Explained | Why has Marc Tessier-Lavigne, the President of Stanford University, resigned?

Marc Tessier-Lavigne speaks to the media at Stanford University in Stanford, February 4, 2016.
| Photo Credit: AP

The president of Stanford University, Marc Tessier-Lavigne, resigned from his post and will be stepping down on August 31 after an investigation found evidence of “manipulation of research data” in widely-cited papers in which he was the principal author. 

According to The Stanford Daily, the university’s news outlet, the investigation found that Dr. Tessier-Lavigne failed to correct mistakes in several scientific papers published over the years. The investigation also found that his lab fostered an unhealthy lab dynamic where Dr. Tessier-Lavigne would reward ‘winners’ while marginalising or shunning ‘losers’. 

Dr. Tessier-Lavigne who is a neuroscientist has been the president of Stanford University for the last seven years.

Why the investigation?

The investigation was launched by the Stanford Board of Trustees after an article by the same news outlet reported in November that Dr. Tessier-Lavigne’s research was under investigation for misconduct. 

After eight months of inquiries, the Scientific Panel constituted by the university’s Board of Trustees special committee released a 95-page report on July 17. The investigation was conducted by Mark Filip, a former deputy attorney general and other well-known scientists such as the Nobel laureate Randy Schekman, former Princeton president Shirley Tilghman, former Harvard provost Steve Hyman and two other members of the National Academies. 

The investigation specifically looked at twelve papers where Dr. Tessier-Lavigne is a co-author which was part of the allegation that emerged for the first time on a website called PubPeer — a crowd-sourced platform where the scientific fraternity discusses issues regarding scientific publications.

The Panel was also charged with looking into any other issues and leads pertaining to the integrity of the scientific process in Dr. Tessier-Lavigne’s work. Under this, certain allegations came up against Dr. Tessier-Lavigne’s work when he was working as an executive and scientist at Genentech, a San Francisco-based biotechnology company. 

What did the report find?

The report specifically pointed out five papers published over the last two decades where Dr. Tessier-Lavigne was the principal author yet “failed to decisively and forthrightly correct mistakes in the scientific record.”

Data | China overtakes the U.S. in scientific research output 

The report concluded that while the results of the research conducted under Dr. Tessier-Lavigne were hedged, the investigators found no evidence that he manipulated the data himself or was aware of manipulation during the review process. 

The fudging of results has not been a lone incident at Stanford University but has “spanned labs at three separate institutions” where Dr. Tessier-Lavigne has worked. 

The report also said that Dr. Tessier-Lavigne “has not been able to provide an adequate explanation” for why he did not correct the mistakes in the papers even when he had multiple opportunities to do so. 

In 2001, a fellow scientist in the field pointed out a possible doctored image in a paper by Dr. Tessier-Lavigne published in the journal Science. According to the report, Dr. Tessier-Lavigne wrote to the colleague that he would contact the journal and issue a correction, however, he did neither.

To date, at least two of Dr. Tessier-Lavigne’s papers published in Science still contain errors. The report noted that Dr. Tessier-Lavigne has not followed up for seven years on unpublished corrections. “Dr. Tessier-Lavigne did not have an explanation for deciding to not follow up on the corrections beyond that he has a practice of drafting many emails to see how they read but only sends a portion of them and that he concluded the communication was unnecessary,” the report said.

A similar incident happened in 2004 when editors of the journal Nature found evidence of manipulated data in a research paper. However, the explanation provided by Dr. Tessier-Lavigne was “ not fully responsive to the range of publicly expressed concerns”, the report said. 

Now what?

As a result of the investigation, Dr. Tessier-Lavigne will have to retract three out of five of his research papers and make extensive corrections in the other two. 

One of these papers was a widely-publicised study on Alzheimer’s which claimed to have turned the understanding of the neurodegenerative disease on its head. The report found the central conclusions of the paper to be incorrect and said that the quality of research in Dr. Tessier-Lavigne’s lab “fell below accepted scientific practices, let alone Dr. Tessier-Lavigne’s self-described standard of scientific excellence.”

The report also said that the panel “believes that mistaken narrative of fraud in certain reporting may stem from a conflation of various events.”

Also Read | Investigation reveals serious scientific misconduct by IIT Dhanbad faculty

What did Marc Tessier-Lavigne say?

Dr. Tessier-Lavigne in a statement issued on July 19 against the findings of the report where he said, “I am gratified that the Panel concluded I did not engage in any fraud or falsification of scientific data.”

He also said that he has “never submitted a scientific paper without firmly believing that the data were correct and accurately represented.”

Responding to the allegation of not doing enough to correct the mistakes in the research paper, Dr. Tessier-Lavigne said that while he took steps in the past to address the issues, in certain cases they have been insufficient.

Dr. Tessier-Lavigne also said that he will be tightening the protocols in place such as systematically matching processed images to the original ones. He will remain at Stanford University as a faculty and keep running his lab.

In the meanwhile, the Board has named Dr Richard Saller, a professor of European Studies and former Dean of Humanities, will serve as interim president starting from September 1.

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Stem Cells Fast Facts | CNN



CNN
 — 

Here is some background information about stem cells.

Scientists believe that stem cell research can be used to treat medical conditions including Parkinson’s disease, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis and rheumatoid arthritis.

Sources: National Institutes of Health, Mayo Clinic

Stem cell research focuses on embryonic stem cells and adult stem cells.

Stem cells have two characteristics that differentiate them from other types of cells:

– They are unspecialized cells that can replicate themselves through cell division over long periods of time.

– Stem cells can be manipulated, under certain conditions, to become mature cells with special functions, such as the beating cells of the heart muscle or insulin-producing cells of the pancreas.

There are many different types of stem cells, including: pluripotent stem cells and adult stem cells.
Pluripotent stem cells (ex: embryonic stem cells) can give rise to any type of cell in the body. These cells are like blank slates, and they have the potential to turn into any type of cell.
Adult stem cells can give rise to multiple types of cells, but are more limited compared with embryonic stem cells. They are more likely to generate within a particular tissue, organ or physiological system. (Ex: blood-forming stem cells/bone marrow cells, sometimes referred to as multipotent stem cells)

Embryonic stem cells are harvested from four to six-day-old embryos. These embryos are either leftover embryos in fertility clinics or embryos created specifically for harvesting stem cells by therapeutic cloning. Only South Korean scientists claim to have successfully created human embryos via therapeutic cloning and have harvested stem cells from them.

