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Although antibodies induced by SARS-CoV-2 infection are largely protective, they do not completely protect against reinfection in young people, as evidenced through a longitudinal, prospective study of more than 3,000 young, healthy members of the US Marines Corps conducted by researchers at the Icahn School of Medicine at Mount Sinai and the Naval Medical Research Center, published April 15 in The Lancet Respiratory Medicine.
“Our findings indicate that reinfection by SARS-CoV-2 in health young adults is common” says Stuart Sealfon, MD, the Sara B. and Seth M. Glickenhaus Professor of Neurology at the Icahn School of Medicine at Mount Sinai and senior author of the paper. “Despite a prior COVID-19 infection, young people can catch the virus again and may still transmit it to others. This is an important point to know and remember as vaccine rollouts continue. Young people should get the vaccine whenever possible, since vaccination is necessary to boost immune responses, prevent reinfection, and reduce transmission.”
The study, conducted between May and November 2020, revealed that around 10 percent (19 out of 189) of participants who were previously infected with SARS-CoV-s (seropositive) became reinfected, compared with new infections in 50 percent (1.079 out of 2,247) of participants who had not been previously infected (seronegative). While seronegative study participants had a five times greater risk of infection than seropositive participants, the study showed that seropositive people are still at risk of reinfection.
The study population consisted of 3,249 predominantly male, 18-20-year-old Marine recruits who, upon arrival at a Marine-supervised two-week quarantine prior to entering basic training, were assessed for baseline SARS-CoV-2 IgG seropositivity (defined as a 1:150 dilution or greater on receptor binding domain and full-length spike protein enzyme-linked immunosorbent [ELISA] assays.) The presence of SARS-CoV-2 was assessed by PCR at initiation, middle and end of quarantine. After appropriate exclusions, including participants with a positive PCR during quarantine, the study team performed three bi-weekly PCR tests in both seronegative and seropositive groups once recruits left quarantine and entered basic training.
Recruits who tested positive for a new second COVID-19 infection during the study were isolated and the study team followed up with additional testing. Levels of neutralising antibodies were also taken from subsequently infected seropositive and selected seropositive participants who were not reinfected during the study period.
Of the 2,346 Marines followed long enough for this analysis of reinfection rate, 189 were seropositive and 2,247 were seronegative at the start of the study. Across both groups of recruits, there were 1,098 (45%) new infections during the study. Among the seropositive participants, 19 (10%) tested positive for a second infection during the study. Of the recruits who were seronegative, 1,079 (48%) became infected during the study.
To understand why these reinfections occurred, the authors studied the reinfected and not infected participants’ antibody responses. They found that, among the seropositive group, participants who became reinfected had lower antibody levels against the SARS-CoV-2 virus than those who did not become reinfected. In addition, in the seropositive group, neutralising antibodies were less common (neutralising antibodies were detected in 45 (83%) of 54 uninfected, and in six (32%) of 19 reinfected participants during the six weeks of observation).
Comparing new infections between seropositive and seronegative participants, the authors found that viral load (the amount of measurable SARS-CoV-2 virus) in reinfected seropositive recruits was on average only 10 times lower than in infected seronegative participants, which could mean that some reinfected individuals could still have a capacity to transmit infection. The authors note that this will need further investigation.
In the study, most new COVID-19 cases were asymptomatic — 84% (16 out of 19 participants) in the seropositive group vs 68% (732 out of 1,079 participants) in the seronegative group — or had mild symptoms and none were hospitalised.
The authors note some limitations to their study, including that it likely underestimates the risk of reinfection in previously infected individuals because it does not account for people with very love antibody levels following their past infection. They strongly suggest that even young people with previous SARS-CoV-2 infection be a target of vaccination since efforts must be made to prevent transmission and prevent infection amongst this group.
This work was supported by the Defense Health Agency through the Naval Medical Research Center and the Defense Advanced Research Projects Agency.

