin E is a lipid-soluble antioxidant that plays an important role in reducing oxidative stress through binding to free radicals.²

Vitamin E also plays a role in immune response and enhances antibody production.¹ The effect of vitamin E is especially obvious in healthy adults over 60 years of age. Research found a positive association between plasma vitamin E and cell-mediated immune response, and a negative association between plasma vitamin E and the risk of infections in this age group.¹ Studies by the Nutrition Research Center on Ageing at Tufts University in Boston demonstrated that vitamin E supplementation at high doses (800 mg/day) enhanced T helper 1 cell-mediated immunity (lymphocyte proliferation and IL-2 production), and improved vaccination response to the hepatitis B virus.¹ The same research group also reported that a daily intake of vitamin E supplement (135mg/day) for a year decreased upper respiratory tract infections, particularly the common cold, in elderly residents of a nursing home.¹ A study from Spain provided further evidence that supplementation of older adults with vitamin E improved their immunity defences.¹

Information on other nutrients to protect ourselves from infectious diseases will be presented in my next blog post.



*Epithelial tissue covers most of the external and internal surfaces of the body and its organs. These tissues serve as the first line of defence against inorganic, organic, and microbial intruders. Epithelial cells are the main cell type of these tissues.⁴
**Phagocytosis is a process of ingesting harmful foreign particles, bacteria, and dead or dying cells.
***Epithelial cells are the main cell type of epithelial tissues, which cover most of the external and internal surfaces of the body and its organs.⁴ Epithelial integrity is very important as a first line of defence against inorganic, organic, and microbial intruders.
^#Superoxide is a reactive oxygen species. It is generated by the immune system to kill invading pathogens in oxygen-dependent killing mechanisms.




References
1. P.C. Calder. Nutrition, immunity and COVID-19. Review. BMJ Nutrition, Prevention & Health. 2020, May 20;3(1):74-92.
2. L. Zhang, and Y. Liu. Potential interventions for novel coronavirus in China: A systematic review. Journal of Medical Virology, 2020, May 92(5):479-490.
3. S.D. Keil, R. Bowen, and S. Marschner. Inactivation of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in plasma products using a riboflavin-based and ultraviolet light-based photochemical treatment. Transfusion. 2016;56:2948-2952.
4. J. Gunther, & H-M. Seyfert. The first line of defence: insights into mechanisms and relevance of phagocytosis in epithelial cells. Semin Immunopathol. 2018; 40(6): 555–565.

Coronavirus (43) Mass asymptomatic testing of SARS-CoV-2 using lateral flow devices (cont’d)

Coronavirus (43) Mass asymptomatic testing of SARS-CoV-2 using lateral flow devices (cont’d)
Continued from my last blog post.
Limitation of lateral flow tests
The lateral flow test kit from Innova for detection of SARS-CoV-2 infections has been tested by Public Health England and validated by the UK government.^1,2 It was initially tested among 132 candidates when the UK government were considering the use of lateral flow devices (LFDs) in mass-testing for COVID-19 in an asymptomatic population.¹

The test report showed that all the tested lateral flow devices have a viral antigen detection rate of >90% at 100,000 RNA copies/ml (for comparison, only 3,600 to 10,000 copies/ml of virus in the sample is already enough to be detected by RT-PCR, which is more than ten times as sensitive). The study found a kit failure rate of 5.6% from 8951 Innova SARS-CoV-2 Antigen Rapid Qualitative Tests. The most common reason for kit failure was poor transfer of the liquid within the device from the reservoir onto the test strip. ¹

The false positive rate was 0.32% from 6954 Innova tests. This means that for every 1,000 people tested, only 3 people would get a false positive result. The study also found that the sensitivity (the detection rate of positive cases) across the sampling cohort is significantly dependent on the test operator. Sensitivity of the tests performed by laboratory scientists was 78.8%, trained healthcare-workers was 70%, while the self-trained members of the public was 57.7%.¹

The above study showed that the kit failure rate for the tests is not low, and they tend to give a more accurate result only if a sample with higher viral concentration is being tested and the user performing the test is well-trained. This means the overall accuracy of the lateral flow tests is generally lower among asymptomatic people who are not well-trained and who have a generally lower viral concentration.

