Ever since cases of Covid-19 emerged in December 2019, a plethora of information has been issued by institutions and individuals in an effort to prevent the spread of the virus within countries and across borders. Despite that, on the 11th March 2020, the World Health Organisation declared it a pandemic (meaning worldwide spread). Then most people realised that this was a major threat to the world. Inevitably, my family and friends knowing that I am retired consultant microbiologist and infection control doctor, have been asking me all sorts of questions about this new devastating virus. I usually say a few things and refer them to various guidelines online. Some come back to me with more questions about their unique circumstances. At the end of our conversations, I always ask them whether what I say makes sense. I decided to put pen to paper and refer them to this blog and take this opportunity to share this information with other people who may find it useful. I base my views on scientific knowledge and experience of dealing with many outbreaks after which lessons were learned.

1. The war between SARS- Cov-2(the cause of Covid-19) and Humans

I have used this war theme before in a short blog entitled the ‘War of attrition: Microorganisms vs Humans’ regarding antibiotic resistance. We all know that in order to win a war, one must know in detail the strengths and weaknesses of the enemy as well as those on one’s side. I will go through these starting with SARS-Cov-2 which I will occasionally refer to as the Coronavirus (Corona meaning ‘crown’ in Latin and what virologists saw under an electron microscope resembling the corona of the sun).One should point out that the war against the Coronavirus is different from the usual human to human war in that you cannot negotiate peace with the virus and the rules of engagement only apply on the human side.

The virus

It is very tiny, measuring between 0.05 to 0.2 micrometres or microns in diameter (1mm=1000 microns). Therefore, it is invisible to the naked eye making it a formidable enemy. It has a very simple structure. In the centre, it has genetic material made of a single stranded RNA (ribonucleic acid) surrounded by a protein coat called capsid. Outside this, is a lipid (fat) membrane which in turn is surrounded by another protein coat with spikes. Damage to any part of the structure makes it unable penetrate host cells and replicate. Unlike larger organisms, it is does not have appendages to move on its own, so it depends on us for transport including air travel. It can mutate (undergo changes in its RNA) and this results in favourable changes like becoming more virulent and making people sicker for a long time or unfavourable changes like inability to replicate which is an advantage for humans. The protein spikes behave like keys when they bind to the ACE2 (Angiotensin Converting Enzyme) receptors of the host cell before it enters the host cell by mimicry and deceit which are widespread in the animal kingdom. The spike has several components namely 1) the protein part which is for the attachment 2) a glycoprotein which has two functional domains -one is a binding receptor and the other is receptor for cell enzymes that break down the host and viral membranes. This second part of the virus also called the cleavage region  determines the lethality of the virus.  Once inside, it takes over the host’s cell functions and resources and start making copies of itself. The protein spikes start appearing on the surface of the infected cell. I call them ‘victory flags of conquer’. The body recognises these as foreign and uses them as an antibody/antigen bond that triggers the destruction of the infected cell with its foreign occupants in a process I will describe later. If the cell is not destroyed by the body, the replication goes on unabated until the cell bursts releasing thousands of copies of the virus ready to attack other host cells. Some of the new virus particles also appear in large numbers in the mucus and inflammation fluid on lining of the respiratory tract ready to be spread to other people by sneezing and coughing as will be described later on. For those that remain in the body, it is a fight to the end of one or both- the virus and the host. In the vast majority, humans win by eliminating the virus from the body, thanks to the host defences outlined below.

The human host

1) Local defences and underlying conditions

The respiratory tract consists of the nose, pharynx, larynx, trachea, bronchi, bronchioles and the lungs the key part of which are the alveoli (air sacs). The whole tract is like an inverted tree with leaves as alveoli and branches and twigs as bronchi and bronchioles respectively. With the exception of the alveoli, the respiratory tract is lined with epithelial cells which have cilia (hair-like structures) on which sits a film of mucus produced by epithelial cells called goblet cells. The mucus traps foreign particles including microorganisms. Synchronised and rhythmic beating of the cilia moves the mucus film up the respiratory tract and it is eventually swallowed. Interestingly, the ACE2 receptors mentioned above are also found in the gastrointestinal tract (GIT). No wonder, there are reports from China revealing that half the patients with respiratory symptoms also presented with GIT symptoms. Other unusual symptoms like anosmia (loss of sense of smell), parosmia (distortion of sense of smell) and ageusia (diminished sense of taste) have also been reported but other viral infections are known to be associated with these symptoms. There is growing evidence indicating that the virus attacks other organs and tissues including the kidneys, muscles and the brain. This may explain the recent reports of clinical features like hallucinations, paranoia, depression, anxiety, obsessive behaviour, fatigue, general weakness and difficulty in breathing all occurring several weeks after onset. These may be as result of the virus attacking the cells of organs via their ACE2 receptors or by a harmful immunological reaction of the body to the virus.

The alveoli and leaves perform the same function as being sites where gas exchange of carbon dioxide and oxygen take place but in the opposite direction. To function well both must not be waterlogged. A condition like cardiac failure that leads to the accumulation of fluid in the lungs (pulmonary oedema), does increase the severity of Covid-19 by compromising the gas exchanges and the ability of the lung defences to eliminate the virus. Conditions that reduce the flow of air in and out of the alveoli like asthma and COPD (chronic obstructive pulmonary disease) by narrowing of bronchi aggravate the effect of the infection, so does smoking which damages the lung and can lead to cancer. Damaged alveoli as in tuberculosis make gas exchanges much worse when there is another lung infection which the fewer alveoli macrophages are unable to fight off. Covid-19 will also make conditions worse for people with cystic fibrosis who have thick mucus blocking the respiratory tree. Acute respiratory distress syndrome (ARDS) happens when the lung becomes so damaged that the alveoli are filled with fluid resulting in very low oxygen levels in the blood (hypoxaemia). This is a serious condition as it affects the whole body through lack of oxygen.

Diseases of the chest wall like kyphoscoliosis and those of diaphragm like muscular dystrophy making breathing difficult will aggravate effect of the infection. Morbid obesity can cause severe mechanical compression of the diaphragm and other parts of the chest preventing the lungs to expand properly. This can make breathlessness much worse during a coronavirus pneumonia.

Cough is a natural reflex which protects lungs from harmful substances. As mentioned above, when the virus attacks the respiratory tract, the lungs are filled with inflammation fluid, mucus and debris which impede oxygenation. Thick mucus plugs can block major airways leading rapid clinical deterioration of a person with covid pneumonia as evidenced by poor blood oxygen saturation levels. Removing the plugs by bronchoscopy can improve the clinical condition dramatically.

