Category: Corona Virus

Researchers from INGENIO, a joint center of the Consejo Superior de Investigaciones Cientficas (CSIC) and the Universitat Politcnica de Valncia (UPV), have recently published, together with two co-authors from the University of Sussex (UK), the results of a study on the organization of the laboratory network to perform Covid-19 PCR testing during the Covid-19 pandemic in Spain and the UK and its subsequent implications.

The work shows how the criteria of medical professionals in Spain (in this case clinical microbiologists in public hospitals) were more influential in the organization of testing laboratories than in the United Kingdom. In the latter country, criteria related to efficiency were imposed, with experts having less influence over decisions on testing activities. These conditions led to creation of new centralized mega-laboratories - the so-called 'Lighthouse Labs', which were criticized for their high cost and low quality of testing.

The consequences of these decisions have been very different in the two countries: while in Spain the influence of microbiologists helped public hospital laboratories to be more prepared today than before the pandemic, in the United Kingdom the large centralized laboratories that were built during the crisis have been dismantled and it seems that they have not helped to improve the country's capabilities."

David Barber, researcher at INGENIO and one of the authors of the study

The study is based on 44 interviews conducted with expert personnel from both countries, from heads of laboratories to health policy makers or public health specialists in both countries, in addition to the analysis of multiple documents.

"Our analysis focuses on the discourses and practices used in the two countries that we conceptualize as "boundary work", i.e., discourses and practices aimed at excluding from the system laboratories that had PCR technology but did not meet the criteria set by the logic of medical professionals (in Spain) or the logic of efficiency (in the United Kingdom)," explains Enrique Meseguer, INGENIO researcher and co-author of the study.

Thus, the study highlights that while in the United Kingdom the established publicly funded clinical laboratories were limited in their testing volumes, in favor of Lighthouse Labs, in Spain university or research laboratories were de facto excluded.

This work is part of the OCTS (Optimising Coronavirus Testing Systems) research project led by the University of Sussex and funded by UKRI (United Kingdom Research & Innovation), the British government funding agency. The project has studied the organization of the testing system in eight countries during the Covid-19 crisis (United Kingdom, Spain, Germany, South Korea, South Africa, Ireland, Australia and Canada). An interdisciplinary team, composed of specialists in innovation in medicine, health emergencies or epidemiology, met weekly during the period June 2020 to May 2022 to discuss different aspects of pandemic testing systems in the countries studied. Investigations have been carried out on issues such as the relationship between testing system capacity and excess mortality in all countries studied, or the organization of testing for international travel. This comparative work focused on Spain and the United Kingdom is the first article published as a result of the research project.

Source:

Journal reference:

BarberaToms, D., et al. (2023). Who can Test. Test. Test.? The interplay between boundary work and institutions in the organisation of diagnostic testing for COVID-19.Innovation: Management, Policy and Practice. doi.org/10.1080/14479338.2023.2254740.

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How Spain's expertise-driven approach in COVID-19 testing helps public hospital labs thrive post-crisis - News-Medical.Net

Since it was detected in August 2023, the JN.1 variant of COVID has spread widely. It has become dominant in Australia and , driving the biggest COVID wave seen in many jurisdictions for at least the past year. The World Health Organization (WHO) and in January strongly stated COVID was a continuing global health threat causing "far too much" preventable disease with worrying potential for long-term health consequences. JN.1 is significant. First as a pathogen it's a surprisingly new-look version of SARS-CoV-2 (the virus that causes COVID) and is rapidly displacing other circulating strains ( ). It's also significant because of what it says about COVID's evolution. Normally, SARS-CoV-2 variants look quite similar to what was there before, accumulating just a few mutations at a time that give the virus a meaningful advantage over its parent. However, occasionally, as was the case when Omicron (B.1.1.529) arose two years ago, variants emerge seemingly out of the blue that have markedly different characteristics to what was there before. This has significant implications for disease and transmission. Until now, it wasn't clear this "step-change" evolution would happen again, especially given the ongoing success of the steadily evolving Omicron variants. JN.1 is so distinct and that many are wondering whether the WHO will recognise JN.1 as the next variant of concern with its own Greek letter. In any case, with JN.1 we've entered a new phase of the pandemic. Where did JN.1 come from? The JN.1 (or BA.2.86.1.1) story begins with the emergence of its parent lineage BA.2.86 around mid-2023, which originated from a much earlier (2022) Omicron sub-variant BA.2.

Chronic infections that may linger unresolved for months (if not years, in some people) likely play a role in the emergence of these step-change variants.

Updated monovalent vaccines, tests and treatments remain effective against JN.1. Source: AAP / Wolfgang Kumm/DPA

The sheer volume of infections occurring globally sets the scene for major viral evolution. SARS-CoV-2 continues to have a very high rate of mutation. Accordingly, JN.1 itself is already mutating and evolving quickly.

The first relates to how the virus evades immunity. JN.1 has inherited more than 30 mutations in its spike protein. It also acquired a new mutation, L455S, which further decreases the ability of antibodies (one part of the immune systems protective response) to bind to the virus and prevent infection.

Whatever the case, these findings show JN.1 (and SARS-CoV-2 in general) can not only navigate its way around our immune system, but is finding new ways to infect cells and transmit effectively. We need to further study how this plays out in people and how it affects clinical outcomes.

