Immunity to coronavirus remains a mystery scientists are trying to crack

Scientists stress that just because someone has recovered from Covid-19 and produced antibodies to the coronavirus does not mean they are protected from contracting it a second time. No one’s yet proven that.
That, then, leaves open the question: What does immunity look like?
Experts anticipate an initial coronavirus infection will lend people some level of immunity for some amount of time. But they still don’t know what potpourri of antibodies, cells, and other markers in a person’s blood will signify that protection. And determining those “correlates of protection”  is crucial both so individuals can know if they are again at risk, and so researchers can understand how well potential vaccines work, how long they last, and how to accelerate their development.

“What you would like is to have some blood measure that serves as a correlate of that protective efficacy or immunity,” said Sarah Fortune, the chair of immunology and infectious diseases at Harvard’s T.H. Chan School of Public Health. “Which sounds like it’s simple, but it’s much more complicated than you’d think.”
Knowing the correlates of protection is different from knowing the mechanism of protection. Immunity is a Rube Goldberg machine, a choreography of different proteins and cells that results in the body fending off a pathogen before it can gain a toehold. The scheme varies from pathogen to pathogen.

Correlates of protection, rather, are signals that someone is protected, the way glancing at a formidable offensive line makes clear that it can hold off the pass rush. They could include the presence of  — as well as the levels of — certain types of antibodies, immune cells, or proteins that act like messengers in the immune system.
Scientists don’t need to fully understand the correlates to make progress on vaccines. Already, researchers have launched a number of clinical trials for vaccine candidates to test whether they are safe and effective against Covid-19, the disease caused by the coronavirus. But scientists are relying on clues from how our bodies protect themselves from other viruses, including the other disease-causing coronaviruses, to guide what kind of immune response vaccines should aim to induce.
“We don’t formally need to know” the correlates of protection, said John Mascola, the director of the National Institutes of Health’s Vaccine Research Center. “One can make the vaccine somewhat empirically, which means make it and test it, and in the old days that’s how all the vaccines were made.”
Now, vaccine research and determining the correlates of protection often take place at the same time, Mascola said. And with the coronavirus, vaccine developers “are taking advantage of the fact that we think we know what kind of antibody response to generate, and that’s what the designs are based on.”
After clinical trials confirm one vaccine’s effectiveness, other immunizations that produce the same immune responses could be accelerated into use, Anthony Fauci, the head of the National Institute of Allergy and Infectious Diseases, recently told STAT.
“If one vaccine proves efficacy in a clinical trial and another vaccine is behind it but it’s getting the same correlate of immunity, you could bridge data and facilitate the approval of the second and the third one based on the efficacy of the first one,” Fauci said.

Experts stress that it’s still key to test vaccines in large-scale clinical trials, and not solely approve them based on correlates of protection. Only clinical trials demonstrate whether a vaccine lowers the risk of infection in people or makes them less likely to get severely ill.
To study the correlates of protection, scientists are now peering into the blood of people who have recovered from Covid-19 to map the defenses the immune system put up when the virus attacked. In recent weeks, they’ve described the type of antibodies produced, finding that they can have powerful effects against one of the virus’ key proteins, and that almost all patients who had the disease, even those who had mild infections, generated antibodies. Those are positive signs, given that a type of antibody, called a neutralizing antibody, is, in sufficient quantities, expected to offer some amount of protection for at least some amount of time. Scientists have also reported the rallying of immune cells, which can be involved in recognizing a virus and stopping it.
The thought is that the defenses the body mounted to vanquish the virus the first time provide clues to what is required to fend off a second attack.

To confirm that people who recover from Covid-19 are protected and to determine how long that lasts, scientists have to track people and see what happens to them if they encounter the virus again. That research often focuses on health care workers who are more likely to be exposed repeatedly. (Scientists can’t ethically expose people to the virus again intentionally.)
But with animals, researchers can “challenge” those that are vaccinated or have had an initial infection to see if they can ward the virus off — which is what recent studies in monkeys demonstrated. Scientists found that the animals generated neutralizing antibodies after they first contracted the virus or when they were given experimental vaccines, and that the higher the level of the antibodies the monkeys had (the higher the “titer,” in scientific parlance), the more protected they were against the pathogen when scientists sprayed a second dose into their noses.
“That is a suggestion that neutralizing antibodies to the virus can protect” against reinfection, said Dan Barouch, the director of Beth Israel Deaconess Medical Center’s Center for Virology and Vaccine Research, who steered that research.
If that finding extends to people, “we will start to be able to use that as a predictor of success,” Barouch said. That is, in experiments with vaccine candidates, researchers can start to see what levels of neutralizing antibodies they are producing, and prioritize those that seem to generate more promising responses.

