Some Coronavirus Patients Test Positive For Weeks. Interpret Those Results With Caution

Some Coronavirus Patients Test Positive For Weeks. Interpret Those ...

PCR tests are precise, but they can also detect the presence of the virus well after it’s no longer contagious.

Dr. Matthew Binnicker, an expert in the diagnosis of infectious disease, explains why someone might still test positive for Covid-19 weeks after they’ve recovered.

To date, the majority of patients with Covid-19 have been diagnosed using a laboratory test called PCR, which detects the virus’ genetic material (i.e., RNA) in clinical samples (e.g., nasal swabs). PCR is a very sensitive laboratory method – meaning it can detect minute amounts of viral RNA – and has been used for nearly 2 decades to diagnose a variety of infectious diseases, including influenza and strep throat. Despite being a rapid and inherently sensitive test, PCR has certain limitations that need to be carefully considered when interpreting the results.

One of those key limitations of PCR is its inability to determine whether a patient is infectious, or not. This is because the test is designed to detect the virus’ RNA, which is generally present when a virus is causing an active infection. However, RNA can also be present, and therefore, detected by PCR after a virus has broken down (i.e., become non-infectious) and released its genome into host cells or body fluids. From prior experience with other infectious diseases, we know that PCR tests can be positive for days or weeks after a patient has recovered from the illness and is no longer infectious.

As more testing is being performed for Covid-19, we are learning that some patients can test positive for weeks following their initial diagnosis. A recent study showed that 16% of patients with Covid-19 continued to test positive for SARS-CoV-2 RNA up to 24 days after resolution of symptoms and discharge from the hospital. In addition, some Covid-19 patients who recover from their illness and test negative by PCR may again test positive (i.e., go from PCR positive to negative to positive). So does this mean they never fully recovered? Are they still infectious? Or did they become reinfected with a new strain of the virus?

Here are some things to understand.


RNA from SARS-CoV-2 might be found in your body long after you’ve recovered from the disease.

Even though they inform isolation and return-to-work decisions, PCR tests don’t measure if someone is contagious

When an individual tests positive for Covid-19, it is a common policy to require that they remain in isolation for a period of 10-14 days. In fact, the Centers for Disease Control and Prevention (CDC) recommends that those who test positive for Covid-19 remain in isolation until they have received two negative PCR results on samples collected at least 24 hours apart.

This is a conservative approach, but has been justified during the early stages of the Covid-19 pandemic due to the lack of data on the period of infectiousness of SARS-CoV-2, as well as the significant repercussions of allowing an infected individual to return-to-work or interact with others before there is confidence they are no longer infectious. However, PCR is not typically used as a ‘test of cure’ for other infectious diseases, since it can remain positive after a patient has cleared an infection.

What does it mean when a patient tests positive after recovering from Covid-19?

While studies are being performed to definitively answer this question, new data are emerging that suggest the period of SARS-CoV-2 infectiousness may not correlate with PCR positivity. In other words, an individual may not be able to infect others for as long as they test positive by PCR. To determine this, researchers have investigated two important questions. First, can the virus be cultured, or grown, from samples that are collected weeks after resolution of a patient’s symptoms but test positive by PCR? And second, do close contacts (e.g., family members, coworkers) of patients with persistently positive PCR tests become sick with Covid-19?

Last week, the South Korean CDC published important data aimed at addressing these questions. The study followed approximately 800 contacts of Covid-19 patients after they had recovered from their illness, tested negative, but once again tested positive by PCR. The researchers found no evidence that the contacts became ill with Covid-19. In addition, the South Korean scientists were unable to grow the virus from samples that were PCR positive at the latest time point.

Although these results suggest that Covid-19 patients may not be infectious for weeks or months following resolution of their symptoms, the exact timeframe over which an individual can transmit the virus to others remains unclear. Additional studies are needed to better define the period of viral infectivity, so that we can prevent the spread of Covid-19 but allow recovered patients the opportunity to emerge from isolation as soon as it is safe to do so.