‘Proning position‘(being on all fours-knees and elbows with the head down) allows the fluid to drain down by gravity and cleared by deep breaths and coughing. This can improve the oxygenation at the bases of the lungs. In the prone position which achieves much the same goal of better oxygenation, the body is flat with the chest down and the back up. If the pillow is used, some people place it lengthwise under the head and the chest to be more comfortable. These techniques and use of an Oximeter which measures blood oxygen levels( normal levels being 95-100%) greatly help in the management of covid pneumonia. There are reports indicating that oximeters currently in use overestimate the blood oxygen levels of people with dark skins. In practical terms, a ” normal ” reading may be false. Therefore other parameters should be taken into account.

Some people advocate the use of remedies that may reduce the viral load in the upper respiratory tract when a significant exposure is suspected and in the early phase of the infection. These include warm salty water gaggles and steam inhalation. They may at least help in soothing the early symptoms.

2) General defences, underlying conditions and immunosuppressive drugs

There are two types of immune systems-the innate immunity and the adaptive immunity. The former is nonspecific and is the first in line to attack foreign invaders. It includes interferons and fever (see below).The adaptive immunity starts which starts about a week recognises and attacks specific antigens.

The body  starts making antibodies by a group of white cells called B lymphocytes. The antibodies neutralise the virus before it attacks other cells. The first class of antibodies to be made and sent to the front line are called Immunoglobulin M (IgM) followed by a smaller but longer lasting IgG. These neutralising antibodies can be used later as evidence of the body having encountered the virus before and make the individual immune to further attacks by the virus. They can be harvested from the blood of a person who has recovered from the infection and be given to a susceptible person to prevent an infection or moderate the course of an active infection. In immunisation terms, this is called passive immunisation in contradistinction to active immunisation when individuals make their own antibodies after vaccination. The effectiveness of passive immunisation lasts for only a few weeks. People with agammaglobulinemia (unable to make sufficient antibodies) are susceptible to many infections and so are people with multiple myeloma – cancer of  the cells that produce antibodies

Activated B lymphocytes from a person who has recovered from an infection can be cloned to make specific monoclonal antibodies for prophylaxis or for modifying the course of the infection. All these are possibilities for managing covid-19.

T-cells another type of white cells, bind to the virus particles and engulf them. Antibody/antigen bonding stimulate some cells to produce substances with remarkable effects. The antivirus antibodies bind to the protein spikes’ victory flags of conquer’ on the surface of infected cells. This triggers a group of cells called killer T-cells to produce perforin and cytotoxin which kill the infected cells and the foreign invaders inside them. If T-cells are depleted by for example an HIV infection, this can be a major defect in the host defences. However, it is not a problem in the example given for those on antiretroviral drugs with stable normal counts.

Interferons also known as cytokines are small proteins produced by white cells called T-cells in response to a viral infection. Fever also boosts the production of interferons. They simulate infected cells and the neighbouring non-infected cells to produce proteins that prevent virus replication. A process sometimes referred to as a ‘cytokine storm’ happens when there is an overproduction of these and other chemicals. They also modulate the immune response to avoid an overreaction which can harm the host. Like in all host defences, a few defects can occur. It has been reported that some individuals many of them relatively young have some interferons with reduced activity. Some have antibodies against interferons and others have mutations that stop them working properly. These individuals tend to get severe Covid-19.

A group drugs called immunomodulators can modify the immune response by reducing the over activity of the T-cells and stimulating the antibody production by the B lymphocytes ( mentioned above).Vitamin D activates the innate (natural)immune system and acts an immunomodulator by dampening an overreacting adaptive immune system-an explanation for the link between vitamin D deficiency and severe viral infections like covid-19. Macrolides, a class of antimicrobial drugs exemplified by Azithromycin have been used in Covid-19 therapy for their immunomodulation effect as well as treating bacterial super infections.

Fever is one of key signs of this infection. It occurs when the body’s thermostat in part of the brain called the hypothalamus is reset at a higher temperature. This may be a warning sign indicating that all is not well. It may also be a defence mechanism as high temperatures are not ideal for virus replication. That is why it is not recommended to take antipyretic drugs that reset the thermostat to a lower temperature before the cause of the fever is known as this gives a false sense of security. In this context, I should point out that there are a group of chemicals called prostaglandins that induce high body temperature by increasing heat production and reducing heat loss, but it is the interferons and other cytokines that cause fever, muscle pain and other ‘flu’ like symptoms of the viral infection. In nature, there is a reason for everything. These symptoms may force us to rest the body so that the host defences can use most of the available energy to fight the infection.

Sneezing is a defensive activity to expel foreign substances. The presence of virus particles in the nose triggers the release of histamines which stimulate the nervous system to initiate sneezing. Coronavirus takes advantage of this to spread to new hosts.

Old age has been mentioned a lot as a risk factor for severe Covid-19. With advancing age, all body systems including the immune system will be on the wane, so severe infections of any type are expected in the elderly. The function and reserves of other major organs like the heart, liver, kidneys and brain will also decline with age. When one organ is affected, there is a ripple effect on others and this may lead to multi organ failure which is usually fatal. It should be noted that one of the common sign of pneumonia in this age group is confusion.

At the other extreme are children, the majority of whom seem to get asymptomatic or mild infections. This may be due to their more robust immune systems especially the innate immunity. There is also a possibility of the children having less developed ACE2 receptors (previously mentioned). Recently, there have reports of children presenting with features of Kawasaki disease including toxic shock- like reactions and testing positive for the coronavirus. The cause of Kawasaki remains unknown but it seems to be an abnormal immune response to an agent including a microorganism. There are also reports of multisystem inflammatory syndrome in children (MIS-C) with abnormal serum inflammatory, coagulation and cardiac markers.

