The global network led by the Oxford Maternal and Perinatal Health Institute (OMPHI) at the University of Oxford has published in the journal Lancet the results of the ‘2022 INTERCOVID Study’ conducted in 41 hospitals across 18 countries, including Ann & Robert H. Lurie Children’s Hospital of Chicago.

To evaluate the impact of the COVID-19 omicron variant on maternal and neonatal outcomes the researchers studied 1,545 pregnant women diagnosed with the variant and 3,073 non-diagnosed, concomitant pregnant women as controls. The study was conducted between November 27, 2021, and June 30, 2022, during which time omicron was the variant of concern. Vaccine effectiveness against the variant was also assessed.

COVID-19 omicron variant during pregnancy was associated with increased risks of maternal morbidity, severe pregnancy complications, and hospital admission, especially among symptomatic and unvaccinated women. In particular, the risk of preeclampsia was increased among women with severe symptoms. Obese/overweight women with severe symptoms were at the highest risk for maternal morbidity and severe complications.

Vaccinated women were well protected against severe COVID-19 symptoms and complications and had a very low risk of admission to an intensive care unit. Prevention of severe COVID-19 symptoms and complications requires women to be completely vaccinated, preferably with a booster dose as well.

In the study, mRNA vaccines were most effective in preventing severe COVID-19 symptoms and complications, although viral vector vaccines with a booster also provided adequate protection—for at least 10 months after the last dose for both mRNA vaccines and viral vector vaccines with a booster.

José Villar, Professor of Perinatal Medicine at the University of Oxford, who co-led INTERCOVID 2022, says, “We have provided robust, evidence-based information on the increased risk of the COVID-19 omicron variant during pregnancy for severe maternal complications among symptomatic and unvaccinated women. Of concern is that severe symptoms of the disease occurred in 4% to 7% of unvaccinated women diagnosed with the COVID-19 omicron variant during pregnancy.

The study clearly indicates the need for a complete vaccination course during pregnancy, preferably with a booster, to provide protection for at least 10 months after the last dose. Antenatal services worldwide should strive to include vaccination against COVID-19 in the routine care of pregnant women.”

Aris Papageorghiou, Professor of Fetal Medicine, University of Oxford, who co-led INTERCOVID 2022, says, “Although the omicron variant may be less harmful than previous variants in the general population, the large proportion of unvaccinated pregnant women worldwide are still at major risk. As it is impossible to predict who will develop severe symptoms or complications, universal complete vaccination is required. Unfortunately, full vaccination coverage among pregnant women is still inadequate even in developed countries.”

Stephen Kennedy, Professor of Reproductive Medicine, University of Oxford, who co-led INTERCOVID 2022, says, “The present study is a shining example of how well-coordinated, multi-national, collaborative research can, in a very short time, provide robust evidence to improve the health of mothers and babies worldwide. The findings from this study and our previous INTERCOVID studies (see below) have contributed to changes in clinical practice and public health policy recommending vaccination for all pregnant women. We hope our work will help to negate the considerable misinformation circulating regarding the pandemic and effectiveness of vaccines.”

Jagjit Teji, neonatologist and site Principal Investigator at Lurie Children’s says, “This study provides robust evidence that vaccination against COVID omicron variant provides protection for mothers and babies.”

Lurie Children’s study participants were recruited from Northwestern Medicine Huntley Hospital’s Maternal, Newborn and Intermediate Care Nursery areas, where Lurie Children’s neonatologists provide coverage.

Ann & Robert H. Lurie Children’s Hospital of Chicago

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As the United States enters a fourth year of COVID-19, there is a new variant called XBB.1.5.

The variant quickly grew in December, from about 1% of cases nationwide to 43% as of Jan. 13, according to data from the Centers for Disease Control and Prevention (CDC).

Natascha Tuznik, associate clinical professor of infectious diseases at UC Davis Health, explains what you need to know about XBB.1.5, including symptoms and vaccine efficacy.

