Hes not. But his assessment, that well live with Covid-19 for many years to come, is a startling admission from the longtime infectious disease expert who said the country could flatten the curve and achieve herd immunity, first through social distancing and then vaccination.
The ever-mutating, highly contagious coronavirus, which no country has conquered, upended those plans. With his career winding down, Fauci wants to help repair the national bonds that the pandemic shredded, and tamp down the partisan polarization that has turned him, and science itself, into a lightning rod. Hes even finding his commonalities with former President Donald Trump, his nemesis in the pandemics first year.
We developed an interesting relationship, said the Brooklyn-born Fauci. Two guys from New York, different in their opinions and their ideology, but still, two guys who grew up in the same environments of this city. I think that we are related to each other in that regard.
Fauci says hes prepared for the onslaught of attacks that could come in a Republican-controlled House or Senate next year with many running in the midterms on campaigns deriding the lockdowns, school closures and masking requirements that Fauci said were necessary pandemic precautions but insists that is not part of his calculus for retirement.
Theyre going to try and come after me, anyway. I mean, probably less so if Im not in the job, he admitted, sitting in his office on the sprawling National Institutes of Health campus in Bethesda, Md. I dont make that a consideration in my career decision.
If called to testify, Fauci will stress the importance of vaccines and boosters, but acknowledge there may never be a definitive moment when the country can claim victory over an evolving virus that has killed more than one million Americans and left thousands with long Covid symptoms.
The diseases toll has slowed, the result of vaccination, acquired immunity and less-deadly strains. But it continues to kill more than 300 Americans a day, and the fear of a deadlier variant is ever-present.
What we have right now, I think were almost at a steady state, Fauci said.
Pedestrians walk past a signs hanging outside Pfizer headquarters in New York and one hanging at a bus stop encouraging the Covid-19 booster, Monday, May 23, 2022.|Mary Altaffer/AP Photo
Americans are flummoxed by what that means for them, especially as federal officials last week said all adults should get a second booster now despite pharmaceutical companies estimating that updated shots targeting the latest strains could be available this fall.
At one point, health officials, including Fauci, expressed cautious optimism that the original regimen and one booster could be enough. Now, amid what Fauci says is a combination of fast-evolving variants and stagnating vaccination rates Americans are left asking when this vaccination cycle ends.
Thats a reasonable question, said Fauci. But the reason not to wait is that were not exactly in a lull.
There are more than 130,000 documented Covid-19 cases a day, a figure that officials and public health experts say could be as much as four or five times lower than the actual infection rate as people take at-home tests or simply do not know they are transmitting the virus.
I think, although I dont know for sure, [that] over the next cycle or so, well be getting towards a once a year boost, like flu, Fauci said, expressing the uncertainty that has plagued scientists and the Biden administration when they contemplate the speed with which a new variant can take hold.
Even with the hope of moving to a flu shot-like schedule, that speed, with new strains sometimes becoming dominant in a matter of weeks, has humbled disease experts and vaccine developers worldwide.
Pfizer-BioNTech and Moderna in late June presented data for updated, Omicron-targeting vaccines to the Food and Drug Administrations advisory panel and predicted shots could be ready in late August. By that time, Omicron subvariants BA.4 and BA.5 already accounted for more than half of U.S. cases. Reformulating the shots for those strains would push timelines through mid-fall.
Its not impossible, but more difficult to develop vaccines for the next dominant coronavirus strain because of the variants pace, said Fauci. A more regular vaccination schedule could be anywhere from six months to two years away, he predicted.
Anthony Fauci of the National Institute of Allergy and Infectious Diseases speaks at the XIX International Aids Conference, Monday, July 23, 2012, in Washington.|Carolyn Kaster/AP Photo
The issue now is whether anyone is listening anymore.
Some rejected his recommendations to get vaccinated, mask up or limit social events from the start, Fauci admits. But now even cautious Americans deferential to experts are tired.
Its becoming more and more difficult to get people to listen, because even the people who are compliant want this behind them, Fauci said. That doesnt mean giving up, he insists. What I try to convince them [of], with my communication method, is were not asking you to dramatically alter your lifestyle. Were not asking you to really interfere with what you do with your life. Were just asking you to consider some simple, doable mitigation methods.
