Houston Methodist COVID-19 study shows rapid spread and potential for mutant viruses

Molecular analysis of COVID-19’s powerful second wave in Houston – from May 12 to July 7 – shows a mutated virus strain linked to higher transmission and infection rates than the coronavirus strains that caused Houston’s first wave. Gene sequencing results from 5,085 COVID-positive patients tested at Houston Methodist since early March show a virus capable of adapting, surviving and thriving – making it more important than ever for physician scientists to understand its evolution as they work to discover effective vaccines and therapies.

In the second major gene sequencing study conducted by James M. Musser, M.D., Ph.D., chair of the Department of Pathology and Genomic Medicine at Houston Methodist, and his team of infectious disease pathologists, they found that the two waves affected different types of patients. The study, preprinted under the title “Molecular architecture of early dissemination and massive second wave of the SARS-CoV-2 virus in a major metropolitan area,” provides the first molecular characterization of SARS-CoV-2 strains causing two distinct COVID-19 disease waves, a problem now occurring extensively in many European countries.

Houston’s second wave hit significantly younger patients who had fewer underlying conditions and were more likely to be Hispanic/Latino living in lower income neighborhoods. In addition, virtually all COVID-19 strains studied during the second wave displayed a Gly614 amino acid replacement in spike protein – the part of the virus that mediates invasion into human cells, gives the coronavirus its telltale crown-like appearance and is the major focus of vaccine efforts worldwide. While this mutation has been linked with increased transmission and infectivity, as well as a higher virus load in the nasopharynx, which connects the nasal cavity with the throat, the mutation did not increase disease severity, researchers said.

The findings reinforce researchers’ concerns of the virus gaining momentum through naturally occurring mutations capable of producing mutant viruses that can escape vaccines – dubbed ‘escapians’ – or mutants that can resist drugs and other therapies.

“This extensive virus genome data gathered from Houston’s earliest cases to date, coupled with the growing database we are building at Houston Methodist, will help us identify the origins of new infection spikes and waves,” said Musser, who is corresponding author on the study. “This information can be an especially helpful community resource as schools and colleges re-open and public health constraints are further relaxed.”

Given the urgency of finding effective treatments for COVID-19, the preliminary report is posted to the preprint server medRxiv, and a manuscript is under peer-review at a prominent scientific journal. This preprint is not the final version of the article.

Wesley Long, M.D., Ph.D., a first author of the study, said it’s critical for people throughout the region, state and nation continue to keep preventive practices in place. “To avoid that third wave and keep cases low, we have to keep wearing masks and social distancing and testing and staying home if we’re sick,” Long said. “The virus is still out there and still circulating.”

The more scientists can understand about this pandemic and put it in context with what they understand about other coronaviruses, Long adds, the more able they may be to discover treatments or vaccines that might protect us from not just COVID-19, but also future pandemics.

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, Hoang A. T. Nguyen, J. Hunter Long and Muthiah Kumaraswami with the Center for Molecular and Translational Human Infectious Diseases Research at the Houston Methodist Research Institute; Hung-Che Kuo, Jule Goike, Jason S. McLellan, Chia-Wei Chou, Kamyab Javanmardi and Ilya J. Finkelstein from the University of Texas at Austin; Daniel Boutz and Jimmy Gollihar with the U.S. Army Combat Capabilities Development Command Army Research Laboratory at UT Austin; and James J. Davis, Maulik Shukl and Marcus Nguyen with the University of Chicago and Argonne National Laboratory.

This study was supported by funding from by the National Institutes of Health (grants AI127521, GM120554 and GM124141), Fondren Foundation, Welch Foundation (grant F-1808), National Science Foundation (grant 1453358), National Institute of Allergy and Infectious Diseases Bacterial and Viral Bioinformatics Resource Center award (contract number 75N93019C00076), U.S. Defense Advanced Research Projects Agency (DARPA) iSENTRY Friend or Foe program award (contract number HR0011937807), Houston Methodist Infectious Diseases Research Fund, Houston Methodist Hospital, Houston Methodist Research Institute and a Cancer Prevention and Research Institute of Texas Individual Investigator Research Award to UT Austin’s Ilya Finkelstein.

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For more information: “Molecular architecture of early dissemination and massive second wave of the SARS-CoV-2 virus in a major metropolitan area.” medRxiv. (Sept. 23, 2020) S. Wesley Long, Randall J. Olsen, Paul A. Christensen, David W. Bernard, James J. Davis, Maulik Shukla, Marcus Nguyen, Matthew Ojeda Saavedra, Concepcion C. Cantu, Prasanti Yerramilli, Layne Pruitt, Sishir Subedi, Hung-Che Kuo, Heather Hendrickson, Ghazaleh Eskandari, Hoang A. T. Nguyen, J. Hunter Long, Muthiah Kumaraswami, Jule Goike, Daniel Boutz, Jimmy Gollihar, Jason S. McLellan, Chia-Wei Chou, Kamyab Javanmardi, Ilya Finkelstein and James M. Musser; (Preprint DOI: https://doi.org/10.1101/2020.09.22.20199125)

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