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New Sweat Sensor can Help Detect Cytokine Levels in COVID-19 Patients

During the initial days of the COVID-19 pandemic, doctors had found that patients who experienced a surge of pro-inflammatory immune proteins, called 'cytokine storm,' were usually the sickest and faced the highest risk of death.

A wristwatch-like device measures cytokine levels in passive sweat. Image Credit: Kai-Chun Lin.

However, a cytokine storm can also take place in other illnesses, like influenza. At present, researchers have reported initial results on a sweat sensor that serves as an early warning system for an imminent cytokine storm, which could allow doctors to treat patients more effectively.

The team will present their findings at the spring meeting of the American Chemical Society (ACS). The ACS Spring 2021 is being conducted online from April 5th to 30th, 2021.

Live sessions will be conducted from April 5th to 16th, 2021, and networking and on-demand content will continue through April 30th, 2021. The meeting includes almost 9,000 presentations on a variety of science topics.

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.

Shalini Prasad, PhD, Project Principal Investigator, The University of Texas at Dallas

Prasad is presenting the study at the meeting.

It is crucial to detect the cytokine storm in the early stage itself because once this condition is unleashed, the extreme inflammation can impair organs, leading to severe illness and death.

On the other hand, if doctors could provide steroidal or other treatments the moment cytokine concentrations begin to increase, hospitalizations and deaths could be brought down. While blood tests can determine cytokine levels, they are not easy to perform at home settings and they cannot constantly track the protein concentrations.

Cytokines are released in sweat at lower concentrations than in blood. To obtain sufficient sweat for testing, investigators have asked patients to do some physical activity; alternatively, they have applied a slight electrical current to the skin of the patients. But such procedures can themselves change the cytokine levels, observed Prasad.

When it comes to cytokines, we found that you have to measure them in passive sweat. But the big challenge is that we don’t sweat much, especially in air-conditioned environments.

Shalini Prasad, PhD, Project Principal Investigator, The University of Texas at Dallas

Prasad, who is currently at the University of Texas at Dallas, believes that the majority of individuals produce just around one-tenth of a drop, or 5 µm, of passive sweat in a 0.5-inch-square of skin over a period of 10 minutes.

Therefore, the investigators wanted to create a highly sensitive technique to quantify the cytokine levels in small quantities of passive sweat. The team drew on their earlier study on a wearable sweat sensor to track the markers of inflammatory bowel disease (IBD).

The device, resembling a wristwatch, is being marketed by EnLiSense LLC (a firm jointly established by Prasad). It quantifies the concentrations of a couple of proteins that increase at the time of IBD flare-ups.

When this device is worn on the arm, it causes the passive sweat to spread onto a disposable sensor strip that, in turn, is linked to an electronic reader, or e-reader.

The sensor strip, containing a pair of electrodes, is coated with antibodies that attach to both the proteins. When the proteins bind to their antibodies, the electrical current flowing via the e-reader is changed.

This data is then wirelessly transferred to a smartphone app through the e-reader and the electrical measurements are converted into protein concentrations by the smartphone app. The old sweat spreads out after a few minutes and the recently discharged sweat penetrates the strip for analysis.

For their novel cytokine sensor (known as the SWEATSENSER Dx), the team created sensor strips integrated with antibodies against seven pro-inflammatory proteins, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, TNF-related apoptosis-inducing ligand, IL-10, C-reactive protein and interferon-γ-induced protein-10.

The team inserted the strips into their device and, in a small observational analysis, tested them on five people with influenza and six healthy individuals. Among these, two of the sick individuals exhibited increased cytokine levels, and in all study participants, cytokines excreted in passive sweat matched with the concentrations of the same serum proteins.

The SWEATSENSER Dx sensor was also sufficiently sensitive to quantify cytokine levels in patients taking anti-inflammatory medications, who release cytokines in the low-picogram-per-milliliter concentration range. The new device monitored cytokine concentrations for up to 168 hours before the sensor strip had to be substituted.

In association with the research team, EnLiSense has now planned clinical trials of the cytokine sensor in individuals suffering from 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. 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.

Shalini Prasad, PhD, Project Principal Investigator, The University of Texas at Dallas

The team acknowledges funding and support from the Biomedical Advanced Research and Development Authority DRIVe program and EnLiSense LLC.


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