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Is the COVID-19 Pandemic Evolving?

“Change is the only constant in life.” Heraclitus


“The only thing that makes life possible is permanent, intolerable uncertainty; not knowing what comes next.” Ursula K. Le Guin, American author

Coronavirus infections are surging throughout Europe, where health officials are warning infection rates in the coming months could mirror those of this past spring. The number of COVID-19 cases has also been climbing in the US. These numbers are disappointing. Some cases may be attributable to relaxed social distancing and less attention to wearing masks, especially among young people. But a greater concern of every epidemiologist and virologist is gene mutation: that is, whether mutations of SARS-Co-V-2, the coronavirus that causes COVID-19, are also playing a role in the uptick of cases. In this Germ Gem post, I discuss the evidence in support of this mutation hypothesis. Before embarking on the issue of how genetic changes of SARS-CoV-2 could influence the future of the COVD-19 pandemic, I review some basic aspects of genes for the lay reader.

Genes—Some Basics. The main function of genes is to encode for (produce) proteins—the building blocks of all cells. Genes are made of either DNA or RNA. While DNA generally captures most of the attention, RNA should be on everyone’s radar. Some scientists theorize that RNA was actually the first genetic molecule to arise on Earth around 4 billion years ago. It arose in a primitive form that later evolved into the RNA and DNA molecules that we have in life today.

The sum total of an organism’s genes is called the genome. The genomes of most organisms are based on DNA. Many very nasty viruses that cause human disease, however, have RNA-based genomes. As a rule, viral RNA genomes are much more mutation-prone than those based on DNA. For example, viruses with RNA-based genomes cause influenza and HIV. And both of these viruses have a proclivity to mutate. In the case of influenza, the composition of the flu vaccine has to be changed every year to account for the gene mutation. Whereas in the case of HIV infection, rapid emergence of mutations to drugs requires that patients be treated simultaneously with multiple antiviral drugs to counteract the mutations.

All viruses must gain access to cells in order to survive. In the case of SARS-CoV-2, the spike (S) protein is the key that gives the virus entry into human cells via ACE-2 receptors. And, importantly, the S protein is the major target of many of the vaccines that are in development.

SARS-CoV-2 genome. The seven types of coronaviruses (SARS-CoV-2 included) that are known to infect humans are all RNA viruses. All viruses that have a RNA genome are known to have a high mutation rate. Each time this viral genome replicates, it can generate quasispecies—a viral population with diverse genomes. Such mutations can contribute to differences in clinical outcomes of the disease, for example, its contagiousness and severity.

Since the beginning of the pandemic in December 2019, scientists have been tracking the genomes of SARS-CoV-2. By January 12, 2020, five genomes of SARS-CoV-2 had been isolated, and by the end of that month the number of genomes increased to 42. As of May 7, 2020, 4,690 SARS-CoV-2 genomes sampled on six continents were publicly available. In July 2020, researchers reported that a more infectious SARS-CoV-2 variant with spike protein G614 had replaced D614 as the dominant form in the pandemic.

Tracking of the SARS-CoV-2 genome is proceeding globally. In one recent study in Houston, Texas the genomes of 5,085 strains causing two COVID-19 disease waves were sequenced. Virtually all strains in the second massive wave were a G614 variant that was linked to increased transmission and infectivity. Patients infected with this variant had significantly higher nasopharyngeal viral loads. We do not know exactly how these more contagious viral strains emerged. But we do know that to ensure its survival the virus needs to get into human cells, and therefore it would certainly be advantageous to be more readily transmissible to human hosts.

Human genome and susceptibility to COVID-19. At the same time that studies of the SARS-CoV-2 genome have been underway to determine how its genome affects infectivity and virulence, researchers have been searching the human genome to see if there are genes that confer resistance or susceptibility to severe infection to COVID-19. In one such study, published in July 2020 in the Journal of the American Association of Medicine, two separate families of patients were described with a rare variant of an innate immune-sensing gene called “toll-like receptor 7”. Young males who inherited this gene on a copy of their X chromosome experienced severe COVID-19 disease.

In a July 4, 2020 New York Times article, “DNA Inherited from Neanderthals May Increase Risk of Covid-19,” Carl Zimmer reported the recent finding that a stretch of DNA in the human genome that was passed down to Homo sapiens by interbreeding with Neanderthals 60,000 years ago increases the risk of severe COVID-19. Such studies devoted to examining the genetic determinants of the severity of the illness are improving our understanding of the pathogenesis of COVID-19.

What’s next? One thing that’s become abundantly clear about the COVID-19 pandemic is that SARS-CoV-2 is full of surprises. But this is an RNA virus. Therefore, we shouldn’t be at all surprised by its disturbing capacity to throw us curveballs by evolving genetically. While we need to be hopeful that the virus’s ability to mutate doesn’t confound the long-term efficacy of vaccines that are on the horizon, it remains essential that we continue to avoid crowds, practice social distancing, wear masks, and wash our hands frequently. Nobody knows when, but someday we will even wash our hands of this virus!

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

 

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© 2020 by Phillip K. Peterson
Germ Gems is a Trademark of Phillip K. Peterson