Houston Methodist researchers find telling clues in virus genes from COVID-19 patients

Newswise — HOUSTON-(May 8, 2020) – Gene sequencing results from the first documented strains of the SARS-CoV-2 virus that causes COVID-19 disease in the Houston area have been released by physician-scientists at Houston Methodist. Their results reveal there were multiple introductions of the virus into the area followed by rapid community spread. No evidence was found of mutations that make any particular strains of the virus more severe than others.

A team of infectious disease pathologists dove deeply into the virus’ RNA, analyzing the entire genomes of 320 strains of the SARS-CoV-2 virus collected from the first COVID-19 patients in the Houston Methodist system of eight hospitals. To date, this is the largest sample of SARS-CoV-2 genes sequenced from patients in the southern United States.

Given the time-sensitive nature of these discoveries, a preliminary report that has not yet been peer-reviewed has been posted on the preprint server bioRxiv. The manuscript, titled “Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas,” has been submitted for review to a prominent scientific journal. This preprint is not the final version of the article. James M. Musser, M.D., Ph.D., chair of the Department of Pathology and Genomic Medicine at Houston Methodist, is the corresponding author on the study.

More than a month before the first COVID-19 patient was diagnosed in Houston, infectious disease pathologists at Houston Methodist assessed the suitability and performance of the World Health Organization (WHO) nucleic acid amplification test. Their early adoption of this molecular test permitted them to rapidly identify infected patients and subsequently analyze the genomic variations among SARS-CoV-2 strains that were causing infections in the greater Houston area.

“We discovered that SARS-CoV-2, the virus that causes COVID-19, was introduced into Houston multiple independent times from diverse geographic regions, including Europe, Asia and South America,” Musser said. “This differs from studies done in New York City and Seattle, which found evidence of introductions mostly from either Europe or Asia, respectively. These findings are reflective of Houston being an ethnically diverse, international city and transportation hub.”

Houston Methodist physician-scientists were able to leverage their central molecular diagnostic laboratory that serves all its hospitals in the Houston area. This study tested specimens representing 40% of all confirmed cases in metropolitan Houston. This large percentage is likely due to being the first hospital-based facility to have molecular testing available.

The information gained from this study provides a critical resource that will help scientists understand the virus’ evolution and the origin of new infection spikes that will arise as social distancing guidelines are relaxed and the region reopens in the absence of herd immunity. It can also be relied upon to facilitate an enhanced public health response and may help guide public health authorities as they craft policy strategies and public health initiatives moving forward, including vaccine efforts.

Studying the virus since the earliest days the pandemic entered Houston has allowed the researchers to look for viral mutations that might impact antiviral resistance, vaccine development and other novel therapies.

“The good news is we didn’t find evidence for mutations in the virus that made any particular strains more severe,” said S. Wesley Long, M.D., Ph.D., a first author of the study. “This finding underscores the connection between severe disease and underlying health conditions.”

Another important discovery is that no resistance-related mutations were found to antiviral drugs like remdesivir, which has been emerging as a promising treatment possibility to fight the virus. In fact, the strains they studied would likely respond well to remdesivir, if this drug proves to be effective for treating COVID-19.

Long said they were also able to confirm there were no mutations of the virus that would render their existing tests useless or cause false negatives.

“These initial findings are just the first step in ongoing research studies of all SARS-CoV-2 isolates collected throughout the Houston Methodist health care system,” Long said. “Multiple additional studies are branching off from this work or making use of the genomic sequencing data to inform their own research. The realization of any goals will be in the weeks and months ahead, until the common goals of effective antiviral therapy and, hopefully, an effective vaccine are realized.”

Other collaborators on this study were Randall J. Olsen and Paul A. Christensen, who are also first authors on the paper, and David W. Bernard, Matthew Ojeda Saavedra, Concepcion C. Cantu, Prasanti Yerramilli, Layne Pruitt, Sishir Subedi, Heather Hendrickson, Ghazaleh Eskandari and Muthiah Kumaraswami with the Center for Molecular and Translational Human Infectious Diseases Research at the Houston Methodist Research Institute; Jason S. McLellan from the University of Texas at Austin; and James R. Davis, Maulik Shukla and Marcus Nguyen from the University of Chicago and Argonne National Laboratory.

This study was supported by the Houston Methodist Infectious Diseases Research Fund, the Fondren Foundation, Houston Methodist Hospital and Houston Methodist Research Institute; National Institutes of Health grants (AI146771-01 and AI139369-01) awarded to Musser and an NIH grant (AI127521) awarded to McLellan; Davis, Shukla and Nguyen are supported by the National Institute of Allergy and Infectious Diseases Bacterial and Viral Bioinformatics Resource Center Award (contract number 75N93019C00076); and Davis and Nguyen are funded by the U.S. Defense Advanced Research Projects Agency iSENTRY Friend or Foe program award (contract number HR0011937807).

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For more information: “Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas.” bioRxiv. (May 3, 2020) S.W. Long, R.J. Olsen, P.A. Christensen, D.W. Bernard, J.R. Davis, M. Shukla, M. Nguyen, M.O. Saavedra, C.C. Cantu, P. Yerramilli, L. Pruitt, S. Subedi, H. Hendrickson, G. Eskandari, M. Kumaraswami, J.S. McLellan and J.M. Musser; (Preprint DOI: https://doi.org/10.1101/2020.05.01.072652)

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