A broad and nimble sequencing program is necessary to track, anticipate, and quash SARS-CoV-2 and other dangerous pathogens that threaten humanity.
In late March 2020, as COVID-19 cut a path of destruction across New York City, a colleague emailed me to ask if I wanted to work with him on sequencing some viral genomes. Eukaryote-infecting viruses like SARS-Cov-2 are far afield from my usual lab work of studying microbial communities in the body and in the oceans, but because I have expertise in genomic analysis, Albert Einstein College of Medicine virologist Kartik Chandran thought I might be able to help. I jumped at his offer and dove into a collaboration to understand SARS-CoV-2’s spread through the Bronx.
Early SARS-CoV-2 virus sequencing efforts in New York City had produced few sequences from the city’s most northerly borough, which was disproportionately affected by the pandemic. By early May 2020, the Bronx led the city with 1 death per 451 residents, nearly twice the rate in Manhattan (1 in 837). However, my colleague, geneticist John Greally, found that earlier in the pandemic only 36 viral genotypes of Bronx cases had been sequenced, compared to 280 in Manhattan. When we started our work, we aimed to determine whether the disproportionate deaths in the Bronx were related to the genetic makeup of the virus. Were our Bronx communities getting infected with a particularly deadly strain of SARS-CoV-2?
Over the ensuing months, we sequenced more than 100 SARS-CoV-2 genomes isolated from Bronx patients. We discovered, with relief, that the answer was no: the viruses in the borough did not differ significantly from those isolated from patients elsewhere in the city. But our work is not finished. A robust and representative genomic sequencing program is crucial for New York—and for the rest of the world. The lack of an established and well-funded program means we are undercutting our chance to stay ahead of this shape-shifting virus and to prevent more suffering.
News earlier this year that two SARS-CoV-2 variants of concern, B.1.1.7 or "Alpha" according to the World Health Organization, which was first identified in the UK, and a novel variant B.1.526 or "Iota," were causing more than half of genome-sequenced coronavirus cases in New York City is the latest case in point. While scientists have seen no convincing evidence that they are any deadlier than earlier circulating strains of the virus, these variants and others emerging around the world threaten to undermine the efficacy of current vaccines and monoclonal antibody treatments.
But genomic sequencing costs money; the number of researchers, level of expertise, and time involved in the process are substantial. Our team at Albert Einstein College of Medicine and Montefiore Health System was able to jump into the fray and prioritize fighting COVID-19. But smaller institutions and people living in underserved communities risk being left out of this research and the findings that follow. This is particularly galling and shortsighted as these are the communities most at risk for SARS-CoV-2 infection and death, due to existing health disparities and greater exposure to the virus as essential workers.
Applying for federal grants is one answer, but the months- to years-long timeframe associated with federal funding awards is a major roadblock to sequencing efforts. This work needs to be done now. The rise of more-transmissible and/or deadlier variants is a persistent concern.
Individual investigators and institutions and small collaborative groups in New York and around the world have been on the variant hunt for months, often using their own internal funds to do this work. Our clinicians regularly send nasal swab samples to the Wadsworth Laboratory in Albany for sequencing. Rapid turnaround at this lab means we can observe the changing landscape of SARS-CoV-2 in the Bronx with just a few weeks from swab to sequence. Targeted work at the city and state level in New York is vastly improving our understanding of the virus within our borders. The New York City Health Department is coordinating efforts, including facilitating collaborations between academic health centers and community testing sites, to estimate the prevalence of viral variants of interest across the city.
And what of smaller communities, or cities and states with no coordinated sequencing efforts? A centralized, federally funded SARS-CoV-2 sequencing resource for the United States will be an invaluable resource to keep us from flying blind in the face of this changing virus. In April, the CDC announced the launch of just such a program, the SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology and Surveillance (SPHERES), that will incorporate data from academic, clinical, public health, and private labs. Such a comprehensive sequencing effort could help us track, contain, and hopefully stamp out this viral scourge.
Our work shows that limited, targeted genomic surveillance is useful in the effort to manage the ongoing COVID-19 pandemic. Building the process and infrastructure would prepare us for new emerging viruses that will inevitably follow.
Libusha Kelly is an associate professor of systems and computational biology and of microbiology and immunology at Albert Einstein College of Medicine. Follow her on Twitter @microbegrrl