Paradoxically, Covid-19 mostly kills its victims through an overreaction of the immune system, whose function is precisely to fight off infections in our body.
In a new review article – explicitly targeted to non-specialists as well – in the journal Frontiers in Public Health, a team of experts from Zunyi Medical University in China review the epidemiology, disease pathway, symptoms, diagnosis and current treatment of severe Covid-19.
They stress the key role of a potentially lethal overreaction of the immune system in the progression of the disease.
In their article, they explain step-by-step what is known about how the virus infects the airways, multiplies inside cells, and in severe cases, causes the immune defenses to overshoot with a “cytokine storm”.
This storm is an over-activation of white blood cells, which release excessive amounts of cytokines – inflammation-stimulating molecules – into the blood.
“Similar to what happens after infection with SARS (severe acute respiratory syndrome) and MERS (Middle Eastern respiratory syndrome), data shows that patients with severe Covid-19 may have a cytokine storm syndrome.
“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, thus causing lung injury,” explains author Professor Dr Liu Daishun.
The cytokine storm ultimately causes high fever, excessive leakiness of blood vessels, blood clotting inside the body, extremely low blood pressure, lack of oxygen and excess acidity of the blood, and build-up of fluids in the lungs (pleural effusion).
White blood cells are misdirected to attack and inflame even healthy tissue, leading to failure of the lungs, heart, liver, intestines, kidneys and genitals, i.e. multiple organ dysfunction syndrome.
This may worsen and shut down the lungs, i.e. acute respiratory distress syndrome, due to the formation of a so-called hyaline membrane – composed of proteins and dead cell debris – that lines the lungs, making absorption of oxygen difficult.
Most deaths due to Covid-19 are therefore due to respiratory failure.
The researchers explain how, in the absence of a cure for Covid-19, the goal of treatment must be to fight the symptoms and lower the death rate through intensive maintenance of organ function, e.g. an artificial liver blood purification system or renal replacement therapy.
Especially important are methods to supplement or replace lung function, e.g. through non-invasive mechanical ventilation through a mask, ventilation through a tube into the windpipe (if possible, with positive end expiratory pressure, where the ventilator delivers extra pressure at the end of each breath to keep lung vesicles open throughout), the administration of heated and humidified oxygen via a tube in the nose (transnasal high-flow oxygen), or a heart-lung bypass.
The authors conclude by stressing the importance of preventing secondary infections: SARS-CoV-2, the virus that causes Covid-19, also invades the intestines, where it causes inflammation and leakiness of the gut lining, allowing the opportunistic entry of other disease-causing microorganisms.
They advocate that this should be prevented with nutritional support, e.g. with probiotics, 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,” says Prof Liu.