Quick Less Precise, but Repeated, Covid-19 Tests Can Be Better Than Slow Precise Tests

(p. A1) Public health experts are increasingly calling for a shift in thinking about Covid-19 testing: It is better to get fast, frequent results that are reasonably accurate than more precise results after dayslong delays.

. . .

Covid-19 tests that don’t require a lab tend to be less sensitive than “gold standard” laboratory-based tests, meaning they are likely to miss more cases. But many public health experts now say that repeat testing can make up for the loss of sensitivity, and such testing could quickly identify the most infectious people and help bring transmission to heel as workplaces and schools resume in-person operations and as influenza season looms.

. . .

(p. A6) “When we looked ahead, we realized we needed a paradigm shift from the still-needed diagnostic tests to the screening tests,” said Jonathan Quick, managing director for pandemic response, preparedness and prevention at the Rockefeller Foundation, which released a report in July [2020] calling for a massive scale-up in quick, cheap tests for Covid-19 screening. “As a practical matter, that meant making much more of a new kind of test,” Dr. Quick said.

Most Covid-19 diagnostic testing in the U.S. is processed in laboratories and uses a technique called rt-PCR that searches for the virus’s genetic material and amplifies it. The tests are incredibly sensitive but expensive to run, and the process often requires shipping samples from a test site to a lab.

. . .

“I think there’s a sense of desperation that we need to do something else,” Ashish Jha, dean of Brown University’s School of Public Health, said at a media briefing in August [2020].

. . .

Antigen tests are better at identifying cases when people have more virus in their system—meaning they will likely find people when they are most infectious, said Michael Mina, an epidemiologist at the Harvard T.H. Chan School of Public Health and an advocate of low-cost, widely available at-home testing that can be done on a paper strip.

. . .

The FDA also has said that rapid tests should have comparable accuracy to PCR diagnostic tests—a requirement that some public health specialists and companies say is overly stringent for surveillance testing.

An FDA official noted sensitivity rates lower than PCR might be acceptable, depending on how the test results are used. The agency has allowed for antigen tests with a sensitivity rate of 80% or better, the official said. “You can even have lower than 80% sensitivity” if it is a recurring or serial test.

For the full story, see:

Brianna Abbott, and Thomas M. Burton. “Speed Over Precision Favored in Covid Tests.” The Wall Street Journal (Wednesday, September 9, 2020): A1 & A6.

(Note: ellipses, and bracketed year, added.)

(Note: the online version of the story has the date Sep. 8, 2020, and has the title “Public Health Officials Pursue Covid-19 Tests That Trade Precision for Speed.” Where there are differences between the print and online versions, the passages above follow the online version.)

The report by The Rockefeller Foundation mentioned above is:

The Rockefeller Foundation. “National Covid-19 Testing & Tracing Action Plan.” Thurs., July 16, 2020.

Randomized Controlled Trials Can Obscure “Nuances and Complexities”

(p. A17) You’ve probably heard of the “gold standard”—randomized controlled trials—for evaluating new pharmaceutical therapies, including for Covid-19. Many treatments that showed promise in other studies have turned up muddy results in randomized controlled trials. But that doesn’t mean they’re necessarily ineffective. Doctors and regulators need to consider the totality of medical evidence when treating patients.

. . .

“Randomized trials for some purposes is the gold standard, but only for some purposes,” Harvard’s Donald Berwick, a former health adviser to President Barack Obama, said in an interview with GNS Health Care CEO Colin Hill in 2013. “Context does matter. We’re learning in a very messy world, and the context that neatens up that world may make it hard to know how to manage in the real world.”

. . .

As Thomas Frieden, who directed the Centers for Disease Control and Prevention under Mr. Obama, wrote in a 2017 New England Journal of Medicine article: “Elevating RCTs at the expense of other potentially highly valuable sources of data is counterproductive.” Such limitations affect their use for “urgent health issues, such as infectious disease outbreaks.” He added: “No study design is flawless, and conflicting findings can emerge from all types of studies.”

. . .

Some experts have dismissed the antimalarial hydroxychloroquine, or HCQ, even though more than a dozen observational studies have found it beneficial. A retrospective observational study of Covid-infected nursing-home residents in France, for instance, found those treated with HCQ and azithromycin were 40% less likely to die.

But a few randomized controlled trials found no benefit. A Spanish randomized trial of HCQ for prophylaxis found it didn’t reduce risk of illness among a large group of people exposed in nursing homes, households and health-care settings. Yet two-thirds of the subjects “reported routine use of masks at the time of exposure,” so they were probably less likely to be infected. Nursing-home residents, who may be less likely to wear masks, were 50% less likely to become sick if they took HCQ. But this finding was statistically insignificant, because the trial included only 293 residents.

