People who have recovered from COVID-19 had a robust antibody response after the first mRNA vaccine dose, but little immune benefit after the second dose, according to new research from the Penn Institute of Immunology. The findings, published today in Science Immunology, suggest only a single vaccine dose may be needed to produce a sufficient antibody response. The team found that those who did not have COVID-19 — called COVID naïve — did not have a full immune response until after receiving their second vaccine dose, reinforcing the importance of completing the two recommended doses for achieving strong levels of immunity.
The study provides more insight on the underlying immunobiology of mRNA vaccines, which could help shape future vaccine strategies.
“These results are encouraging for both short- and long-term vaccine efficacy, and this adds to our understanding of the mRNA vaccine immune response through the analysis of memory B cells,” said senior author E. John Wherry, PhD, chair of the department of Systems Pharmacology and Translational Therapeutics and director of the Penn Institute of Immunology in the Perelman School of Medicine at the University of Pennsylvania.
The human immune response to vaccines and infections result in two major outcomes — the production of antibodies that provide rapid immunity and the creation of memory B cells, which assist in long-term immunity. This study represents one of the first to uncover how memory B cell responses differ after vaccination in people who previously experienced infection, compared to those who have not have COVID-19.
“Previous COVID-19 mRNA vaccine studies on vaccinated individuals have focused on antibodies more than memory B cells. Memory B cells are a strong predictor of future antibody responses, which is why it’s vital to measure B cell responses to these vaccines,” Wherry said. “This effort to examine memory B cells is important for understanding long-term protection and the ability to respond to variants.”
The researchers recruited 44 healthy individuals who received either the BioNTech/Pfizer or Moderna mRNA COVID-19 vaccine at the University of Pennsylvania Health System. Of this cohort, 11 had a prior COVID-19 infection. Blood samples were collected for deep immune analyses four times prior to and after vaccine doses.
The data shows key differences in vaccine immune responses in COVID naïve versus COVID-19 recovered individuals. The findings suggest that only a single vaccine dose in individuals recovered from COVID-19 may be enough to induce a maximal immune response, based on both strong antibody and memory B cell responses. This is likely due to a primary immune response because of their natural infection.
In contrast, it took two vaccine doses to demonstrate considerable antibody and memory B cell responses for those who did not have COVID-19, underlying the importance of the two-dose mRNA vaccine schedule to achieve optimal levels of immunity.
These findings were also reflected in an analysis of antibodies against the D614G mutation and the B.1.351 South African variant of COVID-19. For those who did not have COVID-19, it took a second dose to get a robust enough immunity level against the mutation and variant, whereas those recovered from COVID-19 had a strong enough antibody response after one dose.
“This is important for us to keep in mind as we consider vaccination strategies in the future and potential viral variants,” Wherry said. “We need to make sure people have the strongest memory B cell responses available. If circulating antibodies wane over time, our data suggests that durable memory B cells could provide a rapid source of protection against re-exposure to COVID-19, including variants.”
The researchers also examined vaccine-induced side effects in relation to immune responses. While seen in a smaller cohort of 32 COVID naïve people, they found that those who experienced systemic side effects after receiving a vaccine dose — such as fever, chills, headache, and fatigue — had stronger post-vaccination serum antibodies, but not memory B cells. Although more data is needed and all subjects developed robust immunity, it is possible that inflammation and side effects early after vaccination could signal stronger immune reactions.
“Everyone has good responses to the vaccines. They work to protect people against COVID-19. But for those who may be worried about side effects, they are not necessarily a bad thing — they may actually be an indicator of an even better immune response,” Wherry said.
The way that COVID-19, the infectious respiratory disease caused by the SARS-CoV-2 virus, progresses is different for everyone.
Although some people experience no or only mild flu-like symptoms and emerge unscathed from the infection, some require hospitalization and intubation due to respiratory failure and varying levels of organ support. For other people, it is fatal.
Termed “interindividual variation,” health experts have largely attributed these differences in disease progression and outcome to differences in immune function.