Those methods have been mired in partisan battles. Federal courts have struck Biden administration vaccine-or-test mandates and mask requirements. Vaccination rates have faltered, especially among Republicans. Though nearly 80 percent of eligible Americans have received at least one Covid-19 vaccine, fewer than half have gotten a booster dose. Only 30 percent of kids between five and 11 years old are fully vaccinated, with low expectations for better rates among toddlers and infants.
Sitting in his office in March 2020, days before a federal lockdown would all but end in-person meetups for months, Fauci mulled that partisan divides over the coronavirus response were already more visceral than the early battles of the HIV/AIDS epidemic, when the first president he served, Ronald Reagan, refused to acknowledge the worsening outbreak and many politicians blamed gay men.
Asked about what has changed in more than two years since that conversation, Fauci is focused on how to reinvigorate trust in the science that led his decisions.
I dont think they can say anything about the science, he said about Republicans in Congress calling for probes into his leadership and the Covid-19 response. If thats what you want to investigate, be my guest. My telling somebody that its important to follow fundamental good public health practices what are you going to investigate about that?
Notably, though, when asked what he wants his legacy to be, its not the coronavirus response. Fauci points to the virus that originally led him into infectious disease research and the NIAID director role in 1984, HIV/AIDS.
That work, he is quick to point out, always had bipartisan backing outside of Reagans hesitation. With Faucis urging, Trump pledged in a State of the Union address to end Americas HIV epidemic. President Barack Obama released the federal governments first national HIV/AIDS strategy in 2010. And with President George W. Bush, Fauci says he accomplished what may be the most impactful thing I have done in my career the founding of the Presidents Emergency Plan for AIDS Relief, or PEPFAR, a global program the State Department estimates has saved 21 million lives.
In the decades since Fauci began work on HIV/AIDS, treating and preventing the virus has transformed. People live for years with HIV or can prevent transmission with daily pills and now, injections every few months. But an HIV vaccine remains elusive and, Fauci says, likely many years away.
I dont think there is anything else that I, Tony Fauci, can do except leave behind an institution where I have picked the best people in the country, if not the world, who will continue my vision, he said. I dont need to be there for HIV, because we have enough good people that could carry it on.
More than two years into the COVID-19 pandemic, weve seen the virus mutate with stunning regularity as it circles the globe. Currently, the Omicron variant of the pathogen, as well as its subvariantstweaks to the viruss genetic material that change its composition and can make it more infectious, contagious, or cause more serious diseaseare infecting the most people. More than 75% of new U.S. cases are now linked to the BA.5 variant of Omicron alone.
Regulators acted at the end of June, with the Food and Drug Administration recommending that new COVID-19 booster shots target the BA.4 and BA.5 subvariants specifically.The trouble is, those boosters wont be ready until the fall, as vaccine manufacturer Pfizer notedfollowing the FDA recommendation. And by then an entirely new coronavirus strain may be the one driving a wave of new cases and hospitalizations.
Case in point: The booster for the original BA.1 Omicron variant took an extended period to reach vaccine trials, and the variant still makes up the bulk of clinical booster data that Pfizer and Moderna have collected to date despite largely vanishing from the actual population. Both companies say they are on the cusp of releasing a BA.1-targeted booster should they receive regulators blessing, and the theoretical plan would be that such a booster may at least offer partial protection against BA.4 and BA.5 until another booster arrives, ostensibly by October.
But health experts warn that this dog-chasing-cars approach to COVID-19 boosters is unsustainable, and the lag in launching new booster trials and issuing updated regulatory recommendations is a far cry from the striking turnaround time we saw for the original COVID-19 mRNA vaccines in 2020.
We will be close to 100% BA.5 within a matter of weeks. And no doubt there will be further troublesome variants that lie ahead, be they more in the Omicron family or in a whole new lineage, wrote Dr. Eric Topol, a precision medicine expert and director of the Scripps Research Translational Institute, on his Substack. Should we wait for a BA.5 booster? That will take months, and it should be noted it took more than 7 months for the Omicron BA.1 booster to be tested, a delay that is exceedingly long and unacceptable relative to the timing of validation and production of the original vaccines in 10 months during 2020.
