Fauci: ‘About 40%-45% of Infections Are Asymptomatic’

Anthony Fauci, MD, highlighting the latest COVID-19 developments on Friday, said, “It is now clear that about 40%-45% of infections are asymptomatic.”

Asymptomatic carriers can account for a large proportion — up to 50% — of virus transmissions, Fauci, director of the National Institute of Allergy and Infectious Diseases, told a virtual crowd of critical care clinicians gathered by the Society of Critical Care Medicine (SCCM).

Such transmissions have made response strategies, such as contact tracing, extremely difficult, he said.

Lew Kaplan, MD, president of SCCM, told Medscape Medical News after the presentation, “That really supports the universal wearing of masks and the capstone message from that — you should protect one another.

“That kind of social responsibility that sits within the public health domain to me is as important as the vaccine candidates and the science behind the receptors. It underpins the necessary relationship and the interdependence of the medical community with the public,” Kaplan added.

Fauci’s plenary led the SCCM’s conference, “COVID-19: What’s Next/Preparing for the Second Wave,” running Friday and Saturday.

Why US Response Lags Behind Spain and Italy

“This virus has literally exploded upon the planet in a pandemic manner which is unparalleled to anything we’ve seen in the last 102 years since the pandemic of 1918,” Fauci said.

“Unfortunately, the United States has been hit harder than any other country in the world, with 6 million reported cases.”

He explained that in the European Union countries the disease spiked early on and returned to a low baseline. “Unfortunately for them,” Fauci said, “as they’re trying to open up their economy, it’s coming back up.”

The United States, he explained, plateaued at about 20,000 cases a day, then a surge of cases in Florida, California, Texas, and Arizona brought the cases to 70,000 a day. Now cases have returned to 35,000 to 40,000 a day.

The difference in the trajectory of the response, he said, is that compared with Spain and Italy, for example, the United States has not shut down mobility in parks, outdoor spaces, and grocery stores nearly as much as some European countries did.

He pointed to numerous clusters of cases, spread from social or work gatherings, including the well-known Skagit County Washington state choir practice in March, in which a symptomatic choir member infected 87% of the 61 people rehearsing.

Vaccine by End of the Year

As for a vaccine timeline, Fauci told SCCM members, “We project that by the end of this year, namely November/December, we will know if we have a safe and effective vaccine and we are cautiously optimistic that we will be successful, based on promising data in the animal model as well as good immunological data that we see from the phase 1 and phase 2 trials.”

However, also on Friday, Fauci told MSNBC’s Andrea Mitchell that a sense of normalcy is not likely before the middle of next year.

“By the time you mobilize the distribution of the vaccinations, and you get the majority, or more, of the population vaccinated and protected, that’s likely not going to happen [until] the mid- or end of 2021,” he said.

According to the Centers for Disease Control and Prevention (CDC) case tracker, as of Thursday, COVID-19 had resulted in more than 190,000 deaths overall and more than 256,000 new cases in the United States in the past 7 days.

Fauci has warned that the next few months will be critical in the virus’ trajectory, with the double onslaught of COVID-19 and the flu season.

On Thursday, Fauci said, “We need to hunker down and get through this fall and winter because it’s not going to be easy.”

Fauci remains a top trusted source in COVID-19 information, poll numbers show.

A Kaiser Family Foundation poll released Thursday found that 68% of US adults had a fair amount or a great deal of trust that Fauci would provide reliable information on COVID-19, just slightly more that the 67% who said they trust the CDC information. About half (53%) say they trust Deborah Birx, MD, the coordinator for the White House Coronavirus Task Force, as a reliable source of information.

The poll also found that 54% of Americans said they would not get a COVID-19 vaccine if one was approved by the US Food and Drug Administration before the November election and was made available and free to all who wanted it.

Kaplan and Fauci report no relevant financial relationships.

COVID-19: What’s Next/Preparing for the Second Wave. Presented September 11, 2020.

https://www.medscape.com/viewarticle/937297

Infectious COVID-19 Can Persist in Gut for Weeks

For the first time, researchers detected active and prolonged infection of SARS-CoV-2 virus in the gastrointestinal (GI) tracts of people with confirmed COVID-19. Stool tests were positive among people with no GI symptoms, and in some cases up to 6 days after nasopharyngeal swabs yielded negative results.

