Not all are equal in the face of coronavirus

Are there differences in immunity to the SARS-CoV-2 coronavirus between populations from different geographic regions?

Part of the answer to this question is to be found in the genomes of these groups of people and, more specifically, in the HLA genes responsible for the adaptive immune system. These genes are special in that they often differ between individuals. Thousands of possible variants (or alleles) have been identified, and not all of them are equally effective in fighting a new virus. The frequency of these alleles varies from one population to another due to past migrations and their adaptation to different environments.
In a study to be published in the journal HLA, scientists from the University of Geneva (UNIGE) — working in collaboration with the Max Planck Institute in Jena (Germany) and the University of Adelaide (Australia) — have pinpointed the HLA variants that are potentially the most effective against seven viruses, including the new coronavirus. They have also brought to light significant differences between populations.
The genetic variability of immunity lies particularly in the genes of the HLA (Human Leukocyte Antigen) system. These genes produce HLA molecules that are positioned on the surface of cells. When a virus infects an organism, the invader’s proteins are first cut into small fragments called peptides. The HLA molecules then bind on to these fragments and expose them to the surface of the cells, thereby triggering a cascade of immunity reactions designed to eliminate the virus.
Alicia Sanchez-Mazas, a professor at the Anthropology Unit in UNIGE’s Faculty of Sciences, explains: “From the 450 or so most common HLA molecules in hundreds of populations worldwide, we tried to identify the ones that are most strongly bound to the peptides of the new coronavirus.” Over 7,000 peptides can be derived from all of the viral proteins of the coronavirus.
The Geneva-based researcher and her international team used bioinformatic tools to perform the analysis. These can predict the binding affinities between the HLA molecules and the viral peptides on the basis of their physical and chemical properties. The scientists then turned to statistical models to compare the frequencies of these HLA variants in different human populations.
Classification of HLA molecules
The study classified the approximately 450 HLA molecules according to their relative capacity to bind the coronavirus peptides. It provides an essential reference inventory for identifying the genetic resistance or susceptibility of individuals to the virus. The study has also shown that the frequencies of these HLA variants differ significantly from one population to the next.
José Manuel Nunes, a researcher at the Anthropology Unit — and co-author of the article — further explains: “We were surprised to find that Indigenous populations in America had both the highest frequencies of HLA variants that bind the most strongly to the peptides and the lowest frequencies of those that bind the least strongly.” However, as José Manuel Nunes continues, we should not draw too hasty a conclusion from these results: “HLA molecules contribute to the immune response but they are far from being the only element that can be used to predict effective or ineffective resistance to a virus. This is also verified on the ground since America’s Indigenous populations are apparently no less affected than others by COVID-19.”
“Generalist” molecules
In the same study, the authors also analysed the HLA-peptide bindings for all of the proteins of the six other viruses with pandemic potential (two other coronaviruses, three influenza viruses and the HIV-1 virus of AIDS). This showed that many HLA variants are capable of binding strongly to the peptides of all seven viruses studied. Others do the same for all respiratory-type viruses (coronavirus and influenza). This means that there are numerous “generalist” HLA molecules that are effective against a number of different viruses.
“The differences between populations observed in this study are actually differences in the frequencies of the generalist HLA variants that do not bind specifically to the coronavirus but also to other pathogens,” points out professor Sanchez-Mazas. “This is what makes us think that the current differences between populations are the result of past adaptations to different pathogenic pressures, which is extremely informative for understanding the genetic evolution of our species.”
A logical follow-up to the study will be to determine precisely which coronavirus peptides are most strongly bound to the HLA molecules. It is these peptides that will have the highest chances of triggering an effective immune reaction. Identifying them will be vital for developing a vaccine.

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Story Source:
Materials provided by Université de Genève. Note: Content may be edited for style and length.