Older adults, men, those with preexisting chronic health conditions, and people from minoritized communities are more likely to have severe COVID-19 and die.
When it comes to matters of immunity, however, there is another factor that comes into play: vaccination history.
Vaccines are key elements that train the immune system to fight a variety of pathogens that cause people to fall ill. They also stimulate the “innate” immune response, which is the body’s first line of defense against invaders.
This is the part that has spurred scientists to investigate whether or not previous vaccinations can provide protection against other diseases, including COVID-19.
The notion that old vaccines might help in the fight against COVID-19 has persisted in the scientific community since the early days of the pandemic.
So far, live attenuated vaccines — such as the measles, mumps, and rubella (MMR) vaccine and the bacillus Calmette-Guérin (BCG) vaccine against tuberculosis — have dominated research and discussions on the matter.
For BCG, for example, some research has suggested that the vaccine can “enhance the innate immune response to subsequent infections” and reduce respiratory tract infections.
Newer studies, however, have looked into inactivated vaccines — particularly the diphtheria, tetanus, and pertussis (DTP) vaccines — to see if previous inoculations translate into less severe manifestations of COVID-19.
A 2020 study investigated the bacterial vaccines DTP and meningitis B and deduced that children’s likely protection against SARS-CoV-2 could be down to cross-reactivity prompted by these vaccinations.
Cross-reactivity is an important mechanism for heterologous immunity, which happens when one pathogen induces an immune response to an unrelated pathogen in the future.
Because immunity wanes over time, especially when people do not receive booster shots, the researchers concluded that this could explain why older adults have more susceptibility to COVID-19.
Despite diphtheria, tetanus, and pertussis being caused by bacteria and COVID-19 by a virus, multiple studies have demonstrated heterologous immunityTrusted Source.
A 2021 study in the journal Medical Hypotheses suggested that with the aid of artificial intelligence, tetanus vaccination may be contributing to the reduced severity of COVID-19.
In line with that hypothesis, a recent study — which has not yet undergone peer review — added to existing research and suggested that older adults who have received a diphtheria or tetanus vaccine booster within the past 10 years may have a lower risk of severe COVID-19.
The researchers chose the 10-year timeframe to account for the waning of vaccine-induced antibodies over time. It is also the interval during which experts recommend booster shots.
As part of the study, the researchers analyzed the immunization records and COVID-19 testing data of 103,049 participants, with an average age of 71.5 years, using the UK Biobank cohort.
The researchers took into account age, sex, underlying respiratory diseases, and socioeconomic status.
Participants who had received any of the DTP vaccinations during the past 10 years were, on average, younger and had a higher socioeconomic status than those who had not been vaccinated against these diseases within the same timeframe.
It is important to note that having a lower socioeconomic status, along with a wide range of social determinants of health that contribute to health inequity, may be linked with a higher risk of COVID-19 and worse outcomes, according to previous research.
The results of the UK Biobank analysis showed that those who had received either a tetanus or diphtheria booster were less likely to receive a positive SARS-CoV-2 test. However, more importantly, the researchers found a statistically significant link between the boosters and the likelihood of having severe COVID-19.
Those who had received a tetanus booster were half as likely to develop severe COVID-19, and those who had received a diphtheria booster were 54% less likely.
The researchers found “no significant differences in the likelihood to test positive or [have] a severe case” with the pertussis vaccine, and they noted the small sample size.
The report is available on the medical website medRxiv ahead of peer review.
The Centers for Disease Control and Prevention (CDC) has designated the so-called Delta variant of the coronavirus first identified in India a “variant of concern.”
The designation from the CDC is given to strains of the virus that researchers believe are more transmissible, can cause more severe disease or reduce effectiveness of vaccines or treatments.
The health agency says the B.1.617.2 variant appears to spread more easily from person-to-person than previous strains of the virus and has a “potential reduction in neutralization by post-vaccination sera,” as well as a “potential reduction in neutralization by some EUA monoclonal antibody treatments.”
