This years graduating Harvard Medical School (HMS) students will have the option to receive their diplomas early so that, if they choose, they can quickly be deployed into hospitals where regular staff might soon be overwhelmed with COVID-19 patients.
Fourth-year HMS students who have completed all their training and degree requirements, as well as graduating M.D. students from Boston University, Tufts University, and the University of Massachusetts, are being given the option to receive their diplomas before their scheduled graduation date in May.
The change comes in response to a request to the schools from Massachusetts Gov. Charlie Baker and Massachusetts Secretary of Health and Human Services Marylou Sudders, citing an expected escalation in local health care workforce needs.
Approximately 700 medical students in the Boston area are slated to graduate this spring.
Because Harvard University grants HMS M.D. degrees, there were administrative issues to address before the option can become official for HMS students, including deliberation and voting by the Harvard Corporation and the Universitys Board of Overseers.
On March 30, the governing boards had approved the proposal, voting in view of the extraordinary circumstances posed by the COVID-19 pandemic, to authorize the dean [of the Faculty of Medicine] to approve the early conferral of degrees on students who are currently candidates for Doctor of Medicine (M.D.) degrees scheduled to be conferred in May 2020, once such students have been deemed to have completed the requirements for the M.D. degree by the registrar of Harvard Medical School. The boards said approval must also be granted by University Provost Alan Garber.
Students enter our medical schools aspiring to serve and heal. I have never been more proud of our students, many of whom have already expressed their eagerness to graduate early so they can join our hospitals on the front lines to help treat patients amid this pandemic, said HMS Dean George Q. Daley. We need their skill and compassion now more than ever, and many are ready, willing and able to answer the call.
HMS Dean for Medical Education Edward Hundert told graduating students on a teleconference on March 26 that a number of details must be worked out in the coming weeks. He also emphasized that early graduation will be entirely voluntary and that individual hospital programs where students have matched may or may not build this option into their COVID-19 contingency plans.
I feel very lucky that I am on the cusp of completing medical school at this time because it means I have been trained with skills that might allow me to make a meaningful difference providing clinical care during this pandemic.
Josephine Fisher, graduating HMS student
This is evolving, Hundert told the students, and it will be entirely optional. We want to make this available for those who would like to respond if asked and give our students the option to serve in this way.
Hundert and HMS Dean for Students Fidencio Saldaa told students that those meeting all degree requirements could be allowed to graduate as early as mid-April, more than a month before regularly scheduled Commencement ceremonies and two months before most internships begin.
Any studentcan also choose to wait until May to graduate.
Students considering the early graduation option will have to considerhow losing student status early might affect their health insurance, their housing and visas, and their student loan deferral status. Hundert and Saldaa said HMS is working to provide answers to all such questions before mid-April.
This decision is a personal one, and no one should feel pressured by it, said Saldaa.
Graduating HMS student Josephine Fisher, who matched last week to Massachusetts General Hospitals internal medicine/primary care program, said she is excited that HMS will be offering the early graduation option.
One of the hardest parts for me is feeling that, as of right now, we are not able to help on the front lines as much as we would like, Fisher said. Though I feel nervous about the risks posed to myself, and even more so to my family, who I risk exposing when I return home from work, I feel very lucky that I am on the cusp of completing medical school at this time because it means I have been trained with skills that might allow me to make a meaningful difference providing clinical care during this pandemic.
Hundert said educational leaders at HMS teaching affiliates, such as Mass General, Brigham and Womens Hospital, Beth Israel Deaconess Medical Center, and Cambridge Health Alliance, welcomed the news that they might be able to build the possibility of M.D. student reinforcements into their COVID-19 contingency plans, particularly if current interns and residents become ill and are unable to care for patients.
They all said this was new information for them as it is for us, and that they would assess how this new possibility could potentially enhance their options as they consider workforce needs, Hundert said, telling the students on the call that it would likely be at least a week before hospitals let HMS know how and when graduating students might be invited to participate as needs evolve over the coming weeks.
Each hospital, and each clinical department, will decide whether and how this would enhance their efforts, Hundert said. The hospitals will let HMS and the students know what their needs are.
For many of the graduating students, the next few weeks will be a time of uncertainty.
I know that some residency programs reached out to their future interns inquiring about their willingness to volunteer and join the intern workforce earlier. I will wait and see if my program has such an offering, said graduating HMS student Ameen Barghi,who was accepted into the orthopedic surgery program at Wake Forest Baptist Medical Center in North Carolina.
I have matched at a hospital outside of Massachusetts, so out of this pool of newly minted doctors, I might not be anyones first call. This is because hospitals, for on-boarding and other purposes, will likely bring in those who matched at their institutions first. That being said, if one of the HMS hospitals or my new institution asked me to come in and help patients on the front lines, Id do it in a heartbeat, said Nora Torres Yordan, who matched to the obstetrics/gynecology program at the University of Chicago Medical Center.
According to Sudders, the Massachusetts Board of Registration in Medicine is prepared to grant M.D. students who choose to take the early graduation option a special 90-day limited provisional license to practice, after which they would be able to start in a pre-internship COVID-19 service role, according to Hundert.