The small pilot study suggests a quiescent but active infection in the gut. Stool testing revealed genomic evidence of active infection in seven of the 15 participants tested in one of two hospitals in Hong Kong.

Professors Paul Chan (left), Francis Chan, and Siew Ng of the Centre for Gut Microbiota Research at the Chinese University of Hong Kong.

“We found active and prolonged SARS-CoV-2 infection in the stool of patients with COVID-19, even after recovery, suggesting that coronavirus could remain in the gut of asymptomatic carriers,” senior author Siew C. Ng, MBBS, PhD, told Medscape Medical News.

“Due to the potential threat of fecal-oral transmission, it is important to maintain long-term coronavirus and health surveillance,” said Ng, Associate Director of the Centre for Gut Microbiota Research at the Chinese University of Hong Kong (CUHK).

“Discharged patients and their caretakers should remain vigilant and observe strict personal and toileting hygiene,” she added.

The prospective, observational study was published online July 20 in Gut.

Ramping Up COVID-19 Testing

As a follow-up to these and other findings — including the testing of more than 2000 stool samples in children and the needy arriving at Hong Kong airports starting March 29 — the same investigators are establishing a CUHK Coronavirus Testing Center.

As of August 31, the detection rate in tested children was 0.28%. The Center plans to offer as many as 2000 COVID-19 tests daily going forward to help identify asymptomatic carriers, the investigators announced in a September 7 news release.

In contrast to nasopharyngeal sampling, stool specimens are “more convenient, safe and non-invasive to collect in the pediatric population,” professor Paul Chan, chairman of the Department of Microbiology, CU Medicine, said in the release. “This makes the stool test a better option for COVID-19 screening in babies, young children and those whose respiratory samples are difficult to collect.”

Even though previous researchers identified SARS-CoV-2 in the stool, the activity and infectivity of the virus in the gastrointestinal tract during and after COVID-19 respiratory positivity remained largely unknown.

Active Infection Detected in Stool

This prospective study involved 15 people hospitalized with COVID-19 in March and April. Participants were a median 55 years old (range, 22 years to 71 years) and all presented with respiratory symptoms. Only one patient had concurrent GI symptoms at admission. Median length of stay was 21 days.

Investigators collected fecal samples serially until discharge. They extracted viral DNA to test for transcriptional genetic evidence of active infection, which they detected in seven of 15 patients. The patient with GI symptoms was not in this positive group.

The findings suggest a “quiescent but active GI infection,” the researchers note.

Three of the seven patients continued to test positive for active infection in their stool up to 6 days after respiratory clearance of SARS-CoV-2.

Microbiome Matters

The investigators also extracted, amplified, and sequenced DNA from the stool samples. Their “metagenomic” profile revealed the type and amounts of bacterial strains in each patient’s gut microbiome.

Interestingly, bacterial strains differed between people with high SARS-CoV-2 infectivity vs participants with low to no evidence of active infection.

“Stool with high viral activity had higher abundance of pathogenic bacteria,” Ng said. In contrast, people with low or no infectivity had more beneficial bacterial strains, including bacteria that play critical roles in boosting host immunity.

Each patient’s microbiome composition changed during the course of the study. Whether the microbiome alters the course of COVID-19 or COVID-19 alters the composition of the microbiome requires further study, the authors note.

The US Food and Drug Administration and officials in other countries have contacted the Hong Kong investigators for more details on their stool testing strategy, professor Francis KL Chan, dean of the faculty of medicine and director of the Centre for Gut Microbiota Research at CUHK, stated in the news release.

Further research into revealing the infectivity and pathogenesis of SARS-CoV- 2 in the GI tract is warranted. The value of modulating the human gut microbiome in this patient population could be worthwhile to investigate as well, the researchers said.

Novel Finding

“Some of it is not-so-new news and some is new,” David A. Johnson, MD, told Medscape Medical News when asked to comment on the study.

For example, previous researchers have detected SARS-CoV-2 virus in the stool. However, this study takes it a step further and shows that the virus present in stool can remain infectious on the basis of metagenomic signatures.

Dr David A. Johnson

Furthermore, the virus can remain infectious in the gut even after a patient tests negative for COVID-19 through nasopharyngeal sampling — in this report up to 6 days later, said Johnson, professor of medicine, chief of gastroenterology, Eastern Virginia Medical School in Norfolk, Virginia.

