Floor swabbing could help prevent COVID-19 outbreaks in hospitals

In two Ontario hospitals, high levels of SARS-CoV-2 on floors correlated with COVID-19 cases among healthcare workers and patients, suggesting floor swabbing as a potential method to prevent outbreaks

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Lunenfeld-Tanenbaum Research Institute

COVID-19 is here to stay. As restrictions and human testing have waned, new research is tackling the challenge of how we can monitor, predict, and prevent cases and outbreaks of COVID-19, especially among vulnerable groups like hospitalized patients.

One approach is environmental surveillance. The most well-known incarnation is wastewater surveillance, which rose in prominence following the advent of the COVID-19 pandemic. But the Coronavirus in the Urban Built Environment research team, also known as CUBE, is exploring an alternative—swabbing the floors.

In a recent study at two hospitals in Ontario, CUBE researchers swabbed the floors of healthcare worker areas, such as change rooms, meeting rooms and staff washrooms, and observed a strong association between the amount of SARS-CoV-2 viral matter found on the floor and the number of cases and outbreaks of COVID-19 in the hospital.

“The association between floor swabs and human cases and outbreaks was something we had previously observed in long-term care homes, and we wanted to test the hypothesis in the hospital setting,” says Dr. Caroline Nott, Infectious Disease Physician at The Ottawa Hospital, Assistant Professor at the University of Ottawa Department of Medicine, and one of the principal investigators of CUBE.

For every 10-fold increase in the amount of virus detected on the floor, the researchers observed a corresponding 15-fold increase in patient cases and a 22-fold higher odds of a COVID-19 outbreak. These results add to the mounting evidence that floor swabbing may provide an additional layer of monitoring to help inform infection prevention and control measures in hospitals and other settings.

“To be clear, COVID-19 is not spreading via the floor,” reassures Nott. “It is extremely rare to catch COVID-19 from any surface. Rather, what we are seeing in our floor swabs is a reflection of the burden of infection in the humans occupying the environment where we are swabbing. So if we start seeing an increase in the amount of virus we are finding on the floor, it could be a signal that additional cases and potentially outbreaks are on the way. This kind of early warning may help the hospital prepare and take preventative measures.”

But why would the amount of virus on the floor in healthcare worker areas reflect the burden of COVID-19 in the hospital’s patient population?

“Great question,” says Dr. Michael Fralick, Clinician Scientist at Sinai Health, Associate Professor at the University of Toronto, and CUBE principal investigator. “COVID-19 is a respiratory illness. It spreads via droplets and aerosols, which can travel a relatively long distance before falling to the floor.”

Fralick continues, “We focused on healthcare worker areas mainly for pragmatic reasons: those areas are more straightforward to access and do not disrupt direct patient care, which are important considerations if an approach like this were to be implemented.”

The study was conducted over 39 weeks between July 2022 and March 2023, with a total of 760 floor swabs collected. Swabs were processed for SARS-CoV-2 using quantitative reverse-transcriptase polymerase chain reaction. Grouped fivefold cross-validation was used to evaluate model outbreak discrimination. The paper was published last month in Cambridge University Press’s Infection Control and Hospital Epidemiology.

While COVID-19 has fallen out of the public consciousness, building the capacity in our healthcare systems to prevent illness and death in the event of seasonal resurgence and future variants is paramount, says Nott. “We weren’t prepared for COVID-19, and as a result many people died or have suffered long-term effects, especially vulnerable people like those being treated in hospitals or living in long-term care. We are driven to develop methods to prevent similar suffering in future, whether it is a new COVID-19 variant or a different pathogen altogether.”

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Journal

Infection Control and Hospital Epidemiology

Subject of Research

Not applicable

Article Title

SARS-CoV-2 burden on the floor was associated with COVID-19 cases and outbreaks in two acute care hospitals: a prospective cohort study

 

Why people think they’re right, even when they are wrong

Study finds people may incorrectly believe they have all the facts

Ohio State University

COLUMBUS, Ohio – If you smugly believe you’re right in a disagreement with a friend or colleague, a new study suggests why you may actually be wrong.

 

Researchers found that people naturally assume they have all the information they need to make a decision or support their position, even when they do not.

The researchers called it the “illusion of information adequacy.”

“We found that, in general, people don’t stop to think whether there might be more information that would help them make a more informed decision,” said study co-author Angus Fletcher, a professor of English at The Ohio State University and member of the university’s Project Narrative.

“If you give people a few pieces of information that seems to line up, most will say ‘that sounds about right’ and go with that.”

The study was published today in the journal PLOS ONE. Fletcher completed the work with co-authors Hunter Gehlbach, an educational psychologist at Johns Hopkins University’s School of Education, and Carly Robinson, a senior researcher at Stanford University’s Graduate School of Education

The study involved 1,261 Americans who participated online. 

