(Ahmad Ardity, Pixabay)
14 Oct. 2020. A blood test that measures the ratio of two key immune system proteins is shown in tests with patients to predict the severity of Covid-19 symptoms. The blood test, developed by researchers at Royal College of Surgeons in Ireland, or RCSI, and Beaumont Hospital in Dublin and Brigham and Women’s Hospital in Boston, affiliated with Harvard Medical School, is described last week in the journal EBioMedicine, a Lancet publication.
Many patients with Covid-19 infections produce high levels of proteins called cytokines as a reaction to their infections. This rush of cytokines, called a cytokine storm, can result in severe inflammatory symptoms among patients, including acute respiratory distress syndrome, kidney failure, heart disease, and low blood oxygen levels. Physicians now have only a few tools to treat these symptoms, often reserved for more serious cases: the anti-inflammatory drug remdesivir, steroids, and monoclonal antibodies still in clinical trials and not yet licensed.
The Dublin and Boston researchers are seeking a simple, direct method for identifying early on those Covid-19 patients most likely to develop severe symptoms. The team identified two cytokines where Covid-19 infections result in altered levels: interleukin-6 and interleukin-10. Interleukin-6 promotes inflammation in response to infections, but when uncontrolled can result in chronic inflammatory and autoimmune disorders. Interleukin-10 has anti-inflammatory properties, and plays a role in limiting immune reactions to infections, but if uncontrolled can limit normal immune responses to pathogens.
The team led by RCSI medical school professor Gerry McElvaney created a five-point scale from the changes in ratio of interleukin-6 to interleukin-10 in the blood of patients, from the first diagnosis of Covid-19 on day 0 to day 4. The ratio is then normalized to scores of -2, for best prognosis, to +2 for worst prognosis.
The researchers evaluated this metric, called the Dublin-Boston score, with 80 patients admitted to Beaumont Hospital with Covid-19 infections. The team calculated the Dublin-Boston score for each patient on day 4, and assigned a prognosis of improved, unchanged, or declined. The researchers then compared the outcomes of each patient to that prognosis on day 7, three days after calculating the score. The team also calculated adjustments for age and sex of patients as well as the raw Dublin-Boston scores.
The results show a strong correlation between Dublin-Boston scores and the patients’ day 7 outcomes. The authors note that each increase of 1 point in Dublin-Boston score is associated with 5.6 times the odds of a more severe outcome. The team also assessed the Dublin-Boston ratio against changes in the pro-inflammatory cytokine interleukin-6 alone, and found the changes in the interleukin-6 to interleukin-10 ratio outperformed interleukin-6 measures alone in predicting clinical outcomes.
“The Dublin-Boston score is easily calculated and can be applied to all hospitalized Covid-19 patients,” says McElvaney in an RCSI statement. “More informed prognosis could help determine when to escalate or deescalate care, a key component of the efficient allocation of resources during the current pandemic. The score may also have a role in evaluating whether new therapies designed to decrease inflammation in Covid-19 actually provide benefit.”
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