Children produce different antibodies in response to SARS-CoV-2

Children and adults produce different types and amounts of antibodies in response to infection with the new coronavirus, SARS-CoV-2, a new study from researchers at Columbia University Vagelos College of Physicians and Surgeons has found. 

The differences in antibodies suggest the course of the infection and immune response is distinct in children and most children easily clear the virus from their bodies.

"Our study provides an in-depth examination of SARS-CoV-2 antibodies in kids, revealing a stark contrast with adults," says Columbia University immunologist Donna Farber, Ph.D., the George H. Humphreys II Professor of Surgical Sciences in the Department of Surgery, who led the study with Matteo Porotto, Ph.D., associate professor of viral molecular pathogenesis in Columbia's Department of Pediatrics. The first authors, Stuart Weisberg, MD, Ph.D., assistant professor of pathology & cell biology, and Thomas Connors, MD, assistant professor of pediatrics, enrolled patients into the study and conducted the data analysis.

"In kids, the infectious course is much shorter and probably not as disseminated as in adults," Porotto adds. "Kids may clear this virus more efficiently than adults and they may not need a strong antibody immune response to get rid of it."

Children less affected by SARS-CoV-2

One of the striking manifestations of the COVID-19 pandemic is that the majority of children cope well with the virus while older people struggle.

"This is a new infection for everybody," Farber says, "but children are uniquely adapted to see pathogens for the first time. That's what their immune system is designed to do. Children have a lot of naive T cells that are able to recognize all sorts of new pathogens, whereas older people depend more on our immunological memories. We're not as able to respond to a new pathogen like children can."

Children make fewer SARS-CoV-2 neutralizing antibodies

Among the 47 children in the study, 16 were treated at Columbia University Irving Medical Center for MIS-C and 31 children of similar ages had tested positive for the virus after visiting the medical center for the treatment of other conditions. Half of the children without MIS-C had no COVID-19 symptoms. The 32 adults in the study ranged from severely affected patients admitted to the hospital to those with milder disease who recovered at home.

Both groups of children produced the same antibody profile, the study found, which differed from that of adults.

Compared with adults, children produced fewer antibodies against the virus's spike protein—which the virus uses to infect human cells. The children's antibodies had the least neutralizing activity, while all adults, including young adults in their 20s, produced neutralizing antibodies. The sickest adults had the most neutralizing activity.

Though it may seem counterintuitive that the sickest patients produce antibodies with the greatest neutralizing activity, Farber says that likely reflects the amount of time the virus is present in the sickest patients.

"There is a connection between the magnitude of your immune response and the magnitude of the infection: The more severe the infection, the more robust the immune response, because you need to have more immune cells and immune reactions to clear a higher dose of a pathogen."

Other antibody differences dhow children's infections are limited

In contrast to adults, children also produced very few antibodies against a viral protein that is only visible to the immune system after the virus infects human cells.

"That suggests that in kids, the infection doesn't really spread a lot and doesn't kill a lot of their cells," Farber says.

"Because children clear the natural virus rapidly, they do not have a widespread infection and they do not need a strong antibody response," Porotto says.

The reduced course of infection in children may signify that they are infectious for a shorter period of time compared with adults and therefore less likely to spread the virus, although the researchers did not measure viral load in the children.

"Current studies in other countries indicate that younger school-age children are not vectors for the new coronavirus, so our data are consistent with those findings," Farber says.

Children should respond well to vaccine

The antibody responses found in children do not suggest that children will have a weaker response to a vaccine, the researchers say.

Vaccines under development for SARS-CoV-2 contain pieces of the virus and do not mimic the normal route of infection.

"Even though children don't produce neutralizing antibodies in response to a natural infection with SARS-CoV-2, vaccines are designed to generate a protective immune response in the absence of an infection," Farber says. "Children respond very well to vaccines, and I think they will develop good neutralizing antibody responses to a SARS-CoV-2 vaccine, and they'll probably be better protected than the adults.

"That said, very few vaccine studies are currently enrolling children and we will need this data to really understand how well the vaccines work in children."

What does the adult immune system lack?

Though the findings suggest the course of infection in children and adults is different, it's still not known how the children are able to clear the virus more easily—and what the adult immune system lacks.