Health experts warned the variant could soon become the dominant strain in the U.S. as it currently accounts for about 10 percent of all new cases, raising concerns that outbreaks could hit unvaccinated people this fall.
The Delta variant has become the dominant strain in the U.K. and is believed to be about 60 percent more transmissible than a previous strain known as Alpha, which was previously the dominant strain in the country.
Former Food and Drug Administration (FDA) Commissioner Scott Gottlieb told CBS on Sunday the Delta variant will likely become the dominant strain in the U.S., but “that doesn’t mean we’re going to see a sharp uptick in infections.”
A recent study found the Pfizer-BioNTech and AstraZeneca COVID-19 vaccines offer sufficient protection against the Delta variant.
Public Health England found that the full two-dose Pfizer vaccine offers 96 percent protection against hospitalization, while the AstraZeneca vaccine, not yet approved for use in the U.S., provides 92 percent protection.
The variant has spread to at least 74 countries.
The U.S. is continuing to see a drop in the number of new cases, as nearly 55 percent of adults have been fully vaccinated. The current seven-day moving average of daily new cases has fallen below 14,000, according to the CDC.
A new study from the Cleveland Clinic in Ohio has found that people who’ve already had COVID-19 may not necessarily benefit from vaccination.
The research indicates that out of a large pool of healthcare workers, there were nearly 0 cases of SARS-CoV-2 infection among those who had:
- previously contracted the virus and were unvaccinated
- previously contracted the virus and were vaccinated
- never contracted the virus and were vaccinated
There was, however, a steady increase in cases among unvaccinated people who hadn’t previously contracted SARS-CoV-2.
According to the researchers, the findings suggest that natural infection provides immunity similar to vaccination. Therefore, people who haven’t had COVID-19 can be prioritized for vaccination.
Experts say that more research is needed to determine how long immunity lasts after a case of COVID-19. Until we have that data, some infectious disease specialists are recommending that people who’ve had COVID-19 still get one dose.
There were 52,238 individuals included in the study. Of the 2,579 people who’d previously had COVID-19, 1,359 were unvaccinated.
The remaining 49,659 individuals hadn’t previously had COVID-19, and 22,777 of them were vaccinated.
The individuals were tracked from December 2020 to May 2021, during which time none of the 2,579 people who’d already had COVID-19 (including the 1,359 who remained unvaccinated) contracted the virus.
According to the findings, vaccination significantly lowers the risk of SARS-CoV-2 infection among people who haven’t already had COVID-19 — but not necessarily among people who have already had it.
Those individuals appeared to have similar immunity to those who were fully vaccinated.
Given the limited availability of the vaccines in certain countries, the findings add to the growing belief that the vaccines should be prioritized for those who haven’t previously had COVID-19.
“I’d likely keep those doses for the un-immune, those who haven’t had prior infection, and then go back and decide if we need to immunize [previously ill people],” Dr. Monica Gandhi, an infectious diseases specialist with the University of California San Francisco, told Healthline.
Preliminary dataTrusted Source suggest that immunity from natural infection is long-lived, lasting up to 8 months and likely longer.
And a study from Israel concluded that reinfection was as low in previously ill people as it was it those who’d been fully vaccinated.
“[The Cleveland Clinic study] reinforces what we are seeing clinically, which is the reinfection rate in previously infected people is extremely low and generally follows a less severe clinical course than initial COVID-19 infection,” Dr. Spencer Kroll, a board certified internal medicine specialist in Marlboro, New Jersey, told Healthline.
Our immune system is robust and involves different components that work together to prevent disease.
There are antibodies, which our immune systems produce upon exposure to a pathogen. Antibody levels may wane over time but are still operative even at lower levels, according to Dr. Amesh Adalja, a senior scholar at the Johns Hopkins University Center for Health Security in Maryland and an infectious disease expert.
There’s also the cell-mediated immune response, which involves protective B cells and T cells that appear to increase over time and remain elevated long after infection.
It’s worth noting that people mount variable immune responses to infection, according to Kroll.