Irrespective of age, there are many other conditions and drugs that render people susceptible to severe infections. In the gastro-intestinal system, the disorders include Crohn’s disease and ulcerative colitis both of which are treated with the anti-inflammatory corticosteroids. The same drugs are used to treat alcoholic liver disease. Diabetes mellitus needs a special mention as it is very common and affects many organs. Any infection can make it worse but indications are that the coronavirus adversely affects the course of diabetes. It has been reported that the virus infects the pancreatic beta cells that produce insulin which facilitates the entry of glucose into cells where the energy we all need is generated. The failure to enter  the cells results in high blood glucose (hyperglycaemia) which has many adverse effects on the body including the reduction of nitric oxide  which is a powerful vasodilator. This reduces the amount of oxygen reaching the tissues at the critical times it is needed. This compounds the poor oxygenation in the lungs (inflammation and clotting) produced by the coronavirus. The death of cells due to lack of oxygen leads to an increase in the hydrogen ions making the body acidic. The deficiency of glucose in the cells makes the body turn to an alternative source energy -fat. By-products of this process are ketone bodies which are acidic ( making the acidosis worse)  and toxic leading to coma if present in large numbers. By damaging the insulin producing cells in the pancreas, the coronavirus can make a person with type 2 diabetes have type 1 diabetes as well. Prolonged use of immunomodulators like steroids may make diabetic patients susceptible to fungal infections like mucormycosis.

The narrowing of arteries in hypertension reduces the mount of oxygen reaching various parts of the body. The main target organs affected by this disease include the heart, the kidneys and the brain. Reduction in oxygenation of blood in the lungs caused by coronavirus pneumonia will lead to the deterioration in the function of these vital organs especially in those people with uncontrolled hypertension.

Obesity(previously mentioned in connection with breathing difficulty) is an independent risk factor for the development of  three medical conditions namely type 2 diabetes, hypertension and coronary heart disease. Each of four conditions interact with covid-19 to increase morbidity and mortality.

There is a large group of disorders called autoimmune diseases which are characterised by the body turning against itself and causing damage. They include rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, lupus, psoriasis to mention but a few. They are treated with immunosuppressive drugs to dampen down the harmful activities of the diseases.

There is also another group of people with various types of cancer on chemotherapy and radiotherapy not to mention post-organ transplant patients on immunosuppressive therapy.

The bad covid-19 effect on the whole body caused by the inadequate gas exchange in the alveoli is compounded by poor oxygen carrying capacity of the defective haemoglobins found in people with sickle cell disease and thalassemia syndromes.

There are reports of clotting disorders in people with covid-19 and they fall into three groups.  Clots in large blood vessels near or in the head cause strokes. The second group is that of small clots occurring in lungs and impeding oxygen exchange. Lastly, when the small clots are widespread as in a condition called disseminated intravascular coagulation (DIC), they consume the clotting factors leading to excessive bleeding. There is a possibility of DIC being caused by the virus attacking the endothelial cells that line the surface of blood vessels. If that is the case, the virus is likely to affect all parts of the body. If clotting is suspected, D-dimer test should be done to assess the extent of an active or recent clotting process.

Generally, viral infections tend to be more severe during pregnancy but as far as Covid-19 is concerned, its effects on mother and baby are yet to be investigated. In the meantime, contact with suspected cases should be avoided.

Anxiety in the face of danger is natural but an excess of it can lead to unthinking behaviour and that is panic. The remedy in this context is to give people accurate and timely information so that they can make informed decisions as most people are reasonable. Rational preparedness should not be interpreted as panic.

Chronic stress and the subsequent production of cortisol (the stress hormone) can depress the immune system.

Loneliness is another situation which has profound effect on the body. In this period of lockdowns and social distancing, it is important for us to be on the look out for one another.

Lack of quality or adequate sleep can adversely affect the immune system. Studies show that people who do not have enough sleep are likely to get sick after exposure to a virus. Therefore, good sleep hygiene should be practised by all.

Good nutritional status is vital in fighting infections after all our defences including antibodies (which are proteins) are made from what we eat. A balanced diet of proteins, carbohydrates, fat, minerals and vitamins is what is needed. In the presence of sunlight, one form of vitamin D is synthesised in the skin. Melanin, the pigment that gives the colour of skin protects people from sunburns and cancer. However, a lot of melanin inhibits the synthesis of the vitamin. Low blood levels of vitamin D have been associated with severe viral infections. In order to reduce this risk, people with dark skins living in countries with temperate climates or those who do not get enough sunlight, should eat vitamin D rich foods like fatty fish (salmon, tuna, sardines mackerel etc.) and mushrooms or take Vitamin D supplements. Apart from the skin, the liver and the kidneys play important roles in making two other forms of the Vitamin. Therefore, the functional integrity of the two organs should be taken into account when assessing the effects of the two forms of Vitamin D on the body. In the plasma cells, Vitamin D regulates the copying of messenger RNA, the carrier of genetic codes from the genes to the protein factory( the protective or neutralising antibodies being proteins). It also enhances the production by macrophages of two types of antimicrobial proteins- cathelicidins and beta defensins. In addition all that, Vitamin D modulates the excesses of the ‘cytokine storm’ which is harmful to the body. Also of note, is the deficiency of zinc which results in decreased immunity and increased susceptibility to infections. Its food sources include maitake mushrooms, spinach, pumpkin seeds among many others.

Last but not least, regular exercise helps to keep the body in good working order by preventing health problems as well as managing the existing ones.

All these and many more should be included when people talk about those with underlying conditions. It is good to know that in some countries, doctors have written to their patients informing them of the conditions they have. This could be useful information for admitting doctors in cases of emergency admissions to hospitals.

Lastly, in this fierce war, one should point out that the brain is our most powerful weapon against Covid-19 but it is a double edged sword. It serves us well with ideas and means to fight the virus but it also makes us do things that make us very susceptible to the virus.

2.Infection control measures

Measures to control infections fall into three categories 1) Source person 2) Routes of transmission 3) Susceptible host

1) Source (Isolate)

The source can be asymptomatic or symptomatic. Information from China revealed that the majority of contacts (sources) of positive cases, did not know that they had the virus. The people who transmit the infection include the asymptomatic (have acquired the virus but have no symptoms or have very minor symptoms),the presymptomatic (have acquired the virus and about to show symptoms),the symptomatic (they have symptoms) and those recovering (they no longer have symptoms but continue to carry the virus for varying  periods may up to three weeks or longer)   This means that most source contacts are likely have no symptoms. It has been reported that 50% of transmissions occur before the onset of symptoms.