There are two elements to "severity": first if it is more "intrinsically" severe (worse illness with an infection in the absence of any immunity) and second if the virus has greater transmission, causing greater illness and deaths, simply because it infects more people. The latter is certainly the case with JN.1.

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Why this 'new-look' COVID variant signals a new phase of the pandemic - SBS News

A new COVID-19 variant, JN.1, has taken the title of the most prevalent variant of the virus in the US, and also worldwide, according to the Centers for Disease Control and Prevention (CDC).

JN.1 remains the most widely circulating variant of SARS-CoV-2 in the United States and globally, states their latest report. In fact, as of January 20, the variant makes up almost 86 percent of all COVID-19 cases in the US, per the latest CDC figures.

The highly mutated strain is a descendant of Omicron specifically the Pirola variant, BA.2.86 and was first detected in the States back in September. By the end of October, it was responsible for less than 0.1 percent of SARS-CoV-2 viruses but has been on the rise ever since.

"Most likely, if you're getting COVID right now, you're getting this particular variant mutation," Eyal Oren, a director and professor of epidemiology at the School of Public Health at San Diego State University, told NPR.

Among the reasons for this latest surge of JN.1, Oren added, is the virus's rapid evolution: "our immune systems have not been able to keep up."

Its thought that JN.1 presents similarly to previous variants. According to the CDC, these symptoms include:

However, there has been some evidence that people are reporting slightly different COVID symptoms this season, including trouble sleeping and anxiety.

The fact that JN.1 has become so dominant could be taken as evidence that its more transmissible than previous variants, or better at evading the immune system. However, the CDC assures that currently there is no evidence that it causes more severe disease.

Still, COVID-19 infections, hospitalizations, and deaths have been elevated in recent weeks, especially in the eastern half of the country. People are advised to take the usual precautions by wearing masks, avoiding crowds, staying in when sick, and washing their hands.

The CDC recommends staying up to date with this seasons vaccinations for both COVID-19 and flu, which they say are well-matched to the viruses that are most common and should offer good protection.

Current COVID-19 vaccines are expected to increase protection against JN.1, as they do against other variants, by helping prevent severe illness.

The content of this article is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of qualified health providers with questions you may have regarding medical conditions.

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JN.1 Is Now The Most Prevalent COVID Variant Worldwide - IFLScience

Some people wonder how long the virus that causes COVID-19 can live on surfaces and whether it's possible to be infected by touching a contaminated object in your house, the gym, or a car and then touching your mouth, nose, or eye.

The answer to the first question is that it depends on the surfaces. By and large, the virus that causes COVID-19 persists longer on nonporous surfaces like countertops than on porous surfaces like clothes and fabric.

In terms of transmission of COVID-19 from surfaces, research has long suggested that the risk is low compared to the airborne transmission of the virus. However, newer research suggests that risk may be higher than previously thought, particularly in households.

This article takes a look at how long the virus that causes COVID-19 lives on surfaces and the risk of getting COVID-19 from touching contaminated surfaces. It also explores whether newer virus variants increase the risk and which disinfectants are most effective in preventing infection.

Severe acute respiratory syndrome coronavirus 2(SARSCoV2) virus is a strain ofcoronavirusthat causesCOVID-19.

The transmission (passing) of the virus occurs when fluid droplets or particles get expelled from the mouth or nose of someone with COVID-19 through actions like talking, coughing, or sneezing. Most transmissions occur when people breathe in these infected airborne droplets or particles.

However, larger droplets can settle on surfaces and potentially cause infection if you touch the contaminated surface (called a fomite) and then touch your mouth, nose, or eyes. The passing of the virus by this means is called fomite transmission.

As long as the virus is alive, there is a potential for transmission if certain criteria are met.

When outdoors, virus-containing droplets larger than 5 micrometers tend to travel a few feet and settle on surfaces where they are usually so diffuse that they pose minimal risk of transmission. Environmental exposure to heat, high humidity, and ultraviolet (UV) radiation can also quickly neutralize the virus.

The same may not be true in homes and offices where enclosed spaces (like bathrooms and kitchens) limit the spread of the expelled particles to a smaller area. At the same time, environmental conditions in homes and offices tend to be controlled and more beneficial to the survival of the virus.

Environments with low humidity, low temperatures, and low UV light exposure are most hospitable to the virus that causes COVID-19.

Because of the many variables that influence virus survival, the virus that causes COVID-19 may be able to live on surfaces anywhere from 30 minutes to as long as seven days, according to a 2023 review of studies in Transbound Emerging Diseases.

Studies have shown that COVID-19 virus-containing droplets smaller than 5 micrometers can survive in the air for three hours to threedays and travel long distances.

The survival of the virus that causes COVID-19 may be somewhat different in cars. While the size of a car's interior can concentrate the scattering of expelled fluids on dashboards and other surfaces, the environmental conditions inside the car may be inhospitable to the virus, particularly if the car is parked outdoors.

If exposed to temperatures greater than 72 degrees F (22 degrees C), the virus generally lives no longer than four minutes. Similarly, UV sun exposure through the windshield can inactivate the virus in less than 30 minutes.

Simply put, the virus that causes COVID-19 lives longer on nonporous surfaces like countertops, doorknobs, and handles than on porous surfaces like bedding, clothing, towels, and tissue paper. This is because the expelled droplets in the fibers of porous materials evaporate more quickly.

