HudsonAlpha ED Guidebook 2021_22

NEW FINDINGS — BACTERIA AND VIRUSES

Genetic clues from the 1918 influenza pandemic Although the 1918-19 flu pandemic spread around the globe in three different waves, the second and third were much deadlier than the first. An analysis of viral RNA from preserved patient tissue may bring us closer to understanding how the virus became more lethal.

immune response. First wave samples were more similar to influenza sequences from birds, where the virus is thought to have originated. This suggests the virus gained mutations in this gene between the first and second wave, allowing it to better evade the early immune response and spread unchallenged. The third German sample contained changes in genes for the poly- merase complex, which makes copies of the viral genome as part of the infection process. The altered copying complex was recreated in laboratory cells (no other part of the virus was reproduced). The complex was only half as active as the copying proteins from later viral strains. While it’s difficult to compare controlled lab experiments to real-world human infections, this data hints that early versions of the virus were less efficient at reproducing inside humans. This also may have contributed to the milder first wave. REFERENCE: Patroro L.V. et al. Archival influenza virus genomes from Europe reveal genomic and phenotypic variability during the 1918 pandemic. BioRxiv (2021) https://www.biorxiv.org/content/10.1101/2021.05.14.444134v1. Accessed 28 August 2021. Preprint. vaccines. The Centers for Disease Control’s national SARS-CoV-2 genomic surveillance program (https://covid.cdc.gov/covid-da- ta-tracker/#variant-proportions) identifies and tracks variants circulating in the United States. The human genome has also been a focus of pandemic-related health research, searching for genetic changes that impact our immune response to viral infection. The COVID-19 Host Genetics Initiative analyzed genetic markers from nearly 50,000 COVID-19 patients and 2 million controls across 19 countries. Thirteen regions of the genome were associated with susceptibility to infection or severe illness. Nine of those regions contain biologi- cally plausible genes, several linked to immune function or genes normally expressed in the lungs.

influenza virus

Viral RNA was extracted and sequenced from preserved museum samples of lung tissue collected throughout Germany during 1918- 19. Three were positive for the influenza A strain and two of these were definitively dated to the milder first wave. These were compared to previously sequenced samples from later waves. Several changes were observed in a gene that helps the virus evade the body’s initial

Genomic studies and COVID-19 Genetic tools have been critical to help scientists understand and respond to the COVID-19 pandemic. Genomic sequencing first determined the SARS-CoV-2 virus was responsible for the unidentified cluster of respiratory infections in the Wuhan prov- ince of China. Scientists sequenced genetic material from patient samples and analyzed the non-human genetic fragments. They determined a new member of the coronavirus family was causing the infection. Early studies also found the genetic recipe of the novel virus was very similar to bat coronaviruses, suggesting the virus likely originated in bats. Once laboratories knew the genetic sequence, they could develop tests to diagnose infections. These tests use a technology called polymerase chain reaction (PCR) to detect small amounts of genetic material from the virus. PCR-based tests are the gold standard for diagnosing COVID-19. To reduce costs and maximize impact, some labs combine small amounts of individual patient samples into a single pool. If the pool tests negative, all samples are virus free. If the pool tests positive, researchers test each of the initial samples to determine which contains the virus. A modified version of PCR testing can detect the virus in waste- water samples. This gives college campuses, hospitals, and neighborhoods an important early detection tool. A small fraction of virus samples from patients undergo a genomic "deep dive" to track how the virus changes over time. A worldwide network of labs scans these viral genomes for changes in the genetic recipe (also called variants or mutations). All viruses undergo these modifications over time. Most are un- important, but some alter how the virus infects people or how ill it can make patients. Viral sequencing lets public health experts track the spread of different strains. The alpha, beta, and delta variants are examples of these changes. Researchers then de- termine if the strains are more or less transmissible, have a dif- ferent risk of serious illness, and respond to current treatments/

HudsonAlpha has a number of educational resources related to the COVID-19 pandemic. The initial sequencing of the SARS-CoV-2 virus is discussed in the Shareable Science blogpost The Genetics of Coronavirus. The process of genomic surveillance is explained in the Everyday DNA blogpost Genomic surveillance: using the genome to track and monitor viruses. Lastly, there are more than 70 COVID-specific videos on the Shareable Science beyond the blog site.

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