The nature of mRNA vaccine technology should, in theory, make it easier to adjust boosters to emerging strains once a new coronavirus variant has been genetically sequenced. And the FDA has taken a slew of other measures in recent days and weeks to combat COVID-19, including authorizing vaccines for infants and approving the first new COVID-19 vaccinein more than a year on July 13 (its made by Maryland-based Novavax).
The Novavax jab is a traditional, non-mRNA vaccine more akin to a flu shot, an attribute public health experts hope will sway some of the roughly one-third of Americans who have yet to be fully vaccinated against coronavirus due, in part, to skepticism of the newer biotechnology. Just 32% of the U.S. population has received even one booster shot since they became available to the public in fall 2021, according to The New York Times.
[Image: Centers for Disease Control and Prevention]In the meantime, the efficacy of BA.1-based COVID-19 boosters against BA.4 and BA.5 is questionable, as evidenced by both preliminary vaccine trial data and the reinfection rates for people who already caught Omicron BA.1 but lost natural immunity against BA.5 in just months.
Usually,immediately after youve been infected, within a period of weeks to amonth or so, youre pretty muchprotected because of the immune response, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, during an appearance on CNNs New Day. But if somebody was infected severalmonths ago, particularly if they were infected with Omicron, the protection thats given to you against BA.5 wanes and diminishes pretty rapidly over a period of several months.
Early data from Moderna suggests that its own BA.1-directed booster shot produces only one-third the level of neutralizing antibodies against COVID-19 in patients with BA.4 or BA.5 variants. As for the prospect of a newer, highly infectious COVID-19 variant driving more cases by the time BA.4/5 boosters are available? A subvariant dubbed BA.2.75, which can deflect immunity from previous infection and vaccines, is already circulating in India, the U.S., and other countries.
Public health experts still urge the same precautions against COVID-19 variants as they have for the entirety of the pandemic: Wear effective masks in public enclosed settings and get the latest booster shot as soon as you are eligible. The Centers for Disease Control and Prevention has already recommended adults 50 and older and individuals 12 and older with compromised immune systems receive a second booster shot (even though it wouldnt be tailored toward Omicron) if its been at least four months since they received their first booster.
The lackluster pace of booster uptake in the U.S. may sap some of the urgency companies feel to get ahead of the curve in designing new and updated shots, though Pfizer and Moderna still plan to monitor new variants as they emerge. Fauci and other Biden administration officials have faced calls for a new round of federal vaccine development investments to fund an Operation Warp Speed Part 2,though such an effort would require Congressional legislation that seems unlikely in the near future.
But the fact remains that addressing this ever-changing virus will ultimately require much faster action by vaccine makers and regulators going forwardor, preferably, a universal COVID-19 vaccine that protects against all mutations.
According to Topol, All of this gets back to the vital need for a new generation of vaccines that are universal . . . and the pivotal importance of nasal vaccines to promote mucosal immunity and help block the transmission chain. These goals are paramount, along with more and better antiviral drugs, but they are not getting adequate traction or priority.
Sy Mukherjee has reported on the healthcare industry for a decade. He is a consultant and communications architect at Idea Pharma.
July 19 (Reuters) - The BA.5 subvariant of Omicron was estimated to make up 77.9% of the circulating coronavirus variants in the United States for the week ended July 16, the U.S. Centers for Disease Control and Prevention (CDC) said on Tuesday.
BA.5, which has shown to be particularly good at evading the immune protection afforded either by vaccination or prior infection, have been driving a surge of new infections globally. read more
Omicron subvariant BA.4 was estimated to make up 12.8% of the circulating variants in the United States, the data showed.
Register
The U.S. health regulator has asked vaccine manufacturers to target those variants for a potential fall season booster dose.
U.S. health officials are also urging people aged 50 or more to get a booster shot, adding that doing so would not prevent them from getting another "bivalent" booster designed to fend off Omicron more specifically later this year. read more
The city of Shanghai also discovered a COVID-19 case involving the BA.5, an official told a briefing last week, raising global alarm over the spread of the variant.