When we cough, sneeze, talk, whistle, sing and yes when we laugh, we disperse virus carrying droplets of varying sizes. On one extreme the large droplets measuring about one millimetre(mm) in diameter will fall near the source because of gravity. On the other extreme, the very small droplets also called microdroplets measuring between 0.1 and 10 microns will remain airborne for hours. If the source person continues to cough for a long time in a confined space, these microdroplets will build up to such a considerable concentration to be able to infect many people in that space including those sitting many metres from the source. In winter, the humidity levels are low because cold air holds less moisture. Under these conditions, the influx of the virus-laden droplets will lead to a high concentration of the virus in the air. This and people spending more time indoors may contribute to the higher transmission rates of respiratory infections in the cold weather.  There is also the time factor-the duration of exposure. At a high concentration of the virus in the air, an individual may take a short time to breathe in a particular dose of the virus and acquire the same dose at a lower concentration but over a longer period of time. As dose is likely to be a determining factor in the severity of the infection, it is advisable to limit the time of exposure especially in confined poorly ventilated spaces. The dose can be increased by repeated breathing in of the expelled virus particles from same individual( auto-infection) or from other people nearby (cross-infection).  Wearing of masks (to be mentioned later) by both the source and the susceptible will reduce the dose and the risk of infection.

The force with which the droplets are dispersed and the size the holes through which they pass for example through fingers of a cupped hand when someone coughs, determine the distance they will travel. Talking seems a benign activity but it should be remembered that some syllables can generate considerable jets of aerosols.

As we touch our faces, mouths, and noses and then without washing our hands shake hands with other people or touch things they are likely to touch, we are likely to spread the virus. There is also a possibility of self ‘re-inoculation’. If you re-use tissues, touch your mouth and your nose with contaminated hands, you will reintroduce the virus into your respiratory track and start another wave of infection. This is likely to be significant early on in the infection before you have had enough time to mount an antibody response.

To prevent cross infection, the source person should be put in source isolation. If a person you have just been in contact with is found to be positive for the virus, you should go into self-isolation for 14 days counting from the date of contact (based on the agreed upper limit of the incubation period). If you develop symptoms, self- isolate for 7 days counting from the first day of the symptoms. If the symptoms get worse for example increased breathlessness or a new symptom like coughing blood, seek medical advise at once. Quarantine refers to restriction of movement after exposure to a group of unknown positive cases as happens when you leave a country with a high prevalence of the infections to go to another country. Duration of quarantine is currently 14 days. When there are limited resources, the onset and resolution of symptoms can be used to end isolation-10 days after onset and 3 days after resolution.

2)Routes of transmission (Block)

1) Aerial transmission

Person to person aerial transmission is the most important route for transmitting this virus. The shorter the distance between people, the more likely the transmission will be successful. Wearing surgical masks by the source person can block some of the large droplets but during sneezing and coughing some of the small particles will be forced forward through the holes and sideways through the gaps between mask and face. Occupied or recently occupied confined spaces with still air are not safe. Ventilation with adequate air changes measured in a number per hour makes them safer. Recirculating stale air without any form of filtration to remove the virus particles poses major risks of infection; so does the unidirectional flow of air from a source person without a face-mask to a susceptible person without a face-mask(she/he being downstream).

Assuming the presence of normal host defences and absence of any underlying conditions, the severity of infection is likely to be a product of the dose ( the number of virus particles in the air) and the duration of exposure (in minutes) in other words -area under the curve graphically speaking. Use of face masks is likely to reduce this risk.

Good fitting masks like the N95 are likely to be effective. They filter out 95% of the microdroplets (0.1-10 microns) and all the larger droplets. The penetration of the mask by microdroplets also depends on the volume air flow per minute. The bigger the volume the higher the penetration (the less efficient the mask).With a size of 152 picometres (1 micron=1000,000 picometres), the oxygen molecule easily passes through these masks. So does the carbon dioxide molecule (size of 253 picometres) with hardly any risk of hypercapnia (carbon dioxide toxicity) for those with normal lung function.  The systems that test the efficiency of the masks should give information on the size of the smallest particle measured. This gives us the users confidence on the level of protection offered.

If the good masks not available, improvised masks for example those made of closely woven cotton fabric with multiple layers should be used. Adding layers of chiffon fabric are reported to improve filtration. Such masks can be washed (at least once daily) and reused. As long as  the coronavirus is around, wearing face masks may become part of our routine clothing especially for those known to be susceptible to the virus and those who do not know their immunity status.

It is advisable to continue wearing masks long after effective vaccines become available. People ask ‘Why do we have to do this for the coronavirus when we don’t wear masks for Influenza?’ The main reason is that the coronavirus causes more severe infections including the life changing long Covid and is far more transmittable than Influenza. Secondly, the majority of people with the coronavirus have no symptoms; so they carry on with their normal activities and passing on the virus whereas the majority of people with Influenza have symptoms and tend to go off sick, thus limiting transmission. The other reasons for continuing to wear masks pertain to the vaccines:-1)The new vaccines are unlikely to be 100% effective. You may be in the minority who will not be protected. 2) Some people will remain sceptical and will refuse vaccination while others will delay it while pondering over the safety issues. 3) It will take time to roll out the vaccinations to the cover the whole world.4)The coronavirus is continuously mutating. If a vaccine does not completely prevent infections, a mutant resistant to the immune system of the vaccinee can arise. Wearing masks by all including vaccinated people can reduce the risk of such mutants spreading as  the new variants. As long as a large percentage of the world populations are susceptible to the virus and people continue to test positive, there will always be a risk of acquiring the coronavirus.

Here is another angle of the coronavirus as an airborne microorganism. Olfactory neurons have odour or smell receptors which are stimulated by molecules given off by substances or objects like flowers and perfumes. In relatively still air outside buildings, these molecules can reach high concentrations easily noticeable as we walk past a scented flower. If you substitute the flower molecules for the coronavirus particles which can stay airborne for a long time, you can see the rationale for wearing  masks by very susceptible people when they visit  in public places where a source may have just left the site. Social distancing on its own in these circumstances may give a false sense of security. Air sampling studies to detect virus air contamination (akin to what is currently done for bacteria) should be undertaken to provide the much needed data on this important issue.

Indoors precautions for households where one or more members are positive for the coronavirus antigen include 1) wearing masks in all ‘communal’ areas which should have adequate ventilation (air changes) 2) a person who is positive  or has been in contact with  a positive case being in isolated in singe room( if possible) with the door shut but  mask off ( to avoid autoinfection). 3) positive individuals not sleeping in the same room ( if possible) to avoid increasing their viral loads by cross-infection.

Aerial transmission can also contaminate objects from which a susceptible person can acquire the virus. Coughing and sneezing in the crook of the elbow will block some droplets. People ask questions of how to deal with potentially contaminated wrapped groceries. Wiping them with a cloth soaked in soapy warm water is likely to be effective before putting them away.