The study carries important implications for people who currently test negative following active COVID-19 infection, he added. Centers for Disease Control and Prevention criteria clear a person as negative after two nasopharyngeal swabs at least 24 hours apart.

People in this category could believe they are no longer infectious and might return to a setting where they could infect others, Johnson said.

One potential means for spreading SARS-CoV-2 from the gut is from a toilet plume, as Johnson previously highlighted in a video report for Medscape Medical News.

The study authors disclosed no relevant financial relationships. Johnson serves as an adviser to WebMD/Medscape.

Gut. Published online July 20 2020. Full text

https://www.medscape.com/viewarticle/937256#vp_1

FDA Panel: Reformulated OxyContin Did Not Reduce Overall Abuse

An FDA advisory committee overwhelmingly panned the idea that Purdue Pharma’s abuse-deterrent formulation (ADF) of oxycodone (OxyContin) “meaningfully reduced” overall opioid abuse, overdose and death.

Just two of the 28 members on the FDA’s Drug Safety and Risk Management and Anesthetic and Analgesic Drug Products advisory committees voted “yes” on whether the reformulated OxyContin lessened overall abuse since it was introduced in 2010.

The panel voted 20-7 (one member abstained) that the drug did reduce abuse by non-oral routes; however, it was rejected in a vote of 1-26 (with one abstention) that the ADF version had a substantial impact on overdose rates.

“I do not think that the reformulation has shown a meaningful reduction in abuse overall by any specific group,” said Lewis Nelson, MD, chief of medical toxicology at Rutgers New Jersey Medical School in Newark, who voted no on all three questions. Nelson said that the data were “exceptionally confounded, and dynamic in the nature of population.”

OxyContin’s ADF — which received FDA approval a decade ago — – includes high-molecular-weight polyethylene oxide, a hard coating on the outside that makes tablets difficult to crush, dissolve or break. It also forms a gel when combined with water, aimed at preventing abuse by snorting or injection.

This advisory committee meeting was called simply to review Purdue’s postmarketing data with ADF OxyContin, not because the company sought expanded drug labeling. Throughout two days of presentations, FDA staff emphasized that evidence was sparse that the newer version of the drug lowered overall abuse, despite some data that abuse by snorting or injection declined after the reformulation was approved.

Advisory committee members raised several concerns about the quality of data used in Purdue’s postmarketing studies. The studies, which all compared abuse rates before the reformulation’s approval to the post-approval period, were limited by several unmeasured confounders, including a dynamic population and changes to public health and government interventions that could have impacted the number of opioid overdoses and deaths.

Members were also critical of unintended consequences of the reformulated drug, such as a rise in abuse of illicit drugs like heroin or fentanyl and adverse events, which include reports of dysphagia and thrombotic microangiopathies.

Public comments echoed both sides of the ADF debate, with some pointing to the important role of reformulated opioids in mitigating the epidemic, while others stated that “abuse-deterrence” does not solve the major issue with the crisis: addiction.

“Purdue would like medical community regulators and the public to believe that the opioid crisis is a drug abuse problem,” said Andrew Kolodny, MD, speaking on behalf of the organization Physicians for Responsible Prescribing.

“But we don’t have an epidemic of drug abuse,” Kolodny continued. “We have an epidemic of opioid use disorder.”

In an evaluation of four postmarketing studies conducted by the drug’s manufacturer, FDA staff determined that only one of the studies provided good evidence that ADF OxyContin significantly reduced opioid abuse by non-oral routes. Findings from the retrospective study, which was conducted in a population being assessed for substance abuse treatment, indicated that OxyContin abuse by injection and insufflation dropped 52% after the OxyContin reformulation.

But there was also no decline in the most common form of abuse — swallowing opioid tablets.

Other studies conducted by Purdue, which analyzed data from treatment centers, poison control centers, and both commercial and Medicaid insurance claims, did not produce solid evidence that the reformulation lessened overall OxyContin abuse.

The meeting was originally scheduled to take place in July 2015, when Purdue requested new labeling for the ADF product to include claims of reductions in overdose and death. But the company withdrew that application just before FDA staff reviews were due to be posted.

