Differential Circulating Proteomic Responses Associated with Ancestry during Severe COVID-19 Infection

Area of Science:

• Immunology
• Genetics
• Epidemiology

Background:

• The COVID-19 pandemic revealed disparities in disease severity and outcomes across different ancestral populations.
• Pre-existing evidence suggests a link between an individual's ancestry and their susceptibility and response to severe COVID-19 infection.

Purpose of the Study:

• To investigate differential circulating protein level responses to severe COVID-19 infection across three continental ancestries.
• To identify specific proteins that may account for observed differences in COVID-19 severity among ancestral groups.

Main Methods:

• Utilized the SomaScan platform to measure 4979 circulating proteins from 1272 patient samples.
• Employed a linear mixed-effects model to analyze ancestry-specific associations between protein levels and severe COVID-19 illness.

Main Results:

• A higher percentage of proteins were associated with severe COVID-19 in European-ancestry individuals (62%) compared to African (45%) and East Asian (22%) ancestries, potentially due to sample size variations.
• While protein responses showed strong correlations across ancestries, 39 unique proteins exhibited differential responses (False Discovery Rate <0.05) between the three groups.
• Individuals of European and African ancestry displayed the most similar protein responses, while European and East Asian ancestries showed the least similarity.

Conclusions:

• Circulating protein profiles in response to severe COVID-19 vary significantly across continental ancestries.
• The identified 39 differentially responding proteins represent potential biomarkers for understanding ancestry-related COVID-19 severity disparities.
• Further research into these unique proteins could elucidate mechanisms underlying differential disease outcomes and inform targeted public health strategies.