In the past 30 years, density functional theory (DFT) has emerged as the most widely used electronic structure method to predict the properties of various systems in chemistry, biology, and materials science. Despite a long history of successes, state-of-the-art DFT functionals have crucial limitations. In particular, significant systematic errors are observed for charge densities involving mobile charges and spins. A group developed a framework to train a deep neural network on accurate chemical data and fractional electron constraints. The resulting functional outperforms traditional functionals on thorough benchmarks for main-group atoms and molecules. The present work offers a solution to a long-standing critical problem in DFT and demonstrates the success of combining DFT with the modern machine-learning methodology:
A maze is a popular device among psychologists to assess the learning capacity of mice or rats. But how about robots? Can they learn to successfully navigate the twists and turns of a labyrinth? Now, researchers have demonstrated they can. Their robot bases its decisions on the very system humans use to think and act: the brain. The study paves the way to exciting new applications of neuromorphic devices in health and beyond:
Graphene’s electronic structure has been predicted to lead to an unusual orbital response to magnetic fields. However, detecting this orbital magnetism is difficult because it is usually masked by the signal stemming from spins. A group managed to capture this response by placing two giant magnetoresistance detectors below a sample of graphene sandwiched by layers of hexagonal boron nitride. These detectors picked up a strong diamagnetic response from an undoped sample, consistent with theoretical predictions. The technique may be useful in the investigation of other two-dimensional materials:
Running a current through a superconductor can cause the superconducting gap to close on a section of the Fermi surface. However, observing this segmented Fermi surface directly is tricky. To do so, researchers worked with a thin film of the topological insulator bismuth telluride placed on top of superconducting niobium diselenide. A small applied magnetic field caused a screening current, which in turn led to a segmented Fermi surface in the topological insulator layer. Using a scanning tunnelling microscope, the researchers were able to map out this Fermi surface:
It is well known that oil forms stable droplets that carry a negative electrophoretic mobility (and negative charge) upon dispersing in water. However, the underlying mechanism is a long-debated topic. Using vibrational sum-frequency scattering spectroscopy, researchers recorded the interfacial vibrational spectrum in the oxygen–deuterium and carbon–hydrogen stretching regions of a hexadecane–water interface. Their spectral analysis accompanied by molecular dynamics simulations showed that water molecules form “improper” interfacial hydrogen bonds with alkyl hydrogens, resulting in the water-to-oil charge transfer that stabilizes oil droplets. This work demonstrates that sum-frequency scattering spectroscopy is a powerful technique that can improve our understanding of hydrophobicity in water-mediated chemical and biological systems:
After being flattened by a 4,000-kilogram weight, a puck-shaped sample of a wobbly, gummy-like material can spring back to its original shape within 2 minutes. Jellies normally crack under pressure from the back of a spoon. Researchers sought to create a resilient, soft gel that could spread out and bounce back instead. In most gels, long polymer molecules directly connect to each other to form 3D networks. The team instead opted for an indirect way to link the polymer strands together. In their gel, the long polymer chains are adorned with two types of small ‘guest’ molecule. The guest molecules hang from the polymers and are enclosed, in pairs, by cylindrical molecules, creating links that knit the polymer chains together. When pressure is applied to the gel, the guest molecules slowly break out of their enclosures, allowing the gel to spread like a liquid. When fully flattened, the gummy material transforms into a substance resembling a hard, shatterproof glass. A pressure sensor made from the gel, worn on the sole of the foot, recorded a person walking and jumping in real time. The researchers hope that this gel could one day be incorporated into prosthetics or robotic skin:
Comets and asteroids have bombarded many planets, including Earth in its youth. But the seven Earth-sized worlds in an iconic planetary system have enjoyed a relatively quiet and undisturbed life, research shows. The seven planets circling a star named TRAPPIST-1 are known for being the largest group of Earth-sized planets in a single stellar system. A team simulated what would happen if the TRAPPIST-1 planets had been hit by many space rocks during and after their formation. The team found that the planets could not have been pummelled by anything larger than Earth’s Moon. If they had, their fragile orbital relationship would have been disrupted. Space smash-ups are thought to have supplied water to Earth and other planets. The TRAPPIST-1 planets’ relatively unruffled history suggests that their water must have been there from the start, perhaps in their molten interiors, and was not delivered later by comets or other impactors. The work shows that planets have many ways to acquire water and other ingredients needed for life:
