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Tuesday, July 14, 2020

Primate Study Finds Acquired Immunity Prevents COVID-19 Reinfections

There have been rare reports of people recovering from infection with SARS-CoV-2, the novel coronavirus that causes COVID-19, only to test positive a second time. Such results might be explained by reports that the virus can linger in our systems. Yet some important questions remain: Is it possible that people could beat this virus only to get reinfected a short time later? How long does immunity last after infection? And what can we expect about the duration of protection from a vaccine?
A recent study of rhesus macaques, which are among our close primate relatives, offers relevant insights into the first question. In a paper published in the journal Science, researchers found that after macaques recover from mild SARS-CoV-2 infection, they are protected from reinfection—at least for a while.
In work conducted in the lab of Chuan Qin, Peking Union Medical College, Beijing, China, six macaques were exposed to SARS-CoV-2. Following infection, the animals developed mild-to-moderate illness, including pneumonia and evidence of active infection in their respiratory and gastrointestinal tracts. Twenty-eight days later, when the macaques had cleared the infection and started recovering, four animals were re-exposed to the same strain of SARS-CoV-2. The other two served as controls, with researchers monitoring their continued recovery.
Qin’s team noted that after the second SARS-CoV-2 exposure, the four macaques developed a transient fever that had not been seen after their first infection. No other signs of reinfection were observed or detected in chest X-rays, and the animals tested negative for active virus over a two-week period.
While more study is needed to understand details of the immune responses, researchers did detect a reassuring appearance of antibodies specific to the SARS-CoV-2 spike protein in the macaques over the course of the first infection. The spike protein is what the virus uses to attach to macaque and human cells before infecting them.
Of interest, levels of those neutralizing antibodies were even higher two weeks after the second viral challenge than they were two weeks after the initial exposure. However, researchers note that it remains unclear which factors specifically were responsible for the observed protection against reinfection, and apparently the first exposure was sufficient.
Since the second viral challenge took place just 28 days after the first infection, this study provides a rather limited window into broad landscape of SARS-CoV-2 infection and recovery. Consequently, it will be important to determine to what extent a first infection might afford protection over the course of months and even years. Also, because the macaques in this study developed only mild-to-moderate COVID-19, more research is needed to investigate what happens after recovery from more severe COVID-19.
Of course, macaques are not humans. Nevertheless, the findings lend hope that COVID-19 patients who develop acquired immunity may be at low risk for reinfection, at least in the short term. Additional studies are underway to track people who came down with COVID-19 in New York during March and April to see if any experience reinfection. By the end of this year, we should have better answers.
Reference:
[1] Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques. Deng W, Bao L, Liu J, et al. Science. 2020 Jul 2. [Published online ahead of print].
Links:
Qin Lab (Peking Union Medical College, Beijing, China)