Students also have the option of graduating early and not working in the hospitals immediately, Hundert said, and some hospital programs may not issue a call for them.
It is unclear whether the provisional license issued by Massachusetts would be accepted in other states where HMS students have matched. Saldaa and Hundert said medical schools across the U.S. are considering early graduation options, with New York universities leading the way in giving students the choice.
Nearly one in three licensed doctors in the United States is older than 60 years, an age-group particularly vulnerable to adverse outcomes from COVID-19, according to a study published today on the preprint server medRxiv. And New York and California, two hard-hit states, have the most older physicians.
"The physician workforce is not only at risk of losing time spent in clinical care due to these exposures, but at a personal risk from severe disease that requires hospitalization and is associated with high morbidity and mortality," the authors said, noting that 80% of deaths in China were in people 60 and older and that, in the United States, nearly half of hospitalizations and intensive care admissions and up to 80% of deaths have been in that age-group.
Because excluding doctors older than 60 from patient care would severely strain the medical workforce, the authors suggest limiting their direct patient care and expanding their telehealth capabilities.
The researchers extracted summary data from the 2018 Federation of State Medical Boards physician database on doctor age-groups overall and by state to identify those at high risk due to their age and determine whether it would be feasible to exclude them from the medical workforce for this reason.
They found that of the country's 985,026 licensed doctors, 235,857 (23.9%) are 25 to 40 years old, 447,052 (45.4%) are 40 to 60, 191,794 (19.5%) are 60 to 70, and 106,121 (10.8%) are 70 or older. Age was not reported in 4,202 (0.4%) of doctors.
Overall, 297,915 (30.2%) of physicians are 60 years and older. According to state reports, a median of 5,470 licensed physicians (interquartile range [IQR], 2,394 to 10,108) are 60 years or older.
North Dakota (1,180) and Vermont (1,215) had the fewest doctors 60 and older, while California (50,786) and New York (31,582) had the most. The median proportion of doctors in this age-group across states was 28.9% (IQR, 27.2%, 31.4%), ranging from 25.9% in Nebraska to 32.6% in New Mexico.
"We do not have information on the specialty expertise of physicians, as some physicians may be more prone to encountering patients with COVID-19," the authors wrote. "However, as many individuals in the community may be asymptomatic carriers, physicians across specialties are at risk of acquiring the disease as a part of the patient contact during care delivery."
They also noted that doctors may be licensed in more than one state and that the absence of data on their health status could change their risk levels.
Peter Buerhaus, PhD, RN, director of the Center for Interdisciplinary Health Workforce Studies at Montana State University College of Nursing in Bozeman and co-author of a commentary on older clinicians and coronavirus yesterday in JAMA, said in an interview that healthcare systems need to plan for how to deploy frontline staff in the crisis to ensure workforce continuity and robustness.
"It's time to think about what we do with our older workforce," he said. "Are there things we can do to keep them less exposed?"
While every system will be affected differently depending on outbreak severity and availability of resources, Buerhaus said that some older doctors, particularly in rural areas, may have no choice but to provide direct patient care, exposing themselves to the virus and potentially reducing patient access to care where it is already limited.
But in less hard-hit areas or in hospitals with sufficient resources, it might make sense to have older physicians deliver telemedicine to keep more patients at home and out of the emergency department, as well as protect themselves. "Patients are told 'stay home,' but they may have questions," he said.
Older physicians could also coach less experienced doctors in making the difficult decisions they may face in the pandemic, or be a community resource. "Getting a well-known, respected physician in front of the community can be very powerful," he said.
Buerhaus added that hospital executives need to understand that the death of an older, established healthcare provider not only will result in the loss of that doctor's knowledge and ability to nurture future providers, it can also devastate hospital staff. "If you lose a beloved physician or nurse in an organization, that hurts, and it can have a very harmful effect on morale," Buerhaus said.
WARREN (WJW)A couple months ago a Warrenfamily says they werent too concerned about the Coronavirus.
Irene Culetsu said she felt her family was safe. She said she, her husband and two adult sons did not recently travel outside the United States. They all worked locally, she as a teacher, and her husband at the Trumbull County maintenance department.
I figured we wouldnt get the Coronavirus because we dont do anything, Irene told the Fox 8 I-Team. We stay home, but boy was I wrong.
She, her husband, her two sons Dino and Manoli, and Dinos girlfriend, MaryFay Dimitriadis, all have tested positive for COVID-19.
It started around March 15, when her son Manoli, and her husband of 31 years, George, started coughing. At first, they thought it was just the normal cough George seems to get yearly but soon he developed a fever. He went to a drive-in test site on March 20 and was admitted to a hospital.
His oxygen levels were low and they said he had pneumonia, Irene said. He got worse and last Wednesday they put him on a ventilator.
On Friday they learned George tested positive for COVID-19. The family then got tested and learned they too had the virus. They are quarantined at home, while George remains hospitalized and in a medically induced coma.
We need a miracle, Irene said. When he was very sick and they were worried about him not making it, they said only two people can go to see him. How could I choose which son would come up with me? I couldnt so I had the priest came up with me.
They continue to call the hospital several times a day for an update.
