Foreign aid for health care is directly linked to an increase in life expectancy and a decrease in child mortality in developing countries, according to a new study by Stanford researchers.

The researchers examined both public and private health-aid programs between 1974 and 2010 in 140 countries and found that, contrary to common perceptions about the waste and ineffectiveness of aid, these health-aid grants led to significant health improvements with lasting effects over time.

Countries receiving more health aid witnessed a more rapid rise in life expectancy and saw measurably larger declines in mortality among children under the age of 5 than countries that received less health aid, said Eran Bendavid, MD, an assistant professor in Stanford Medical School's Division of General Medical Disciplines and lead author of the study. If these trends continue, he said, an increase in health aid of just 4 percent, or $1 billion, could have major implications for child mortality.

“If health aid continues to be as effective as it has been, we estimate there will be 364,800 fewer deaths in children under 5,” he said. “We are talking about $1 billion, which is a relatively small commitment for developed countries.”

The study was published online April 21 in JAMA Internal Medicine. The study’s co-author, Jay Bhattacharya, MD, PhD, is an associate professor of medicine.

Bendavid and Bhattacharya are core faculty members at Stanford’s Center for Health Policy and Center for Primary Care and Outcomes Research at the university's Freeman Spogli Institute for International Studies.

Does it work?

Bendavid noted that there is much debate around foreign aid. Critics question whether it’s used effectively and reaches its intended recipients. They often argue that it discourages local development and displaces domestic resources that might otherwise be devoted to health. So the researchers devised a statistical tool to address the basic unanswered question: Do investments in health really lead to health improvements?

Bendavid said there are many reasons to suspect the answer would be no, though the findings proved just the contrary, with health-related aid leading to direct, beneficial outcomes.

“I think for many people, that will be surprising,” he said. “But for me, it fits with other evidence of the incredible success of public health promotion in developing countries.” In a previous study, for instance, he found that hundreds of thousands of lives were saved through the U.S. President’s Emergency Plan for AIDS Relief, or PEPFAR, in which the U.S. government invested billions of dollars in antiretroviral treatment and other AIDS-related prevention and treatment initiatives.

In the latest study, the two investigators used data from the Creditor Reporting System of the Organization for Economic Cooperation and Development, the world’s most extensive source of information on foreign aid. While aid programs for health grew during the 36-year study period, the largest period of growth occurred between 2000 and 2010, they found.

Stepped-up investments

It was during this decade that many governments and private groups stepped up their investments in health, including PEPFAR; the World Bank; the Global Fund to Fight AIDS, Tuberculosis and Malaria; the Gates Foundation; and the GAVI Alliance, among others, he said.

As a result, while health aid in 1990 accounted for 4 percent of total foreign aid, it now amounts to 15 percent of all aid, he said. And it’s become an important part of health budgets in recipient countries, accounting for 25-30 percent of all health-care spending in low-income countries, Bendavid said.

The researchers found that these funds were used effectively, largely because of the targeting of aid to disease priorities where improved technologies — such as new vaccines, insecticide-treated bed nets for malarial prevention and antiretroviral drugs for HIV — could make a real difference.

They observed the greatest health impacts between 2000 and 2010, when donor investments were at their peak. During the decade, under-5 child mortality declined from a mean of 109.2 to 72.4 deaths per 1,000, or 36.8 fewer deaths among those children in the countries that received the most health aid, the researchers found (a 34 percent reduction). In the countries receiving the least, under-5 mortality fell from 31.6 to 23.2 deaths per 1,000, or 8.4 fewer deaths per 1,000 live births (a 26 percent reduction), the researchers reported.

Life expectancy increases

During that period, life-expectancy figures also grew faster in countries with a greater infusion of health aid, Bendavid said. Life expectancy rose from 57.5 to 62.3 — an increase of 4.8 years — among the countries receiving the most aid. Among the countries receiving the least health aid, life expectancy increased by 2.7 years, from 69.8 to 72.5 years.

Bendavid said previous experience has shown that, on average, life expectancy has increased by nearly one year every four years in developed countries. But health-aid programs literally cut in half the time it took to reach this goal in developing countries. “In that same four-year span, they increased life expectancy by two years, rather than one year,” he said.

He said the results are not surprising if one considers some of the new health technologies made available to developing nations as a result of foreign aid. Childhood vaccines, including those for diphtheria, tetanus, polio and measles, have all but wiped out what used to be among the top killers of young children in the developing world. Health aid directed to providing insecticide-treated malarial bed nets also has been credited in recent studies with reducing malarial deaths among young children, he noted.

Among both adults and children, aid that has expanded the availability of antiretroviral drugs in the developing world has had a major impact on reducing deaths and improving overall life expectancies, he said. For instance, in a study published in 2012, Bendavid and colleagues found that PEPFAR’s health aid resulted in more than 740,000 lives saved between 2004 and 2008 in nine countries.

The researchers also found that the benefits of aid have a lasting effect: The telltale signs of aid’s relationship to reducing under-5 mortality were detectable for three years following the distribution of aid. The correlation between health aid and longer life expectancy overall was detectable for five years after the aid was distributed.

With aid commitments flattening amid the economic downturn, Bendavid said donors will have to be that much smarter in how they invest future dollars, focusing on the most cost-effective interventions and technologies.

“To date, there has been little consideration of how to use development aid in the most cost-effective manner,” he said. “That will have to change now that the funding level has reached a plateau.”

The study was funded by the George Rosenkranz Fellowship for Health Policy Research in Developing Countries and by the National Institutes of Health (grant K01AI084582).

A new analysis found that the National Institutes of Health is funding more conservative research projects, which does not promote great new discoveries, the authors argue.

Science moves forward when scientists take risks.

"For example, one of the hottest new ideas in cancer treatment involves using patients' own immune cells to treat their cancer," writes Stanford Health Policy's Jay Bhattacharya, MD, PhD, in a recent policy brief. "The researchers who worked on these ideas when they were novel risked failure, but still pursued them."

The National Institutes of Health plays an important role in addressing this fail-to-win strategy underlying scientific research, Bhattacharya said. With a $37 billion annual budget, the NIH is the world's largest funder of biomedical research.

"As a public institution, it can be thought of as 'patient capital,' a funding source with a longtime horizon and an understanding that good ideas frequently lead down blind alleys," Bhattacharya writes with his colleague, Mikko Packalen, PhD, a Stanford alumnus and associate professor of economics at the University of Waterloo in Ontario, Canada.

"By that standard, NIH ought to be putting money into novel ideas that cannot get funding from private sources," they write.

But that doesn't appear to be the case.

Bhattacharya and Packalen conducted a quantitative analysis to measure the extent to which NIH funds novel ideas. "An article was considered novel if the newest idea on which it was built upon was relatively recent in the sense that the idea had first appeared in any biomedical research paper at most a few years prior," they explained.

They looked at 24 million biomedical research articles in the MEDLINE database published between 1950 and 2017 with an American first author.

They found that from 2010 to 2016, the NIH disproportionately funded biomedical research based neither on the most recent ideas nor on the most longstanding ideas, but rather on those of intermediate vintage introduced into the literature between 1990 and 2005.