Farber, Porotto, and their colleagues at Columbia are now looking for differences in T-cell response (antibodies are produced by the immune system's B cells), especially T cells that reside in the lung. [Previous research from Farber's lab has shown these "stay-at-home" T cells are more important in fighting lung infections than T cells that travel through the body via the bloodstream].

Children infected with SARS-CoV-2 also may generate a stronger response from the innate immune system, which deploys interferon and cells called macrophages to indiscriminately attack cells infected by pathogens. Earlier studies suggest that the innate immune response may be delayed in adults infected with SARS-CoV-2.

"If the innate response is really strong, that can reduce the viral load in the lungs, and the antibodies and T cells of the adaptive response have less to clear up," Farber says.

It's also possible that the virus is less able to infect children's cells, possibly because children's cells express fewer proteins the virus needs to infect human cells.

The Columbia researchers are now testing these possibilities with cells from children versus adults.

"There are still all these issues that we have very little information about," Porotto says. "The interaction between the virus and the host is the reason why we see so much diversity in responses to this virus, but we don't understand enough about this virus yet to really determine what leads to severe disease and what leads to mild disease."

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More information: Stuart P. Weisberg et al, Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum, Nature Immunology (2020). DOI: 10.1038/s41590-020-00826-9

https://medicalxpress.com/news/2020-11-children-antibodies-response-sars-cov-.html

Mutant COVID-19 strain in Denmark’s mink could cause ‘new pandemic’

The coronavirus mutation discovered in Denmark’s mink could spark a new wave of the illness in the country, scientists warn.

Authorities in Denmark — the world’s largest producer of mink furs — said five cases of the new virus strain had been recorded on mink farms and 12 cases in humans.

The mutation showed a decreased sensitivity against antibodies, meaning it could potentially cause a COVID-19 vaccine to be less effective, experts said.

“The worst-case scenario is that we would start off a new pandemic in Denmark,” Prof. Kare Molbak, a vaccine expert and director of infectious diseases at Denmark’s State Serum Institute told The Guardian.

“There’s a risk that this mutated virus is so different from the others that we’d have to put new things in a vaccine and therefore [the mutation] would slam us all in the whole world back to the start.”

The Scandinavian nation announced on Wednesday that it would cull its mink population of up to 17 million over the new virus strain.

“We have a great responsibility towards our own population, but with the mutation that has now been found, we have an even greater responsibility for the rest of the world as well,” Prime Minister Mette Frederiksen said at a news conference.

Outbreaks at mink farms have persisted in the country despite repeated efforts to exterminate infected animals since June.

https://nypost.com/2020/11/05/covid-19-strain-in-denmark-mink-could-cause-new-pandemic-scientist/

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China Is Winning the Vaccine Race

In 2020, China bungled its initial response to COVID-19. As a result, the disease spread around the world, crippling economies, killing more than 1.2 million people, and badly damaging Beijing’s image. In 2021, China plans to redeem itself by vaccinating a large chunk of the global population. Although it faces stiff competition from the United States and other Western nations in the race to develop the first vaccine, Beijing is poised to dominate the distribution of vaccines to the developing world—and to reap the strategic benefits of doing so.

Worldwide, 11 COVID-19 vaccine candidates are currently in phase three trials, the final stage before regulatory approval. Four are Chinese. The most promising of these, developed by Wuhan-based Sinopharm, is already being given to frontline workers in the United Arab Emirates. According to Wu Guizhen, chief biosafety expert at the Chinese Center for Disease Control and Prevention, Sinopharm’s candidate is on track for full approval this month or next.

Leading American vaccine candidates from Moderna and Pfizer could be approved on a similar timeline. But the administration of U.S. President Donald Trump has no plan to compete with China to distribute vaccines to the more than half of humanity that lives in the developing world. The United States has declined to participate in a World Health Organization (WHO) initiative to deliver two billion vaccine doses to at-risk populations in developing countries, and it has not extended financing to or signed preferential vaccine distribution deals with such countries, as China has done. The U.S. approach to vaccine development and distribution, as to so much else during this administration, has been “America first.” By ceding the public health field to China, the United States will allow Beijing to recast itself not just as a global leader in vaccine development and distribution but as the savior of the developing world.