. . .

Another problem with Covid-19 randomized trials: Patients at different stages of an illness are often assigned the same dosage. Trials don’t reveal differences in how patients respond to a drug at different dosages or illness severity.

Observational studies can do so. Consider a large study by the Mayo Clinic, which found no overall benefit among patients who received a higher-antibody convalescent plasma versus a lower one. Yet the researchers reported a 37% reduction in mortality among patients under 80 who weren’t on a ventilator and received a high-antibody plasma within three days of hospitalizations.

A randomized trial might have obscured these nuances and complexities, denying doctors important information about treatment options. Randomized controlled trials can yield important insights, but it is a medical mistake and a disservice to patients to dismiss other types of evidence.

For the full commentary, see:

Allysia Finley. “Medical Research’s Cross of ‘Gold’ Imperils Covid Treatments.” The Wall Street Journal (Wednesday, September 9, 2020): A17.

(Note: ellipses added.)

(Note: the online version of the commentary has the date Sep. 8, 2020, and has the same title as the print version.)

The review article by Frieden mentioned above is:

Frieden, Thomas R. “Evidence for Health Decision Making — Beyond Randomized, Controlled Trials.” New England Journal of Medicine 377, no. 5 (Aug. 3, 2017): 465-75.

Masks Blocked Covid-19 at Hair Salon

(p. A6) Vigilant mask wearing might have spared nearly 140 people from catching the coronavirus at a hair salon in Missouri, according to a report published on Tuesday [July 14, 2020] by the Centers for Disease Control and Prevention. In May [2020], the people interacted with two hair stylists with confirmed coronavirus infections, but none ended up showing symptoms of Covid-19.

. . .

But policies instructing locals to cover their mouths and noses, put in place by the city of Springfield and by the salon where the stylists worked, Great Clips, appear to have played a substantial role in curbing the spread of disease.

For the full story, see:

Katherine J. Wu. “Report on Hair Salon Affirms Value of Masks.” The New York Times (Thursday, July 16, 2020): A6.

(Note: ellipsis, and bracketed dates, added.)

(Note: the online version of the story was updated July 17 [sic], 2020, and has the title “2 Stylists Had Coronavirus, but Wore Masks. 139 Clients Didn’t Fall Sick.”)

The CDC report mentioned above is:

Hendrix MJ, Walde C, Findley K, Trotman R. Absence of Apparent Transmission of SARS-CoV-2 from Two Stylists After Exposure at a Hair Salon with a Universal Face Covering Policy — Springfield, Missouri, May 2020. MMWR Morb Mortal Wkly Rep 2020;69:930-932.

Our Government Sends 19-Year-Olds to War but Does Not Allow Them to Try High-Risk, High-Reward Covid-19 Drugs and Vaccines

(p. A11) “Many drug programs are suspended or not pursued at all—not because of flaws in the science but because of commercial and strategic reasons,” Mr. Milken says. Researchers screen those programs, and he calls in his partners either to fund the ideas or promote their development at other companies if the inventors make them available.

It’s a niche in the pharmaceutical world that public funding can’t fill. Mr. Milken sustains a model “where a person could just give me a five-page summary and get a meeting. Government isn’t going to fund that, but philanthropy does.” “These little companies,” he adds—“they’re not Johnson & Johnson, they’re not Novartis, they’re not Amgen. They need financial capital.”

. . .

Mr. Milken’s deals not tinged by controversy, such as his 1983 issuance of bonds to finance telecom company MCI’s long-distance network, show the same preference that shapes his philanthropy: high risk for a high reward.

. . .

A perennial struggle for Mr. Milken has been to convince regulators to share that urgency. He says drug trials generally are too rigid: “We send 19-year-olds into war zones knowing that no matter what we do, some number—greater than zero—will lose their lives or their limbs. But we tell a patient who is going to die not to try something because it could be dangerous.”

Nonetheless, the partners he’s made in his search for cures prove that imagination and activity are still scattered through the country. Discussing the coronavirus with biotech founders and Nobel Prize winners, Mr. Milken says he’s been “thrust back into the 1970s and early ’80s, where any time someone had a new idea—a new company, a passion for something—I had set aside time every day to listen.” On the day a vaccine or effective cure for Covid-19 is finally announced, Americans will owe thanks to such risk takers, who Mr. Milken says “invest in where the world is going, not where it is.”