They were split into three groups who read an article about a fictional school that lacked adequate water. One group read an article that only gave reasons why the school should merge with another that had adequate water; a second group’s article only gave reasons for staying separate and hoping for other solutions; and the third control group read all the arguments for the schools merging and for staying separate.

The findings showed that the two groups who read only half the story – either just the pro-merging or the just the anti-merging arguments – still believed they had enough information to make a good decision, Fletcher said.  Most of them said they would follow the recommendations in the article they read.

“Those with only half the information were actually more confident in their decision to merge or remain separate than those who had the complete story,” Fletcher said.

“They were quite sure that their decision was the right one, even though they didn’t have all the information.”

In addition, participants who had half the information said that they thought that most other people would make the same decision they did.

There was one piece of good news from the study, Fletcher said. Some of the participants who had read only one side of the story later read the arguments for the other side. And many of those participants were willing to change their minds about their decision, once they had all the facts.

That may not work all the time, especially on entrenched ideological issues, he said.  In those cases, people may not trust new information, or they may try to reframe it to fit their preexisting views.

“But most interpersonal conflicts aren’t about ideology. They are just misunderstandings in the course of daily life,” Fletcher said.

These findings offer a complement to research on what is called naïve realism, the belief people have that their subjective understanding of a situation is the objective truth, Fletcher explained.  Research on naïve realism often focuses on how people have different understandings of the same situation.

But the illusion of information adequacy shows that people may share the same understanding – if they both have enough information.

Fletcher, who studies how people are influenced by the power of stories, said people should make sure they have the full story about a situation before they take a stand or make a decision.

“As we found in this study, there’s this default mode in which people think they know all the relevant facts, even if they don’t,” he said.

“Your first move when you disagree with someone should be to think, ‘Is there something that I’m missing that would help me see their perspective and understand their position better?’ That’s the way to fight this illusion of information adequacy.”

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Journal

PLoS ONE

DOI

10.1371/journal.pone.0310216 

Method of Research

Experimental study

Subject of Research

People

Article Title

The illusion of information adequacy

Article Publication Date

9-Oct-2024

Neglecting “unknown unknowns” may influence decision-making

Study proposes a new bias: the tendency to assume one has adequate information to make a decision

PLOS

 

image: 

The authors suggest that the ability to navigate other perspectives might be improved by encouraging people to consider whether they may be lacking key information.

view more 

Credit: geralt, Pixabay, CC0 (https://creativecommons.org/publicdomain/zero/1.0/)

New experimental data support the idea that people tend to assume the information they have is adequate to comprehend a given situation, without considering that they might be lacking key information. Hunter Gehlbach of Johns Hopkins University and colleagues present these findings in the open-access journal PLOS ONE on October 9, 2024.

When navigating alternative perspectives, people may demonstrate psychological biases that influence their ability to understand others’ viewpoints. For instance, in the bias of naïve realism, people presume their own subjective perspective is objective truth.

Gehlbach and colleagues now propose the existence of a related bias, which they call the illusion of information adequacy: the failure to consider the possibility that one might be missing key information. For instance, one driver might honk at a car stopped in front of them, only to then see a pedestrian crossing the road—a possibility they hadn’t considered.

To demonstrate the illusion of information adequacy, the researchers presented 1,261 study participants with a hypothetical scenario in which they had to recommend whether two schools should be merged or not, as well as answer questions about their perceptions. Some participants received information about the benefits of merging, some about the benefits of staying separate, and some about both.

In line with the illusion of information adequacy, participants who—unbeknownst to them—lacked either the pro-merge or the pro-separate information tended to assume that the information they had was just as adequate as others’ information, that they were just as well equipped to make a thoughtful recommendation, and that most others would make a similar decision. Indeed, people lacking pro-merge information tended to recommend the schools remain separate, and vice versa.

Notably, a subgroup of participants who later received the information they initially lacked tended to stick with their original decisions. However, this subgroup’s combined final recommendations did mirror the recommendations of the subgroup that initially received all the information.

The authors suggest that the ability to navigate other perspectives might be improved by encouraging people to consider whether they may be lacking key information. Meanwhile, additional research could deepen understanding of this type of bias.

The authors add: “A major source of misunderstanding and conflict in our daily lives arises from this paradox: We know that, in theory, there are plenty of things that we don't know we don't know. Yet, in practice, we almost always behave as though we have adequate information to voice our opinions, make good decisions, and pass judgment on others. A little more intellectual humility about what we do and don't know would serve us well.”

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In your coverage please use this URL to provide access to the freely available article in PLOS ONE: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0310216

Citation: Gehlbach H, Robinson CD, Fletcher A (2024) The illusion of information adequacy. PLoS ONE 19(10): e0310216. https://doi.org/10.1371/journal.pone.0310216

Author Countries: U.S.A.