How Jefferson and Franklin Helped End Smallpox in America

Drawing Lessons from a Government Protest in North Dakota

As the world eagerly awaits a vaccine for the coronavirus, 200 years ago a smallpox cure struggled to gain acceptance. This is how our founding fathers helped promote the medical breakthrough that saved countless lives.

The great scourge of Thomas Jefferson’s era (1743-1826) was smallpox. Historians have estimated that perhaps as many as 2 billion people have died of smallpox in recorded history. That’s a pretty arbitrary figure, but it certainly indicates how serious the problem was. Modern epidemiology has not only eliminated smallpox as a threat to civilization but has been engaged in a protracted debate about whether to snuff it out altogether once and for all, or to keep a tiny bit of it alive in a handful of tightly secured vials in case we need to study it in the face of other disease epidemics. It was officially declared eradicated in 1980.

For most of human history, you either got it or you didn’t and then you either survived it or you didn’t. George Washington was infected by smallpox in Barbados in 1751. He survived, and though he was slightly disfigured, he was thereafter immune to the disease. It is possible that this early brush with smallpox saved the American Revolution 20 years later. In 18th-century Europe, 400,000 people died annually of smallpox.

By the time Jefferson was born in 1743, there was an experimental inoculation procedure, but it was quite dangerous and therefore highly controversial. The idea was to give healthy individuals a very tiny amount of actual smallpox under quarantine and very carefully controlled conditions and simply hope that the person’s immune system would be able to fight it off. Survival would immunize that individual for life. The procedure required many weeks of quarantine, fasting, puking, and rest, followed by a very light diet through convalescence. John Adams wrote a fascinating account of his own inoculation in 1764. He was 28 years old.

Young Thomas Jefferson’s first journey out of his native Virginia was to Philadelphia in 1766 to be inoculated. He would have undertaken the procedure in Williamsburg or Norfolk had it been available. He made the long journey (eight to 10 days in either direction) because he wanted to protect himself from the disease and study the procedure at the same time for possible incorporation into his own community at Monticello. With his characteristic taciturnity about personal things, Jefferson did not leave us a detailed account of the medical procedure, which required prolonged isolation, personal discipline and a great deal of patience.

Inoculation was first introduced in Europe 40 years earlier. Lady Mary Wortley Montague (1689-1762) had spent time in Turkey as the wife of the British ambassador to the Ottoman Empire. There she had witnessed inoculation in the zenanas (segregated women’s quarters) she visited. She called the procedure “engrafting,” which she described in an important “Letter to a Friend” on April 1, 1717. Mrs. Montagu’s brother had died of smallpox four years earlier and she herself had survived a bout of smallpox in 1715, but with her famous beauty disfigured. She had her five-year-old son Edward inoculated in the British Embassy in Turkey.

Lady Mary Wortley Montagu in Ottoman Travel Dress. She was the first to introduce smallpox inoculation in Europe.

When she returned with her family to Britain, she became an outspoken advocate for the procedure. The English medical establishment decried inoculation and denounced Mary Montagu. Still, in 1721 when a smallpox epidemic broke out in England, she had her daughter inoculated in London. This was the first recorded use of the procedure in England. The medical establishment was slow to accept the efficacy of inoculation, which it regarded as an “oriental folk remedy.” It seemed counter-intuitive and just wrong-headed to give a healthy person a dose of smallpox to try to prevent her or him from getting it by accident. 

Franklin Learns About Inoculation the Hard Way

New England Puritan minister Cotton Mather (1663-1728) first promoted inoculation in America. In 1706, Reverend Mather purchased a black slave he named Onesimus (from the Epistle to Philemon). Ten years later, Onesimus told Mather he had been made immune to smallpox in Africa by having the pus of an infected person rubbed on an open wound on his arm. This is known as the variolation method. Mather interrogated other slaves to learn more, confirmed the story, and became an advocate for inoculation. He was subjected to the usual criticism and pushback. An explosive device was thrown through the window of his home. In this instance, racism joined fear as a means of discrediting the medical procedure. What possible wisdom could come from a slave?