Adult stem cells are already designated for a certain organ or tissue. Some adult stem cells can be coaxed into or be reprogrammed into turning into a different type of specialized cell within the tissue type – for example, a heart stem cell can give rise to a functional heart muscle cell, but it is still unclear whether they can give rise to all different cell types of the body.

The primary role of adult stem cells is to maintain and repair the tissue in which they are found.

Regenerative medicine uses cell-based therapies to treat disease.

Scientists who research stem cells are trying to identify how undifferentiated stem cells become differentiated as serious medical conditions, such as cancer and birth defects, are due to abnormal cell division and differentiation.

Scientists believe stem cells can be used to generate cells and tissues that could be used for cell-based therapies as the need for donated organs and tissues outweighs the supply.

Stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases, including Alzheimer’s diseases.

Cloning human embryos for stem cells is very controversial.

The goal of therapeutic cloning research is not to make babies, but to make embryonic stem cells, which can be harvested and used for cell-based therapies.

Using fertilized eggs left over at fertility clinics is also controversial because removing the stem cells destroys them.

Questions of ethics arise because embryos are destroyed as the cells are extracted, such as: When does human life begin? What is the moral status of the human embryo?

1998 – President Bill Clinton requests a National Bioethics Advisory Commission to study the question of stem cell research.

1999 – The National Bioethics Advisory Commission recommends that the government allow federal funds to be used to support research on human embryonic stem cells.

2000 – During his campaign, George W. Bush says he opposes any research that involves the destruction of embryos.

2000 – The National Institutes of Health (NIH) issues guidelines for the use of embryonic stem cells in research, specifying that scientists receiving federal funds can use only extra embryos that would otherwise be discarded. President Clinton approves federal funding for stem cell research but Congress does not fund it.

August 9, 2001 – President Bush announces he will allow federal funding for about 60 existing stem cell lines created before this date.

January 18, 2002 – A panel of experts at the National Academy of Sciences (NAS) recommends a complete ban on human reproductive cloning, but supports so-called therapeutic cloning for medical purposes.

February 27, 2002 – For the second time in two years, the House passes a ban on all cloning of human embryos.

July 11, 2002 – The President’s Council on Bioethics recommends a four-year ban on cloning for medical research to allow time for debate.

February 2005 – South Korean scientist Hwang Woo Suk publishes a study in Science announcing he has successfully created stem cell lines using therapeutic cloning.

December 2005 – Experts from Seoul National University accuse Hwang of faking some of his research. Hwang asks to have his paper withdrawn while his work is being investigated and resigns his post.

January 10, 2006 – An investigative panel from Seoul National University accuses Hwang of faking his research.

July 18, 2006 – The Senate votes 63-37 to loosen President Bush’s limits on federal funding for embryonic stem-cell research.

July 19, 2006 – President Bush vetoes the embryonic stem-cell research bill passed by the Senate (the Stem Cell Research Enhancement Act of 2005), his first veto since taking office.

June 20, 2007 – President Bush vetoes the Stem Cell Research Enhancement Act of 2007.

January 23, 2009 – The FDA approves a request from Geron Corp. to test embryonic stem cells on eight to 10 patients with severe spinal cord injuries. This will be the world’s first test in humans of a therapy derived from human embryonic stem cells. The tests will use stem cells cultured from embryos left over in fertility clinics.

March 9, 2009 – President Barack Obama signs an executive order overturning an order signed by President Bush in August 2001 that barred the NIH from funding research on embryonic stem cells beyond using 60 cell lines that existed at that time.

August 23, 2010 – US District Judge Royce C. Lamberth issues a preliminary injunction that prohibits the federal funding of embryonic stem cell research.

September 9, 2010 – A three-judge panel of the US Court of Appeals for the District of Columbia Circuit grants a request from the Justice Department to lift a temporary injunction that blocked federal funding of stem cell research.

September 28, 2010 – The US Court of Appeals for the DC Circuit lifts an injunction imposed by a federal judge, thereby allowing federally funded embryonic stem-cell research to continue while the Obama Administration appeals the judge’s original ruling against use of public funds in such research.

October 8, 2010 – The first human is injected with cells from human embryonic stem cells in a clinical trial sponsored by Geron Corp.

November 22, 2010 – William Caldwell, CEO of Advanced Cell Technology, tells CNN that the FDA has granted approval for his company to start a clinical trial using cells grown from human embryonic stem cells. The treatment will be for an inherited degenerative eye disease.

April 29, 2011 – The US Court of Appeals for the District of Columbia lifts an injunction, imposed last year, banning the Obama administration from funding embryonic stem-cell research.

May 11, 2011 – Stem cell therapy in sports medicine is spotlighted after New York Yankees pitcher Bartolo Colon is revealed to have had fat and bone marrow stem cells injected into his injured elbow and shoulder while in the Dominican Republic.

July 27, 2011 – Judge Lamberth dismisses a lawsuit that tried to block funding of stem cell research on human embryos.

February 13, 2012 – Early research published by scientists at Cedars-Sinai Medical Center and Johns Hopkins University shows that a patient’s own stem cells can be used to regenerate heart tissue and help undo damage caused by a heart attack. It is the first instance of therapeutic regeneration.

May 2013 – Scientists make the first embryonic stem cell from human skin cells by reprogramming human skin cells back to their embryonic state, according to a study published in the journal, Cell.

April 2014 – For the first time scientists are able to use cloning technologies to generate stem cells that are genetically matched to adult patients,according to a study published in the journal, Cell Stem Cell.

October 2014 – Researchers say that human embryonic stem cells have restored the sight of several nearly blind patients – and that their latest study shows the cells are safe to use long-term. According to a report published in The Lancet, the researchers transplanted stem cells into 18 patients with severe vision loss as a result of two types of macular degeneration.

May 2, 2018 – The science journal Nature reports that scientists have created a structure like a blastocyst – an early embryo – using mouse stem cells instead of the usual sperm and egg.

June 4, 2018 – The University of California reports that the first in utero stem cell transplant trial has led to the live birth of an infant that had been diagnosed in utero with alpha thalassemia, a blood disorder that is usually fatal for fetuses.