OFF TO THE RACES

Even if China wins the race to develop a vaccine, its producers are unlikely to compete in U.S., European, or Japanese markets. Chinese vaccine makers have struggled to clear the regulatory hurdles required to sell to developed Western markets. And in part because of the coronavirus pandemic, many developed Western countries are trying to “re-shore” production of medical supplies from China. Most have already signed enormous procurement deals with the major Western vaccine makers Moderna, Pfizer, and AstraZeneca. For a high-income country, the price of vaccinating every citizen is tiny compared with the cost of another lockdown. (Moderna estimates that its vaccine will cost between $64 and $74 per person, including the required booster shot.)

But in the vast emerging markets of Asia, Africa, the Middle East, and Latin America, where more than half the global population lives and many governments can barely afford vaccines, Chinese producers are poised to dominate. Chinese vaccines are in phase three clinical trials in 18 countries, including Argentina, Bahrain, Bangladesh, Brazil, Egypt, Indonesia, Morocco, Pakistan, Peru, Russia, Saudi Arabia, Turkey, and the United Arab Emirates. That is an enormous potential market, even if Beijing ultimately subsidizes most of the vaccine sticker price.

Indeed, Beijing’s vaccine distribution strategy is likely to rely heavily on subsidies. Chinese President Xi Jinping first alluded to this strategy in May, when he promised that any Chinese vaccine for COVID-19 would be a “global public good.” True to his word, Xi has promised $1 billion in loans to Latin American and Caribbean countries to pay for access to Chinese vaccines. Last month, Mexico signed a deal with CanSino, another Chinese vaccine maker with a candidate in phase three trials, to buy 70 million doses with a promised Chinese loan. China plans to begin exporting these doses even before it has vaccinated all of its own people, a gesture that is sure to generate additional goodwill.

China will use such preferential vaccine deals to consolidate partnerships with governments in regions that it regards as strategically important—such as Southeast Asia, Africa, Latin America, and the Caribbean. Since 2013, Beijing has used preferential financing for major infrastructure projects to similar effect through its Belt and Road Initiative. Many of these megaprojects have run aground this year, as the pandemic and subsequent economic crisis have strained the finances of recipient countries. In 2021, by refocusing the world’s attention on the “Health Silk Road,” China will seek to rebrand itself as a technological leader and patron of global public health, skirting American accusations that it is a “bully” and a “predatory” lender.

AT WHAT COST

Even subsidized Chinese vaccines will come at a price. Although Beijing is unlikely to demand specific political concessions, it will at minimum expect recipient countries to grovel and show their gratitude. Early in the COVID-19 crisis, Serbian President Aleksandar Vucic kissed the Chinese flag after a planeload of supplies arrived from China. Soon after, an enormous billboard went up in front of the National Assembly building in Belgrade. “Thank you, Big Brother Xi!” it read. On March 24, the week that deaths from COVID-19 peaked in Italy, Italian Foreign Minister Luigi di Maio credited Chinese ventilators and masks with preventing a bad situation from getting worse. “Those who scoffed at our participation in the Belt and Road Initiative now have to admit that investing in that friendship allowed us to save lives,” he said. When China distributes vaccines worldwide next year, some scenes from this movie may rerun.

It isn’t just national governments that will embrace China’s newfound dedication to global public health. International institutions will keep praising China for making grandiose commitments, hoping—reasonably—that by flattering Xi, they can encourage him to deliver. “President Xi’s proposal for a Health Silk Road, which strengthens and renews ancient links between cultures and people, with health at its core, is indeed visionary,” WHO Director General Tedros Adhanom Ghebreyesus said in a 2017 speech in Beijing. The WHO is unlikely to change tack if Trump cuts funding and withdraws next July, as he has promised to do if reelected.

Although China initially paid a diplomatic price for its failure to control the novel coronavirus, it is poised to repair its damaged reputation by reinventing itself as the public health provider for the developing world. If Washington keeps refusing to compete, it won’t just risk losing the vaccine race. It will allow China to win the prestige of a first-rate technological power, the goodwill of a slew of new potential allies, and a legitimate claim to global leadership.