Scientists have figured out how to modify CRISPR’s basic architecture to extend its reach beyond the genome and into what’s known as the epigenome — proteins and small molecules that latch onto DNA and control when and where genes are switched on or off.
In a paper published April 9, 2021, in the journal Cell, researchers at UC San Francisco and the Whitehead Institute describe a novel CRISPR-based tool called “CRISPRoff,” which allows scientists to switch off almost any gene in human cells without making a single edit to the genetic code. The researchers also show that once a gene is switched off, it remains inert in the cell’s descendants for hundreds of generations, unless it is switched back on with a complementary tool called CRISPRon, also described in the paper.
Because the epigenome plays a central role in many diseases, from viral infection to cancer, CRISPRoff technology may one day lead to powerful epigenetic therapies. And since this approach doesn’t involve any DNA edits, it’s likely to be safer than conventional CRISPR therapeutics, which have been known to cause unwanted and potentially harmful changes to the genome.
“Though genetic and cellular therapies are the future of medicine, there are potential safety concerns around permanently changing the genome, which is why we’re trying to come up with other ways to use CRISPR to treat disease,” said Luke Gilbert, PhD, a professor at UCSF’s Helen Diller Family Comprehensive Cancer Center and co-senior author of the new paper.
Transforming CRISPR From Genome to Epigenome Editor
Conventional CRISPR is equipped with two pieces of molecular hardware that make it an effective gene-editing tool. One component is a DNA-snipping enzyme, which gives CRISPR the ability to alter DNA sequences. The other is a homing device that can be programmed to zero in on any DNA sequence of interest, imparting precise control over where edits are made.

Putting a risk in context: The rate of blood clots is extremely low, but the pause in the Johnson & Johnson vaccine could reveal more cases.A mass vaccination site in Elgin, Ill., closed for a day because of the pause put on the Johnson & Johnson vaccine.Rick West/Daily Herald, via Associated PressWhen federal officials paused administration of the Johnson & Johnson vaccine after six cases of a rare clotting disorder, one fatal, among the 6.9 million people who had received the vaccine, many critics noted that the chance of a serious ailment was so rare as to be negligible — less frequent than being struck by lightning.But that roughly one-in-a-million rate is far from certain. Doctors may ultimately find the vaccine is not responsible for the ailment. However, if the two are linked, it’s also possible that the chance of an adverse effect will be higher, even if it remains low.“Numbers seem quite solid, like, ‘Oh, it’s 10,’” said Caitlin Rivers, an assistant professor at Johns Hopkins University, who studies infectious disease. She said epidemiologists deal with similar matters of uncertainty at the beginning of disease outbreaks. “But they’re estimates, and they will need to be refined, and they may need to be refined a lot, especially since they are small numbers.”How do we know how common this event is?If there is a connection between the vaccine and this rare syndrome, new cases are likely to emerge now that the word is out. Regulators announced the pause in part to alert doctors to the existence of this syndrome; as people begin looking, they may be more likely to find and report it. With numbers so low, the addition of even a few more cases could increase the rate. (In the last few days, Johnson & Johnson has reported two more possible cases, one in a woman, and one in a man.)Cases of rare blood clotsReported cases of cerebral venous sinus thrombosis in those receiving the Johnson & Johnson vaccine, compared with the number of cases that would normally be expected in that many people over 20.5 days.

Gary Stewart’s wife Jude died from the coronavirus at the start of the year. She had been living in a care home and he hadn’t been able to see her for months.Because of restrictions caused by the pandemic, no more than 30 people could attend and they had to socially distance.Gary, who lives near Peterborough, describes his wife’s funeral as “a ridiculous non-event” and not “what she deserved”.He spoke to the BBC ahead of Prince Philip’s funeral this Saturday, which will only have 30 mourners in line with Covid rules.

