“Until the end of this first week, they are stable,” said Darley, a doctor at Saint Vincent’s Hospital in Sydney. “And then suddenly, they have this hyper-inflammatory response. The proteins involved in this inflammation start to circulate in the body at high levels. “
In these patients, the lungs begin to struggle. The blood pressure decreases. Other organs, including the kidneys, may start to close. Blood clots form throughout the body. The brain and intestines can also be affected. Some suffer from personality changes, suggesting brain damage.
“I think what’s going on is a very specific set of stages of the disease and for some reason not everyone goes through all of the stages,” said Darley. “Some go through the most severe stage and require breathing support and oxygen. These patients who are serious tend to be older, they are more likely to be men and also have other medical conditions such as diabetes, high blood pressure or cardiovascular disease. “
But there is no way of knowing which patients will be affected by the most severe symptoms. Clinicians like Darley hope that a disease biomarker – a unique feature in blood, body fluids or tissue – will eventually be discovered at each stage.
“It would help clinicians predict the stage of the patient and perhaps even progress to the next stage of the disease,” he said. “It could help us predict who needs to be observed more closely in hospitals and it would mean that all systems are ready to go if they deteriorate. And it would give us more confidence to send them home if a biomarker says they are at low risk of developing a serious illness. “
Darley is one of the researchers working on a long-term study by St Vincent on patients admitted to hospital with Covid-19. Patients will be followed for a year after discharge, receiving tests at regular intervals to see if there are any lasting effects or changes in the body’s immune system and blood. They will also be evaluated for any continuous change in pulmonary, intestinal and cerebral functions. No one yet knows if the virus is causing permanent or long-term damage.
“I don’t think it’s clear yet if it’s the virus that infects the lungs and blood vessels, or if it’s the body’s immune system that gets out of control which then causes damage to the lungs and blood vessels” said Darley. “Or, it could be a combination of the two.
“The pathogenesis is not yet clear. We observe inflammation of the brain in a subgroup of patients, and in these patients we find restlessness and a change in behavior or personality. It’s really interesting, and there are reports from some people, including younger patients, with stroke. It is unclear whether the virus infects the cells of the lining of blood vessels in the brain, or whether the patient’s blood is excessively clotted due to all the inflammation, leading to a stroke. “
A renowned specialist in intensive care in Italy, Professor Luciano Gattinoni, said that this type of coagulation in respiratory diseases is “extremely unusual”.
The 75-year-old has worked in intensive care for 40 years and said he has never seen anything like it that happens to the lungs of some Covid-19 patients. What is particularly confusing is that the patients have poor oxygenation but little lung damage. This type of presentation is more typical of patients with altitude sickness than a viral infection, says Gattignoni. As a result, patients who are very sick may not feel like they are really having trouble breathing – even if they are severely starved for oxygen.
” How is it possible? Gattinoni told Guardian Australia of the intensive care department of the German hospital where he works as a visiting professor. “Poor oxygenation and good lungs tell me it must have something to do with the blood vessels. But these ships are everywhere. In the brain. In the kidneys. Thus, in some patients, many organs are affected. “
The problem is that mechanical ventilation in intensive care replaces the strength of the respiratory muscles. If patients have trouble breathing but their lung structure is correct, this ventilation does not help much and can actually be harmful, said Gattinoni, since mechanical ventilation is invasive.
He said that while only a small number of patients were severe enough to require ventilation, a significant proportion of those on respirators died, continuing to show low levels of oxygen in the blood despite mechanical assistance.
Gattinoni said doctors should only use ventilators when necessary and at the right time. Doing it right can improve survival rates, he believes, and thinks that poorly synchronized ventilation is the reason why some intensive care units that treat Covid-19 patients have higher death rates than others.
“It is absolutely essential to choose the timing of this disease,” he said. “Ventilation cannot start too early or too late. In the meantime, patients are receiving blood thinners, drugs that prevent or slow blood clotting in the hopes of preventing a stroke.
Darley said the analyzes of the lungs in Covid-19 patients are unique, showing “frosted glass opacity”, a fuzzy pattern that does not obscure the underlying lung structure. Lung cancer, for example, usually appears on a CT scan as a dark, solid lesion, masking other structures in the lungs. While other diseases, such as bacterial infections, can cause the opaque glass to appear cloudy on a scan, there were unusual features on the scans for Covid-19, said Darley.
“He has a classic Covid style,” he said.
He suspects that men are more severely affected than women because the virus is activated by an enzyme controlled by androgens, a group of hormones that play a role in male characteristics. But more research is needed to test this hypothesis. Darley added that any research on the virus must be conducted ethically and with sound scientific protocols.
“In the absence of treatment for this virus, all we can do for severe patients right now is to provide supportive care,” he said. “If the fluid level is low, we can replace it. If they need ventilation, we can help them breathe. But the treatments for this disease can only come from clinical trials.
“Our commitment in our hospital is to work with the highest level of scientific research. People are in desperate need of treatment, but we are hesitant to try treatment outside of clinical trials here.
“If we don’t make it clear that a treatment is better than a placebo or other treatments, we could create noise and add to the current chaos of the scientific community. Our responsibility is to find treatments that work. “
Gattinoni agrees. He said that scientists have been trying for decades to find drugs that moderate the inflammatory response, and he said that these drugs were “fictionalized and popularized” in the race for treatments for Covid-19.
“But in thousands of experiences over the years trying to block inflammatory responses, we have had only a lot of bad results,” said Gattinoni. “Like many other things in medicine, we have to be patient. “