January 13, 2020 – In a study published in the Proceedings of the National Academy of Sciences, researchers announce they have created the world’s first living, self-healing robots using stem cells from frogs. Named xenobots after the African clawed frog (Xenopus laevis), the machines are less than a millimeter (0.04 inches) wide, small enough to travel inside human bodies. Less than two years later, scientists announce that these robots can now reproduce.

February 15, 2022 – A US woman becomes the third known person to go into HIV remission, and the first mixed-race woman, thanks to a transplant of stem cells from umbilical cord blood, according to research presented at a scientific conference on Retroviruses and Opportunistic Infections.

November 7, 2022 – Scientists announce they have transfused lab-made red blood cells grown from stem cells into a human volunteer in a world-first trial that experts say has major potential for people with hard-to-match blood types or conditions such as sickle cell disease.

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Covid-19 Pandemic Timeline Fast Facts | CNN



CNN
 — 

Here’s a look at the coronavirus outbreak, declared a worldwide pandemic by the World Health Organization. The coronavirus, called Covid-19 by WHO, originated in China and is the cousin of the SARS virus.

Coronaviruses are a large group of viruses that are common among animals. The viruses can make people sick, usually with a mild to moderate upper respiratory tract illness, similar to a common cold. Coronavirus symptoms include a runny nose, cough, sore throat, possibly a headache and maybe a fever, which can last for a couple of days.

WHO Situation Reports

Coronavirus Map

CNN’s early reporting on the coronavirus

December 31, 2019 – Cases of pneumonia detected in Wuhan, China, are first reported to WHO. During this reported period, the virus is unknown. The cases occur between December 12 and December 29, according to Wuhan Municipal Health.

January 1, 2020 – Chinese health authorities close the Huanan Seafood Wholesale Market after it is discovered that wild animals sold there may be the source of the virus.

January 5, 2020 – China announces that the unknown pneumonia cases in Wuhan are not SARS or MERS. In a statement, the Wuhan Municipal Health Commission says a retrospective probe into the outbreak has been initiated.

January 7, 2020 – Chinese authorities confirm that they have identified the virus as a novel coronavirus, initially named 2019-nCoV by WHO.

January 11, 2020 – The Wuhan Municipal Health Commission announces the first death caused by the coronavirus. A 61-year-old man, exposed to the virus at the seafood market, died on January 9 after respiratory failure caused by severe pneumonia.

January 17, 2020 – Chinese health officials confirm that a second person has died in China. The United States responds to the outbreak by implementing screenings for symptoms at airports in San Francisco, New York and Los Angeles.

January 20, 2020 – China reports 139 new cases of the sickness, including a third death. On the same day, WHO’s first situation report confirms cases in Japan, South Korea and Thailand.

January 20, 2020 – The National Institutes of Health announces that it is working on a vaccine against the coronavirus. “The NIH is in the process of taking the first steps towards the development of a vaccine,” says Dr. Anthony Fauci, director of the National Institutes of Allergy and Infectious Diseases.

January 21, 2020 – Officials in Washington state confirm the first case on US soil.

January 23, 2020 – At an emergency committee, WHO says that the coronavirus does not yet constitute a public health emergency of international concern.

January 23, 2020 – The Beijing Culture and Tourism Bureau cancels all large-scale Lunar New Year celebrations in an effort to contain the growing spread of coronavirus. On the same day, Chinese authorities enforce a partial lockdown of transport in and out of Wuhan. Authorities in the nearby cities of Huanggang and Ezhou Huanggang announce a series of similar measures.

January 28, 2020 – Chinese President Xi Jinping meets with WHO Director General Tedros Adhanom in Beijing. At the meeting, Xi and WHO agree to send a team of international experts, including US Centers for Disease Control and Prevention staff, to China to investigate the coronavirus outbreak.

January 29, 2020 – The White House announces the formation of a new task force that will help monitor and contain the spread of the virus, and ensure Americans have accurate and up-to-date health and travel information, it says.

January 30, 2020 – The United States reports its first confirmed case of person-to-person transmission of the coronavirus. On the same day, WHO determines that the outbreak constitutes a Public Health Emergency of International Concern (PHEIC).

January 31, 2020 – The Donald Trump administration announces it will deny entry to foreign nationals who have traveled in China in the last 14 days.

February 2, 2020 – A man in the Philippines dies from the coronavirus – the first time a death has been reported outside mainland China since the outbreak began.

February 3, 2020 – China’s Foreign Ministry accuses the US government of inappropriately reacting to the outbreak and spreading fear by enforcing travel restrictions.

February 4, 2020 – The Japanese Health Ministry announces that ten people aboard the Diamond Princess cruise ship moored in Yokohama Bay are confirmed to have the coronavirus. The ship, which is carrying more than 3,700 people, is placed under quarantine scheduled to end on February 19.

February 6, 2020 – First Covid-19 death in the United States: A person in California’s Santa Clara County dies of coronavirus, but the link is not confirmed until April 21.

February 7, 2020 – Li Wenliang, a Wuhan doctor who was targeted by police for trying to sound the alarm on a “SARS-like” virus in December, dies of the coronavirus. Following news of Li’s death, the topics “Wuhan government owes Dr. Li Wenliang an apology,” and “We want freedom of speech,” trend on China’s Twitter-like platform, Weibo, before disappearing from the heavily censored platform.

February 8, 2020 – The US Embassy in Beijing confirms that a 60-year-old US national died in Wuhan on February 6, marking the first confirmed death of a foreigner.

February 10, 2020 – Xi inspects efforts to contain the coronavirus in Beijing, the first time he has appeared on the front lines of the fight against the outbreak. On the same day, a team of international experts from WHO arrive in China to assist with containing the coronavirus outbreak.

February 10, 2020 – The Anthem of the Seas, a Royal Caribbean cruise ship, sets sail from Bayonne, New Jersey, after a coronavirus scare had kept it docked and its passengers waiting for days.

February 11, 2020 – WHO names the coronavirus Covid-19.

February 13, 2020 – China’s state-run Xinhua News Agency announces that Shanghai mayor Ying Yong will be replacing Jiang Chaoliang amid the outbreak. Wuhan Communist Party chief Ma Guoqiang has also been replaced by Wang Zhonglin, party chief of Jinan city in Shandong province, according to Xinhua.

February 14, 2020 – A Chinese tourist who tested positive for the virus dies in France, becoming the first person to die in the outbreak in Europe. On the same day, Egypt announces its first case of coronavirus, marking the first case in Africa.