XBB.1.5., now dubbed “the Kraken” is the result of two BA.2 omicron variants. Research from John Hopkins shows that this variant has stronger binding capabilities to the target host receptor. That makes it more efficient at spreading and infectious. It has been named the most contagious strain of any COVID-19 variant by the World Health Organization (WHO) thus far.

With current available data, the symptoms are similar to the prior strains with no evidence of more severe infection. Recent mutations of COVID-19 have led to less severe disease. This is because the virus must give up something, in this case its ability to do harm, to survive.

A perspective from Paul Offit, director of the Vaccine Education Center and attending physician in the Division of Infectious Diseases at Children’s Hospital of Philadelphia, showed that the updated bivalent booster may not be more effective as compared the original, monovalent vaccine. This included the new booster not showing an appreciably greater antibody response against the newer omicron variants including BQ.1, BQ1.1, XBB, and XBB.1.5.

This is NOT to say that the vaccine is not effective, just that the bivalent boosters may not be more effective than the original monovalent vaccine. That said, the bivalent booster would still be important for people at highest risk of getting severe disease. This includes those ages 65 and older and those who are immunocompromised. Even small, additional increases in antibody production are critically important for them.

Lastly, boosters will continue to help as our antibody production from both natural infection and vaccination decreases over time.

These things remain important for people to avoid COVID-19:

There are several reasons it’s important to avoid getting COVID-19. Getting infected puts you at risk of severe illness, potential hospitalization, and death, especially if you are high-risk and unvaccinated. The likelihood of an unvaccinated person dying from COVID-19 has been reported as being between 10-20 times higher than that of a vaccinated person.

In addition, if more people get seriously ill, it could place an unnecessary strain on an already overwhelmed hospital system. Current strains are also better at evading our immune defenses as compared to prior strains. Therefore, your risk of reinfection is higher. Getting infected also puts vulnerable populations at unnecessary risk of infection including severe illness, hospitalization and death.

Last, you could end up with long COVID. There are currently too many unknowns regarding who is more likely to get long COVID, but the risk of developing this chronic condition after infection is very real. Millions of people have developed this and suffer for many months, including time and money lost by the inability to work.

COVID-19 is unlikely to go away completely. There are still many unknown variables. Virologists wonder whether it will behave like other coronaviruses—many of which cause the common cold. It may end up reappearing seasonally, like most of our viruses do.

In prior epidemics, viruses eventually reach a saturation threshold, meaning most of the population will be or has already been infected. At this point, when the virus has fewer people to infect, the epidemic will decrease naturally.

Hopefully, this will equate to an endemic instead of a pandemic. Endemic is a disease that is still around but at a more manageable level, without causing spikes in deaths, for example. Instead, the disease is more manageable in terms of not overwhelming the system. The hope is that if COVID-19 is not eliminated, it would become more like the common cold.

UC Davis

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A new Boston University–led study by an international team of researchers may provide some answers. In a paper published online in Nature, they identify the mutations that help omicron dodge prior immunity and show that a previously unheralded virus protein—known as NSP6—might be an essential factor in the variant’s lower disease-causing potential, or its pathogenicity.

A draft containing some of the paper’s early results had previously made international headlines in October when a series of false reports sensationally misconstrued its findings. But the study’s senior author, BU virologist Mohsan Saeed, says their research could have a major positive impact, potentially helping provide a new target for vaccines and therapeutics.

“This is an important piece of work showing that the spike protein has only minimal contribution to omicron’s lower pathogenicity—and that mutations in another protein, NSP6, play an essential role,” says Saeed, a BU Chobanian & Avedisian School of Medicine assistant professor of biochemistry. “This provides us with an exciting new concept for future vaccines and therapeutics—if we know how to weaken the virus, we can better fight it.”