The smallpox plague that disturbed Britain in 1721 found its way that same year to Boston. Now Mather and Dr. Zabdiel Boylston, the only physician in Boston who supported the technique, offered their inoculation services to anyone who would trust them. Of the 242 people Boylston inoculated, only six died, or one in 40. Of those who did not undergo the procedure, one in seven died.

America’s greatest exemplar of the Enlightenment, Benjamin Franklin, became a passionate advocate of the procedure after his first son Franky died of smallpox on Nov. 21, 1736, at the age of four. Because Franklin was known to be a friend to inoculation, rumors spread in Philadelphia that Franky had died from the procedure. To set the record straight, the grieving father wrote an article in the Pennsylvania Gazette on Dec. 30, 1736: He had “intended to get [Francis] inoculated as soon as he should have recovered sufficient strength from a flux with which he had been long afflicted.” Franklin assured the public that his son “received the distemper in the common way of infection.”

In 1774, Franklin, who was an indefatigable creator of associations, societies, clubs and public institutions, including volunteer fire departments and lending libraries, established the Society for Inoculating the Poor Gratis to help the poor people of Philadelphia have access to inoculation. In his famous autobiography, Franklin wrote: “In 1736 I lost one of my sons, a fine boy of four years old, by the smallpox taken in the common way. I long regretted bitterly and still regret that I had not given it to him by inoculation. This I mention for the sake of the parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it.”

Edward Jenner and the Fight to Vaccinate

As a young man, the future English physician Edward Jenner (1749-1823) overheard an English milkmaid say, “I shall never have smallpox for I have had cowpox. I shall never have an ugly pockmarked face.” Many years later, remembering the incident, Jenner, now a doctor, interrogated other milkmaids and then experienced one of the most important “eureka” moments in history. Without understanding how germs work, with no knowledge of anything called a virus, Dr. Jenner realized that cowpox (also known as kinepox) must be closely related to smallpox, and that surviving it seemed to make individuals immune to the more deadly disease. He reckoned that cowpox and smallpox must share some essential epidemiological element and since cowpox was neither lethal nor usually disfiguring, careful use of cowpox material would represent a superior protection against smallpox than variolation, which was a more dangerous procedure.

On May 14, 1796, Jenner inoculated an eight-year-old boy named James Phipps with kinepox pus. Phipps developed mild fever and discomfort. Ten days later he felt fine. Two months after that, Dr. Jenner inoculated the boy again, but this time with serum from a fresh smallpox sore. No disease developed. The smallpox vaccine had been born. Our term “vaccination” dates from this episode. Vaccination comes from the Latin word for cow, “vacca.” Jenner called the cowpox serum “vaccinia.” The terminology reminds us that all western vaccination stems from this moment in 1796.

No good deed goes unpunished, apparently, not even one that changes the history of the planet. In Britain, Edward Jenner was subjected to the usual harassment and ridicule. The paper he submitted to the Royal Society of England was rejected by none other than Sir Joseph Banks, one of Britain’s premier naturalists, botanists, and patrons of science. It took many years and the vaccination experiments of other physicians and scientists before Jenner’s work was vindicated.

Eventually, Jenner received worldwide recognition for his discovery. Devoted like Jefferson to the philanthropic principles of the Enlightenment, Dr. Jenner not only made no effort to enrich himself but devoted so much of his time and energy to promoting vaccination that he endured periods of real poverty. Finally, in 1802, the British Parliament voted him a reward of £10,000. Five years later he received £20,000 more from Parliament.