Register
Reporting by Manas Mishra and Bhanvi Satija in Bengaluru; Editing by Shinjini Ganguli
Our Standards: The Thomson Reuters Trust Principles.
Patient deaths: 1,021,306
Total vaccine doses distributed: 779,563,765
Patients whove received the first dose: 260,728,030
Patients whove received the second dose: 222,682,315
% of population fully vaccinated (both doses, not including boosters): 67.1%
% tied to Omicron variant: 100%
% tied to Other: 0%
More than 40% of Utahns live in counties with high COVID-19 levels and should be universally masking in public indoor spaces to protect themselves and others from the latest coronavirus variant, according to the Centers for Disease Control and Prevention.
The seven Utah counties considered to have high COVID-19 community levels are: Salt Lake, San Juan, Summit, Tooele, Wasatch, Wayne and Piute, with a combined total population of almost 1.4 million residents. Thats about 2 in 5 Utahns.
The CDCs first recommendation for high-transmission counties is unambiguous: Wear a well-fitting mask indoors in public, regardless of vaccination status. That includes K-12 schools and other indoor community settings.
None of the states 29 counties requires public indoor masking. In Utah, county health departments can issue mask mandates; cities and local school districts cannot. However, county governing bodies as well as the Legislature can overturn them, as state lawmakers did in January, immediately ending the mask mandates issued in Salt Lake and Summit counties amid the winter omicron variant surge.
This summer, the new, even more transmissible BA.5 omicron subvariant is sweeping across the country, driving up case counts. It became the dominant variant in the U.S. by late June.
As of this week, 16 Utah counties are considered to have medium COVID-19 community levels: Beaver, Cache, Daggett, Davis, Duchesne, Garfield, Grand, Iron, Juab, Kane, Millard, Sanpete, Sevier, Uintah, Utah and Washington.
Six counties are considered to have low COVID-19 community levels: Box Elder, Carbon, Emery, Morgan, Rich and Weber.
Dr. Russell Vinik, chief medical operations officer at University of Utah Health, also advised that Utahns in high-transmission counties should be wearing masks when they are indoors in a public place, noting that BA.5 is the most transmissible strain yet.
More and more people are getting sick, he said. And we know that the publicly reported numbers are a significant underestimate as compared to previous waves, because so many people are home testing. Whereas during the January wave, people couldnt get their hands on a home test.
The first week of April, there were 699 new cases of COVID-19 reported in Utah. The state averaged 1,082 cases per week that month.
Last week, 7,819 new cases were reported. Over the past four weeks, Utah has averaged 7,014 new weekly cases again, not counting anyone who tested positive at home.
We see this even with our own employees getting sick; we know that there is significant transmission going on, Vinik said. And so its completely appropriate to be wearing a mask, particularly indoors or in crowded spaces. But that doesnt seem to be what were doing.
He reiterated that well-fitted, high-quality masks dont only protect the people wearing them.
We require people to wear masks in our hospital. We need to protect our vulnerable patients, Vinki said. But there are patients wherever you go that have weakened immune systems.
More people in Utah also are being hospitalized with COVID-19 than back in April. But Vinik noted that the documented rise is nowhere near the levels we saw in December through February.
And those that get hospitalized arent as critically ill as what weve seen in the past, Vinik said.
He said researchers believe BA.5 carries a similar risk of hospitalization that the omicron variant did in January and February, but they estimate that there are not nearly as many infections this summer as there were in the winter.
Still, he noted it is difficult if not impossible to compare because, again, fewer coronavirus cases are being recorded as more people rely on home tests.
Dr. Brandon Webb, chair of Intermountain Healthcares COVID-19 therapeutics team, also said providers are currently seeing fewer severe cases of COVID-19 than in the winter, in part because more people have been immunized.
Although were seeing reinfections and new strains that are able to escape that immunity, what were not seeing are nearly the same numbers of severe cases requiring hospitalization, ICU care or death, Webb said.
