Category: Health

High Viral Load Increases Odds of Long Covid

(p. 18) It is one of many mysteries about long Covid: Who is more prone to developing it? Are some people more likely than others to experience physical, neurological or cognitive symptoms that can emerge, or linger for, months after their coronavirus infections have cleared?

Now, a team of researchers who followed more than 200 patients for two to three months after their Covid diagnoses report that they have identified biological factors that might help predict if a person will develop long Covid.

The study, published Tuesday [January 25, 2022] by the journal Cell, found four factors that could be identified early in a person’s coronavirus infection that appeared to correlate with increased risk of having lasting symptoms weeks later.

. . .

One of the four factors researchers identified is the level of coronavirus RNA in the blood early in the infection, an indicator of viral load. Another is the presence of certain autoantibodies — antibodies that mistakenly attack tissues in the body as they do in conditions like lupus and rheumatoid arthritis. A third factor is the reactivation of Epstein-Barr virus, a virus that infects most people, often when they are young, and then usually becomes dormant.

The final factor is having Type 2 diabetes, although the researchers and other experts said that in studies involving larger numbers of patients, it might turn out that diabetes is only one of several medical conditions that increase the risk of long Covid.

. . .

One persuasive conclusion, several experts said, was the suggestion that because patients with high viral loads early on often developed long Covid, giving people antivirals soon after diagnosis might help prevent long-term symptoms.

“The quicker one can eliminate the virus, the less likelihood of developing persistent virus or autoimmunity, which may drive long Covid,” Dr. Iwasaki said.

For the full story, see:

Pam Belluck. “New Research Hints at 4 Factors That May Increase Chances of Long Covid.” The New York Times, First Section (Sunday, January 30, 2022): 18.

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

(Note: the online version of the story has the date Jan. 25, 2022, and has the same title as the print version.)

The “Gold Standard” of Randomized Clinical Trials “Has Its Own Issues”

(p. R2) . . ., closely held Epic Systems Corp., maker of one of the most widely used electronic health record systems, searched a segment of its database in the spring of 2020 to find that routine breast, colon and cervical cancer screenings in the U.S. had each dropped by more than 85% during the first weeks of the Covid-19 pandemic. The report helped spur efforts to persuade people to make up for missed screenings.

But researchers have a much more ambitious vision for this data: to help guide how doctors treat individual patients in real time.

“The evidence from real-world data is a different and exciting new path,” says Jackie Gerhart, a physician who works with the informatics team at Epic. “You can get a lot of outcomes information from medical records that can help change care for individual patients.”

. . .

To be sure, patient records are observational, and thus subject to confounders and other shortcomings that can undercut their reliability in pointing to treatment options.

But the gold standard has its own issues. Randomized clinical trials, which control for differences in patient health status and other variables, are the preferred evidence to inform patient care. Yet such trials generally exclude an especially common group of patients—those with multiple ailments. Moreover, the elderly, children, women, minority groups and people who live far from medical research centers have long been underrepresented in such studies.

As a result, the highest-quality evidence that medicine produces doesn’t apply to most patients doctors see in daily practice. “There are so many clinical situations where the evidence that is needed does not exist,” says Nigam Shah, professor of medicine and biomedical data science at Stanford University Medical School.

Researchers have believed for at least a half-century that data in patient medical records could help fill the gaps.

. . .

The struggles of International Business Machines Corp.’s Watson raises [a] . . . yellow flag. It had ambitions to develop a tool for cancer doctors that would mine patient health records and thousands of pages of research from the peer-reviewed medical literature for treatment advice. But it hit walls, including accuracy and the complexity of combining data from electronic health records, billing claims and published research to provide a cohesive product. Doctors who used the service rarely changed treatment plans. IBM says it discontinued Watson for Oncology at the end of 2020.

For the full story, see:

Ron Winslow. “Mining the Gold in Patient Records.” The Wall Street Journal (Thursday, December 9, 2021): R2.

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

(Note: the online version of the story has the date December 3, 2021, and has the title “Medical Records Data Offers Doctors Hope of Better Patient Care.” In a couple of passages there are a few extra words in the online version, which is the version quoted above.)