This is evidenced from a 2022 review of studies, which described the maximum survival time of the virus that causes COVID-19 on different surfaces based on the current body of evidence.

It is well known that each new COVID-19 virus variant that emerges has the potential to become more virulent (meaning more easily spread). This is because the viral mutations that are able to evade the body's immune defenses are the mutations that are most likely to spread.

This is evidenced by a 2023 study in Frontiers of Health in which the duration of contagiousness of the Delta variantthe 12th COVID virus variant identified in 2020was more than twice as long as the initial SARS-CoV-2 virus of 2019.

While this may suggest that newer variants can persist longer on surfaces, there is little evidence of that to date. In fact, certain mutations appear to make the virus less fit for survival once it is outside of the body.

By way of example, a 2023 study in Emerging Microbes & Infections reported the Omicron variant, first seen in 2021, had a far faster decay rate on surfaces like cardboard than the original SARS-CoV-2 virus.

It is also important to note that increased virulence does not mean that a virus is more pathogenic (able to cause disease). In fact, the Omicron variant is largely regarded to be less pathogenic than even the preceding Delta variant.

Most public health experts, including the Centers for Disease and Prevention (CDC), believe that the risk of fomite transmission of COVID-19 is low when compared to the risk of airborne transmission.

This is because, for a COVID-19 infection to occur, there needs to be a sufficient amount of viable viruses on a contaminated surface, which then needs to be transferred in sufficient quantity to the mucous membranes of the mouth, nose, or eyes. Unless these conditions are met, the odds of infection are low.

In the end, only a fraction of virus-containing particles may be transferred from surfaces to hands to mucous membranes. If only a few viruses are present, the immune system can usually block transmission.

This is not to say that you can't get COVID-19 from touched surfaces or that preventive measures like disinfecting surfaces are any less essential than they were during the pandemic. Some researchers argue that the risk of fomite transmission may be higher than previously thought.

A 2023 study published in Lancet Microbe monitored 279 households in which one member was diagnosed with COVID-19. Tracing the pattern of infections to other household members, the researchers found that the risk of infection was 1.7 times greater if the person first diagnosed with COVID-19 had detectable viruses on their hands compared to those with no viruses on their hands.

While this doesn't necessarily mean that fomite transmission was the cause of infection in these households, it does highlight the need for preventive measures like handwashing and surface disinfection to reduce the risk.

This is especially true in households with younger children with COVID-19, who are most likely to be asymptomatic (without symptoms) but still able to spread the virus to others.

Along with handwashing, face masks, and social distancing, cleaning surfaces has become one of the cornerstones of COVID-19 prevention. But only certain types of disinfectants are considered effective in eradicating the virus from surfaces.

The Environmental Protection Agency (EPA) is the federal body that regulates disinfectants in the United States. It lists over 35 agents, including alcohol, chlorine, and ammonia, that can neutralize the virus that causes COVID-19. Products intended for this purpose must be registered with the EPA.

When searching for a home disinfectant for the virus that causes COVID-19, opt for those that have the EPA registration number printed on the back product label. You'll find the number posted after "EPA REG NO." Avoid products that do not have this number, even if they claim to kill the virus that causes COVID-19.

With that being said, the EPA advises that thorough cleaning with soap and water is often enough to reduce the risk of transmission.The same applies to washing clothes with regular laundry detergent.

On the other hand, the EPA advises against products like UV lights or ozone generators sold as "germ sanitizers" as these have not proven to be effective against COVID-19.

There is a low likelihood of acquiring a COVID-19 infection from touching a contaminated surface. However good hand hygiene and cleaning surfaces regularly are still beneficial to reduce the risk further.

The virus that causes COVID-19 can live on surfaces anywhere from minutes to days, depending on whether the surface is porous or nonporous. Temperature, humidity, and UV light exposure also influence survival times. On nonporous surfaces like plastic and stainless steel, the virus has been known to persist for as long as seven days.

Even so, public health officials say that the risk of infection from touched surfaces is low. To reduce the risk, wash your hands and clean surfaces regularly with soap and water. If you decide to use disinfectants, opt for those that have been registered with the EPA.

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How Long COVID-19 Lives on Surfaces and Fabrics (in Days) - Verywell Health

A large seven-country study has shed light on how serious people find the COVID-19 pandemic compared to other major public health problems. The results were surprising and provide guidance to healthcare providers as well as policymakers.

Researchers from seven Environment for Development (EfD) centers plus the EfD Global Hub, located at the University of Gothenburg, have conducted an extensive survey on how serious people perceive COVID-19. This study is now bearing fruit in the form of publications, the first being: Perceptions of the seriousness of major public health problems during the COVID-19 pandemic in seven middle-income countries.

Over 10,000 respondents ranked the seriousness of the seven health problems (alcoholism and drug use, HIV/AIDS, malaria, tuberculosis, lung cancer and respiratory diseases caused by air pollution and smoking, and water-borne diseases like diarrhea).

Their answers revealed that in most countries respiratory illnesses were perceived to be a more serious problem than COVID-19. Surprisingly, in six of the seven countries, respondents ranked waterborne diseases as the least serious health problem. In the seventh country (South Africa) it was ranked next to last. In Africa, people felt that alcoholism and drug use were also more serious than COVID-19.

