We think of Covid-19 as a respiratory virus – one that simply attacks the lungs.
But scientists are now wondering if it is much more than that, with a stream of medical papers being published over the last few weeks which suggests the contagion can get deep into our vascular system and even our brains.
“We are seeing a range of illness; some people develop blood clots, others heart attacks or kidney failure,” said Prof Ajay Shah, BHF Professor and consultant cardiologist at King’s College Hospital, London.
“There are still many unknowns, but the amount of research effort that is going on to try and understand exactly what is happening to patients with Covid is absolutely phenomenal.”
So how does the virus attack?
Nose and throat
It is here that the infection begins, colonising the upper nasal tract, often blocking out our sense of smell, before moving down into the throat.
The cells here are rich in an enzyme known as ACE2. They enable the “spike proteins” on the surface of the virus to latch on and replicate at pace.
At this point patients are highly infectious, but may not yet be suffering any symptoms. It’s one of the virus’s most devious and unusual tricks – to get its human hosts to spread it to others without letting them know they are ill.
If the body’s immune system doesn’t kill it off at this early stage, the virus travels down the windpipe and into the lungs.
It is inside the lungs that the virus turns nasty. It invades the millions of tiny air sacs in the lungs, causing them to become inflamed.
“It’s what we would call pneumonitis – inflammation of the lung tissue – and stops the oxygen being taken up properly, it makes the lungs wet and heavy,” said Dr Duncan Young, professor of intensive care medicine at the Nuffield Department of Clinical Neurosciences.
For some patients, this can lead to acute respiratory distress syndrome (ARDS) – a potentially fatal condition where blood oxygen levels drop to a dangerously low level.
“You can stop them dying from a lack of oxygen on a ventilator,” said Dr Young. “But that doesn’t stop the course of the infection, it carries on. You’re keeping them alive hoping that their own immune system fights the virus.”
Unfortunately, for many people, the immune system overreacts to the infection – triggering a a “cytokine storm” whereby the body essentially attacks itself.
“This body-wide inflammatory process causes you to get a high heart rate. It makes blood vessels leak fluid, a bit like a blister. It’s what makes the 20 per cent of people who get kidney failure get kidney failure, and it probably is what causes people to get heart problems,” said Dr Young.
“So when patients die in ICU, they primarily die of this cytokine storm. They die of multiple organ failure as everything gives up.”
Heart and blood vessels
The lungs may be ground zero for Covid-19 but scientists think it may also invade the circulatory system, getting deep into our veins.
Precisely how the virus attacks the heart and blood vessels remains a mystery, but experts believe infection may cause blood clots, heart attacks and cardiac inflammation as the virus binds to ACE2 receptors on cells lining our blood vessels.
“Patients ill in hospital with Covid are showing signs of significant heart and vascular problems,” said Prof Shah. “We’re seeing a significant proportion of patients developing clots in the arteries feeding into the heart.”
One study in JAMA Cardiology journal, found that 20 per cent of 416 patients hospitalised in Wuhan with the coronavirus had heart damage.
“Increased likelihood of clot formation seems to be one of the features of severe Covid disease,” Prof Shah added. “We’re also seeing patients get clots elsewhere, including the legs and lungs.”
This may explain why patients with diabetes and heart disease are at risk of severe illness with Covid-19 as their vascular systems are already under additional strain.
Elevated enzyme levels in the liver have been observed in a significant number of Covid-19 hospitalisations, indicating organ impairment. It’s not clear if this damage is caused by the immune system in overdrive, drugs given to fight the virus or even the virus itself.
In severe cases, Covid-19 can cause kidney damage – one preprint study of 85 hospitalised patients in Wuhan found 27 per cent had kidney failure.
It is unclear whether this happens because the virus attacks the kidneys directly – there is an abundance of ACE2 receptors within the organ – or it’s the body’s response to something else, such as plummeting blood pressure.
Either way it could massively increase demand for dialysis machines.
Doctors are so far unclear on how the virus affects the brain, but studies have detailed Covid-19 patients who have suffered strokes, seizures, confusion and brain inflammation.
“From observation on patients, a lot of patients do come in confused or become confused after they come in, which is basically a sign that something’s not quite right in the brain,” said Dr Young.
“Whether the virus is directly affecting the brain, or if it’s a sign that oxygen levels are just too low, we can’t be sure yet.”
But one case study from Japan reported traces of the virus in the cerebrospinal fluid of a Covid-19 patient who developed meningitis and encephalitis. This suggests that Sars-Cov-2 may be able to penetrate the central nervous system.
“Even if most of the disease starts in the lungs, which it almost certainly does, there are clearly consequences for many other parts of the body,” said Prof Shah.