Johan Hultin Self-Funded Trip to Find 1918 Flu Virus in the Permafrost

(p. B9) Dr. Hultin’s quest to find victims of the 1918 flu was sparked in 1950 by an offhand remark over lunch with a University of Iowa microbiologist, William Hale. Dr. Hale mentioned that there was just one way to figure out what caused the 1918 pandemic: finding victims buried in permafrost and isolating the virus from lungs that might be still frozen and preserved.

Dr. Hultin, a medical student in Sweden who was spending six months at the university, immediately realized that he was uniquely positioned to do just that. The previous summer, he and his first wife, Gunvor, spent weeks assisting a German paleontologist, Otto Geist, on a dig in Alaska. Dr. Geist could help him find villages in areas of permafrost that also had good records of deaths from the 1918 flu.

After persuading the university to provide him with a $10,000 stipend, Dr. Hultin set off for Alaska. It was early June 1951.

. . .

He removed still-frozen lung tissue from the victims, closed the grave and took the tissue back to Iowa, keeping it frozen on dry ice in the passenger compartment of a small plane.

Back in the lab, Dr. Hultin tried to grow the virus by injecting the lung tissue into fertilized chicken eggs — the standard way to grow flu viruses. He was caught up in the excitement of his experiment, he said, and had not thought about the possible danger of introducing a deadly virus into the world.

“I remember the sleepless nights,” he said. “I couldn’t wait for morning to come to charge into my lab and look at the eggs.”

But the virus was not growing.

He tried squirting lung tissue into the nostrils of guinea pigs, white mice and ferrets, but again he failed to revive the virus.

“The virus was dead,” he said.

Dr. Hultin never published his results but bided his time, working as a pathologist in private practice in San Francisco and hoping for another opportunity to resurrect that virus.

His chance came in 1997, when, sitting by a pool on vacation with his wife in Costa Rica, he noticed a paper published in Science by Dr. Jeffery K. Taubenberger, now chief of the viral pathogenesis and evolution section at the National Institute of Allergy and Infectious Diseases.

It reported a remarkable discovery. Dr. Taubenberger had searched a federal repository of pathology samples dating to the 1860s and found fragments of the 1918 virus in snippets of lung tissue from two soldiers who had died in that pandemic. The tissue had been removed at autopsy, wrapped in paraffin and stored in the warehouse.

Dr. Hultin immediately wrote to Dr. Taubenberger, telling him about his trip to Alaska. He offered to return to Brevig to see if he could find more flu victims.

“I remember getting that letter and thinking: ‘Gosh. This is really incredible. This is amazing,’” Dr. Taubenberger said in an interview this week. He thought the next step would be to apply for a grant for Dr. Hultin to return to Brevig. If all went well, Dr. Hultin might go back in a year or two.

Dr. Hultin had a different idea.

“I can’t go this week, but maybe I can go next week,” he told Dr. Taubenberger.

He added that he would go alone and pay for the trip himself so that there would be no objections from funding agencies, no delays, no ethics committees and no publicity.

. . .

Using the tissue Dr. Hultin provided, Dr. Taubenberger’s group published a paper that provided the genetic sequence of a crucial gene, hemagglutinin, which the virus had used to enter cells. The group subsequently used that tissue to determine the complete sequence of all eight of the virus’s genes.

. . .

Before results from the study of the Brevig woman’s virus were published, Dr. Hultin asked the villagers if they wanted the village to be identified in a news release and a journal article. They might be besieged by media. “Maybe you won’t like that,” he warned them.

The Brevig residents came to a consensus: Publish the paper and identify the village. Dr. Hultin was listed as a co-author.

For the full obituary, see:

Gina Kolata. “Dr. Johan Hultin, 97, Whose Work Helped Map 1918 Pandemic, Dies.” The New York Times (Friday, January 28, 2022): B9.

(Note: ellipses added.)

(Note: the online version of the obituary was updated January 28, 2022, and has the title “Johan Hultin, Who Found Frozen Clues to 1918 Virus, Dies at 97.”)

Gina Kolata devotes a chapter to Hultin’s search for the 1918 flu virus in her book:

Kolata, Gina. Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It. New York: Farrar, Straus & Giroux, Inc., 1999.