New Approach May Greatly Improve Damaged Lungs to be Used in Transplants

Scientists at Columbia University and Vanderbilt University have been working on ways to revive damaged lungs for the last eight years. In a study published in Nature Medicine, they describe how they were able to successfully restore badly damaged lungs in order to use them for lung transplants.
The authors of the study note that patients who are on waiting lists for lung transplants “face high wait-list mortality, as injury precludes the use of most donor lungs.” A process known as ex vivo lung perfusion (EVLP) can improve the quality of donor’s lungs that are marginal but extending room temperature (normothermic) support past six hours has been difficult.
In their research, they placed each damaged lung in a plastic box. The attached a respirator to the lung, allowing it to “breathe.” The lung was then connected to a vein in the neck of a live pig. This allowed for the blood to flow through the vessels in the lung. They found that within 24 hours, the lungs appeared viable and laboratory tests confirmed that the lungs had been resuscitated.
The researchers are now investigating the possibility of using humans instead of a pig. A catheter in the patient’s neck would transfer blood to the damaged lung, which would be in a respirator in the room.
Although a long way from being ready for clinical use, it’s an approach that is showing quite a bit of promise, particularly in the face of significant need. In the U.S. in 2018, 2,562 lung transplants were performed. In the same year, 3,134 patients were added to the wait-list. Meanwhile, about 365 patients died waiting for a transplant lung to become available or were too ill to undergo surgery.
And unfortunately, the COVID-19 pandemic is increasing the need for lung transplants. In June, a lung transplant for a COVID-19 patient, a woman in her 20s, was the first person to receive a double-lung transplant as a result of COVID-19. She received the transplant at Northwestern Memorial Hospital in Chicago. The woman was otherwise healthy, but after contracting COVID-19, spent almost two months in intensive care on a ventilator and an ECMO machine that pumps and oxygenates blood outside the body. The woman eventually eliminated the virus from her system, but was in severe condition and her lungs were irreversibly damaged.
Of the experiments with pigs, Zachary N. Kon, surgical director of the lung transplant center at New York University Langone Center, told The New York Times, “Would I consider doing this? Absolutely. It’s a transformative idea that would allow a jump forward in the field.”
David W. Roe, a lung transplant surgeon at Indiana University, told the Times, “This is all on the outer cusp, but I don’t think it is out of the realm of possibility. It all makes sense.”
The lead author of the new study, Matthew D. Bachetta, a lung transplant surgeon at Vanderbilt, indicated that with current surgery standards, only about 20% of donated lungs are usable. If there was a way to increase that to 40%, the waiting list for transplantable lungs could be eliminated.
The criteria for eligibility are high because of limited supply. Typically, medical centers rule out patients 70 years of age or older, people who are frail, and even teenagers if their frailty is caused by damaged lungs.
“If we could expand the donor pool,” Bacchetta said, “we could avoid a lot of waiting-list deaths and could be more open-minded about who could have a transplant.”
One of the researchers in the group, Gordana Vunjak-Novakovic, from Columbia, tried to bioengineer lungs by removing all the cells from the lungs, which left a scaffold to build new lungs from.
“It looked very cool, but it was leaky,” Vunjak-Novakovic said. “This caused a massive loss of blood. This was telling us that, unlike other tissues, you cannot make a lung in the lab.”
But researchers at the University of Toronto had developed a way to resuscitate lung by filtrating the damaged lungs with a clear nutrient fluid and hooking the lungs to a ventilator. It worked reasonably well, but the lungs could only be maintained for hours, not days. And not many lungs can be fixed that way.
Funjak-Novakovic and her group developed this new method to improve on the Toronto technique and appears to be successful.

Reactions mixed to HHS’ new protocol for hospitals reporting COVID-19 data

Hospitals will begin reporting their daily coronavirus information including patients, bed counts and available supplies to HHS on July 15 instead of the CDC.
The Trump administration on July 10 changed the protocols for coronavirus data reporting, which in March originally required hospital administrators to send data on coronavirus testing, capacity and patient flow to the CDC on a daily basis. The switch in data collection responsibility follows public health experts’ concerns that the administration is undermining disease control centers and politicizing science, Nicole Lurie, MD, told The New York Times.
“Centralizing control of all data under the umbrella of an inherently political apparatus is dangerous and breeds distrust,” said Dr. Lurie, who served as assistant secretary for preparedness and response under former President Barack Obama. “It appears to cut off the ability of agencies like CDC to do its basic job.”
HHS said that taking control of the daily reports will help the federal government better monitor resource usage and allocate supplies including personal protective equipment and antiviral drug remdesivir during the pandemic. White House coronavirus response coordinator Deborah Birx, MD, assembled a group of government and hospital officials to coordinate the new reporting process several weeks ago after learning hospitals were not properly reporting their data, according to the report.
Some hospital officials told the Times they support the change because it will relieve them of having to respond to data requests from multiple federal agencies. However, news of the data reporting shift shocked the CDC, according to two officials who spoke on condition of anonymity, because the agency has traditionally overseen the gathering of public health data.
U.S. Rep. Donna Shalala, D-Fla., told the Times that the CDC is the proper agency to handle health data reporting and if its systems have flaws, they should be fixed. “Only the CDC has the expertise to collect data,” said Ms. Shalala, who served as health secretary under former President Bill Clinton. “I think any move to take responsibility away from the people who have the expertise is politicizing.”
A spokesman for the disease control centers referred the Times‘ questions to HHS, which did not respond to a request for comment.

