Enlarge / SOUTH TANGERANG, INDONESIA - JANUARY 7, 2021: A patient recovered from COVID-19 donate plasma at Indonesia Red Cross Transfusion Center in South Tangerang. (credit: Barcroft Media / Getty Images )

It's clear that the immune system can mount a robust response to SARS-CoV-2, as the vaccine trials have made clear. Beyond that, though, there are a lot of question marks. People exposed to the virus don't always produce much in the way of antibodies to it, and there have been a number of cases of reinfection. We're not sure how long immunity lasts or whether it correlates with antibody levels or something else–there hasn't even been great evidence that antibodies are helpful.

To give some sense of the challenge of sorting all of this out, we're going to look at three recently published papers that get at the interplay between the immune system and COVID-19. One finally provides some evidence that antibodies might be protective, another indicates that tamping down the inflammatory response might help, while the third suggests that immunosuppressives don't affect disease outcomes at all.

Antibodies good

Antibodies are a relatively easy way to track an immune response, and they've been used for that throughout the pandemic. But early studies found the number of antibodies produced in response to an infection varied dramatically between patients. There have also been clinical trials testing whether using antibodies obtained from those formerly infected could help treat those suffering from COVID-19 symptoms, with the FDA eventually granting this a controversial Emergency Use Authorization. President Trump also received an experimental treatment of mass produced SARS-CoV-2-specific antibodies.

Enlarge / Large flock of jackdaws in silhouette flying in the evening sky over the trees. (credit: iStock / Getty Images Plus )

There's rarely time to write about every cool science-y story that comes our way. So this year, we're once again running a special Twelve Days of Christmas series of posts, highlighting one science story that fell through the cracks in 2020, each day from December 25 through January 5. Today: why flocks of jackdaws will change their flying patterns depending on whether they are returning to roost, or banding together to drive away predators.

Flocks of wild jackdaws will change their flying patterns depending on whether they are returning to roost or banding together to drive away predators, according to research originally slated to be presented at the 2020 APS March Meeting, which was cancelled due to the coronavirus pandemic. The work builds upon earlier findings published in a November 2019 paper in Nature Communications. This could one day lead to the development of autonomous robotic swarms capable of changing their interaction rules to perform different tasks in response to environmental cues.

Co-author Nicholas Ouellette (no relation), a physicist-turned-environmental engineer at Stanford University, has long been fascinated by biological swarms after noting how flocks of starlings in flight formed unusual patterns that, to his physicist's eye, looked a lot like turbulence. He thought there must be underlying mechanisms behind the formation of those patterns—possibly even a set of universal laws that could apply to collective behavior across different species.

Enlarge / Ophelia (1852) by John Everett Millais, inspired by the character in Shakespeare's Hamlet , who goes mad and drowns in a brook. It can be challenging for forensic scientists to determine how long a dead body has been submerged in water.

There's rarely time to write about every cool science-y story that comes our way. So this year, we're once again running a special Twelve Days of Christmas series of posts, highlighting one science story that fell through the cracks in 2020, each day from December 25 through January 5. Today: identifying potential biomarkers (in mice) for pegging time of death in waterlogged corpses.

Correctly estimating time of death looks so easy in fictional police procedurals, but it's one of the more challenging aspects of a forensic pathologist's job. This is particularly true for corpses found in water, where a multitude of additional variables make it even more difficult to determine how long a body has been submerged. A team of scientists at Northumbria University in Newcastle, UK, have hit upon a new method for making that determination, involving the measurement of levels of certain proteins in bones. They described their findings in an April paper in the Journal of Proteome Research.

Co-author Noemi Procopio has been interested in forensic science since she was 14, but initially studied biotechnology because her home country of Italy didn't have forensic science programs. When she moved to the University of Manchester in the UK to complete her PhD, she chose to specialize in the application of proteomics  (the large-scale study of proteins) to the field, thanks to the influence of a former supervisor, an archaeologist who applied proteomics to bones.

Enlarge / Sampling microbes from Leonardo da Vinci's Portrait of a Man in Red Chalk (1512). (credit: Guadalupe Piñar et al.)

Microbiomes are all the scientific rage, even in art conservation, where studying the microbial species that congregate on works of art may lead to new ways to slow down the deterioration of priceless aging artwork, as well as potentially unmask counterfeits. For instance, scientists have analyzed the microbes found on seven of Leonardo da Vinci's drawings, according to a recent paper published in the journal Frontiers in Microbiology. And back in March, scientists at the J. Craig Venter Institute (JCVI) collected and analyzed swabs taken from centuries-old art in a private collection housed in Florence, Italy, and published their findings in the journal Microbial Ecology.

The researchers behind the earlier March paper were JCVI geneticists who collaborated with the Leonardo da Vinci DNA Project in France. The work built on a prior study looking for microbial signatures and possible geographic patterns in hairs collected from people in the District of Columbia and San Diego, California. They concluded from that analysis that microbes could be a useful geographic signature.

For the March study, the JCVI geneticists took swabs of microbes from Renaissance-style pieces and confirmed the presence of so-called "oxidase positive" microbes on painted wood and canvas surfaces. These microbes munch on the compounds found in paint, glue, and cellulose (found in paper, canvas, and wood), in turn producing water or hydrogen peroxide as byproducts.

Enlarge (credit: Eric Sonstroem / Flickr )

Did anyone have "mink farms" on their 2020 catastrophe bingo cards? It turns out that the SARS-CoV-2 virus readily spreads to mink, leading to outbreaks on mink farms in Europe and the United States . Denmark responded by culling its entire mink population, which naturally went wrong as mink bodies began resurfacing from their mass graves, forcing the country to rebury them . Because 2020 didn't seem apocalyptic enough.