“Some people with documented infection do not generate antibodies,” Kroll said.
Adalja said that natural immunity should influence vaccination policy.
“Natural immunity is not trivial and does contribute to population level immunity along with vaccinations,” Adalja told Healthline.
Scientists are still exploring whether there are benefits to vaccinating people who’ve already had the infection. They’re also examining how natural immunity compares to immunity from vaccination.
Gandhi said that she’s often asked whether previously ill people should get vaccinated. She said that the truth is, there isn’t enough data, and we don’t yet know how long natural immunity lasts.
Her solution: Just get the first dose. Even if it’s unnecessary, that single dose can act as an immune booster.
“I’m recommending one dose after natural infection, not because of any evidence I can find,” explained Gandhi, “but because of emotion.”
One study found that previously sick individuals who took one dose of the vaccine had a stronger antibody response compared to people who hadn’t had the infection but had received both doses of the vaccine.
Another reportTrusted Source concluded that one dose in previously sick people produced an immune response similar to people who didn’t have prior infection but received both doses.
Adalja is also for the one-dose strategy. “A single dose of a two-dose vaccine regimen may be all that is necessary for someone with a prior infection,” he said.
As San Diego County’s COVID-19 cases decline and vaccination numbers increase, local researchers are still engaged in the search for treatments for the disease and have found several potential treatments in existing medications, with long-range implications for treating not only the current pandemic but also any in the future.
The results of a Scripps Research study published June 3 in Nature Communications identify 90 known drugs that demonstrate antiviral activity against COVID-19.
Of those, four drugs approved by the U.S. Food and Drug Administration and nine others in various stages of development for use on other diseases were found to have potential to be repurposed as COVID-19 therapies.
Arnab Chatterjee, one of the study’s authors and vice president of medicinal chemistry at Calibr, the drug discovery division of Scripps Research in La Jolla, said the existing drugs were found to “slow down the replication” of SARS-CoV-2, the virus that causes COVID-19.
“The really interesting part,” he said, “is that those molecules … work in one or multiple different cellular systems, acting directly with the protein that’s encoded by the virus” and inhibiting the virus’s replication “through affecting the host cells, the cells that are actually being taken over by the virus to propagate its growth.”
The drugs screened in the study came from Calibr’s ReFRAME drug repurposing library, Chatterjee said. Those involved in the study tested more than 12,000 known drugs against SARS-CoV-2.
Chatterjee said the “value of drug repurposing is that one could imagine, at the onset of a pandemic or new disease, that one could take existing drugs already approved” for use in humans for testing on the new disease in clinical trials, as the drugs’ safety has already been established.
“First and foremost, I think safety is important,” he said.
“The second part that’s also important is understanding how the drug currently works, the way that it’s used or has been developed for, and whether or not that mechanism … [overlaps] with what we think would be involved in replication of the virus.”
Chatterjee said a set of 19 compounds, while not found to entirely inhibit replication of the virus, were found “to work to some extent,” especially when used with remdesivir, the only FDA-approved therapy for COVID-19.
“We do believe that in a world where you’re using drug combinations, an individual drug itself may not be very effective but it could be potentially combined,” he said.
The study shows “there are clearly some compounds that don’t work well on their own, but they do work well combined with something else,” he added.
Using a combination of drugs, he said, increases the effectiveness of the treatment and broadens options to fight variants of a virus, which develop over time as a virus “either changes the way that it enters cells” or becomes resistant to drug therapies.
Chatterjee said “we really need drugs to be able to not only be more effective treatments when combined but trick the virus into being unable to develop drug resistance, which obviously you can only do once you add more than one drug into a cocktail.”
“These drugs could potentially be used in the context of future coronavirus infections,” he said. “The fact that the drugs work in inhibiting replication of the virus in and of itself could be useful for future pandemics.”
A more important implication, however, is that the study “allows us to be able to understand the drugs,” Chatterjee said. “We need to have those systems to be able to then optimize and make new drugs … that could be much more effective treatments.”