The experimental antiviral drug MK-4482 significantly decreased levels of virus and disease damage in the lungs of hamsters treated for SARS-CoV-2 infection, according to a new study from National Institutes of Health scientists. SARS-CoV-2 is the virus that causes COVID-19. MK-4482, delivered orally, is now in human clinical trials. Remdesivir, an antiviral drug already approved by the U.S. Food and Drug Administration for use against COVID-19, must be provided intravenously, making its use primarily limited to clinical settings.
In their study, published in the journal Nature Communications, the scientists found MK-4482 treatment effective when provided up to 12 hours before or 12 hours after infecting the hamsters with SARS-CoV-2. These data suggest that MK-4482 treatment potentially could mitigate high-risk exposures to SARS-CoV-2, and might be used to treat established SARS-CoV-2 infection alone or possibly in combination with other agents.
The same research group, located at Rocky Mountain Laboratories, part of NIH’s National Institute of Allergy and Infectious Diseases in Hamilton, Montana, developed the hamster model last year to mimic SARS-CoV-2 infection and mild disease in people. The University of Plymouth in the United Kingdom collaborated on these most recent studies.
The project involved three groups of hamsters: a pre-infection treatment group; a post-infection treatment group; and an untreated control group. For the two treatment groups, scientists administered MK-4482 orally every 12 hours for three days. At the conclusion of the study, the animals in each of the treatment groups had 100 times less infectious virus in their lungs than the control group. Animals in the two treatment groups also had significantly fewer lesions in the lungs than the control group.
The scientists determined the MK-4482 treatment doses for this study based on previous experiments performed in mouse models of SARS-CoV-1 and MERS-CoV. In those studies, MK-4482 was effective at stopping the viruses from replicating.
With funding support from NIAID, Emory University’s Drug Innovation Ventures group in Atlanta developed MK-4482 (also known as molnupiravir and EIDD-2801) to treat influenza. Merck and Ridgeback Biotherapeutics are now jointly developing and evaluating MK-4482 as a potential COVID-19 treatment. The drug is in Phase 2 and 3 human clinical studies.
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Materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Content may be edited for style and length.

Many long for a return to a post-pandemic “normal,” which, for some, may entail concerts, travel, and large gatherings. But how to keep safe amid these potential public health risks?
One possibility, according to a new study, is dogs. A proof-of-concept investigation published today in the journal PLOS ONE suggests that specially trained detection dogs can sniff out COVID-19-positive samples with 96% accuracy.
“This is not a simple thing we’re asking the dogs to do,” says Cynthia Otto, senior author on the work and director of the University of Pennsylvania School of Veterinary Medicine Working Dog Center. “Dogs have to be specific about detecting the odor of the infection, but they also have to generalize across the background odors of different people: men and women, adults and children, people of different ethnicities and geographies.”
In this initial study, researchers found the dogs could do that, but training must proceed with great care and, ideally, with many samples. The findings are feeding into another investigation that Otto and colleagues have dubbed “the T-shirt study,” in which dogs are being trained to discriminate between the odors of COVID-positive, -negative, and -vaccinated individuals based on the volatile organic compounds they leave on a T-shirt worn overnight.
“We are collecting many more samples in that study — hundreds or more — than we did in this first one, and are hopeful that will get the dogs closer to what they might encounter in a community setting,” Otto says.
Through the Working Dog Center, she and colleagues have had years of experience training medical-detection dogs, including those that can identify ovarian cancer. When the pandemic arrived, they leveraged that expertise to design a coronavirus detection study.

Some survivors of ebolavirus outbreaks make antibodies that can broadly neutralize these viruses — and now, scientists at Scripps Research have illuminated how these antibodies can disable the viruses so effectively. The insights may be helpful for developing effective therapies.
Ebolavirus is a family of often-deadly viruses that includes Ebola virus and many lesser-known viruses such as Bundibugyo virus, Sudan virus and Reston virus.
Structural biologists at Scripps Research used electron microscopy techniques to visualize a set of antibodies that target a key site on these viruses called the “glycan cap.” Their research showed that the antibodies work against ebolaviruses using the same three mechanisms to prevent the virus from infecting host cells.
The research, published in Cell Reports, is a step toward the creation of an antibody-based treatment that will be useful against a broad range of ebolaviruses.
“We now understand the molecular basis for these antibodies’ abilities to neutralize ebolviruses with broad reactivity against different viral species,” says the study’s first author Daniel Murin, PhD, a staff scientist in the laboratory of Andrew Ward, PhD.
Ward, a professor in the Department of Integrative Structural and Computational Biology at Scripps Research, says he hopes the work will contribute the development of a “cocktail” of therapeutic antibodies that can save lives by treating many forms of the Ebola virus.