Not being able to hold him, or talk to him is a nightmare, its a nightmare, Irene said. He needs a rotating bed to help him with his breathing and we are working with the doctors to try and get him one.
The family says they are praying for everyone who has the Coronavirus and are asking for prayers for George. He is 67-years-old and has a birthday Friday.
He is a good man, Irene said. We are praying for George, asking God to answer our prayers and put his hands over him and heal him.
The United States Environmental Protection Agency (EPA) announced on Thursday that it is temporarily relaxing enforcement of environmental regulations and fines during the COVID-19 outbreak. The enforcement discretion policy applies retroactively to March 13, with no end date set yet.
The new policy follows lobbying from industries including oil and gas, which told the Trump administration that relaxed regulations will allow them to more efficiently distribute fuel during the outbreak, but because it is broadly written, it could potentially influence companies actions in a large range of industries, including tech.
It may also create new challenges for researchers and scientists, since while the policy is in effect, companies are being asked only to make data from monitoring available to the EPA if requested by the agency.
The EPA said the policy addresses different categories of noncompliance differently. For example, the EPA said it will not seek penalties for noncompliance with monitoring and reporting that are the result of the COVID-19 pandemic, but that it still expects public water systems to provide safe drinking water.
EPA is committed to protecting human health and the environment, but recognizes the challenges resulting from efforts to protect workers and the public from COVID-19 may directly impact the ability of regulated facilities to meet all federal regulatory requirements, said EPA administrator Andrew Wheeler in the agencys announcement.
The policy places more onus for adhering to environmental regulations on the private sector. Depending on how the policy is carried out and how long it lasts, it may impact the work of tech companies that are developing tools to measure air pollution (for example, Googles Project Air View, which launched last year to provide air quality data gathered with startup Aclimas sensors to scientists and researchers), or that focus on environmental monitoring and compliance.
Susan Parker Bodine, the assistant administrator for enforcement and compliance assurance at the EPA, wrote in a memo about the policy that in general, the EPA does not expect to seek penalties for violations of routine compliance monitoring, integrity testing, sampling, laboratory analysis, training, and reporting or certification obligations in situations where the EPA agrees that COVID-19 was the cause of the noncompliance and the entity provides supporting documentation to the EPA upon request.
In July 2019, data released by the EPA showed that the number of unhealthy air days in major U.S. cities had increased over the past two years, even as combined emissions of major air pollutants fell.
Critics say that the policy will not only result in more pollution, but also make it impossible to fully assess the environmental damage.
In a statement to the Hill, Cynthia Giles, who headed the EPAs Office of Enforcement during the Obama administration, said the new policy tells companies across the country that they will not face enforcement even if they emit unlawful air and water pollution in violation of environmental laws, so long as they claim that those failures are in some way caused by the virus pandemic. And it allows them an out on monitoring too, so we may never know how bad the violating pollution was.
Tuesday afternoon, Governor Gretchen Whitmer sat down with 9&10 News for an interview over video chat to give updates on the fight against COVID-19.
It can and will impact everyone so everyone of us needs to do our part, says Gov. Whitmer.
Its been exactly three weeks since Michigan announced their first positive COVID-19 tests.
As of Tuesday, the number is over 7,600 with more than 250 deaths.
This conversation that were having, people are looking at numbers on the news and not really pausing to take in that its a serious situation, says Whitmer.
She says the biggest hurdles are mitigating spread through executive order and keeping up with supplies from out of state sources.
112,000 masks sounds like we fixed the problem, says Whitmer, But really it just bought us a couple more days.
Last night, Bridge Magazine reported Whitmer will cancel the rest of the school year.
They do great reporting, says Whitmer, But theyre not on the mark on this one. I have not made a final decision yet.
Cancellation would cut the school year short by three months.
If it was a matter of just flipping a switch and saying we just all transition to online learning and everyone had the capacity to do it, that would be one thing, says Whitmer, But we know thats out of reach. Thats why its really important that we take the time to make sure that we get it right.
This morning, Representative Triston Cole asked for softer restrictions on the stay at home order for certain workers.
It is possible for many of the entities listed in the letter to conduct business while being responsible with social distancing, says Rep. Cole.
Like landscapers, construction workers and farmers.
I am hopeful, says Cole, That this is something that I will get a positive response from.
No, says Whitmer.
She says this is not the time to let up.
The more porous our policy, the less likely it is to work, says Whitmer, Thats precisely why we have to be aggressive. Weve been on the leading edge and yet were still a national hotspot right now.
The governor reassures this will eventually end and some good can come of this, like lessons for the future.
Its really important that we take these lessons and we get serious about building up the United States for times like these, says Whitmer, Because there will be more.
Jennifer Haller receives the first administration of an mRNA vaccine, made by the biotech firm Moderna, against the pandemic coronavirus.
By Jon CohenMar. 31, 2020 , 5:15 PM
Sciences COVID-19 reporting is supported by the Pulitzer Center.
