COVID-19 Genomics Research Network

Colleagues,

The rapidly unfolding events in New York and globally, emphasize the need to quickly decode the host-pathogen biology of SARS-CoV-2 and the associated COVID-19 disease. Among the science proposed in the community is understanding the evolution of the viral genome and possible host genomic factors from the germline or immune response, which may explain pathophysiology of COVID-19. New York is fortunate to have many experts in each of the relevant areas at all institutions. We believe the best chance of rapid progress will come from pooling efforts and resources across centers. To assist with this effort, the New York Genome Center is proposing the establishment of a city-wide genomics-focused research network to bring the genomics capacity and expertise in conjunction with area research programs on COVID-19. We believe these efforts, if well-coordinated and described, will be in position to rapidly attract the resources needed to enact them.

NYGC is proposing the following initial areas of intramural/extramural scientific focus and network capacity, and we would welcome concrete proposals in additional areas:

• • Large scale full length viral sequencing to determine viral evolution and spread across the community – As the virus is currently estimated to acquire approximately one new RNA mutation every 2 weeks, or every 2-3 transmissions, one can use the pattern of sequence variation to determine how far back any two infections can be traced to a single host and, with deep enough sampling, estimate where that host was and how the virus has moved through human populations. Such data could also be used to estimate important factors for epidemiological models such as how many introductions of the virus have occurred in a specific region and the number of unique clusters of transmission. These data will also provide insights to the number of undetected cases that are currently transmitting in the population.

 

• • Whole genome germline sequencing and immune repertoire sequencing of affected individuals, focused on extreme phenotypes to examine host factors and immune responses – Although the age and co-morbidity cofactors for COVID-19 have revealed high mortality rates in individuals of older age and those with pre-existing immune, cardiovascular or lung diseases, a striking observation is respiratory failure in some otherwise healthy young individuals. A known risk factor appears to be heavy exposure to viral load especially among frontline healthcare workers. It is likely germline variation will explain some aspects of extreme responses to SARS-CoV-2, which may in turn guide risk mitigation, vaccine development and implementation, and other strategies. Possibilities include DNA sequence polymorphisms that influence protein function and/or outlier gene expression in ACE2, TMPRSS2, and other proteins involved in viral entry, genes controlling surfactant alveolar cell development and function, polymorphisms in HLA, innate, or cellular immune responses, polymorphisms affecting cardiovascular function, intracellular RNA processing and others. Host-pathogen interaction with the genotype of the viral load may also be important, thus knowledge of both the viral sequences present, as well as host factors will be crucial. The information obtained could not only be impactful in the current pandemic but could also inform future pandemics.

 

• • Single cell sequencing to examine tissue responses and provide a genome variation of expression context for viral responses.

 

• • Establishment of a data commons for the research network so that full availability of data to investigators can be provided.

 

To achieve progress in this critical research, we propose organizing a network of treatment and research sites in the New York area to share samples and data. Viral and germline samples from patients could be prepped at hospitals and sequenced in a distributed or centralized manner, and the data shared across all participating sites. This network would be open to any site seeing patients and any site with research capacity. We have already joined in a number of local efforts but joining together as one NYC/NJ-based COVID-19 research initiative would bring a strength in numbers and resources that we could all benefit from. A collective effort could quickly establish the optimal infrastructure required to do this effectively. There are many challenges of such an effort including identifying, recruiting and consenting interested participants, collecting and processing samples, rapid data analysis and data sharing. There are many people in New York with the necessary experience in organizing large studies to make this a success, several of whom have already begun to make progress on COVID-19 related research. I hope you will all agree with the importance of building this network and join. I would like to offer our help in organizing a centralized effort, we could be a site for sequencing and analysis, as well as provide help coordinating effective data sharing.

Key actions:

• • We would like to identify from each interested institution one clinical lead and one research lead with whom we could engage to help shape the network.

 

• • We host a call every other Monday at 2pm with all interested parties. If there are researchers or clinicians at your institution that would be interested, please forward this to them. If you would like to join the call, please email info@covidgenomics.org to be added to the invite.

 

We are aware of a wide range of ongoing research at your institutions and hope to have the opportunity to work together. If there are other ongoing research projects, activities and ideas that would benefit from a concerted and cooperative research program, please connect them with us and/or bring them up at the meeting. If there is sufficient interest and enthusiasm for a city-wide effort, we can begin building the means of communication and coordination.

I look forward to hearing from all of you, 

 

Tom Maniatis, PhD
Scientific Director and CEO
New York Genome Center