"Specifically, NIH funded research based on 10- to 25-year-old ideas at a 55 percent rate, compared with a 45 percent funding rate for more recent or older idea," they write. "By contrast, from 1990 to 1999, NIH funded research based on new ideas at a higher rate than it funded research drawing on well-established ideas.

"This indicates that NIH has become less likely to support edge science over the past two decades," the researchers concluded. "These results are disheartening and consistent with a growing body of scholarship that finds NIH review panels becoming more conservative and risk-averse."

The authors note the NIH recognizes the danger of underfunding high-risk ideas and has taken steps to counter "a creeping conservative bias" by increasing the number of training awards, paying bonuses to young researchers and developing methods for identifying high-risk ideas.

But more needs to be done, they said, recommending that the NIH:

• Reform the review process and rethink how review panel members are selected;

• Change the way it measures success to increase tolerance of failure;

• Develop ways to directly measure the novelty of ideas;

• Find additional ways to reward scientists working on novel ideas by taking steps to advance their careers.

"If the world's foremost supporter of biomedical research has indeed become less open to edge science, as our analysis indicates, it bodes poorly for science," they wrote.

Arecent report from the Centers for Disease Control and Prevention contained a sobering surprise: Life expectancy at birth in the U.S. declined a tenth of a year to 78.6 years. The update also included information on the leading causes of death.

Jay Bhattacharya, MD, PhD, a senior fellow of the Freeman Spogli Institute for International Studies, helped make sense of the findings:

Did anything surprise you about the studies?

JB: "The academic discourse around life expectancy in the past few years has really just been focused on looking for signs of a possible slowdown in the rate at which it has been increasing. What the CDC has now revealed is a real reduction in the anticipated life spans of human beings born today. Up until recently, we as demographers had been debating what the limits to human longevity might be, but now we're now being forced to answer a totally different question about why that positive trend, which we'd assumed was going to" continue for a while, has been so suddenly thrown into reverse."

What possible reasons have been floated to explain this decline?

JB: "A lot of the discussion in the media after the CDC released these reports was focused on increased deaths from opioid abuse and suicide. The theory goes that because of the increasing prevalence of suicide, depression, drug abuse, and so forth  —  which tend to begin in younger populations  —  that there's more of an impact on life expectancy relative to, for example, a disease hitting people who are 80- or 90-years-old. But my personal view is that these factors, although they might have a particular political salience right now, aren't actually the main reasons for the decline that the CDC is reporting."

What alternative would you offer?

JB: "A lot of the previous demographic literature has focused on changes in chronic disease rates in the American population and in particular on obesity. There's been this enormous and persistent rise in the prevalence of obesity going back decades... In the U.S. today, around 40 percent of the adult population is obese and correlates very strongly, causally even, with diabetes and all kinds of other chronic conditions that are not just expensive to treat but also lead to increased mortality."

How should we go about reversing these trends?

JB: "One thing that I think we need to be better at is distinguishing between primary prevention and secondary care. The latter we've gotten very good at, the former not so much. For instance, while chronic disease rates have risen dramatically in the U.S., disability from that chronic disease hasn't to the same extent. We're better at treating people who've had a heart attack or a stroke so that they don't end up seriously disabled, but in terms of preventing those primary health events from happening, by targeting risk factors like obesity, we're not doing enough."

How should we be spending health care dollars to maximize their positive impact on outcomes like life expectancy?

JB: "This is a tricky question, because it gets into the highly-political distributional questions around health care, as well as the way that these questions tie into other types of social inequality. When it comes to socioeconomic status, the lowest quintile has experienced almost no change in life expectancy over the last 20 years whereas as the highest quintiles experienced very substantial life-expectancy increases. In developed countries, it also tends to be the relatively poor who are most likely to be obese; about 1.5 times more likely in the U.S. Exactly how we should go about addressing this imbalance isn't clear... Certainly though, we should be asking where the marginal value of health care dollars is highest and target those areas. For instance, the costs of preventative or primary medicine relative to rehabilitative or secondary care are much lower, so working on novel and effective ways to encourage people to take better care of themselves before they experience some kind of major illness will be critical."

A longer version of this piece was originally published by the Freeman Spogli Institute for International Studies. [HITS - But it was written in 2014. Saved as PDF here :  [HE00AZ][GDrive]   ] 

If it’s true that the novel coronavirus would kill millions without shelter-in-place orders and quarantines, then the extraordinary measures being carried out in cities and states around the country are surely justified. But there’s little evidence to confirm that premise—and projections of the death toll could plausibly be orders of magnitude too high.

Fear of Covid-19 is based on its high estimated case fatality rate—2% to 4% of people with confirmed Covid-19 have died, according to the World Health Organization and others. So if 100 million Americans ultimately get the disease, two million to four million could die. We believe that estimate is deeply flawed. The true fatality rate is the portion of those infected who die, not the deaths from identified positive cases. 

The latter rate is misleading because of selection bias in testing. The degree of bias is uncertain because available data are limited. But it could make the difference between an epidemic that kills 20,000 and one that kills two million. If the number of actual infections is much larger than the number of cases—orders of magnitude larger—then the true fatality rate is much lower as well. That’s not only plausible but likely based on what we know so far.

Population samples from China, Italy, Iceland and the U.S. provide relevant evidence. On or around Jan. 31, countries sent planes to evacuate citizens from Wuhan, China. When those planes landed, the passengers were tested for Covid-19 and quarantined. After 14 days, the percentage who tested positive was 0.9%. If this was the prevalence in the greater Wuhan area on Jan. 31, then, with a population of about 20 million, greater Wuhan had 178,000 infections, about 30-fold more than the number of reported cases. The fatality rate, then, would be at least 10-fold lower than estimates based on reported cases.

Next, the northeastern Italian town of Vò, near the provincial capital of Padua. On March 6, all 3,300 people of Vò were tested, and 90 were positive, a prevalence of 2.7%. Applying that prevalence to the whole province (population 955,000), which had 198 reported cases, suggests there were actually 26,000 infections at that time. That’s more than 130-fold the number of actual reported cases. Since Italy’s case fatality rate of 8% is estimated using the confirmed cases, the real fatality rate could in fact be closer to 0.06%.

In Iceland, deCode Genetics is working with the government to perform widespread testing. In a sample of nearly 2,000 entirely asymptomatic people, researchers estimated disease prevalence of just over 1%. Iceland’s first case was reported on Feb. 28, weeks behind the U.S. It’s plausible that the proportion of the U.S. population that has been infected is double, triple or even 10 times as high as the estimates from Iceland. That also implies a dramatically lower fatality rate.

The best (albeit very weak) evidence in the U.S. comes from the National Basketball Association. Between March 11 and 19, a substantial number of NBA players and teams received testing. By March 19, 10 out of 450 rostered players were positive. Since not everyone was tested, that represents a lower bound on the prevalence of 2.2%. The NBA isn’t a representative population, and contact among players might have facilitated transmission. But if we extend that lower-bound assumption to cities with NBA teams (population 45 million), we get at least 990,000 infections in the U.S. The number of cases reported on March 19 in the U.S. was 13,677, more than 72-fold lower. These numbers imply a fatality rate from Covid-19 orders of magnitude smaller than it appears.