What’s next for Anthony Fauci, if the White House continues to sour on him?

The White House in recent days has accelerated an effort that President Trump began months ago: openly discrediting the guidance of Anthony Fauci, the country’s top infectious diseases researcher.
Trump accused Fauci of making “a lot of mistakes” since the onset of the Covid-19 pandemic in a recent interview, justifying his continued disagreements with the veteran scientist on issues as routine as the number of new coronavirus cases. He also said he disagreed with Fauci’s assessment that the U.S. was handling the crisis poorly compared to other nations — which, given the 60,000-plus Americans being diagnosed with the disease each day, is a simple reality. On Sunday, the Washington Post reported the White House had begun circulating a list of Fauci’s early predictions and guidance surrounding the Covid-19 pandemic that many, in hindsight, have labeled as overly optimistic, though several lacked context.
The latest broadsides have reignited fears that Trump could take far more drastic action to limit Fauci’s public health power and platform — or even remove him from his post, the way Trump has unceremoniously axed so many other federal officials.
Fauci’s future role in the U.S. government’s pandemic response will follow one of three paths. Though Trump can’t easily fire him, administration officials could remove him from his post leading the National Institute of Allergy and Infectious Diseases and reassign him elsewhere in government. Trump could also attempt to formally bar Fauci from conducting public briefings or interviews, effectively silencing one of the administration’s most recognizable public health experts.
Or Trump could continue to quietly diminish Fauci’s role and subtly limit his public platform — as he has for months.
Fauci’s role in public outreach has visibly diminished since spring, when he would regularly accompany Trump to daily White House coronavirus task force press briefings. His public role has since been reduced to sporadic appearances on podcasts, at scientific gatherings, or in print news stories. Fauci said recently he hasn’t briefed the president since June.
Even at the since-discontinued briefings, Trump would challenge Fauci, once admitting “we disagree a little bit” on lack of evidence surrounding hydroxychloroquine, the malaria drug, in preventing Covid-19, allowing that his view was “just a feeling.”
For now, however, the White House has insisted that Fauci remains in good standing and is not in jeopardy of losing his job. Trump even boasted of his “very good relationship” with Fauci on Monday.
Outside experts, however, feel that as long as Fauci continues to speak the truth on the realities of the pandemic, he’ll keep making enemies within the administration.
“If they do punish Fauci for telling the truth, then where are we?” said Elias Zerhouni, the former NIH director who famously testified to Congress that former president George W. Bush’s ban on scientific use of embryonic stem cells was stifling research. “You can ignore it, you can say I don’t take [your advice] into account, I changed my mind, I’m the policymaker. But don’t say you’re going to punish the messenger.”
Below, STAT walks through the possible futures for Fauci — and why some are likelier than others.