The CDC recommends that residents in counties with high COVID-19 community levels who are immunocompromised or at high risk of severe disease: 1) wear a mask or respirator; 2) consider avoiding non-essential indoor activities in public; 3) consider testing and have home tests on hand; and 4) talk to their health care provider about treatments including oral antivirals, PrEP and monoclonal antibodies.
The CDC also recommends that everyone stay up to date on COVID-19 vaccines and boosters.
Though they may not be 100% protective, and theyre not as protective as they were in preventing illness, theyre still very effective in preventing severe illness and hospitalization, Vinik said.
The fact that people are getting infected despite being vaccinated dont let that serve as a reason not to get vaccinated. Because vaccines will keep you out of the hospital, Vinik said. They will keep you out of the ICU. Keep you off a ventilator.
People who have contracted and recovered from COVID-19 should also get vaccinated.
Previous infection is not going to get you lifelong immunity, Vinik said. We certainly see people who were infected just in the last six to nine months getting reinfected. So dont rely on your previous infection to protect you.
He recommended that anyone age 60 and older get a second booster and not wait for a new version thats in the works.
Theyre at very high risk of getting significant disease if they were to get infected with COVID. And for those people, waiting probably doesnt make sense, Vinik said. For people that are relatively healthy in their 50s, waiting is probably OK.
Thats a bit of a gamble, however, even though the data we have so far suggests that the vaccines thatll be coming out will be significantly more effective than the original vaccines.
Its very difficult to turn down something today for something that we dont know when its going to be available, Vinik said. We think late August, September but theres no guarantee on that. For people who are frail or have suppressed immune system, thats certainly not a risk that I would take.
We dont have a crystal ball, Vinik said, but generally, as viruses mutate, they work to be more transmissible, but not necessarily cause as severe disease.
He pointed to the natural selection of virology: If you kill your host, the virus cant replicate it as well, he said.
Thats the case with the BA.5 variant, which is more transmissible but is sending fewer people to the hospital with serious cases. And killing fewer people.
And so, yes, were going in the right direction as far as that severity of disease, Vinik said.
Researchers in Iran have lost a paper on Covid-19 infection in a two-month-old boy after the journal learned that theyd fabricated ethics approval for the article.
Its the 250th Covid-19 retraction by our count.
Coronavirus disease 2019 in a 2-month-old male infant: a case report from Iran appeared in December 2020 in Clinical and Experimental Pediatrics. The senior author of the paper was Sajjad Ahmadpour, of the Gastroenterology and Hepatology Diseases Research Center at Qom University of Medical Sciences.
According to the retraction notice (which doesnt appear in the expected place but can be found here):
Coronavirus disease 2019 in a 2-month-old male infant: A case report from Iran, published in Clinical and Experimental Pediatrics in December 2020, has been retracted from publication.
The authors violated the journals publication ethics policy by falsifying IRB approval.
The ethical ID submitted by the authors is not relevant to this case report, and no valid ethical ID was subsequently provided.
Therefore, the CEP ethics committee has decided to retract this paper from the journal. We apologize to readers and assure them that we aim to thoroughly screen for ethics violations prior to publishing papers in Clinical and Experimental Pediatrics.
In an email to Retraction Watch, Ahmadpour objected to the retraction and denied that his group had fabricated IRB approval:
We are not agree that our article be retracted. As mentioned for several times, our case report be approved by ethical commite of Qom university of Medical Sciences. This case report is a partial part of mega research related to the COVID19 risk factor in pediatrics. This article previously approved by 3 reviewrs and non of them mentioned any ethical issue for this case report. We dont fabricate IRB approval for this case report.
For several times we said that this study had IRB approval. However, we can provide a IRB approval for this particular paper in 7 working days
Weve asked for a copy. Meanwhile, Ahmadpour said his group provided the journal evidence of IRB approval for the megaproject although not this particular study but apparently that did not impress. About that megaproject:
We included more than 1000 COVID19 pediatrics in a mega projects. During following we noticed to this particular study. We report the study with ethical approval and also get written consent form from the family of case who reported in this article.