IBM Sells Failed Watson Artificial Intelligence Health Unit

(p. B3) International Business Machines Corp. agreed to sell the data and analytics assets from its Watson Health business to investment firm Francisco Partners, the companies said Friday [January 21, 2022].

. . .

The Watson Health business uses artificial intelligence to analyze diagnostic tests and other health data and to manage care.

IBM had big aspirations for its Watson artificial intelligence to help in medical research and improve patient outcomes, but the technology’s impact has fallen short of early hopes. Partners and clients have moved away from projects that were built around Watson technology in recent years, although IBM had spent billions of dollars making acquisitions to bolster the business.

“IBM took a risk of becoming a disrupter in the complex health care industry but was only able to garner limited success,” UBS analyst David Vogt said in a note Friday.

For the full story, see:

Matt Grossman. “IBM Sells Its Watson Health Assets To Investment Firm as It Refocuses.” The Wall Street Journal (Saturday, January 22, 2022): B3.

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

(Note: the online version of the story was updated Jan. 21, 2022, and has the title “IBM Sells Watson Health Assets to Investment Firm.”)

Instead of Centralizing With C.D.C., the Need for Speed Requires “Clinical and Commercial Labs to Create and Deploy Tests”

(p. A22) The faulty coronavirus testing kits developed by the Centers for Disease Control and Prevention in the early weeks of the pandemic were not only contaminated but had a basic design flaw, according to an internal review by the agency.

Health officials had already acknowledged that the test kits were contaminated, but the internal report, whose findings were published in PLOS ONE on Wednesday, also documented a design error that caused false positives.

. . .

The C.D.C.’s test was designed to detect three distinct regions, or target sequences, of the virus’s genetic material. The test kits contain a set of what are known as primers, which bind to and make copies of the target sequences, and probes, which produce a fluorescent signal when these copies are made, indicating that genetic material from the virus is present.

The primers and probes need to be carefully designed so that they bind to the target sequences and not to each other. In this case, that did not happen. One of the probes in the kit sometimes bound to one of the primers, producing the fluorescent signal and generating a false positive.

“It’s something that should have been caught in the design phase,” said Susan Butler-Wu, a clinical microbiologist at the Keck School of Medicine of the University of Southern California. “That’s one thing that you check for.”

. . .

The bigger lesson, Dr. Butler-Wu said, is that the responsibility for developing diagnostic tests should be distributed more widely during a public health emergency. Rather than relying on the C.D.C. to be the sole test developer, officials could also enlist clinical and commercial labs to create and deploy tests.

“It’s great that there’s all these additional checks in place, but what are you going to do when there’s a new emerging pathogen and we need to respond quickly?” she said. “I don’t think that’s a viable model for responding to a pandemic.”

For the full story, see:

Emily Anthes. “C.D.C. Finds Design Error In Testing Kits It Distributed.” The New York Times Thursday, December 16, 2021): A22.

(Note: ellipses added.)

(Note: the online version of the story has the date Dec. 15, 2021, and has the title “C.D.C. Virus Tests Were Contaminated and Poorly Designed, Agency Says.”)

The PLOS ONE article mentioned above is:

Lee, Justin S., Jason M. Goldstein, Jonathan L. Moon, Owen Herzegh, Dennis A. Bagarozzi, Jr., M. Steven Oberste, Heather Hughes, Kanwar Bedi, Dorothie Gerard, Brenique Cameron, Christopher Benton, Asiya Chida, Ausaf Ahmad, David J. Petway, Jr., Xiaoling Tang, Nicky Sulaiman, Dawit Teklu, Dhwani Batra, Dakota Howard, Mili Sheth, Wendi Kuhnert, Stephanie R. Bialek, Christina L. Hutson, Jan Pohl, and Darin S. Carroll. “Analysis of the Initial Lot of the CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel.” PLOS ONE 16, no. 12 (Dec. 15, 2021). DOI: 10.1371/journal.pone.0260487.