February 15, 2020 – The official Communist Party journal Qiushi publishes the transcript of a speech made on February 3 by Xi in which he “issued requirements for the prevention and control of the new coronavirus” on January 7, revealing Xi knew about and was directing the response to the virus on almost two weeks before he commented on it publicly.

February 17, 2020 – A second person in California’s Santa Clara County dies of coronavirus, but the link is not confirmed until April 21.

February 18, 2020 – Xi says in a phone call with British Prime Minister Boris Johnson that China’s measures to prevent and control the epidemic “are achieving visible progress,” according to state news Xinhua.

February 21, 2020 – The CDC changes criteria for counting confirmed cases of novel coronavirus in the United States and begins tracking two separate and distinct groups: those repatriated by the US Department of State and those identified by the US public health network.

February 25, 2020 – The NIH announces that a clinical trial to evaluate the safety and effectiveness of the antiviral drug remdesivir in adults diagnosed with coronavirus has started at the University of Nebraska Medical Center in Omaha. The first participant is an American who was evacuated from the Diamond Princess cruise ship docked in Japan.

February 25, 2020 – In an effort to contain the largest outbreak in Europe, Italy’s Lombardy region press office issues a list of towns and villages that are in complete lockdown. Around 100,000 people are affected by the travel restrictions.

February 26, 2020 – CDC officials say that a California patient being treated for novel coronavirus is the first US case of unknown origin. The patient, who didn’t have any relevant travel history nor exposure to another known patient, is the first possible US case of “community spread.”

February 26, 2020 – Trump places Vice President Mike Pence in charge of the US government response to the novel coronavirus, amid growing criticism of the White House’s handling of the outbreak.

February 29, 2020 – A patient dies of coronavirus in Washington state. For almost two months, this is considered the first death due to the virus in the United States, until autopsy results announced April 21 reveal two earlier deaths in California.

March 3, 2020 – The Federal Reserve slashes interest rates by half a percentage point in an attempt to give the US economy a jolt in the face of concerns about the coronavirus outbreak. It is the first unscheduled, emergency rate cut since 2008, and it also marks the biggest one-time cut since then.

March 3, 2020 – Officials announce that Iran will temporarily release 54,000 people from prisons and deploy hundreds of thousands of health workers as officials announced a slew of measures to contain the world’s deadliest coronavirus outbreak outside China. It is also announced that 23 members of Iran’s parliament tested positive for the virus.

March 4, 2020 – The CDC formally removes earlier restrictions that limited coronavirus testing of the general public to people in the hospital, unless they had close contact with confirmed coronavirus cases. According to the CDC, clinicians should now “use their judgment to determine if a patient has signs and symptoms compatible with COVID-19 and whether the patient should be tested.”

March 8, 2020 – Italian Prime Minister Giuseppe Conte signs a decree placing travel restrictions on the entire Lombardy region and 14 other provinces, restricting the movements of more than 10 million people in the northern part of the country.

March 9, 2020 – Conte announces that the whole country of Italy is on lockdown.

March 11, 2020 – WHO declares the novel coronavirus outbreak to be a pandemic. WHO says the outbreak is the first pandemic caused by a coronavirus. In an Oval Office address, Trump announces that he is restricting travel from Europe to the United States for 30 days in an attempt to slow the spread of coronavirus. The ban, which applies to the 26 countries in the Schengen Area, applies only to foreign nationals and not American citizens and permanent residents who’d be screened before entering the country.

March 13, 2020 – Trump declares a national emergency to free up $50 billion in federal resources to combat coronavirus.

March 18, 2020 – Trump signs into law a coronavirus relief package that includes provisions for free testing for Covid-19 and paid emergency leave.

March 19, 2020 – At a news conference, officials from China’s National Health Commission report no new locally transmitted coronavirus cases for the first time since the pandemic began.

March 23, 2020 – United Nations Secretary-General António Guterres calls for an immediate global ceasefire amid the pandemic to fight “the common enemy.”

March 24, 2020 – Japan’s Prime Minister Shinzo Abe and International Olympic Committee (IOC) president Thomas Bach agree to postpone the Olympics until 2021 amid the outbreak.

March 25, 2020 – The White House and Senate leaders reach an agreement on a $2 trillion stimulus deal to offset the economic damage of coronavirus, producing one of the most expensive and far-reaching measures in the history of Congress.

March 27, 2020 – Trump signs the stimulus package into law.

April 2, 2020 – According to the Department of Labor, 6.6 million US workers file for their first week of unemployment benefits in the week ending March 28, the highest number of initial claims in history. Globally, the total number of coronavirus cases surpasses 1 million, according to Johns Hopkins University’s tally.

April 3, 2020 – Trump says his administration is now recommending Americans wear “non-medical cloth” face coverings, a reversal of previous guidance that suggested masks were unnecessary for people who weren’t sick.

April 8, 2020 – China reopens Wuhan after a 76-day lockdown.

April 14, 2020 – Trump announces he is halting funding to WHO while a review is conducted, saying the review will cover WHO’s “role in severely mismanaging and covering up the spread of coronavirus.”

April 20, 2020 – Chilean health officials announce that Chile will begin issuing the world’s first digital immunity cards to people who have recovered from coronavirus, saying the cards will help identify individuals who no longer pose a health risk to others.

April 21, 2020 – California’s Santa Clara County announces autopsy results that show two Californians died of novel coronavirus in early and mid-February – up to three weeks before the previously known first US death from the virus.

April 28, 2020 – The United States passes one million confirmed cases of the virus, according to Johns Hopkins.

May 1, 2020 – The US Food and Drug Administration issues an emergency-use authorization for remdesivir in hospitalized patients with severe Covid-19. FDA Commissioner Stephen Hahn says remdesivir is the first authorized therapy drug for Covid-19.

May 4, 2020 – During a virtual pledging conference co-hosted by the European Union, world leaders pledge a total of $8 billion for the development and deployment of diagnostics, treatments and vaccines against the novel coronavirus.

May 11, 2020 – Trump and his administration announce that the federal government is sending $11 billion to states to expand coronavirus testing capabilities. The relief package signed on April 24 includes $25 billion for testing, with $11 billion for states, localities, territories and tribes.

May 13, 2020 – Dr. Mike Ryan, executive director of WHO’s health emergencies program, warns that the coronavirus may never go away and may just join the mix of viruses that kill people around the world every year.