The true vaccine found its way to America thanks to Dr. John Haygarth of Bath. He sent some of Jenner’s material to Benjamin Waterhouse, a professor of physics at Harvard University. Waterhouse, in turn sent serum and reports of the vaccine’s efficacy to Thomas Jefferson, now the third president of the United States.

Dr. Edward Jenner discovered the true smallpox vaccine in 1796.

Jefferson’s Scientific Approach to Vaccines

In the new world, inoculation had a very rough reception. When John Dalgleish and Archibald Campbell began inoculating individuals in Norfolk, Virginia, an angry mob burned down Campbell’s house. Similar incidents occurred in Salem and Marblehead, Mass. In Charleston, S.C., an inoculation control law of 1738 imposed a fine of £500 on anyone providing or receiving inoculation within two miles of the city. A similar law was passed in New York City in 1747.

The measures in New England were so draconian that Benjamin Waterhouse noted the paradox: “New England, the most democratical region on the face of the earth voluntarily submitted to more restrictions and abridgements of liberty, to secure themselves against that terrific scourge, than any absolute monarch could have enforced.” (This, strangely prescient, anticipates the current debate about liberty versus public health). It was in the middle colonies — Maryland, Pennsylvania, New Jersey — that inoculation was most tolerated in the second half of the 18th century. That’s why Jefferson made the long journey to Philadelphia to be inoculated in 1766.

Jefferson first became aware of the discovery of a true smallpox vaccine from the newspapers he read in Philadelphia and the new capitol in Washington, D.C. Then, on Dec. 1, 1800, just after Jefferson’s election to the presidency, Benjamin Waterhouse sent him his pamphlet on the vaccine with a lovely cover letter saying that he regarded Jefferson as “one of our most distinguished patriots and philosophers.” Jefferson responded immediately, thanking Waterhouse for the publication and declaring, with his usual grace, that “every friend of humanity must look with pleasure on this discovery, by which one evil the [more] is withdrawn from the condition of man: and contemplating the possibility that future improvements & discoveries, may still more & more lessen the catalogue of evils. in this line of proceeding you deserve well of your [country?] and I pray you to accept my portion of the tribute due you.”

The following June, Waterhouse sent Jefferson a long letter explaining how the vaccine must be administered, how the serum could be preserved over time, and how much the controversial procedure needed the public support of a man of Jefferson’s stature in the “republic of letters.” President Jefferson became known as a defender and promoter of vaccination. In fact, he even arranged for his protégé Meriwether Lewis to carry some of the serum with him up the Missouri River in 1804-05, instructing him to “carry with you some matter of the kine pox, inform those of them with whom you may be, of its efficacy as a preservative from the small pox; and instruct & encourage them in the use of it. This may be especially done wherever you may winter.” Unfortunately, by the time the Lewis and Clark Expedition reached their winter encampment in today’s North Dakota, the serum had become inert. Thus Jefferson’s philanthropic initiative to vaccinate the Native Americans of the American West was stillborn.

Then, on May 14, 1806, now in his second term, Jefferson wrote perhaps the greatest presidential fan letter of all time. He took time from his duties as president to write the following letter to Edward Jenner. I quote it in its entirety:

SIR,— I have received a copy of the evidence at large respecting the discovery of the vaccine inoculation which you have been pleased to send me, and for which I return you my thanks. Having been among the early converts, in this part of the globe, to its efficiency, I took an early part in recommending it to my countrymen. I avail myself of this occasion of rendering you a portion of the tribute of gratitude due to you from the whole human family. Medicine has never before produced any single improvement of such utility. Harvey’s discovery of the circulation of the blood was a beautiful addition to our knowledge of the animal economy, but on a review of the practice of medicine before and since that epoch, I do not see any great amelioration which has been derived from that discovery. You have erased from the calendar of human afflictions one of its greatest. Yours is the comfortable reflection that mankind can never forget that you have lived. Future nations will know by history only that the loathsome small-pox has existed and by you has been extirpated. Accept my fervent wishes for your health and happiness and assurances of the greatest respect and consideration.