These findings are important because they show that people still care about the health problems they were facing before the pandemic.

"An important lesson for health ministries is to not get too carried away by what media focuses on a particular point in time. It is important to avoid crowding out ordinary health services," says Dale Whittington.

"It's also clear that public perceptions of the seriousness of health problems can differ considerably within and across countries and population segments defined by demographics and knowledge."

EfD Director Gunnar Khlin notes that the study is unique in the way it has tied together researchers from seven countries in the Global South with leading researchers in the US and Sweden in a joint data collection and analysis effort.

"A study like this can put novel phenomena, such as the COVID-19 pandemic, into a perspective of the more persistent challenges the countries in the Global South face," he says.

Originally posted here:

Study sheds light on how serious people find COVID-19 compared to other health problems - News-Medical.Net

A new treatment for Covid-19 can shorten illness among adults with mild cases of the virus, according to a study in the New England Journal of Medicine.

Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that was developed by Simcere Pharmaceutical in partnership with two Chinese academic institutions. It wasapproved in China under an emergency authorisation for the treatment of mild-to-moderate Covid-19 in January 2023. Like the antiviral Paxlovid (nirmatrelvir/ritonavir), it is administered in combination with ritonavir, which limits the breakdown of simnotrelvir.

In the latest phase 2-3 study, 1208 patients with mild-to-moderate Covid-19 were randomised to receive either simnotrelvir and ritonavir or a matching placebo twice daily for five days. The treatment was given within three days of symptom onset.

The researchers found that the time to sustained resolution of Covid-19 symptoms was around 1.5 days shorter in the simnotrelvir group than in the placebo group. On day five of treatment, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group. There were also no evident safety concerns with most adverse events recorded as mild or moderate.

According to the researchers, simnotrelvir is the most popular Covid-19 antiviral in China, and can be bought at a fraction of the price of Paxlovid.

More here:

New Covid-19 antiviral cuts symptoms by 1.5 days | Business - Chemistry World

Sandman is a risk communication consultant.

On December 31, 2023, the World Health Organization's Maria Van Kerkhove, PhD, MS, tweeted that COVID-19 is "still a pandemic." Her long thread went on to detail the paradox of COVID's continued threat to health, the variety of ways to reduce the risk, and the high level of public complacency.

She is surely right about the complacency. As far as the U.S. media and general public are concerned, the COVID pandemic is over. Anyone who argues to the contrary is shrugged off as a doomsayer (if not a shill for Big Pharma).

It's been that way for a while. President Joe Biden said the pandemic was over in September 2022. A March 2023 WebMD headline read: "It's (Finally) Time to Stop Calling It a Pandemic: Experts." By June 2023, 64% of Americans had reached the same conclusion, according to a Gallup Poll.

Now, in January 2024, news articles about COVID are much less common -- and the few remaining articles, if they use the word "pandemic" at all, mostly do so in the past tense. Even articles urging people to take COVID precautions seldom resort to the "p" word. Just because the pandemic is over, they seem to be saying, that's no reason to throw caution to the wind.

An ever-growing majority of Americans desperately want to throw caution to the wind. To justify doing so, they are deeply committed to insisting that the pandemic is over.

This gets things exactly backwards. If we're lucky, the pandemic is not over. Here's why.

Deadliness Comparisons

According to CDC, COVID killed 42,670 people in the U.S. in the first half of 2023. (All COVID statistics are squishy and debatable -- consider the debate between died "of" COVID and died "with" COVID -- but the CDC statistics will do for comparison purposes.) In the first half of 2021, according to the same CDC spreadsheet, COVID killed 219,222 people in the U.S. By this measure, COVID was a little over five times deadlier to Americans 2 years ago than it is today. That's a big piece of why people feel entitled to claim the pandemic is over.

But consider a different comparator: flu. That same CDC spreadsheet says flu killed 23,613 people in the U.S. in the first half of 2023 -- making COVID 1.8 times as deadly as flu.

Okay, so COVID today is about five times less deadly than it was 2 years ago, and still almost twice as deadly as flu.

The big question is what's going to happen to COVID's deadliness in the years ahead. The experts are pretty sure the virus is not going to die out. But that's about all they're sure of. Given the COVID mutation lottery, they won't be terribly surprised if COVID gets deadlier again. Nor will they be very surprised if it stays pretty much as deadly as it is right now, or if it starts oscillating between parameters we will eventually come to understand and expect, the way flu does, with good years and bad years.

The other possibility, the happiest one and some people think the likeliest one, is that COVID keeps killing fewer and fewer Americans in the next several years before settling into a pattern significantly less deadly than it is now. Maybe similar to flu. Maybe less deadly than flu.

Why is that a reasonable expectation? Our immunity keeps improving. Thanks to repeated vaccination, repeated infection, or both, our bodies (our antibodies, really) are getting better at fighting off SARS-CoV-2. We still get infected but we don't get as sick. New and improved antivirals and other treatments contribute to the rosy prognosis. Yes, the virus might mutate in a way that makes it deadlier. But there's a good chance, maybe better-than-even chance, that COVID will be a lesser health threat in the 2030s than it was in the 2020s.

The chronic disease picture isn't so rosy. We don't know yet how bad or how "long" long COVID will be. But it's almost certainly going to be worse and longer than long flu.