With some diseases, researchers also run “human challenge trials” of vaccines — in which volunteers are given an experimental vaccine and then exposed to the virus — in an attempt to speed up the process of testing them. Scientists are divided over the ethics of such trials for the coronavirus, but those who are supportive say one benefit could be establishing the correlates of protection, indicating which parts of the immune system need to be active to insulate someone from the virus.
Scientists often home in on neutralizing antibodies as correlates, but there can be other markers as well. They include other types of antibodies, like binding antibodies; immune cells like T cells and B cells; and cytokines — small proteins released by immune cells that serve as messengers. In the monkey study, for example, Barouch and colleagues also found an association between protection and the level of another type of antibody, though it wasn’t as strong as the correlation between protection and neutralizing antibodies.
“There are a whole bunch of other things that people look at for correlates of protection,” said virologist Angela Rasmussen of Columbia University.
One challenge is that people respond differently to infections; some studies, for example, have found people who recovered from Covid-19 actually generated low levels of antibodies. But because the immune system is so complex, having low levels of antibodies does not necessarily mean that a person won’t be safeguarded. All that can make it harder to define exactly what immunity looks like.
“Some people who’ve had this have not had high antibody titers or have had low antibody titers,” said Anna Durbin, a vaccine researcher at Johns Hopkins University. “We still don’t know what’s going to happen to them if they’re re-exposed.”

Durbin also noted that what’s happening with immune cells and antibodies in someone’s blood may not mean the cells in the upper airway — which the coronavirus targets — are similarly defended. Certain antibodies in the blood might stave off severe illness, but they won’t necessarily be able to fully prevent the virus from reinfecting cells in the nose and throat.
Because of the difficulties of stopping upper respiratory infections, scientists are already anticipating that Covid-19 vaccines may not provide complete protection — called sterilizing immunity — but will rather reduce the risk of contracting the virus and of getting critically sick.
“I am not convinced we’re going to have a singular, absolute correlate of protection,” Durbin said.

With Covid-19, immunity — whether from an infection or a vaccine — is expected to wane over perhaps a few years; that is what happens with the four human coronaviruses that cause colds. If that pattern extends to this virus, people will gradually become more susceptible to the virus after some amount of time (though they may be less likely to get a severe case). Tracking the levels of the different correlates could provide clues to how long immunity lasts, and when a person becomes vulnerable again. It could also indicate when people might need another dose of the vaccine.
“When we’re trying to evaluate an immune response, we don’t only want to see we engage the proper immune responses for protection,” said Scott Hale, a University of Utah immunologist. “We also want to make sure there’s some form of long-lasting immunity in case you’re exposed to the pathogen in a year or five years or 10 years.”

Immunity to the coronavirus remains a mystery. Scientists are trying to crack the case