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Journal Reference:

1. Rodrigo Barquera, Evelyn Collen, Da Di, Stéphane Buhler, João Teixeira, Bastien Llamas, José M. Nunes, Alicia Sanchez‐Mazas. Binding affinities of 438 HLA proteins to complete proteomes of seven pandemic viruses and distributions of strongest and weakest HLA peptide binders in populations worldwide. HLA, 2020; DOI: 10.1111/tan.13956

https://www.sciencedaily.com/releases/2020/06/200610102730.htm

Fauci says ‘real normality’ in the US unlikely until next year

Dr. Anthony Fauci says the US will likely not return to life resembling “real normality” during the coronavirus pandemic until next year, according to a report.
“I would hope to get to some degree of real normality within a year or so. But I don’t think it’s this winter or fall,” Fauci, director of the National Institute of Allergy and Infectious Diseases, told The Telegraph on Sunday.
Fauci said that he anticipates a few cycles of the virus “coming back and forth” before the country is able to return to normal.
“We were successful in suppressing the virus in cities where there were major outbreaks – New York, Chicago, Detroit, New Orleans,” he told the newspaper. “But we’re seeing several states, as they try to reopen and get back to normal, starting to see early indications [that] infections are higher than previously.”
He said that without measures to contain the virus, the states are at risk of experiencing a “full-blown” outbreak.
“The question is will they have the capability to do the appropriate and effective isolation, and contact tracing, to prevent this increase from becoming a full-blown outbreak?” Fauci said. “I’m concerned it’s happening. I hope the individual states can blunt that. It [the virus] could go on for a couple of cycles, coming back and forth.”
But Fauci was optimistic that there’s an end in sight to the pandemic, noting there were several potential vaccines in the works.
“This will end. As stressful and devastating as it is, it will end,” Fauci told the newspaper. “We are all in it together as a global community, and I do see the light at the end of the tunnel.”
https://nypost.com/2020/06/14/fauci-says-real-normality-in-the-us-unlikely-until-next-year/

Rod-shaped particles might distract an out-of-control COVID immune response

A long-ignored white blood cell may be central to the immune system overreaction that is the most common cause of death for COVID-19 patients — and University of Michigan researchers found that rod-shaped particles can take them out of circulation.

The No. 1 cause of death for COVID-19 patients echoes the way the 1918 influenza pandemic killed: their lungs fill with fluid and they essentially drown. This is called acute respiratory distress syndrome. But a new way of drawing immune cells out of the lungs might be able to prevent this outcome. This research is among the essential projects at U-M that have continued through the pandemic uninterrupted.
ARDS is a manifestation of a condition known as cytokine storm, in which the immune system overreacts and begins attacking the person’s own organs. In ARDS, out-of-control white blood cells break down lung tissue and cause fluid to build up. Helping to lead the charge is a type of white blood cell called the neutrophil, which makes up 60% to 70% of intruder-eating “phagocyte” cells in humans.
“They’re like the Coast Guard — their main job is to make sure your boundaries aren’t breached,” said Lola Eniola-Adefeso, University Diversity and Social Transformation Professor and a professor of chemical engineering, who led the research.
Neutrophils aren’t specialized, which enables them to respond to many threats, she explained. But sometimes, that lack of specialization means they don’t know when to quit.
“As long as there’s cues, neutrophils keep acting. In some instances, the feedback loop is broken, and that turns what is meant to be a good response into a bad response,” Eniola-Adefeso said.
One of their actions is to emit signaling molecules called cytokines that tell cells to break down barriers and let blood and fluid into a problem site. When that response turns bad, the neutrophils need to be stopped so that other cells can step in and repair the damage.
Previously, Eniola-Adefeso’s group showed that plastic microparticles injected into the blood of mice could distract neutrophils, diverting them away from areas of severe inflammation in their lungs. The neutrophils would grab the particle and head to the liver to dispose of it. Microplastics used in this way eased ARDS in mice.
But any type of phagocyte might take up a sphere, which means a sphere-based therapy is likely to affect other parts of the immune response. However, it was already known that other phagocytes aren’t fond of rod-shaped particles. Eniola-Adefeso said they “get lazy” with the long wrapping process around a rod.
“We asked, do neutrophils also have a disdain for eating rods?” she said. “We found the complete opposite. They actually have a preference for eating rods.”
And that preference is useful for targeting neutrophils and leaving other white blood cells to do their jobs. They found that when they offered rods to different phagocytes, 80% of the neutrophils ate them, whereas only 5% to 10% of other phagocytes did. The comparisons included macrophages, another cell that eats intruders, and dendritic cells, which capture intruders and then show the other immune cells what to look for.
The team is currently exploring whether neutrophil-distracting particles can be made from medications rather than plastic. Eniola-Adefeso is now working with the U-M Office of Technology Transfer to advance her delivery system toward clinical trials, in hopes that it may prove useful in the fight against COVID-19. U-M has applied for patent protection and has launched a start-up company, Asalyxa.
Eniola-Adefeso is also a professor of biomedical engineering and professor of macromolecular science and engineering.
The research is funded by the Falk Medical Research Trust, the National Institutes of Health and the University of Michigan.

