Newer variant of COVID-19-causing virus dominates global infections

Newer variant of COVID-19

Research out today in the journal Cell shows that a specific change in the SARS-CoV-2 coronavirus virus genome, previously associated with increased viral transmission and the spread of COVID-19, is more infectious in cell culture. The variant in question, D614G, makes a small but effective change in the virus's 'Spike' protein, which the virus uses to enter human cells.

Bette Korber, a theoretical biologist at Los Alamos National Laboratory and lead author of the study, noted, "The D614G variant first came to our attention in early April, as we had observed a strikingly repetitive pattern. All over the world, even when local epidemics had many cases of the original form circulating, soon after the D614G variant was introduced into a region it became the prevalent form."

Geographic information from samples from the GISAID COVID-19 viral sequence database enabled tracking of this highly recurrent pattern, a shift in the viral population from the original form to the D614G variant. This occurred at every geographic level: country, subcountry, county, and city.

Two independent lines of experimental evidence that support these initial results are included in today's paper. These additional experiments, led by Professor Erica Ollmann Saphire, Ph.D., at the La Jolla Institute, and by Professor David Montefiori, Ph.D., at Duke University, showed that the D614G change increases the virus's infectivity in the laboratory. These new experiments, as well as more extensive sequence and clinical data and improved statistical models, are presented in the Cell paper. More in vivo work remains to be done to determine the full implications of the change.

The SARS-CoV-2 virus has a low mutation rate overall (much lower than the viruses that cause influenza and HIV-AIDS). The D614G variant appears as part of a set of four linked mutations that appear to have arisen once and then moved together around the world as a consistent set of variations.

"It's remarkable to me," commented Will Fischer of Los Alamos, an author on the study, "both that this increase in infectivity was detected by careful observation of sequence data alone, and that our experimental colleagues could confirm it with live virus in such a short time."

Fortunately, "the clinical data in this paper from Sheffield showed that even though patients with the new G virus carried more copies of the virus than patients infected with D, there wasn't a corresponding increase in the severity of illness," said Saphire, who leads the Gates Foundation-supported Coronavirus Immunotherapy Consortium (CoVIC).

Korber noted, "These findings suggest that the newer form of the virus may be even more readily transmitted than the original form -- whether or not that conclusion is ultimately confirmed, it highlights the value of what were already good ideas: to wear masks and to maintain social distancing."

Research partners from Los Alamos National Laboratory, Duke University, and the University of Sheffield initially published work on this analysis on the bioRxiv site in an April 2020 preprint. That work also included observations of COVID-19 patients from Sheffield that suggested an association of the D614G variant with higher viral loads in the upper respiratory tract.

"It is possible to track SARS-CoV-2 evolution globally because researchers worldwide are rapidly making their viral sequence data available through the GISAID viral sequence database," Korber said. Currently tens of thousands of sequences are available through this project, and this enabled Korber and the research team to identify the emergence of the D614G variant.

GISAID was established to encourage collaboration among influenza researchers, but early in the epidemic the consortium established a SARS-CoV-2 database, which soon became the de facto standard for sharing outbreak sequences among researchers worldwide.

The study, "Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus" was supported by the Medical Research Council (MRC) part of UK Research & Innovation (UKRI the National Institute of Health Research (NIHR); Genome Research Limited, operating as the Wellcome Sanger Institute; CoVIC, INV-006133 of the COVID-19 Therapeutics Accelerator, supported by the Bill and Melinda Gates Foundation, Mastercard, Wellcome; private philanthropic support, as well as the Overton family; a FastGrant, from Emergent Ventures, in aid of COVID-19 research; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Interagency Agreement No. AAI12007-001-00000, and the Los Alamos Laboratory Directed Research and Development program.

Additional study authors included S. Gnanakaran, H. Yoon, J. Theiler, W. Abfalterer, N. Hengartner, E.E. Giorgi, T. Bhattacharya, B. Foley, K.M. Hastie, M.D. Parker, D.G. Partridge, C.M. Evans, T.M. Freeman, T.I. de Silva, C. McDanal, L.G. Perez, H. Tang, A. Moon-Walker, S.P. Whelan, C.C. LaBranche.

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Materials provided by DOE/Los Alamos National Laboratory. Note: Content may be edited for style and length.