Judge limits Gov. Newsom’s emergency rule-making powers

A California judge on Friday sided with Republican legislators who said Gov. Gavin Newsom overstepped his powers with dozens of emergency orders during the coronavirus crisis that changed everything from how public meetings are conducted to when tenants can be evicted.
Sutter County Superior Court Judge Perry Parker only halted one of the orders, involving the November election, but ordered Newsom to refrain from new orders that might be interpreted as usurping the Legislature’s responsibilities.
The judge appeared to adopt without changes a proposed order submitted to him by GOP Assemblymen James Gallagher and Kevin Kiley, who challenged the election order.
Parker barred Newsom “from further exercising any legislative powers in violation of the California Constitution and applicable statute, specifically from unilaterally amending, altering, or changing existing statutory law or making new statutory law.” He scheduled a hearing for June 26 to consider issuing a preliminary injunction.
“This is a victory for separation of powers,” the lawmakers said in a joint statement. “The governor has continued to brazenly legislate by fiat without public input and without the deliberative process provided by the Legislature. Today the judicial branch finally gave him the check that was needed and that the Constitution requires.”
The state attorney general’s office referred questions to the governor’s office because he is their client in the case.
Newsom spokesman Jesse Melgar said in a statement that, “We are disappointed in this initial ruling and look forward to the opportunity to brief the Court on the issues.”
Newsom broadly and repeatedly used his executive and emergency authority during the first weeks of the pandemic to virtually shut down the state and its economy. He’s had the backing of federal and state courts that have blocked previous challenges to his efforts to slow the spread of the coronavirus.
Richard Hasen, a professor of law and political science at the University of California, Irvine, said Parker’s order appears to block executive orders “that would suspend or alter statutory law or further exercise ‘legislative powers.’”
“There can of course be disagreements about what that means in the context of particular executive orders,” he said.
Erwin Chemerinsky, dean of the law school at the University of California, Berkeley, said the judge’s order “says only that the governor cannot issue orders that violate the law.”
“The paragraph in the order is vague, but I think it clearly does not forbid all executive orders, just those that are unconstitutional or violate statutes,” he said.
Lawmakers of both political parties have criticized Newsom, a Democrat, for not sufficiently including them in his sweeping declarations and budget decisions since the pandemic began. The governor has issued more than 40 executive orders, according to a court filing by Gallagher.
They include halting evictions, delaying late fees for paying taxes or renewing drivers licenses, allowing grocery stores to once again hand out single-use bags for free — even allowing couples to be married by video or teleconference, with marriage licenses and certificates digitally signed and sent by email.
They are in a 28-page list submitted by Kiley of Newsom’s orders that alter existing state laws.
They also include allowing local and state governments to hold public telephone meetings instead of meeting in person; extending deadlines for various businesses to pay fees, file reports or renew licenses; suspending rules intended to protect patients’ medical privacy; suspending deadlines and instructional requirements for local school districts; and suspending election deadlines and procedures.
Parker’s broad language forbidding future orders was at the end of a five-paragraph ruling specifically halting a June 3 executive order requiring county election officials to establish hundreds of locations around the state where voters can cast ballots in person in the November election.
Parker temporarily blocked that order, calling it “an impermissible use of legislative powers in violation of the California Constitution and the laws of the State of California.”
Newsom previously had ordered officials to send every registered voter a mail-in ballot for the election as one of many responses to the coronavirus pandemic. Republicans from President Donald Trump on down have criticized that move as allowing for potential voter fraud, but Parker’s ruling did not address that earlier order.
Separately, however, the conservative group Judicial Watch said it has filed a motion in its own federal lawsuit seeking a preliminary injunction against Newom’s order that ballots be sent to every voter.
State lawmakers, meanwhile, are advancing their own bills that would direct counties to send mail-in ballots to every registered voter. The Assemblymen’s lawsuit notes that they have been back in session since May 4, including when Newsom issued the elections order, despite having suspended the legislative session at the start of the pandemic.