When it comes to the real world evaluation of Innova SARS-CoV-2 Antigen Rapid Qualitative Test, the sensitivity of the test is found to be much lower than the above report. The Innova lateral flow test was used in a mass test of the population in Liverpool last November.³ By evaluation of the performance of the Innova lateral flow test against RT-PCR testing using data from 5,869 people, it was found that 60% of infected people could not be detected by the lateral flow tests. On the other hand, the test performed better for detecting cases in people with higher viral loads, with test sensitivity in this group at 66.7%.³ Similar to the result from the other study, the specificity was 99.9% in this study.^1,3 This means the positive results from the lateral flow tests are highly accurate.

Based on these research studies, the general sensitivity of the lateral flow tests are 40–76%, which means that about half of infected people may be missed.^1,3,4 Those carrying COVID-19 who were wrongly told they were free of the virus could transmit to more people than those who do not have the tests, due to a false sense of security. Therefore, many scientists called on the government at least to pause the rollout of rapid asymptomatic testing using the Innova tests, as they are sceptical that the lateral flow tests are able to control effectively the transmission of infection.^5,6

Can the lateral flow test detect COVID-19 variants?
There has no research paper or data available yet on the efficiency of the Innova SARS-CoV-2 Antigen Rapid Qualitative Test to detect the Kent and Indian variants which are now prevalent in the UK. The planned rollouts of lateral flow tests in schools were paused because of concerns about the risk of missing cases caused by the new and more transmissible SARS-CoV-2 variants.⁷

Where can we get the free lateral flow test?
After reading all the information about the free of charge lateral flow test scheme, you might want to try to have one yourself. The free rapid lateral flow tests are being made available by the government in England. As long as you are in England, aged 11 or above, and have no COVID-19 symptoms, you can order one pack of lateral flow tests per day online and it will be delivered to your home. Each pack contains 7 tests.⁶

​ The tests can also be collected at local PCR test sites and most of the local pharmacies in England. It is very important to remember that the tests are just for asymptomatic people: if you have COVID-19 symptoms, you should not go outside to collect a test; instead, you should order a PCR test and self-isolate.⁶

Who could benefit from the free lateral flow tests?
The sensitivity of lateral flow tests are in doubt, and the usefulness of the lateral flow tests being used as a tool to control the transmission of infection is being questioned by some scientists. However, as long as the tests are repeated twice a week as suggested by the government, there is still a chance of the asymptomatic infections being detected. Therefore, the free lateral flow test scheme available in England provides certain degree of protection for the households who have members working in patient-facing or customer-facing sectors.

However, you have to remember that the test on average misses about half of the COVID-19 infectious cases, i.e. a negative result does not rule out a COVID-19 infection. If your result is negative from the lateral flow test, it is very important to still follow all the current restrictions imposed by the government.



References
1. Peto T & UK COVID-19 Lateral Flow Oversight Team. COVID-19: rapid antigen detection for SARS-CoV-2 by lateral flow assay: a national systematic evaluation for mass-testing. medRxiv. 2021; (published online Jan 26.) (preprint). https://doi.org/10.1101/2021.01.13.21249563
(Later published online in Lancet, May 29, 2021. DOI:https://doi.org/10.1016/j.eclinm.2021.100924)
2. Order coronavirus (COVID-19) rapid lateral flow tests. GOV.UK website. https://www.gov.uk/order-coronavirus-rapid-lateral-flow-tests
3. Liverpool COVID-19 community testing pilot. Interim evaluation report by the University of Liverpool. 23 December, 2020. https://www.liverpool.ac.uk/media/livacuk/coronavirus/Liverpool,Community,Testing,Pilot,Interim,Evaluation.pdf
4. RT-LAMP assay: Fail to detect positive cases more than 50% in November in Manchester. “Covid-19: Rapid test missed over 50% of positive cases in Manchester pilot. BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4323 (Published 06 November 2020) Cite this as: BMJ 2020;371:m4323”
5.UK government must urgently rethink lateral flow test roll out, warn experts. The BMJ news, 11/01/21. https://www.bmj.com/company/newsroom/uk-government-must-urgently-rethink-lateral-flow-test-roll-out-warn-experts/
6. Covid-19: UK regulator approves lateral flow test for home use despite accuracy concerns. BMJ news, 2020; 371 doi: https://doi.org/10.1136/bmj.m4950 (Published 23 December 2020)
7. Mass testing of COVID-19: January update on lateral flow tests. UK Parliament Post, 29 January 2021. https://post.parliament.uk/mass-testing-for-covid-19-january-update-on-lateral-flow-tests/