The paper, which will also appear in print, was coauthored by researchers from BU and Cleveland Clinic Florida Research and Innovation Center, Loyola University, Brigham and Women’s Hospital (BWH), Harvard Medical School (HMS), University of Wisconsin–Madison, and Friedrich-Alexander-Universität Erlangen-Nürnberg and Johannes Gutenberg-Universität Mainz, both in Germany. One of the coauthors, Jonathan Li, a BWH and HMS associate professor of medicine, says that while lots of research has been concentrated on SARS-CoV-2’s spike protein, little is known about the rest of its genome.

“The non-spike portions of the viral genome have been grossly understudied. Studies like this are helping us understand which parts of the viral genome impact pathogenesis, something we still don’t know,” says Li, who points out that it’s not, for example, clear why the omicron BA.5 subvariant easily outcompeted the BA.4 version—despite the two variants sharing the same spike sequences.

“Dr. Saeed’s research is showing us the relative impact of different SARS-CoV-2 gene segments on disease severity. This type of research has the potential to not only predict which variants might lead to new waves of infection, but also identify targets for new therapeutics against COVID-19.”

Saeed’s lab has been studying SARS-CoV-2 since the beginning of the outbreak, examining the first coronavirus strain to be recovered from a patient in the United States, known as the Washington or wild-type isolate. When the omicron variant crashed onto the scene in late 2021, it soon became clear that it was spreading faster than previous variants. However, omicron was also weaker, or attenuated—less deadly. Saeed wanted to know why.

“It caused relatively less severe disease,” says Saeed. “What is so special about omicron that it inflicts milder disease? That’s how this project started—we wanted to investigate that question.”

In a secure lab in BU’s National Emerging Infectious Diseases Laboratories (NEIDL), researchers started by looking at the virus’ spike protein, a molecule that helps SARS-CoV-2 invade a cell and begin its infection—and that has also been co-opted into most vaccines. One reason for the focus on the spike is that scientists had determined it was the main differentiator between omicron and the original virus: most of the mutations were concentrated in this one protein.

“The first experiment we did was take the spike of omicron and put it into the wild-type virus,” says Saeed, who’s an investigator at the NEIDL. That created a chimeric recombinant virus—a modified virus containing genetic fragments of different viruses—they called Omi-S, a version of the original dented with an omicron protein. “The thought process here was that if spike was behind omicron’s attenuation, then the Omi-S and omicron viruses should cause a similarly mild disease.”

In some ways, he adds, nature was showing the way forward.

“Omicron causes relatively mild disease—nature is already telling us how to attenuate the virus, how the virus can become weak,” says Saeed. Making viruses weak has long been used by scientists to fight back against deadly diseases, from polio to yellow fever—Louis Pasteur was experimenting with live-attenuated vaccines using weaker versions of viruses back in the 1800s. “We can learn from nature. If we can unravel or decode nature’s path, it can help us in making vaccines.”

Unlike in Pasteur’s time, researchers today who modify any virus have to follow a very strict protocol. If they see any sign that the virus is getting stronger rather than weaker—something known as gain of function—they are required to pause their research and eradicate the virus to avoid any possibility of a more dangerous version reaching the public.

“The tradition in the field is that if you are generating a chimeric virus, you have to compare it with the backbone virus. In our case, that was the Washington isolate,” says Saeed. “Think of it this way: out of around 30 proteins, one is coming from omicron, all others from the Washington isolate.”

In this case, the chimeric virus was attenuated and stayed that way throughout the study. When the researchers compared omicron, Washington, and Omi-S in cells grown in petri dishes, says Saeed, “We found the chimeric virus was weaker compared to the wild-type virus.”

But it still wasn’t as weak as omicron, suggesting it wasn’t just the spike that was responsible for that variant’s relative lack of pathogenicity.

“We showed that spike had minimal contribution to the disease-causing ability of omicron,” says Saeed.

They also tested the three virus variants in bioengineered animal models—mice engineered to be more susceptible to disease—and saw the same patterns emerge.