Funding: Dr. Hunter Gehlbach received start-up funds from Johns Hopkins University School of Education. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Journal

PLoS ONE

DOI

10.1371/journal.pone.0310216 

Method of Research

Experimental study

Subject of Research

People

Article Title

The illusion of information adequacy

Article Publication Date

9-Oct-2024

Are ideas contagious?

University of Virginia College and Graduate School of Arts & Sciences

The COVID-19 pandemic gave the global medical community the opportunity to take giant strides forward in understanding how to develop vaccines and implement public health measures designed to control the spread of disease, but the crisis also offered researchers the chance to learn more about another kind of contagion: ideas. 

Mathematician and assistant professor of biology Nicholas Landry, an expert in the study of contagion, is exploring how the structure of human-interaction networks affect the spread of both illness and information with the aim of understanding the role social connections play in not only the transmission of disease but also the spread of ideas and ideology.

In a paper published this fall in Physical Review E with collaborators at the University of Vermont, Landry explores a hybrid approach to understanding social networks that involves inferring not just social contacts but also the rules that govern how contagion and information spread.

“With the pandemic, we have more data than we’ve ever had on diseases,” Landry said.  “The question is, What can we do with that data and how much data do you need to figure out how people are connected?”

The key to making use of the data, Landry explained, is to understand their limitations and understand how much confidence we can have when using epidemic models to make predictions.

Landry’s findings suggest that reconstructing underlying social networks and their impacts on contagion is much more feasible for diseases like SARS-CoV-2, Mpox or rhinovirus but may be less effective in understanding how more highly infectious diseases like measles or chickenpox spread.

However, for extremely viral trends or information, Landry suggests it may be possible to track how they spread with more precision than we can achieve for diseases, a discovery that will better inform future efforts to understand the pathways of both contagion and misinformation.

---

Journal

Physical Review E

DOI

10.1103/PhysRevE.110.L042301 

Article Title

Reconstructing networks from simple and complex contagions

Article Publication Date

7-Oct-2024

 

Are ideas contagious?

University of Virginia College and Graduate School of Arts & Sciences

The COVID-19 pandemic gave the global medical community the opportunity to take giant strides forward in understanding how to develop vaccines and implement public health measures designed to control the spread of disease, but the crisis also offered researchers the chance to learn more about another kind of contagion: ideas. 

Mathematician and assistant professor of biology Nicholas Landry, an expert in the study of contagion, is exploring how the structure of human-interaction networks affect the spread of both illness and information with the aim of understanding the role social connections play in not only the transmission of disease but also the spread of ideas and ideology.

In a paper published this fall in Physical Review E with collaborators at the University of Vermont, Landry explores a hybrid approach to understanding social networks that involves inferring not just social contacts but also the rules that govern how contagion and information spread.

“With the pandemic, we have more data than we’ve ever had on diseases,” Landry said.  “The question is, What can we do with that data and how much data do you need to figure out how people are connected?”

The key to making use of the data, Landry explained, is to understand their limitations and understand how much confidence we can have when using epidemic models to make predictions.

Landry’s findings suggest that reconstructing underlying social networks and their impacts on contagion is much more feasible for diseases like SARS-CoV-2, Mpox or rhinovirus but may be less effective in understanding how more highly infectious diseases like measles or chickenpox spread.

However, for extremely viral trends or information, Landry suggests it may be possible to track how they spread with more precision than we can achieve for diseases, a discovery that will better inform future efforts to understand the pathways of both contagion and misinformation.

---

Journal

Physical Review E

DOI

10.1103/PhysRevE.110.L042301 

Article Title

Reconstructing networks from simple and complex contagions

Article Publication Date

7-Oct-2024

Nobel Prize: Victor Ambros, Gary Ruvkun win medicine award

Matthew Ward Agius

DW

7/10/24

Victor Ambros and Gary Ruvkun have been awarded the Nobel Prize in physiology or medicine for their research into microRNA.

Victor Ambros and Gary Ruvkun were announced as the joint recipients of the 2024 Nobel Prize in medicine or physiology on Monday

Image: Steffen Trumpf/dpa/picture alliance


American scientists Victor Ambros and Gary Ruvkun have been jointly awarded the Nobel Prize in medicine or physiology for their shared discovery of microRNA and the role it plays in post-transcriptional gene regulation.

At the announcement by the Nobel Assembly at the Karolinska Institutet in Sweden on Monday morning, Nobel Committee vice-chair Professor Olle Kämpe described the discovery of microRNA as "a tiny molecule that has opened a new field in gene regulation."

Though the pair worked in separate labs, their joint research focus led to them combining their resources to expand knowledge of microRNA and its role.

"The seminal discovery of microRNA has introduced a new and unexpected mechanism of gene regulation," said Kämpe.