Judge limits Gov. Newsom’s emergency rule-making powers

Indonesia Claims Five Drug Combinations Effectively Reduce Novel Coronavirus

Researchers from Airlangga University, Government’s Covid-19 Task Force, and State Intelligence Agency (BIN) have claimed to have found combinations of medicine that effectively reduce the number of Sars-Cov-2, the coronavirus that causees Covid-19 disease, in the human body.
The researchers have submitted the result to several scientific journals for peer review.
“We have been conducting research on medicine combination regiment and two kinds of stem cells that quite good for eliminating the virus. We use the Sars-Cov-2 virus from Indonesia,” Purwati, the head of Airlangga University’s Stem Cell Research and Development Center, said on Friday.
Purwati said the first medicine combination comprises of Lopinavir, Ritonavir, and Azithromycin. The second combination includes of Lopinavir, Ritonavir, and Doxycycline. The third combination includes of Lopinavir, Ritonavir, and Clarithromycin. The fourth combination comprises of Hydroxychloroquine and Azithromycin. Meanwhile, the fifth combination comprises of Hydroxychloroquine and Doxycycline
“We have observed those combinations gradually from 24 hours, 48 hours, and 72 hours and it showed that the number of viruses lowered from hundreds of thousands to undetected,” she said in a virtual press conference.
Purwati said the researchers examined 14 medicine regiments in total, but only found that were effective against the novel coronavirus.
She also explained the researchers decided to use a combination regiment because it has better potency and effectiveness than the single regiment.
“The combination regiment also requires less dosage, one-fifth to one-third of the normal dosage, thus decrease the medicine toxicity in a healthy body,” Purwati added.
Purwati said the medicines used in the combinations are the ones that already in the market. The medication, she said, has been through various testing of National Drug and Food Control Agency (BPOM) such as in-vitro testing, animal testing, and post-marketing drug testing and obtained circulation permit.
She said the researchers had ensured the medicine compound safety through several steps.
“First, we ensure whether the medicine contained toxic or not. Second, we observe the medicine’s capability to kill the virus. Third, we check the medicine’s effectiveness and how long the effects could last. We also check the medicine’s inflammatory and anti-inflammatory factors,” Purwati said.
Aside from that, Airlangga University, Government’s Covid-19 Task Force and State Intelligence Agency have run research on two kinds of stem cells, natural-killer cell and hematopoietic cell.
“Based on the observation, the natural-killer cell and the hematopoietic cell can inactivate 80 percent to 90 percent of the virus within 48 hours to 72 hours,” Purwati said.
She said the cells had been taken from the patient’s blood with a breeding time of 3 to 4 days for hematopoietic cell and 7 to 14 days for the natural-killer cell. Purwanti said, for preventive settings, the natural-killer cell can last for approximately four months.
“We hope what we have been doing with the Covid-19 Task Force and BIN can be useful for Indonesia and the world. We have also disseminated this research by submitting seven journals about this research,” Purwati said.
https://jakartaglobe.id/news/indonesia-claims-five-drug-combinations-effectively-reduce-novel-coronavirus

Silicones may lead to cell death

Silicone molecules from breast implants can initiate processes in human cells that lead to cell death. Researchers from Radboud University have demonstrated this in a new study that will be published on 12 June in Scientific Reports. “However, there are still many questions about what this could mean for the health effects of silicone breast implants. More research is therefore urgently needed,” says Ger Pruijn, professor of Biomolecular Chemistry at Radboud University.

The possible side effects of silicone breast implants have been debated for decades. There are known cases where the implants have led to severe fatigue, fever, muscle and joint aches, and concentration disturbance. However, there is as yet no scientific study demonstrating the effect silicone molecules can have on human cells that could explain these side effects.
Silicone in the body
It is a known fact that breast implants ‘bleed’, i.e. silicone molecules from the implant pass through the shell and enter the body. Earlier research, in 2016, by Dr Rita Kappel, plastic surgeon, and Radboud university medical center, found that silicone molecules can then migrate through the body via the bloodstream or lymphatic system. The biochemists at Radboud University next asked themselves the follow-up question: what effect might silicone molecules have on cells exposed to it?
Cultured cells
Experiments with cultured cells showed that silicones appeared to initiate molecular processes that lead to cell death. “We observed similarities with molecular processes related to programmed cell death, a natural process called apoptosis that has an important function in clearing cells in our body. This effect appeared to depend on the dose of silicone and the size of the silicone molecules. The smaller the molecule, the stronger the effect,” according to Pruijn.
To investigate the effect of silicones on human cells, the researchers have added small silicone molecules — which also occur in silicone breast implants — to three different types of cultured human cells. “One cell was more sensitive to the effect of silicones than the other two cell types. This suggests that the sensitivity of human cells to silicones varies.”
Open questions
The effects the researchers have found lead to many new questions. “We observed that silicones induce molecular changes in cells, but we don’t know yet whether these changes could, for example, lead to an autoimmune response, which could in part explain the negative side effects of implants,” says Pruijn.
“Caution is advised with drawing conclusions based on these findings because we used cultured cells in our research, not specific human cells such as brain cells or muscle cells. Further research is required to get more clarity.”