May 19, 2020 – WHO agrees to hold an inquiry into the global response to the coronavirus pandemic. WHO member states adopt the proposal with no objections during the World Health Assembly meeting, after the European Union and Australia led calls for an investigation.

May 23, 2020 – China reports no new symptomatic coronavirus cases, the first time since the beginning of the outbreak in December.

May 27, 2020 – Data collected by Johns Hopkins University reports that the coronavirus has killed more than 100,000 people across the US, meaning that an average of almost 900 Americans died each day since the first known coronavirus-related death was reported nearly four months earlier.

June 2, 2020 – Wuhan’s Health Commission announces that it has completed coronavirus tests on 9.9 million of its residents with no new confirmed cases found.

June 8, 2020 – New Zealand Prime Minister Jacinda Ardern announces that almost all coronavirus restrictions in New Zealand will be lifted after the country reported no active cases.

June 11, 2020 – The United States passes 2 million confirmed cases of the virus, according to Johns Hopkins.

June 16, 2020 – University of Oxford scientists leading the Recovery Trial, a large UK-based trial investigating potential Covid-19 treatments, announce that a low-dose regimen of dexamethasone for 10 days was found to reduce the risk of death by a third among hospitalized patients requiring ventilation in the trial.

June 20, 2020 – The NIH announces that it has halted a clinical trial evaluating the safety and effectiveness of drug hydroxychloroquine as a treatment for the coronavirus. “A data and safety monitoring board met late Friday and determined that while there was no harm, the study drug was very unlikely to be beneficial to hospitalized patients with Covid-19,” the NIH says in a statement.

June 26, 2020 – During a virtual media briefing, WHO announces that it plans to deliver about 2 billion doses of a coronavirus vaccine to people across the globe. One billion of those doses will be purchased for low- and middle-income countries, according to WHO.

July 1, 2020 – The European Union announces it will allow travelers from 14 countries outside the bloc to visit EU countries, months after it shut its external borders in response to the pandemic. The list does not include the US, which doesn’t meet the criteria set by the EU for it to be considered a “safe country.”

July 6, 2020 – In an open letter published in the journal Clinical Infectious Diseases, 239 scientists from around the world urge WHO and other health agencies to be more forthright in explaining the potential airborne transmission of coronavirus. In the letter, scientists write that studies “have demonstrated beyond any reasonable doubt that viruses are released during exhalation, talking, and coughing in microdroplets small enough to remain aloft in air and pose a risk of exposure at distances beyond 1 to 2 meters (yards) from an infected individual.”

July 7, 2020 – The Trump administration notifies Congress and the United Nations that the United States is formally withdrawing from WHO. The withdrawal goes into effect on July 6, 2021.

July 21, 2020 – European leaders agree to create a €750 billion ($858 billion) recovery fund to rebuild EU economies ravaged by the coronavirus.

July 27, 2020 – A vaccine being developed by the Vaccine Research Center at the National Institutes of Health’s National Institute of Allergy and Infectious Diseases, in partnership with the biotechnology company Moderna, enters Phase 3 testing. The trial is expected to enroll about 30,000 adult volunteers and evaluates the safety of the vaccine and whether it can prevent symptomatic Covid-19 after two doses, among other outcomes.

August 11, 2020 – In a live teleconference, Russian President Vladimir Putin announces that Russia has approved a coronavirus vaccine for public use before completion of Phase 3 trials, which usually precedes approval. The vaccine, which is named Sputnik-V, is developed by the Moscow-based Gamaleya Institute with funding from the Russian Direct Investment Fund (RDIF).

August 15, 2020 – Russia begins production on Sputnik-V, according to Russian state news agency TASS.

August 23, 2020 – The FDA issues an emergency use authorization for the use of convalescent plasma to treat Covid-19. It is made using the blood of people who have recovered from coronavirus infections.

August 27, 2020 – The CDC notifies public health officials around the United States to prepare to distribute a potential coronavirus vaccine as soon as late October. In the documents, posted by The New York Times, the CDC provides planning scenarios to help states prepare and advises on who should get vaccinated first – healthcare professionals, essential workers, national security “populations” and long-term care facility residents and staff.

September 4, 2020 – The first peer-reviewed results of Phase 1 and Phase 2 clinical trials of Russia’s Covid-19 vaccine are published in the medical journal The Lancet. The results “have a good safety profile” and the vaccine induced antibody responses in all participants, The Lancet says.

October 2, 2020 – Trump announces that he and first lady Melania Trump have tested positive for Covid-19. He spends three nights at Walter Reed National Military Medical Center receiving treatment before returning to the White House.

October 12, 2020 – Drugmaker Johnson & Johnson announces it has paused the advanced clinical trial of its experimental coronavirus vaccine because of an unexplained illness in one of the volunteers.”Following our guidelines, the participant’s illness is being reviewed and evaluated by the ENSEMBLE independent Data Safety Monitoring Board (DSMB) as well as our internal clinical and safety physicians,” the company said in a statement. ENSEMBLE is the name of the study. The trial resumes later in the month.

December 10, 2020 – Vaccine advisers to the FDA vote to recommend the agency grant emergency use authorization to Pfizer and BioNTech’s coronavirus vaccine.

December 14, 2020 – US officials announce the first doses of the FDA authorized Pfizer vaccine have been delivered to all 50 states, the District of Columbia and Puerto Rico.

December 18, 2020 – The FDA authorizes a second coronavirus vaccine made by Moderna for emergency use. “The emergency use authorization allows the vaccine to be distributed in the U.S. for use in individuals 18 years and older,” the FDA said in a tweet.

January 14, 2021 – The WHO team tasked with investigating the origins of the outbreak in Wuhan arrive in China.

January 20, 2021 – Newly elected US President Joe Biden halts the United States’ withdrawal from WHO.

February 22, 2021 – The death toll from Covid-19 exceeds 500,000 in the United States.

February 27, 2021 – The FDA grants emergency use authorization to Johnson & Johnson’s Covid-19 vaccine, the first single dose Covid-19 vaccine available in the US.

March 30, 2021 – According to a 120-page report from WHO, the novel coronavirus that causes Covid-19 probably spread to people through an animal, and probably started spreading among humans no more than a month or two before it was noticed in December of 2019. The report says a scenario where it spread via an intermediate animal host, possibly a wild animal captured and then raised on a farm, is “very likely.”