Even so, the toll of acute COVID deaths (and COVID hospitalizations) has declined precipitously in the past 2 years, and there's a pretty good chance that it will keep declining in the next few years.

What does that mean for the question of whether the pandemic is over?

Hope for Dwindling, Not "Over"

There's no universally accepted definition of the term "pandemic," but there are some universally accepted components. Most definitions include some combination of these variables. Disease outbreaks are called "pandemic" when:

Seasonal flu is serious, transmissible, and widespread, but it has been around for centuries and we know what to expect. So it's not pandemic. From time to time a new flu strain starts circulating. Precisely because it's new, it's unpredictable. If it is also serious, transmissible, and widespread, we've got ourselves a flu epidemic -- or pandemic if it spreads globally. A year or two later, when the new strain becomes predictable, part of the new normal, the experts declare the flu pandemic over.

Once COVID settles into a predictable pattern, the experts will declare the COVID pandemic over. If 2024 and 2025 and 2026 turn out pretty much like 2023, we will know in hindsight that the COVID pandemic of 2020-2022 ended in 2023. If so, we'll have to face a new normal with a brand new disease nearly twice as deadly as flu...on top of flu and all the other diseases we face.

I'm hoping for better. I'm hoping that 2024 sees fewer COVID deaths than 2023, and 2025 sees fewer than 2024. I'm hoping that by 2030 COVID will have settled into a newly familiar pattern significantly less deadly than it was in 2023. I'm hoping the COVID pandemic dwindles for a few more years before it ends.

And that's why I hope the COVID pandemic isn't over.

Peter M. Sandman, PhD, MA, is a mostly retired risk communication consultant. His writing on pandemics and other risk communication topics can be found at http://www.psandman.com.

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Opinion | Why I Hope the COVID Pandemic Isn't Over - Medpage Today

image:

LJI Research Instructor Annie Elong Ngono (left) and LJI Postdoctoral Fellow Rbens Alves, Ph.D., served as co-first authors of the new SARS-CoV-2 study.

Credit: Matthew Ellenbogen, LJI Creative Producer

Scientistsat La Jolla Institute for Immunology (LJI) have found direct evidence that exposure to common cold coronaviruses can train T cells to fight SARS-CoV-2. In fact, prior exposure to a common cold coronavirus appears to partially protect mice from lung damage during a subsequent SARS-CoV-2 infection.

The new research,published recently inNature Communications, provides an important first look at how "cross-reactive" T cellswhich can fight multiple viruses from the same familydevelop in an animal model. "We are learning how these immune cells develop and function," says study co-leader LJI Research Instructor Annie Elong Ngono, Ph.D.

The Shresta Laboratoryis now working to develop novel vaccines purposefully designed to harness these powerful T cells. Those vaccines would protect against SARS-CoV-2 and provide immunity against several other coronaviruses with pandemic potential.

"Our research willhelp scientists design and improve 'pan-coronavirus' vaccines that elicit broad, cross-protective responses," adds LJI ProfessorSujan Shresta, Ph.D., study senior leader and member ofLJI's Center for Vaccine Innovation.

How powerful areT cells?

T cells tendto be specialists. They learn to hunt down specific molecular targets, called epitopes, that belong to specific pathogens. "Cross-reactive" T cells are important for human health because they recognize epitope targets on differentbut closely relatedpathogens, such as different members of the coronavirus family. This viral family includes common cold coronaviruses and serious pathogens such as SARS-CoV-2.

The COVID-19 pandemicput cross-reactive T cells in the spotlight.In early 2020, LJI ProfessorsShane Crotty, Ph.D., andAlessandro Sette, Dr.Biol.Sci., discovered that many peoplewho had never been exposed to SARS-CoV-2already had T cells that recognized the novel coronavirus. How did these T cells know what to look for?

SARS-CoV-2 only emergedin 2019, but many people had contracted common cold coronaviruses long before then. LJI scientists showed that cross-reactive T cells could recognize targets on both viruses. In follow-up studies, researchers even found an association between cross-reactive T cells and a lower risk of developing severe COVID-19.

If T cellscould learn to target both viruses at once, perhaps scientists could design a vaccine against many types of coronaviruses, including new SARS-CoV-2 variants. That was the hopebut there was still a lot to learn.

"To design bettervaccines we need to know exactly how these protective T cells develop and how long that window of protection lasts," says LJI Postdoctoral Fellow Rbens Alves, Ph.D., who served as first author of the new study.

The Shresta Labis working to answer those questions. The lab members specialize in developing humanized mouse models, which allows them to study infectious diseases and human-relevant immune cell responses in a controlled environment.

Cross-reactive T cellsto the rescue

For the newstudy, the researchers used mouse strains that can produce the exact same variety of T cells as the ones found in humans. The researchers infected these mice with one of the most widespread common cold coronaviruses, called OC43. SARS-CoV-2 and OC43 are both betacoronaviruses.

The scientists foundthat mice infected with OC43 produced CD4+ "helper" T cells and CD8+ "killer" T cells that cross-reacted with SARS-CoV-2. Those cells targeted the same epitopes as T cells collected from humans with SARS-CoV-2 exposure.

Next, the researchersdeveloped a model of sequential infectionwith OC43 infection followed by SARS-CoV-2 in these humanized mice. They examined whether the cross-reactive T cells actually helped protect the mice from severe COVID-19.