"MicroRNAs are important for our understanding of embryological development, normal cell physiology and diseases such as cancer. As an example, tumors often perturb microRNA networks to grow."

Mutations in the roundworm species Caenorhabditis elegans were the first signs of microRNA in living organisms

.Image: Washington University School of Medicin/dpa/picture alliance

Nobel Prize microRNA discovery started with a tiny roundworm

This Nobel Prize is all about foundational genetics.

At the heart of what makes a living organism function is the ability of double-stranded DNA to be translated by single-stranded RNA molecules. These "messenger" RNA (mRNA) create an "information molecule" from DNA and move into a cell’s protein factory — a ribosome — where amino acids align to this template and then fold into specialized proteins.

These proteins are the building blocks of all living organisms. But mutations or variations to genes can cause changes in function — often benign, but potentially disease-causing.

This general pathway to organism metabolism has been understood for a long time, but as Kämpe posed, "What determines that only the right genes are transcribed into messenger RNA and then translated into the right, tissue-specific proteins at the right time?"

The answer starts with one specific organism, the roundworm species Caenorhabditis elegans. Despite its size, the roundworm has 20,000 genes that code for proteins — about the same number as a human, making it an ideal lab ‘model’ for physiological research.

Different mutations to C. elegans genes were found to cause growth changes. One triggered excessive growth via a repeating developmental pathway. Another restricted growth due to a different gene variation.

Ambros found the enlarging "lin-4" variant in 1993, with Ruvkun isolating the "lin-14" mutation present in the miniature worms a year later. What wasn’t clear was how these variations interacted and influenced cell regulation. The pair joined forces to find the answer.

A micro discovery leads to big implications for science

Ambros and Ruvkun found their respective mutations interacted — specifically, that a sequence of code on the lin-4 gene corresponded to part of a lin-14 sequence.

This was the critical moment when microRNA was determined to exist, as a distinct form of RNA.

"At this point they had discovered a novel and unexpected mechanism of gene regulation — microRNA," said Kämpe. "For a long time, however, microRNA was believed to be an oddity peculiar to C. elegans."

It required more evidence to confirm their findings.

It came in 2000, when Ruvkun found another gene — "let-7" — which was found not just in roundworm, but in humans and most animals.

Many microRNAs, it turns out, are highly conserved across animals, plants and fungi, meaning that they are largely unchanged from species-to-species and across hundreds of millions of years of biological evolution.

More than 1,000 microRNA genes have been found in humans.

"Every microRNA regulates several genes," said Kämpe. "And each mRNA is regulated by many distinct microRNAs, creating a robust system for gene regulation."

Nobel Prize in Medicine honors mRNA groundwork 02:12

When did RNA enter the public spotlight?

RNA was thrust into the public consciousness with the rise of RNA-based vaccine technology at the height of the COVID-19 pandemic.

These vaccine products could be developed relatively quickly by creating imitation proteins based on small sections of genetic code from the SARS-CoV-2 virus.

When used in a vaccine, these proteins provide a non-disease-causing target for the human immune system to find and create antibodies ready for the real virus.

Katalin Kariko and Drew Weissman were awarded last year’s prize for their work developing mRNA vaccine technology.

However while last year’s prize was very much in recognition of work that had led to direct medical applications, this year’s is more research focused.

"This year’s prize is definitely a physiology prize," said Professor Gunilla Karlsson Hederstam, chair of the Nobel Committee for Physiology or Medicine. "Last year, of course, [was] much a more applied discovery that was translated into vaccine development, so two quite different prizes.

"Although there are no very clear applications available yet, understanding them, knowing that they exist, understanding their regulatory networks is always the first step."

Joint laureate in the 2024 Nobel Prize for Physiology, Victor Ambros laughs with colleagues.

Image: Steven Senne/AP/picture alliance

Why type of products are being developed which utilize microRNA technology?

So while this year’s prize is very much focused on discovery rather than application, the realization of the Ambros-Ruvkun research may not be far away. There are currently several vaccine-type products in clinical trial stage for cancer, cardiovascular and other diseases that use microRNA technology.

The challenge is hitting the right target. Take a cancer cell. There may be a specific gene that a vaccine needs to address, but microRNAs regulate many different genes. The risk is that a product may act more like a bulldozer than a scalpel.

"But there might be ways around that," said Kämpe, "Tumors quite often perturb the microRNA networks and they can do that by deleting the genes or mutating the genes that process the microRNA.

"In [this] case there are promising first tests to see if you can modulate the RNA-binding proteins, but to deliver microRNAs to cells and think you get one effect, I think will be very difficult."

Two more Nobel science prizes will be awarded this week, with the physics laureate to be revealed on Tuesday, and chemistry prize on Wednesday.

Joint laureate in the 2024 Nobel Prize for Physiology, Gary Ruvkun.