“It’s really about tailoring drugs, making them really fit for purpose,” he said. “You can’t do [that] unless you have all of the right systems in the lab to really understand [if we’re] actually making better compounds.”
To that end, Chatterjee and his colleagues are continuing to profile and test the drugs and compounds discovered. “We want to make sure for anything we put into clinical development that the compounds work well against multiple systems, so it adds to a level of confidence” for use in humans, he said.
The experimental drug TEMPOL may be a promising oral antiviral treatment for COVID-19, suggests a study of cell cultures by researchers at the National Institutes of Health.
TEMPOL can limit SARS-CoV-2 infection by impairing the activity of a viral enzyme called RNA replicase. The work was led by researchers at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study appears in Science.
“We urgently need additional effective, accessible treatments for COVID-19,” said Diana W. Bianchi, M.D., NICHD Director. “An oral drug that prevents SARS-CoV-2 from replicating would be an important tool for reducing the severity of the disease.”
The study team was led by Tracey A. Rouault, M.D., head of the NICHD Section on Human Iron Metabolism. It discovered TEMPOL’s effectiveness by evaluating a more basic question on how the virus uses its RNA replicase, an enzyme that allows SARS-CoV-2 to replicate its genome and make copies of itself once inside a cell.
Researchers tested whether the RNA replicase (specifically the enzyme’s nsp12 subunit) requires iron-sulfur clusters for structural support. Their findings indicate that the SARS-CoV-2 RNA replicase requires two iron-sulfur clusters to function optimally. Earlier studies had mistakenly identified these iron-sulfur cluster binding sites for zinc-binding sites, likely because iron-sulfur clusters degrade easily under standard experimental conditions.
Identifying this characteristic of the RNA replicase also enables researchers to exploit a weakness in the virus. TEMPOL can degrade iron-sulfur clusters, and previous research from the Rouault Lab has shown the drug may be effective in other diseases that involve iron-sulfur clusters. In cell culture experiments with live SARS-CoV-2 virus, the study team found that the drug can inhibit viral replication.
Based on previous animal studies of TEMPOL in other diseases, the study authors noted that the TEMPOL doses used in their antiviral experiments could likely be achieved in tissues that are primary targets for the virus, such as the salivary glands and the lungs.
“Given TEMPOL’s safety profile and the dosage considered therapeutic in our study, we are hopeful,” said Dr. Rouault. “However, clinical studies are needed to determine if the drug is effective in patients, particularly early in the disease course when the virus begins to replicate.”
The study team plans on conducting additional animal studies and will seek opportunities to evaluate TEMPOL in a clinical study of COVID-19.
NIH authors on the study include researchers from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the National Institute of Neurological Disorders and Stroke. Authors from the Pennsylvania State University are funded by NIH’s National Institute of General Medical Sciences.
Vaccines against COVID-19 were developed in record time, but the successful advancement of therapeutics, particularly those that could disrupt the SARS-CoV-2 virus cycle, have been slower to move through the clinic. Researchers at multiple companies and institutes are doggedly pursuing that goal so the virus can become little more than a hindrance in the future.
A recent PBS report highlighted some of these efforts, focusing on clinical programs that have the potential to halt viral reproduction and keep those infected out of the hospitals. Experimental medications such as molnupiravir, in development by Merck and Florida-based Ridgeback Biotherapeutics, have the potential to fill the treatment gaps that vaccines cannot. Merck and Ridgeback are jointly developing molnupiravir, an orally available antiviral candidate for the treatment of COVID-19.
Earlier this year, the two companies noted a slight setback in the development of that program. In April, Merck announced it was moving molnupiravir into the Phase III portion of the Phase II/III MOVE-OUT study in outpatient COVID-19 patients based on a planned interim analysis from the Phase II part of the study. However, at the time, the companies said the Phase III portion of another study, the Phase II/III MOVE-IN study in hospitalized patients, will not proceed due to data that suggests molnupiravir is unlikely to demonstrate a clinical benefit in that patient population.
