With a 130-foot antenna, MARSIS flies over the planet, bouncing radio waves over a selected area and then receiving and analyzing the echoes or reflections. Any near-surface liquid water should send a strong bright signal, whereas the radar signal for ice and rock would be much smaller.

Because conventional models assume the Mars south polar cap experiences temperatures much lower than the melting point of water, many scientists have questioned the presence of liquid water. Clay, hydrated salts and saline ices have been proposed as potential explanations for the source of the bright basal reflections. The Italian-led team investigating the proposed phenomena used previously published data, simulations and new laboratory measurements.

“Lakes of liquid water actually exist beneath glaciers in Arctic and Antarctic regions, so we have Earth analogs for finding liquid water below ice,” said Stillman, a specialist in detecting water in any format — liquid, ice or absorbed — on planetary bodies and co-author of a paper describing these findings. “The exotic salts that we know exist on Mars have amazing ‘antifreeze’ properties allowing brines to remain liquid down to -103 degrees Fahrenheit. We studied these salts in our lab to understand how they would respond to radar.”

Stillman has over a decade of experience measuring the properties of materials at cold temperatures to detect and characterize subsurface ice, unfrozen water and the potential for life throughout the solar system. For this project, Stillman measured the properties of perchlorate brines in an SwRI environmental chamber that produces near-liquid-nitrogen temperatures at Mars-like pressures.

“My Italian colleagues reached out to see if my laboratory experiment data would support the presence of liquid water beneath the Martian ice cap,” Stillman said. “The research showed that we don’t have to have lakes of perchlorate and chloride brines, but that these brines could exist between the grains of ice or sediments and are enough to exhibit a strong dielectric response. This is similar to how seawater saturates grains of sand at the shoreline or how flavoring permeates a slushie, but at -103 degrees Fahrenheit below a mile of ice near the South Pole of Mars.”

The search for water in the cosmos is rooted in searching for potential habitability, because all known life requires water.

“In this case ‘following the water’ has led us to place so cold that life as we know it couldn’t flourish,” Stillman said. “But it’s still interesting, and who knows what evolutionary paths extraterrestrial life may have taken?”

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The treatment, known as convalescent plasma, is still considered experimental by the U.S. Food and Drug Administration (FDA). Plasma contains antibodies, blood proteins that are part of the immune system. Shaped so they can attach to the virus that causes COVID-19, SARS-CoV-2, antibodies glom onto and tag it for removal from the body, researchers say.

Led by researchers at NYU Grossman School of Medicine, the study showed that among 2,341 men and women, those who received an injection of convalescent plasma soon after hospitalization were 15% less likely to die within a month from COVID-19 than those who did not receive convalescent plasma or those who received an inactive saline placebo.

Notably, the researchers found that the biggest benefits for the therapy were among patients most at risk for severe complications because of pre-existing conditions, such as diabetes or heart disease. The treatment, which contains antibodies and other immune cells needed to fight the infection, also appears to benefit those with type A or AB blood.

“Our results show that, overall, patients hospitalized with COVID-19 may derive modest benefit from convalescent plasma, with some patient subgroups benefiting more than others,” says study lead investigator and biostatistician Andrea Troxel, ScD. With respect to the groups most likely to benefit, the FDA on Dec. 28, 2021, revised the Emergency Use Authorization for convalescent plasma, limiting its use to patients with diseases that suppress their immune systems, or that receive medical treatments with the same effect.

“Patients with co-existing disease were most likely to show improvement from convalescent plasma, probably because they have the most difficulty producing antibodies to fight their infection,” adds Troxel. “The infused plasma boosts their body’s ability to fight the virus, but only in the early stage of the disease and before the illness overwhelms their body.”

The current study findings, published in the journal JAMA Network Open online Jan. 25, come from the pooling of patient information from eight recently completed studies in the United States, Belgium, Brazil, India, the Netherlands, and Spain on the effects of convalescent plasma for COVID-19.

These benefits of the treatment are only likely to become clear as more data from the trials become available, says Troxel, a professor in the Department of Population Health at NYU Langone. This is because the data from individual trials are too small to show the treatment’s overall impact on subsets of patients, she says. Some individual studies have showed the therapy to be ineffective or of limited value.

