We are six months on and it appears that best practise is steadily imnproving without any serious glitches.
You can see that it is still a challenge to work with and that it really demands early testing. Not least because it is novel and does look like any number of colds and the like. THe real tip off is a low grade fever. Then you run to get tested.
You may still have it with no fever, and you immune system is handling it. Not getting sick is good, but then you are a real unwitting carrier.
hopefullly safe testing is soon available..
How the coronavirus kills people – and how to stop it
HEALTH 24 June 2020
By Clare Wilson
Coronavirus particles (yellow) on the surface of a dying cell
DEXAMETHASONE has become the first drug shown to lower the death rate from covid-19. The discovery of the benefits of this widely available steroid, which damps down an overactive immune system, was seen as a much-needed piece of good news. But we will need lots of other treatments to help us turn the tide of severe covid-19.
Many of the coronavirus drug trials so far have looked at antiviral medicines that may stop the virus from replicating. While some of these appear to shorten the length of time that an infected person is ill, none has yet been shown to reduce mortality. To save the lives of those who are seriously ill, we need treatments that tackle the effects of severe covid-19, which occur after the virus has already replicated within the body.
Evidence suggests that the virus kills through a two-pronged attack that perturbs both our immune defences and our blood-clotting system. Covid-19 was initially seen as a respiratory illness, but some of those who die from it experience not only lung failure but also heart attacks, strokes, kidney damage and other conditions caused by blood clots.
The good news is that several existing and novel treatments to fight both of those impacts are being investigated and some are already in use. “We think we know the mechanisms for how it [kills],” says Chris Meadows, an intensive care doctor at Guy’s and St Thomas’ hospitals trust in London. “Treatment is now directed against those mechanisms, largely towards reducing inflammation and clots. I think we are pretty close to working it all out.”
The coronavirus enters our body through cells lining the nose or mouth by latching on to a molecule on their surface called the ACE2 receptor. In some people, the virus spreads down into the lungs, where cells also bear the ACE2 receptor. Here it causes inflammation and leakage of fluid into the lung’s air sacs, interfering with breathing. This can lead a person’s oxygen levels to fall and mean they require treatment with supplementary oxygen or a ventilator. But even with intensive support, death rates for covid-19 patients receiving ventilation have been relatively high.
From early in the outbreak, doctors suspected that part of the problem was in how the immune system reacts to the virus. Normally, our immune cells fight off viruses or bacteria, but in some cases they overreact, pumping out too many cytokines – chemicals that recruit yet more immune cells in a vicious circle known as a cytokine storm. “There is fluid and inflammatory cells flooding into where air should be,” says Meadows. “This is like having a raging fire within the lungs.” The phenomenon has been seen before, including in the SARS coronavirus outbreak of 2003 and in a type of bird flu.
Drugs with the potential to block the cytokine storm are being investigated, but dexamethasone is the first demonstrated success. Steroids have been used for years to calm the immune system in other kinds of lung inflammation, but it wasn’t certain that they would help in covid-19.
The first randomised trial of dexamethasone has found that it lowers the death rate in ventilated covid-19 patients from 40 to 28 per cent. “The survival benefit is clear and large, so dexamethasone should now become standard of care,” said one of the researchers, Peter Horby at the University of Oxford, in a statement.
The finding is good news, but isn’t enough on its own. Other groups are looking for ways to tackle the way covid-19 leads to unwanted blood clotting – and there is hope that existing blood-thinning medicines could help.
Clotting in the body is normally tightly controlled to ensure that blood flows freely through our blood vessels, yet the slightest injury triggers a cascade of chemical reactions that turns this fluid into a plug. Cytokine storms were already known to predispose people to clots somewhat, but with covid-19, this was taken to a new level. Doctors saw clots in people’s lungs on scans and could even see clots forming as they tried to put tubes into people’s veins. “People were saying something odd is going on,” says Danny Jonigk at Hannover Medical School in Germany.
As well as these visible clots, autopsies have found small blood vessels in the lungs suffused with smaller clots. These were 10 times as common in seven people who died from covid-19 as in seven who died from bird flu, according to a study published last month (NEJM, doi.org/ggwtrb). “This is a disease that targets blood vessels,” says Jonigk, who worked on the study.
The key insight is realising that the virus can enter the cells of blood vessel walls, which also bear the ACE2 receptor, argued Peter Carmeliet at KU Leuven in Belgium in a review article last month (Nature Reviews Immunology, doi.org/dz55). Part of the problem is that ACE2 receptors on blood vessel cells normally regulate hormones that affect clotting, and this is prevented by the virus binding to them. The virus also kills blood vessel cells. “That’s a very strong stimulus to the formation of blood clots,” says Carmeliet.
Dexamethasone and heparin are being tested for treating covid-19
Most people in intensive care are already given low doses of the blood-thinning drug heparin, as being immobile and having a lot of medical procedures raises the risk of clots forming. Now, many hospitals are increasing the amount of heparin given to their covid-19 patients, as well as monitoring the “stickiness” of their blood so the dose can be finely adjusted.
This is now standard practice at University Hospitals Leuven in Belgium, says intensive care doctor Geert Meyfroidt. He believes this is behind the relatively low death rate for the hospital’s covid-19 patients of less than 25 per cent.
Other strategies are being investigated worldwide against both blood clotting and cytokine storms, in the hope that the death rate can be lowered further still. Beyond these, alternative approaches include using antibodies from recovered covid-19 patients and antiviral drugs like remdesivir, which has been found to shorten the time people spend in hospital or require extra oxygen.
One problem in some European countries, such as Belgium, is that they now have so few new cases of coronavirus, it is hard to carry out trials for potential treatments, says Meyfroidt. “But when it comes back, we need to be ready.”
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