Daria Hazuda, vice president of infectious disease and vaccine discovery research at Merck, said they are hopeful the Phase III portion of the study, expected to be complete later this year, will demonstrate that molnupiravir is an effective treatment for mild to moderate cases of COVID-19.
Beyond Merck, PBS noted research conducted by Adolfo Garcia-Sastre, the director of the Global Health and Emerging Pathogens Institute at Icahn School of Medicine at Mount Sinai and the University of California, San Francisco’s Quantitative Biosciences Institute. After extensive research on multiple antiviral options, the collaborators put their focus on plitidepsin, an injectable multiple myeloma drug medicine developed by Spain’s PharmaMar. Plitidepsin acts by blocking the protein eEF1A, present in human cells, which SARS-CoV-2 uses to reproduce and infect other cells. Through this inhibition, the expectation is that reproduction of the virus inside the cell is prevented, making this propagation to the rest of the cells unviable.
Phase III research of plitidepsin was greenlit by Spanish health authorities last month. The scientific team hopes to see if the oncology drug effectively reduces days in the hospital for COVID-19 patients.
In its report, the results of compare plitidepsin’s effectiveness in the Phase III study would be compared to Gilead Sciences’ remdesivir, which is currently the standard of care for COVID-19. Remdesivir, the only antiviral approved to treat COVID-19, can shorten the hospital stay of COVID-19 patients, it has fallen short in treating patients. Garcia-Sastre told PBS he hopes plitidepsin will demonstrate live-saving potential.
Another potential antiviral highlighted by the news outlet is ivermectin, a decades-old drug approved to treat head lice infections as well as the treatment of some parasitic worms. Research has shown in a laboratory setting that the use of ivermectin inhibited the SARS-CoV-2 virus within 24 to 48 hours of treatment. The preclinical data showed that ivermectin prevented the virus’ RNA from replicating. While COVID-19 is not a parasitic disease, the laboratory tests showed that the drug targets the disease like one.
People who recover from mild COVID-19 have bone-marrow cells that can churn out antibodies for decades, although viral variants could dampen some of the protection they offer.
Many people who have been infected with SARS-CoV-2 will probably make antibodies against the virus for most of their lives. So suggest researchers who have identified long-lived antibody-producing cells in the bone marrow of people who have recovered from COVID-19.
The study provides evidence that immunity triggered by SARS-CoV-2 infection will be extraordinarily long-lasting. Adding to the good news, “the implications are that vaccines will have the same durable effect”, says Menno van Zelm, an immunologist at Monash University in Melbourne, Australia.
Antibodies — proteins that can recognize and help to inactivate viral particles — are a key immune defence. After a new infection, short-lived cells called plasmablasts are an early source of antibodies.
But these cells recede soon after a virus is cleared from the body, and other, longer-lasting cells make antibodies: memory B cells patrol the blood for reinfection, while bone marrow plasma cells (BMPCs) hide away in bones, trickling out antibodies for decades.
“A plasma cell is our life history, in terms of the pathogens we’ve been exposed to,” says Ali Ellebedy, a B-cell immunologist at Washington University in St. Louis, Missouri, who led the study, published in Nature on 24 May.
Researchers presumed that SARS-CoV-2 infection would trigger the development of BMPCs — nearly all viral infections do — but there have been signs that severe COVID-19 might disrupt the cells’ formation. Some early COVID-19 immunity studies also stoked worries, when they found that antibody levels plunged not long after recovery.
Ellebedy’s team tracked antibody production in 77 people who had recovered from mostly mild cases of COVID-19. As expected, SARS-CoV-2 antibodies plummeted in the four months after infection. But this decline slowed, and up to 11 months after infection, the researchers could still detect antibodies that recognized the SARS-CoV-2 spike protein.
To identify the source of the antibodies, Ellebedy’s team collected memory B cells and bone marrow from a subset of participants. Seven months after developing symptoms, most of these participants still had memory B cells that recognized SARS-CoV-2. In 15 of the 18 bone-marrow samples, the scientists found ultra-low but detectable populations of BMPCs whose formation had been triggered by the individuals’ coronavirus infections 7–8 months before. Levels of these cells were stable in all five people who gave another bone-marrow sample several months later.
