High-throughput SARS-CoV-2 and host genome sequencing from single nasopharyngeal swabs (preprint)

During COVID19 and other viral pandemics, rapid generation of host and pathogen genomic data is critical to tracking infection and informing therapies. There is an urgent need for efficient approaches to this data generation at scale. We have developed a scalable, high throughput approach to generate high fidelity low pass whole genome and HLA sequencing, viral genomes, and representation of human transcriptome from single nasopharyngeal swabs of COVID19 patients.

Initial Review and Analysis of COVID-19 Host Genetics and Associated Phenotypes (preprint)

The global pandemic of COVID-19 accounts for more than 14,000 deaths worldwide. However, little is known about the host genetics interaction with infection and COVID-19 progression. To better understand the role of host genetics, we review the current literature, aggregate readily available genetic resources, and provide some updated analysis relevant to COVID-19 and associated phenotypes. Using the unrelated individuals in UK Biobank (total n = 337,579 across 5 populations), we aggregate human leukocyte antigen and ABO blood type frequencies. We find significant and consistent risk reduction of blood group O reported in Zhao et al. and encourage broad sharing of ABO blood type frequencies that are readily accessible across COVID-19 with mild, moderate, and severe/critical symptoms for robust inferences at https://tinyurl.com/abo-covid19. In addition, we generate polygenic risk scores (PRSs) weights for 29 blood measurements, including clinically relevant haematological measurements for COVID-19, such as lymphocyte count and percentage. Focusing on the 8 most COVID-19 clinically relevant blood measurements, we performed PRS-PheWAS analysis across 44 disease antigen measurements (n = 6,643 unrelated individuals in White British group), infectious diseases and acute respiratory infections (n = 20,928 cases and 349,000 controls across 3 population groups) and deaths (n = 1,846 cases and 368,082 controls), recorded in hospital inpatient record and death registry data, respectively, in UK Biobank, and find host genetic PRS associations with disease risk. Taken together, we anticipate these resources (https://github.com/rivas-lab/covid19) will aid in improving our understanding of host genetic risk factors playing a role in SARS-CoV-2 infection and COVID-19 disease severity.