In a recent study posted to Research Square* preprint server, and currently under consideration at the Journal of Inflammation, researchers conducted an observational study to evaluate the association of white blood cell (WBC) variability with clinical outcomes, such as deaths and hospital discharge rates, in coronavirus disease 2019 (COVID-19) patients.
They analyzed data from the ORCHID (outcomes related to COVID-19 treated with hydroxychloroquine among in-patients with symptomatic disease) trial.
COVID-19 is an acute and highly infectious respiratory tract infection associated with high morbidity and mortality across the globe. This disease is characterized by systemic inflammation with an increase in pro-inflammatory cytokines, such as interleukins-6 and 10 (IL-6 and IL-10), as a result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evasion of protective host immune mechanisms regulated by WBCs. The viral immune escape, due to increased viral spike (S) protein and angiotensin-converting enzyme 2 (ACE2) receptor-binding, facilitates viral entry into human cells thereby causing increased viral transmission and replication.
WBC count is a test performed to measure the number of WBCs in blood. This count is an important measure of inflammation. Elevated counts (higher than 11,000 WBCs per unit microliter of blood) could alter the hospital discharge rates and deaths in COVID-19 patients. Thus, WBC variations could contribute to increased clinical severity and be a direct indicator of the poor prognosis of SARS-CoV-2 infections.
Although the present study is the first of its kind to evaluate the relationship between WBC immune-inflammatory variability and COVID-19 prognosis, previous studies have extensively investigated and reported positive associations between variations in blood glucose, heart rate, body mass index (BMI), blood pressure, and adverse disease outcomes such as increased mortality and development of severe COVID-19. Elevated neutrophil-lymphocyte ratios (NLR) have been significantly associated with the rapid progression of the disease and increased mortality in SARS-CoV-2 infections.
About the study
In this study, the researchers secondarily evaluated data obtained from the government-registered ORCHID trial to assess the effect of WBC count fluctuations on COVID-19 severity over 28 days using WBC indices, such as standard deviation (SD) and coefficient of variation (CV), and a mathematically computed hazard ratio of variabilities in the WBC counts and related deaths and hospitalizations using the Cox regression method. The data obtained were adjusted for sex, age, corticosteroid use, BMI, presence of comorbidities, baseline and elevated WBC levels, and sequential organ failure assessment scores.
Secondary analysis inclusive of sub-group analysis for age (above and below 65 years), gender (males versus females), and treatment (hydroxychloroquine versus placebo), as well as sensitivity analysis by using lowest WBC count values instead of highest WBC counts, was performed by the team to obtain associations of independent WBC variables with clinical outcomes. Cox regression was used to compute the hazard ratio for WBC variability and associated hospitalization and death over 28 days.
Results and discussion
Out of a total of 424 hospitalized COVID-19 patients, 42.2% were females, of which 60.6% were Latino or Hispanic with comorbidities such as hypertension (57%) and diabetes mellitus (35%). A majority (81.4%) of patients got discharged from the hospital whereas only 46 (10.8%) patients died within 28 days. However, reduced hospital discharges and increased deaths were observed with increased WBC counts.
Significantly higher and gradually increasing median WBC count values were observed after five days of hospital admission. The observed WBC values were higher in patients with higher SD values and were independent of WBC CV values.
The absence of significant interactions between the stratifications in the sub-group analysis indicated homogeneous results across all groups. Sensitivity analysis confirmed primary analysis findings. Statistic regression models confirmed the independent, linear, and positive association of both WBC parameters - SD and CV - with decreased hospital discharge and increased death rates.
Dynamic and dramatic variations in the peripheral blood WBC counts could be attributed to the underlying dysregulated immune responses to viral escape of immune mechanisms and subsequent viral replication in the human body.
Based on the study findings, the team concluded that the WBC count variations worsen clinical outcomes such as severity, mortality, and hospital discharge rates leading to a poorer prognosis in COVID-19 patients. Thus, healthcare facilities must regularly monitor WBC counts in hospitalized COVID-19 patients to enable prompt action and early treatment of disease adversities.
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