“This is a very important observation,” given claims of dwindling SARS-CoV-2 antibodies, says Rafi Ahmed, an immunologist at Emory University in Atlanta, Georgia, whose team co-discovered the cells in the late 1990s. What’s not clear is what antibody levels will look like in the long term and whether they offer any protection, Ahmed adds. “We’re early in the game. We’re not looking at five years, ten years after infection.”
Ellebedy’s team has observed early signs that Pfizer’s mRNA vaccine should trigger the production of the same cells. But the persistence of antibody production, whether elicited by vaccination or by infection, does not ensure long-lasting immunity to COVID-19. The ability of some emerging SARS-CoV-2 variants to blunt the protective effects of antibodies means that additional immunizations may be needed to restore levels, says Ellebedy. “My presumption is, we will need a booster.”doi: https://doi.org/10.1038/d41586-021-01442-9
Rarely in recent memory has the world faced such an immediate and widespread global threat as complex as COVID-19. In its face, a select few have risen to the occasion, none more cherished and admired perhaps than the health care workers staffing the front lines. But standing close behind them in the trenches are the scientists and researchers who are among the very few who truly understand the scope of our evolutionary battle with the virus. Since the start of the pandemic, our scientists have acted with unprecedented speed and coordinated action to deliver us an armamentarium of medical weaponry to confront this global threat.
For someone who has spent a lifetime in science, someone who understands the pressures and constraints faced each day in every lab, it has been phenomenal to witness the transformation that has taken place within the scientific community. It is not just the speed and focus with which the scientific community responded, nor simply the use of new technologies to draw out new discoveries, but rather the singular willingness of scientists, all over the world, to share new ideas and data immediately and transparently, in some cases well before the idea or the research is fully formed.
Within weeks of the first case of COVID being reported, Chinese researchers had identified the virus they suspected of causing the disease and had decoded an initial genome sequence. It was a remarkable achievement in such a short amount of time, made more remarkable by the fact that the researchers published the sequence in an open discussion forum online, and encouraged a fellow researcher in Sydney, Australia, to share it via Twitter with the world.
During the first 24 hours after publication, an evolutionary biologist in Scotland had figured out the similarities between this virus and SARS-CoV-1 and, like the Chinese researchers, shared the findings immediately online. A researcher in the U.S. openly published the new virus’ phylogenetic tree. And another started reverse-engineering a live virus from the sequence, letting colleagues around the world know that the first steps towards developing an antibody test were already underway. At each moment, the goal was not acclaim or attention, but rather the possibility that openly sharing an early finding may influence the work of others and inch the world ever closer to a treatment or a cure.
Of all the arenas in life that COVID has upended, science is perhaps the field that has been transformed the most. The pandemic has created an entirely new research environment, one that is now structured for collaboration and communication above all else. This revolution was inspired by the initial transparency of those early researchers but has since been institutionalized by some of the most well-respected research institutes in the world today, including our very own biomedical nerve center in Boston.
Shortly after the virus emerged, Harvard Medical School pulled 20 Boston-area universities, medical schools and research institutes together to launch the Massachusetts Consortium on Pathogen Readiness (MassCPR). The initial goal was to formally join forces with researchers in China to answer the call to action to take down the emerging threat, with the hope that any lessons learned from this outbreak would enable a more rapid response to future emergencies.
This alone was a notable step. The scientific community in Boston typically works in relatively isolated fashion, with barriers built up between departments, disciplines and entire institutions. But with COVID-19 and MassCPR those floodgates between institutes upriver and down were quickly opened.
With a collaborative research grant from the Evergrande Group, MassCPR began funding dozens of new research projects, some of which have led to field-defining studies on the epidemiology, pathogenesis and immunopathology of COVID-19. Over the past year, MassCPR clinicians have written clinical management guidelines that have influenced patient care across the globe, and the consortium’s investigators have conceptualized, designed and developed the single-dose Johnson & Johnson vaccine and spearheaded clinical trials for the Moderna one.