FDA Only Approves Drugs That Fight Diseases and FDA Does Not See Aging as a Disease

(p. R2) Will people eventually routinely live—and live healthily—longer? That’s the vision of the burgeoning field of aging research, where scientists are trying to extrapolate tantalizing life-prolonging findings from animal experiments into medicines that slow, prevent or even reverse the aging process for humans.

Leading candidates for stanching aging include two familiar drugs—metformin, a front-line diabetes treatment, and rapamycin, long used to prevent transplant patients from rejecting donated organs. Both have been shown to increase longevity in animal studies and both target molecular processes linked to the aging of cells.

Another approach is a new class of drugs called senolytics, which clear the body of so-called senescent cells, old cells that stop dividing but don’t die. They accumulate in tissues throughout the body and secrete factors that damage other cells. They are linked to such aging conditions as frailty, cognitive impairment and lack of physical resilience.

Also in the mix is a strategy called cellular reprogramming in which scientists are seeking to turn back the clock on aging cells, restoring functions characteristic of younger cells.

. . .

. . ., the Food and Drug Administration doesn’t recognize aging as a disease to be treated, meaning there isn’t a clear path to approval for a drug that targets the biology of aging. Researchers instead have to design trials that can quantify whether a drug improves health or extends survival in a specific age-related disease. A pill that a large and generally healthy population would take, perhaps for decades, would have to clear a high safety bar.

. . .

Researchers are working to develop biomarkers in blood or other bodily sources that can quantify the aging process and serve as drug targets or as proxies to indicate a drug is working or not. Without validated biomarkers, it could take 20 or 30 years in some cases to run a randomized trial to prove whether a drug safely extended life.

For the full story, see:

Ron Winslow. “A Pill to Turn Back the Clock.” The Wall Street Journal (Thursday, Jan. 13, 2022): R2.

(Note: ellipses added.)

(Note: the online version of the story has the date January 11, 2022, and has the title “Can You Fight Aging? Scientists Are Testing Drugs to Help.”)

Diamond to Give “How to Cure Cancer” Talk at Gustavus Adolphus College

I appreciate Marta Podemska-Mikluch’s perseverance over the long pandemic in arranging my conversations with Gustavus Adolphus College students on some of my current research on medical entrepreneurship. I am looking forward to my visit!

Surgical Masks Provide Wearer Modest Protection Against Infection from Covid-19

(p. A17) The first large randomized community-level study, published last month in Science, found that while generic surgical masks provided a modest (about 10%) reduction in the risk of infection from Delta, cloth masks didn’t significantly reduce risk. Masks may be even less protective against an extremely contagious variant like Omicron.

For the full commentary, see:

Daniel Halperin. “Omicron Is Spreading. Resistance Is Futile.” The Wall Street Journal (Tuesday, January 25, 2022): A17.

(Note: the online version of the commentary has the date Jan. 24, 2022, and has the same title as the print version.)

The article in Science mentioned above is:

Abaluck, Jason, Laura H. Kwong, Ashley Styczynski, Ashraful Haque, Md. Alamgir Kabir, Ellen Bates-Jefferys, Emily Crawford, Jade Benjamin-Chung, Shabib Raihan, Shadman Rahman, Salim Benhachmi, Neeti Zaman Bintee, Peter J. Winch, Maqsud Hossain, Hasan Mahmud Reza, Abdullah All Jaber, Shawkee Gulshan Momen, Aura Rahman, Faika Laz Banti, Tahrima Saiha Huq, Stephen P. Luby, and Ahmed Mushfiq Mobarak. “Impact of Community Masking on Covid-19: A Cluster-Randomized Trial in Bangladesh.” Science 375, no. 6577 (Jan. 14, 2022). DOI: 10.1126/science.abi9069.

Alan Scott’s Use of Botulism to Fix Eye Muscles Led to Serendipitous Discovery of Botox to Smooth Wrinkles

(p. B11) It is a neurotoxin 100 times more deadly than cyanide and the cause of the food-borne illness known as botulism. During World War II and for some years after, the Department of Defense hoped to develop it as a chemical weapon. But it wasn’t until the 1970s that Alan Scott, an ophthalmologist, turned the botulinum toxin into a pharmaceutical, when he began to investigate it as a medical treatment for serious eye impairments.

. . .