For the full interview, see:

Mene Ukueberuwa, interviewer. “THE WEEKEND INTERVIEW; What Would You Risk for a Faster Cure?” The Wall Street Journal (Saturday, May 2, 2020): A11.

(Note: ellipses added.)

(Note: the online version of the interview has the date May 1, 2020, and has the same title as the print version.)

Former FDA Research Virologist Suggests “Accelerated Approvals” of Covid-19 Vaccines

(p. A15) Covid-19 is a genuine emergency. Drug and biotech companies and academic institutions are doing their part, and regulators need to, as well. Having been a research virologist who spent 15 years at the FDA as the agency’s “biotechnology czar,” I have some suggestions:

. . .

• The FDA should issue “accelerated approvals” after testing in only limited populations. Additional subgroups—children, pregnant women, etc.—can be tested after approval. The accelerated approvals should be granted before the duration of postvaccination immunity has been ascertained. More-comprehensive trials can then confirm safety, efficacy and the length of time that immunity lasts.

• Establish reciprocity of approvals between the FDA and trusted counterparts in certain foreign countries (Australia, Canada, New Zealand, Japan, the Scandinavian countries and the European Medicines Agency), so that if one of them approves a vaccine, it is automatically approved in the other countries.

For the full commentary, see:

Henry I. Miller. “A Covid Vaccine: Faster, Please.” The Wall Street Journal (Thursday, April 23, 2020): A15.

(Note: ellipsis added.)

(Note: the online version of the commentary has the date April 22, 2020, and has the title “A Coronavirus Vaccine: Faster, Please.”)

Patients Die Due to Doctors Who Are “Busy Entering Health Care Data” Required by “Mandated Protocols”

(p. 18) Doctors today often complain of working in an occupational black hole in which patient encounters are compressed into smaller and smaller space and time. You can do a passable job in a 10-minute visit, they say, but it is impossible to appreciate the subtleties of patient care when you are rushing.

Enter “Slow Medicine: The Way to Healing,” a wonderful new memoir by Dr. Victoria Sweet.

. . .

One of the most compelling stories in the book is about Joey, a 3-year-old who is diagnosed with terminal lung disease after a near-drowning but against the odds makes it off the ventilator and out of the hospital. Sweet interprets Joey’s recovery in part as a victory for prayer. “Prayer worked,” she writes, “at least that once and maybe sometimes and maybe always.” I would see it differently: Joey was saved because a lung specialist slowly decreased airway pressure and tidal volume over several weeks in a patient with acute respiratory distress syndrome. And, as Sweet points out, it was slow medicine that allowed that doctor to make the proper adjustments.

Perhaps Sweet’s most depressing conclusion is that Joey would have died today. His doctors “would have been too busy entering health care data” that was required “according to all the mandated protocols.”

For the full review, see:

Sandeep Jauhar. “Heals Over Time.” The New York Times Book Review (Sunday, January 28, 2018): 18.

(Note: ellipsis added.)

(Note: the online version of the review has the date Jan. 26, 2018, and has the title “A Doctor Argues That Her Profession Needs to Slow Down, Stat.”)

The book under review is:

Sweet, Victoria. Slow Medicine: The Way to Healing. New York: Riverhead Books, 2017.

“Fat Cats” Fund Cancer Detection “Holy Grail”

(p. A15) So often the future shows up when you’re looking for something else. In 2013, DNA sequencing company Illumina bought Verinata Health and began offering noninvasive prenatal testing. Using a pregnant woman’s blood, a now-$500 DNA test can spot Down syndrome and other chromosomal conditions. Since then, the use of very invasive needle-to-the-womb amniocentesis testing has dropped.

But that’s not the story here. Of the first 100,000 women tested, 10 (or 0.01%) had unusual chromosome patterns. The fetus was fine, but in each case, the mother had cancer of differing types.

. . .

So Illumina spun out a new company named Grail in Menlo Park, Calif., to do what’s known as Circulating Cell-free Genome Atlas studies. Running DNA sequencing on regular blood samples, Grail generates hundreds of gigabytes of data per person—the well-known A-T-G-C nucleotides, but also the “methylation status,” or whether a particular DNA site’s function is turned on or off (technically, whether or not it represses gene transcription).

. . .

. . . , Grail’s chief medical officer Josh Ofman tells me, “cancer may show up as thousands of methylation changes, a much richer signal to teach machine learning algorithms to find cancer” vs. a single site. “There are 30 million methylation sites in the entire human genome on 100,000 DNA fragments. Grail looks at a million of them.” It takes industrial-grade artificial intelligence to find patterns in all this data, something a human eye would never see.