April 17, 2021 – The global tally of deaths from Covid-19 surpasses 3 million, according to data compiled by Johns Hopkins.

August 3, 2021 – According to figures published by the CDC, the more contagious Delta variant accounts for an estimated 93.4% of coronavirus circulating in the United States during the last two weeks of July. The figures show a rapid increase over the past two months, up from around 3% in the two weeks ending May 22.

August 12, 2021 – The FDA authorizes an additional Covid-19 vaccine dose for certain immunocompromised people.

August 23, 2021 – The FDA grants full approval to the Pfizer/BioNTech Covid-19 vaccine for people age 16 and older, making it the first coronavirus vaccine approved by the FDA.

September 24, 2021 CDC Director Dr. Rochelle Walensky diverges from the agency’s independent vaccine advisers to recommend boosters for a broader group of people – those ages 18 to 64 who are at increased risk of Covid-19 because of their workplaces or institutional settings – in addition to older adults, long-term care facility residents and some people with underlying health conditions.

November 2, 2021 – Walensky says she is endorsing a recommendation to vaccinate children ages 5-11 against Covid-19, clearing the way for immediate vaccination of the youngest age group yet in the US.

November 19, 2021 – The FDA authorizes boosters of the Pfizer/BioNTech and Moderna Covid-19 vaccines for all adults. The same day, the CDC also endorses boosters for all adults.

December 16, 2021 – The CDC changes its recommendations for Covid-19 vaccines to make clear that shots made by Moderna and Pfizer/BioNTech are preferred over Johnson & Johnson’s vaccine.

December 22, 2021 – The FDA authorizes Pfizer’s antiviral pill, Paxlovid, to treat Covid-19, the first antiviral Covid-19 pill authorized in the United States for ill people to take at home, before they get sick enough to be hospitalized. The following day, the FDA authorizes Merck’s antiviral pill, molnupiravir.

December 27, 2021 The CDC shortens the recommended times that people should isolate when they’ve tested positive for Covid-19 from 10 days to five days if they don’t have symptoms – and if they wear a mask around others for at least five more days. The CDC also shortens the recommended time for people to quarantine if they are exposed to the virus to a similar five days if they are vaccinated.

January 31, 2022 – The FDA grants full approval to Moderna’s Covid-19 vaccine for those ages 18 and older. This is the second coronavirus vaccine given full approval by the FDA.

March 29, 2022 – The FDA authorizes a second booster of the Pfizer/BioNTech and Moderna Covid-19 vaccines for adults 50 and older. That same day, the CDC also endorses a second booster for the same age group.

April 25, 2022 – The FDA expands approval of the drug remdesivir to treat patients as young as 28 days and weighing about seven pounds.

May 17, 2022 – The FDA authorizes a booster dose of Pfizer/BioNTech’s Covid-19 vaccine for children ages 5 to 11 at least five months after completion of the primary vaccine series. On May 19, the CDC also endorses a booster dose for the same age group.

June 18, 2022 – The CDC recommends Covid-19 vaccines for children as young as 6 months.

August 31, 2022 – The FDA authorizes updated Covid-19 vaccine booster shots from Moderna and Pfizer. Both are bivalent vaccines that combine the companies’ original vaccine with one that targets the BA.4 and BA.5 Omicron sublineages. The CDC signs off on the updated booster shots the following day.

May 5, 2023 – The WHO says Covid-19 is no longer a global health emergency.



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Recently identified inflammatory disease VEXAS syndrome may be more common than thought, study suggests | CNN



CNN
 — 

David Adams spent half a decade fighting an illness he couldn’t name. He was in and out of the hospital several times per year. His inflamed joints made his hands feel like they had been squeezed into gloves – and he could no longer play his beloved classical and jazz guitars.

He had constant fevers and fatigue. He even developed pain and swelling in his genitalia, which was his first sign that something was really wrong.

“At the turn of the year 2016, I started with some really painful effects in the male anatomy,” said Adams, now 70. “After that, again, a lot of fatigue – my primary care physician at that point had blood tests done, and my white blood cell count was very, very low.”

Next, Adams, who lives in Alexandria, Virginia, saw a hematologist, a pulmonologist, a urologist, a rheumatologist and then a dermatologist. Some of them thought he might have cancer.

Adams’ symptoms continued, with even more fatigue, pneumonia and a large rash below his waist. He tried at least a dozen medications, saw about two dozen doctors, and nothing helped.

In 2019, worsening symptoms forced him to retire early from his decades-long career in clinical data systems. But he remained in the dark about what was causing the problems.

Finally, in 2020, scientists at the National Institutes of Health discovered and named a rare genetic disorder: VEXAS syndrome, which wreaks havoc on the body through inflammation and blood problems.

Adams had an appointment with his rheumatologist at the time, and when he walked into the office, he saw that his physician “was giddy like a little kid.”

In his doctor’s hands was a copy of a paper in the New England Journal of Medicine detailing the discovery of VEXAS syndrome.

Adams had his answer.

“For the first time, there was a one-to-one correlation of symptoms,” he said. “It was quite a shock.”

An estimated 1 in about 13,500 people in the United States may have VEXAS syndrome, a new study suggests, which means the mysterious and sometimes deadly inflammatory disorder may be more common than previously thought.

In comparison, the genetic disorder spinal muscular atrophy affects about 1 in 10,000 people and Huntington’s disease occurs in about 1 in every 10,000 to 20,000 people.

Since its discovery, occasional VEXAS cases have been reported in medical research, but the study reveals new estimates of its prevalence.

The research, published Tuesday in the journal JAMA, suggests that about 1 in 13,591 people in the US have mutations in the UBA1 gene, which develop later in life and cause VEXAS syndrome.

“This study is demonstrating that there’s likely tens of thousands of patients in the US that have this disease, and the vast majority of them are probably not being recognized because physicians aren’t really considering this as a diagnosis more broadly,” said Dr. David Beck, an assistant professor in the Department of Medicine at NYU Langone Health and a lead author of the study.

VEXAS syndrome is not inherited, so people who have it don’t pass the disease to their children. But the UBA1 gene is on the X chromosome, so the syndrome is an X-linked disease. It predominantly affects men, who carry only one X chromosome. Women have two X chromosomes, so if they have a mutation in a gene on one X chromosome but not the other, they are generally unaffected.

