In a recent study published on the medRxiv* preprint server, researchers examine the genetic factors influencing hematological parameters in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
In hospitalized patients with coronavirus disease 2019 (COVID-19), various studies have reported hematological abnormalities, as well as respiratory symptoms and pulmonary manifestations. These hematological alterations have been linked to the severity of COVID-19; however, their causal pathways influencing SARS-CoV-2 manifestations are not yet established.
Study: Genetic examination of hematological parameters in SARS-CoV-2 and COVID-19 infection. Image Credit: luchschenF / Shutterstock.com
About the study
The present study aimed to determine whether genetically determined histological parameters assessed at baseline prior to COVID-19 infection impact the susceptibility and severity of COVID-19.
Data from 500,000 people aged 40 to 69 were obtained from the United Kingdom Biobank (UKB). Hematology trait analysis and genotyping of the personalized Axiom chips were performed on blood and urine samples collected from the participants.
Clinical cohort samples were obtained from Vanderbilt University Medical Center (VUMC), which incorporated data including procedure and diagnosis codes, clinical care data, medications, laboratory results, and demographics such as age, gender, race and ethnicity. The team also collected COVID-19 statistics for three phenotypes, the critically ill phenotype and the hospitalized phenotype, which functioned as a binary indicator.
Blood cell indices were assessed from blood samples taken during in-person visits to UKB. The correlation of each blood cell parameter with SARS-CoV-2 infection status and associated hospitalization was assessed in data collected from the UKB.
Hospitalized cases were defined as a case with a positive COVID-19 result, tested either when the patient was hospitalized, 14 days prior to hospitalization, during a hospital episode, or seven days after hospital discharge.
Data collected from the VUMC was also assessed for the association of blood cell parameters with positive tests for SARS-CoV-2 and associated hospitalizations. Hospitalizations for SARS-CoV-2 were defined as cases with a positive SARS-CoV-2 test within seven days before or 30 days after a positive test for COVID-19. Race and ethnicity were used as covariates in case and control cohort analyses.
The study also assessed evidence supporting genetic association signals coinciding with COVID-19 loci, which were associated with blood cell traits. The genetic correlation between blood cell parameters and COVID-19 phenotypes was estimated using linkage disequilibrium (LD) score regression. Additionally, the causal effect of various hematological traits on COVID-19 phenotypes was estimated using Mendelian randomization (MR).
Among the 423,358 UKB participants eligible for the study, baseline measures of 15 haematological traits and their association with COVID-19 infection and hospitalization were assessed. In UKB participants, percentage of basophils at baseline was associated with SARS-CoV-2 infection, while mean cell hemoglobin levels and mean cell volumes were associated with hospitalization at baseline. COVID-19. However, no significant correlation of these hematological traits with COVID-19 outcomes was observed in 1,037,358 VUMC participants.
In follow-up analysis, total white blood cell count (WBC) in VUMC was associated with both COVID-19 and related hospitalization. Red blood cell (RBC) distribution width was also linked to COVID-19 hospitalization, while SARS-CoV-2 infection was associated with hematocrit levels.
Analysis of SARS-CoV-2 loci coinciding with blood cell traits revealed moderate linkage disequilibrium of five SARS-CoV-2-linked sentinel variants, with at least one blood cell trait variant. Three of these five sentinel variants were associated with COVID-19 that overlapped with the genome-wide red blood cell-associated association study (GWAS), while severe COVID-19 illness and related hospitalization overlapped platelet and lymphocyte phenotypes, as well as the locus for the number of monocytes and percentage.
MR analyzes revealed that basophil proportions were associated with COVID-19 hospitalization with notable directional pleiotropy effects. A hematological trait was also correlated with reported SARS-CoV-2 infection, while increased mean platelet volume values were associated with a higher risk of COVID-19-related hospitalization. In contrast, red blood cells had a negative association with reported SARS-CoV-2 infection.
Despite considerable links associating blood cell traits and COVID-19-related phenotypes in individuals infected with SARS-CoV-2, the correlation between hematological parameters measured before infection and patient susceptibility to infection by SARS-CoV-2 and disease severity was insignificant. However, the coincidence of certain genetic loci supported the association of SARS-CoV-2 infection and related severity with certain blood cell-related traits.
The researchers believed that increasing sample sizes to facilitate more balanced case-control studies would allow more definitive conclusions to be drawn about the potential association of COVID-19-related outcomes and blood cell count variants.
medRxiv 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.