. . .

Grail is detecting the signature of actual cancer cells in your blood. According to validation data published in the Annals of Oncology, the test can find 50 different types, more than half of all known cancers.

. . .

Grail has raised almost $2 billion, including from Bill Gates and Jeff Bezos. Isn’t that interesting? Though much maligned as fat cats sitting on piles of gold coins and monopolists out to control the world, Messrs. Gates and Bezos are investing in technology—this is not philanthropy—that may save you or a relative’s life someday.

Innovation comes through surprises. This is a big one. And while worrywarts brood over artificial intelligence and robot overlords, early detection of cancer is really what machine learning is meant for. This is the Holy Grail.

For the full commentary, see:

Andy Kessler. “INSIDE VIEW; Cancer Screening Leaps Forward.” The Wall Street Journal (Monday, July 6, 2020): A15.

(Note: ellipses added.)

(Note: the online version of the commentary has the date July 5, 2020, and has the same title as the print version.)

Fauci Criticizes Russia for Allowing Citizens to Take Covid-19 Vaccine After Passing Phase 2 Safety Trials

Milton Friedman thought that, at the very least, the FDA should allow Americans the freedom to choose to take drugs or vaccines after their safety has been established (basically meaning after passing the Phase 2 safety trials). Isn’t it strange that in the FDA’s United States, citizens may not do so, but in Putin’s authoritarian Russia, citizens are allowed that choice?

(p. A4) In a panel discussion, Dr. Anthony S. Fauci, the nation’s top infections disease expert, criticized Russia’s rushed clearance of a coronavirus vaccine. The vaccine, called Sputnik V, was approved without evidence that Phase 3 clinical trials had been completed, an essential part of the development pipeline to prove a product is safe and effective in people.

. . .

Dr. Fauci called attention to the many other coronavirus vaccines vying for eventual clearance, including several that are in Phase 3 trials in the United States. The process for testing vaccines can last months and usually involves thousands of people.

“So if we wanted to take the chance of hurting a lot of people or giving them something that doesn’t work, we could start doing this, you know, next week if we wanted to,” Dr. Fauci said. “But that’s not the way this works.”

For the full story, see:

Barron, James. “Coronavirus Update.” The New York Times (Thursday, August 11, 2020): A4.

(Note: ellipsis added.)

(Note: the online version of the story was updated August 14, 2020, and has the title “U.S. Coronavirus Death Toll Reflects Sun Belt Outbreaks.” Where there are slight differences in wording between the versions in the passages quoted, the online version appears above. The online version does not list an author. I cite James Barron, who is listed as the author in the print version.)

Viruses Mutate More Nimbly Than Therapies Hobbled by FDA Regulations

(p. A7) In a laboratory in New York City, researchers coaxed a key piece of the coronavirus — its infamous outer “spike” — to mutate so that it became invisible to disease-fighting antibodies, according to a new study that has not yet been published in a scientific journal.

The provocative finding should not set off alarm bells, experts said. The altered spikes were not attached to the real coronavirus, which mutates at a much slower pace than most laboratory viruses. But the study does underscore the need for treatments and vaccines that attack the virus in different ways, so that if the pathogen manages to evade one approach, another will be waiting in the wings.

“It’s an old story for virology,” said Dr. Sallie Permar, a virologist and pediatrician at Duke University who was not involved in the study. “If you only target one little region, that virus is going to find a way to get away from it. It’s why viruses are so successful in this world.”

. . .

Several types of monoclonal antibodies are now in clinical trials. If all goes well, such concoctions might not only treat coronavirus infections but also prevent them. That could help millions of people, especially as the world awaits a vaccine, said Akiko Iwasaki, an immunologist at Yale University who was not involved in the study.

But the new findings also hint that single-antibody formulations “may not be as successful,” Dr. Taylor said, at least in the long term. Developing a cocktail containing a diverse blend of antibodies could be a safer bet.

Such mixtures would also more accurately mimic the body’s natural response to the coronavirus. In the study, viruses flushed with samples of convalescent plasma — fractions of blood donated by people who have recovered from Covid-19 — struggled to infect cells.

Some scientists, including those at American biotechnology company Regeneron, are already attempting this combo approach, mixing two potent types of monoclonal antibodies into a single treatment.

But Dr. Iwasaki pointed out that antibody cocktails might be tougher to bring to market. “Every time you make a drug, you get approval for each component separately,” she said. . . .