A study published today in JAMA Internal Medicine shows that wearing two face coverings can nearly double the effectiveness of filtering out SARS-CoV-2-sized particles, preventing them from reaching the wearer’s nose and mouth and causing COVID-19. The reason for the enhanced filtration isn’t so much adding layers of cloth, but eliminating any gaps or poor-fitting areas of a mask.
“The medical procedure masks are designed to have very good filtration potential based on their material, but the way they fit our faces isn’t perfect,” said Emily Sickbert-Bennett, PhD, associate professor of infectious diseases at the UNC School of Medicine and lead author of the study.
To test the fitted filtration efficiency (FFE) of a range of masks, UNC researchers worked with James Samet, PhD, and colleagues in the USEPA Human Studies Facility on the campus of UNC-Chapel Hill. There they filled a 10-foot by 10-foot stainless-steel exposure chamber with small salt particle aerosols, and had researchers don combinations of masks to test how effective they were at keeping particles out of their breathing space.
Each individual mask or layered mask combination was fitted with a metal sample port, which was attached to tubing in the exposure chamber that measured the concentration of particles entering the breathing space underneath the researcher’s mask. A second tube measured the ambient concentration of particles in the chamber. By measuring particle concentration in the breathing space underneath the mask compared to that in the chamber, researchers determined the FFE.
“We also had the researchers in the chamber undergo a series of range-of-motion activities to simulate the typical motions a person may do throughout their day — bending at the waist, talking, and looking left, right, up and down,” said Phillip Clapp, PhD, an inhalation toxicologist in the UNC School of Medicine who has been testing mask FFE with Sickbert-Bennett since the pandemic began.
According to their findings, the baseline fitted filtration efficiency (FFE) of a mask differs person to person, due to each person’s unique face and mask fit. But generally, a procedure mask without altering the fit, is about 40-60% effective at keeping COVID-19-sized particles out. A cloth mask is about 40% effective.
Their recent findings on doubling of face masks, shows that when a cloth mask is placed over a surgical mask, the FFE improved by about 20%, and improved even more with a snug-fitting, sleeve-type mask, such as a gaiter. When layered over procedure masks, cloth masks improve fit by eliminating gaps and holding the procedure mask closer to the face, consistently covering the nose and mouth. When a procedure mask is worn over a cloth mask, FFE improved by 16%.
“We’ve found that wearing two loosely fitted masks will not give you the filtration benefit that one, snug-fitting procedure mask will,” Sickbert-Bennett said. “And with the current data supporting how effective mask-wearing is at preventing the spread of COVID-19, the best kind of double-masking is when you and the person you are interacting with are each correctly wearing a very snug-fitting mask.”
This study was partially funded by a grant from the Centers for Disease Control and Prevention (CDC), and expands upon research conducted by the agency earlier this year, which supported the CDC’s recommendation of double-masking to the public. Sickbert-Bennett and Clapp have previously discussed this recommendation and their research on the importance of mask fit with news outlets in a recorded conversation (https://news.unchealthcare.org/2021/02/unc-health-media-briefing-double-masking-importance-of-mask-fit/).
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Materials provided by University of North Carolina Health Care. Note: Content may be edited for style and length.