The original virus killed 100 percent of infected mice, Omi-S had an 80 percent mortality rate, and all mice survived their brush with omicron. When those results were originally released by Saeed’s research team in a draft form, they sparked some confusion, with a number of largely right-wing media outlets wrongly assuming that those percentages meant the viruses had the same mortality or kill rates in humans. That was not true, says Saeed—and it’s a point he and his coauthors clarified in the final paper.

In fact, the mice used in the studies are engineered to be highly sensitive to the virus, so researchers can more quickly and effectively examine its disease-causing potential. While 100 percent of these mice die when infected with the original Washington strain of the virus, for example, the disease outcomes are massively different in humans. Less than 5 percent of patients who caught the original virus are estimated to have died as a result.

The Omi-S version of the virus was not only less lethal to the mice than the type that passed from person-to-person when COVID first struck America, it was also only so lethal to the rodents because they were bioengineered to be more prone to it.

“There’s a huge difference in disease presentation and outcome between these artificially engineered mice and human beings,” says Saeed, whose team did all of their work in biosafety cabinets in NEIDL’s Biosafety Level 3 facilities. (In order to even enter their lab, the fully vaccinated researchers have to go through a series of rooms and interlocking doors, donning multiple layers of protective gear, including an astronaut-like suit and hood.)

Having established that the spike protein was not the sole player in diluting omicron’s potency, Saeed and the research team set out to discover what else might be the cause. They eventually landed on a different protein: nonstructural protein 6, or NSP6.

In addition to the spike protein, SARS-CoV-2 is made up of a bunch of other molecules that help it do its dirty work. At least four—including the spike—are structural proteins, which form the virus particle as it comes out of an infected cell. Another 16 are nonstructural—they help the virus replicate, creating the environment it needs in an infected cell to make copies of itself. One of those nonstructural proteins is NSP6. Its job, says Saeed, is to “contribute to the formation of certain membrane vesicles in infected cells, which serve as factories for viral genome amplification.”

When they repeated their experiments using a chimeric virus that added omicron’s NSP6 protein to Omi-S, “we observed a strong decrease in viral replication, with infection kinetics mimicking those of omicron in cell culture,” according to the paper. The Omi-S plus NSP6 virus was weaker. It also showed decreased bronchial infection in the lungs of infected mice compared to Omi-S.

“The field has been focusing for months on the impact of spike in driving omicron attenuation. This study is unique because it identifies for the first time another SARS-CoV-2 protein, NSP6, that contributes to omicron attenuation in addition to spike,” says Florian Douam, a coauthor on the study and a BU Chobanian & Avedisian School of Medicine assistant professor of microbiology. “While spike remains important in defining omicron attenuation, a lot is going on in other, more understudied, SARS-CoV-2 proteins, and this study is the first to point this out.”

Saeed says that the NSP6 protein has also been implicated in inflammation.

“When people get infected with SARS-CoV-2, there is inflammation in the lungs, leading to pneumonia and acute respiratory distress syndrome,” says Saeed. “NSP6 seems to have a role in that. I think our study will really provide impetus to study NSP6 and see what other functions it has in virus replication and the subsequent lung disease—it’s not one of the heavily studied proteins.”

The research team will begin digging further into NSP6 soon, but say the latest findings are exciting, because they open up a new route for taking down COVID. Understanding the small genetic differences between variants is crucial to providing new insights into how the virus causes disease, according to Douam.

“By swapping genetic characteristics between two variants with different virulence, researchers can identify key components involved in SARS-CoV-2’s disease-causing potential,” he says. “This research is critically important, not only because it tells us what the elements of the virus that regulate its virulence are, but it also highlights the potential of these virus elements to serve as great drug targets—ultimately expanding the toolbox to curve the pandemic.”

Saeed, who was recently a coauthor on a Dana-Farber Cancer Institute–led study that discovered a new receptor decoy drug that neutralizes SARS-CoV-2, says research like his can help scientists “tailor their efforts to develop antiviral drugs to a particular protein.”

