MIRCA readouts are associated with clinical indicators of disease severity. Median NOI (A) and HOI (B) values were higher by 2.64% (P = .04) and 10.75% (P = .004) in 62 and 44 adults compared with 41 and 21 children, respectively. Median NOI (C) and HOI (D) values were lower by 6% (P = .002) and 18.2% (P = .001) in 11 and 7 HbSC/HbSβ⁺/HbSE individuals compared with 87 and 57 HbSS/HbSβ⁰ individuals, respectively. (E) Twenty-two individuals on MTD of HU (dosage >35 mg/kg per d ay or <4 × 10³ ANC/μL) had HOI values lower by 6.9% compared with 19 individuals not on MTD (P = .04). No significant difference (P = .85) was observed in the median HOI of individuals (n = 23) not on HU and those on HU but not HU MTD. (F) NOIs from 62 individuals who developed chronic SCD complications (priapism, splenic infarction, kidney injury, retinopathy, chronic pain) within 1 year before sample collection were found to have 3.1% higher NOI values compared with 45 individuals who did not have any SCD complication (P = .015). In panels A-F, all comparisons were performed using a Mann-Whitney U test to compare sample medians. (G) The margins plot of NOI and cumulative incidence rate of acute complications (VOE + ACS) within the past year reveals that 1 unit increase in NOI was associated with 6.3% high risk of acute complications (P = .025; negative binomial model). ∗P ≤ .05; ∗∗P ≤ .01. ns, not significant.