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

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Journal Reference:

1. Carla Onnekink, Rita M. Kappel, Wilbert C. Boelens, Ger J. M. Pruijn. Low molecular weight silicones induce cell death in cultured cells. Scientific Reports, 2020; 10 (1) DOI: 10.1038/s41598-020-66666-7

https://www.sciencedaily.com/releases/2020/06/200612111353.htm

COVID-19: Tradeoffs between economics and public health

Banks and bookstores. Gyms and juice bars. Dental offices and department stores. The Covid-19 crisis has shuttered some kinds of businesses, while others have stayed open. But which places represent the best and worst tradeoffs, in terms of the economic benefits and health risks?

A new study by MIT researchers uses a variety of data on consumer and business activity to tackle that question, measuring 26 types of businesses by both their usefulness and risk. Vital forms of commerce that are relatively uncrowded fare the best in the study; less significant types of businesses that generate crowds perform worse. The results can help inform the policy decisions of government officials during the ongoing pandemic.
As it happens, banks perform the best in the study, being economically significant and relatively uncrowded.
“Banks have an outsize economic impact and tend to be bigger spaces that people visit only once in a while,” says Seth G. Benzell, a postdoc at the MIT Initiative on the Digital Economy (IDE) and co-author of a paper published Wednesday that outlines the study. Indeed, in the study, banks rank first in economic importance, out of the 26 business types, but just 14th in risk.
By contrast, other business types create much more crowding while having far less economic importance. These include liquor and tobacco stores; sporting goods stores; cafes, juice bars, and dessert parlors; and gyms. All of those are in the bottom half of the study’s rankings of economic importance. At the same time, cafes, juice bars, and dessert parlors, taken together, rank third-highest out of the 26 business types in risk, while gyms are the fifth-riskiest according to the study’s metrics — which include cellphone location data revealing how crowded U.S. businesses get.
“Policymakers have not been making clear explanations about how they are coming to their decisions,” says Avinash Collis PhD ’20, an MIT-trained economist and co-author of the new paper. “That’s why we wanted to provide a more data-driven policy guide.”
And if the Covid-19 pandemic worsens again, the research can apply to shuttering businesses again.
“This is not only about which locations should reopen first,” says Christos Nicolaides PhD ’14, a digital fellow at IDE and study co-author. “You can also look at it from the perspective of which locations should close first, in another future wave of Covid-19.”
The paper, “Rationing Social Contact During the COVID-19 Pandemic: Transmission Risk and Social Benefits of U.S. Location,” appears in Proceedings of the National Academy of Science, with Benzell, Collis, and Nicolaides as the authors. Benzell is about to start a new position as an assistant professor at Chapman University; in July, Collis will become an assistant professor at the University of Texas at Austin; Nicolaides is also a faculty member at the University of Cyprus.
Cumulative risk
To conduct the study, the team examined anonymized location data from 47 million cellphones, from January 2019 through March 2020. The data included visits to 6 million distinct business venues in the U.S. The 26 types of businesses in the study accounted for 57 percent of those visits, meaning the study covers a broad swath of the economy.
By examining the location data over an extended time period, the scholars were able to determine what the typical crowding level is for all business types in the study.
The study also used payroll, revenue, and employment data from U.S. Census Bureau to rate the centrality of different industries to the economy. Businesses in the study represented 1.43 million firms, 32 million employees, $1.1 trillion in payroll, and $5.6 trillion in revenues. The researchers also added a survey of 1,099 people people to gauge public preferences about different types of business.
A key to the researchers’ approach is recognizing that during the pandemic, many consumers are trying to limit trips that generate interaction with strangers, while still needing to get essential and useful transactions done.
As Benzell notes, “The idea was, how can we think about rationing social contacts in a way that gives us the most bang for our buck, in terms of meetings, while keeping the risk of Covid transmission as low as possible?”
The study also rates risk on the basis of aggregate public exposure, per business type. On an individual basis, spending a couple of hours in a movie theater with strangers might seem quite risky. But in February 2020, movie theaters had about 17.6 million consumer visits in the U.S., whereas sit-down restaurants had almost 900 million visits in the same month. As a business category, sit-down restaurants would likely generate much more total transmission of Covid-19.
“It’s not danger per visit, but it’s a cumulative danger,” Nicolaides explains. “If you look at movie theaters, they seem dangerous, but not that many people go to the movies every day … and restaurants are a good counter-example.”
Outlier: Liquor stores staying open
In many cases, the researchers say, policymakers have made reasonable decisions about which types of businesses should be open and closed. But there are exceptions to this. Take liquor stores, which have been deemed an “essential” business in many U.S. states.
“What really jumps out at us is liquor and tobacco stores,” Benzell says. “Most states have allowed liquor stores to remain open. This is a bit of a bad call from our perspective, because liquor stores don’t create a lot of social value. If you ask people which stores they want to be open, liquor stores are near the bottom of that list. They don’t have that many receipts or employees, and they tend to be these small, crowded places where people are up against each other trying to navigate.”
In the study, liquor stores rate 20th out of the 26 business types in economic importance, but 12th highest in risk.
By contrast, the researchers are more bullish about the public health dynamics of college and universities, which they rank 8th out of the 26 business types in economic importance, but just 17th in terms of risk. If campus living arrangements could be made more safe, the researchers think, the other parts of university life could offer relatively reasonable conditions.
“Colleges and universities actually have the potential to offer pretty good social contact tradeoffs,” Benzell says. “They tend to be places with big campuses, they tend to be [composed of] consistently the same group of young people, visiting the same places. When people are worried about colleges and universities, they’re mostly worried about dormitories and parties, people getting infected that way, and that’s fair enough. But [for] research and teaching, these are big spaces, with pretty modest groups of people that produce a lot of economic and social value.”
The scholars note that the study contains national ratings, and acknowledge that there might be some regional variation in effect as well.
“If a local government would like to apply this paper [to their policies], it may be a better idea to put in their own data to make decisions,” says Nicolaides. That said, the study did not indicate significantly different results for urban and rural settings, something the researchers evaluated.
To be sure, some businesses are adapting to the pandemic by using new protocols or safety measures, such as limited customers in hair salons or safety partitions at supermarket checkout counters. Studying business venues with such safety measures in place would also be valuable, the scholars note.
“Moving forward, an interesting exercise would be to see how dangerous these locations are once you implement these mitigation strategies.” Collis says. “Those are all interesting open questions, seeing which business adapt. And some of these adaptations will probably be temporary changes, but other business practices may stick in the Covid age.”
Research support was provided by MIT’s Initiative on the Digital Economy.

