Monday, May 11, 2020

Very Brief Blog: Preprint Article Highlights Host Vulnerability to COVID

There is a global host-response consortium for studying the radically different responses of different person to COVID-19 infection - see early article at Genomeweb here, see consortium website here.  See a review of human genomics relative to COVID virus in Genetic in Medicine, Murray et al., here.

May 10, trade press Tomislav Mestrovic (here) on a preprint article by Kachuri et al., "Landscape of Host Genetic Factors Involved in Infection in Common Viruses and SARS-CoV-2" (here).    

For viral response as a whole, the authors write, "We conducted a comprehensive study in the UK biobank linking germline genetic variation and gene expression with 28 antigens for 16 viruses in 7924 subjects. We discovered 7 novel loci associated with antibody response (P<5.0×10-8), including FUT2 for human polyomavirus BKV, TMEM173 for Merkel cell polyomavirus (MCV), and TBKBP1 for human herpesvirus 7."  Turning more specifically to COVID, they write, "Based on 1028 subjects tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we identify 7 class II HLA susceptibility alleles (5 [also] associated with other viruses). We also observe that genetic determinants of ACE2 expression may influence SARS- CoV-2 susceptibility. Our findings elucidate the genetic architecture of host response to viral infection, with potential implications for complex diseases and COVID-19."  Kachuri et al. are mostly UCSF-based, and used data from the UK genomes biobank.

Notably, most of the odds ratios for SNPs and likelihood of COVID-positive testing were small (0.4-1.6).  However, this is a non-clinical study, and the more important factor, the odds of COVID hospitalization or death, were not studied.  It may turn out that genetic factors play a largely role in the cascade of host response than in turning test-positive or not.