The coronavirus that for weeks had been crippling hospitals in her hometown of Seattle changed Jennifer Hallers life on 16 Marchbut not because she caught it. Haller, an operations manager at a tech company in the city, became the first person outside of China to receive an experimental vaccine against the pandemic virus, and in the days since, she has been flooded by an outpouring of gratitude. Theres been overwhelming positivity, love, and prayers coming at me from strangers around the world, Haller says. We all just feel so helpless, right? This was one of the few things happening that people could latch on to and say, OK, weve got a vaccine coming. Disregard that its going to take at least 18 months, but its just one bright light in some really devastating news across the world.
The vaccine Haller volunteered to test is made by Moderna, a well-financed biotech thathas yet to bring a product to market. Moderna and Chinas CanSino Biologics are the first to launch small clinical trials of vaccines against coronavirus disease 2019 (COVID-19) to see whether they are safe and can trigger immune responses. (The CanSino vaccine trial also began on 16 March, according to researchers from the Chinese militarys Institute of Biotechnology, which is collaborating on it.) An ever-growing table put together by the World Health Organization now lists 52 other vaccine candidates that could soon follow. This is a wonderful response from the biomedical community to an epidemic, says Lawrence Corey, a virologist at the Fred Hutchinson Cancer Research Center who has run vaccine trials against a dozen diseases but is not involved with a COVID-19 effort. Its both gratifying and problematic in the sense of how do you winnow all this down?
Broadly speaking, these vaccines group into eight different platformsamong them old standbys such as inactivated or weakened whole viruses, genetically engineered proteins, and the newer messenger RNA (mRNA) technology that is the backbone of the Moderna vaccineand their makers include biotechs, academia, military researchers, and a few major pharmaceutical companies. On 30 March, Johnson & Johnson (J&J) announced what it said could bea $1 billion COVID-19 vaccine project, with about half the money coming from the U.S. Biomedical Advanced Research and Development Authority if milestones are met.
Many viruses, including HIV and hepatitis C, have thwarted vaccine developers. But the new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), doesnt appear to be a particularly formidable target. It changes slowly, which means its not very good at dodging the immune system, and vaccines against the related coronaviruses that cause SARS and Middle East respiratory syndrome (MERS) have worked in animal models. Corey heads the United Statess HIV Vaccine Trials Network, which has seen one candidate vaccine after another crash and burn,is optimistic about a SARS-CoV-2 vaccine. I dont think this is going to be that tough.
One concern is whether people develop durable immunity to SARS-CoV-2, which is crucial given that vaccines try to mimic a natural infection. Infections with the four human coronaviruses that typically cause minor colds dont trigger long-lasting immunity. Then again, researchers have found long-lasting immune responses to the viruses causing SARS and MERS, and genetically they are far more like SARS-CoV-2. And unlike cold-causing viruses, which stay in the nose and throat, the new coronavirus targets the lower respiratory tract, where the immune response to a pathogen can be stronger, says Mark Slifka, an immunologist who studies vaccines at the Oregon National Primate Research Center. When you get an infection in the lungs, you actually get high levels of antibodies and other immune cells from your bloodstream into that space.
Even with this all-out effort, Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases (NIAID), predicts getting a vaccine to the public is going to take a year, a year and a half, at least. And Fauci adds at least because side effects, dosing issues, and manufacturing problems can all cause delays. Already some are calling for an ethically fraught shortcut to speed up clinical trials: giving people candidate vaccines and then intentionally attempting to infect them to see whether theyre protected.
A new vaccine might also be made available to health care workers and others at high risk even before phase III efficacy trials are completed. And Stanley Perlman, a veteran coronavirus researcher at the University of Iowa, suggests a vaccine that only offers limited protection and durability could be good enoughat first. In this kind of epidemic setting, as long as you have something that tides us along and prevents a lot of deaths, that may be adequate, he says.
On 13 January, 3 days after Chinese researchers first made public the full RNA sequence of SARS-CoV-2, NIAID immunologist Barney Graham at sent Moderna an optimized version of a gene that would become the backbone of its vaccine. Sixty-three days later, the first dose of the vaccine went into Haller and other volunteers participating in the small trial at the Kaiser Permanente Washington Health Research Institute. In 2016, Graham had made a Zika virus vaccine that went from lab bench to the first volunteer in what he then thought was a lightning-fast 190 days. We beat that record by nearly 130 days, he says.
The effort benefited from lessons Graham learned from his past vaccine efforts, including his work on respiratory syncytial virus (RSV). The search for an RSV vaccine has a checkered past: in 1966, a trial of a candidate vaccine was linked to the death of two children. Later studies identified the problem as vaccine-triggered antibodies that bound to the surface protein of the virus but did not neutralize its ability to infect cells. This antibody-viral complex, in turn, sometimes led to haywire immune responses.
The World Health Organization has tallied dozens of vaccine candidates, based on a variety of technologies. Two have started human safety trials (*).
Studying the 3D structures of the RSV surface protein, Graham discovered that the dynamic molecule had different orientations before and after fusing with the cell. Only the pre-fusion state, it turned out, triggered high levels of neutralizing antibodies, so in 2013 he engineered a stable form of the molecule in that configuration. It was so clear at that point that if you didnt have structure, you didnt really know what you were doing, Graham says. An RSV vaccine that built on this concept hasworked wellinearly trials.
