Covid-19 Treatment

Treatment

Covid-19 is an entirely new virus and the medical and scientific communities are still studying the virus, how it spreads, what it does to the body, and how best to treat it.

Mild and moderate cases

• Symptoms include a new dry cough, fever, and loss of taste and smell. Some people also report stomach upsets and diarrhoea, 'brain fog', and exhaustion, If you have these symptoms you are advised to self-isolate at home. 
• If you develop difficulty breathing, people in the UK should phone 111 for advice; they may need hospital care. 
• Favipiravir is being trialled as a first anti-viral treatment for against mild Covid-19. Anti-viral drugs stop viruses replicating. Already in use as a flu drug, this trial will see if it stops Covid-19 symptoms progressing. If effective, it could be taken following a positive test or known exposure to a carrier. Trials in Glasgow and London hope to have early results around Sept. 2021.

Severe cases
One factor in serious and critical cases is the immune system going haywire, causing widespread inflammation inside the body and ultimately leading to fatal organ damage. This reaction can be measured using a standard blood test for a compound called C-reactive protein (CRP). Patients can be checked as soon as they come into hospital, and those with worrying CRP levels flagged as needing extra attention.

Covid-19 also leads to a higher risk of blood clots in the lungs (this happens with flu as well but it is worse with Covid-19). Now this is known, blood-thinning treatment can be given early on.

It is possible that different drugs work best at different times during illness with Covid-19.

• People with difficulty breathing are treated in hospital, initially in the Intensive Care Unit. Here specific treatment will be given to help breathing by using nasal tubes or continuous air pressure (CPAP) face masks. In addition, any pre-existing medical conditions will also be treated.
• Moving patients to the prone (face down) position relieves pressure on the lungs and can be helpful. It requires eight staff to turn patients in this way.
• If symptoms worsen, patients are moved to Critical Care.
• Olumiant (baricitinib) is an arthritis drug. It reduces the ability of the virus to infect lung cells. Cuts deaths in hospital by 71% in those with moderate or severe Covid-19, including the elderly. 
• Actemra (tocilzumab), an anti-inflammatory used for rheumatoid arthritis. Stops the potentially fatal cytokine storm - an over-reaction of the immune system causing inflammation. Helps critically-ill patient recovery, with 87% likely to see symptoms improve within 28 days. Reduced intensive care deaths from 36% to 27%.
• Interferon beta is part of the body's first line of defence against viruses, warning it to expect a virus attack. Covid-19 seems to suppress its production as part of its strategy to evade our immune systems. Interferon beta is already used as a drug used to treat active, relapsing multiple sclerosis (MS). The new drug is a special formulation delivered directly to the airways via a nebuliser which makes the protein into an aerosol. Early findings show it cuts the risk of Covid-19 hospital patients developing severe disease (e.g. requiring ventilation) by almost 80%. A large scale trial with Covid-19 patients in hospital was begun in January 2021, with results expected summer 2021. 

Critical cases For the critically ill, the disease causes such severe inflammation and blood clotting that it attacks multiple organs and causes life-threatening problems that cascade around the body.

• Patients are put on ventilator machines which will breath for them. A tube is inserted into the air passage (trachea) through a small slit in the throat made under sedation. Patients remain under sedation while on the machine.
• Doctors are now finding that patients may have small blood clots in the lungs; these are life threatening. 'Blood thinner' drugs are being tried but results are variable and under investigation through clinical trials at present. (Precise figures are not known but it may be that 30% (or even more) have this.)
• Dexamethasone is a steroid, that reduces inflammation by mimicking anti-inflammatory hormones produced by the body. Used if the immune system goes into overdrive. Only suitable for hospital patients receiving oxygen or mechanical ventilation, as suppressing the immune system of those with milder symptoms would not be helpful. Trials indicate one in three deaths could be  prevented if ventilated, and one in five deaths of those on oxygen. [First made in 1957, it is now out of patent and so is low-cost, therefore widely available worldwide. BBC News https://www.bbc.co.uk/news/health-53077879 ]
  
• Monoclonal antibody treatment. Made by Regeneron, it contains large doses of two specific antibodies, made in the lab, that are good and binding to the virus to stop it infecting cells and replicating. The Recovery trial found that given in addition to the anti-inflammatory steroid drug dexamethasone, which itself cuts death risk for the sickest Covid patients, it further reduces the risk of death, the length of hospital stay (by four days on average), and the likelihood of needing a ventilator to breathe. It is expected that only those who have not already made any antibodies of their own to fight the virus should be given the treatment, which costs between £1,000 and £2,000. https://www.bbc.co.uk/news/health-57488150
• Hydrocortisone is a corticosteroid used for treating a range of conditions. It decreases your immune system's response to various diseases to reduce symptoms such as pain, swelling and allergic-type reactions. It has been found to cut Covid-19 deaths by up to 31% and improve outcomes by up to 93% in critically ill patients. The best dosage is still under investigation.
• Tocilizumab and Sarilumab are both anti-inflammatories, administered by drip. Jan 2021: UK approved for Covid-19 treatment if despite Dexomethasone treatment the patient is still deteriorating and needs intensive care. They reduce deaths by 1 in 12 (8%) but also speed up recovery and reduce time spent in hospital. Tocilizumab and Sarilumab are more expensive than Dexamethasone at £75 to £1K per patient, but an intensive care bed costs around £2K per day.