How can we reconcile these estimates with the epidemiological models? First, the test used to identify cases doesn’t catch people who were infected and recovered. Second, testing rates were woefully low for a long time and typically reserved for the severely ill. Together, these facts imply that the confirmed cases are likely orders of magnitude less than the true number of infections. Epidemiological modelers haven’t adequately adapted their estimates to account for these factors. 

The epidemic started in China sometime in November or December. The first confirmed U.S. cases included a person who traveled from Wuhan on Jan. 15, and it is likely that the virus entered before that: Tens of thousands of people traveled from Wuhan to the U.S. in December. Existing evidence suggests that the virus is highly transmissible and that the number of infections doubles roughly every three days. An epidemic seed on Jan. 1 implies that by March 9 about six million people in the U.S. would have been infected. As of March 23, according to the Centers for Disease Control and Prevention, there were 499 Covid-19 deaths in the U.S. If our surmise of six million cases is accurate, that’s a mortality rate of 0.01%, assuming a two week lag between infection and death. This is one-tenth of the flu mortality rate of 0.1%. Such a low death rate would be cause for optimism.

This does not make Covid-19 a nonissue. The daily reports from Italy and across the U.S. show real struggles and overwhelmed health systems. But a 20,000- or 40,000-death epidemic is a far less severe problem than one that kills two million. Given the enormous consequences of decisions around Covid-19 response, getting clear data to guide decisions now is critical. We don’t know the true infection rate in the U.S. Antibody testing of representative samples to measure disease prevalence (including the recovered) is crucial. Nearly every day a new lab gets approval for antibody testing, so population testing using this technology is now feasible.

If we’re right about the limited scale of the epidemic, then measures focused on older populations and hospitals are sensible. Elective procedures will need to be rescheduled. Hospital resources will need to be reallocated to care for critically ill patients. Triage will need to improve. And policy makers will need to focus on reducing risks for older adults and people with underlying medical conditions. 

A universal quarantine may not be worth the costs it imposes on the economy, community and individual mental and physical health. We should undertake immediate steps to evaluate the empirical basis of the current lockdowns. 

An antiviral drug that one Palo Alto woman has credited in her recovery [see https://www.paloaltoonline.com/news/2020/03/21/covid-19-put-her-in-the-hospital-for-nearly-2-weeks-a-clinical-trial-drug-was-her-saving-grace/ ]  from a severe case of COVID-19 in March is undergoing numerous fast-tracked clinical trials across the globe, and some researchers are hoping to see it gain approval from the U.S. Food and Drug Administration (FDA) in as little as a month.

Researchers are taking a close look at remdesivir, an experimental drug developed by Foster City-based biopharmaceutical company Gilead Sciences Inc. for use against the Ebola virus.

Scientists, including a team at Stanford Hospital, are examining whether remdesivir can prevent the coronavirus from replicating.

“The RNA virus gets into the cells and uses them as little hotels (to replicate),” said Kari Nadeau, co-investigator and professor of pediatric food allergy, immunology and asthma at the School of Medicine.

With the virus proliferating, some COVID-19 patients’ immune systems overreact, causing severe symptoms that lead to death. Researchers hope that limiting the virus’ replication will prevent the immune system from becoming overly active.

The study of remdesivir, one of two taking place at Stanford Hospital, began enrolling patients on March 30. Stanford is collaborating with 65 other sites worldwide; the aim is to study the drug’s effects on 600 patients.

The Stanford patients will receive an intravenous dose of the medication daily for 10 days. The researchers will see how the patients do over a 15-day period. Nadeau said they expect to see a difference between the control group and those who receive the drug. They hope the drug will result in fewer people needing ventilators and fewer deaths.

Neera Ahuja, the study’s principal investigator and division chief of hospital medicine at Stanford University School of Medicine, said if the evidence is convincing of the drug’s effectiveness, and the side effects and adverse reactions pass federal scrutiny, the FDA approval could come within a month.

“That’s unheard of in the non-pandemic world,” she said.

But the ambition to see approval of the drug speaks to the urgent need to treat COVID-19, which has thus far sickened 1.3 million people and killed nearly 75,000 globally. Testing of remdesivir has in some clinical trials already reached Phase 3, the stage prior to FDA approval.

Gilead stated in an announcement that the drug has shown promising results in animals against the forms of coronavirus that cause Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS).

Ahuja said currently, remdesivir can only be administered intravenously in the hospital. If it is approved by the FDA, there’s also hope it could eventually be available in a capsule or liquid and administered in an outpatient setting, similar to Tamiflu, an antiviral drug that is used against influenza.

Other trials of remdesivir are ongoing: Among the National Institutes of Health (NIH) trials of the drug is one involving patients who are on ventilators; another is studying patients with moderate COVID-19 symptoms. A third will compare the results for moderately ill patients who will be given the drug and for people who only receive standard care. The studies involve dozens of hospitals throughout California, including the VA Palo Alto Health Care System, Stanford Hospital and Clinics, Kaiser Permanente and the Regional Medical Center in San Jose. Gilead also is involved in studies using remdesivir in China and France.

Though researchers are focused on whether remdesivir can aid in the treatment of COVID-19 patients, much is still unknown about the coronavirus, including whether it could mutate.

Some coronaviruses, such as the ones causing the “common cold,” can mutate readily.

“A cousin of the coronavirus, the rhinovirus, mutates a lot,” Nadeau said.

A rapidly mutating virus can make it difficult for researchers to develop a vaccine, she said. But “so far, we are not seeing the degree of mutation in COVID-19 as in the common cold.”

Researchers also want to know if a person will develop lifetime immunity if they have the virus.

On April 4, Gilead announced it has produced 1.5 million doses of remdesivir to treat about 140,000 patients, which includes its drug trials, compassionate-care supplies to hospitals for pregnant women and children, and its expanded-access program for patients who are in the most serious condition and can’t be part of a clinical trial. Gilead is supplying the doses at no charge.

The company is expanding its production of the drug and could have 500,000 treatment courses by October and 1 million by the end of the year, it said.

Three weeks into a virus-induced shutdown, as downtown streets remain silent and the economy finds itself teetering on the brink of a steep and sudden recession, a research boom is sweeping through local universities, hospitals and commercial labs. For scientists working nonstop behind the scenes, the race is on to defeat a deadly virus that has brought the whole world to its knees.

Their war has many fronts, but chief among them are testing and treatment, which are seeing a flurry of activity. Stanford University and University of California, San Francisco (UCSF) have ramped up their testing capacity and launched clinical trials at a furious pace. Since the coronavirus pandemic took off, Stanford’s epidemiologists have been working with Santa Clara County health officials to model the pandemic’s trajectory; its virologists have developed various ways to test for virus; and its medical researchers are now launching clinical trials for promising drugs that have proved effective for fighting Ebola, the flu and Hepatitis D.

Researchers also are collaborating with counterparts in other universities as well as public agencies and private labs to share — and scale — their breakthroughs.