Image: Steven Senne/AP/picture alliance

What is the history of the Nobel Prize in Physiology or Medicine?

This year's Prize, set at 11 million Swedish kronor (about $1.06 million USD), is yet another recognition of genetic discovery.

Arthur Kornberg and Severo Ochoa were recognized in 1959 for identifying the synthesis mechanisms of DNA and RNA, while the famed trio Crick, Watson and Wilkins were awarded the prize in 1952 for unravelling the DNA Double Helix.

Fire and Mello (2006), and Karikó and Weissman (2023) have also had their work on RNA recognized.

Famed Austrian neurologist and founder of psychoanalysis Sigmund Freud (1856-1939) was nominated for his work in Physiology and Medicine but was never named as a recipient.

At 31, Canadian surgeon and pharmacologist Frederick G. Banting is the youngest recipient of the Prize in Physiology or Medicine. He was recognized in 1923 for his discovery of insulin.

The American pathologist Francis Peyton Rous is the oldest, receiving his award in 1966 aged 87 for his discovery of tumor-inducing viruses.

The prize has been declined once. In 1939, Gerhard Domagk was prevented by Germany's Nazi Government from receiving his award for his discovery of an antibiotic against Streptococcus infections. He was later able to receive his diploma and medal in 1947.

Edited by Wesley Dockery

What is microRNA? Nobel-winning discovery explained

Agence France-Presse
October 7, 2024 

Victor Ambros and Gary Ruvkun won the Nobel for medicine for their discovery of microRNA © Jonathan NACKSTRAND / AFPn/liVictor Ambros and Gary Ruvkun won the Nobel for medicine for their discovery of microRNA © Jonathan NACKSTRAND / AFP

The Nobel Prize in Medicine was awarded on Monday to two US scientists for discovering microRNA, a previously unknown type of genetic switch which is hoped can pave the way for new medical breakthroughs.

But while several treatments and tests are under development using microRNAs against cancer, heart disease, viruses and other illnesses, none have actually yet reached patients.

And the world paid little attention when the new Nobel laureates Victor Ambros and Gary Ruvkun revealed their discovery decades ago, thinking it was just "something weird about worms", Cambridge University geneticist Eric Miska told AFP.

Here is an explainer about how exactly these tiny genetic switches work inside our bodies.

What is microRNA?

Each cell in the human body has the same set of instructions, called DNA. Some turn into brain cells, while others become muscles.

So how do the cells know what to become? The relevant part of the DNA's instructions is pointed to via a process called gene regulation.

Ribonucleic acid (RNA) normally serves as a messenger. It delivers the instructions from the DNA to proteins, which are the building blocks of life that turn cells into brains -- or muscles.

Miska gave the example of the messenger RNA vaccines rolled out against Covid-19 during the pandemic, which insert a message with new instructions to build proteins that block viruses.

Nobel prize for medicine 2024 © Valentina BRESCHI, Sylvie HUSSON, Lise KIENNEMANN, Thierno TOURE / AFP

But the two new Nobel winners Ambros and Ruvkun discovered a whole new type of gene regulator that had previously been overlooked by science.

Rather than being the messenger which relays information, microRNA instead acts as a switch to turn other genes off and on.


"This was a whole new level of control that we had totally missed," said Miska, who has worked on microRNA for two decades, including with the new Nobel laureates.

"The discovery of microRNAs brought an additional level of complexity by revealing that regions that were thought to be non-coding play a role in gene regulation," French researcher Benoit Ballester told AFP.

What did the Nobel winners do?


Back in the 1980s, Ambros and Ruvkun had been working separately on how genes interact in one-millimetre-long roundworms called C.elegans.

When they compared their work, it led to the discovery of microRNA. Ambros revealed the finding in a 1993 paper.

"Nobody really paid much attention," Miska said, explaining that most scientists at the time thought it only applied to worms.


Then in 2000, Ruvkun published research showing that microRNA is present right across the animal kingdom, including in humans and even some viruses.

"This was not just something weird that worms do, but in fact all animals and plants are totally dependent for development and normal function on them," Miska said.

More than a thousand genes that respond to microRNAs are now believed to be in the human body.

How could this help us?

There are numerous new treatments and tests using microRNA that are undergoing trials but none have been made widely available.

"Though there are no very clear applications available yet in microRNAs, understanding them, knowing that they exist, understanding their counter-regulatory networks, is always the first step," the Karolinska Institute's Gunilla Karlsson Hedestam told journalists in Stockholm.


MicroRNAs are particularly promising for fighting cancer because some of these switches "act as a tumour suppressor, so they put a brake on cells dividing inappropriately," Miska said.

Others, meanwhile, induce "cells to divide, which can lead to cancer", he added.

Because many viruses use microRNAs, several antiviral drugs are at varying stages of development, including for hepatitis C.