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Story Source:
Materials provided by Massachusetts Institute of Technology. Original written by Peter Dizikes. Note: Content may be edited for style and length.

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Journal Reference:

1. Seth G. Benzell, Avinash Collis, Christos Nicolaides. Rationing social contact during the COVID-19 pandemic: Transmission risk and social benefits of US locations. Proceedings of the National Academy of Sciences, 2020; 202008025 DOI: 10.1073/pnas.2008025117

https://www.sciencedaily.com/releases/2020/06/200611183930.htm

COVID-19 fuels major unknowns as insurers tackle 2021 rate setting

• Insurers face myriad challenges as they set premium rates for 2021 in the individual and small group market in the midst of the COVID-19 pandemic. The crisis is forcing payers to consider a slew of scenarios, laid out in an annual issue brief from the American Academy of Actuaries.
• The brief notes the pandemic has fueled “significant uncertainty” in projecting claims and lists a number of scenarios, including the potential for additional waves of infection this year and next.
• At first blush, the financial picture may seem hopeful for insurers, with deferred care outweighing the increased medical costs to treat COVID-19 patients. But the brief spells out challenges that may lead to higher spend, including a shift in coverage leading to adverse selection, deteriorating health for those delaying care and pressure on reimbursement rates as providers seek to make up for losses.

Even in the midst of a pandemic, the nation’s largest insurers have seemed cautiously optimistic about 2020, mainly due to the fact that the plunge in patient volumes has offset the increased costs to treat those infected with the novel coronavirus.
In fact, the depressed patient volumes have lead to an unprecedented descent in healthcare spending. For decades, healthcare spending has steadily ticked upward, until this spring when it took a nose dive, according to figures from the Kaiser Family Foundation.