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Story Source:
Materials provided by University of Michigan. Note: Content may be edited for style and length.

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Journal Reference:

1. Hanieh Safari, William J. Kelley, Eiji Saito, Nicholas Kaczorowski, Lauren Carethers, Lonnie D. Shea, Omolola Eniola-Adefeso. Neutrophils preferentially phagocytose elongated particles—An opportunity for selective targeting in acute inflammatory diseases. Science Advances, 2020; 6 (24): eaba1474 DOI: 10.1126/sciadv.aba1474

https://www.sciencedaily.com/releases/2020/06/200610151959.htm

Spain to open borders to some visitors on June 21, plans aid for auto sector

Spain will reopen its borders to visitors from Europe’s open-border Schengen area from June 21, 10 days earlier than previously planned, Prime Minister Pedro Sanchez said on Sunday, in a further easing of coronavirus lockdown restrictions.

Sanchez also said a planned aid package to rescue Spain’s automobile sector, hard hit by the pandemic lockdown, would total 3.7 billion euros, adding that further details would be announced on Monday.
“We have been able to corner the virus in our country and on the European continent… but the risk has not disappeared,” Sanchez told a news briefing after talks with leaders of Spain’s 17 regions.
“Tourism is a key sector for the economic recovery,” he said, announcing the opening of Spain’s borders on June 21 to visitors from the Schengen area, which includes most of the European Union and some non-EU nations such as Norway.

Spain’s state of emergency ends that same day. Limits on mobility will be lifted but wearing masks in public will remain mandatory until a cure or vaccine for COVID-19, the lung disease caused by the virus, is found.
However, Sanchez said Spain’s land border with Portugal would remain closed till July 1, without saying why.
Visitors from outside the Schengen area will be able to visit Spain from July 1, though that will hinge on specific border agreements. Britain and Ireland are outside Schengen.
Spain’s borders are currently closed to tourists and those exempted from the entry ban must then spend 14 days in quarantine as a precaution against the spread of COVID-19, which has so far killed more than 27,000 people in Spain.

In a small prelude to the wider opening of its borders, Spain will allow German tourists to start visiting its Balearic Islands from Monday in a test programme.
The government has said it will announce support measures for the tourism sector on Thursday. Together, tourism and automobiles account for over 20% of Spain’s gross domestic product.
The lockdown has hammered car sales in Spain, and last month Nissan Motor Co [7201.T] said it would close its 3,000-workforce plants in Barcelona. The government has said it will try to reverse the decision.
https://www.reuters.com/article/us-health-coronavirus-spain/spain-brings-forward-border-opening-for-schengen-countries-to-june-21-idUSKBN23L0FE?il=0

Britain urgently reviewing distancing rules, could ease quarantine

Britain is urgently reviewing its social distancing rule and might be able to relax quarantine for travellers to help its economy recover from a coronavirus crisis collapse, the country’s finance minister Rishi Sunak said.

Progress in tackling the coronavirus pandemic meant Britain was able to take a “fresh look” at the two-metre rule, which many employers have said will make it harder to get back up to speed after the lockdown, Sunak said on Sunday.

Prime Minister Boris Johnson’s government, which says it has always followed scientific advice in its handling of the pandemic, faces the difficult balancing act of reviving the economy without allowing a second wave of coronavirus cases.
Britain has the third highest number of coronavirus deaths after the United States and Brazil, something critics of the government say reflects its response to the crisis.