“It’s present in 1 in 4,000 men over the age of 50. So we think it’s a disease that should be thought about in terms of testing for individuals that have the symptoms,” said Beck, who also led the federal research team that identified the shared UBA1 mutation among VEXAS patients in 2020.

“The benefit of VEXAS syndrome is that we have a test. We have a genetic test that can help directly provide the diagnosis,” he said. “It’s just a question of patients who meet the criteria – who are older individuals with systemic inflammation, low blood counts, who really aren’t responding to anything but steroids – then advocating to their doctors to get genetic testing to get a diagnosis.”

Adams, who became a patient of Beck’s, said that finally getting a diagnosis – and understanding the cause of his symptoms – was life-changing.

“It really was incredibly freeing to have the diagnosis,” he said.

“You can’t fight your enemy unless your enemy has a name,” he added. “We finally had something where we could point to and say, ‘OK, we understand what’s going on. This is VEXAS.’ “

For the new study, Beck and his colleagues at the NIH, New York University, Geisinger Research and other institutions analyzed data on 163,096 patients in a health system in central and northeastern Pennsylvania, from January 1996 to January 2022, including electronic health records and blood samples.

Eleven of the patients had a disease-causing UBA1 variant, and a 12th person had a “highly suspicious” variant.

Only three of the 12 are still alive. A five-year survival rate of 63% has been previously reported with VEXAS.

Among the 11 patients in the new study who had pathogenic variants in UBA1, only two were women. Seven had arthritis as a symptom, and four had been diagnosed with rheumatologic diseases, such as psoriasis of the skin or sarcoidosis, which causes swollen lumps in the body. All had anemia or low blood cell counts.

“None had been previously clinically diagnosed with VEXAS syndrome,” Beck said.

The finding “is emphasizing how it’s important to be able to pick these patients out, give them the diagnosis and start the aggressive therapies or aggressive treatments to keep their inflammation in check,” he said.

VEXAS – an acronym for five clinical characteristics of the disease – has no standardized treatment or cure, but Beck said symptoms can be managed with medications like the steroid prednisone or other immunosuppressants.

“But the toxicities of prednisone over years is challenging. There are other anti-inflammatory medications that we use, but they’re only partially effective at the moment,” he said. “One treatment for individuals that we’ve seen that’s very effective is bone marrow transplantation. That comes with its own risks, but that’s just underscoring the severe nature of the disease.”

Although the new study helps provide estimates of the prevalence and symptoms of VEXAS syndrome, the data is not representative of the entire United States, and Beck said that more research needs to be done on a larger, more diverse group of people.

Some men might be hesitant to seek medical care for VEXAS symptoms, but Adams said that doing so could save their life.

“Eventually, it’s going to get so bad that you’ll end up like my first hospitalization, where you’re on death’s door,” Adams said. “You don’t want to be in that situation.”

Adams has been taking prednisone to ease his symptoms, and it’s helped. But because steroid use can have side effects such as cataracts and weight gain, he has been working with his doctors to find other therapies so he can reduce his intake of the medication.

Beck and his colleagues are studying targeted therapies for VEXAS syndrome, as well as conducting stem cell bone marrow transplant trials at the NIH.

“There are many different facets of the disease,” Dr. Bhavisha Patel, a hematologist and researcher in the National Heart, Lung and Blood Institute’s Hematopoiesis and Bone Marrow Failure Laboratory, said in an NIH news release last month.

“I believe that is what is challenging when we think about treatment, because it’s so heterogeneous,” said Patel, who was not involved in the new study.

“Both at NIH and worldwide, the groups that have dedicated themselves to VEXAS are looking for medical therapies to offer to other patients who don’t qualify for a bone marrow transplant,” she said. “We continue to collaborate on many projects in order to categorize this disease further and ultimately come up with the best treatment options.”

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Study shows convalescent plasma works for immune-compromised Covid-19 patients, but it can be hard to find | CNN



CNN
 — 

Convalescent plasma – a once-celebrated treatment for Covid-19 that has largely fallen out of favor – does work well for people who are immune-compromised, according to a study published Thursday.

The report in the journal JAMA Network Open analyzed the results of nine studies and found that immune-compromised Covid-19 patients were 37% less likely to die if they got convalescent plasma, an antibody-rich blood product from people who’d recovered from the virus.

Although it’s legal to use convalescent plasma to treat Covid patients who are immune-compromised, as inpatients or outpatients, government guidelines are neutral about whether the treatment works, so some hospitals offer it but others do not.

“Our concern is that many patients who need [convalescent plasma] are not getting it,” said Dr. Arturo Casadevall, an infectious disease expert at Johns Hopkins University and a co-author of the new study. “This is really important because these people can be treated, and they could have better outcomes with this material if we can just get the word out.”

He said it’s to everyone’s advantage to treat immune-compromised patients quickly.

Immune-compromised people sometimes have “smoldering Covid” for months because they lack the antibodies to fight it off, which gives the virus plenty of opportunities to mutate in the person’s body.

“These immune-compromised patients are essentially variant factories,” said Dr. Michael Joyner, an anesthesiologist at the Mayo Clinic and another study co-author. “And you do not want a bunch of people running around out there making weird variants.”

There are about 7 million immune-compromised people in the US, and treating them if they contract Covid-19 has proved challenging.

Many of them can’t take the antiviral drug Paxlovid because it interferes with other medicines they take.

Monoclonal antibodies, once popular for prevention and treatment for this group, aren’t used anymore because coronavirus variants have changed over time. One of the advantages of convalescent plasma is that as long as it’s been donated recently, there’s a high likelihood it will have antibodies to currently circulating variants, according to advocates for the treatment.

But the National Institutes of Health’s Covid-19 treatment guidelines say there’s not enough evidence to recommend either for or against the use of convalescent plasma in people with compromised immune systems.

Three times last year – in May, August and December – Casadevall, Joyner and dozens of other doctors from Harvard, Stanford, Mayo, Columbia and other academic medical centers wrote emails to scientists at the National Institutes of Health, sending them research materials and urging them to revise the guidelines. They say they have not received a response.

Joyner said he’s “frustrated” with the NIH’s “bureaucratic rope-a-dope,” calling the agency’s guidelines a “wet blanket” that discourages doctors from trying convalescent plasma on these people.

Some patient advocates say they’re angry.

“This lack of response to the researchers is infuriating,” said Janet Handal, co-founder of the Transplant Recipient and Immunocompromised Patient Advocacy Group.