Who would not have wished to receive this magnificent, selfless, public-spirited, and enlightened letter? Unfortunately, we do not know how or even if Dr. Jenner responded. Except in medical circles, Edward Jenner has been largely forgotten.






Huge Study Throws Cold Water on Antimalarials for COVID-19

Huge Study Throws Cold Water on Antimalarials for COVID-19 ...

— No support for continued use seen in analysis of 15,000 patients who got controversial drugs

Chloroquine or hydroxychloroquine (HCQ), with or without an antibiotic, in hospitalized COVID-19 patients were associated with increased risk of death in the hospital and higher rates of arrhythmias, analysis of outcomes in nearly 100,000 patients indicated.

The 15,000 patients who received HCQ or chloroquine were about twice as likely to die compared to controls who did not receive these agents after adjusting for covariates (18.o% for hydroxychloroquine and 16% for chloroquine versus 9.3% for controls), reported Mandeep Mehra, MD, of Brigham and Women’s Hospital in Boston, and colleagues.

The drug was also associated with a higher risk of ventricular arrhythmia during hospitalization (6.1% for hydroxychloroquine, 4.3% for chloroquine versus 0.3% for controls), the authors wrote in The Lancet.

Moreover, risks for both in-hospital mortality and ventricular arrhythmia were even higher compared to controls when either drug was combined with a macrolide antibiotic, they noted.

Mehra said in a statement these drugs should not be used as treatments for COVID-19 outside of clinical trials.

“This is the first large scale study to find statistically robust evidence that treatment with chloroquine or hydroxychloroquine does not benefit patients with COVID-19,” he said. “Instead, our findings suggest it may be associated with an increased risk of serious heart problems and increased risk of death. Randomised clinical trials are essential to confirm any harms or benefits associated with these agents.”

Mehra’s group analyzed some 96,000 patients from 671 hospitals on six continents with COVID-19 infection, from Dec. 20 to April 14, all of whom had either died or been discharged from the hospital by April 21.

Overall, 14,888 patients were treated with hydroxychloroquine, chloroquine, hydroxychloroquine with a macrolide antibiotic or chloroquine with an antibiotic, and their results were compared to 81,144 controls who did not receive these drugs.

Authors adjusted for demographic factors, as well as cardiovascular disease, diabetes, lung disease, smoking, immunosuppressed conditions and baseline disease severity.

The estimated excess risk attributable to the drug regimen rather than other factors, such as comorbidities, ranged from 34% to 35%.

Arrhythmia’s greatest risk was in the group who received hydroxychloroquine and a macrolide antibiotic such as azithromycin (8% versus 0.3% of controls), and this regimen was associated with a more than five-fold risk of developing an arrhythmia while hospitalized, though cause and effect cannot be inferred, the group noted.

“Previous small-scale studies have failed to identify robust evidence of a benefit and larger, randomised controlled trials are not yet completed,” said co-author Frank Ruschitzka, MD, Director of the Heart Center at University Hospital Zurich in a statement. “However, we now know from our study that the chance that these medications improve outcomes in COVID-19 is quite low.”

An accompanying editorial by Christian Funck-Brentano, MD, PhD, and Joe-Elie Salem, MD, PhD, of Sorbonne Université in Paris, noted limitations of the observational data, but said the authors “should be commended for providing results from a well designed and controlled study … in a very large sample of hospitalized patients.”

They also cautioned against attributing the increased risk of hospital deaths to the higher incidence of arrhythmias, noting that “the relationship between death and ventricular tachycardia was not studied and causes of deaths (i.e., arrhythmic vs non-arrhythmic) were not adjudicated.”

The editorialists nevertheless concluded both hydroxychloroquine and chloroquine, with or without azithromycin, “are not useful and could be harmful in hospitalized patients with COVID-19,” and stressed the importance of clinical trials for these drugs.