Like Retraction Watch? You can make atax-deductible contribution to support our work, follow uson Twitter, like uson Facebook, add us to yourRSS reader, or subscribe to ourdaily digest. If you find a retraction thatsnot in our database, you canlet us know here. For comments or feedback, email us at team@retractionwatch.com.
Related
From the start of the pandemic, patients and doctors alike have been frustrated by the sizable minority of coronavirus infections that turn into long COVID, a perplexing collection of lingering and often disabling symptoms that persist weeks, months or years after the initial infection subsides.
The condition has been reported in both children and adults; in those who had preexisting conditions and those in robust health; in patients hospitalized with COVID-19 and those who experienced only mild symptoms during their initial infection.
A new study from researchers at USC offers some insights into the prevalence of long COVID and suggests some early clues for who might be more likely to develop long-term symptoms.
The study, published this month in Scientific Reports, found that 23% of people who had coronavirus infections between March 2020 and March 2021 were still reporting symptoms up to 12 weeks later.
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Researchers recruited roughly 8,000 people, some infected and some not, to answer biweekly questions about their overall health and COVID-19 status. By the end of the yearlong survey period, they had a sample of 308 people who had gotten the disease at some point in the year.
After filtering out respondents with symptoms such as headache and fatigue prior to infection as a result of unrelated conditions like seasonal allergies, the team found that nearly 1 in 4 COVID-19 sufferers were still grappling with symptoms 12 weeks after becoming infected.
These people are not able to do necessarily all the activities they would want to do, not able to fully work and take care of their families, said Eileen Crimmins, a demographer at USCs Leonard Davis School of Gerontology and a coauthor of the study.
Thats an aspect of this disease that needs to be recognized, because its not really as benign as some people think, she said. Even people who have relatively few symptoms to start with can end up with long COVID.
Determining who is at greater risk for long COVID has proved a challenge to demographers and healthcare providers.
Several previous studies have identified women as being at greater risk. But the USC study found no relationship in its sample between long COVID and age, gender, race or preexisting health conditions including cancer, diabetes, hypertension and heart disease.
It did note a higher risk in patients who had obesity prior to infection. And it also spotted some associations between specific symptoms people experienced during their initial infection and the likelihood of developing long COVID. Patients who reported sore throats, headaches and, intriguingly, hair loss after testing positive were more likely to have lingering symptoms months later.
Our assumption is that that hair loss reflects extreme stress, potentially a reaction to a high fever or medications, Crimmins said. So its probably some indication of how severe the illness was.
Because it covered only the first year of the pandemic, the study doesnt account for two major developments: vaccines and variants. None of the COVID-19 patients in the sample were eligible for vaccines during the study period, and all were infected before the Alpha variant from the U.K reached U.S. shores.
While the studys 308 respondents were representative of the population, no snapshot of a few hundred people can tell the whole story of the roughly 200 million people in the U.S. who have had the virus, according to estimates from the Centers for Disease Control and Prevention.
The authors made a commendable effort to identify factors associated with long COVID, said Dr. Alain Lekoubou Looti, a neurologist at Penn State University who was not involved with the study. However, these factors may need to be confirmed in larger samples.
The most common long COVID symptoms reported were headache, nasal congestion, abdominal pain, fatigue and diarrhea. But the study did not address many of the symptoms people living with long COVID describe as the most debilitating, said Hannah Davis, a co-founder of the Patient-Led Research Collaborative, a research group that focuses on the condition.
We need work like this, but this work also indicates they arent very familiar with what long COVID is, Davis said. The list of symptoms are predominantly acute COVID symptoms and dont include the most common symptoms of post-exertional malaise, cognitive dysfunction, memory loss, sensorimotor symptoms and others.
Defining long COVID presents a challenge to those attempting to track or treat it. COVID-19 is a chimerical beast symptoms evolve as the condition drags on, and can vary widely among patients.
The fluidity of long COVID makes it hard to gauge its prevalence. Various studies have placed the percentage of people reporting enduring symptoms 12 weeks after their initial infection at anywhere from 3% to 50%.