2) Direct contact

This occurs during kissing. As far as the virus is concerned, this is the best and direct route. Blocking this route of transmission is left to the imagination of the participants.

3) Indirect contact

An indirect contact transmission occurs when a susceptible person touches a contaminated object and transfers the virus to the nose or mouth before washing hands. Frequent hand washing with soap and water blocks this route of transmission. Soap or detergent kills the virus by dissolving its fat membrane. Water helps in physical removal of the virus and droplets from the hands. Alcohol of at least 60% contained in the wipes or gels inactivates the viral protein. Disinfectants including sodium hypochlorite, hydrogen peroxide, quaternary ammonium compounds and many others inactivate the virus. Criteria for choice of a good disinfectant or antiseptic include its ability to kill the virus, quick action (alcohol is the best for that), residual antiviral activity (alcohol is the worst for this) and lack of inactivation by the organic matter. Ultraviolet(UV) light in the sunlight can also kill viruses. Heat and detergents used in washing and laundry machines decontaminate clothes. All these render the virus unable to spread and infect cells of new susceptible people. Many people ask how long the virus stays viable on surfaces. Depending of the type of surface, it varies from a few hours to several days, but this is of little practical significance to most people. Washing hands with soap and water for at least 20 seconds is what should be remembered.

The other day, I saw a man wearing disposable gloves in public. I thought it made sense as it may be awkward to touch one’s nose and mouth with a gloved hand. I hope he disposed of them safely.

3)Susceptible person (Protect)

Anybody who has not encountered SARS-cov-2 is susceptible to the virus and this is the vast majority of the people in the world, 7.8 billion of us. The virus takes advantage of what people do during their social activities. As we listen to the source person face to face talk, open our mouth to interrupt, or laugh or moisten our dry lips, or touch our mouths or nose, the virus enters our bodies. Another port of entry of the virus to the respiratory tract is the eye which has a connection to the nasal cavity. The other route from the eye is the way of tears rolling down over the face to the nose and mouth. The common activivity of removing an eyelash or a foreign body from the eye can contaminate the eye. Luckily, the eyes are protected by tears which contain an enzyme called lysozyme with antimicrobial activity. People with dry eyes may be susceptible.

The number of virus particles entering the body is a very important factor that affects the severity and course of the disease i.e. the dose received. A single high dose can overwhelm the host defences but many small doses over a short period can have the same effect. This may explain why people with no underlying condition get severe infection but they may have some unknown risk factors. That is why nobody should take risks. The virus only needs to be lucky once.

80% of the population will be asymptomatic or have mild Covid-19. The remaining 20% have reduced host defences or underlying conditions some of which have been mentioned above. These are likely to get moderate to severe infections. If they are in hospital or such institution and are likely to be in danger of exposure to the virus, they should therefore be put in protective isolation.

By nature of their work, healthcare staff are at special risk of Covid-19. They should therefore be given personal protective equipment (PPE) as a top priority.

As a general precaution, the practice of ‘social/physical distancing’ has been advocated. This entails reducing socialising in public places and if this cannot be helped individuals have to sit or stand apart a distance of not less than two metres.

In the face of rapidly increasing number of infections, some authorities implemented draconian measures including banning sports events, concerts and many other events while others have gone for a complete lockdown to stem the tide of spread. The ideal situation will be to stop all transmissions all over the world for a period of time to let the events take their natural course in the infected people. That would imply stopping all human activities which is impossible. The other possibility is the virus mutating to a less virulent or non-virulent strain. In some instances, microorganism seem to be ‘territorial’ in that one strain at a time seems to cause an epidemic. That scenario can be to our advantage.

The more practical remedy is the long-awaited vaccine. Vaccines and new drugs take a long time to develop and test in mandatory clinical trials. As the new vaccines become available the principles of assessing them remain much the same namely:- a) Efficacy -usually expressed as a percentage – the higher the better b) The number of doses for a course -the lower the better c) Cost d)Safety – side effects and consideration of special groups like children and pregnant women e) Temperature of storage -convenient for all parts of the world f) Duration of immunity and g) Mass testing for post-vaccination immunity-this is unlikely to be practical and cost-effective for Covid-19.

The repurposed drugs have to be efficacious for the new indication.

3.Relaxing infection control measures (easing lockdowns)

1.Preparations and prerequisites

This is a tricky course of action as it involves two seemingly opposing forces. On the one hand, we must control the spread of covid-19 with its considerable morbidity and mortality. On the other hand, there is an urgent need to restart a frozen economy and people going back to their normal activities. The two are intertwined but we must tackle the threat to health properly if the economy to grow without further interruptions. We should take several preparatory actions as well as setting a few prerequisites to solve the puzzle.

a) Patience is required to do whatever is necessary to achieve our goals which are minimising morbidity and mortality as well as keeping the various components of the economy viable.

b) We should move away from being guided by imaginary peaks of graphs, which are produced from incomplete data for example the number of infected people and deaths both of which, at moment are estimates. Instead, we should follow the well established principles of infection control.

c) If possible, countries sharing land borders should have similar policies because of the possible undetected movements of people across the borders.

d)The diagnosis of covid-19 must be confirmed with a reliable test in a recognised laboratory as this is the key criteria for the case definition of a person who presents with a combination of any of these ( some already mentioned): fever, headache, cough, sore throat,  new loss of taste or smell, hearing loss(may be in one ear), shortness of breath, muscle pain, chills, diarrhoea, manifestation of clotting disorders including strokes and toxic shock in children or those who present with no symptoms (found by contact tracing or screening).The term ‘long covid’ has been added to the list of symptoms. It consists of symptoms that occur long after the initial symptoms some of which might have been very mild. The long covid symptoms reflect the dysfunctions of the interconnected body systems as follows:-1)Respiratory system: Breathlessness, cough.. 2)Central nervous system: Depression, anxiety, sleeplessness, post traumatic stress disorder (PSTD) features..3)Cardiovascular system: Palpitations, breathlessness(due to heart failure), chest pain(due to lack of oxygen to the heart muscle)..4) Musculoskeletal system: Chest tightness, joint pain, muscle weakness and pain. Other features will be added as we learn more about Covid-19.  There are reports indicating that repeated SARS-cov-2 infections may make existing long  covid conditions worse. This is may be akin to people who gets repeated Group A Streptococcal infections (certain strains) being at the most risk for rheumatic heart disease.

e) Hospitals and other such institutions where susceptible people congregate should have adequate capacity to isolate all suspected and confirmed cases of covid-19.

f) There should be reliable sources and distributors of good PPE for all healthcare staff who are at the constant risk of exposure to the coronavirus. In this context, extreme exhaustion may lead to mistakes in the proper use of PPE, consequently reducing their effectiveness. Therefore, adequate rest periods should be observed.

g) Good methods and technologies should in place for contact tracing of all cases of covid-19. New technologies include the use of Apps which will necessitate many people carrying their mobile phones all the time but with an advantage of faster, automated and more reliable contact tracing.

h) Sentinel surveillance (testing for rates of immunity to the virus in small samples to estimate the rates in entire population) should be performed. If the percentage is less than 60%, there is a real risk of an increase in morbidity and mortality when the measures are relaxed unless other measures like wearing good masks by all in public places are instituted. Eventually, the percentage will increase with an immunisation program when an effective vaccine becomes available. We hope that vaccines will confer longer lasting immunity than that acquired from natural coronavirus infection.

i) Places of work to be reopened must have adequate hand washing facilities as well as sanitisers. Public health authorities should formulate tailor-made guidelines for various places of work while licensing authorities where applicable ensure adherence to the guidelines.

2.The process of reopening should be done by: –

a) age group and giving reasons for the choice of that group, for example, primary schools being reopened because children get mild infections. In this example, the risk to teachers and other adult staff must properly assessed so that adequate protection can be given to them.

b) the type of industry and the reason given can be ‘a vital industry’. Related/interdependent industries should be reopened at the same time.

During the whole process, the authorities should fully inform and empower the public, making sure the information given makes sense

3.Easing restrictions on social contact.

As people from different families or the same family living in separate houses start having ‘normal’ activities like visiting or going out together, serious risk assessment of their situations in relation to the virus should be done. One should only socially interact with individuals who believe and practice the following:-

a) Wearing masks in public confined spaces including places of work or in a home situation where a family member is self-isolating.

b) Social/physical distancing in public places.

c) Frequent hand washing/decontamination with a sanitiser and or as necessary.

d) Source and protective isolation in home situations as instructed by health authorities.

The people who are about to interact should be aware of the fact that the coronavirus dose and duration of exposure are important factors in the initiation and severity of the infection. They should have had frequent discussions on matters related to covid-19 to establish trust which should not only be based on being relatives or on the duration of the relationship. They should also know each others recent relevant medical history including mental health and underlying conditions (mentioned in the blog). Last but not least is the prevalence of the virus  in terms of covid-19- the disease and the positive antigen tests at the time of the risk assessment. The assessment should not be based on the duration of the lockdown or the availability of a vaccine which may or may not protect some people.

The target containment mode for a country should be one positive in one million per day.  Therefore, for a country with of a population of 67 million, the figure should be 67 positive cases per day. All this assumes extensive testing.

4.Testing

There are two main reasons for performing tests in this context. The first one is as part of surveillance to find out the extent of the spread of the virus. This is extremely important in controlling the spread of the virus. It should be started as soon as possible and should be very extensive. Basic data of age, gender and address should be collected at the same time and used for contact tracing and formulation of control policies (as mentioned above under ‘ Relaxing infection control measure..).Positivity rate is the number of positive tests as a proportion of the total  number of tests done in a locality. A rising rate is below 10% is a warning sign and above that is worrisome. During the specified period the tests are performed, one test per person should be counted. This will give more meaningful results. Another frequently used rate for monitoring trends and comparing infections of different localities is the number of cases per 100,000 people. Sequencing which is the process of determining the sequence(order) the nucleotides in a piece of RNA or DNA is a very important aspect of surveillance. 

Variants

Like many other viruses, the coronavirus is continuously mutating. A virus with one or more new mutations is a variant.  The more prevalent it is in a community, the higher the risk of the occurrence of a dangerous variant. The risk is a function of number of virus particles around, the number of susceptible people as well as the number of those who are partially immune. The worst variant from our perspective is one which is highly transmissible, very virulent (causing severe infections and deaths), evasive of immunity (from natural infection and vaccination-reducing the efficacy of the some vaccines) and very hardy (staying viable in the environment for a long time). It is important to be conversant with the other terms that are often used in this context. The coronavirus genes which are made of RNA (ribonucleic acid) encode for the making of viral proteins. Mutation which is the change in RNA is translated into change in sequence of the amino acids in the protein being assembled. For example, in mutant N501Y, amino acid asparagine (N) has been replaced by tyrosine (Y) at position 501. The protein made is known to have increased binding affinity which may confer increased transmissibility as more virus particles bind to the host cells in the nasopharynx. In this example, it can be referred to as N501Y mutation. If the genome (which is the complete set of genes for the virus or indeed any organism) mutated further to another mutant X, then we have a N501Y/X lineage. Examples of lineages include A,AV.1, B, B-1, B.1.1,B.1.25, B.1.1207, B.1.1.7 (alpha), B.1.351,B.1.427, B.1.429/CAL.20C,  B.1.525,B.1.617.1, B.1.617.2,B.1.617.3,B.1.617(2 two mutations E484Q & L452R), D614, 501.V2, P.1, P.2 and many others. Some have been named after countries where there were first detected. This system can be misleading as such countries have facilities to perform sequencing and does not reflect the true distribution of the variants in the world. Of late, the most dominant variants have been named alpha and delta, the latter being far more transmissible than the former. While the delta variant rules supreme, the latest variant of concern now in late November 2021, is B.1.1.529(omicron). As expected another wave of mutants is sweeping the globe in 2022. They are subvariants of omicron – BA.4 and BA.5. They are more transmissible but apparently causing less severe infections because of acquired immunity from infections and vaccinations, the later probably playing a more important role. More than 30 mutations for the spike proteins have been detected in recent variants. When a new variant is detected in one locality, all routes of transmission to other areas should be blocked without any delay. Vaccine makers should map out the new epitope ( part of the spike protein to which antibody attaches itself) and modify the new vaccines to reduce the risk of immune escape by the virus.