“It’s important that we look at it comprehensively, in the round, and that’s what we will do urgently,” Sunak told Sky News about the social distancing rule, adding that preliminary work had already begun.
Reducing the distance people must keep apart from each other would mean three quarters of pubs could reopen, rather than about one third with a two-metre rule.
Sunak also said the government could make changes to a 14-day quarantine for people coming into the country, such as the introduction of travel corridors with specific countries.

Airlines have warned of huge job losses because of the quarantine introduced last week.
“The transport secretary is actively looking at options as we continue to make progress against the virus. We might be able to do more here as well,” Sunak said.
Sunak said he would reopen the economy “slowly and safely”, starting with the retail sector this week, and he hoped the hospitality sector would follow in early July.

The scale of the economic slump was laid bare by data last week which showed output shrank by a quarter over March and April, but the focus was now on the recovery phase.
Sunak said he wanted to encourage companies to hire workers and there needed to be more skills training, while higher levels of household savings represented a positive for the economy.
Asked if he might cut value-added tax to spur spending, Sunak said it was something Britain had done previously.
“Before we have that conversation we need to actually reopen those sectors. There’s no point in cutting VAT on a sector that is actually closed,” he said.
https://www.reuters.com/article/us-health-coronavirus-britain-sunak/britain-urgently-reviewing-distancing-rules-could-ease-quarantine-idUSKBN23L092?il=0

New wave of COVID-19 cases from Beijing market spreads to nearby province

After weeks with almost no new coronavirus infections, Beijing has recorded dozens of new cases in recent days, all linked to a major wholesale food market, raising concerns about a resurgence of the disease.

There had been almost no new cases in the city for almost two months until an infection was reported on June 12, and since then the total number has climbed to 51, including eight more in the first seven hours of Sunday.
According to the city’s health authority, contact tracing showed all the infected people had either worked or shopped inside Xinfadi, said to be the largest food market in Asia, or had been in contact with someone who was there.

“Beijing has entered an extraordinary period,” city spokesman Xu Hejian told a news conference on Sunday.
The market was closed before dawn on Saturday and the district containing the market put itself on a “wartime” footing.
The Beijing outbreak has already spread to the neighbouring northeastern province of Liaoning. According to the provincial health authority, the two new cases confirmed in Liaoning on Sunday were both people who had been in close contact with confirmed cases in Beijing.

At least 10 Chinese cities, including Harbin and Dalian, have urged residents not to travel to the capital or to report to authorities if they have done so recently.
Huaxiang, a neighbourhood in the same district as the food market and which has one of China’s biggest used car centers, raised its epidemic risk level to high on Sunday, becoming the only neighbourhood in the country to be on high alert. This status means there can be no economic activity until the outbreak is controlled.
As of 3 p.m. on Sunday, 10 neighbourhoods in Beijing, such as Financial Street, had raised their risk levels from low to medium.
“Beijing will not turn into a second Wuhan, spreading the virus to many cities all over the country and needing a lockdown,” a government epidemic expert told Health Times on Sunday, referring to the city where the epidemic in China first emerged late last year.

Zeng Guang, former chief epidemiologist at Chinese Center for Disease Control and Prevention and currently a senior expert with the National Health Commission, predicted that the outbreak will likely be controlled after the initial spike of a few days, according to the report by Health Times, a paper run by state media People’s Daily.
Like other countries around the world, China is concerned to prevent a second wave from emerging after easing lockdowns that hammered its economy earlier this year.

MARKET UNDER SCRUTINY

An epidemiologist with the Beijing government said on Sunday that a DNA sequencing of the virus showed the latest outbreak in the market could have come from Europe.