Cross-reactive CD4+ "helper"T cells did indeed help counteract the virus's assault on the respiratory system. Mice with previous OC43 exposure showed lower levels of SARS-CoV-2 infection in their airways and were less likely to develop pneumonia and lung damage. Cross-reactive T cells really did help prevent severe disease.

"Our lab's expertisein mouse models has allowed us to go deeper into what human studies have suggested," says Elong Ngono.

Next steps forvaccine design

SARS-CoV-2 is notthe first coronavirus to cause a deadly outbreak. SARS, which caused a deadly outbreak in 2003, was also a coronavirus. So is MERS. This new study is an important step in understanding how T cells might learn to recognize and cross-react to many coronaviruses at onceincluding emerging SARS-CoV-2 variants and other family members with pandemic potential.

Going forward, theteam would like to investigate how exposure to other kinds of common cold coronaviruses affects T cells. Will cross-reactive T cells still develop? Would they seek the same shared epitopes or different targets?

"We now havethe mouse model to study different human infection scenarios, such as the common situation when a person has been infected many times by different common cold coronaviruses before encountering SARS-CoV-2," says Shresta. "We even have a model now to characterize different SARS-CoV-2 vaccine-elicited human relevant T cell responses and determine the contribution of these T cells to the vaccine-induced protection."

Shresta says theInstitute is well equipped to move forward with this pandemic prevention research. She credits the LJI for making sure LJI scientists have the vital training and facilities for infectious disease research. Shresta also emphasizes that philanthropic support made it possible for the Institute to construct a biosafety level 3 laboratory for thisand many othercritical studies.

Additional authors ofthe study, "Common cold coronavirus-elicited CD4+ T cells protect against SARS-CoV-2 in HLA transgenic mice," include Julia Timis, Robyn Miller, Kristen Valentine, Paolla Beatriz Almeida Pinto, Andrew Gonzalez, Jose Angel Regla-Nava, Erin Maule, Michael N Nguyen, Norazizah Shafee, Sara Landeras Bueno, Eduardo Olmedillas, Brett Laffey, Katarzyna Dobaczewska, Zbigniew Mikulski, Sara McArdle, Sarah R. Leist, Kenneth Kim, Ralph S. Baric, and Erica Ollmann Saphire.

This research wassupported by the National Institutes of Health (grants U19 AI142790, U01 AI151810, and AI149644), the Overton family, and the Arvin Gottlieb Foundation.

DOI:10.1038/s41467-024-45043-2

About La JollaInstitute

La Jolla Institutefor Immunology is dedicated to understanding the intricacies and power of the immune system so that we may apply that knowledge to promote human health and prevent a wide range of diseases. Since its founding in 1988 as an independent, nonprofit research organization, the Institute has made numerous advances leading toward its goal: life without disease. Visitlji.orgfor more information.

Nature Communications

Experimental study

Animals

"Human coronavirus OC43-elicited CD4+ T cells protect against SARS-CoV-2 in HLA transgenic mice"

26-Jan-2024

The authors declare no competing interests.

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Common cold or COVID-19? Some T cells are ready to combat both - EurekAlert

Babies of mothers infected by COVID-19 during pregnancy had three times the risk of respiratory distress compared with unexposed infants, even though the infants themselves were not infected with the virus, in a recent study. The risk of respiratory distress was significantly lower when the mothers were previously vaccinated. According to the researchers, even one mRNA vaccine dose prior to infection significantly reduced the odds that a full term infant would develop respiratory distress. Their report appears today in Nature Communications,

We found unusually high rates of respiratory distress shortly after birth in the full-term babies born to mothers who had COVID-19 during pregnancy, said senior author Karin Nielsen, professor of pediatrics in the division of pediatric infectious diseases at the David Geffen School of Medicine at UCLA. The mothers had not been vaccinated prior to acquiring COVID, indicating that vaccination protects against this complication.

The study also found that in-utero exposure to SARS-CoV-2 sparked an inflammatory cascade in the infants, increasing the risk of a breathing disorder.

SARS-CoV-2 infection during pregnancy has been associated with adverse maternal and neonatal outcomes, including increased risk of prematurity, stillbirths, and severe maternal morbidity and mortality. Estimates of vertical transmission of SARS-CoV-2 from mother to child are low, but there is growing concern about long-term health consequences for babies who were exposed in utero. Specifically, these authors write Several authors have reported cases of infant respiratory distress (RD) among SARS-CoV-2-exposed uninfected (SEU) term neonates.

The researchers used proteomics to determine that whip-like structures called motile cilia that help clear mucus from the respiratory tract did not function normally in the exposed infants stricken with respiratory distress. In addition, these infants had higher production of immunoglobulin E (IgE) antibodies.

Of the 221 mothers enrolled in the study, 151 (68%) were unvaccinated prior to infection, with severe or critical COVID disease present in 23 women (16%), compared with only three (4%) of vaccinated mothers.

The researchers found that 34 (17%) of 199 exposed infants followed in the study had respiratory distress, which is a very high frequency, as in the general, unexposed population respiratory distress happens in 56% of babies only. Twenty-one percent of babies with respiratory distress were born to mothers with severe or critical COVID-19, while only six percent of babies without respiratory distress were born to women with severe disease, a finding that was statistically significant.