Several large randomized clinical trials on the general population, including one in India and one in the UK, have found that convalescent plasma did not reduce Covid-19 deaths or prevent severe illness, and the treatment is no longer authorized in the US for people who have healthy immune systems.

The nine studies analyzed in the new report are much smaller and looked only at immune-compromised patients.

Dr. Peter Horby, a professor at the University of Oxford and the co-principal investigator of the large UK study, said that a large randomized clinical trial should be done on immune-compromised patients before clinical practice guidelines for this group are changed.

He said that support for convalescent plasma to treat Covid-19 has been based on “an emotional feeling that something had to be done.”

“We’ve seen time and again that people’s beliefs and emotions about what works can be wildly wrong, and so the best thing to do is to evaluate these things properly in trials,” he said.

At the beginning of the pandemic, there was great enthusiasm for convalescent plasma as Covid-19 survivors sought to save lives, donating antibodies against the virus to people who were sometimes at death’s door.

In August 2020, the US Food and Drug Administration granted emergency use authorization for the treatment, but some questioned whether it was politically motivated and whether the data really showed that it worked.

Then, the large clinical trials suggested convalescent plasma didn’t work.

“We didn’t see a benefit,” said Horby, director of Oxford’s Pandemic Sciences Institute.

But there was one exception.

Horby said his study did find “some evidence of some benefit” in Covid-19 patients who had not developed antibodies against the virus. This would most likely include immune-compromised patients because their faulty immune systems don’t always generate antibodies the way they should, even after infection.

When this group of patients received convalescent plasma, Horby said, they had a slightly shortened hospital stay and a slightly lower risk of ending up on a ventilator compared with similar patients who did not receive convalescent plasma.

Joyner and Casadevall, the Mayo and Hopkins doctors, point to that finding – and a similar one in a large trial in Australia, Canada, the UK and the US, as well as results of smaller studies – as an indication that convalescent plasma is worth trying in immune-compromised patients.

Immune-compromised patients who catch Covid-19 can get convalescent plasma relatively easily if they’re patients at Hopkins, Mayo or several other medical centers.

But many other people might have a difficult time accessing it.

It took Bernadette Kay of Manhattan Beach, California, months to get it, and she had to be “relentless” and call in the help of several “angels” in New York, Maryland, Minnesota and California to finally make it work.

Kay, 64, who has a compromised immune system because of a drug she takes for rheumatoid arthritis, got Covid-19 in July. She took two monoclonal antibodies, as well as remdesivir and Paxlovid – twice. But she still tested positive on and off for months and had fatigue, congestion and headaches.

“I felt like half a person,” she said. “I was not an able-bodied person. I was disabled because of lack of energy. It feels dark – a heavy feeling in your forehead and your face.”

Kay said she saw several doctors and none of them suggested convalescent plasma. That’s where her first angel came in: her daughter, who had signed her up for the Transplant Recipient and Immunocompromised Patient Advocacy Group.

That group, as well as the CLL Society, an advocacy organization for cancer patients, have been helping immune-compromised people when they get infected with Covid-19, connecting them with experts and offering guidance on how to arrange to have the plasma ordered.

Kay says Handal, the co-founder of the immune-compromised patients’ group, was her second angel, because she pointed her to angels No. 3 and 4: Joyner, the Mayo doctor, and Dr. Shmuel Shoham, an infectious disease expert at Hopkins.

Joyner and Shoham pointed Kay to her fifth angel: Chaim Lebovits, a businessman, leader in the New York’s Hasidic Jewish community and co-founder of the Covid Plasma Initiative.

Lebovits reached out to a hospital and blood bank near Kay that could procure the plasma once a doctor ordered it. Kay then reached out to six local doctors, most of them infectious disease experts, inquiring about convalescent plasma, but she didn’t make any progress.

“I think they thought it was quack medicine,” she said.

By this time, it was November, four months after she initially tested positive for Covid. She sought out a seventh doctor, sending him information from plasma experts, including a slide presentation by Joyner and Casdevall. She said that doctor, after conferring with someone at the blood bank that Libovits had suggested, agreed to order the plasma.

That’s where her sixth angel came in: Robert Simpson, vice president for hospital services at the San Diego Blood Bank, who arranged to have the blood flown in from Stanford University Medical Center.

“Robert watched the flight on Flight Tracker and had a courier waiting to bring it to the hospital,” Kay said, adding that she calls her angels collectively her “circle of love.”

Two to three weeks after her infusion, she began to feel better. She tested negative on January 4 and has continued to feel well and test negative since then.

“My energy level is back to normal. I don’t feel like half a person,” she said.

She said she’ll never know for sure exactly what spurred her recovery, but “I think it was plasma that made the difference, because in six months, nothing else made a difference.”

Kay, who works in health care, said most other people wouldn’t have known how to navigate the system like she did or might have given up in frustration.

“With the help of Janet [Handal] and her team of scientists, I’ve been able to get where I am today,” she said. “But it was not easy. This was driven by my bullheaded advocacy, because that’s who I am. I think I’m a total anomaly. No one has the persistence that I have.”

Joyner said that while he and his colleagues wait for a response from their emails to the NIH, they’ve formed the National Covid-19 Convalescent Plasma Project, and they have a phone meeting every Thursday night to discuss their progress.

“We’ve encountered many roadblocks,” said Dr. Liise-anne Pirofski, chief of the Division of Infectious Diseases at the Albert Einstein College of Medicine. “It’s just not viewed as part of the Covid-19 treatment armamentarium, and it should be.”

Pirofski, Joyner and Casadevall say they receive no financial benefit from convalescent plasma. They think one reason convalescent plasma isn’t more widely used is that there isn’t a pharmaceutical company spending money to advocate for it.

Handal, who runs the Facebook group for people who are immune-compromised, said that after she sent several emails to the NIH, agency scientists wrote back, inviting her and other leaders of her group to a meeting next week.

She plans to tell them that they need to review their Covid-19 plasma guidelines and fund more research on the coronavirus and the immune-compromised, as they have few treatment options and so often isolate at home with their families to avoid the virus.

“It is unconscionable that the NIH has let stand for months its guideline on Covid convalescent plasma, which says there is not enough information to make a recommendation, while we who are immune-compromised see our treatments dwindle,” she said. “The NIH needs to speak to the clinician researchers who are experts, prioritize the immune-compromised and fund the research needed to keep us safe.”

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