Device studies SWEAT to spot signs of the deadly 'cytokine storm'

Watch-sized device analyses SWEAT to spot signs of the deadly ‘cytokine storm’ caused by Covid-19 and other infections

  • A cytokine storm can lead to an overload of immune cells that can cause death
  • Researchers say an early warning system can allow doctors to treat the issue
  • The new device monitors passive sweat levels for a rapid increase in cytokines
  • If they are detected doctors can deliver steroids before it can increase further 

A device the size of a watch can analyse sweat and spot signs of an impending, and deadly, cytokine storm that is caused by Covid-19 and other infections.

The phenomenon happens when chemicals in the bloodstream, called cytokines, multiply rapidly and run out of control. 

These small chemicals are designed to restrict and control the immune system and when they go awry it can lead to inflammation and organ damage. 

Early in the COVID-19 pandemic, doctors recognised that patients who developed a ‘cytokine storm’ were often the sickest and at highest risk of dying. 

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A device the size of a watch can analyse sweat and spot signs of an impending, and deadly, cytokine storm that is caused by Covid-19 and other infections

A cytokine storm happens when cytokines in the body rampage through the bloodstream, causing the creation of other immune cells, leading to organ damage

What is the ‘cytokine storm’ and can it be treated?  

SARS-CoV-2, the coronavirus which causes Covid-19, is recognised by the body’s immune system after the pathogen invades cells. 

This leads to an immune response being mounted, with the body trying to destroy the virus. 

One mechanism it uses is cytokines, small chemicals which are intended to regulate the production of other immune cells, keeping the process in check. 

But in Covid, and some other diseases, this mechanism goes awry, and too many cytokines are produced, 

As a result, the chemicals run out of control and this initiates a destructive chain reaction which sees it attack its own healthy and uninfected tissue and cause severe inflammation. 

In many Covid cases this is what proves fatal and finding a way to dampen this process has been a priority for doctors. 

Some drugs, such as dexamethasone, can suppress this out-of-control event and give the body chance to regain equilibrium. 

Anti-inflammatory drugs tocilizumab and sarilumab, recently approved for use in ICU patients on the NHS, also target cytokines, but more specifically than dexamethasone. 

They too are effective at reducing the risk of death.  

University of Texas at Dallas researchers made sensor strips with antibodies against seven pro-inflammatory proteins and tested them on six healthy people and five people with the flu, another virus that can trigger a cytokine storm.

Two of the sick people showed elevated cytokine levels while all participants had cytokines in their sweat that corresponded with expected values based on previous research. 

An early warning system would allow doctors to administer steroids quickly, reducing the risk the cytokine storm would run out of control,’ the researchers said.  

‘Especially now in the context of COVID-19, if you could monitor pro-inflammatory cytokines and see them trending upwards, you could treat patients early, even before they develop symptoms,’ study author Shalini Prasad said.

Early detection is important because once a cytokine storm has been unleashed, the excessive inflammation can damage organs, causing severe illness and death. 

In contrast, if doctors could administer steroidal or other therapies as soon as cytokine levels begin to rise, hospitalisations and deaths could be reduced.

Although blood tests can measure cytokines, they are difficult to perform at home, and they can’t continuously monitor the proteins’ levels. 

Cytokines are excreted in sweat at lower levels than in blood. 

To collect enough sweat for testing, scientists have asked patients to exercise, or they have applied a small electrical current to patients’ skin.

However, these procedures can themselves alter cytokine levels, according to Prasad. 

‘When it comes to cytokines, we found that you have to measure them in passive sweat,’ the lead investigator said.

‘But the big challenge is that we don’t sweat much, especially in air-conditioned environments,’ she says. 

The team estimates that most people produce only about 5 microliters, or one-tenth of a drop, of passive sweat in a 0.5-inch square of skin in 10 minutes.

So the researchers wanted to develop an extremely sensitive method to measure cytokine levels in tiny amounts of passive sweat. 

They drew on their previous work on a wearable sweat sensor to monitor markers of inflammatory bowel disease (IBD). 

The wristwatch-like device measures levels of two proteins that spike during IBD flare-ups and when worn on the arm, passive sweat diffuses into a sensor strip.

The sensor, which contains two electrodes, is coated with antibodies that bind to the two proteins, a process that changes the electrical current going to the reader. 

The reader then wirelessly transfers the data to a smartphone app that converts electrical measurements to protein concentrations. 

Early detection is important because once a cytokine storm has been unleashed, the excessive inflammation can damage organs, causing severe illness and death, says study author Shalini Prasad (pictured centre)

University of Texas at Dallas researchers made sensor strips with antibodies against seven pro-inflammatory proteins and tested them on six healthy people and five people with the flu, another virus that can trigger a cytokine storm

HOW DOES THE SWEATSENSER Dx WORK

The wristwatch-like device measures the levels of proteins that spike during.

When the device is worn on the arm, passive sweat diffuses onto a disposable sensor strip that is attached to an electronic reader. 

The sensor strip, which contains two electrodes, is coated with antibodies that bind to the proteins. 

Binding of the proteins to their antibodies changes the electrical current flowing through the e-reader.

The reader then wirelessly transfers these data to a smartphone app that converts electrical measurements to protein concentrations. 

After a few minutes, the old sweat diffuses out, and newly excreted sweat enters the strip for analysis.  

After a few minutes, the old sweat diffuses out, and newly excreted sweat enters the strip for analysis.

For their new cytokine sensor, known as SWEATSENSER Dx, the researchers made sensor strips with antibodies against seven pro-inflammatory proteins.

They inserted the strips into their device and, in a small observational study, they tested them on six healthy people and five people with influenza. 

Two of the sick people showed elevated cytokine levels, and in all participants, cytokines in passive sweat correlated with levels of the same proteins in serum.

The SWEATSENSER Dx was even sensitive enough to measure cytokines in patients taking anti-inflammatory drugs, who excrete far fewer cytokines.

The device tracked cytokine levels for up to 168 hours before the sensor strip needed to be replaced.

EnLiSense, in partnership with the researchers, is now planning clinical trials of the cytokine sensor in people with respiratory infections. 

‘Access to COVID-19 patients has been a challenge because healthcare workers are overwhelmed and don’t have time to test investigational devices,’ Prasad says. 

‘But we’re going to continue to test it for all respiratory infections because the disease trigger itself doesn’t matter – it’s what’s happening with the cytokines that we’re interested in monitoring.’

The findings are being presented at the ACS Spring 2021 meeting. 

People who have already caught the coronavirus ‘are not fully protected against reinfection’, study warns 

Young people that have previously been infected with coronavirus will not be fully protected against reinfection, according to a new study.

Researchers from Icahn School of Medicine at Mount Sinai analysed data on more than 3,000 healthy members of the US Marine Corps aged 18 to 20.

They found that about 10 per cent of those involved in the study that had been previously infected with Covid-19 had become reinfected.

Study authors warned that despite previous infection and the presence of antibodies, vaccination is still necessary to boost immune responses, prevent reinfection and reduce transmission.

They added that young people should take up the vaccine whenever possible.

 

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