“The global community awaits the results of ongoing, well powered randomized controlled trials showing the effects of chloroquine and hydroxychloroquine on COVID-19 clinical outcomes,” they wrote.





Vaccine experts say Moderna didn’t produce data critical to assessing Covid-19 vaccine

Vaccine experts say Moderna didn’t produce data critical to assessing Covid-19 vaccine

Moderna taps $1.34B stock offering to bankroll its promising COVID ...

Heavy hearts soared Monday with news that Moderna’s Covid-19 vaccine candidate — the frontrunner in the American market — seemed to be generating an immune response in Phase 1 trial subjects. The company’s stock valuation also surged, hitting $29 billion, an astonishing feat for a company that currently sells zero products.

But was there good reason for so much enthusiasm? Several vaccine experts asked by STAT concluded that, based on the information made available by the Cambridge, Mass.-based company, there’s really no way to know how impressive — or not — the vaccine may be.

While Moderna blitzed the media, it revealed very little information — and most of what it did disclose were words, not data. That’s important: If you ask scientists to read a journal article, they will scour data tables, not corporate statements. With science, numbers speak much louder than words.

Even the figures the company did release don’t mean much on their own, because critical information — effectively the key to interpreting them — was withheld.

Experts suggest we ought to take the early readout with a big grain of salt. Here are a few reasons why.

The silence of the NIAID

The National Institute for Allergy and Infectious Diseases has partnered with Moderna on this vaccine. Scientists at NIAID made the vaccine’s construct, or prototype, and the agency is running the Phase 1 trial. This week’s Moderna readout came from the earliest of data from the NIAID-led Phase 1.

NIAID doesn’t hide its light under a bushel. The institute generally trumpets its findings, often offering director Anthony Fauci — who, fair enough, is pretty busy these days — or other senior personnel for interviews.

But NIAID did not put out a press release Monday and declined to provide comment on Moderna’s announcement.

The n = 8 thing

The company’s statement led with the fact that all 45 subjects (in this analysis) who received doses of 25 micrograms (two doses each), 100 micrograms (two doses each), or a 250 micrograms (one dose) developed binding antibodies.

Later, the statement indicated that eight volunteers — four each from the 25-microgram and 100-microgram arms — developed neutralizing antibodies. Of the two types, these are the ones you’d really want to see.

We don’t know results from the other 37 trial participants. This doesn’t mean that they didn’t develop neutralizing antibodies. Testing for neutralizing antibodies is more time-consuming than other antibody tests and must be done in a biosecurity level 3 laboratory. Moderna disclosed the findings from eight subjects because that’s all it had at that point. Still, it’s a reason for caution.

Separately, while the Phase 1 trial included healthy volunteers ages 18 to 55 years, the exact ages of these eight people are unknown. If, by chance, they mostly clustered around the younger end of the age spectrum, you might expect a better response to the vaccine than if they were mostly from the senior end of it. And given who is at highest risk from the SARS-CoV-2 coronavirus, protecting older adults is what Covid-19 vaccines need to do.

There’s no way to know how durable the response will be

The report of neutralizing antibodies in subjects who were vaccinated comes from blood drawn two weeks after they received their second dose of vaccine.

Two weeks.

“That’s very early. We don’t know if those antibodies are durable,” said Anna Durbin, a vaccine researcher at Johns Hopkins University.

There’s no real way to contextualize the findings

Moderna stated that the antibody levels seen were on a par with — or greater than, in the case of the 100-microgram dose — those seen in people who have recovered from Covid-19 infection.

But studies have shown antibody levels among people who have recovered from the illness vary enormously; the range that may be influenced by the severity of a person’s disease. John “Jack” Rose, a vaccine researcher from Yale University, pointed STAT to a study from China that showed that, among 175 recovered Covid-19 patients studied, 10 had no detectable neutralizing antibodies. Recovered patients at the other end of the spectrum had really high antibody levels.