Study co-investigator Eva Petkova, PhD, says the team is using its study data to create a scoring system of patient descriptors, including age, stage of COVID-19, and co-existing diseases, making it easier for clinicians to calculate who stands to benefit most from use of convalescent plasma.

“Our treatment benefit index is designed to serve as a quick and effective tool for physicians to use in deciding when to administer convalescent plasma for COVID-19,” says Petkova, a professor in the Departments of Population Health and Child and Adolescent Psychiatry at NYU Langone.

For the study, researchers grouped all patient information from smaller, separate clinical investigations about convalescent plasma therapy, including trials at NYU Langone, Albert Einstein College of Medicine and Montefiore Medical Center, Zuckerberg San Francisco General Hospital, and the University of Pennsylvania in Philadelphia. Researchers hoped any benefits or disadvantages in treatment would be easier to spot among the largest possible sample of patients. All trials were randomized and controlled, meaning that the patient had a random chance of being assigned to receive convalescent plasma or not to receive it.

Included in the analysis were data from another multicenter U.S. study published separately in December 2021 in JAMA Internal Medicine. That study in 941 patients hospitalized with COVID-19 showed that patients receiving high doses of convalescent plasma therapy and not on other medications, such as remdesivir or corticosteroids, were likely to benefit from the blood plasma treatment. Study co-primary investigator Mila Ortigoza, MD, PhD, an assistant professor in the Departments of Medicine and Microbiology at NYU Langone, says these initial results supported the idea that convalescent plasma could be a feasible treatment option, especially when other therapies are not yet available, as at the beginning of a pandemic.

In addition, convalescent plasma collected from previously infected and subsequently vaccinated donors (VaxPlasma) would contain antibodies in high enough quantities and diversity that could provide added protection against emerging viral variants, says Ortigoza. Viruses typically mutate genetically (acquire random changes in their DNA or RNA codes) over the course of any pandemic. For this reason, convalescent plasma has the potential to offer effective treatment more quickly after such mutations than treatment types that tend to become less effective with time and must undergo a re-design process to address a new variant, such as monoclonal antibody treatments.

Besides Troxel, Petkova, and Ortigoza, other NYU Langone researchers involved in the studies are Keith Goldfeld, DrPh; Mengling Liu, PhD; Hyung Park, PhD; Thaddeus Tarpey, PhD; Yinxiang Wu, MA; Danni Wu, MS; Yi Li, MS; Corita Grudzen, MD; and Judith Hochman, MD. Other study investigators include Anup Agarwal, MD; Gunjan Kumar, MD; and Aparna Mukherjee, MD, PhD; at the Indian Council of Medical Research in New Delhi; Cristina Avendaño-Sola, MD; Rafael Duarte, MD, PhD, and Arantxa Sancho-Lopez, MD; at the Hospital Universitario Puerta de Hierro Majadahonda in Madrid, Spain; Emma Bainbridge, MD, MPH; Priscilla Hsue, MD; and Annie Luetkemeyer, MD; at the University of California San Francisco; Katherine Bar, MD; and Pamela Shaw, PhD; at the University of Pennsylvania in Philadelphia (now at Kaiser Permanente); Timothy Devos, MD, PhD; and Geert Meyfroidt, MD, PhD; at Katholieke Universiteit in Leuven, Belgium; André Nicola, MD, PhD; at the University of Brasilia in Brazil; Liise-Anne Pirofski, MD, PhD; and Hyun-Ah Yoon, MD; at Albert Einstein College of Medicine in New York City; Bart Rijnders, MD, PhD; and Casper Rokx, MD, PhD; at Erasmus University in the Netherlands; and Elliott Antman, MD, at Harvard University in Boston. Funding support for the studies was provided by National Institutes of Health grant UL1TR001445.

A new study finds that two forms of immunity — breakthrough infections following vaccination or natural infection followed by vaccination — provide roughly equal levels of enhanced immune protection.

The new study published online today in the journal Science Immunology.