We need a universal case definition before we can really understand the prevalence of long COVID. Right now, the definition varies wildly across studies, leading to a big range in prevalence estimates, said Jana Hirschtick, an epidemiologist with the University of Michigans School of Public Health. After all this time, we still dont have a clear picture of who is at greatest risk.
The absence of strict diagnostic criteria is also a major issue for patients attempting to seek treatment. At the moment, long COVID is considered an exclusionary diagnosis, meaning one that is given only after all other valid possibilities have been ruled out, said Melissa Pinto, an associate professor of nursing at UC Irvine who studies the condition. In the U.S., that can mean a long and expensive process of submitting to various tests and specialists.
For many long COVID patients, 12 weeks is just the beginning of a months- or years-long ordeal.
Ive known people that have had this now for 2 years, Pinto said. Theres no safety net, really, for these individuals.
Gladstone researchers find new evidence against using BET inhibitors to treat COVID-19
SAN FRANCISCO, July 19, 2022 /PRNewswire/ -- A while ago, some researchers had suggested that blocking a set of proteins, known as bromodomain and extraterminal (BET) proteins, might be a way to fight COVID-19. However, in a surprising study, scientists at Gladstone Institutes and UC San Francisco (UCSF)discovered that BET proteins are actually crucial for the body to fight the infection. In fact, the SARS-CoV-2 virus itself blocks the proteins to try to gain an advantage and continue to spread.
Gladstone Graduate Student Irene Chen (right) is first author of a new study showing that BET proteins both enable and fight off COVID-19. Shown here in the lab with Tongcui Ma (left). Photo: Michael Short/Gladstone Institutes
The new research, published in the journal Cell Reports, found that BET proteins have two distinct roles that affect how SARS-CoV-2 interacts with human cells: they give the virus a window into cells while also helping our cells defend themselves. These opposing functions explain the mixed results of previous experiments studying of the effect of targeting BET proteins on SARS-CoV-2 infection.
"Our study shows how complex and nuanced interactions between virus and host cells can be," saysMelanie Ott, MD, PhD,director of the Gladstone Institute of Virology and co-senior author of the new paper. "Even though blocking some BET proteins before viral exposure can help prevent infections, blocking other BET proteins actually plays right into the hands of the virus."
The study's other co-senior author is DanicaGaloni Fujimori, PhD, a professor of cellular and molecular pharmacology at UCSF.
Directions from a Map
In 2020, Nevan Krogan, PhD, a senior investigator at Gladstone Institutes and director of the Quantitative Biosciences Institute at UCSF, assembled a detailed map showing which SARS-CoV-2 proteins directly interact with which proteins in infected human cells. When they perused Krogan's results, Ott and Fujimori were surprised by one pairing: the virus's envelope protein bound to BRD2 and BRD4, two members of the BET family of proteins.
Story continues
Scientists thereafter discovered that one of the genes turned on by these BET proteins is ACE2, the same protein that SARS-CoV-2 relies on to get into cells. Indeed, it had been shown that completely blocking BET proteins prior to exposure to the virus could protect cells from infection.
But Ott's lab had already been studying BET proteins in the context of HIV infection, and knew that they also control activation of genes related to inflammation, immunity, and cancer. They wondered how and why SARS-CoV-2 would be directly interacting with BRD2 and BRD4 given their known roles in cellular responses to invading pathogens.
New Insight into BETs
In this study, Gladstone graduate student Irene Chen and the rest of the team discovered that, in SARS-CoV-2 infected cells, the BET proteins turn on genes that ward off virusesthis is in addition to turning on the gene ACE2, which lets SARS-CoV-2 enter human cells. When the researchers blocked the BET protein BRD4 in mice already infected with COVID-19, rather than before infection, the mice's symptoms grew worse and they experienced more severe disease.
These results suggested that BET proteins play a role in both enabling and fighting off COVID-19, yet still didn't explain why or how the virus was directly binding to BRD2 or BRD4.
But a close look at SARS-CoV-2 revealed that the envelope protein has a small section that closely resembles human histones, which are complexes of proteins found along DNA. With additional experiments, the researchers revealed that SARS-CoV-2 was able to engage the BRD4 protein at the periphery of the cell nucleus by mimicking the histones that BET proteins naturally bind toand this, in turn, prevented BRD4 from activating antiviral genes.