One complicating factor has been that microRNAs can be unstable.

But scientists also hope they can be used as a test called a "biomarker", which could reveal what type of cancer a patient could be suffering from, for example.
What next?


It also appears probable that microRNAs could be involved in the evolution of our species, Miska said.

While human brains are difficult to study, Miska hoped future research will discover more.

© 2024 AFP

Wider use of convalescent plasma might have saved thousands more lives during pandemic

Authors say findings support considering convalescent plasma deployment for future infectious diseases emergencies

Johns Hopkins Bloomberg School of Public Health

A new study led by researchers at Johns Hopkins Bloomberg School of Public Health estimates that thousands of lives could have been saved during the first year of the COVID-19 pandemic if convalescent plasma had been used more broadly, particularly in outpatients at high risk for severe disease and in hospitalized patients during their first few days of admission.

Convalescent plasma from patients who had recovered from COVID was used starting in the early months of the pandemic at the urging of a group of physicians who cited the blood byproduct’s success as a therapy in earlier infectious disease emergencies, including the global influenza pandemic of 1918–1920, and the SARS epidemic of 2002–2004. Plasma from patients recently recovered from a pathogenic infection, such as COVID, typically contains antibodies that may block or reduce the severity of the infection in others.

Over 500,000 patients were treated with convalescent plasma in the U.S. in the first year of the pandemic. 

In their new paper, published online October 1 in the Proceedings of the National Academy of Science, the authors estimate that treating hospitalized COVID patients with convalescent plasma saved between 16,476 and 66,296 lives in the United States between July 2020 and March 2021. For these estimates of actual lives saved, the researchers drew from convalescent plasma weekly use data, weekly national mortality data, and convalescent mortality reduction data from meta-analyses of randomized controlled trials. 

The researchers also estimated the number of potential lives that would have been saved had convalescent plasma been more widely used among patients being treated for COVID in hospitals. The researchers used the most optimistic assumptions possible: Had 100% of patients hospitalized with COVID been administered high-titer convalescent plasma within three days of admission between July 2020 and March 2021, the authors concluded that—depending on which mortality estimates they used for their analysis—between 37,467 to 149,318 (an approximately 125% increase) or between 53,943 to 215,614 (an approximately 225% increase) lives would have been saved in the first year of the pandemic. 

A total of 647,795 units of plasma was given to inpatients with COVID between July 2020 and March 2021. The team used this as a measure of the number of patients treated.

“This is a therapy that can reduce mortality, be immediately available, and is relatively inexpensive—we should be prepared to use it much more in a future infectious disease emergency or pandemic,” says study senior author Arturo Casadevall, MD, PhD, Bloomberg Distinguished Professor of Molecular Microbiology and Immunology and Infectious Diseases at the Bloomberg School.

Casadevall was one of the earliest proponents of convalescent plasma at the start of the pandemic. The study’s first author is Quigly Dragotakes, PhD, a postdoctoral fellow in the Casadevall laboratory.

The authors also estimated the number of hospitalizations that might have been avoided between July 2020 and March 2021 using a range of assumptions: 

• If 15% of outpatients had received convalescent plasma, the authors estimate that between 85,268 and 227,377 hospitalizations would have been avoided. 
• If 75% of outpatients received convalescent plasma, between 426,331 and 1,136,880 hospitalizations would have been avoided. 

During the first year of the pandemic, convalescent plasma was approved only for use in patients hospitalized with COVID.

Initial studies of the effectiveness of convalescent plasma in the U.S. and other countries had mixed results. Casadevall and colleagues note this was due in part to the challenges of ensuring that convalescent plasma contained sufficiently high anti-SARS-CoV-2 antibody concentrations. Another issue with many early studies, the researchers say, was that convalescent plasma was given to patients hospitalized with COVID already too sick to benefit much from the therapy.

Later studies showed convalescent plasma could be effective, including a clinical trial led by Johns Hopkins researchers that found that early use of convalescent plasma among outpatients reduced the relative risk of hospitalization by 54%. (Those findings were announced in December 2021.)

The researchers note that use of convalescent plasma during the pandemic was safe and its cost—averaging about $750 per unit in the U.S.—is lower than newer, patented COVID treatments.

The authors recommend that public health preparedness planning for future infectious disease outbreaks, epidemics, and pandemics include readiness to collect and deliver convalescent plasma at scale.

The authors note that the study has several limitations. While estimates of convalescent plasma units used in their analysis captured most convalescent plasma used during the study period, the exact number of units used is not known. This is likely due in part to the national Blood Centers of America not capturing convalescent plasma treatments administered locally in the early stages of the pandemic. In addition, the mortality reduction estimates the authors used to calculate lives saved varied widely. It’s not known if they mirrored use and efficacy of convalescent plasma use in clinical settings throughout the U.S. 