Astronomers have spotted the tiniest, most metal-based planet yet, an iron-rich world that is light years away from Earth and zips around its star once every eight hours. The planet, known as GJ 367b, is three-quarters the size of Earth, but much denser. It’s more like Mercury, in that it is made mostly of iron and is superheated by blazing radiation from its star. GJ 367b is a searing 1,500°C during the day, nearly hot enough for its iron to begin to melt. GJ 367b is the smallest planet outside the Solar System for which scientists have been able to determine the composition. Astronomers have discovered more than a dozen ‘ultrashort-period’ planets, which are so close to their stars that they make a complete orbit in less than a day. The GJ 367b discovery showcases our ability to measure the mass of tiny, sub-Earth planets. Being able to observe such planets is fascinating and promises many Earth-like planet discoveries in the future:
If a child had been asked to draw a planet 30 years ago, they would have had a relatively straightforward task. Perhaps they would draw Earth in orbit around the Sun, or maybe Saturn with its beautiful ring system. Now, the options are dizzying; as detection techniques have become more powerful, myriad planetary systems have been discovered, hosting planets with a range of masses, charting varied orbits around a diverse population of stars. A team have further stretched our collective imagination of what a planetary system looks like, by directly imaging a planet of roughly ten times the mass of Jupiter, orbiting not one, but two stars, whose combined mass is nearly ten times that of the Sun:
Scientists have published an analysis laying out how the tiny beads of glass inside many meteorites came to be, and what they can tell us about what happened in the early solar system:
Maybe this should be in the section above. The use of deep learning has revolutionized the field of protein modelling. Researchers combined this approach with proteome-wide, coevolution-guided protein interaction identification to conduct a large-scale screen of protein-protein interactions in yeast. The authors generated predicted interactions and accurate structures for complexes spanning key biological processes in Saccharomyces cerevisiae. The complexes include larger protein assemblies such as trimers, tetramers, and pentamers and provide insights into biological function:
The long, narrow leaves of grasses look rather different from the often shorter, flatter leaves of eudicot plants. A team combined developmental genetics and computational modelling to reveal that these two types of leaves, which are widely separated by evolution, have more in common than expected. Expression of similar patterning genes in the primordial zone is confined to a wedge for the eudicot leaf but expanded to concentric domains in the grass leaf, driving development of the cylindrical, encircling sheath characteristic of these leaves. Addition or removal of gene expression in a marginal zone contributes to the development of the broader leaf characteristic of eudicots. Thus, grass and eudicot leaves are diversified elaborations of shared toolkits:
One approach to enhancing cellular regeneration in the brain is to exploit the molecular mechanisms used by the juvenile brain when regeneration potential is high. A team found that irradiation injury in the neonatal cerebellum causes a progenitor cell that usually makes glial cells to instead switch its potential and make neurons. Single-cell sequencing implicated the transcription factor Ascl1 as the factor that controls this switch in potential, and the switch did not occur in the absence of Ascl1. This study provides new insight into the plasticity potential of the juvenile brain and potential targets to enhance regeneration after injury:
Research has revealed a correlation between being particularly proficient in tool use and having good syntactic ability. A new study has now shown that both skills rely on the same neurological resources, which are located in the same brain region. Furthermore, motor training using a tool improves our ability to understand the syntax of complex sentences and, vice-versa, syntactic training improves our proficiency in using tools:
As transient structures in early brain development, the ganglionic eminences generate dozens of different types of interneurons that go on to migrate throughout and weave together the developing brain. A team analysed human fetal ganglionic eminences. Single-cell transcriptomics revealed unexpected diversity in the types of progenitor cells involved. The human ganglionic eminence depends more heavily on intermediate progenitor cells as workhorses than does the developing neocortex, with its greater reliance on radial glial cells:
The desire to consume food is one of the strongest drives in nature, and its opposition by inhibitory signals is required to maintain an optimal energy balance. In calorie-rich environments, how much we eat is jointly influenced by our internal state (for example, how hungry we feel) and the effect of environmental cues, such as the aroma or visual appeal of food. When we are hungry and see or smell a meal, we initiate a series of actions that will lead to us consuming the food. If we feel full or lack an appetite, we would probably push the plate away and end the meal. Researchers show that neuronal cells in a brain region called the cerebellum have a key role in regulating satiety and meal termination:
You might see the gigantic Haast’s eagle in your nightmares, but never aloft in the New Zealand skies, because it went extinct centuries ago. But was this largest known eagle of all time, weighing as much as 15 kilograms, a fearsome hunter or simply a scavenger? A group used fossils of the Haast’s eagle (Hieraaetus moorei) to create computer models of its talons and skull1. The authors then compared these features to those of extant hunting and scavenging birds. Hunting birds typically have relatively long talons that they use to secure struggling prey, and tough beaks and skulls that function as weapon systems. The team finds that the Haast’s eagle had talons and a beak like those of modern eagles, whereas the rest of the skull was more vulture-like. Simulations show that it would have been good at pulling its head back, a motion commonly made by scavengers tearing tissue from a carcass. But it could also bite hard. The eagle emerges as a raptor capable of hunting and killing live prey much larger than itself, which it would then feast on while on the ground, perhaps even by plunging its featherless head into the still-warm viscera. Sweet dreams:
Hailed a superfood, quinoa has seen its popularity soar in the past decade. But the grain-like seed was already prized some 3,000 years ago: researchers have found that it helped to fuel an ancient Andean civilization in an inhospitable climate through centuries of political upheaval. A group reconstructed the diets of people living in the Andean highlands near Lake Titicaca between 1400 BC and AD 1100. During this time, the region evolved from an agricultural society to a powerful empire whose political centre was Tiwanaku, located at an altitude of nearly 4,000 metres, in modern Bolivia. The researchers found that, for millennia, quinoa, potatoes and llama meat were the staple foods of people in the region, including the Tiwanaku people. They ate little fish, despite living near a lake, and used maize (corn) to make an alcoholic drink, which they consumed on special occasions. The findings suggest that locally grown quinoa, potatoes and llamas provided long-term food security, which helped the Tiwanaku culture to flourish:
Pallid swifts are the marathoners of the sky, spending most of their lives in flight. Tracking devices now show that pallid swifts have not only endurance but also speed: some cross the Sahara Desert at an average pace of 400 kilometres per day. For 2 years, a team tracked pallid swifts (Apus pallidus brehmorum) from a single breeding colony in Gibraltar, which is located on the Iberian Peninsula’s southern coast. After breeding, the birds flew to Africa, crossed the Sahara and then moved south into the neighbouring savannah, where they stayed for about a month before flying further south into a forested zone. Four months later, the birds began the northward journey back to their breeding grounds. The researchers found that one bird traversed the core of the Sahara, a distance of about 1,000 kilometres, in 30 hours, flying non-stop and around the clock. And two of the tracked swifts lived in the airspace above Africa for eight months without landing once. The findings suggest that migrating pallid swifts are on the wing even at night, the researchers say:
Even for embryology researchers, it is difficult to grasp that the entire human body is derived from a single cell. In the first weeks of life, this cell divides, building all the embryonic as well as the supportive tissues, such as the placenta. Advances in technologies to study individual cells have provided unprecedented mechanistic insights into the initial ‘decisions’ that determine the fate and lineages of cells in the early embryo, before it implants into the wall of the uterus. However, the events that follow implantation have remained a ‘black box’, with knowledge based mostly on limited historical histological collections, or on experimental work performed on model organisms or in vitro model systems. A group provide a glimpse into this black box by profiling gene expression in individual cells in a post-implantation human embryo, using a method called single-cell RNA sequencing:
The way we instinctively speak to babies, higher pitch, slower speed, exaggerated pronunciation, not only appeals to them, but likely helps them learn to understand what we're saying. New research suggests that baby talk can have another, previously unknown benefit: helping babies learn to produce their own speech. By mimicking the sound of a smaller vocal tract, the researchers think, we're cluing babies in to how the words should sound coming out of their own mouths:
For the first time, scientists have identified a rare population of potentially toxic senescent cells in human brains that can serve as a target for a new Alzheimer's disease treatment. Senescent cells are old, sick cells that cannot properly repair themselves and don't die off when they should. Instead, they function abnormally and release substances that kill surrounding healthy cells and cause inflammation. Over time, they continue to build up in tissues throughout the body contributing to the aging process, neurocognitive decline and cancer. The eigengenes developed may be useful in future senescence profiling studies as they identified senescent cells accurately in snRNA-Seq datasets and predicted biomarkers for histological investigation:
Gut bacteria are both positively and negatively influenced by common medicines, new research shows. Medications that lower cholesterol and blood pressure are associated with a healthier composition and function of gut bacteria, while gastric acid inhibitors and antibiotics interfere with health-promoting bacterial communities:
A new method for quantifying plant evolution reveals that after the onset of early seed plants, complexity halted for 250 million years until the diversification of flowering plants about 100 million years ago:
Retiring ‘super polluting’ power plants to aid the climate could have another benefit: saving millions of lives. Power plants that burn coal and other organic materials such as wood are major sources of harmful air pollution, especially in Asia. To examine how efforts to slow global warming would affect these toxic emissions, a US group estimated the global health impacts of fossil-fuel-burning power plants. They found that in 2010, air pollution from these plants caused around 860,000 premature deaths. The researchers’ modelling showed that the plants’ annual death toll could drop to less than 200,000 by 2050. But that improvement could be achieved only under certain conditions. Climate policies would have to be stringent enough to limit warming to within 1.5°C of pre-industrial temperatures, plants would need to institute strict pollution-control measures, and the most polluting plants would have to be retired very early. Climate-driven policies alone will not be sufficient to avert the greatest number of deaths, the authors say, policies targeting the plants’ health impacts will also be needed:
Although deforestation is rampant across the tropics, forest has a strong capacity to regrow on abandoned lands. These “secondary” forests may increasingly play important roles in biodiversity conservation, climate change mitigation, and landscape restoration. A group analysed the patterns of recovery in forest attributes (related to soil, plant functioning, structure, and diversity) in 77 secondary forest sites in the Americas and West Africa. They found that different attributes recovered at different rates, with soil recovering in less than a decade and species diversity and biomass recovering in little more than a century. The authors discuss how these findings can be applied in efforts to promote forest restoration:
The goal of mitigating climate change requires a global commitment to reducing greenhouse-gas emissions to avoid substantial temperature increases. However, achieving this objective is complicated by uncertainty over how much carbon dioxide will be absorbed naturally by trees and other plants. A group have constrained estimates of this uncertainty by drawing empirical links between observations of the current climate and multi-model predictions of the land-carbon sink. The relationships between these observations and predictions are known as emergent constraints:
Where are we with neutralisation assays and lab work other than me saying we need real world data? Thus far, and in summary 2 European labs, two South African labs and Pfizer datasets suggest the primary series of 2 vaccine doses provide limited protection while 3 doses provide some. While each of the papers uses different time points, different sera samples and each has a limited data set (no one has more than 34 samples), the overall conclusion is generally consistent:
Sigal et. al: Based on 12 samples, the paper suggests that neutralisation for 2 doses of Pfizer's vaccine is reduced by ~41x. People who were vaccinated after they were infected had a smaller drop (left 2 panels below):
Sheward et al: Using 34 samples of previously infected individuals and hospital workers (with some who also received vaccination and some who were boosted) a wide variety of titre drops were observed. Using the control WHO sera samples, a 40x reduction in neutralisation was observed (right 2 panels below):
Wilhelm et al: Two doses of Pfizer or Moderna's vaccine had limited to no neutralisation. 2 doses plus a homologous or heterologous boost provided some level of protection:
Kimpel et al: Two doses of vaccination broadly provided no protection. A heterologous series of ChAdOx plus Pfizer had some limited protection. The sera from the Pfizer vaccine were taken at an earlier timepoint than the Moderna vaccine which may impact the differences in results coupled with the small numbers (10 for Moderna and 20 for Pfizer):
Pfizer: Management indicated that there was a 25x drop in neutralisation after 2 doses of vaccine. We would note that based on the data, the sera after two doses were below the limit of detection (LOD) of the assay suggesting limited to no protection. A 3rd dose returned sera to some level of protection, but we would also note that the boost occurred off a very low base and produced a significantly higher fold change compared to boosts for other variants suggesting we need more samples to confirm the results (n=19-20, I cannot work out if 19 or 20):
The limited impact of two vaccine doses on infection control suggest breakthrough infections should increase significantly assuming Omicron becomes widespread: While it is important that 3 doses provide some protection against infection, the vast majority of the world only has 2 vaccine doses or none at all. Thus, the global protection against symptomatic disease from Omicron is limited. Therefore, assuming Omicron continues to spread broadly and overtakes Delta, the global infection rate should increase significantly in the coming weeks and could be higher than the prior Delta waves:
Initial Pfizer T-cell data suggests protection against severe outcomes even with only 2 doses. Importantly, as we have previously written, vaccines should still limit the occurrence of severe outcomes such as hospitalisation and death. In particular, initial T cell data from Pfizer's vaccine suggests that most of the T cell epitopes are conserved with Omicron. While vaccination should decouple hospitalisations from infections, if the absolute number of infections is high, hospitalisations could still be substantial.