Those outside of the scientific community who’ve been following the progress of this particular study may wonder why the final version—with a different summary, or abstract, and additional data—isn’t a straight copy, with dotted I’s and crossed T’s, of the earlier draft version that sparked worldwide attention.

The main reason: academic openness about the scientific journey. As part of Nature‘s publication process, the research team posted an early, work-in-progress look at their findings on bioRxiv, an online archive of draft—officially called preprint—biology articles. It’s used by researchers to be transparent about their work, share initial findings, and receive suggestions for improving their final papers before peer review.

It’s a bit like when an architect shows you their first plan for an addition or new kitchen; it gives you a flavor of the project, but not all the final details and refinements. A regular part of the scientific process in the modern age, publishing preprints is great for promoting open-access, but can routinely mean—just like the journey from kitchen sketch to finished design—published articles have advanced from their early drafts.

That preprint paper was written back in March 2022, and shared just one piece of the overall findings—the team’s study of the spike protein. The vital work on NSP6, which happened in part at the encouragement of peer scientists, was completed after that initial paper was written; it was added to the original material—which remains in the final paper—months later.

“In the sense of evolution, especially in the ultrafast pace of viral replication, each genomic mutation means something, and can be a hint to reveal yet another important phenomenon in infection and disease development,” says Da-Yuan Chen, a postdoctoral researcher in Saeed’s lab and the lead author on the Nature paper. “Little by little, the more we understand the virus, the more correct information we will get. Then, there will be more entry points, drugs, and strategies that we can consider as tools in disease treatment and pandemic control.”

Despite the furor sparked by the inaccurate reporting of the team’s initial findings, Saeed is hopeful that the strength of their science will outlast the false headlines.

“I think the quality of our science is more permanent,” he says. “Our discovery is important. It’s going to have an impact in the field and I think the scientific community is going to be appreciative of this work.”

Boston University

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Patients with cancer have an increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection and worse outcomes, with the highest risk seen for patients with hematologic cancer, according to a study published online Dec. 29 in JAMA Oncology.

Inna Y. Gong, M.D., Ph.D., from the University of Toronto and Sunnybrook Health Sciences Centre, and colleagues examined the association of COVID-19 vaccination with breakthrough infections and complications in patients with cancer versus non-cancer controls. Data were included for 289,400 vaccinated patients with cancer (39,880 with hematologic cancer and 249,520 with solid cancer) and 1,157,600 matched noncancer controls.

The researchers found that patients with hematologic cancer had an increased risk for SARS-CoV-2 breakthrough infection (adjusted hazard ratio [aHR], 1.33; 95 percent confidence interval [CI], 1.20 to 1.46; P

“Our findings support the prioritization of high-risk populations for booster vaccination, forthcoming variant-specific vaccine products, pre-exposure prophylaxis (where available), and rapid antiviral treatment in the face of SARS-CoV-2 infection as COVID-19 continues to be relevant with ongoing surges leading to excess morbidity and mortality,” the authors write.

Copyright © 2022 HealthDay. All rights reserved.

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Individuals with mpox infection ≥14 days after receipt of one JYNNEOS vaccine dose have less hospitalization, fever, headache, malaise, myalgia, and chills compared with unvaccinated individuals, according to research published in the Dec. 30 issue of the U.S. Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report.

Jennifer L. Farrar, M.P.H., from the CDC Mpox Emergency Response Team, and colleagues describe the demographic and clinical characteristics of mpox cases occurring ≥14 days after receipt of one dose of the JYNNEOS vaccine and compared them to characteristics of unvaccinated persons with mpox. The analysis included 6,605 mpox cases during May 22 to Sept. 3, 2022, with available vaccination information.

The researchers found that overall, 276 cases (4.2 percent) occurred among people who had received one dose of vaccine ≥14 days before onset of illness. Mpox cases that occurred in vaccinated individuals versus unvaccinated individuals were associated with a lower percentage of hospitalization (2.1 versus 7.5 percent), fever, headache, malaise, myalgia, and chills.