“We should be ready to set up outpatient centers to treat people early on with convalescent plasma during a future outbreak,” Casadevall says. “It would require designating spaces in hospitals for that purpose, but we wouldn’t need any new technology—this is well-established medical knowledge and practice.”

“Estimates of Actual and Potential Lives Saved in the United States from the Use of COVID-19 Convalescent Plasma” was co-authored by Quigly Dragotakes, Patrick Johnson, Matthew Buras, Rickey Carter, Michael Joyner, Evan Bloch, Kelly Gebo, Daniel Hanley, Jeffrey Henderson, Liise-anne Pirofski, Shmuel Shoham, Jonathon Senefeld, Aaron Tobian, Chad Wiggins, R. Scott Wright, Nigel Paneth, David Sullivan, and Arturo Casadevall.

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Journal

Proceedings of the National Academy of Sciences

 

Houston Methodist part of national consortium to develop vaccine against herpesviruses

Computational design expert Jimmy Gollihar Co-PI on ARPA-H award for developing America’s SHIELD

Houston Methodist

 

image: 

Jimmy D. Gollihar, Ph.D. is the head of the Antibody Discovery & Accelerated Protein Therapeutics (ADAPT) laboratory at the Houston Methodist Research Institute. The ADAPT lab is a modern synthetic biology and protein engineering lab.

view more 

Credit: Houston Methodist

Houston Methodist researchers will be part of a national consortium funded by an up to $49 million award from the U.S. Government’s Advanced Research Projects Agency for Health (ARPA-H) to develop a vaccine against two of the most common and destructive strains of herpesviruses that latently infect a majority of Americans and can lead to acute infections, multiple forms of cancer, autoimmune disease and birth defects.

 

The award is part of ARPA-H’s Antigens Predicted for Broad Viral Efficacy through Computational Experimentation (APECx) program and will fund the America’s SHIELD project to develop prophylactic and therapeutic vaccines against the β-  and γ- herpesviruses. Through the SHIELD (Strategic Herpesvirus Immune Evasion and Latency Defense) program, researchers will develop an integrated computational toolkit for antigen engineering with the potential to transform vaccine development against a myriad of pathogens.

 

These two herpesvirus subfamilies include human cytomegalovirus and Epstein-Barr virus, respectively, which clinically impact the largest proportion of the U.S. population, dormantly infecting Americans at an annual cost of at least $4 billion.

 

Epstein-Barr causes significant disease in adolescents and young adults as the cause of mono and also can later cause lymphomas, gastric and nasopharyngeal cancer, multiple sclerosis and diseases like non-Hodgkin’s lymphoma and certain leukemias in transplant patients. The human cytomegalovirus is the leading cause of congenital birth defects, as in-utero infection can result in permanent hearing loss or more profound neurodevelopmental impairments that disproportionately impact socioeconomically disadvantaged children.

 

Jimmy D. Gollihar, Ph.D., who is a protein engineer, synthetic biologist and head of the Antibody Discovery & Accelerated Protein Therapeutics (ADAPT) laboratory at the Houston Methodist Research Institute, is a co-principal investigator with Erica Ollmann Saphire, Ph.D., M.B.A., president, CEO and a professor with the La Jolla Institute for Immunology and project leader of the consortium. They are among a team of leading scientists from 19 laboratories across the U.S. that are working on herpesviruses.

 

As one of the artificial intelligence and machine learning experts of this consortium, Gollihar will generate new gene sequences encoding viral antigens for these mRNA vaccines through the ADAPT lab, which is a modern synthetic biology and protein engineering lab. During the COVID-19 pandemic, Gollihar’s group was directly involved in genomic surveillance, antigen production, serological testing and use of convalescent plasma, as well as monoclonal antibody discovery and engineering.

 

“A critical and innovative aspect to our strategy is the targeting of antigens essential to distinct stages of viral infection – beyond initial entry – to also include cell-to-cell spread, immune evasion and the reactivation stages linked to cancer, autoimmune disease and other complications,” Gollihar said.

 

Joining Gollihar from Houston Methodist are co-investigators John P. Cooke, M.D., Ph.D., who is the medical director of the Center for RNA Therapeutics, and Francesca Taraballi, Ph.D., who is the director for the Center for Musculoskeletal Regeneration and also works closely with Cooke as a faculty member in the Center for RNA Therapeutics.

 

Led by Cooke, the Houston Methodist Research Institute’s RNA Core, which has the capacity to synthesize molecular targeted drugs for first-in-human clinical trials under tightly controlled FDA regulations, will generate these mRNA herpesvirus vaccines. Taraballi, who also is an adjunct faculty member with the Department of Nanomedicine, will provide a nanoscale drug delivery platform with her group that will encapsulate the vaccines in lipid nanoparticles (LNPs) for testing and validation by the other investigators.