Private companies also have stepped up, with commercial labs developing tests and distributing drugs that they believe may become critical weapons in the war against COVID-19 and with manufacturers joining the effort to create personal protective equipment, such as masks and face shields, for health care workers.

Thus far in the battle, public health strategies have led the charge, deploying the tactic of social distancing. On Tuesday, Santa Clara County residents received a glimmer of hope: Staying home to help “flatten the curve” appears to be working, even though the number of COVID-19 cases is still expected to climb between now and May 1, Dr. Sara Cody, the county’s health official, told the county Board of Supervisors during her April 7 update.

Yet the hopeful news came with another message: Numerous conditions have to be met before officials can relax their social-distancing orders.

The county will need to get to a point where widespread testing for COVID-19 is available and hospitals can safely and effectively treat everyone living in the county.

“We have to at least be able to test everyone who has symptoms,” Cody said. “And we also have to have enough testing capacity so that we can test where we think there is some risk of accelerated transmission or there is risk in a particular community. So we’ve got to have testing capacity.”

Testing as defense

While Cody said she is optimistic about the latest data on COVID-19 cases, county, state and federal officials have consistently pointed to testing as a glaring weakness in the collective response to coronavirus. As of Thursday, only 13,360 people in Santa Clara County have been tested for COVID-19, county data show, with 1,442 testing positive — a rate of 10.79%. It takes an average of 2.27 days to get a test result, a problem that Dr. Karen Smith of Santa Clara Public Health Department attributed Tuesday to delays at just about every step of the testing process.

Testing, she said, is limited by a shortage of swabs that are used to take samples and by the worldwide shortage of reagent, a key chemical for sample analysis.

That said, where the government has lagged, Stanford has been able to rev up its testing capacity. One of the nation’s first coronavirus tests came from Benjamin Pinsky, associate professor of pathology and of infectious diseases at Stanford School of Medicine who has been developing a COVID-19 test since late January and whose team was validating and confirming results throughout February, according to Stanford.

In early March, Stanford’s Clinical Virology Laboratory, of which Pinsky is medical director, was capable of conducting 1,000 daily tests, with a turnaround time for results between 36 and 48 hours, according to the university. Now, the lab can now perform 2,000 tests daily, Pinsky told this news organization in an email, and the turnaround time has been cut down to 24 hours.

Pinsky said the team has been able to optimize its workflow and boost production over the past month by validating multiple additional extraction instruments and thermal cyclers — machines that amplify DNA segments using a copying process called polymerase chain reaction.

UCSF also has boosted its testing capacity by opening a new lab that can process more than 2,000 samples per day and return results in 24 hours. In early March, when UCSF began testing for COVID-19, it had a capacity to test only 60 to 100 tests daily, according to the university.

On Tuesday, UCSF Health President and CEO Mark R. Laret and UCSF Chancellor Sam Hawgood co-wrote in a letter that it will allow public health officials from the nine Bay Area counties, including San Mateo and Santa Clara, to submit their samples to UCSF for free analysis.

While virology labs at Stanford and UCSF are using the polymerase chain reaction (PCR) technique to zoom in on the virus’ DNA segments, a research team headed by Eran Bendavid, associate professor of medicine at Stanford, is looking at blood samples for evidence. On April 3 and 4, the team took 2,500 blood samples from volunteers at drive-thru sites in Mountain View, Los Gatos and San Jose. The team used targeted Facebook surveys in an attempt to get a population-representative sample of the county for its experiment.

The goal of the study is to examine the antibodies in the blood sample, a technique known as serology, to gauge the percentage of county residents who are — or have been — infected with COVID-19. A similar study was concurrently conducted in the Los Angeles area by researchers from University of Southern California.

“We need to understand how widespread the disease actually is,” Jay Bhattacharya, a professor of medicine at Stanford University who is involved with the project, said on Saturday morning, as the second day trial was kicking off. “To do that, we need to understand how many people are infected. The current test people use to check whether they have the condition — the PCR test — it just checks whether you currently have the virus in you. It doesn’t check whether you had it and recovered. An antibody test does both.”

Stanford Health is also using blood samples to test its employees for COVID-19. On April 6, the serologic test that was developed by Stanford Medicine was launched at the university’s medical facilities. While the university is currently only testing health care workers, Stanford Health spokesperson Lisa Kim said Stanford hopes to deploy these tests more broadly within the next two months.

“The test will enable us to determine which health care workers might be at low risk for working with COVID-19 patients, as well as understanding disease prevalence in our communities,” Kim said.

Going on the offensive

Just as testing has accelerated, so have medical trials of potentially life-saving drugs. At an April 2 virtual town hall put on by medical leaders at Stanford, Dr. Yvonne Maldonado and Dean of Stanford Medicine Dr. Lloyd Minor, both said that the university’s early development of the PCR test has increased the university’s capacity to stage trials.

“Because we are one of the first to launch our own PCR test — and we hope we’ll have serologic testing available in the near future as well — it gives us the capacity to monitor patients for not only immediate medical care but clinical trials,” Maldonado said.

Two of Stanford’s trials involve remdesivir, a drug produced by the Foster City-based company Gilead Sciences, Inc. Scientists from various institutions across the globe, including a team at Stanford Hospital, are examining whether remdesivir can prevent the coronavirus from replicating.

“The RNA virus gets into the cells and uses them as little hotels (to replicate),” said Kari Nadeau, co-investigator and professor of pediatric food allergy, immunology and asthma at the School of Medicine.

With the virus proliferating, some COVID-19 patients’ immune systems overreact, causing severe symptoms that lead to death. Researchers hope that limiting the virus’ replication will prevent the immune system from becoming overly active.

Gilead announced on April 4 that it has produced 1.5 million doses of remdesivir, enough to treat 140,000 patients. It plans to supply the drug at no charge.

Nadeau’s trial began enrolling patients on March 30. Stanford is collaborating with 65 other sites worldwide; the aim is to study the drug’s effects on 600 patients.

For the trial, Stanford patients will receive an intravenous dose of the medication daily for 10 days. The researchers will see how the patients do over a 15-day period. Nadeau said they expect to see a difference between the control group and those who receive the drug. They hope the drug will result in fewer people needing ventilators and fewer deaths.

Neera Ahuja, the study’s principal investigator and division chief of hospital medicine at Stanford University School of Medicine, said if the evidence is convincing of the drug’s effectiveness, and the side effects and adverse reactions pass federal scrutiny, the FDA approval could come within a month.

“That’s unheard of in the non-pandemic world,” she said.

Stanford is one of many institutions now looking at remdesivir. Among the National Institutes of Health trials of the drug is one involving patients who are on ventilators; another is studying patients with moderate COVID-19 symptoms. A third will compare the results for moderately ill patients who will be given the drug and for people who only receive standard care.

The studies involve dozens of hospitals throughout California, including the VA Palo Alto Health Care System, Stanford Health Care, Kaiser Permanente and the Regional Medical Center in San Jose. Gilead also is involved in studies using remdesivir in China and France.