I keep in mind this previously. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles:
A new algorithm may be able to alert the wearers of Fitbits, Apple Watches and other fitness trackers to pre-symptomatic Covid-19 infection, according to a big study. Spotting the signs of Covid-19 and other respiratory infections before symptoms develop has become a hot area. In the new study, researchers developed a system that generated alerts based on changes in overnight resting heart rate and tracked them over the course of several months. The system sent alerts to 80% of people who went on to test positive for Covid, picking up the signals a median three days before symptoms set in. But the alerts didn’t always point to Covid: user surveys revealed they also, in most cases, simply signalled other infections, stress, or poor sleep:
Linking automated texts to phone assessment of deteriorating patients was associated with lower mortality. Concerns about preventing infection, as well as other stresses on the health care system due to the pandemic, have prompted innovative approaches to patient monitoring and triage. A large health care system in Philadelphia developed a simple, automated, twice-daily texting tool (COVID Watch) that queried enrolled SARS-CoV-2–positive patients regarding health status; those with worsening symptoms were contacted by a health care provider for further assessment. Now, investigators report outcomes from March 23 to November 30, 2020, in 3488 COVID Watch enrolees compared with 4377 SARS-CoV-2–positive patients who received standard care. Almost 87% of COVID Watch participants responded to at least one text, and in 14% of these, the response elicited contact from an RN. More telemedicine and emergency department visits occurred in the COVID Watch group within 30 days. The overall number of deaths at 60 days was small: 16 (0.37%) in usual care and 5 (0.14%) in COVID Watch, with 2.5 fewer deaths per 1000 patients in the COVID Watch group. No deaths outside of the hospital occurred in the COVID Watch group versus 6 (37.5%) in the usual care group:
In a nationwide Swedish cohort study, risk for SARS-CoV-2 infection in nonimmune family members fell by up to 97% as the number of immune family members increased. While COVID-19 vaccination reduces incidence, severity, and transmission of SARS-CoV-2 infection, more-detailed information is lacking regarding the effects of immunity (whether due to vaccination or previous infection) in households that also include nonimmune family members. Now, a population-level study in Sweden provides further information on family transmission in partially immune households. Using government health records, Nordström et al. assessed about 1,800,000 individuals from >800,000 families with two to five members for the development of COVID-19 in nonimmune family members. Between April 14 and May 26, 2021, 5.7% of nonimmune family members developed COVID-19. Risk for infection was reduced by 45% to 61% if one family member was immune and up to 97% if four family members were immune. Reductions in infection risk were similar whether immunity was due to previous infection or vaccination:
Decreases in neutralisation are predictive of vaccine efficacy, although no correlate of protection (CoP) for SARS-COV-2 has been fully established. In-vitro neutralisation titres remain a correlate of protection from SARS-CoV-2 variants and modelling of the effects of waning immunity predicts a loss of protection to the variants after vaccination. A recent meta-analysis in the Lancet analysed data from 24 identified studies on in-vitro neutralisation and clinical protection to understand the loss of neutralisation to existing SARS-CoV-2 variants of concern:
In booster news, people who got two Pfizer-BioNTech shots may get as much benefit from a J&J booster as a Pfizer one, according to a small study posted yesterday:
A fascinating AI modelling study estimates that Omicron is twice as transmissible as Delta, and twice as likely to escape vaccines:
The evolution of viral variants and waning antibody levels over time raise questions regarding the longevity of vaccine-induced immune protection. A group examined B and T lymphocyte responses in individuals who received SARS-CoV-2 messenger RNA vaccines. They performed a 6-month longitudinal study of individuals who never had SARS-CoV-2 infection compared with people who had recovered from SARS-CoV-2. Humoral and cellular immune memory was observed in vaccinated individuals, as were functional immune responses against the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) viral variants. Analysis of T cell activity suggested that robust cellular immune memory may prevent hospitalisation by limiting the development of severe disease:
A randomized trial involving various COVID-19 and influenza vaccines found that concomitant administration was safe and immunogenic. When COVID-19 vaccines were first authorized, administration of other vaccines was generally separated by at least 2 weeks. As experience accumulated, however, concomitant administration of COVID-19 vaccines with other immunisations became the norm. Now, a randomized clinical trial in the U.K. supports this practice. About 680 participants were recruited for a six-cohort study of two different COVID-19 vaccines (ChAdOx1 [AstraZeneca] or BNT162b2 [Pfizer-BioNTech]) and three different influenza vaccines. Participants received the second dose of each COVID-19 vaccine either concomitantly with one of the influenza vaccines or spaced apart by 3 weeks. Mild and moderate vaccine reactions were common, but rates were similar in most cohorts and no safety concerns arose. Antibody responses to SARS-CoV-2 and to influenza were similar between those who received concomitant or staggered administration of the vaccines:
Researchers demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralisation by therapeutic antibodies and serum from vaccine recipients. They identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralisation. These findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans:
COVID-19 vaccines have resulted in robust humoral responses and protective efficacy in human trials, but efficacy trials excluded individuals with a prior diagnosis of COVID-19. As a result, little is known about how immune responses induced by mRNA vaccines differ in individuals who recovered from COVID-19. Here, we evaluated longitudinal immune responses to two-dose BNT162b2 mRNA vaccination in 15 adults who had experienced COVID-19, compared to 21 adults who did not have prior COVID-19. Consistent with prior studies of mRNA vaccines, we observed robust cytotoxic CD8+ T cell responses in both cohorts following the second dose. Furthermore, SARS-CoV-2-naive individuals had progressive increases in humoral and antigen-specific antibody-secreting cell (ASC) responses following each dose of vaccine, whereas SARS-CoV-2-experienced individuals demonstrated strong humoral and antigen-specific ASC responses to the first dose but these responses were not further enhanced after the second dose of the vaccine at the time points studied. Together, these data highlight the relevance of immunological history for understanding vaccine immune responses and may have implications for personalizing mRNA vaccination regimens used to prevent COVID-19, including for the deployment of booster shots:
A particular mutation could have occurred in a host simultaneously infected by SARS-CoV-2, also known as the novel coronavirus, and the HCoV-229E coronavirus, which can cause the common cold. The shared genetic code with HCoV-229E has not been detected in other novel coronavirus variants, the scientists said.” The study is in preprint and has not been peer-reviewed, but the similarity between omicron and HCoV-229E is “striking”:
In what might be another spillover effect from the pandemic, blood pressure levels went up in more people than went down compared to pre-pandemic readings, a potential sign of more cardiovascular disease to come, a new study suggests. Researchers tracked monthly blood pressure readings for more than 460,000 people taken as part of workplace wellness programs. Compared to levels recorded before the pandemic, 27% of participants moved to a higher blood pressure category while 22% dropped to a lower one from April through December 2020. The uptick in blood pressure wasn’t tied to weight gain, the researchers conclude, because the proportion of people whose weight rose was similar before and after the pandemic began. Still, even small increases in blood pressure matter, they warn:
A team asked what are the sociodemographic, clinical, and epidemiologic characteristics of persons diagnosed with tuberculosis (TB) and COVID-19 in close succession in California? In this cross-sectional analysis of public health surveillance records from California residents, 91 individuals diagnosed with TB and COVID-19 more commonly had Hispanic or Latino ethnicity, diabetes, and residence in a low health equity census tract compared with those who received a TB diagnosis before the COVID-19 pandemic. Mortality rates among those diagnosed with TB and COVID-19 in close succession were higher than mortality rates among those with TB before the COVID-19 pandemic and those with COVID-19 alone. The findings of this analysis suggest that addressing long-standing health inequities and integrating prevention measures for COVID-19 and TB in California may reduce the co-occurrence of these diseases and prevent deaths:
Researchers asked what is the effectiveness of SARS-CoV-2 vaccination in patients with cancer? In this cohort study of US Veterans Affairs patients who received systemic therapy for cancer between August 15, 2010, and May 4, 2021, a proxy measure for effectiveness of the vaccine starting 14 days after the second dose was 58%. The measure of effectiveness starting 14 days after the second dose was 85% in patients who had not received systemic therapy within the 6 months prior to vaccination and 76% among those receiving hormonal treatment. Results suggest that SARS-CoV-2 vaccination associated with lower infection rates in patients with cancer, especially in those not receiving current systemic therapy and those receiving hormonal treatment:
A study shows longer mRNA vaccine dosing intervals demonstrated improved immunogenicity, which was consistent when responses were measured based on timing of the first or second dose. These data suggest that extending dosing intervals may be particularly advantageous against the Delta variant. A delayed second-dose strategy could yield faster partial protection to a larger proportion of the population when vaccine supplies are limited. Modelling studies have estimated overall decreased mortality with delayed second doses when accounting for partial protection provided after 1 dose, even without taking into consideration the potential benefits of delayed second doses on long-term vaccine effectiveness. However, the trade-off of lower individual immune protection after 1 dose may be unfavourable in at-risk groups or settings where COVID-19 prevalence is high:
An article by the CDC reports on the effect of hospital strain resulting from the COVID-19 pandemic. This strain is characterized by a reduction in preventative and electoral procedures, and a general shift in focus toward immediate care for patients infected with SARS-CoV-2 at the expense of patients with other needs. This shift has been correlated to an increase in intensive care unit (ICU) bed occupancy, as well as all-cause death, i.e., deaths from both COVID-19 and COVID-19-independent causes. A negative binomial regression model was generated based on two sets of data from the period of July 2020 to July 2021: 1) excess death from all-causes (defined as the difference between actual deaths and expected deaths), and 2) hospital strain (based on ICU bed occupancy). The model predicts that as ICU bed occupancy reaches 75%, 12,000 excess deaths could occur within the following two weeks. Because the model predicts an exponential relationship, excess deaths could reach 80,000 in the two weeks following 100% occupancy. At both occupancy rates, the model predicts additional deaths at weeks four and six. The article emphasizes how this correlation is an important call-to-action for using preventative measures to control case rates and the need for COVID-19-related hospitalisation:
Researchers asked does the use of high-flow oxygen therapy through a nasal cannula, compared with conventional oxygen therapy, reduce requirement of intubation and time to clinical improvement among patients with severe COVID-19? In this randomized clinical trial that included 220 patients with severe COVID-19, the rate of intubation and mechanical ventilation for those treated with high-flow oxygen therapy through a nasal cannula vs with conventional oxygen therapy was 34.3% vs 51.0%, respectively; the median time to clinical recovery was 11 days vs 14 days. Both comparisons were statistically significant. Among patients with severe COVID-19, treatment with high-flow oxygen therapy compared with conventional oxygen therapy reduced the likelihood of invasive mechanical ventilation and decreased time to clinical recovery:
Preliminary Report - Early release, subject to modification
Quantification of the neutralization resistance of the Omicron Variant of Concern.
Daniel J. Sheward1,2, Changil Kim1, Alec Pankow1, Xaquin Castro Dopico1, Darren Martin2, Joakim Dillner3, Gunilla B. Karlsson Hedestam1, Jan Albert1,4, Ben Murrell1
1 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden 2Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa
3 Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden. 4 Dept of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden
Summary: The reduction in neutralization of the newly-emerged SARS-CoV-2 B.1.1.529 (Omicron) variant of concern1is highly variable. Fold-reduction, relative to the pandemic founder, ranged from 1 to 23, with quartiles of 2.5, 5.5, and 11, measured by lentiviral pseudotype neutralization assay. This was estimated from two cohorts: 17 random recent blood donors in Stockholm, and a set of 17 previously-infected hospital workers with higher mean neutralizing antibody titers against the WuHu-1 founder variant than those observed in the blood donors. Almost all serum samples evaluated retained some neutralization activity against the Omicron variant. The First WHO International Standard (20/136) showed a ±40-fold reduction in the neutralization of Omicron (IC50from 0.6 IU/ml to 23.4 IU/ml). These preliminary data on the neutralization sensitivity of the Omicron variant require both internal and independent confirmation, and the clinical impact of natural and vaccine-induced immunity with respect to protection from infection and severe disease needs urgent investigation.
