COVID-19 Clinical Care: Study Finds Correlation Between White Blood Cell Count And Severe COVID-19
COVID-19 Clinical Care
: Researchers from the department of Genetics, University of Georgia-U.S. and Shanghai Jiao Tong University School of Medicine, Shanghai-China in a collaborative study have discovered a correlation between the white blood cell count and COVID-19 disease severity. The white blood cells are a critical component of the body’s immune system that helps fight infections.
The study findings suggest 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.
The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2020.10.14.20212993v1
A large percentage of infected individuals 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.
Scientist 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.
Past 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. https://pubmed.ncbi.nlm.nih.gov/32171076/
But in other research, white blood cells' exact roles and subtypes in severe COVID-19 are still unclear.
The study team comments, "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.
The utilization of Mendelian randomization (MR) which is a mathematical method that uses genetic variants as variables to approximate exposure and outcome status could help provide a better perspective said the study team.
Typically 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.
A detailed 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.
For the study, the GWAS that was utilized 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 data 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.
Significantly, 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.
The study team said, "White blood cell count, myeloid white blood cell count, and granulocyte count had consistent, negative effects on the risk of severe COVID-19".
The study findings 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)
Lymphopenia, as a response to viral infection, has been frequently associated with severe COVID-19 risk. However, the study team did not detect a causal effect of lymphocyte count on severe COVID-19. This discrepancy may reflect reverse causality in retrospective and prospective observational studies, with depleted lymphocyte count as a result of immune response to SARS-CoV-2 infection. Due to the limited number of SNPs associated with severe COVID-19, performing reverse MR analyses between severe COVID-19 and white blood cell traits is challenging. Using linkage disequilibrium (LD) assessment, only one SNP at locus 3p21.31 was retained in the previously published genome-wide significant SNPs. The team recently showed that SNPs at this locus are associated with multiple blood cell traits, suggesting they may have pleiotropic effects and are not suitable to be used as genetic instruments. As more COVID-19-associated SNPs are identified in the future, reverse MR analysis will be valuable to understand the effect of COVID-19 on blood cell traits
The study team concluded that there is a potential for using white blood cell counts as a marker for severe CVOID-19.
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