The experience came in handy in 2015, when a member of Grahams lab made a pilgrimage to Mecca, Saudi Arabia, and came back ill. Worried that it might be MERS, which is endemic in Saudi Arabian camels and repeatedly jumps into humans there, Grahams team checked for the virus and instead pulled out a common cold coronavirus. It was relatively easy to determine the structure of its spike, which then allowed the team to make stable forms of the spikes for the SARS and MERS viruses, and, in January, for SARS-CoV-2s. Thats the basis of the Moderna COVID-19 vaccine, which contains m RNA that directs a persons cells to produce this optimized spike protein.
Still a new strategy, no mRNA vaccine has yet reached a phase III clinical trial, let alone been approved for use. But producing huge numbers of vaccine doses may be easier for mRNA vaccines than for traditional ones, says Mariola Fotin-Mleczek of the German company CureVac, which is also working on mRNA vaccine for the new coronavirus. CureVacs experimental rabies vaccine showed a strong immune response with a single microgram of mRNA. That means 1 gram could be used to vaccinate 1 million people. Ideally, what you have to do is produce maybe hundreds of grams. And that would be enough, Fotin-Mleczek says.
Many companies are relying on time-tested techniques. Sinovac Biotech is making a SARS-CoV-2 vaccine byinactivating whole virus particles with formaldehyde and adding an immune booster called alum. Sinovac used the same strategy for a SARS vaccine it developed and tested in a phase I clinical trial 16 years ago, says Meng Weining, a vice president at Sinovac. We immediately just restarted the approach we already know. The companys SARS vaccine worked in monkeys and although there were concerns that an inactivated coronavirus vaccine might trigger the sort of antibody enhancement disease that occurred with the RSV vaccine, Meng stresses that no such problems surfaced in their animal studies.
Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai, says inactivated virus vaccines have the advantage of being a tried-and-true technology that can be scaled up in many countries. Those manufacturing plants are out there, and they can be used, says Krammer, who co-authored a status report about COVID-19 vaccines that appears online inImmunity.
CanSino is now testing another approach. Its vaccine uses a nonreplicating version of adenovirus-5 (Ad5), which also causes the common cold, as a vector to carry in the gene for the coronavirus spike protein. Other vaccine researchers worry that because many people have immunity to Ad5, they could mount an immune response against the vector, preventing it from delivering the spike protein gene into human cellsor it might even cause harm, as seemed to happen in a trial of an Ad5-basedHIV vaccine made by Merck that was stopped early in 2007. But the same Chinese collaboration produced an Ebola vaccine, which Chinese regulators approved in 2017, and a company press release claimed its new candidate generated strong immune responses in animal models and has a good safety profile. I think pre-existing Ad5 immunity and HIV vaccine risk are not a problem, Hou Lihua, a scientist working on the project at the Institute of Biotechnology, wrote in an email to Science, noting that the Ebola vaccine trial results adds to their confidence that these will not be issues.
Disregard that [a vaccine is] going to take at least 18 months, but its just one bright light in some really devastating news across the world.
Other COVID-19 vaccine platforms include a laboratory-weakened version of SARS-CoV-2, a replicating but harmless measles vaccine virus that serves as the vector for the spike gene, genetically engineered protein subunits of the virus, a loop of DNA known as a plasmid that carries a gene from the virus, and SARS-CoV-2 proteins that self-assemble into viruslike particles. J&J is using another adenovirus, Ad26, which does not commonly infect humans, as its vector. These different approaches can stimulate different arms of the immune system, and researchers are already challenging vaccinated animals with SARS-CoV-2 to see which responses best correlate with protection.
Many researchers assume protection will largely come from neutralizing antibodies, which primarily prevent viruses from entering cells. Yet Joseph Kim, CEO of Inovio Pharmaceuticals, which is making a DNA COVID-19 vaccine, says a response by T cellswhich clear infected cellsproved a better correlate of immunity in monkey studies of the companys MERS vaccine, which is now in phase II trials. I think having a balance of antibody and T cell responses probably is the best approach.
Kim and others applaud the variety of strategies. At this early stage, I think it makes sense to try anything plausible, he says. As Stephan Bancel, CEO of Moderna, says, Nobody knows which vaccines are going to work.
Spurring many of the efforts in the nascent COVID-19 field has been the Coalition for Epidemic Preparedness Innovations (CEPI), a nonprofit set up to coordinate R&D for vaccines against emerging infectious diseases. So far, CEPI has invested nearly $30 million in vaccine development at Moderna, Inovio, and six other groups. We have gone through a selective process to pick the ones that we think have the greatest likelihood of meeting our goalswhich we think ought to be the worlds goalsof speed, scale, and access, says CEPI CEO Richard Hatchett.But he is rooting for other candidates as well. We dont want to be in a situation where we have [one] successful vaccine and we have a contamination event [during manufacturing] and suddenly we dont have any vaccine supply.
CEPI invests in manufacturing facilities at the same time it puts money into staging clinical trials. By doing things in parallel rather than in serial fashion, we hope to compress the overall timelines, Hatchett says. After reviewing phase I data and animal model data, CEPI plans to move six of the eight products into larger safety studies to arrive at three that are worthy of full-scale efficacy trials that enroll perhaps 5000 participants.