The second reason for testing is to perform diagnostic tests when investigating a person with clinical signs and symptoms of an infection. The other diagnostic tests can include white cell counts to rule out bacterial infections and a ‘Flu’ test to rule out Influenza virus infection. In some centres a CT scan is also performed on people suspected of Covid-19 pneumonia as they show characteristic peripheral opacities in the lung fields. At the moment, the test used for both screening and confirming the diagnosis detects viral RNA by a technique called Polymerase Chain Reaction(PCR).One of the types of this test commonly used in good laboratories is called real-time quantitative PCR(RT-qPCR).In another variation of test, RT stands for Reverse Transcriptase an enzyme that coverts RNA to DNA).Quantitative refers to the amount viral RNA or viral load in the sample. The viral load is measured in terms of PCR cycle threshold(Ct)value. PCR amplifies the amount of viral RNA by running the test a number of times to enable detection by the system at a specified threshold. Detection at a high threshold value is indicative of a low viral load and vice versa for low threshold value. Many laboratories use a Ct cut off of 40 to interpret a test as positive. The quantitative information is very important for infection control purposes as the number of viral RNA copies in a positive sample varies from a few hundreds to millions.

As the key element of the case definition of Covid-19 is a positive test upon which important decisions and actions are based, its accuracy is paramount. The result of a test is affected by several factors including:-

a) The quality of the specimen: A poor sample ( with little or no material on a swab as can happen with a shallow nasal swab) is likely to give a negative result.

b) Specificity of the test (a test with 100% specificity will identify all people without the disease- in this case without the virus).With less than 100% specificity, the test will give false positives meaning that the tested person does not have the virus. False positives are not good for the economy as people are unnecessarily put in isolation when they should be at work.

c) Sensitivity of the test (a test with 100% sensitivity will identify all people with the disease-in this case with the virus).With less than 100% sensitivity, the test will give false negatives meaning that the tested person does actually have the virus. False negatives are not good for public health and the economy as pass on the infection to other workers.

That is why the specificity and sensitivity of a test must be known for the proper interpretation of the results. The other important  element of a good service is the timeliness of the test results.

As a diagnostic test, relevant clinical information should be put on request form to accompany a specimen of a throat or nasal swab. An example of such information can be ‘Suspected Covid-19 pneumonia, admitted from X nursing home’. If the test is positive, suitable comments in line with clinical information should be added to the report to look something like this:-

Clinical information given: ‘Suspected Covid-19 pneumonia, admitted from X nursing home’.

SARS -Cov-2 RNA detected by RT-qPCR. This is likely to be causative virus. Please take source isolation precautions to prevent spread. X nursing home has been informed.

As a clinical microbiologist working in the laboratory, I always took it as my responsibility to add such comments. I felt that it strengthened formal communications between the laboratory and the clinicians. A clinician should not have to contact the laboratory to ask ‘What does this result mean?’ Meaningful results would also be easily understood by the patients.

Hopefully tests that can detect an antibody response to the virus will soon be widely available. These tests should be specific and sensitive as mentioned above. They should be able to indicate active and recent infections by detecting IgM (a class of antibodies that can do this) or two samples of blood collected several days apart and demonstrating a significant rise in titres of another class of antibodies (IgG)

At this juncture, there are reports of rapid point-of-care tests just coming on the market. They fall into the two categories mentioned above:-1) Detecting antigens-parts of the virus in this case its RNA or protein in throat or nose swabs. 2) Detecting antibodies -IgM and IgG in a finger-prick blood sample by an antibody/antigen immunoassay test. The results for both are available in minutes.

The rapid antigen test is ideal as a clearance test for recently positive people whose type of work brings them in close contact with the public or a family member with a very susceptible person before discontinuing source isolation. Two consecutive negatives are ideal, the first taken 48 hours after symptoms stop. Prospective cohort studies of PCR tests should be done to find out the duration of carriage of the virus. These will provide valuable data for protecting very vulnerable people. It has been reported that

The last thing to mention on the laboratory investigations is the role of post-mortems. They are particularly important in the study of new diseases like Covid-19 but also if the cause of death is doubtful, they will distinguish those who died of from those who died with as the virus can cause asymptomatic and mild infections. In instances when it was not possible to collect specimens before death,  swabs can be collected for PCR  soon after. This would be important in conforming or ruling out the diagnosis of Covid-19.

Announcing fatality rates in the middle of an outbreak is not helpful because the numerators and denominators are unlikely to be accurate. Stratified high rates are likely to frighten the group concerned while the low rate will give a false sense of security. The rates should be published when the outbreak is over as one of the lessons learnt from the outbreak.

The tool of descriptive diagnosis

I used this tool as a practising microbiologist for many years and mentioned it in my recent book ‘The bugs doctor with a passion for music’ published in 2015.

Descriptive diagnosis is a formal statement that includes relevant words or phrases with treatment and management implications. It is a tool that can be used in many fields including economics. As far as infections are concerned the key components of it are:-

1)The causative organism-the more specific the better. In this context it is Sars-cov-2. If available, the right antiviral drug of proven efficacy would be given.

2 The site of infection– For Covid-19, it is upper respiratory tract infection or lower respiratory tract infection (pneumonia). Only a drug that can reach the site in high enough concentration to kill the virus should be used. Knowing the site of infection also helps managing the local host defences if necessary.

3) The state of the host defences a) locally – in this case the respiratory tract b) generally -the number and quality of T cells, ability to make antibodies and whether on immunosuppressive drugs. If the host defences are very depleted or absent, we would depend on the power of the anti-microbial drug to eliminate the pathogen.

Other words which have treatment implications can be added for example ‘severe’-indicating immediate hospitalisation, oxygen therapy, to be put on a ventilator etc.

In case of Covid-19, a typical descriptive diagnosis will be:-

Severe SARS-cov-2 pneumonia with COPD, immunosuppressive drugs for rheumatoid arthritis.

After a week in ICU on a ventilator, the patient may acquire MRSA pneumonia. The descriptive diagnosis then is:-

Post-Covid-19 ventilator associated MRSA(Methicillin resistant Staphylococcus aureus) pneumonia with COPD, immunosuppressive drugs for rheumatoid arthritis.

Post-Covid-19 is mentioned because it damages the respiratory tract making it susceptible to bacterial infection. For comparison, Influenza virus pneumonia is known to make people susceptible to Staph. aureus pneumonia. The presence of a foreign body in form of an endotracheal tube in the upper respiratory tract compromises the local host defences. That is why the ventilator is mentioned as makes the patient susceptible to hospital acquired infections like MRSA. In this case it should also be mentioned that they require antimicrobial drug therapy for it. In this example, there are three factors that compromise local host defences and one for general host defence. If the patient is elderly, that will have to be mentioned to make it two factors for general host defences.

I found this tool very useful when giving advice to my colleagues on the rational use of antimicrobial drugs. It also empowers patients to understand how the infections they have are managed. Collecting data in this format can makes it easier to analyse it and getting out clinically useful information.