More seriously, health authorities are carefully monitoring things like mink farms because the spread of the virus to our domesticated animals raises two risks. One is that the virus will be under different evolutionary selection in these animals, producing mutant strains that then pose different risks if they transfer back to humans. So far, fortunately, that seems not to be happening . The second risk is that these animals will provide a reservoir from which the virus can spread back to humans, circumventing pandemic control focused on human interactions.

Heightening those worries, mid-December saw a report that the US Department of Agriculture had found a wild mink near a mink farm that had picked up the virus, presumably from its domesticated peers. Fortunately, so far at least, the transfer to wild populations seems very limited.

Enlarge (credit: CDC.gov )

A variant of the pandemic coronavirus, SARS-CoV-2, is now dominating headlines and inspiring precautionary travel bans worldwide. But scientists are still trying to get a grip on what the variant can actually do differently and what it might mean for the nearly year-old pandemic.

Researchers in the United Kingdom—where the variant was identified and is now rapidly circulating—suggested it may be up to 70 percent more transmissible than other SARS-CoV-2 strains, stoking fear of surges-upon-surges of disease on the eve of year-end holidays. But other researchers are now rapidly working to collect data on the variant's interactions with human cells and immune responses to see if those interactions differ from those seen by other SARS-CoV-2 strains.

What we know

While much remains to be known about the variant, dubbed B.1.1.7, there are some reassuring aspects. For one thing, it's normal for viruses to accumulate the small genetic changes, such as those that created the new UK variant (more on that below). Many other variants have been identified throughout the pandemic, and none has spawned any nightmare scenarios.

Enlarge / Researchers have looked at whether there are genetic influences on who experiences a case of severe COVID-19. (credit: ALBERTO PIZZOLI / Getty Images )

The body's response to SARS-CoV-2 infection range from imperceptible to death, raising an obvious question: what makes the difference? If we could identify the factors that make COVID-19 so dangerous for some people, we could do our best to address these factors, and provide extra protections for those who are at highest risk. But aside from the obvious&dmash;health disparities associated with poverty and race seem to be at play here, too—we've had trouble identifying the factors that make a difference.

A recently published study takes a look at one potential influence: genetics. In a large study of UK COVID-19 patients, researchers have found a number of genes that appear to be associated with severe cases, most of them involved in immune function. But the results don't clarify how immune function is linked to the disease's progression.

All in the genes

The work took place in the UK, one of the countries involved in the GenOMICC ( Genetics Of Mortality In Critical Care ) project, which has already been exploring the genetics underlying hospitalization for communicable diseases. For the new study, the researchers worked with over 200 intensive care units in the UK to identify study participants. All told, they managed to get genetic data for over 2,700 critical COVID-19 patients. These were matched with people in the UK's Biobank who had similar demographics in order to provide a control population. The one weakness of this design is that some people in the Biobank may be susceptible to severe COVID-19 but simply haven't been infected yet, which would tend to weaken any genetic signals.

Enlarge / Richard Watkins,49, (in bed) is suffering from complications caused by Sickle cell disease. (credit: Washington Post/Getty Images )

Gene therapy has had a long and sometimes difficult history. Plenty of human genetic disorders can be traced to problems with a single gene, and that makes them a tempting target for correction. But someone died in a very early gene-therapy trial, which set the entire field back considerably. And, despite a far more cautious approach, the risks are still considerable, as two deaths during a trial occurred just this year .

But for researchers in the field, and those suffering from genetic diseases, this week provides some hope that the field's long-delayed promise might eventually be met. At a virtual scientific conference, a group presented the results of a large safety trial that saw 50 of 52 patients able to discontinue treatments for hemophilia. And a separate paper describes the use of CRISPR gene-editing and a blood stem cell transplant to successfully treat patients with sickle cell anemia or a related disorder.

Restoring clotting

The hemophilia trial was typical of most early efforts at gene therapy. In this case, the disease is caused by a defect in a single gene, so providing cells with a new copy will correct the problem. And, since the protein that's encoded by that gene circulates in the blood, you don't have to target a small and potentially difficult-to-access population of cells in order to correct things—targeting a new copy of the gene to any cells that can export proteins to the bloodstream will work.

Enlarge / Proteins rapidly form complicated structures which had proven difficult to predict. (credit: Argonne National Lab )

Today, DeepMind announced that it had seemingly solved one of biology's outstanding problems: how the string of amino acids in a protein folds up into a three-dimensional shape that enables their complex functions. It's a computational challenge that has resisted the efforts of many very smart biologists for decades, despite the application of supercomputer-level hardware for these calculations. DeepMind instead trained its system using 128 specialized processors for a couple of weeks; it now returns potential structures within a couple of days.

The limitations of the system aren't yet clear—DeepMind says it's currently planning on a peer-reviewed paper, and has only made a blog post and some press releases available. But it clearly performs better than anything that's come before it, after having more than doubled the performance of the best system in just four years. Even if it's not useful in every circumstance, the advance likely means that the structure of many proteins can now be predicted from nothing more than the DNA sequence of the gene that encodes them, which would mark a major change for biology.

Between the folds

To make proteins, our cells (and those of every other organism) chemically link amino acids to form a chain. This works because every amino acid shares a backbone that can be chemically connected to form a polymer. But each of the 20 amino acids used by life has a distinct set of atoms attached to that backbone. These can be charged or neutral, acidic or basic, etc., and these properties determine how each amino acid interacts with its neighbors and the environment.