Figure 1: Pseudovirus neutralization titers for Blood Donors (BD; N=17) and Hospital Workers (HW; N=17) against the pandemic founder variant (WT), the B.1.617.2 variant (Delta) and the B.1.1.529 variant (Omicron).
Figure 2: Fold reduction in neutralization of the Omicron variant compared to the pandemic founder variant for Blood Donors (BD, N=17) and Hospital Workers (HW, N=17) from Stockholm, Sweden.
Donor sample description: Two cohorts were studied. Cohort 1 comprised serum samples with detectable neutralization against the Wu-Hu-1 founder variant from 17 anonymized blood donors (“BD”), donated during week 48, 2021, in Stockholm, Sweden. Cohort 2 comprised 17 serum samples from Hospital Workers (“HW”) at the Karolinska University Hospital in Stockholm, who were invited to participate in a study that aimed to characterize their antibody responses following SARS-CoV-2 infection and subsequent vaccinations. Participants were confirmed PCR positive in May 2020 and serum samples collected in November 2021 were analyzed.
Assay details: A region of spike (with codons corresponding to amino acid positions 43 to 1000) incorporating all of the Omicron variant reference mutations was amplified from cDNA derived from a later-confirmed B.1.1.529 clinical sample obtained from a set of anonymized early cases of suspected Omicron infections. The spike fragment was subcloned by Gibson Assembly into a codon-optimized SARS-CoV-2 Spike expression vector (in pcDNA3.1), harbouring a mutation that introduces a stop codon that truncates the last 19 amino acids of the cytoplasmic tail (facilitating efficient incorporation onto lentiviral particles). The spike-encoding expression vector was confirmed by sequencing to be identical, by amino acid, to the Omicron consensus. Omicron Spike-pseudotyped lentivirus particles were generated by the co-transfection of HEK293T cells with the Omicron variant spike plasmid, an HIV gag-pol packaging plasmid (Addgene #8455), and a lentiviral transfer plasmid encoding firefly luciferase (Addgene #170674). Neutralization was assessed in HEK293T-ACE2 cells, and all samples were run simultaneously.
Statistical analysis: Individual ID50 values for each sample against each variant were calculated in GraphPad Prism v9 by fitting a four-parameter logistic curve to neutralization by serial 3-fold dilutions of serum, as described previously2.
HW cohort: Informed consent was obtained from all participants as part of an ethics approval (Decision number 2020-01620) from the National Ethical Review Agency of Sweden. BD cohort and Omicron-positive samples were anonymized, and not subject to ethical approvals.
We acknowledge the G2P-UK National Virology consortium funded by MRC/UKRI (grant ref: MR/W005611/1) and the Barclay Lab at Imperial College for providing the B.1 and B.1.617.2 spike-encoding plasmids. pCMV-dR8.2 dvpr was a gift from Bob Weinberg (Addgene plasmid # 8455; http://n2t.net/addgene:8455; RRID:Addgene_8455). pBOBI-FLuc was a gift from David Nemazee (Addgene plasmid # 170674; http://n2t.net/addgene:170674; RRID:Addgene_170674)
This project was supported, in part, by funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 101003653 (CoroNAb) to G.B.K.H., and B.M; from the SciLifeLab Call 4.1: Laboratory preparedness for pandemics (Reg no. VC-2021-0033) to B.M. and J.A.; from the Erling Persson Foundation to B.M and G.B.K.H.
We acknowledge all staff at the Department of Clinical Microbiology, Karolinska University Hospital involved in SARS-CoV-2 routine diagnostics, S-gene screening and sequencing.
- Classification of Omicron (B.1.1.529): SARS-CoV-2 variant of Concern. https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2- variant-of-concern.
- Sheward, D. J. et al. Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models. Cell Rep Med 2, 100450 (2021).