Retrieved from Kaiser Family Foundation on June 11, 2020

Yet, the nation is long from thwarting the virus without an effective treatment or a vaccine readily available. And as states across the country lift social distancing restrictions, infections will most likely continue to rise.
Compounding the issue is the staggering drop in employment. The unemployment rate reached a record of 14.7% in April, though slightly improved to 13.3% in May as many returned to work. With job loss comes the risk of losing health insurance coverage for millions of Americans, the majority of whom receive coverage through work.
Job losses are expected to spur a shift in coverage as people who lose insurance turn to plans on the Affordable Care Act exchanges or elect COBRA. Others may be eligible for Medicaid.
For insurers, this shift can result in adverse selection for them, ending up with a member who is less healthy and costs more. However, people in the employer market tend to be viewed as healthier.
“For instance, when individuals lose coverage, they must decide whether to purchase coverage, and less-healthy people are generally thought to be more likely to purchase coverage than healthy individuals,” according to the issue brief.
On the flip side, the pandemic may motivate some to purchase insurance due to the risk of getting sick while uninsured, according to the brief.
Another scenario laid out in the paper that makes pricing more difficult is coverage for testing for the virus, which public health experts have said is key to containing and controlling future outbreaks. But who will pay for continued testing as it’s used as a public health tool is still a muddied question.
If insurers are expected to pay, outside the need for confirming as a means for diagnosis and treatment, it could pump up costs. Not to mention the potential costs if a vaccine is available.
As patients return to providers, the delayed care could have resulted in poor health, particularly those who put off cancer or other key screenings. If there is a degradation in health status for people, it will likely lead to increased per member costs.
Plus, providers are likely to pressure insurers for higher reimbursements as they seek to make up for losses experienced during the downturn toward the end of the first quarter amid mandated social distancing.
https://www.healthcaredive.com/news/covid-19-fuels-major-unknowns-as-insurers-tackle-2021-rate-setting/579634/

Sugar coating locks and loads coronavirus for infection

They say you can’t judge a book by its cover. But the human immune system does just that when it comes to finding and attacking harmful microbes such as the coronavirus. It relies on being able to recognize foreign intruders and generate antibodies to destroy them. Unfortunately, the coronavirus uses a sugary coating of molecules called glycans to camouflage itself as harmless from the defending antibodies.

Simulations on the National Science Foundation (NSF)-funded Frontera supercomputer at the Texas Advanced Computing Center (TACC) have revealed the atomic makeup of the coronavirus’s sugary shield. What’s more, simulation and modeling show that glycans also prime the coronavirus for infection by changing the shape of its spike protein. Scientists hope this basic research will add to the arsenal of knowledge needed to defeat the COVID-19 virus.
Sugar-like molecules called glycans coat each of the 65-odd spike proteins that adorn the coronavirus. Glycans account for about 40 percent of the spike protein by weight. The spike proteins are critical to cell infection because they lock onto the cell surface, giving the virus entry into the cell.
“You really see how effective its glycan shield is,” said Rommie Amaro, a professor of chemistry and biochemistry at the University of California, San Diego. “That’s because you see the glycans covering the surface of the viral spike protein, which is the most exposed bit and the part that’s responsible for the initial infection in the human cell,” she said.
Amaro is a corresponding author of a study published June 12, 2020 on bioRxiv.org—an open-access repository of electronic preprints—that discovered a potential structural role of the shielding glycans that cover the SARS-CoV-2 spike protein. “You can see very clearly that from the open conformation, the spike protein has to undergo a large structural change to actually get into the human cell,” Amaro said.
But even to make an initial connection, she said that one of the pieces of the spike protein in its receptor binding domain has to lift up. “When that receptor binding domain lifts up into the open conformation, it actually lifts the important bits of the protein up over the glycan shield,” Amaro explained.
This is in contrast to the closed conformation, where the shield covers the spike protein. “Our analysis gives a potential reason why it does have to undergo these conformational changes, because if it just stays in the down position those glycans are basically going to block the binding from actually happening,” she said.
Another aspect of their study showed how shifts in the conformations of the glycans triggered changes in the spike protein structure. “One thing that really jumped out at us is that in the open conformation there are two glycans that basically prop up the protein in that open conformation,” Amaro said.
“That was really surprising to see. It’s one of the major results of our study. It suggests that the role of glycans in this case is going beyond shielding to potentially having these chemical groups actually being involved in the dynamics of the spike protein,” she added.
She likened the action of the glycan to pulling the trigger of a gun. “When that bit of the spike goes up, the finger is on the trigger of the infection machinery. That’s when it’s in its most dangerous mode—it is locked and loaded,” Amaro said. “When it gets like that, all it has to do is come up against an ACE2 receptor in the human cell, and then it’s going to bind super tightly and the cell is basically infected.”