In the era of Covid-19,other diagnoses (based on proper history taking, examination and investigations) must continue to be made; otherwise, their mortality will increase.

4.General remarks

The SARS-cov-2 combines the high transmissibility of the common cold coronaviruses (20% of common colds are caused by coronaviruses) and the virulence of SARS-cov-1 which causes pneumonia to make it a very dangerous virus.

There are many strengths and weaknesses on both sides of the war. Humans will win this one but at a cost. The challenge is to make sure the demand in fighting covid-19 does not outstrip the resources we have.

At the individual level, when the body is fighting the coronavirus, host defences need a lot of energy. Therefore, bed rest is vital in the recovery process. This includes resting the brain which at resting state consumes about 20% of the body’s energy. Consuming high energy sugary foods may be counterproductive as the inflammatory process may go into overdrive making some symptoms worse. Drinking water is a safe alternative if not contraindicated on medical grounds.

I hope that the blog provides a framework to which people who have found it useful can add their own information on the virus, the human body, prevention and control of infection, testing and managing covid-19.

If the virus mutates and the herd immunity to the current virus gives no protection to the new virus, then we will have a brand new enemy. Only time will tell.

The immune response to a vaccine ranges from non-response to full response (sometimes graded as no response , poor response, moderate response, good response) and the protection which varies with different variants as well as the individual’s  underlying conditions (which affect the severity of Covid-19). As long as the coronavirus exists with a large number of unvaccinated people and those whose true immune status is unknown, it is prudent to continue  wearing masks. All people should assess their own risks and circumstances.

Emmanuel Ndawula 31/03/2020

UPDATES

1) 06/04/2020-In nature, there is a reason for everything (under fever),Wearing masks (under aerial transmission), the importance of bed rest( under the general comments).

2) 07/04/2020 Sickle cell disease and thalassemia syndromes (under General defences, underlying conditions and immunosuppressive drugs).

3) 11/04/2020 –Obesity ( under Local defences–),HIV infection, uncontrolled hypertension( under General defences—),Unsafe confined spaces with still air, improvised masks, decontaminating wrapped groceries (Under aerial transmission) and repurposed drugs ( under susceptible host).

4) 20/04/2020 Relaxing infection control measures (easing lockdowns) –a new addition.

5) 22/04/2020  Good sleep hygiene (under General defences..), Adequate rest periods (under Relaxing infection control measures).

6) 27/04/2020 Use of Apps for contact tracing ( under Relaxing infection control measures (easing lockdowns).

7) 02/05/2020 Clotting disorders (under General defences.. and Relaxing infection control measures (easing lockdowns)

8) 11/05/20 Vitamin D as an immunomodulator (under General defences..), Vitamin D deficiency associated with severe viral infections(under General defences..), Kawasaki disease and coronavirus (under General defences..),and Dose and duration of exposure  in relation to severity of infection(under aerial transmission).

9) 26/05/20 Size of the Coronavirus (under The Virus), Sizes of droplets and microdroplets (under Source) and N95 masks and their efficiency (under aerial transmission)

10) 01/06/2020 The role Macrolides e.g. Azithromycin in Covid-19 therapy (under local and underlying conditions)

11) 11/06/2020 The importance of dose(the number of virus particles taken in),distance from source and duration of exposure(under Source)

12) 15/06/2020 Different source contacts including the asymptomatic, presymptomatic, the symptomatic and those recovering (under Source)

13) 13/07/2020 Long term ill health of Covid-19 as a result of the virus attacking other organs and tissues-the kidneys, muscles and the brain ( under local defences and underling conditions), Ventilation, air changes, the risk of circulating unfiltered stale air and unidirectional airflow ( under aerial transmission)and Positivity rates as part of surveillance ( under Testing)

14) 22/07/2020 The risk assessment checklist for family and friends before social interaction(under easing lockdowns).

15) 26/07/2020 How Obesity, Type 2 diabetes. Hypertension and Coronary heart disease interact with Covid-19 to increase morbidity and mortality( under General defences , underlying conditions….)

16) 09/08/2020 Proning position improves oxygenation of lung bases (under local defences- cough..)

17) 12/09/2020 Quality of specimens, specificity and sensitivity of tests and interpretation of results (under Testing)

18) 16/09/2020 Target for containment mode (under Relaxing Infection control measures)

19) 05/10/2020 Defects in interferon activity that render young people susceptible to severe Covid-19( under local defences and underlying conditions- Interferons

20) 07/10/2020 ‘Long covid’ (under easing lockdowns-case definition)

21) 14/10/2020 Quantitative PCR test and its value in infection control(under testing)

22) 20/10/2020 Why is the risk of transmission of respiratory infections higher in the cold weather?(under infection control: source)

23) 16/11/2020 The rationale for continuing to wear mask after vaccines become available.(under aerial transmission)

24) 27/12/2020 Details of the main component of the coronavirus spikes ( under the virus), Wearing of masks reducing the risk of the spread of vaccine resistant variants ( under aerial transmission),principles for assessing new vaccines ( under Susceptible person) and sequencing as an important aspect of surveillance(under Testing)

25) 20/04/2021 Variants(under Testing)

26) 24/04/2021 A rationale for susceptible people to wear masks in public places ( under Aerial Transmission)

27) 18/05/2021 A rationale for vaccinated people to continue wearing masks ( under general remarks)

28) 17/06/2021 An outlook on diabetes mellitus and the coronavirus (under general conditions and immunosuppressive drugs)

29) 29/07/2021 Alpha and Delta variants: the need to take precautions in other areas as soon as the emerge in one locality (under Testing)

30) 11/08/2021 Multisystem inflammatory syndrome in children MIS-C (under General defences…)

31) 30/08/2021 Indoor precautions for household where one or more members are positive ( under Aerial transmission)

32) 08/10/2021 The two immune systems- innate and adaptive (under general defences). The role of Vitamin D in immunity ( under Good nutritional status).Fever boosting the production of interferons( under Interferons)

33) 26/11/2021 Caution: Use of oximeters in people with dark skins ( under Local defences and underlying conditions-Respiratory tact). The latest variant-Nu variant(under Testing-Variants)

34) 03/07/2022 New subvariants of Omicron -BA.4 and BA.5 ( under Testing)

35) 13/07/2022 Modifying new vaccines to reduce the risk of immune escape by new variants ( under variants) Long covid conditions made worse by repeated coronavirus infections ( under The diagnosis of Covid-19)