How stress can make you sick explained

COVID-19 mostly kills through an overreaction of the immune system, whose function is precisely to fight infections, say scientists who have decoded the mechanisms, symptoms, and diagnosis of the disease caused by the SARS-Cov-2 coronavirus.

In a study published in the journal Frontiers in Public Health, the researchers explained step-by-step how the virus infects the airways, multiplies inside cells, and in severe cases causes the immune defences to overshoot with a "cytokine storm".

This storm is an over-activation of white blood cells, which release too-great amounts of cytokines -- inflammation-stimulating molecules --into the blood, they said.

"Similar to what happens after infection with SARS and MERS, data show that patients with severe COVID-19 may have a cytokine storm syndrome," said study author Daishun Liu, Professor at Zunyi Medical University in China.

"The rapidly increased cytokines attract an excess of immune cells such as lymphocytes and neutrophils, resulting in an infiltration of these cells into lung tissue and thus cause lung injury," Liu said.

The researchers explained that the cytokine storm ultimately causes high fever, excessive leakiness of blood vessels, and blood clotting inside the body.

It also causes extremely low blood pressure, lack of oxygen and excess acidity of the blood, and build-up of fluids in the lungs, they said.

The researchers noted that white blood cells are misdirected to attack and inflame even healthy tissue, leading to failure of the lungs, heart, liver, intestines, kidneys, and genitals.

This multiple organ dysfunction syndrome (MODS) may worsen and shutdown the lungs, a condition called acute respiratory distress syndrome, (ARDS), they said.

This, the researchers explained, happens due to the formation of a so-called hyaline membrane -- composed of debris of proteins and dead cells -- lining the lungs, which makes absorption of oxygen difficult.

Most deaths due to COVID-19 are therefore due to respiratory failure, they said.

The researchers explained that in the absence of a specific antiviral cure for COVID-19, the goal of treatment must be to the fight the symptoms, and lowering the mortality rate through intensive maintenance of organ function.

For example, an artificial liver blood purification system or renal replacement therapy can be used to filter the blood through mechanical means, they said.

The team noted that especially important are methods to supplement or replace lung function, for example with non-invasive mechanical ventilation through a mask, ventilation through a tube into the windpipe, the administration of heated and humidified oxygen via a tube in the nose, or a heart-lung bypass.

The researchers stressed the importance of preventing secondary infections.

They noted that SARS-Cov-2 also invades the intestines, where it causes inflammation and leakiness of the gut lining, allowing the opportunistic entry of other disease-causing microorganisms.

The researchers advocate that this should be prevented with nutritional support, for example with probiotics -- beneficial bacteria that protect against the establishment of harmful ones -- and nutrients and amino acids to improve the immune defences and function of the intestine.

"Because treatment for now relies on aggressive treatment of symptoms, preventative protection against secondary infections, such as bacteria and fungi, is particularly important to support organ function, especially in the heart, kidneys, and liver, to try and avoid further deterioration of their condition," Liu added.

Clinician-scientists have found that Irish patients admitted to hospital with severe coronavirus (COVID-19) infection are experiencing abnormal blood clotting that contributes to death in some patients.

The research team from the Royal College of Surgeons in Ireland found that abnormal blood clotting occurs in Irish patients with severe COVID-19 infection, causing micro-clots within the lungs.

According to the study, they also found that Irish patients with higher levels of blood clotting activity had a significantly worse prognosis and were more likely to require ICU admission.

"Our novel findings demonstrate that COVID-19 is associated with a unique type of blood clotting disorder that is primarily focussed within the lungs and which undoubtedly contributes to the high levels of mortality being seen in patients with COVID-19," said Professor James O'Donnell from St James's Hospital in Ireland.

In addition to pneumonia affecting the small air sacs within the lungs, the research team has also hundreds of small blood clots throughout the lungs.

This scenario is not seen with other types of lung infection and explains why blood oxygen levels fall dramatically in severe COVID-19 infection, the study, published in the British Journal of Haematology said.

"Understanding how these micro-clots are being formed within the lung is critical so that we can develop more effective treatments for our patients, particularly those in high-risk groups," O'Donnell said.

"Further studies will be required to investigate whether different blood-thinning treatments may have a role in selected high-risk patients in order to reduce the risk of clot formation," Professor O'Donnell added.

According to the study, emerging evidence also shows that the abnormal blood-clotting problem in COVID-19 results in a significantly increased risk of heart attacks and strokes.

As of Friday morning, the cases increased to 20,612 cases in Ireland, with 1,232 deaths so far, according to the Johns Hopkins University.

Early treatment with the antiviral drug remdesivir has been found to reduce viral load and prevent lung disease in macaques infected with SARS-CoV-2 that causes COVID-19, according to a study.

The findings, published in the journal Nature on Tuesday, support the early use of remdesivir treatment in patients with COVID-19 to prevent progression to pneumonia.

Researchers from the National Institutes of Health in the US noted that remdesivir has broad antiviral activity and has been shown to be effective against infections with SARS-CoV and MERS-CoV in animal models.

The drug is being tested in human clinical trials for the treatment of COVID-19, they said.

Researcher Emmie de Wit and colleagues investigated the effects of remdesivir treatment in rhesus macaques, a recently established model of SARS-CoV-2 infection.

Two sets of six macaques were inoculated with SARS-CoV-2.

One group was treated with remdesivir 12 hours later -- close to the peak of virus reproduction in the lungs -- and these macaques received treatment every 24 hours until six days after inoculation.

In contrast to the control group, the researchers found that macaques that received remdesivir did not show signs of respiratory disease, and had reduced damage to the lungs.

Viral loads in the lower respiratory tract were also reduced in the treated animals; viral levels were around 100 times lower in the lower-respiratory tract of remdesivir-treated macaques 12 hours after the first dose, they said.

The researchers said that infectious virus could no longer be detected in the treatment group three days after initial infection, but was still detectable in four out of six control animals.

Despite this virus reduction in the lower respiratory tract, no reduction in virus shedding was observed, which indicates that clinical improvement may not equate to a lack of infectiousness, they said.

Dosing of remdesivir in the rhesus macaques is equivalent to that used in humans, the researchers noted.

They cautioned that it is difficult to directly translate the timing of treatment used in corresponding disease stages in humans, because rhesus macaques normally develop only mild disease.

However, researchers said the results indicate that remdesivir treatment of COVID-19 should be initiated as early as possible to achieve the maximum treatment effect.