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Infectious Diseases

Updated 07 August 2020

Immune system markers could predict severity of Covid-19

Elevated cytokines and chemokines are a major severity indicator, leading to worse – and sometimes terminal – outcomes for severely infected patients.

  • Researchers found immune system markers that could predict the progress of Covid-19 
  • Those with severe disease showed signs of a downward trajectory with misfiring immune systems
  • Targeted treatment that blocks these markers could help prevent terminal outcomes

Researchers have found certain immune system markers that could predict the severity of Covid-19.

Publishing their findings in Nature, they analysed 113 Covid-19 patients with moderate and severe illness to find out how their immune systems responded to the disease.

These systems were analysed at different intervals to map the progress of the disease and what changes it caused in the patients' immune systems through the various phases.

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Importance of cytokines

One major indicator was elevated cytokines and chemokines, which led to worse outcomes for the severely infected patients, including death.

Cytokines are proteins that are secreted by cells to help coordinate immune response, while chemokines are smaller versions of these proteins.  

Those with moderate Covid-19 who didn't need to be admitted to the ICU had lower levels of proinflammatory cytokines and an immune system with an enhanced growth factor to repair tissue and heal wounds.

Study method

The patients were split into moderate and severe, based on their oxygen levels and ICU-need.  Healthcare workers were included in the study as a healthy control group.

Despite differences in immune systems, they didn't find that age or sex made a difference to which cases were severe and which ones were moderate, but they did find that body mass index (BMI) was higher in severe patients, and a very high BMI was associated with a higher risk of mortality. 

Those in ICU were also 27.27% more likely to die than those with moderate illness, but there was no difference when it came to the type of symptoms experienced. 

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'Core Covid-19 signature'

The study analysed three types of immune responses – against viruses, against parasites and against fungi and bacteria – and how a person's type of immune system reacted to disease and influenced its trajectory. 

The patients' T-cell numbers were considerably decreased and presented frequency in both CD4+ and CD8+ T-cells (white blood cells that fight infection and kill invaders). 

"We observed a 'core Covid-19 signature' shared by both moderate and severe groups of patients defined by ... inflammatory cytokines that positively correlated with each other," wrote the researchers. 

They observed an additional cluster of cytokines in patients with severe Covid-19. 

"These data highlight the broad inflammatory changes, involving concomitant release of type-1, type-2 and type-3 cytokines in severe Covid-19 patients."

But the difference comes in when these inflammatory biomarkers steadily decrease in moderate patients 10 days after infection, while levels remained constant in patients with severe Covid-19 symptoms.

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Viral load differences

They also found that the viral load slowly decreased over time in moderate patients compared to severe patients, suggesting that viral load may drive these cytokines, and that interferons in charge of regulating the immune system do not successfully control the virus.

Moreover, patients who ultimately died of Covid-19 exhibited significantly elevated levels of certain interferons as well as chemokines associated with white blood cells and T-cells' recruitment and survival.

"These findings were consistent with generalised estimating equations that identified relationships between the risk of death and cytokines or immune cells populations over time," the writers added.

"Together, these results identify groups of inflammatory, as well as potentially protective, markers that correlated with Covid-19 trajectory."

These findings could help healthcare professionals make more targeted treatment decisions when analysing immune system responses in the early infection stages.

Doctors could also pursue combination therapy to block the specific cytokines found in the study that contribute to severe disease and that will also enhance tissue regrowth.

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Image credit: Getty Images