Stanford is also looking at other drugs, including those that have in the past proved effective in treating other infections. Maldonado said at the April 2 town hall that in addition to its work on remdesivir, Stanford is preparing to move ahead with trials for Lambda, an immunomodulator, and the viral inhibitors Camostat and favipiravir.

“They have been studied in other infections, so we think we can obtain rapid FDA INDs so that we can start doing primarily outpatient trials for these drugs,” Maldonado said, referring to “investigational new drug” authorization.

“So if they work in reducing symptoms and perhaps prevent spread by reducing viral shedding from an infected person, then these could be scaled up in the not too distant future. We’re hoping those will enroll (patients) pretty quickly.”

Prassana Jagganathan, a Stanford infectious disease specialist who is heading the trial on Lambda, said the drug may be able to strengthen the human immune system to better fight COVID-19. Lambda, he said, appears to target cells that are located on the epithelium (outer tissue layer) of respiratory tracts, including areas such as lungs and pharynx. As such it can be particularly suitable for treating patients with COVID-19, which can trigger respiratory failure.

“It’s a molecule that we think can actually stimulate and aid antiviral defenses against a multitude of different viruses,” Jagganathan said.

While Lambda had not been used to treat respiratory illnesses, another interferon called Alfa had proven effective, he said. The problem with using Alfa to treat COVID-19, Jagganathan said, is that the receptors for Alfa are far more distributed throughout the human body, including in immune cells. Thus, side effects of Alfa include fever or the flu, symptoms that resemble those of COVID-19.

The primary outcome of the randomized clinical trial, which will include 120 participants, is to see how long people are shedding the virus, Jagganathan said.

“We are hypothesizing that the folks who get Lambda will have a shorter duration of virus that we can detect,” Jagganathan said.

In addition to drugs, Stanford is experimenting with another promising remedy: the antibodies from patients who have already contracted — and recovered from — COVID-19. The new experimental therapy program, which Stanford Blood Center announced on April 7, takes blood from the recovered patients, removes the plasma containing the antibodies, and returns the remaining blood components such as red blood cells back to the donor. The antibodies are then given to critically ill COVID-19 patients through a transfusion, the center stated.

The blood center is working with Stanford Medicine in hopes that the antibodies, which are immune proteins that attack pathogens such as viruses, might help lessen the severity of the COVID-19.

Though the use of antibodies to treat COVID-19 patients is in the investigational phase, the technique, also known as passive antibody therapy, dates back as far as the 1890s. And prior outbreaks with other coronaviruses, including the one that caused SARS, showed that neutralizing antibodies were helpful in reducing the effects of the disease.

Likewise, the technique was used in the 2009-2010 H1N1 influenza virus pandemic to reduce patients’ respiratory viral load, inflammatory reactions and death, researchers Arturo Casadevall and Liise-anne Pirofski wrote in an article published in The Journal of Clinical Investigation on March 13. It also was used in the 2013 West African Ebola epidemic.

Stanford Blood Center will begin collecting the plasma this week and plans to increase collections in the following weeks as it identifies more donors. The donors must be fully recovered and symptom-free for at least 14 days. If they are only symptom-free for 14 to 28 days, they will be asked to retake a COVID-19 test at no cost. The repeat test must be negative to be eligible to donate.

The process takes about one to two hours using standard blood- and plasma-removal methods. The collections take place at the center’s Palo Alto headquarters at 3373 Hillview Ave. in Palo Alto, where special care will be taken by a small team in a dedicated room, according to Dr. Suchi Pandey, the blood center’s chief medical officer. (Interested donors can visit stanfordbloodcenter.org/covid19plasma and fill out an intake form.)

Getting enough of the antibodies to treat many patients could take time. Pandey said in an email that there’s also no known way to cultivate or increase the amount of plasma in a laboratory, so blood centers and hospitals rely on donors.

“The volume of plasma collected from a donor is based on specific donor parameters such as weight. Depending on the volume of plasma collected, the unit may be divided into separate plasma components, which can be used to treat up to three patients,” she said.

The U.S. Food and Drug Administration recently approved use of the antibody treatment by hospitals, initially only for critically ill patients.

It will later be used in clinical trials on patients in different stages of the disease, according to the blood center.

Find comprehensive coverage on the Midpeninsula’s response to the new coronavirus by Palo Alto Online, the Mountain View Voice and the Almanac here.

Jay Bhattacharya, a professor of medicine at Stanford University, wanted to conduct large-scale research to understand the prevalence of the novel coronavirus. Daniel Eichner, the president of Sports Medicine Research and Testing Laboratory, had the enormous number of testing kits necessary. Major League Baseball had a representative group of subjects to generate scientifically viable results.

So they teamed up—and the result will be the most thorough Covid-19 antibody study in the U.S.

About 10,000 employees from 27 of MLB’s 30 teams are being tested to detect whether they have already contracted and potentially recovered from the coronavirus. Participants span the organizational payroll, including owners, front-office executives, scouts, stadium ushers, hot-dog vendors and, in some cases, the players themselves. 

The data will allow researchers to “know how far along we are in the epidemic and how dangerous getting the virus actually is,” Dr. Bhattacharya said. 

Public health experts and authorities are eager for the rollout of these blood tests, also called serology tests, to better understand who has already been infected with the novel coronavirus and how far the virus has spread. The tests look for specific antibodies in a person’s blood, which develop after a person has been infected. 

The antibody tests are different from the diagnostic tests being used to determine whether a patient actively has the virus in his or her system and are not redirected from front-line testing programs. 

A growing number of hospitals are investigating antibody testing and blood plasma therapy as a way to combat the new coronavirus in sick patients. WSJ’s Daniela Hernandez explains. Photo illustration: Laura Kammermann

The doctors involved said that a study of this nature typically would take a year or more to complete. With MLB’s help, the process is already near its conclusion after about a month. Pinprick blood tests, to be self-administered by employees at their homes, generate a result within 10 minutes and should be completed by the end of the week. Dr. Bhattacharya said he plans to write a paper over the weekend and send it out for peer review.

“If you don’t know how far along the disease is we can’t do good forecasts,” Dr. Bhattacharya said. “If we can’t do forecasts we can’t understand when it’s safe to open up the economy.”

The researchers are quick to point out that this study will not necessarily allow MLB to resume its season any faster. “As best as I can tell, they’re not in this just to help their athletes,” Dr. Bhattacharya said. “They want to do public health good.”

Opening day, which had been scheduled for March 26, has been indefinitely delayed. The league is tentatively exploring a plan to sequester all players and other essential personnel in the Phoenix area and stage an abbreviated season at fields around the region. MLB has no financial stake in the study, which is being funded by private donors. The Major League Baseball Players Association is aware of the study and is comfortable with players participating because testing is anonymous and optional. 

But while the findings won’t necessarily lead to baseball’s speedy return, they could help facilitate the reopening of businesses across the country—including sports. 

“Is this directly going to help baseball get back? No,” Dr. Eichner said. “It’ll help everyone get back to work. The data will help everyone try to get back.”