 

By integrating advanced computational models with immunological data, this comprehensive, multidisciplinary approach will not only accelerate herpesvirus vaccine development, but also will enable the rapid design and optimization of immunizing agents to trigger an immune response in the body against a myriad of other viruses. This will facilitate swifter responses to emerging viral threats, potentially transforming vaccine development and preparedness for future pandemics.

 

For more information about Houston Methodist, visit our newsroom or our social media pages on X, Facebook, LinkedIn, Instagram and TikTok or our On Health and Leading Medicine blogs.

 

Houston Methodist prepares for next pandemic as part of national NIH-funded consortium

Houston Methodist

 

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Jimmy D. Gollihar, Ph.D. is the head of the Antibody Discovery & Accelerated Protein Therapeutics (ADAPT) laboratory at the Houston Methodist Research Institute. The ADAPT lab is a modern synthetic biology and protein engineering lab. Gollihar will discover and engineer monoclonal antibodies to viruses in the Nairoviridae, Hantaviridae and Paramyxoviridae families, as well as contribute to the generation of gene sequences encoding stabilized viral antigens for potential mRNA vaccines through his ADAPT lab. 

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Credit: Houston Methodist

The question isn’t if, but when, the next pandemic will hit. Research and observation have identified strong potential for the next pandemic-causing virus to come from one or more of five different virus families. Houston Methodist scientists will focus on three of these as part of a national research consortium funded by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID). The consortium is led by Albert Einstein College of Medicine in New York.

 

Scientists from the Houston Methodist Research Institute will work to develop efficacious vaccines and therapeutic antibodies for viruses in the Nairoviridae, Hantaviridae and Paramyxoviridae families. The potential exists for a virus member in one or all of these families to be the cause of the next major pandemic. The specific viruses in these families that will be looked at by Houston Methodist researchers include:

• Nairoviruses (primarily caused by ticks)
  • Crimean-Congo hemorrhagic fever
  • Hazara virus
  • Andes
• Hantaviruses (caused by exposure to urine, saliva or droppings of infected rodents)
  • Sin Nombre
  • Hantaan virus
• Paramyxoviruses (respiratory viruses that occur in animals and humans spread through respiratory droplets or direct contact) 
  • Menangle
  • Tioman
  • Sosuga
  • Nipah virus

 

“To prepare for potential outbreaks of these target viruses, we will investigate the antigenic determinants of these viruses, similar to what was done with the years of research into coronaviruses that led to vaccine developers being able to rapidly provide solutions to the SARS-CoV-2 virus,” said Jimmy D. Gollihar, Ph.D., one of PROVIDENT’s co-principal investigators and head of the Antibody Discovery & Accelerated Protein Therapeutics (ADAPT) laboratory at the Houston Methodist Research Institute. “We propose to target viruses within these families by manufacturing and testing monoclonal antibodies and RNA vaccines that can effectively treat and prevent disease caused by these viruses. Our work will provide the foundational knowledge to develop effective medical countermeasures in response to a potential outbreak and pandemic.”

 

Gollihar will discover and engineer monoclonal antibodies to these viruses, as well as contribute to the generation of gene sequences encoding stabilized viral antigens for potential mRNA vaccines through his ADAPT lab, which is a modern synthetic biology and protein engineering lab. His team will also collaborate with the RNA Core, led by John P. Cooke, M.D., Ph.D., medical director of the Center for RNA Therapeutics, to construct, encapsulate and validate them. Working with Cooke on this will be Francesca Taraballi, Ph.D., who is the director for the Center for Musculoskeletal Regeneration and works closely as a faculty member in the Center for RNA Therapeutics. She will provide a nanoscale drug delivery platform that will encapsulate the vaccines in lipid nanoparticles (LNPs) for testing and validation by the other investigators.

 

The use of mRNA encapsulated in LNPs was also something that greatly enhanced the ability of vaccine developers during the COVID-19 pandemic to rapidly provide the public with an effective vaccine against the SARS-CoV-2 virus.

 

Led by Kartik Chandran, Ph.D., at Albert Einstein College of Medicine under a five-year grant of $14 million per year (award number 1U19AI181977-01), the PROVIDENT (Prepositioning Optimized Strategies for Vaccines and Immunotherapeutics Against Diverse Emerging Infectious Threats) consortium is part of the Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness (ReVAMPP) Network, focusing its research efforts on representative pathogens from virus families known to infect humans. By studying and developing solutions for these high-priority pathogens with the potential to cause deadly diseases, the scientists in the PROVIDENT consortium will build a knowledge base with the potential to be applied to other related viruses.

 

For more information about Houston Methodist, visit our newsroom or our social media pages on X, Facebook, LinkedIn, Instagram and TikTok or our On Health and Leading Medicine blogs.

 

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