So though the company said the antibody levels induced by vaccine were as good as those generated by infection, there’s no real way to know what that comparison means.

STAT asked Moderna for information on the antibody levels it used as a comparator. The response: That will be disclosed in an eventual journal article from NIAID, which is part of the National Institutes of Health.

“The convalescent sera levels are not being detailed in our data readout, but would be expected in a downstream full data exposition with NIH and its academic collaborators,” Colleen Hussey, the company’s senior manager for corporate communications, said in an email.

Durbin was struck by the wording of the company’s statement, pointing to this sentence: “The levels of neutralizing antibodies at day 43 were at or above levels generally seen in convalescent sera.”

“I thought: Generally? What does that mean?” Durbin said. Her question, for the time being, can’t be answered.

Rose said the company should disclose the information. “When a company like Moderna with such incredibly vast resources says they have generated SARS-2 neutralizing antibodies in a human trial, I would really like to see numbers from whatever assay they are using,” he said.

Moderna’s approach to disclosure

The company has not yet brought a vaccine to market, but it has a variety of vaccines for infectious diseases in its pipeline. It doesn’t publish on its work in scientific journals. What is known has been disclosed through press releases. That’s not enough to generate confidence within the scientific community.

“My guess is that their numbers are marginal or they would say more,” Rose said about the company’s SARS-2 vaccine, echoing a suspicion that others have about some of the company’s other work.

“I do think it’s a bit of a concern that they haven’t published the results of any of their ongoing trials that they mention in their press release. They have not published any of that,” Durbin noted.

Still, she characterized herself as “cautiously optimistic” based on what the company has said so far.

“I would like to see the data to make my own interpretation of the data. But I think it is at least encouraging that we’ve seen immune responses with this RNA vaccine that we haven’t seen with previous RNA vaccines for other pathogens. Whether it’s going to be enough, we don’t know,” Durbin said.

Moderna has been more forthcoming with data on at least one of its other vaccine candidates. In a statement issued in January about a Phase 1 trial for its cytomegalovirus (CMV) vaccine, it quantified how far over baseline measures antibody levels rose in vaccines.




New Coronavirus Vaccine Candidate Shows Promise In Early, Limited Trial

Moderna's coronavirus vaccine shows promise in first human trial ...

A vaccine manufacturer is reporting preliminary data suggesting its COVID-19 vaccine is safe, and appears to be eliciting in test subjects the kind of immune response capable of preventing disease.

Moderna, Inc., of Cambridge, Mass., developed the vaccine in collaboration with the National Institute of Allergy and Infectious Diseases. The results reported Monday come from an initial analysis of a Phase I study primarily designed to see if the vaccine is safe.

The company reports no serious side-effects; however, modest side-effects included redness at the injection site, headache, fever and flu-like symptoms, although none of these lasted more than a day.

The first 45 volunteers for the vaccine trial were divided into three groups, with each group getting a different dose of the vaccine. All groups got an initial shot, followed by a booster shot a month later.

In addition to safety, the company also looked at the vaccine’s ability to induce antibodies to the coronavirus — what’s known as its immunogenicity. It did, for all subjects at all dose levels. In addition, eight of the subjects were tested for the presence of neutralizing antibodies that prevent the virus from infecting cells in the laboratory. All eight did.

The Food and Drug Administration has given Moderna the green light to begin a Phase II study expected to enroll an additional 600 volunteers — half older than 55 — to provide additional immunogenicity data. The company hopes by July to begin a Phase III study, aimed at showing that the vaccine can actually prevent disease.

The Moderna vaccine is made using messenger RNA, or mRNA, a molecule containing the genetic instructions to make a protein on the coronavirus surface that is recognized by our immune systems. Although mRNA vaccines have been studied for several years, so far none has been licensed by the FDA.

The advantage of mRNA vaccines over more traditional vaccines is they can be made quickly. The company says it was just 63 days from the time Chinese scientists revealed the genetic sequence to the time a vaccine was injected into the first volunteer.