SARS-CoV-2, the virus that causes COVID-19, likely does not directly infect the brain but can still inflict significant neurological damage, according to a new study from neuropathologists, neurologists, and neuroradiologists at Columbia University Vagelos College of Physicians and Surgeons.
“There’s been considerable debate about whether this virus infects the brain, but we were unable to find any signs of virus inside brain cells of more than 40 COVID-19 patients,” says James E. Goldman, MD, PhD, professor of pathology & cell biology (in psychiatry), who led the study with Peter D. Canoll, MD, PhD, professor of pathology & cell biology, and Kiran T. Thakur, MD, the Winifred Mercer Pitkin Assistant Professor of Neurology.
“At the same time, we observed many pathological changes in these brains, which could explain why severely ill patients experience confusion and delirium and other serious neurological effects — and why those with mild cases may experience ‘brain fog’ for weeks and months.”
The study, published in the journal Brain, is the largest and most detailed COVID-19 brain autopsy report published to date, suggests that the neurological changes often seen in these patients may result from inflammation triggered by the virus in other parts of the body or in the brain’s blood vessels.
No Virus in Brain Cells
The study examined the brains of 41 patients with COVID-19 who succumbed to the disease during their hospitalization. The patients ranged in age from 38 to 97; about half had been intubated and all had lung damage caused by the virus. Many of the patients were of Hispanic ethnicity. There was a wide range of hospital length with some patients dying soon after arrival to the emergency room while others remained in the hospital for months. All of the patients had extensive clinical and laboratory investigations, and some had brain MRI and CT scans.

A person who owns a car or who has a college education may be less vulnerable to COVID-19, according to an analysis of cases in Tehran, Iran, one of the early epicenters of the pandemic. While such variables do not inherently lower a person’s risk, they do indicate an infrastructure of protection that persists despite how densely populated a person’s district might be.
The international collaboration published their results on April 3 in Sustainable Cities and Society.
“In the past few decades, there have been various efforts aimed at increasing urban density to enhance efficiency and contribute to climate change mitigation — but the COVID-19 pandemic has brought questions about the desirability of compact urban development to the forefront,” said paper author Ayyoob Sharifi, associate professor in the Graduate School of Humanities and Social Sciences and in the Graduate School of Advanced Science and Engineering at Hiroshima University. Sharifi is also affiliated with the Network for Education and Research on Peace and Sustainability.
Through a comprehensive data analysis from the early months of the pandemic (to April 4 and June 27, 2020), the researchers found that a population’s demographic structure — age, social and economic class, access to resources — is far more influential than simply how dense a population is. However, density is distinctly different than overcrowding for the resources available, the researchers said.
“We found that what drives the spread of infectious disease during a pandemic is overcrowding, which can occur in districts even with low density,” said paper author Amir Reza Khavarian-Garmsir, assistant professor in the Department of Geography and Urban Planning in the Faculty of Geographical Sciences and Planning at the University of Isfahan.
While a person less likely to be aware of or follow public health guidelines or more likely to use public transportation may be more at risk for the disease, the researchers didn’t find a statistically significant difference in urban districts with lower income and lower age compositions — indicating that age was one of the most significant risk factors for COVID-19 infection, despite density of living.
The data was obtained from Iran’s AC-19 app, which tracks positive cases and deaths by geographic location, the researchers assessed whether certain variables affected infection rates across the 22 districts and roughly 8.6 million residents of Tehran. They used structural equation modeling, which can use multiple factors to indicate the influence of unobservable variables, such as likelihood to follow public health recommendations, in combination with measurable factors, such as ease of access to medical facilities.
There are some drawbacks to the study, the researchers said, the main one of which is data availability and accuracy. The pandemic evolved so rapidly in the early months that tracking may not capture the full picture; and testing shortages and cost, as well as a relative lack of severe symptoms in children and young adults, may skew the number of true positive cases.
“It is perhaps too early to draw definitive conclusions, so future research should continue to investigate the relationship between urban density and transmission patterns of infectious disease,” Moradpour said.
The researchers said they hope their work will help policy makers develop guidelines to benefit all during urban and pandemic-preparedness planning.
“The next step is to further examine the impacts of urban density in other contexts,” Shafiri said. “In addition, we are trying to examine the long-term impacts of the pandemic on compact urban development policies.”
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Materials provided by Hiroshima University. Note: Content may be edited for style and length.