“Our preliminary assessment is the virus came from overseas. We still can’t determine how it got here. It might’ve been on contaminated seafood or meat, or spread from the faeces of people inside the market,” state media quoted Yang Peng as saying.
Officials said anyone who had been to or had contact with people who had been to Xinfadi since May 30 will be required to report to their work or residential units and get tested for coronavirus, the Beijing Daily said on Saturday.
Long queues for tests formed outside a hospital near the market on Sunday, pictures in the People’s Daily showed
Beijing health authority spokesman Gao Xiaojun told the news conference on Sunday that anyone in the city with a fever will be given tests for the coronavirus, a blood test and a CT scan.
More than 1,500 tonnes of seafood, 18,000 tonnes of vegetables and 20,000 tonnes of fruit are traded at the market daily, according to its website.
https://www.reuters.com/article/us-health-coronavirus-china-cases/new-wave-of-covid-19-cases-from-beijing-market-spreads-to-liaoning-idUSKBN23L01I

Washington State sounds alarm over rising coronavirus cases

Health officials in Washington are warning that the coronavirus is spreading more widely throughout the state, an increase likely driven by transmissions that took place over Memorial Day Weekend.
In a report issued Saturday, the state Department of Health pointed to two distinct hotspots, both of which are showing worrying signs of increased spreading.
Confirmed COVID-19 cases are rising fastest in four counties east of the Cascade Mountains, mostly rural and agricultural areas that were spared from the first substantial outbreak in Washington.
Both cases and the rate at which tests are coming back positive are increasing in Yakima, Spokane, Franklin and Benton counties. Projections in three of those counties show they are at risk of recording hundreds of new cases a day by the end of the month; Yakima County is already recording cases at that rapid rate.
The outbreaks east of the Cascades are now comparable to the worst days of the coronavirus epidemic in King County, home to Seattle, in mid-March. Though they are much more sparsely populated, there are as many cases per capita now in the eastern counties as there were in Seattle during the height of its outbreak.
King County has a population 2.25 million and has recorded 8,611 coronavirus cases, according to state Health Department figures, or a little under four cases per 1,000 residents. Yakima County, population 250,000, has recorded 5,129 confirmed cases, a per capita ratio five times higher than King County.
The state Health Department also said they were concerned about a growing number of cases confirmed in Western Washington. Models maintained by epidemiologists at the University of Washington show the estimated reproductive threshold — the average number of people someone infected with the virus infects — rising above the 1.0 threshold needed to keep cases on the decline.
Washington, the state that suffered the first confirmed coronavirus case back in January, is now beginning to reopen its economy. In a statement Saturday, Gov. Jay Inslee (D) said the new report was cause for concern.
“The report estimates cases and deaths will soon increase substantially if COVID-19 continues to spread at current levels,” Inslee said. “This data will force us to look for some creative solutions and strengthen our strong local – state partnerships to address the disease activity.”
He asked Washingtonians to wear masks more vigilantly, and to maintain physical distancing practices.
“This is not the time to give up on efforts to protect ourselves, our families and our communities. We are still in the middle of a pandemic that is continuing to infect and kill Washingtonians,” Inslee said.
In a statement, Washington State health officer Kathy Lofy said the increased number of cases was likely a result of Memorial Day Weekend festivities about three weeks ago. That stretch of time would give people a sufficient period of time in which to get sick, develop symptoms and progress to a state in which they seek treatment for their illness.
Lofy said the numbers of new cases are not indicative of any spread at protests over the murder of George Floyd, an unarmed black man who was killed by police in Minneapolis. The protests that have been especially large in Seattle, Tacoma and other Western Washington towns.
Any new cases among protestors probably have not had time to manifest in substantial ways yet; any new cases spread during the protests probably would not show up for at least another week.
After about a month at a stable plateau, the number of confirmed coronavirus cases across the country has started to rise. More than 20,000 new cases have been identified on each of the last four days, according to the COVID Tracking Project. Doctors confirmed nearly 24,000 cases on Thursday, and more than 26,000 cases on Friday.
States that raced to reopen their economies, like Texas, Florida, Arizona and the Carolinas, are seeing substantial increases. But so too are states like Washington, where restrictions have been lifted more slowly.
More than 2,066,000 people in the United States have been diagnosed with the coronavirus. More than 115,000 have died, by far the highest total of any country in the world.
https://thehill.com/homenews/coronavirus-report/502620-washington-state-sounds-alarm-over-rising-coronavirus-cases