SMRTL, Dr. Eichner’s lab in Salt Lake City, usually assists MLB and other leagues with its performance-enhancing drug test program. But with the sports world shut down, Dr. Eichner decided to use his Ph.D. in viral immunology, which had long been sitting dormant, to good use. He purchased 15,000 antibody test kits from Premier Biotech in Minneapolis to try to organize a study and approached MLB about taking part, because its teams have nationwide coverage, diverse demographics and access to physicians who can help with the administration and logistics.

MLB agreed, and Dr. Eichner contacted the researchers in California, who are also running antibody-testing programs in Los Angeles and Santa Clara counties to gather more data.

The Premier Biotech test currently doesn’t have emergency authorization and hasn’t been reviewed by the U.S. Food and Drug Administration. It can be used for research purposes and has been validated separately.

While researchers and public health authorities are clamoring for wider serological testing, many are also cautioning that the tests must also be accurate, and issues with accuracy have already stalled widespread testing efforts in the U.K. 

Stanford validated the test independently, said Eran Bendavid, an infectious disease physician at Stanford Health Policy and one of the researchers spearheading the charge to do surveillance testing in the two California counties. The test resulted in very few false positives, Dr. Bendavid said, while the false negative rate left “something to be desired.” 

These discrepancies, however, are more easily accounted for when doing population surveillance rather than determining an individual’s status, he said. 

Dr. Bhattacharya said that a person testing positive for novel coronavirus antibodies does not necessarily mean he or she has long-lasting immunity to the disease. He said there is “active debate in the scientific community about how much antibodies convey against future infection.” Nonetheless, he described the study as “critically important”—and not possible without MLB’s assistance. 

“Sport is such an important part of society,” Dr. Eichner said. “Now it has a chance to give back.”

Statement of Jay Bhattacharya, MD, PhD

July 13, 2020

Good morning Chairman Krishnamoorthi, Ranking Member Cloud, and other committee members, thank you for the opportunity to speak with you today.  My name is Jay Bhattacharya and I am a health economist and Professor of Medicine at Stanford University, where I direct the Center for Demography and Economics of Health and Aging. I hold an MD and a PhD in Economics and I have 20 years of experience working on the economics of infectious disease. My published work over the past decades includes studies on H1N1 flu, H5N1 flu, and on SARS-CoV-2. In addition to my academic work, I have worked closely with federal regulatory agencies on health policy issues. Over the past decade, I have work with the Center for Medicare and Medicaid Services (CMS) On a issues related to physician payment, measurement of costs and quality of care, geographic variation in health care practices, risk adjustment modeling, and access to care.  Additionally, I have worked with the FDA over the past several years, and in particular with the Center for Biologics Evaluation and Research (CBER), on postmarket surveillance of biologics products, including studies involving the safety of flu vaccines.

In my opening remarks today, I will address two topics related to vaccine development in the context of COVID-19 – (1) the regulation of the safety of SARS-CoV-2 vaccines currently under development, and (2) policy mechanisms to prioritize access to the vaccines by vulnerable populatoins, should they prove safe and effective.

The development of vaccine candidates for SARS-CoV-2 has proceeded at a remarkable pace.  In a report released yesterday, the World Health Organization identified 23 candidate vaccines currently in clinical evaluation, which means being tested on human populations, and 137 vaccine candidates in preclinical evaluation. The vaccine candidates employ a variety of technologies, both traditional and novel, all with the same goal of producing a sustained antibody response that can neutralize SARS-CoV-2 virus and prevent COVID-19 infection. This is an extraordinary scientific effort in a short period of time in response to the extraordinary challenge posed by the COVID-19 epidemic.

The rapid development of vaccine candidates naturally brings with it worries about the safety of the ultimately approved vaccine. These are not idle worries, as vaccines are biologically potent agents and need to be tested thoroughly in a very wide population before they are deployed widely. At the same time, even discredited challenges to the safety of a vaccine, like in the case of the MMR vaccine, can lead many people to avoid vaccination with unfortunate consequences for the spread of deadly disease.

I want to make two points to assure you and the American public about the process that the FDA will safety of the SARS-CoV-2 vaccines. First, in my experience working with them over the past years, I have found the FDA scientists and epidemiologists who work on drug and biologics safety to be among the most careful and conscientious researchers I have ever worked encountered. They are immune from political influence and follow the data diligently in their decision making. 

The FDA is a conservative organization in the sense that it would much rather ask for more study to make sure that a product it is evaluating is actually safe and effective (even at the cost of delaying access to a good drug or vaccine) than take the risk of approving something that ex post proves unsafe.  A study published last year in Biostatistics found that the FDA approved only a third of all vaccine candidates that entered clinical evaluation.  The FDA is not afraid to say no to a vaccine candidate if the evidence warrants it.  In the case of the SARS-CoV-2 vaccine candidates, my understanding is that the Phase 3 studies currently underway will enroll tens of thousands of patients, so that even relatively rare adverse events can be detected. 

Even after a vaccine is approved, the FDA will continue to play a key role in monitoring for safety issues. Even for a well-tested vaccine with clinical studies involving tens of thousands of patients, safety issues may arise when the vaccine is provided to hundreds of millions of people that were not found in the studies. To this end, the FDA conducts post-market surveillance studies of drug and vaccine long past the approval of the vaccine for widespread use.

Second, I wanted to address Operation Warp Speed, which as you know is the Administration’s plan to accelerate research and development efforts for a SARS-CoV-2 vaccine. To my knowledge, the operation has two main parts: (1) to provide financial support for studies of the safety and efficacy of the most promising vaccine candidates, and (2) to make financial commitments for the large scale production of vaccine doses even before the regulatory process for drug approval is complete. The main thing I want to emphasize about the first part is that the studies that will be conducted will be evaluated by the FDA regulatory process I just mentioned. Cutting corners on safety evaluation will be impossible under the FDA’s watchful eye. The second part is a gamble – what if we invest a large amount of money to manufacture a vaccine that, after the studies are complete, turn out to not work very well?  That’s the downside. The upside is that if the vaccine is safe and it works, tens of millions of doses will be available and we will not need to fight so hard over who gets the first doses among the limited supply. This is a big gamble, but one that makes sense given the huge economic costs and health harms of the COVID-19 epidemic.

I will finish by briefly giving my thoughts on who should be prioritized to receive a safe and effective vaccine. To my mind, the answer is simple and is driven by who is most vulnerable. An overwhelming body of clinical evidence shows that the elderly – and especially the oldest old -- are at highest risk of hospitalization and death from COVID-19 infection. This problem is compounded by the fact that patients with multiple chronic diseases are also at high risk, and of course elderly patients are at highest risk to have chronic diseases. In my view, if there are limited doses of the vaccine available initially, the priority should go to Medicare patients. An additional advantage of this approach is that this can readily be accomplished though existing Medicare programs, to provide the vaccine to the Medicare beneficiaries – at no cost to them.

While there has been a lot of political clash over a wide range of issues regarding COVID-19, I believe that all Americans (and indeed the whole world) can celebrate together if and when a safe and effective is developed.  Soon I hope. 

As the coronavirus pandemic erupted this spring, two Stanford University professors — Dr. Jay Bhattacharya and Dr. Scott W. Atlas — bonded over a shared concern that lockdowns were creating economic and societal devastation.

