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

COVID-19 led to a disruption in nearly all aspects of society, yet these impacts were not the same across populations. During the pandemic, it became apparent that ancestry was associated with COVID-19 severity and morbidity. This study examines the differential circulating protein levels between three continental ancestries in response to severe COVID-19 infection. 4979 circulating proteins from 1272 samples were measured using the SomaScan platform. We used a linear mixed model to assess the ancestry-specific association between protein levels and severe COVID-19 illness. Comparing ancestries, we found that 62% of the tested proteins are associated with severe COVID-19 infectionin European-ancestry individuals, compared to 45% and 22% of the tested proteins between COVID-19-infected and control individuals in people of African and East Asian ancestry, respectively, likely reflecting differences in sample sizes. We found that all ancestries had strong correlations between each other with individuals of European and African ancestry having the most similar response and European and East Asian ancestries having the least similar. However, we did find 39 unique proteins that responded differently (FDR <0.05) between the three ancestries. These proteins could be investigated to assess whether they explain the differences in observed severity of COVID-19 between ancestral populations.