RESUMEN
Background: Inflammation parameters, such as white blood cell (WBC) counts, are closely related to the severity and mortality of Coronavirus disease 2019 (COVID-19). Nevertheless, the association between inflammation fluctuation and clinical outcomes in patients with COVID‐19 is not clear.Methods: We performed a secondary analysis of the ORCHID trial. Inflammation fluctuation was assessed by WBC variability indices (SD [standard deviation], and CV [coefficient of variation]). Cox regression was used to compute the hazard ratio for WBC variability and associated hospitalization and death over 28 days.Results: During the 28 days post-randomization, 46 (10.8%) patients died, and 345 (81.4%) patients were discharged. In multivariable analysis, a worse clinical outcome, including decreased risk of hospital discharge (SD: HR: 2.32; P<0.001; CV: 1.72; P=0.001) and increased mortality (SD: HR: 1.51; P=0.002; CV: 1.35; P=0.006), was found with increased WBC variability. Furthermore, WBC variability had moderate performances in predicting discharge (C-index, SD: 0.705; CV: 0.703), and all-cause death over 28 days (C-index, SD: 0.632, CV: 0.688). Sensitivity analyses that involved changing 28-day mortality to in-hospital mortality, recalculating the WBC indices by using the lowest WBC value, and using the competing risk model generated confirmatory results. Most of the interactions between sex, age (>65), hydroxychloroquine treatment group, and WBC variability indices were not significant (P>0.05).Conclusion: In conclusion, our results showed that COVID-19 patients with higher WBC variability had lower discharge rates and higher mortality. Our study contributes to our understanding of the relationship between inflammation and COVID-19-related adverse outcomes.Clinical trial registration: URL: https://clinicaltrials.gov. Unique identifier: NCT04332991.