• EYCK FREYMANN is the author of the forthcoming book One Belt One Road: Chinese Power Meets the World.
• JUSTIN STEBBING is Professor of Cancer Medicine and Oncology, Imperial College London.

https://www.foreignaffairs.com/articles/united-states/2020-11-05/china-winning-vaccine-race

More Than 3K Mink Dead From Coronavirus At Wisconsin Farm

Nearly 3,400 mink have died from the coronavirus at a mink farm in Taylor County over the last month, according to the latest numbers from the state Department of Agriculture, Trade and Consumer Protection (DATCP).

DATCP confirmed the first mink deaths from the virus on a farm Oct. 8. At that time, Wisconsin State Veterinarian Dr. Darlene Konkle said several hundred mink at the affected farm had died.

The agency has said it will not release information about the affected farm or parties involved while an investigation into the virus is active.

DATCP spokesperson Kevin Hoffman said all animals or animal products are still quarantined on the farm. He said federal and state officials will use testing and other data to determine when the quarantine can end.

"One of the promising developments up there right now is the rate at which the mink are dying has slowed to normal rates," Hoffman said. "A farm might experience loss due to illness that they might typically see during this time of the year, like pneumonia for example. So that’s what they’re experiencing right now."

Hoffman said there have been no indications that the virus has spread to other mink farms in the state.

But some in the mink industry say farms are bracing for the impact of surging coronavirus cases in the state’s human population.

Dr. John Easley, a veterinarian from Glenbeulah in Sheboygan County and a mink industry consultant, said most mink farms already had biosecurity precautions in place before the pandemic to guard against infections in their animals. He said farms have become even more strict about limiting visitors and using personal protective equipment in response to the coronavirus. But farms will likely see more cases as the virus spreads in humans.

"It just increases the potential of someone that works on a farm becoming infected and not knowingly then bringing the virus onto the farm," Easley said. "As the pandemic develops and is maintained even at whatever level, it's always a risk to our mink farms."

Just like in humans, Easley said much is still unknown about how the virus spreads among mink and what makes some animals more susceptible to serious illness than others.

"There's probably some mink that are asymptomatic, certainly. With any infection that gets into a population, you're going to see different individuals respond in different levels or different intensities of clinical signs," Easley said. "Just like with people, a lot of the mink get the infection but then get over it. Are there any long term effects to that? How long does the immunity last?"

He said researchers are also working to develop a vaccine to protect mink and other susceptible animals like cats and dogs. But Easley said controlling the virus among humans would have a big impact on minimizing the potential for exposure on mink farms.

In response to the coronavirus outbreaks on mink farms, organizations against animal cruelty have called on Gov. Tony Evers to work with federal agencies to phase out the mink industry in the state and across the United States.

Animal Wellness Action and the Center for a Humane Economy say the susceptibility of mink to the virus make it "very hard to justify keeping this receding industry alive as it becomes a potential superspreader of the virus" to other animals and potentially people. The groups have called for a government buy-out of mink farms in the state.

On Wednesday, Reuters reported Denmark authorities will cull the nation's mink population after health officials discovered a mutation of the coronavirus spread from mink to people. Officials say a mutated virus could pose a risk to the effectiveness of a vaccine for humans.

In October, DATCP officials said there was little evidence that infected mink have transmitted the coronavirus to humans. There have been no reports of other types of farm animals, like cattle, hogs or poultry, being infected by the virus.

https://www.wpr.org/more-3k-mink-dead-coronavirus-taylor-county-mink-farm

Human recombinant soluble ACE2 (hrsACE2) shows promise for treating severe COVID­19

• Tarek Mohamed Abd El-Aziz,
• Ahmed Al-Sabi &
• James D. Stockand 

Signal Transduction and Targeted Therapy volume 5, Article number: 258 (2020)

PDF: https://www.nature.com/articles/s41392-020-00374-6.pdf

A recent study by Zoufaly et al. published in The Lancet Respiratory Medicine describes encouraging data from the first severe COVID-19 patient successfully treated with human recombinant soluble angiotensin-converting enzyme-2 (hrsACE2).¹ The published data document upon treatment of an adaptive immune response, the disappearance of the virus swiftly from the serum, the nasal cavity and lungs, and a reduction of inflammatory cytokine levels that are critical for COVID-19 pathology. Notably, the use of hrsACE2 did not impede the generation of neutralizing antibodies, leading to a significant clinical improvement of the treated patient.

https://www.nature.com/articles/s41392-020-00374-6/