Recovery

• Once over the crisis, hospitalized patients may need several weeks to recover enough to leave hospital.
• This may include physiotherapy as the lungs heal, and for having lain still for so long, and speech therapy if they have been on a ventilator.

Other treatments being studied

Because Covid-19 is a new disease, medical doctors and scientists are observing a variety of symptoms and damage, and are still researching potential ways to most effectively treat it. The following are currently being studied and used in clinical trials. It will take some time for the results to be fully evaluated. News item links are given when available.

Treatments discontinued as ineffective 

• Remdesivir is a broad-spectrum antiviral medication originally developed to treat Ebola. Clinical trials were initially promising, so it was approved by regulators for selected patients. However, further data shows that it appears to have little or no effect on death rates, length of hospital stay or severity of illness.  
• Blood plasma donations from patients who have recovered from Covid-19. Trials show this does not reduce deaths or improve outcomes for those in intensive care.  

T- cell function

• Those with the most severe form of the disease have extremely low numbers of an immune cell called a T-cell, which clear infection from the body. A clinical trial will evaluate if using a interleukin 7 (a drug known to increase T-cell numbers) can aid recovery. [Read in full.]

Oxygen levels and mechanical ventilation

• Some patients have very low levels of oxygen (O2) in their blood but are functioning relatively well. The usual aim is to keep the O2 level at 90% or above. It is thought that the inflammation may be stopping the O2 getting into the blood but the lungs themselves may not be so affected. Many doctors now question whether mechanical ventilation is always the right course of treatment or is the wrong treatment at the wrong time. [Read in full.]

Blood clots

Various studies are looking at the use of 'blood thinner' medications already used to prevent blood clots.

• When the lining of the blood vessels gets inflamed, the blood is more likely to clot. Covid-19 creates very thick, sticky blood in seriously ill patients, causing small clots in the small arteries of the lungs, but also big clots in the bid arteries of the lungs. More than a quarter of these patients have significant clots. You are also more likely to have a deep vein thrombosis (a blood clot in your leg) or a pulmonary embolism, where a deep vein thrombosis travels and blocks the blood supply to the lungs. [Read in full.]
• Blood clots also prevent proper circulation of the blood to other organs such as the heart and the brain, making it more likely Covid-19 patients could have a heart attack or a stroke. One warning sign is the level of fibrinogen (the main protein that forms blood clots) in your blood. Normally between 2 and 4 grams per liter of blood, Covid-19 patients may have levels as high as 10 to 14 grams per litre. [Read in full.]
• Another clotting risk measure is the level of a blood protein called a D-dimer. Healthy levels are in the tens or hundreds, but  Covid-19 patients often have levels of 60 or 70, or even 80,000. As well as indicating the presence of multiple blood clots, D-dimers can also indicate a severe infection that triggers a lethal over-reaction from the body's immune system. [Read in full.]
• More than 2,000 Covid patients admitted to intensive care have suffered kidney failure. Using dialysis machine support has problems as the blood flowing through the machines clots far more readily than usual, so increased amounts of blood thinning medication are needed.

Inflammation

• Ibuprofen is well known as an anti-inflammatory drug, but is also an anti-inflammatory. Animal studies suggest it might treat acute respiratory distress syndrome (one of the complications of Covid-19) and the hope is that the low-cost treatment can keep patients off ventilators. The trial will use a special formulation of the drug. [Read in full.]
• Cytokines are small molecules produced by the body as a chemical warning system to the immune system. They lead to inflammation that allows you to fight an infection, but in some Covid-19 patients, if the infection overwhelms the response, there is a massive release of cytokines, causing even more inflammation, leading to breathing problems and damage to other organs - the kidneys, the heart, the liver and seen severely inflamed muscle which is doing a lot of damage. [Read in full.]
• A growing number of patients are having significant inflammation of the brain, causing everything from delirium and confusion, to fits and diffuse encephalitis (people not waking up properly when taken off a ventilator.) [Read in full.]

Vitamin K deficiency

A study in the Netherlands has found that patients admitted to intensive care with Covid-19 have been found to be deficient in vitamin K, which is found in spinach, eggs, and hard and blue cheeses and absorbed in the gastrointestinal tract. Vitamin K is key to the production of proteins that regulate blood clotting and can protect against lung disease. 

The virus causes blood clotting and leads to the degradation of elastic fibres in the lungs. Dutch researchers are seeking funding for a clinical trial of high dose vitamin K on very sick patients, unless they are already on blood-clotting ('blood thinning') medications.

Vitamin K1 is found in spinach, broccoli, green vegetables, blueberries - in fact, all types of fruit and vegetables. Vitamin K2 is better absorbed by the body and is found in cheeses, especially hard and blue cheeses, and additionally in a Japanese delicacy of fermented soya beans, known as natto. [Read in full.]

Questions still to be answered are: 

• Existing medications are being investigated for potential benefit of Covid-19 patients. It is thought that anti-virals may be more effective in the early stages of the infection, and the immune drugs later in the disease, but this still needs to be confirmed.
• When is the right time to mechanically ventilate Covid-19 patients?
• What are the best anti-viral drugs to use?
• What are the right doses of anti-inflammatory or immune-suppressing drugs to use?
• Can using convalescent plasma (antibodies from patients who have recovered) be part of the solution?
• Do low vitamin D levels pose a greater risk to being infected or recovering from Covid-19?

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