“Although infection ≥14 days after receipt of one JYNNEOS vaccine dose is infrequent, the occurrence of such cases and the unknown duration of protection conferred by one vaccine dose highlights the need for providers and public health officials to encourage completion of the two-dose vaccination series among persons at risk,” the authors write.

Copyright © 2022 HealthDay. All rights reserved.

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Crisis-wracked Haiti has received a first shipment of cholera vaccines to help battle the intensifying outbreak of the deadly disease, the World Health Organization said Tuesday.

The UN health agency said its regional office PAHO had helped deliver 1.17 million doses of oral cholera vaccines to help battle the disease as cases surge.

Haiti, an impoverished country beset by horrific gang violence and political instability, has been facing a resurgence of cholera since October.

It comes just three years after the Caribbean nation finally stamped out an outbreak that began in 2010 and killed more than 10,000 people.

According to Haiti’s national department of epidemiology, there have so far been 1,220 confirmed cases of the disease in the current outbreak and more than 280 deaths across eight of the country’s 10 departments.

Another 14,100 suspected cases spread across all 10 departments have also been reported.

“Haiti has experience in managing cholera, but the fragile security situation has slowed down response efforts, so the arrival of these vaccines is most welcome,” said PAHO chief Carissa Etienne.

The doses were requested by the country’s health ministry and are being provided by the International Coordinating Group on Vaccine Provision (ICG), which manages the global cholera vaccine stockpile, WHO said.

And around 500,000 more doses of the vaccine, called Evichol, were expected to arrive in Haiti in coming weeks.

A large-scale vaccination campaign was due to start in coming days, WHO said, adding that it would initially target people over the age of one in the areas where most cholera cases have been reported, including in the capital Port-au-Prince and in the slum known as Cite Soleil.

WHO stressed that vaccination should be used in combination with other measures, in particular water, sanitation and hygiene interventions, to prevent the spread of the water-borne disease.

© 2022 AFP

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Among those who have recovered from a coronavirus infection, vaccinated people have a halved risk of becoming infected a second time or contracting COVID-19 again with severe symptoms compared to those who are not vaccinated.

These findings were revealed in an analysis published in the journal Frontiers in Medicine, which was coordinated by Lamberto Manzoli, medical epidemiologist as well as Director of the School of Public Health and Hygiene of the University of Bologna.

“Our results confirm that, among the recovered, those who have received two or three doses of vaccine have a 50% to 60% lower risk of reinfection than those who are not vaccinated,” explains Professor Manzoli.

“Considering that the number of people who recovered is now in the hundreds of millions worldwide, these results appear particularly encouraging and provide strategic information for future pandemic control policies.”

The study also involved scholars from the University of Ferrara and the Sapienza University of Rome and was carried out by collecting and analyzing data from 18 studies conducted in different parts of the world and including a sample of overall 18 million people.

Scholars evaluated several aspects of COVID-19 reinfection through a series of analyses of the data collected. These included differences between people vaccinated with two and three doses, the persistence of protection 12 months after the last infection, and the severity and contagiousness of different variants.

Two main results emerged. One shows that vaccination halves the likelihood of COVID-19 reinfections compared to natural immunity alone obtained with a recovery from the virus. Moreover, data show that even if a second infection occurs, the likelihood of developing severe symptoms is halved in vaccinated people. Similar levels of protection were observed in people vaccinated with only one dose, even for the omicron variant and up to 12 months since the last infection.

“It is worth noting that vaccines have reduced a thankfully already low risk: in absolute terms, the number of reinfections may seem worrying, but cases of severe or fatal COVID-19 symptoms among people who have already recovered once are relatively infrequent: less than 1 in 1,000,” adds Manzoli. “These findings can thus be useful for planning specific immunization strategies for people who have already contracted the coronavirus.”

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