The connection between severe COVID-19 and white blood cell counts

By Dr. Ananya Mandal, MDOct 19 2020Reviewed by Aimee Molineux

American and Chinese researchers collaborated to study the association between a severe course of COVID-19 and white blood cell counts in the body.

White blood cells are known to be part of the body's immune system that helps fight infections. COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic that has brought the world to a standstill with over 40 million people infected and over 1.1 million lives lost.

Many of the infected persons require hospital admission, especially intensive care admission and ventilation. Because of the novel nature of the infection, not much is clear about the infection's pathology.

Research shedding light on the infection's pathology could help scientists understand the disease and develop possible medications to treat COVID-19.

A new study titled "White blood cells and severe COVID-19: a Mendelian randomization study" was released as a pre-print on the medRxiv* server.

Study: White blood cells and severe COVID-19: a Mendelian randomization study. Image Credit: Rost9 / Shutterstock

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Background

Researchers explained that while all individuals are at risk of contracting the infection, some with certain pre-existing conditions are at a greater risk of developing severe disease. Some of these pre-existing conditions include cardiovascular disease, diabetes, chronic respiratory disease, hypertension, and cancers. Those of advancing age and men are also at a greater risk of severe disease. They added that certain genetic studies have shown that multiple genetic loci could predict the risk of severe COVID-19. Identification of these risk factors accurately could help develop preventive strategies and also help develop effective treatment strategies.

White blood cells and neutrophil-to-lymphocyte ratio

Some studies have revealed that raised white blood cell and neutrophil counts along with a fall in lymphocyte count are seen in some patients with COVID-19. Other studies have shown that determining the neutrophil-to-lymphocyte ratio could serve as a biomarker that could predict the infection's outcome.

However, in other research, white blood cells' exact roles and subtypes in severe COVID-19 are still unclear. The team writes, "It is unknown if blood cell counts before infection are associated with the risk of developing severe COVID-19." They explained that the numbers of these cell types could be influenced by several factors such as age, gender, disease status, and medications.

Mendelian randomization

Mendelian randomization (MR) is a mathematical method that uses genetic variants as variables to approximate exposure and outcome status. The genetic traits or alleles are randomly allocated at conception, and other factors do not influence these variants. This MR study aimed to test the causal effects of white blood cell traits on severe COVID-19.

What was done?

A two-sample MR analysis was performed using recent genome-wide association studies (GWAS) to assess the causal associations between various white blood cell traits and severe COVID-19.

The GWAS that was utilized in this study included 173,480 European ancestry individuals from 3 cohorts. The data was available at the IEU OpenGWAS database. Genetic associations for each white blood cell trait were studied based on the criteria :

• p < 8.31×10^-9 for association with the exposure
• linkage disequilibrium (LD) clumping based on r² > 0.001

The outcome was obtained from COVID-19 Host Genetics Initiative (HGI, release 3, accessed on July 2, 2020). Data from 3,199 hospitalized COVID-19 patients was compared to 897,488 from the general population. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test was applied.

What was found?

The MR results showed that white blood cell count, myeloid white blood cell count, and granulocyte count have a negative causal relationship with severe COVID-19. They write, "white blood cell count, myeloid white blood cell count, and granulocyte count had consistent, negative effects on the risk of severe COVID-19". Overall results were::

• An odds ratio of 0.84 (95% CI: 0.72-0.98) of white blood cell count and severe COVID-19
• An odds ratio of 0.81 (95% CI: 0.70-0.94) of myeloid white blood cell count and severe COVID-19
• An odds ratio of 0.84 (95% CI: 0.71-0.99) of granulocyte count and severe COVID-19
• An Odds ratio of 0.75, (CI: 125 0.58-0.96, p = 0.023) of basophil count and severe COVID-19
• Negative association for sum of neutrophil eosinophil counts (OR = 0.85, CI: 0.73-1.00, p = 0.051)
• Increasing eosinophil percentage of white blood cells was associated with a greater risk of severe COVID-19 (OR: 1.22, 95% CI: 1.03-1.45)

Conclusions and implications

Researchers concluded that there is a potential for using white blood cell counts as a marker for severe CVOID-19. They wrote, "the potential causal effects of lower white blood cell count, lower myeloid white blood cell count, lower granulocyte count, and higher eosinophil percentage of white blood cells on an increased risk of severe COVID-19," can be concluded from their study.

This study was supported by the University of Georgia Research Foundation.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources