White blood cell count as a prognostic indicator of COVID-19

In a recent study published on Research Square* preprint server, and currently under study at Inflammation Diary, researchers conducted an observational study to assess the association of white blood cell (WBC) variability with clinical outcomes, such as deaths and hospital discharge rates, in patients with coronavirus disease 2019 (COVID-19).

They analyzed data from the ORCHID trial (outcomes related to COVID-19 treated with hydroxychloroquine in hospitalized patients with symptomatic disease).

Study: White blood cell variability and clinical outcomes in hospitalized patients with COVID-19. Image Credit: cenksns/Shutterstock

COVID-19 is an acute and highly infectious respiratory tract infection associated with high morbidity and mortality worldwide. 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 the host’s protective immune mechanisms regulated by white blood cells. Viral immune evasion, due to increased viral spike protein (S) and angiotensin-converting enzyme 2 (ACE2) receptor binding, facilitates viral entry into human cells , thereby causing increased viral transmission and replication.

The white blood cell count is a test done to measure the number of white blood cells in the blood. This number is an important measure of inflammation. High counts (greater than 11,000 white blood cells per unit microliter of blood) could alter hospital discharge rates and deaths in COVID-19 patients. Thus, variations in WBC 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.

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About the study

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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.

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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.

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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.

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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.

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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.

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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.

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Conclusion

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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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*Important notice

Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.

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