Now Dr. Atlas is President Trump’s pandemic adviser, a powerful voice inside the White House. And Dr. Bhattacharya is one of three authors of the so-called Great Barrington Declaration, a scientific treatise that calls for allowing the coronavirus to spread naturally in order to achieve herd immunity — the point at which enough people have been infected to stall transmission of the pathogen in the community.

While Dr. Atlas and administration officials have denied advocating this approach, they have praised the ideas in the declaration. The message is aligned with Mr. Trump’s vocal opposition on the campaign trail to lockdowns, even as the country grapples with renewed surges of the virus.

The central proposition — which, according to the declaration’s website, is supported by thousands of signatories who identify as science or health professionals — is that to contain the coronavirus, people “who are not vulnerable should immediately be allowed to resume life as normal” while those at high risk are protected from infection. 

Younger Americans should return to workplaces, schools, shops and restaurants, while older Americans would remain cloistered from the virus as it spreads, receiving such services as grocery deliveries and medical care.

Eventually so many younger Americans will have been exposed, and presumably will have developed some immunity, that the virus will not be able to maintain its hold on the communities, the declaration contends.

But it does not offer details on how the strategy would work in practice. Dr. Anthony Fauci, the government’s top infectious disease expert, has dismissed the declaration as unscientific, dangerous and “total nonsense.” Others have called it unethical, particularly for multigenerational families and communities of color.

Alarmed and angry, 80 experts on Wednesday published a manifesto of their own, the John Snow Memorandum (named after a legendary epidemiologist), saying that the declaration’s approach would endanger Americans who have underlying conditions that put them at high risk from severe Covid-19 — at least one-third of U.S. citizens, by most estimates — and result in perhaps a half-million deaths.

“I think it’s wrong, I think it’s unsafe, I think it invites people to act in ways that have the potential to do an enormous amount of harm,” said Dr. Rochelle Walensky, an infectious disease expert at Harvard University and one of the signatories to the Snow memo. “You don’t roll out disease — you roll out vaccination.”

The declaration grew out of a gathering hosted in Great Barrington, Mass., by the American Institute for Economic Research, a think tank dedicated to free-market principles whose partners include the Charles Koch Institute, founded by the billionaire industrialist to provide support to libertarian-leaning causes and organizations.

On Oct. 5, the day after the declaration was made public, the three authors — Dr. Bhattacharya, Sunetra Gupta of Oxford University and Martin Kulldorff of Harvard — arrived in Washington at the invitation of Dr. Atlas to present their plan to a small but powerful audience: the health and human services secretary, Alex M. Azar II.

Over the course of an hourlong meeting in a wood-paneled, sixth-floor suite atop the health department’s headquarters, the researchers walked the secretary and Dr. Atlas through their thinking.

Mr. Azar later tweeted: “We heard strong reinforcement of the Trump Administration’s strategy of aggressively protecting the vulnerable while opening schools and the workplace.”

Battered by lost jobs, pandemic fatigue and isolation, and worried for their children, there is little doubt that Americans loathe lockdowns, although many still see them as necessary to control the virus.

Among scientists, too, there is near-universal agreement that lockdowns are harmful. Even Dr. Fauci has suggested that another national lockdown must be instituted only as a last resort.

But mostly, scientific disagreement centers on whether lockdowns are a necessary move when other strategies to contain the virus have not even been put in place, or have failed.

“This has been wrongly framed as a debate between lockdown and no lockdown,” said Dr. Deepti Gurdasani, a clinical epidemiologist at Queen Mary University of London.

Dr. David Nabarro, a special envoy to the World Health Organization, has urged governments not to resort to lockdowns as the primary method to control the virus. Masks, social distancing, fewer crowds, testing and tracing — these are the ways to control the virus in the long run, he said in an interview.

But the lockdowns in the spring were necessary, he added, as emergency measures to give countries time to put in place strategies to control the virus.

“There is a middle way,” Dr. Nabarro added, between strict lockdowns and letting the virus freely infect people. “If only we had a few more world leaders who would understand this, we wouldn’t have this debate going on.”

But Dr. Bhattacharya and his supporters go further. They say that governments should never have imposed lockdowns at all, and never should have tried to institute coronavirus testing and contact-tracing. Instead, the trillions of dollars in economic aid approved by Congress should have been spent on programs to protect those at highest risk of illness and death.

The manifesto’s central tenet is that young people should be free to resume normal life — to re-enter the work force, attend college, dine in restaurants. They would become infected, hopefully without much illness, and gain immunity.

Eventually the virus would not be able to find new victims and would fade away.

“People who are more at risk may participate if they wish, while society as a whole enjoys the protection conferred upon the vulnerable by those who have built up herd immunity,” the declaration said.

The strategy includes keeping older people cloistered, with regular testing to detect possible outbreaks in nursing homes, and with groceries and other necessities delivered to anyone over 60 sheltering at home. Alternately, older people might move to other facilities for isolation or quarantine.

There would be no widespread surveillance for the coronavirus. People would be given information about testing, with an emphasis on those who have symptoms — but when and how to get tested, and whether to isolate if infected, would be left up to individuals.

“Testing and isolating indiscriminately causes too much collateral damage for it to be useful,” Dr. Bhattacharya said.

‘How’s this supposed to go?’

But some experts said the strategy was highly impractical, given the difficulty in determining who is truly susceptible. The risk of death from Covid-19 rises sharply with age, but about 37 percent of adults in America also are at significant risk because of obesity, diabetes or other underlying conditions.

The most recent statistics indicate that 20 percent of deaths from Covid-19 occur in people under age 65. And about a third of people who have recovered from the disease, including the young, still struggle with symptoms weeks later (a phenomenon the Barrington authors contest). “It’s amazingly irresponsible” not to take these risks into account, Dr. Nabarro said.

The declaration’s strategy is both unethical and fails to account for human behavior, said Ruth Faden, a bioethicist at Johns Hopkins University.

Many high-risk groups — people who live in multigenerational families or in crowded living situations, or who have diabetes and obesity — are disproportionately found in poor communities, she said. The declaration’s strategy would require them to move away from their families or to risk having younger family members bring the virus home.

“Are we going to compel these people to leave? And if we’re not going to compel them to leave, then how’s this supposed to go?” she said. “Then you are going to see the deaths that you say we’re not going to see.”

Reopening schools when community levels of the virus are high similarly rests on a misguided assumption that parents and teachers would agree to the strategy, she added.

Scientists who have signed the declaration did not offer many details for putting its ideas in place.

“I don’t know exactly how it would work,” said Gabriela Gomes, a mathematical modeler at the University of Strathclyde in Britain and one of 42 co-signers.

Another supporter, Paul McKeigue, a genetic epidemiologist at the University of Edinburgh in Scotland, said, “Specific control measures for preventing coronavirus transmission are not my area of expertise.”

The lack of a clear plan has turned away even some would-be supporters. Dr. Stefan Baral, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health, attended part of the Great Barrington, Mass., meeting and said he was sympathetic to the effort.