Moderna’s is one of about a dozen COVID-19 vaccine candidates that have begun studies in humans.




The coronavirus is a moving target

The coronavirus is a moving target for efforts to tackle it - Axios

Solutions for COVID-19 are being developed at the same time as knowledge about the disease evolves, a serious challenge for doctors treating patients and for researchers trying to create vaccines and treatments.

Why it matters: What was first thought of as a respiratory infection now appears much more complex, making efforts to tackle the disease more complicated.

“We’re laying the track as the train is moving and the train is coming very fast,” says Mark Poznansky, director of the Vaccine & Immunotherapy Center at Massachusetts General Hospital. “That is an extraordinary place to be at the global level.”

What’s happening: When the world first encountered COVID-19 four months ago, it was deemed a respiratory infection that hammers the lungs. That’s still the case but in recent weeks, clinicians have been reporting wide-ranging manifestations of the disease in some people.

  • Some of this could be that, with enough cases, there are outliers and anomalies. But that underscores that doctors and researchers are learning as they go.

Details: Renal failure, sepsis, damaged blood vessels, skin lesions, stroke, gastrointestinal problems and blood clots in the lungs and kidneys are being seen in some COVID-19 patients.

  • 20% of hospitalized patients in one study in Wuhan, China had heart damage.
  • 31% of people with the disease studied in a Danish ICU had blood clots.

“It comes across more as a systemic disease exhibited initially as a respiratory disease,” says Poznansky. It’s unclear whether the cause is the virus itself, the immune system’s response to it, or the treatment received.

That has implications for developing vaccines. The goal is to prevent infection but not exacerbate the immune effects in response to the virus.

  • “Is [a vaccine] protective or not in a context where we don’t know what exactly defines a protective immune response to COVID-19?” asks Poznansky.
  • The evolving understanding underscores the need to have multiple vaccines in development. (The current count is 123, per the Milken Institute’s tracker.)

What to watch: The changing percent of the disease will feature in regulatory discussions.

  • “This is the question companies will be discussing with regulators: which surrogate endpoints are acceptable as a proxy for going all the way to the worst possible outcomes in a patient?” says Phyllis Arthur, vice president of infectious diseases and diagnostics policy at biotech trade organization BIO.

The bottom line: Pandemics bring a potent mix of uncertainty and urgency to science that experts say requires both nimbleness and rigor to navigate.

  • “This is what a pandemic is like. It’s uncomfortable,” says Arthur. “You need to move swiftly and do good, solid, evidence-based, risk-benefit ratio assessments and understand what you know and don’t know, and make evidence based policy decisions knowing you don’t have perfect information.”




Reopening the U.S. Economy

Click to access report.pdf

Allison Nathan, senior strategist for Goldman Sachs Research, discusses her latest Top of Mind report where she speaks with leading experts across health and policy to understand how well-positioned the U.S. is to achieve a safe reopening of the economy and how quickly it would translate into economic recovery. 

With COVID-19 mitigation measures leading to an apparent leveling off of case
growth globally at the same time that the economic costs of such measures continue
to mount, several countries around the world have begun to plan for—or have
already started to implement—economic reopening. But absent herd immunity or
a vaccine for the virus, such reopenings increase the risk of disease resurgence.
With this in mind, what a safe reopening might look like, how well-positioned the
US is to achieve one and how quickly reopening would really translate into economic
recovery is Top of Mind. We consult three experts on these questions: University of
Pennsylvania’s Dr. Zeke Emanuel, Duke University’s Dr. Mark McClellan and Harvard
University’s Dr. Barry Bloom. And we share our own take on a potential US recovery path, informed by lessons from
China’s reopening experience so far. Finally, with more complete economic normalization only likely with an effective
testing regime, treatments, or a widely available vaccine for COVID-19-we discuss where we are on all of the above.