The FDA is not required to follow recommendations of its advisory committees, but it typically does. The agency will use the recommendations to determine regulatory actions for OxyContin’s ADF.

https://www.medpagetoday.com/publichealthpolicy/opioids/88583

The Real Reason Post-COVID Myocarditis Is a Worry

It’s not often that myocarditis trends on Twitter, but cardiac MRI findings after recovery from acute COVID-19 symptoms have rocketed to public attention for their impact on decisions being made about sports.

One (as yet unpublished) study found myocarditis in 15% of college athletes who tested positive, largely after mild or no symptoms. A more alarming statement by Penn State football’s team doctor put that rate at 30% to 35%, but that claim has since been walked back.

Before that was a German cardiac MRI study in non-athletes that turned up lingering myocardial inflammation and other cardiac abnormalities in 78 of 100 people. While the study was subsequently corrected, the message remained the same: even a mild course of COVID-19 in relatively healthy people could leave a mark on the heart.

That study, too, received an enormous amount of attention due, in part, to its use by colleges and sports programs to determine the future of the fall athletics season.

“We did expect high uptake, but we didn’t expect that much of a focus,” said Eike Nagel, MD, PhD, of University Hospital Frankfurt in Germany, who was the senior author on the German MRI paper. “A lot of papers get downloaded 10 times, maybe 20 times; this paper got downloaded 550,000 times.”

Myocarditis is the top concern around COVID-19 for college athletics, due to the risk it poses for cardiac arrhythmia and sudden cardiac death.

Darrel Francis, MD, of the National Heart and Lung Institute of Imperial College London, saw reason for reassurance in Nagel’s corrected data rather than reason to stop sports.

The troponin and C-reactive protein (CRP) measurements were elevated but still within the normal range, he told MedPage Today. “These are much more reassuring, that there isn’t a huge amount of myocarditis going on unnoticed in COVID survivors.”

However, focusing on sports not only politicizes the findings but misses the point, Nagel argued in an interview with MedPage Today.

There are no long-term data to indicate whether this inflammation is clinically relevant for an individual, whether it will lead to heart failure, arrhythmias, or other chronic complications, Nagel said.

Nor is it clear how long it might take to disappear in those who suffer no long-term consequences. That process took around 2 years for the lingering pulmonary function issues seen with the prior SARS coronavirus outbreak.

But Nagel’s study suggested that for some subset of patients there really will be clinical consequences for the heart long-term.

Significantly abnormal native T2 indicating edema — more than four standard deviations above normal — was found in 22% of the COVID survivors tested versus none of the risk factor-matched people, Nagel noted. Also, nonischemic scar tissue by late enhancement was found in 20% of the COVID patients and 7% of the risk factor-matched group.

“We know that the presence of scar tissue, late enhancement by MRI, is prognostically relevant in almost any disease that has been looked at,” he said. “The same for inflammation.”

Even so, while that “will change their outcome statistically, again that doesn’t mean on an individual level,” Nagel said. “The person who has that doesn’t need to worry that they are now going to die sooner. But on a population level, if you have a million people with COVID and 22% of them develop more scar…there is a relevant risk that we’ll have a larger incidence of heart failure and chain of outcome in 10 years’ time.”

Even small but measureable elevations in troponin and CRP chronically, while of no pathologic value, can be relevant for cardiovascular outcome, he added.

“In the long term, we need to change our attitude toward these things, because we are trained to look at these enzymes or ejection fraction or whatever in patients where there’s severe damage — like myocarditis,” Nagel argued. “They say the others heal with no damage at all. This is too binary for me. For me, myocarditis is a spectrum. … There are loads of people who have some cardiac damage; it doesn’t have to be massive, it can be just minimal.”

There might not be any guideline-directed therapy to offer those without overt heart failure, but these post-COVID cases need to be studied to check for functional changes at 6 months and beyond, he said.

“We’ve seen with other viruses where there is inflammation of the heart, there are individuals for whom there is spontaneous recovery,” Gregg Fonarow, MD, of the University of California Los Angeles, said in a news article from the American Heart Association. “And in some people, we can treat this effectively with medication. The question becomes specifically with COVID-19, what is that frequency and does it differ from other viruses that infect the heart.”

Newly released European Society of Cardiology guidelines suggested that people with myocarditis should hold off on vigorous exercise likely for 3 to 6 months. And based on “pretty much no data,” it makes sense to apply that to COVID-related cardiac inflammation and fibrosis too, Nagel said.

https://www.medpagetoday.com/infectiousdisease/covid19/88487