When, in 1978, Dr. Scott first injected the powerful paralytic into the eye muscles of a patient who had undergone retinal detachment surgery that had left his eye pulled to one side, he didn’t know who was more nervous, himself or the patient, he told Scientific American magazine in 2016.

But the procedure succeeded, and Dr. Scott would go on to refine one of the world’s deadliest poisons into a life-altering treatment — he called it Oculinum — for those who suffered from conditions like strabismus, a misalignment of the eyes.

Doctors also began using it to treat migraines and jaw-clenching, among other ailments, and as they did so many of their delighted patients noticed a curious byproduct: The toxin’s ability to paralyze targeted facial muscles smoothed the lines around them, though its effects wore off after a few months.

For the full obituary, see:

Penelope Green. “Alan Scott, 89, Eye Doctor Behind Medical Use of Botox.” The New York Times (Tuesday, January 18, 2022): B11.

(Note: ellipsis added.)

(Note: the online version of the obituary was updated Jan. 20, 2022, and has the title “Alan Scott, Doctor Behind the Medical Use of Botox, Dies at 89.”)

Socialist Mayor’s Environmental Bicycles Turn Paris Streets into Risky Chaos

(p. 4) PARIS — On a recent afternoon, the Rue de Rivoli looked like this: Cyclists blowing through red lights in two directions. Delivery bike riders fixating on their cellphones. Electric scooters careening across lanes. Jaywalkers and nervous pedestrians scrambling as if in a video game.

Sarah Famery, a 20-year resident of the Marais neighborhood, braced for the tumult. She looked left, then right, then left and right again before venturing into a crosswalk, only to break into a rant-laden sprint as two cyclists came within inches of grazing her.

“It’s chaos!” exclaimed Ms. Famery, shaking a fist at the swarm of bikes that have displaced cars on the Rue de Rivoli ever since it was remade into a multilane highway for cyclists last year. “Politicians want to make Paris a cycling city, but no one is following any rules,” she said. “It’s becoming risky just to cross the street!”

The mayhem on Rue de Rivoli — a major traffic artery stretching from the Bastille past the Louvre to the Place de la Concorde — is playing out on streets across Paris as the authorities pursue an ambitious goal of making the city a European cycling capital by 2024.

Mayor Anne Hidalgo, who is campaigning for the French presidency, has been burnishing her credentials as an ecologically minded Socialist candidate. She has earned admirers and enemies alike with a bold program to transform greater Paris into the world’s leading environmentally sustainable metropolis, reclaiming vast swaths of the city from cars for parks, pedestrians and a Copenhagen-style cycling revolution.

For the full story, see:

Liz Alderman. “PARIS DISPATCH; Europe’s New Cycling Capital, or a Pedestrian’s Nightmare?” The New York Times, First Section (Sunday, Oct. 3, 2021): 4.

(Note: the online version of the story was updated Oct. 4, 2021, and has the title “PARIS DISPATCH; As Bikers Throng the Streets, ‘It’s Like Paris Is in Anarchy’.”)

COVID-19 Vaccines Were Built on “Decades-Long Efforts to Create Other Vaccines”

Gregory Zuckerman’s The Frackers was a great deep dive into the lives of important non-Silicon Valley entrepreneurs. So far I am also enjoying Zuckerman’s new book, reviewed in the brief passages quoted below.

(p. 26) Zuckerman answers a question still circulating among both vaccine fans and skeptics: How could scientists develop the Covid-19 vaccines so quickly?

The answer is that they didn’t. The Covid-19 vaccines were built on the backs of decades-long efforts to create other vaccines, like one for the Zika virus and, in particular, several failures to develop a useful H.I.V. vaccine.

For the full, but short, review, see:

Eve Fairbanks. “THE SHORTLIST; Covid.” The New York Times Book Review (Sunday, January 9, 2022): 26.

(Note: the online version of the review has the date Dec. 29, 2021, and has the title “THE SHORTLIST; New Books Explore the Many Ways Covid Has Altered Our Lives.”)

The book under review is:

Zuckerman, Gregory. A Shot to Save the World: The inside Story of the Life-or-Death Race for a Covid-19. New York: Portfolio/Penguin, 2021.