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.

In a study published in January in Stem Cell Reports, researchers from Osaka University report that heart cells from a patient with an inherited heart disease called arrhythmogenic cardiomyopathy do not contract correctly when grown in the laboratory, and that replacing the mutated gene responsible for this effect fixes this defect.

Arrhythmogenic cardiomyopathy occurs due to mutations in genes involved in desmosomes, which form ‘welds’ between cells that help them communicate and move in a coordinated way. One of these genes, PKP2, encodes a protein known as plakophilin-2 that is crucial to maintaining heart cell structure.

“Previous studies carried out in cardiomyocytes have shown that mutations in PKP2 play a pathological role in arrhythmogenic cardiomyopathy,” says lead author of the study Hiroyuki Inoue. “However, the cells used in those experiments were derived from healthy individuals and were not assessed for contractile function.”

To investigate how cells derived from patients behave in the laboratory, the researchers first took a blood sample from a young patient with arrhythmogenic cardiomyopathy, induced some of the blood cells to become stem cells, and then differentiated these stem cells into heart cells. They then modified this original batch of heart cells into three different cell lines with precisely adjusted PKP2 expression based on how many mutated or intact copies of the gene were present.

“The cells with two mutated copies of PKP2 clearly exhibited reduced contractility and impaired desmosome assembly due to plakophilin-2 deficiency,” explains Shuichiro Higo, senior author. “These effects were also observed in cells with only one mutated copy of PKP2, although they were less severe.”

Replacing the mutated PKP2 with an intact copy of the gene repaired the defects in both cell contraction and desmosome assembly, which the researchers were able to observe using a time-lapse approach and fluorescently labeled desmosomes.

“These findings suggest that our cardiomyocyte cell lines recapitulate the pathology of arrhythmogenic cardiomyopathy and provide a rapid and convenient platform for developing gene-based therapies for this disease,” says Higo.

Given that PKP2 is the most common gene associated with arrhythmogenic cardiomyopathy, and that PKP2 mutations can lead to severe disease, new therapeutic approaches could help halt disease progression. The findings from this study suggest that gene replacement therapy could be a valuable way of treating patients with this condition and the cell lines created in this study are a viable model to test new therapies for arrhythmogenic cardiomyopathy on.

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Research participants who used social media excessively were found to have higher levels of C-reactive protein (CRP), a biological marker of chronic inflammation that predicts serious illnesses, such as diabetes, certain cancers and cardiovascular disease. In addition to elevated CRP levels, results suggest higher social media use was also related to somatic symptoms, like headaches, chest and back pains, and more frequent visits to doctors and health centers for the treatment of illness.

“Social media use has become an integral part of many young adults’ daily lives,” said David Lee, PhD, the paper’s first author and assistant professor of communication in the UB College of Arts and Sciences. “It’s critical that we understand how engagement across these platforms contributes to physical health.”

The findings appear in the journal Cyberpsychology, Behavior, and Social Networking.

For decades, researchers have devoted attention to how social media engagement relates to users’ mental health, but its effects on physical health have not been thoroughly investigated. Recent surveys indicate social media usage is particularly high for people in their late teens and early 20s, a population that spends about six hours a day texting, online or using social media. And though a few studies have found links between social media usage and physical health, that research relied largely on self-reporting or the effects of usage with exclusively one platform.

“Our goal was to extend prior work by examining how social media use across several platforms is associated with physical health outcomes measured with biological, behavioral and self-report measures,” said Lee, an expert on health outcomes related to social interactions.

Researchers recruited a diverse sample of 251 undergraduate students between the ages of 18 and 24 for the study. Blood samples were collected through finger sticks, and participants also completed questionnaires on physical health and social media usage on Facebook, Twitter, Snapchat, and Instagram, the most popular platforms at the time the data were collected in 2017. Those responses were crosschecked with another survey that measured validity by determining the degree to which participants took their role in the study seriously.

“We were able to establish a correlation between the amount of social media use and these physical health indicators,” said Lee. “The more participants used social media, the more somatic symptoms they experienced and visits to the doctor they reported. They also showed higher levels of chronic inflammation.”

Lee says this study is just the beginning of understanding the relationship between social media and physical health.

“By looking at a biological marker in the blood, we were able to find a relatively more objective association between social media usage and physical health, but this correlational finding can’t rule out the possibility that poor health impacts social media usage,” said Lee.

Lee says the aphorism could hold true with social media use and physical health: The rich get richer while the poor get poorer. “In our previous research, we found those high in self-esteem benefited from using social media, but people low in self-esteem did not. So, the effect may be more nuanced.”

“There’s still work to be done,” said Lee. “But right now, I wanted to get the word out there that social media use may have a link to important physical health outcomes.”

Lee’s research team for the current study included colleagues from The Ohio State University: Tao Jiang, a graduate student; Jennifer Crocker, PhD, professor of social psychology; and Baldwin Way, PhD, associate professor of psychology.

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Materials provided by University at Buffalo. Original written by Bert Gambini. Note: Content may be edited for style and length.

A new study conducted at the University of Turku, Finland, examined the association between the neighbourhood socioeconomic disadvantage and the development of children’s body mass index and the risk of overweight from birth to school age. The children’s growth data was acquired from a national register of well-baby clinics.

Information on the socioeconomic status of the neighbourhood was linked to the participants with address coordinates using the national grid database of Statistics Finland. The database contains information that is based on all Finnish residents on social and economic characteristics at the level of 250 m x 250 m grids.

– The socioeconomic status of the neighbourhood was measured with education level, household income, and unemployment rate. The results were independent of the education level, economic situation, marital status and health of the children’s parents, says lead author, Docent Hanna Lagström from the Department of Public Health of the University of Turku.

Living in a less prosperous neighbourhood posed a major risk for children to develop overweight by school age in the population-based data, even when the researchers considered factors that can increase the risk of overweight in childhood. These included e.g. mother’s type 2 diabetes, mother’s smoking, and child’s high birth weight. In neighbourhoods with a higher socioeconomic status, children weighted more at birth, but their weight development stabilised already by the age of four.

– This could implicate that neighbourhoods can offer very different types of development environments for children, and that the risk of overweight grows before school age in neighbourhoods with lower socio-economic status. The results of our research are an important factor to take into consideration in e.g. city planning to ensure that inequality is stopped right from the childhood, says Lagström.

The study is based on 2008-2010 data from the Southwest Finland Birth Cohort (SFBC). The Birth Cohort consists of all children born in the Hospital District of Southwest Finland during those three years. In this study, the participants consisted of the first children born to the mothers during this this time.

The research was funded by the Academy of Finland and Juho Vainio Foundation as well as the Hospital District of Southwest Finland.

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