“It makes no difference whether you get infected-and-then-vaccinated, or if you get vaccinated-and-then-a-breakthrough infection,” said co-senior author Fikadu Tafesse, Ph.D., assistant professor of molecular microbiology and immunology in the OHSU School of Medicine. “In either case, you will get a really, really robust immune response — amazingly high.”

The research follows an OHSU study published in December that described extremely high levels of immune response following breakthrough infections — so-called “super immunity.” That study was the first to use multiple live SARS-CoV-2 variants to measure cross-neutralization of blood serum from breakthrough cases.

The new study found that it doesn’t matter whether someone gets a breakthrough infection or gets vaccinated after a natural infection. In both cases, the immune response measured in blood serum revealed antibodies that were equally more abundant and more potent — at least 10 times more potent — than immunity generated by vaccination alone.

The study was done before the emergence of the omicron variant, but researchers expect the hybrid immune responses would be similar with the new highly transmissible variant.

“The likelihood of getting breakthrough infections is high because there is so much virus around us right now,” Tafesse said. “But we position ourselves better by getting vaccinated. And if the virus comes, we’ll get a milder case and end up with this super immunity.”

Researchers recruited a total of 104 people, all OHSU employees who were vaccinated by the Pfizer vaccine, and then carefully divided them into three groups: 42 who were vaccinated with no infection, 31 who were vaccinated after an infection, and 31 who had breakthrough infections following vaccination. Controlling for age, sex and time from vaccination and infection, the researchers drew blood samples from each participant and exposed the samples to three variants of the live SARS-CoV-2 virus in a Biosafety Level 3 lab on OHSU’s Marquam Hill campus.

They found both of the groups with “hybrid immunity” generated greater levels of immunity compared with the group that was vaccinated with no infection.

A path toward endemic COVID

With the wildly contagious omicron variant now circulating across the globe, the new findings suggest each new breakthrough infection potentially brings the pandemic closer to the end.

“I would expect at this point many vaccinated people are going to wind up with breakthrough infections — and hence a form of hybrid immunity,” said senior co-author Bill Messer, M.D., Ph.D., assistant professor of molecular microbiology and immunology and medicine (infectious diseases) in the OHSU School of Medicine

Over time, the virus will run into an ever-expanding pool of human immunity.

OHSU scientists say they haven’t tested multiple rounds of natural infection, although many people will likely find themselves in that category given that millions of people in the United States and around the world remain entirely unvaccinated. With the spread of the highly contagious omicron variant, many unvaccinated people who were previously infected are likely to confront the virus again.

For that group, previous research reveals a much more variable level of immune response than vaccination, Messer said.

“I can guarantee that such immunity will be variable, with some people getting equivalent immunity to vaccination, but most will not,” he said. “And there is no way, short of laboratory testing, to know who gets what immunity. Vaccination makes it much more likely to be assured of a good immune response.”

Senior co-author Marcel Curlin, M.D., agreed.

“Immunity from natural infection alone is variable. Some people produce a strong response and others do not,” said Curlin, associate professor of medicine (infectious diseases) in the OHSU School of Medicine and director of OHSU Occupational Health. “But vaccination combined with immunity from infection almost always provides very strong responses.

“These results together with our previous work point to a time when SARS-CoV-2 may become a mostly mild endemic infection like a seasonal respiratory tract infection instead of a worldwide pandemic.”

In addition to Tafesse, Messer and Curlin, co-authors included Timothy Bates, Savannah McBride, Hans Leier, Gaelen Guzman, Zoe Lyski, Devin Schoen, Bradie Winders, Joon-Yong Lee of the Pacific Northwest National Laboratory and David Xthona Lee.

The study was funded by a grant from the M.J. Murdock Charitable Trust; an unrestricted grant from the OHSU Foundation; the National Institutes of Health, training grant T32HL083808 and grant R01AI145835; and OHSU Innovative IDEA grant 1018784.

The study authors acknowledge the research participants for their generous contributions; OHSU’s COVID-19 serology study team and the OHSU Occupational Health Department for recruitment and sample acquisition; and the OHSU clinical laboratory under the direction of Donna Hansel, M.D., Ph.D., and Xuan Qin, Ph.D., for SARS-CoV-2 testing and reporting.