The dean of Harvard Medical School, George Daley, leads the effort, along with Arlene Sharpe, Bruce Walker and David Golan. As Daley describes it, “Our collective efforts over the last year have given us demonstrable proof that we are strongest when we work together across institutional boundaries, when we reach out across geographic and national borders. We are strongest when we transcend scientific silos and build bridges across disciplines. Cooperation to confront a common threat is what MassCPR represents, and the achievements speak for themselves.”
MassCPR’s immediate efforts are focused on the basic biology of SARS-CoV-2 and the pathogenesis of COVID-19—developing new diagnostic tools, vaccines and therapies. But while the researchers stay firmly focused on the now, they are also looking towards tomorrow. “We must refine our capacity to track the rise of new viral variants,” warns Daley. “We must refine our prevention strategies—an armamentarium of treatments—by developing new antiviral drugs, panviral therapies, and polivariant vaccines. And we must anticipate the post pandemic realities of COVID-19. A major goal of MassCPR 2.0 will be to define the scope of post-COVID-19 syndrome and understand the long-term effects of multiple organ systems. The knowledge will have relevance beyond this pandemic and, indeed, beyond this pathogen.”
Beyond MassCPR, other critical global partnerships have emerged over the course of the past year to bring recent scientific advancements on the virus to the masses, not the least of which is the Access to COVID-19 Tools (ACT) Accelerator and its vaccines pillar, COVAX. The ACT Accelerator is a global philanthropic partnership—not a new agency or institution but rather a framework for collaboration launched by the WHO, the European Commission, France and the Bill & Melinda Gates Foundation in April 2020.
Researchers have discovered a new coronavirus, found in a child with pneumonia in Malaysia in 2018, that appears to have jumped from dog to human.
If confirmed as a pathogen, the novel canine-like coronavirus could represent the eighth unique coronavirus known to cause disease in humans. The discovery also suggests coronaviruses are being transmitted from animals to humans more commonly than was previously thought.
“How common this virus is, and whether it can be transmitted efficiently from dogs to humans or between humans, nobody knows,” said Gregory Gray, M.D., a professor of medicine, global health and environmental health at Duke University.
“What’s more important is that these coronaviruses are likely spilling over to humans from animals much more frequently than we know,” said Gray, who led the research that appears in the journal Clinical Infectious Diseases. “We are missing them because most hospital diagnostic tests only pick up known human coronaviruses.”
Working with visiting scholar Leshan Xiu, a Ph.D. student, Gray was on a team that in 2020 developed a molecular diagnostic tool to detect most coronaviruses from the Coronaviridae family that includes SARS-CoV-2, which causes COVID-19.
The team used that tool to examine 301 archived pneumonia cases and picked up signals for canine coronaviruses from eight people hospitalized with pneumonia in Sarawak, a state in East Malaysia.
Researchers at Ohio State, led by Anastasia N. Vlasova, grew a virus from one of the clinical specimens, and through a painstaking process of genome reconstruction, were able to identify it as a novel canine coronavirus.
“There are probably multiple canine coronaviruses circulating and spilling over into humans that we don’t know about,” Gray said. Sarawak could be a rich place to detect them, he said, since it’s an equatorial area with rich biodiversity.
“Many of those spillovers are dead ends, they don’t ever leave that first human host,” Gray said. “But if we really want to mitigate the threat, we need better surveillance where humans and animals intersect, and among people who are sick enough to get hospitalized for novel viruses.”
Gray said diagnostic tools like the one developed to find this virus have the potential to identify other viruses new to humans before they can cause a pandemic.
“These pathogens don’t just cause a pandemic overnight,” Gray said. “It takes many years for them to adapt to the human immune system and cause infection, and then to become efficient in human-to-human transmission. We need to look for these pathogens and detect them early.”