The lesson of diversity might be even more powerful for vaccines, which can marshal a multifaceted immune response. Some immune cells and molecules will be tailored to home in on the spike, whereas others might prefer other parts of the virus. Vaccines that present the body with many pieces of the coronavirus, rather than the spike alone, could have a better shot at triggering a suite of these defenses, said Dr. Taia Wang, an immunologist at Stanford University who was not involved in the study.

For the full story, see:

Katherine J. Wu. “Experiment on Spike Protein Shows Obstacles of Mutation.” The New York Times (Wednesday, July 29, 2020): A7.

(Note: ellipsis added.)

(Note: the online version of the story has the date July 28, 2020, and has the title “The Coronavirus Could Dodge Some Treatments, Study Suggests.” The online version has an extra paragraph that does not appear in the print version. In my quotations above, I stick to the print version.)

Paper Towels Spread Fewer Germs Than Hot-Air Drying

(p. R1) In the age of coronavirus, handwashing can save lives. But proper hand-drying matters, too.

“It might sound pedantic, but it’s actually critical,” says John Gammon, professor of infection prevention and control at Swansea University in the U.K.

Prof. Gammon was the lead author of a review of hand-drying research and published his findings in the March 2019 issue of the Journal of Infection Prevention. His paper, “The Neglected Element of Hand Hygiene,” examined the effectiveness of paper towels, cloth towels and dryers that use hot air or high-velocity air.

In a clinical situation, such as a hospital, disposable paper towels are generally the quickest, most efficient and hygienic method of hand drying. “The mechanical action of rubbing with paper towels has an effect on reducing microorganisms on hands,” Prof. Gammon says. Paper towels are also less likely to spread germs into the surrounding environment than hot-air and high-velocity air dryers, he adds.

For the full story, see:

Beth DeCarbo. “The Best Way to Dry Your Hands.” The Wall Street Journal (Friday, April 3, 2020): R1.

(Note: the online version of the story was updated April 2, 2020, and has the title “You’ve Perfected Your Handwashing Technique. Here’s How to Dry Them.” Where there is a slight difference in wording between the versions, the passages quoted above follow the online version.)

Gammon’s academic paper, mentioned above, is:

Gammon, John, and Julian Hunt. “The Neglected Element of Hand Hygiene – Significance of Hand Drying, Efficiency of Different Methods and Clinical Implication: A Review.” Journal of Infection Prevention 20, no. 2 (March 2019): 66-74.

After Age 65, Men Lose More “Antibody-Producing B Cells” Than Women Lose

(p. B5) By examining gender-based distinctions in the immune system, cell structure, brain and other systems, researchers are discovering how and why men and women grow older in clearly different ways.

Their findings could help explain why Covid-19 has had a greater impact on older men than older women. A recent study found that men, after the age of 65, lost important antibody-producing B cells in the blood, while women didn’t.

“It was surprising,” said Duygu Ucar, an associate professor who led the study at the Jackson Laboratory for Genomic Medicine in Farmington, Conn. The research team also found that men, as they age, experience greater inflammation in their blood, which has been associated with severe cases of Covid-19.

. . .

Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine, looked at the blood of men and women between the ages of 65 and 95 and found protein levels changed at different rates. Less change means more stability, he said. Men’s levels changed far more than women’s, with 600 significant changes versus 277 for women, according to the study, published in December.

“The female biology seems to be more stable than men’s,” says Dr. Barzilai, the author of “Age Later” who specializes in geroscience.

For the full story, see:

Clare Ansberry. “Women and Men Age Differently—-And in More Ways Than Just Longevity.” The Wall Street Journal (Wednesday, July 15, 2020): A13.

(Note: ellipsis added.)

(Note: the online version of the story has the date July 14, 2020, and has the title “Women and Men Age Differently—in More Ways Than Just Longevity.” The last couple of paragraphs quoted above, appeared in the online, but not the print, version of the article.)

The “recent study” mentioned above is:

Márquez, Eladio J., Cheng-han Chung, Radu Marches, Robert J. Rossi, Djamel Nehar-Belaid, Alper Eroglu, David J. Mellert, George A. Kuchel, Jacques Banchereau, and Duygu Ucar. “Sexual-Dimorphism in Human Immune System Aging.” Nature Communications 11, Article #751 (Feb. 6, 2020): 1-17.

The book by Barzilai, mentioned above, is:

Barzilai, Nir. Age Later: Health Span, Life Span, and the New Science of Longevity. New York: St. Martin’s Press, 2020.