"This is an example of a viral protein that can actually mimic one our own proteins to fool our cells and prevent them from activating immune defenses that would kill the virus," says Chen, who is a co-first author of the new paper along with James Longbotham, PhD, a former postdoctoral fellow at UCSF.
A Target for Treatment
The new findings indicate that existing drugs that simultaneously block all BET proteins likely won't be effective in treating COVID-19at least in patients who are already infected.
However, the new study also confirmed that different BET proteins play different roles in the infection cycle, which could lead to future therapeutics that target only specific BET proteins, or parts of these proteins. More research is also needed to understand how the timing of such treatment with an infection could work.
"It's clear from our results that the BET drugs currently available are not suitable for COVID-19," says Ott. "But certain elements of these drugs could be adapted for future drug development."
About the Research Project
The paper "Viral E Protein Neutralizes BET Protein-Mediated Post-Entry Antagonism of SARS-CoV-2" was published in the journal Cell Reports on July 19, 2022.
Other authors are SarahMcMahon,Rahul K.Suryawanshi, Mir M. Khalid, Taha Y.Taha, Takako Tabata, Jennifer M.Hayashi, Frank W.Soveg, and Nevan Krogan of Gladstone; JaredCarlson-Stevermer, Jennifer Oki, and KevinHolden of Synthego; MeghnaGupta,Meng YaoZhang,Victor L.Lam,YangLi, ZanlinYu,ErronTitus, and AmyDiallo of UCSF.
The work was supported by the National Institutes of Health (NCI R01CA250459, NIAID R01AI137270, NIAID R37AI083139, and F31 AI164671-01), the Tobacco-Related Disease Research Program (T30DT1006), a UCSF Discovery Fellowship, philanthropic support from Quantitative Biosciences Institute COVID-19 Research Group donors, and the James B. Pendleton Charitable Trust.
About Gladstone Institutes
To ensure our work does the greatest good, Gladstone Institutes focuses on conditions with profound medical, economic, and social impactunsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. It has an academic affiliation with the University of California, San Francisco.
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SOURCE Gladstone Institutes
Tori Burket, manager of Denvers epidemiology program, told Denverite last week people cant count on using case rates any more to gauge COVID risks, because at-home tests are rarely reported to officials.
That number, by itself, is not reliable, she said. Its not a true indicator of whats happening in the community.
Mehta said the pandemic continues to challenge mightily the health care system, from providers dealing with the still on-going crisis to a patient population now ailing in worrisome ways.
Hospital patients are just much sicker, and taking a lot more time in terms of management, and more complex thinking, he said. These are patients that either didn't seek out care for a couple of years, didn't have access to care or in a lot of cases, especially at Denver Health, have really been abusing themselves in a variety of ways with a lot of substances. So we're seeing a lot of that.
Editors note: The state is adapting its COVID-19 dashboard and changing some of its metrics and CPR News is changing its as well. Weve updated our COVID-19 page to reflect the metrics that well be watching closely to understand what the virus is doing in Colorado particularly hospitalizations and wastewater monitoring. We know a lot of our readers have come to rely on COVID stats, and the change is an attempt to keep providing you with information that is accurate and useful.
Since the onset of the Omicron variant of COVID-19, the kind of symptoms commonly associated with the illness has changed. While with the Delta variant, that is said to have driven the second wave of infection in India, the symptoms were more severe and life-threatening, with Omicron, the ailments are considerably milder.
According to experts, while the Delta affected the lower respiratory tract, the Omicron is said to attack the upper respiratory tract, causing symptoms of sore throat, runny nose, sneezing, headache, muscle pain, fever, etc.
However, these upper respiratory symptoms are also reported in people who suffer from allergies, which are caused by an entirely different property i.e. airborne substances like pollen.
Therefore, nasal congestion, sneezing, coughing, headache, and tiredness are also symptoms of allergies, which may make it difficult to identify the cause of your illness.
Also read: Heart disease: Your ankles can indicate a serious health risk