1. Trump moves to dismiss Fauci

The most dramatic — and least likely — move: Trump could try to fire Fauci.
But federal law prevents the president from firing most government employees without cause.
“Tony Fauci is not a presidential appointee,” Zerhouni said. “He’s a civil [servant] for 35, 40 years. So you can’t really fire him from the government — that’s not in the powers of the president.”
But if push came to shove, Trump could almost certainly order Fauci’s superiors — health secretary Alex Azar or NIH chief Francis Collins — to reassign him to a different role within the Department of Health and Human Services.
There’s precedent for such a move even during the Covid-19 pandemic. In late April, the Trump administration abruptly made a leadership change at BARDA, an agency explicitly tasked with keeping the nation prepared for a pandemic or bioterrorism.
The agency’s ousted leader, Rick Bright, was reassigned to a post at NIH focused on developing diagnostic tests. He soon claimed in a whistleblower lawsuit that his reassignment was retribution for his opposition to the president’s enthusiasm for hydroxychloroquine.
Zerhouni stressed that he does not believe Trump would move to reassign Fauci. But if he did, he said, it would put Azar and Collins in a difficult position.
It would be “like the Saturday Night Massacre, to be honest with you,” Zerhouni said, referencing the infamous 1973 night when former president Richard Nixon ordered his attorney general to fire a special prosecutor investigating the White House, only for the attorney general and his deputy to resign in protest instead of carrying out his order.
“If they do that, a lot of other people would resign,” he said.

2. Trump sidelines and bars Fauci from speaking

A slightly less severe, though no less noticeable, step: Trump could cut off Fauci from making any media appearances whatsoever.
Already in March, White House officials started requiring federal health experts to get their approval for any public speaking engagement. And Fauci’s seen his time limited as the pandemic has dragged on, especially after the administration’s Covid-19 task force stopped conducting daily briefings.
It’s not an out-of-the-ordinary arrangement; NIH leadership had to clear its media appearances with the White House in Zerhouni’s time too, the former NIH director said.
“You have to go by the rules of communication in the government,” he said. “It’s very typical.”
But Trump has, at least in one case, taken things much farther. In late February, Nancy Messonnier, a high-ranking Centers for Disease Control and Prevention official, delivered a stark warning in a press briefing: The agency expected the coronavirus would soon begin spreading through American communities, and the disruptions to daily life could be “severe.”
The remarks now seem prescient, even unreasonably calm. But when they were published, stock markets nosedived, and Trump was enraged, and reportedly advocated for firing Messonnier. The end result has been functionally similar, at least in terms of Messonnier’s public-facing role: She has not briefed reporters, or spoken publicly in any way, since.
That’s far more concerning, Zerhouni said.
“The fact that they don’t let you for a long time — that is something else. I never had that,” he said. “I always cleared it with the White House and HHS and it was usually OK, and I don’t recall an instance where I was censored to not talk.”
Even if the White House did bar Fauci from any future media appearances, he could still continue in arguably his most important function: helping to oversee the development of coronavirus vaccines and therapeutics. Messonnier, in fact, has presumably done much the same at CDC, returning to run an agency office focused on vaccines and respiratory diseases.
Attempting to silence Fauci from his role as a public health messenger, however, seems both difficult and unlikely: He is well-liked and trusted among Americans, effectively a household name.

3. Fauci stays in the background

Fauci, who has served six presidents and led the NIAID since 1984, isn’t necessarily the natural face of public health. His main job at NIAID is to oversee nearly $6 billion in grants and in-house research conducted into vaccines and medicines.
Fauci’s role, technically, is that of a researcher — not that of a public health adviser. It’s only after decades playing a leading role advising presidents like Ronald Reagan during the HIV epidemic and Barack Obama during the Ebola outbreak in Western Africa that the public has come to view him as a key part of any president’s public health apparatus — a role that could easily be filled by CDC or others within the federal health department.
But because Fauci’s role as a public spokesman is not a formal part of his job, it’s also easy for Trump and other federal officials to limit how much of that work falls to him.
Experts view this as the most likely scenario, in large part because it is the one that is currently happening. And despite the low-grade attacks, former NIH director Harold Varmus argued it’s a tolerable status quo — as long as decisions about what research the agency funds and conducts doesn’t become more politicized, too.
“So far, [criticism of Fauci] has not affected the way NIH conducts and supports scientific research, he said. “On the other hand, certainly, the government should have a representative who speaks the truth about what’s going on and no one is as well equipped as Tony Fauci to do that.”