Scientists have developed a score that can accurately predict which patients will develop a severe form of COVID-19. The study is led by researchers at RCSI University of Medicine and Health Sciences. The measurement, called the Dublin-Boston score, is designed to enable clinicians to make more informed decisions when identifying patients who may benefit from therapies, such as steroids, and admission to intensive care units.
Until this study, no COVID-19-specific prognostic scores were available to guide clinical decision-making. The Dublin-Boston score can now accurately predict how severe the infection will be on day seven after measuring the patient's blood for the first four days.
The blood test works by measuring the levels of two molecules that send messages to the body's immune system and control inflammation. One of these molecules, interleukin (IL)-6, is pro-inflammatory, and a different one, called IL-10, is anti-inflammatory. The levels of both are altered in severe COVID-19 patients.
Based on the changes in the ratio of these two molecules over time, the researchers developed a point system where each 1-point increase was associated with a 5.6-times increased odds for a more severe outcome.
"The Dublin-Boston score is easily calculated and can be applied to all hospitalised Covid-19 patients," said RCSI professor of medicine Gerry McElvaney, the study's senior author and a consultant in Beaumont Hospital.
"More informed prognosis could help determine when to escalate or de-escalate 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."
The Dublin-Boston score uses the ratio of IL-6 to IL-10 because it significantly outperformed measuring the change in IL-6 alone.
Despite high levels in blood, using only IL-6 measurements as a COVID-19 prognostic tool is hindered by several factors. IL-6 levels within the same patient vary over the course of any given day, and the magnitude of the IL-6 response to infection varies between different patients.
The Dublin-Boston score was developed by researchers from RCSI, Harvard University, Beaumont Hospital in Dublin and the Brigham and Women's Hospital in Boston.
Abstract
Background: Prognostic tools are required to guide clinical decision-making in COVID-19.
Methods: We studied the relationship between the ratio of interleukin (IL)-6 to IL-10 and clinical outcome in 80 patients hospitalized for COVID-19, and created a simple 5-point linear score predictor of clinical outcome, the Dublin-Boston score. Clinical outcome was analysed as a three-level ordinal variable (“Improved”, “Unchanged”, or “Declined”). For both IL-6:IL-10 ratio and IL-6 alone, we associated clinical outcome with a) baseline biomarker levels, b) change in biomarker level from day 0 to day 2, c) change in biomarker from day 0 to day 4, and d) slope of biomarker change throughout the study. The associations between ordinal clinical outcome and each of the different predictors were performed with proportional odds logistic regression. Associations were run both “unadjusted” and adjusted for age and sex. Nested cross-validation was used to identify the model for incorporation into the Dublin-Boston score.
Findings:The 4-day change in IL-6:IL-10 ratio was chosen to derive the Dublin-Boston score. Each 1 point increase in the score was associated with a 5.6 times increased odds for a more severe outcome (OR 5.62, 95% CI -3.22–9.81, P = 1.2 × 10−9). Both the Dublin-Boston score and the 4-day change in IL-6:IL-10 significantly outperformed IL-6 alone in predicting clinical outcome at day 7.
Interpretation: The Dublin-Boston score is easily calculated and can be applied to a spectrum of hospitalized COVID-19 patients. More informed prognosis could help determine when to escalate care, institute or remove mechanical ventilation, or drive considerations for therapies.
Funding: Funding was received from the Elaine Galwey Research Fellowship, American Thoracic Society, National Institutes of Health and the Parker B Francis Research Opportunity Award.
Authors
Oliver J McElvaney, Brian D Hobbs, Dandi Qiao, Oisín F McElvaney, Matthew Moll, Natalie L McEvoy, Jennifer Clarke, Eoin O'Connor, Seán Walsh, Michael H Cho, Gerard F Curley, Noel G McElvaney
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