Amaro and her colleagues use computational methods to build data-centric models of the SARS-CoV-2 virus, and then use computer simulations to explore different scientific questions about the virus.
They started with various experimental datasets that revealed the structure of the virus. This included cryo-EM structures from the Jason McLellan Lab of The University of Texas at Austin; and from the lab of David Veesler at the University of Washington. “Their structures are really amazing because they give researchers a picture of what these important molecular machines actually look like,” Amaro said.
Unfortunately, even the most powerful microscopes on Earth still can’t resolve movement of the protein at the atomic scale. “What we do with computers is that we take the beautiful and wonderful and important data that they give us, but then we use methods to build in missing bits of information,” Amaro said.
What’s more, details of the glycan shielding have been too difficult for experiments to resolve. “What people really want to know, for example vaccine developers and drug developers, is what are the vulnerabilities that are present in this shield,” Amaro said.
The computer simulations allowed Amaro and colleagues to create a cohesive picture of the spike protein that includes the glycans. “The reason why the computer resources at TACC are so important is that we can’t understand what these glycans look like if we don’t use simulation,” Amaro said.
Amaro was awarded compute time on the NSF-funded Frontera supercomputer of TACC. Her team has used about 2.3 million node hours for molecular dynamics simulations and modeling , the most among any researchers using the system to study COVID-19. She used up to 4,000 nodes, or about 250,000 processing cores. Frontera—the leadership-class system in NSF’s cyberinfrastructure ecosystem—ranks as the fifth most powerful supercomputer in the world and the fastest academic system, according to November 2019 rankings of the Top500 organization.
In order to animate the dynamics of the 1.7 million atom system under study, a lot of computing power was needed, said Amaro. “That’s really where Frontera has been fantastic, because we need to sample relatively long dynamics, microsecond to millisecond timescales, to understand how this protein is actually working.”
“We’ve been able to do that with Frontera and the COVID-19 HPC Consortium,” Amaro said. “Now we’re trying to share our data with as many people as we can, because people want a dynamical understanding of what’s happening—not only with other academic groups but also with different pharmaceutical and biotech companies that are conducting neutralizing antibody development,” she said.
Basic research is making a difference in winning the war against the SARS-CoV-2 virus, Amaro explained. “The more we know about it, the more of its abilities that we’re going to be able to go after and potentially take out,” she added.
Said Amaro: “It’s of such great importance that we learn as much as we can about the virus. And then hopefully we can translate those understandings into things that will be useful either in the clinic, or the streets, for example if we’re trying to reduce transmission for what we know now about aerosols and wearing masks. All these things will be part of it. Basic research has a huge role to play in the war against COVID-19. And I’m happy to be a part of it. It’s a strength that we have Frontera and TACC in our arsenal.”
The study, “Shielding and Beyond: The Roles of Glycans in SARS-CoV-2 Spike Protein,” was published on bioRxiv.org June 12, 2020. The study authors are Lorenzo Casalino, Zied Gaieb, Abigail C. Dommer, Rommie E. Amaro of the Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA; and Aoife M Harbison, Carl A Fogarty, Elisa Fadda of the Department of Chemistry and Hamilton Institute, Maynooth University, Dublin, Ireland. This work was supported by NIH GM132826, NSF RAPID MCB-2032054, an award from the RCSA Research Corp., a UC San Diego Moore’s Cancer Center 2020 SARS-COV-2 seed grant, the Visible Molecular Cell Consortium, and the Irish Research Council.

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Coronavirus massive simulations completed on Frontera supercomputer

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More information: Lorenzo Casalino et al. Shielding and Beyond: The Roles of Glycans in SARS-CoV-2 Spike Protein, bioRxiv (2020). DOI: 10.1101/2020.06.11.146522

https://phys.org/news/2020-06-sugar-coating-coronavirus-infection.html