But Dr. Baral, a Swedish citizen who supports that country’s approach, said he did not sign the declaration because it did not lay out a plan for workplace or housing accommodations for people at risk.

Sweden adopted an unrestrictive approach, offering guidelines to its citizens but leaving compliance up to them. The country is often cited as the model for controlling the virus without restrictions, but has among the highest death rates in the world, particularly among the elderly. It has also suffered economic losses comparable to those of other Nordic countries.

It’s possible to avoid even those risks without lockdowns if governments impose some reasonable restrictions like physical distancing and universal masks and install test and trace strategies, Dr. Nabarro said.

“I will contest anybody who says it is undoable,” he added. “It’s doable without collateral damage if you bring together all the local communities.”

The town of Great Barrington, Mass., home to the American Institute for Economic Research, recently distanced itself from the declaration, saying the strategy it proposed could “cost millions of lives.”

“Anyone who might avoid Great Barrington, due to confusion over the Declaration, is invited to visit and see how COVID-safe works in a small New England town,” the town’s leaders wrote.

“Please wear a mask.”

President-elect Donald J. Trump said on Tuesday evening that he had selected Dr. Jay Bhattacharya, a Stanford physician and economist whose authorship of an anti-lockdown treatise during the coronavirus pandemic made him a central figure in a bitter public health debate, to be the director of the National Institutes of Health.

“Together, Jay and RFK Jr. will restore the NIH to a Gold Standard of Medical Research as they examine the underlying causes of, and solutions to, America’s biggest health challenges, including our Crisis of Chronic Illness and Disease,” Mr. Trump wrote on social media, referring to Robert F. Kennedy Jr., his choice to lead the N.I.H.’s parent agency, the Department of Health and Human Services.

If confirmed by the Senate, Dr. Bhattacharya would lead the world’s premier medical research agency, with a $48 billion budget and 27 separate institutes and centers, each with its own research agenda, focusing on different diseases like cancer and diabetes. Dr. Bhattacharya, who is not a practicing physician, has called for overhauling the N.I.H. and limiting the power of civil servants who, he believes, played too prominent a role in shaping federal policy during the pandemic.

He is the latest in a series of Trump health picks who came to prominence during the coronavirus pandemic and who hold views on medicine and public health that are at times outside the mainstream. The president-elect’s health choices, experts agree, suggest a shake-up is coming to the nation’s public health and biomedical establishment.

Dr. Bhattacharya is one of three lead authors of the Great Barrington Declaration, a manifesto issued in 2020 that contended that the virus should be allowed to spread among young healthy people who were “at minimal risk of death” and could thus develop natural immunity, while prevention efforts were targeted to older people and the vulnerable.

Through a connection with a Stanford colleague, Dr. Scott Atlas, who was advising Mr. Trump during his first term, Dr. Bhattacharya presented his views to Alex M. Azar II, Mr. Trump’s health secretary. The condemnation from the public health establishment was swift. Dr. Bhattacharya and his fellow authors were promptly dismissed as cranks whose “fringe” policy prescriptions would lead to millions of unnecessary deaths.

Dr. Bhattacharya also became a go-to witness in court cases challenging federal and state Covid policies. He joined a group of plaintiffs in suing the Biden administration over what he called “Covid censorship,” arguing that the administration violated the First Amendment in working with social media companies to tamp down on Covid misinformation.

He also argued against mask mandates for schoolchildren in Florida and Tennessee. Judges in both states dismissed him as unqualified to make medical pronouncements on the matter.

“His demeanor and tone while testifying suggest that he is advancing a personal agenda,” Judge Waverly D. Crenshaw Jr. of the U.S. District Court for the Middle District of Tennessee wrote in 2021, adding that he was “simply unwilling to trust Dr. Bhattacharya.”

More recently, amid widespread recognition of the economic and mental health harms caused by lockdowns and school closures, Dr. Bhattacharya’s views have been getting a second look, to the consternation of his critics, who have accused those entertaining his ideas of “sane-washing” him.

Perhaps the most notable reflection has come from Dr. Francis Collins, the former director of the National Institutes of Health. In 2020, Dr. Collins called Dr. Bhattacharya and his co-authors “fringe epidemiologists.” Last year, Dr. Collins suggested that he and other policymakers might have been too narrowly focused on public health goals — saving lives at any cost — and not attuned enough to balancing health needs with economic ones.

“I think a lot of us involved in trying to make those recommendations had that mind-set — and that was really unfortunate, it’s another mistake we made,” Dr. Collins said in December 2023, at a conversation hosted by Braver Angels, a group that addresses political polarization. He did not address Dr. Bhattacharya or the Great Barrington Declaration specifically.

But Dr. Bhattacharya still provokes extremely strong feelings. Dr. Jonathan Howard, an associate professor of neurology and psychiatry at NYU Langone Health, who treated patients at Bellevue Hospital at the height of the pandemic, has assailed Dr. Bhattacharya in a book, “We Want Them Infected.”

Dr. Howard said Dr. Bhattacharya “bungled basic facts” about the pandemic. In March 2020, for example, Dr. Bhattacharya suggested in a Wall Street Journal opinion essay that the pandemic was not as deadly as it was being made out to be, and that the death toll might top out at 40,000 Americans; in the end, 1.2 million died.

Dr. Bhattacharya responded on social media by calling Dr. Howard “unhinged” and his book “inane,” advising him to “take an epidemiology class if you don’t want to keep embarrassing yourself.”

The Great Barrington Declaration grew out of a meeting in Great Barrington, Mass., convened by the American Institute for Economic Research, a think tank dedicated to free-market principles. Its authors, who included doctors, scientists and epidemiologists, wrote that they had “grave concerns about the damaging physical and mental health impacts of the prevailing Covid-19 policies.” They called their approach “Focused Protection.”

Alarmed and angry, 80 experts published a manifesto of their own, the John Snow Memorandum (named after the 19th-century English epidemiologist), saying that the declaration’s approach would endanger Americans who had underlying conditions that put them at high risk from severe Covid-19 — at least one-third of U.S. citizens, by most estimates — and result in perhaps a half-million deaths.

“I think it’s wrong, I think it’s unsafe, I think it invites people to act in ways that have the potential to do an enormous amount of harm,” Dr. Rochelle P. Walensky, a Harvard infectious disease specialist, said at the time. Dr. Walensky later became director of the Centers for Disease Control and Prevention when President Biden took office.

Last month, Dr. Bhattacharya hosted a forum on pandemic policy at Stanford, saying he had hoped to bring together people of different views who would “talk to each other in a civil way.” But the forum itself became the target of attacks — a development that Stanford’s president, Jonathan Levin, called “dispiriting.”

One of Dr. Bhattacharya’s Stanford colleagues, Dr. Pantea Javidan of the Department of Psychiatry and Behavioral Sciences, was quoted in The San Jose Mercury News as saying the symposium gave “a platform for discredited figures who continually promote dangerous, scientifically unsupported or thoroughly debunked approaches to Covid.”

Sheryl Gay Stolberg covers health policy for The Times from Washington. A former congressional and White House correspondent, she focuses on the intersection of health policy and politics.