CEPI has less than $300 million in its coffers for the effort, and Hatchett estimates the price tag at $2 billion. He says CEPI hopes to raise this money from governments, private philanthropies, industry, and the United Nations Foundation.
Seth Berkley, who heads Gavi, the Vaccine Alliance, arguedin an editorial in the 27 March issue ofSciencethat the world needs to come together even more to streamline the search for a COVID-19 vaccine. If ever there was a case for a coordinated global vaccine development effort using a big science approach, it is now, Berkley wrote, stressing that there must be extraordinary sharing of data, coordination of clinical trials, and funding. You cant move 100 vaccines forward, he says.
Moderna and J&J both say that if everything goes perfectly, they could launch an efficacy trial with about 5000 people by late November and determine by January 2021 or so whether the vaccine works. Meng says that, depending on approval from Chinese regulatory agencies, Sinovac could move its vaccine through small phase I and II tests by June. But, because of Chinas success at controlling its epidemic, the company may have to find another country that has high transmission of SARS-CoV-2 to stage an efficacy trial quickly.
Haller has had no serious side effects from the mRNA injected into her arm but realizes that the phase I study will not determine whether the vaccine is effective. The chances of the one that I got being really anything? I dont know, Haller says. This is just the first of many, many vaccines, and its just stupid luck that I was the first one.
With reporting by Kai Kupferschmidt.
The biopharmaceutical industry will be able to make a Covid-19 vaccine probably a few of themusing various existing vaccine technologies. But many people worry that Covid-19 will mutate and evade our vaccines, as the flu virus does each season. Covid-19 is fundamentally different from flu viruses, though, in ways that will allow our first-generation vaccines to hold up well. To the extent that Covid does mutate, its likely to do so much more slowly than the flu virus does, buying us time to create new and improved vaccines.
Every virus has a genome composed of genetic material (either RNA or DNA) that encodes instructions for replicating the virus. When a virus infects a cell, it accesses machinery for making copies of its genomic instructions and follows those instructions to make viral proteins that assemble, with copies of the instructions, to form more viruses (which then pop out of the cell to infect new cells, either in the same host or in someone new).
There is a critical difference between coronaviruses and flu. The novel coronavirus genome is made of one long strand of genetic code. This makes it an unsegmented viruslike a set of instructions that fit on a single page. The flu virus has eight genomic segments, so its code fits on eight pages. Thats not common for viruses, and it gives the flu a special ability. Because the major parts of the flu virus are described on separate pages (segments) of its genome, when two different flu viruses infect the same cell, they can swap pages.
Imagine two people with eight-page reports fighting over a copy machine. In the tussle, some copies might turn out to have a mix of pages from two different reports. This page-swapping process, where viruses exchange parts of their genome, is called reassortment. The flu can change rapidly when multiple strains pass through the same host. But coronavirus, as a one-page report, tends to stay together, and while coronaviruses can swap sectionsin a process known as recombinationit is difficult to achieve and thus rare. (Imagine two pages ripping in the same way and swapping pieces that get glued together again.)
Coronavirus does mutate. All viruses mutate, in a way that can be likened to typos introduced by the copying process. Instead of a copy machine, imagine that a page of text is read by a scanner that then attempts to transcribe the words into a text file. The scanner may transcribe a page of text imperfectly, introducing a I for a l, and when thats printed out and then scanned again, the scanner makes more transcription mistakes on top of the old ones. After many cycles, the accumulating mutations in the code cause features of the virus to change gradually, a process called drift. When flu virus swaps entire pages with a different flu virus in a reassortment, we call that shift. Drift through typos tends to cause small changes. Shift through reassortment causes bigger ones.
A vaccine is like a description of a wanted criminal: it tells your immune cells whom to look out for. So long as the suspects appearance doesnt change too much, then the vaccine works. To the extent that the flu virus we see one year is only slightly different than the ones weve seen in recent years, our immune systems are at least partially prepared, and so we are partly protected. Even if we do get infected, it might be a milder illness because our immune system can react more quickly to fight it off.
Laboratories around the world are constantly surveilling todays flu strains and giving flu-vaccine manufacturers a heads-up as to what the viruses look like. So if we see a new strain of flu in Asia, its probably a good idea to start making a vaccine against it for the U.S. before that strain comes to our shores. Because large-scale manufacturing of current flu vaccines takes about six months from the time when we spot a new flu strain, the vaccines are six months out of date by the time we get them. Some years, the flu swaps out a genomic page with a less familiar strainmaybe one we havent seen for a decade or soand we get the vaccine wrong. When that happens, we suffer through a bad flu season, since our immune systems are less ready to fight it off.
In the worst case, the flu can suddenly pick up a page from a bird- or pig-flu strain to which most humans have had zero exposure. This can be far more deadly, because the new virus can evade our herd immunity entirely, cutting through the population unopposed. Thats a flu pandemic.
