A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19

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.</p

Corrigendum to 'A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19'

The authors wish to correct a typographical error in the manuscript. In both the abstract and Section 3.4 of the original manuscript, a 1-point increase in the Dublin-Boston score was described as being associated with a 5.6 times increased odds (OR 5.62, 95% CI = 3.229.81, P = 1.2 £ 109 ) for a more severe outcome. While the OR and P-value stated are correct, the CI should instead have read “3.229.81”. The CI listed in Table 3 of the original manuscript, which accompanied Section 3.4, is correct. The authors regret any confusion caused, and appreciate the opportunity to correct this mistake.</div

Analysis configurations and number of genetic variants incorporated.

Analysis configurations and number of genetic variants incorporated.</p

Power curves for RITSS1, RITSS2, GESAT, and GAMsv over increasing signal density <i>p</i>_<i>XE</i>.

Significance level α = 0.005, μXE = 0.1, and results based on 1,000 replicates. Power was simulated for pXE = 0.05, 0.1, 0.2, 0.3, 0.4, 0.5.</p

Power curves for RITSS1, RITSS2, GESAT, and GAMsv over increasing signal density <i>p</i>_<i>XE</i>.

Significance level α = 0.005, μXE = 0.05, and results based on 1,000 replicates. Power was simulated for pXE = 0.05, 0.1, 0.2, 0.3, 0.4, 0.5.</p

Type 1 error: Quantile-quantile-plots for RITSS1, RITSS2, GESAT, and GAMsv for scenarios 1–5 with SELECT:no.

All results based on 10,000 replicates. P-values with p−10 were set to p = 10−10. SELECT:no refers to the scenario where all simulated genetic variants are included in the analysis.</p

Density plots for standardized residuals for all four traits in the analysis.

FEV1: forced expiratory volume in 1 second, FVC: forced vital capacity. (TIF)</p

Additional information regarding genetic variants tested in the UK Biobank analysis.

These tables contain all genetic variants as well as the m4/m3 information for the sex-interaction analysis in the UK Biobank. (XLSX)</p

Results of the interaction testing using the two approaches RITSS1 and RITSS2 in the UK Biobank.

The environmental factor tested for interaction is denoted by Eit. |m| is the number of total SNPs in the analysis, |m4| and |m3| are the number of SNPs that are shared by all four and exactly three interaction scores, respectively. P-Y-S: pack-years of smoking, E-S: ever-smoking.</p

Visualization of the RITSS algorithm.

Visualization of the RITSS algorithm.</p