Journal Reference:

1. B. Korber, W.M. Fischer, S. Gnanakaran, H. Yoon, J. Theiler, W. Abfalterer, N. Hengartner, E.E. Giorgi, T. Bhattacharya, B. Foley, K.M. Hastie, M.D. Parker, D.G. Partridge, C.M. Evans, T.M. Freeman, T.I. de Silva, C. McDanal, L.G. Perez, H. Tang, A. Moon-Walker, S.P. Whelan, C.C. LaBranche, E.O. Saphire, D.C. Montefiori, on behalf of theSheffield COVID-19 Genomics Group. Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell, July 2, 2020; DOI: 10.1016/j.cell.2020.06.043

High temperatures due to global warming will be dramatic even for tardigrades

Tardigrade (stock image).

Global warming, a major aspect of climate change, is already causing a wide range of negative impacts on many habitats of our planet. It is thus of the utmost importance to understand how rising temperatures may affect animal health and welfare.

A research group from Department of Biology, University of Copenhagen has just shown that tardigrades are very vulnerable to long-term high temperature exposures. The tiny animals, in their desiccated state, are best known for their extraordinary tolerance to extreme environments.

In a study published recently in Scientific Reports, Ricardo Neves and Nadja Møbjerg and colleagues at Department of Biology, University of Copenhagen present results on the tolerance to high temperatures of a tardigrade species.

Tardigrades, commonly known as water bears or moss piglets, are microscopic invertebrates distributed worldwide in marine, freshwater and terrestrial microhabitats.

Ricardo Neves, Nadja Møbjerg and colleagues investigated the tolerance to high temperatures of Ramazzottius varieornatus, a tardigrade frequently found in transient freshwater habitats.

"The specimens used in this study were obtained from roof gutters of a house located in Nivå, Denmark. We evaluated the effect of exposures to high temperature in active and desiccated tardigrades, and we also investigated the effect of a brief acclimation period on active animals," explains postdoc Ricardo Neves.

Rather surprisingly the researchers estimated that for non-acclimated active tardigrades the median lethal temperature is 37.1°C, though a short acclimation periods leads to a small but significant increase of the median lethal temperature to 37.6°C. Interestingly, this temperature is not far from the currently measured maximum temperature in Denmark, i.e. 36.4°C. As for the desiccated specimens, the authors observed that the estimated 50% mortality temperature is 82.7°C following 1 hour exposures, though a significant decrease to 63.1°C following 24 hour exposures was registered.

The research group used logistic models to estimate the median lethal temperature (at which 50% mortality is achieved) both for active and desiccated tardigrades.

Approximately 1300 tardigrade species have been described so far. The body of these minute animals is barrel-shaped (or dorsoventrally compressed) and divided into a head and a trunk with four pairs of legs. Their body length varies between 50 micrometers and 1.2 millimeters. Apart from their impressive ability to tolerate extreme environments, tardigrades are also very interesting because of their close evolutionary relationship with arthropods (e.g., insects, crustaceans, spiders).

As aquatic animals, tardigrades need to be surrounded in a film of water to be in their active state (i.e., feeding and reproducing). However, these critters are able to endure periods of desiccation (anhydrobiosis) by entering cryptobiosis, i.e., a reversible ametabolic state common especially among limno-terrestrial species. Succinctly, tardigrades enter the so-called "tun" state by contracting their anterior-posterior body axis, retracting their legs and rearranging the internal organs. This provides them with the capacity to tolerate severe environmental conditions including oxygen depletion (anoxybiosis), high toxicant concentrations (chemobiosis), high solute concentration (osmobiosis) and extremely low temperatures (cryobiosis).

The extraordinary tolerance of tardigrades to extreme environments includes also high temperature endurance. Some tardigrade species were reported to tolerate temperatures as high as 151°C. However, the exposure time was only of 30 minutes. Other studies on thermotolerance of desiccated (anhydrobiotic) tardigrades revealed that exposures higher than 80°C for 1 hour resulted in high mortality, with almost all specimens dying at temperatures above 103°C. It remained, yet, unknown how anhydrobiotic tardigrades handle exposures to high temperatures for long periods, i.e., exceeding 1 hour.

"From this study, we can conclude that active tardigrades are vulnerable to high temperatures, though it seems that these critters would be able to acclimatize to increasing temperatures in their natural habitat. Desiccated tardigrades are much more resilient and can endure temperatures much higher than those endured by active tardigrades. However, exposure-time is clearly a limiting factor that constrains their tolerance to high temperatures," says Ricardo Neves.

Indeed, although tardigrades are able to tolerate a diverse set of severe environmental conditions, their endurance to high temperatures is noticeably limited and this might actually be the Achilles heel of these otherwise super-resistant animals.

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Materials provided by Faculty of Science - University of Copenhagen. Note: Content may be edited for style and length.