Todays novel coronavirus was brewing within bats for a long time, mutating into its current form through various typos and, to a lesser extent, rare recombination events among coronaviruses. Now that its here, its as new to us as a shifted flu strain that weve never seen before, and its causing a pandemic. But once weve developed a vaccine for this strainand once weve all taken itwell have herd immunity to it.
That immunity may fade as our immune system forgets the picture that the vaccine showed it, but we can solve that by getting booster shots of the same Covid-19 vaccine periodically. What we dont have to worry about is the virus rapidly mutating away from our vaccines as fast as flu can, because owing to its simplicity, it cant pull off the flus face-swapping tricks.
We hear reports that the novel coronavirus is already mutating into new strains, but these mutations are minor, and theyre unlikely to add up to anything significant. Even identical human twins have many genetic differences between them, but we still think of them as identical. In the case of Covid-19, very few of the changes weve seen so far would affect a vaccine. But if such changes do accumulate over time, our vaccine programs will be able to keep up.
Think of it this way: if flu evolves with the speed of a growing vine, then coronavirus is like a cactus. If you look very closely, a cactus can appear to be changing from day to day, but its nothing like a vine.
Were now inventing new vaccines from scratch and could plausibly go from nothing to a marketed vaccine in about a year. If laboratories around the world detect that this coronavirus is changing gradually, well most likely have time to match new strains before they change enough to cause a new outbreak. Rest assured: a vaccine is coming, it will work, and it will continue to work for as long as humanity must contend with Covid-19. Until then, we must maintain our social distancing so that our strained health-care system can keep up with the infections that we cant seem to prevent.
Peter Kolchinsky, a biotechnology investor and scientist, is Managing Partner of RA Capital Management, L.P., and author of The Great American Drug Deal.
Photo: Meyer & Meyer/iStock
The devastation that coronavirus is causing around the globe will come to an end, but the questions on everyones lips is 'how' and 'when'. Despite strategies deployed to contain and limit the spread of the disease, the answer to the first part of the question is with the introduction of a vaccine. The second part regarding a timescale is at best an estimation.
Numerous companies across the globe are attempting to find a workable vaccine, and progress has been aided by the sharing of early information on the virus by China. The analysis that has followed in laboratories has advanced at pace, with studies into just how Sars-CoV-2 infects human cells. It is believed that there are already at least four organisations with potential vaccines, which are being tested on animals to see the effects. One, by American company Moderna, is expected to enter human trials very soon.
It may not feel like it to the average person who is suffering through the current situation, but scientists have had a head start on finding a solution to Covid-19. We have, in recent memory, experienced other coronavirus epidemics - with Sars in China (2002-04) and Mers from Saudi Arabia (2012) - and the work being done on a vaccine now builds on the back of that done then and put to one side.
Picture shows containers for the samples taken to drivers at a drive-through testing point for the COVID-19 disease at the University Hospital in Burgos.CESAR MANSO(AFP)
Human clinical trials take time. First the vaccine must be checked for safety, then for effectiveness to a group of a few hundred, and finally in a much larger group. Jumping ahead of this process - which can be tempting given the large number of people dying on a daily basis - is not prudent and this is why having a decent batch of candidates is important. Many of them will fail at one of the stages, and the hope is that one of them passes through to final approval.
Despite the blindly optimistic claims from US President, Donald Trump in early March, vaccines have sometimes taken decades to reach that approval stage. The general advice from the experts in this field suggest that around 18 months will be required. That takes us to the summer of 2021, quite some distance away, but a relatively speedy delivery in the world of vaccinologists.
Sin tituloA researcher works on the development of a vaccine against the new coronavirus COVID-19, in Belo Horizonte, state of Minas Gerais, Brazil.DOUGLAS MAGNO(AFP)
And having a vaccine approved is sadly not the end of the process. Political and economic challenges can make it a complicated to get the vaccine out to the many millions who require it. Often countries prioritise their key workers, like those in healthcare, as well as the defined at risk groups of the population. Richer countries tend to use their financial muscle too, meaning others can lose out relatively.
Providing people with an accurate date therefore of when a vaccine for Covid-19 will be ready for them to be administered is impossible. The belief is that we will come out of the worst of this, and possibly go through another spell at least, before one is ready for the general population. Clearly, there is an abundance of work being done to have it available as soon as it can be. Until then, the general advice of isolation, distancing, hygiene, etc, as well as the introduction of mass testing, must be followed to keep the spread in check.
Johnson & Johnson says it could have a COVID-19 vaccine available by early 2021 with the capability to produce as many as a billion doses. In a press release, the company says its planning to start clinical trials in September and has begun investing in a rapid production capability to make the vaccine at scale should it prove safe and effective. Johnson & Johnson began work on a possible vaccine in January and has now selected a lead candidate vaccine and two backups which will enter early production phases to prepare for the expected overwhelming demand. If early trials validate the companys vaccine, the company would need an emergency use authorization from the FDA to begin providing the vaccine.
While many scientists are working on developing a coronavirus vaccine, others are busy testing antiviral drugs.
Vaccines are generally only effective when administered prior to infection, but antiviral agents are important because they can treat people who already have COVID-19.
Heres an overview of antiviral drugs scientists are investigating for coronavirus.