Of the 34 infants with respiratory distress, only five (16%) were born to mothers vaccinated prior to infection, compared to 63 (41%) without the breathing disorder, indicating that vaccination had a protective effect.

Not only do our results show higher rates of RD [respiratory distress] in SEU [SARS-CoV-2 exposed uninfected] infants when compared to the general population, the researchers write, but we observed more cases of RD at later gestational ages than anticipated, when neonates should presumably have more mature lung anatomy.

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COVID-19 in Pregnancy Increases Baby's Risk of Respiratory Distress - Inside Precision Medicine

Severe COVID-19 causes early lung capillary thrombosis, leading to respiratory distress, with studies emphasizing prompt anti-coagulation treatment to mitigate complications.

Blood clot formation (thrombosis) in the small blood vessels of the lungs is an early result of severe COVID-19, often occurring before the breathing difficulties caused by widespread damage to the air sacs, according to a Brazilian study reported in an article published in the Journal of Applied Physiology. Post-mortem examinations of nine individuals who passed away from severe COVID-19 revealed a distinct pattern of changes in lung blood vessel structure and thrombosis.

For the first time, the article describes sub-cellular aspects of the endothelial damage and associated thrombotic phenomena caused by the infection. It notes the impact of acute inflammation on lung microvascular circulation as the key factor in severe COVID-19, contributing to a deeper understanding of the pathophysiology of the disease and the development of novel therapeutic strategies.

This study furnished the final proof of what wed been pointing out since the very start of the pandemic that severe COVID-19 is a thrombotic disease. The virus SARS-CoV-2 has a tropism for [is attracted to] the endothelium, the layer of cells that lines blood vessels. When it invades endothelial cells, it first affects microvascular circulation. The problem starts in the capillaries of the lungs [the tiny blood vessels that surround the alveoli], followed by clotting in the larger vessels that can reach any other organ, said pulmonologist Elnara Negri, first author of the article and a professor at the University of So Paulos Medical School (FM-USP). She was one of the first researchers in the world to reach the conclusion that severe COVID-19 is a thrombotic disease.

The researchers at USP analyzed lung tissue from nine patients who died from COVID-19. Credit: Elia Caldini

In the study, which was supported by FAPESP, the researchers used transmission and scanning electron microscopy to observe the effects of the virus on lung endothelial cells from severe COVID-19 patients who died at Hospital das Clnicas, the hospital complex operated by FM-USP.

All nine samples obtained by minimally invasive autopsies displayed a high prevalence of thrombotic microangiopathy microscopic blood clots in small arteries and capillaries that can lead to organ damage and ischemic tissue injury. The samples came from patients who were hospitalized between March and May 2020, required intubation and intensive care, and died owing to refractory hypoxemia and acute respiratory failure.

It is worth noting that none of the patients included in the study was treated with anti-coagulants, as this was not part of the COVID-19 treatment protocol at the time. Nor were any COVID-19 vaccines available in the period.

Negri explained that the endothelium is itself lined by a gel-like layer of glycoproteins called the glycocalyx, which acts as a barrier to regulate the access of macromolecules and blood cells to the endothelial surface. This barrier prevents clotting in blood vessels by inhibiting platelet interaction with the endothelium.

Previous studies conducted by Helena Nader at UNIFESP [the Federal University of So Paulo] showed that SARS-CoV-2 invades cells mainly by binding to the receptor ACE-2 [a protein on the surface of various cell types, including epithelial and endothelial cells in the respiratory system] but before that, it binds to heparan sulfate [a polysaccharide], a major component of the glycocalyx in endothelial cells. When it invades the endothelium, it triggers shedding and destruction of the glycocalyx, resulting in tissue exposure and intravascular clotting. The process starts in the microcirculation, Negri explained.

Because the virus initially acts on the pulmonary microcirculation, contrast examinations performed during the pandemic to investigate the presence of blood clots in larger vessels in severe COVID-19 patients failed to detect the problem at any early stage, she added. However, endothelial dysfunction is a key phenomenon in COVID-19 since it is directly associated with the activation of the inflammatory response that is characteristic of the disease.

Massive viral invasion and destruction of the endothelium break down the endothelial barrier and impair the recruitment of circulating immune cells, activating pathways associated with thrombogenesis and inflammation, she said.

In the study, the researchers found that endothelial injury tended to precede two common processes in cases of respiratory distress: significant alveolar-capillary membrane leakage, and intra-alveolar accumulation of fibrin (associated with blood clotting and wound healing).

A study by the same group at FM-USP, led by Thais Mauad and including transcriptomics (analysis of all RNA transcripts, coding, and non-coding), showed that several pathways associated with blood clotting and platelet activation had been activated prior to inflammation in the lungs of patients with alveolar damage.

The analysis also confirmed that the clotting was not typical of the usual process triggered by the activation of coagulation factors. In COVID-19, the clotting is due to endothelial injury and exacerbated by NETosis [an immune mechanism involving programmed cell death via formation of neutrophil extracellular traps or NETs], dysmorphic red blood cells and platelet activation, all of which makes the blood thicker and causes many complications, Negri said.

When the blood is thick and highly thrombogenic, she added, the patient must be kept hydrated, whereas diffuse alveolar damage in acute respiratory distress syndromes due to other causes requires reduced hydration. Also, the timing and rigorous control of anti-coagulation are fundamental, she stressed.