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How do antiviral drugs work? First, its important to understand the genome of animals and plants is composed of deoxyribonucleic acid (DNA), but viral genomes can also be comprised of ribonucleic acid (RNA). This is the case for SARS-CoV-2 coronavirus the virus that causes COVID-19.
In order to replicate, an RNA virus needs to make more copies of its RNA genome. This means antiviral drugs which block the copying of RNA genomes can potentially help treat COVID-19 patients. These drugs are known as RNA-polymerase inhibitors.
Read more: Here's why the WHO says a coronavirus vaccine is 18 months away
These types of drugs have successfully cured people of chronic hepatitis C another RNA virus infection.
But not all viral RNA polymerases are the same, so the drugs that work for hepatitis C virus will not necessarily work for human coronaviruses.
Favilavir is an RNA polymerase inhibitor drug scientists are currently trialling against coronavirus.
Another successful antiviral drug strategy is to use non-functional analogues, or inauthentic copies of the basic building blocks of the viral RNA genome. The presence of these analogues in the viral genome blocks the viral polymerase, meaning the virus cannot make another copy of its RNA. Acyclovir, ribavirin and azidothymidine (AZT) are examples of these drugs.
Unfortunately, this coronavirus is a bit tricky, because it proofreads the authenticity of its RNA genome. As such, it identifies the analogues as being inauthentic and removes them. This stops certain antiviral drugs like ribavirin from being effective.
Fortunately, the coronavirus proofreading powers dont block a similar drug, remdesivir. So remdesivir potently halts coronavirus replication and represents a promising drug option for COVID-19 patients.
Remdesivir is also effective against other RNA viruses including Ebola virus and the coronaviruses SARS and Middle Eastern respiratory syndrome (MERS).
Scientists are currently assessing remdesivir in clinical trials in the United States and China. Time will tell if remdesivir is effective for COVID-19 patients. But doctors are already considering how the drug is best administered for optimal results and whether it should be used in combination with other drugs or as a single agent.
Read more: COVID-19 treatment might already exist in old drugs we're using pieces of the coronavirus itself to find them
Many RNA viruses produce a single multi-protein thats later broken down into individual proteins via enzymes called proteases. Any molecules that inhibit these proteases have potential as antiviral drugs. Viral protease inhibitor drugs have been highly effective in treating the human immunodeficiency virus (HIV) and hepatitis C virus.
Lopinavir and ritonavir are a combination protease-inhibitor drug (Kaletra) that can inhibit coronaviruses in human cells. Kaletra has already been used to treat a patient with COVID-19 in South Korea, but a larger trial found its effects were unconvincing. The reasons for these discrepancies are currently unclear and more research is obviously needed.
With any antiviral drug, the sooner its administered once a patient is infected, the better the outcome. This is because viruses replicate quickly, producing tens to hundreds of new infectious viruses.
In respiratory infections caused by influenza or SARS-CoV-2 viruses, clinically serious infection involves whats called a cytokine storm. Here, a strong immune response results in the production of high levels of inflammatory mediators: cytokines and chemokines.
These molecules recruit inflammatory cells to the site of the virus infection, for example, the lungs of patients with COVID-19. These cytokines and cells then fight the virus infection, but their presence also partly obstructs the air sacs where oxygen exchange occurs.
Researchers are now considering add-on therapies that partly limit the inflammatory response by blocking the effects of certain cytokines and chemokines. These add-on therapies include antibody-based drugs, such as tocilizumab that blocks the interleukin-6 cytokine receptor or leronlimab that blocks the chemokine receptor CCR5. When cytokine receptors and chemokine receptors are blocked then it matters less that there are high levels of cytokines or chemokines, because their effects are significantly minimised.
The good news is antibody-based drugs have minimal side effects, and have proved effective for many human chronic inflammatory diseases. Expanding these drugs for use in COVID-19 patients is therefore an attractive possibility. Although this would require caution for careful dosing, and these drugs would need to be co-administered together with an antiviral drug.
Chloroquine, a well-known anti-malarial drug, has also gained attention. One study tested it together with a broad-spectrum antibiotic azithromycin. While some COVID-19 patients in this small study recovered, other patients died (despite chloroquine treatment), and some patients ceased treatment for a variety of reasons including the severity of their symptoms.
Nevertheless, people are interested in how chloroquine and azithromycin might work for coronavirus. Chloroquine exhibits antiviral activity and is currently used to treat autoimmune diseases because it also has anti-inflammatory properties. Azithromycin is an antibiotic used to treat bacterial infections, but it, too, exhibits antiviral activity, including against rhinovirus that causes the common cold. Chloroquine might need to be given early after infection to be most effective against coronavirus.
Read more: Could chloroquine treat coronavirus? 5 questions answered about a promising, problematic and unproven use for an antimalarial drug
The World Health Organisation has announced a global clinical trial program testing possible COVID-19 treatments, including remdesivir, lopinavir/ritonavir, chloroquine, and certain antiviral cytokines.
The escalating number of coronavirus patients worldwide means alongside vaccine development, the focus must remain squarely on finding effective antiviral drugs that can treat those already seriously ill from SARS-CoV-2 infection.