Another study by the same group of researchers, including Marisa Dolhnikoff and Elia Caldini, showed lung damage in severe COVID-19 to be associated with the degree of NETosis: the higher the level of NETs in lung tissue obtained by autopsy, the more the lungs were damaged.

Negri said she began to suspect there was a link between COVID-19 and thrombosis early in the pandemic when she noticed a phenomenon recalling her experience some 30 years ago with patients who had microvascular clotting after open-heart surgery with extracorporeal circulation and a bubble oxygenator, no longer used because it causes endothelial damage.

It was a widely used technique 30 years ago, but it causes lung injury very similar to that seen in COVID-19. So Id already seen it. Besides the pulmonary injury, another similarity is the occurrence of peripheral thrombotic phenomena, such as red toes, for example, she said.

As severe COVID-19 sets in, the drop in blood oxygen levels is secondary to pulmonary capillary thrombosis. Initially, theres no buildup of fluid in the lungs, which arent saturated and dont lose their compliance or elasticity. This means the lungs in early severe COVID-19 patients dont look like sponges full of liquid, as they do in acute respiratory distress syndrome [ARDS] patients. On the contrary, the respiratory failure associated with severe COVID-19 involves dehydration of the lungs. The alveoli fill with air but the oxygen cant enter the bloodstream because of capillary clotting. This leads to what we call happy hypoxia, where patients dont experience shortness of breath and arent aware their oxygen saturation is dangerously low.

While observing the intubation of a severe COVID-19 patient, Negri realized the treatment of such cases should be entirely different from what it was at the start of the pandemic. The secret to treating severe COVID-19 patients is keeping them hydrated and using anti-coagulant at the right dose, meaning the dose required in the hospital environment at the onset of oxygen desaturation, i.e. low levels of oxygen in the blood, she said. After that, the therapeutic dose of anti-coagulant must be calculated daily on the basis of blood work, always in the hospital environment to avoid any risk of bleeding. Prophylaxis is required for an average of four to six weeks after discharge because thats how long the endothelium takes to regenerate.

This hydration and anti-coagulation protocol is needed because, in contrast with other kinds of ARDS in which oxygen in the lungs is prevented from entering the bloodstream mainly by alveolar inflammation, lung capillary endothelial damage is the main obstacle in early severe COVID-19, she explained.

No one knew about this difference between COVID-19 and other types of ARDS at the very start of the pandemic. Indeed, this is why so many Italian patients died in ICUs [intensive care units], for example. The treatment protocol used then was different, she recalled.

In 2020, before the study was reported in the Journal of Applied Physiology, Negri and her group had already observed that the use of the anti-coagulant heparin improved oxygen saturation in critical patients. In 2021, in collaboration with colleagues in several countries, they conducted a randomized clinical trial in which they succeeded in demonstrating that treatment with heparin reduced severe COVID-19 mortality. The findings were published in the British Medical Journal.

That study helped bring about a global change in COVID-19 treatment guidelines by showing that COVID-19 mortality risk fell 78% when anti-coagulation was started in patients who needed oxygen supplementation but werent yet in intensive care, Negri said.

Endothelial dysfunction should be reversed without delay in severe COVID-19, using an anti-coagulant, she explained. Blood clotting has to be stopped as soon as possible in order to avert the development of acute respiratory distress and other consequences of the disease, such as the problems now known as long COVID, she said.

An article recently published in Nature Medicine by researchers affiliated with institutions in the United Kingdom reinforces the thrombotic nature of the disease, reporting a study in which the only long COVID prognostic markers identified were fibrinogen and D-dimer, proteins associated with coagulation.

The study shows that long COVID results from inadequately treated thrombosis. The microcirculatory problem can persist in several organs, including the brain, heart, and muscles, as if the patient were having small heart attacks, Negri said.

Reference: Ultrastructural characterization of alveolar microvascular damage in severe COVID-19 respiratory failure by Elnara Marcia Negri, Marlene Benchimol, Thais Mauad, Amaro Nunes Duarte-Neto, Maiara Gottardi, Luiz Fernando Ferraz da Silva, Paulo Hilario Nascimento Saldiva, Marisa Dolhnikoff, Wanderley de Souza and Elia Garcia Caldini, 1 October 2023, Journal of Applied Physiology. DOI: 10.1152/japplphysiol.00424.2023

Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization by Maxime Taquet, Zuzanna Skorniewska, Adam Hampshire, James D. Chalmers, Ling-Pei Ho, Alex Horsley, Michael Marks, Krisnah Poinasamy, Betty Raman, Olivia C. Leavy, Matthew Richardson, Omer Elneima, Hamish J. C. McAuley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Ruth M. Saunders, Victoria C. Harris, Linzy Houchen-Wolloff, Neil J. Greening, Parisa Mansoori, Ewen M. Harrison, Annemarie B. Docherty, Nazir I. Lone, Jennifer Quint, Naveed Sattar, Christopher E. Brightling, Louise V. Wain, Rachael E. Evans, John R. Geddes, Paul J. Harrison and PHOSP-COVID Study Collaborative Group, 31 August 2023, Nature Medicine. DOI: 10.1038/s41591-023-02525-y

The study was funded by the So Paulo Research Foundation.

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Scientists Have Proven That Severe COVID-19 Is a Thrombotic Disease - SciTechDaily