Science Update

Science Update

Non-COVID papers:

To promote biomedical research, genomic data are often shared in controlled settings or public repositories, posing a privacy risk if they can be algorithmically reassociated with an individual. Researchers now show that the average risk to privacy in this setting is relatively low and decreases further with more individuals in the data. The authors analysed public genomes and face images to link faces to phenotypes (e.g., eye, hair, and skin colour) using current deep learning tools and to link genomes to phenotypes using single-nucleotide polymorphisms. However, technological advances could pose new risks, and targeted privacy risks remain. These findings highlight the potential for future privacy risks as technology continues to advance:

https://www.science.org/doi/10.1126/sciadv.abg3296

Satellites organized in flexible networks known as constellations are more agile and resilient than are those operating alone. Manoeuvring satellites into such constellations requires inexpensive, reliable and efficient engines. Many networked satellites have electric propulsion thrusters, which generate thrust by using electrical energy to accelerate the ions of a propellant gas. However, the choice of gas presents a problem. Ionizing xenon requires a relatively small amount of energy, but xenon gas is expensive and needs to be compressed in high-pressure tanks to fit on board a satellite. Krypton is cheaper, but still requires a complex and heavy gas-storage and -supply system. Now a team report a successful demonstration of an iodine-ion thruster in space — offering a cheaper and simpler alternative to xenon or krypton:

https://www.nature.com/articles/d41586-021-03384-8

The atmosphere of Jupiter consists of bands of winds rotating at different rates, punctuated by giant storms. The largest storm is the Great Red Spot (GRS), which has persisted for more than a century. It has been unclear whether the storms are confined to a thin layer near the top of the atmosphere or if they extend deep into the planet. Bolton et al. used microwave observations from the Juno spacecraft to observe several storms and vortices. They found that the storms extended below the depths at which water and ammonia are expected to condense, implying a connection with the deep atmosphere. Scientists analysed gravity measurements taken while Juno flew over the GRS. They detected a perturbation in the planet’s gravitational field caused by the storm, finding that it was no more than 500 kilometres deep. In combination, these results constrain how Jupiter’s meteorology links to its deep interior:

https://www.science.org/doi/10.1126/science.abf1396

Two identical fermions cannot occupy the same quantum state, or so says the Pauli principle. For a cold gas of fermionic atoms, this means that all states up to the Fermi energy will be occupied, with only the atoms with the highest energy able to change their state. Such conditions have long been predicted to suppress light scattering off gases because the atoms receiving a kick from collisions with photons would have no state to move to. Three teams now describe this so-called Pauli blocking of light scattering:

https://www.science.org/doi/10.1126/science.abh3470

For most alloys, conventional or high entropy, increasing strength comes at the cost of poor ductility. Although there are many strategies to break this inverse relationship, scientists show that cyclic torsion on a high-entropy alloy enhances strength without degrading ductility (see the Perspective by Yeh). Cyclic torsion creates a gradient of dislocations and low-angle grain boundaries from the surface to the interior that organize into tiny stacking faults and twin when straining begins. These structures allow for good ductility while simultaneously helping to work harden the alloy:

https://www.science.org/doi/10.1126/science.abj8114

Despite decades of research, the role of quantum mechanical effects in molecular scattering has not yet been fully investigated and can still demonstrate fascinating results, even for simple triatomic systems. Researchers now show that the entangled bond axis orientations in the biaxial state of a deuterium molecule can act as the two slits of a double-slit interferometer for rotationally inelastic collision with a helium atom, giving rise to quantum interference between two indistinguishable pathways. The present work presents an elegant example of quantum interference in molecular scattering that is conceptually similar to the famous Young’s optical double-slit experiment. The proposed molecular interferometer could be used to coherently control the phases in various molecular processes in future experiments:

https://www.science.org/doi/10.1126/science.abl4143

Disposable masks and gloves might have helped to relieve the COVID-19 pandemic, but they have worsened the world’s plastic-waste crisis. Thousands of tonnes of plastic from hospital waste, face masks and other single-use items are flooding the oceans, a study shows. A group estimate that, from the start of the pandemic until 23 August 2021, the 193 countries they studied generated a total of more than 8 million tonnes of pandemic-related plastic waste, 87% of which was medical waste from hospitals. The researchers calculated that rivers carried nearly 26,000 tonnes of pandemic-associated plastic to the oceans — Asian rivers accounted for about 70% of the total. The team also used a mathematical model to simulate the fate of the plastic in the oceans. By the end of 2021, small amounts of pandemic plastic will have sunk to the sea floor; however, 71% is expected to wash up onto beaches. By 2025, the remaining plastic waste will have formed large garbage patches or become trapped in the Arctic Ocean. The authors call for better management of medical waste, especially in low-income countries:

https://www.pnas.org/content/118/47/e2111530118

Informal, low-income settlements in tropical cities will be hit even harder than predicted by climate change, resulting in dire income losses and declining health. Models predict that the tropics will experience the world’s largest increase in the frequency of extreme heat events in the next few decades. But these forecasts are based on data collected at weather stations, which can differ from the temperatures in places where people live. A team placed sensors in more than 100 houses in urban informal settlements in Makassar, Indonesia — neighbourhoods that they say are representative of living conditions for some 370 million people in East and southeast Asia. They used the sensor data to estimate the heat stress experienced by residents. Ramsay’s team found that 80% of the sensor recordings during the rainy season of 2018–19 surpassed thresholds above which health and work are negatively impacted. They also found that heat-related conditions in the settlement are approaching the upper limits of human survivability. The authors say that their findings are particularly worrisome because many people in informal settlements depend on labour-intensive employment, which makes them particularly vulnerable to heat stress. Furthermore, most households lack air conditioning and other ways to mitigate the heat:

https://linkinghub.elsevier.com/retrieve/pii/S2589004221012177

A high-resolution scanner roughly as thick as a human hair can be wrapped around objects about 1 centimetre in diameter, allowing it to image fingerprints as well as documents. Crystalline materials called metal halide perovskites have excellent optical and electronic properties, which make them useful for solar cells, lasers and light detectors. But it has been difficult to produce flexible, high-resolution scanners based on these materials. Researchers have now created such a device, which relies on an array of metal-halide-perovskite light sensors. To make them, the team fabricated a plate consisting of thin, flexible transistors that are typically used in high-resolution computer monitors. The plate was then coated with a metal-halide-perovskite-containing solution. The researchers suggest that the resulting wrap-around device could be embedded in mobile phones and door handles for fingerprint authentication, and might have applications in medical imaging, surveillance and optical communication:

https://www.nature.com/articles/s41928-021-00662-1

Researchers have harnessed the world’s brightest X-rays to create intricate maps of human organs at various scales, from the entire organ down to individual cells. They call their new method hierarchical phase-contrast tomography (HiP-CT). It scans post-mortem samples with X-rays from the European Synchrotron in Grenoble, France, that are 100 billion times brighter than those in a typical hospital X-ray machine. The method can discern structures that are only a few micrometres across — about the size of a red blood cell. Other imaging methods either provide lower resolution or take months to complete and involve processes that change the organ’s shape. HiP-CT works in under a day and requires minimal changes to organs. When applied to the lung of a man who had died from COVID-19, the method revealed degraded tissue and blockages in blood vessels so small that they are usually observed using microscopes. Images from seven individual organs have been compiled to form a Human Organ Atlas that the researchers plan to expand. This might help scientists to understand the deterioration caused by conditions such as cancer and Alzheimer’s disease:

https://www.nature.com/articles/s41592-021-01317-x

An African beetle achieves its glittering green forewings thanks to a unique type of light-reflecting crystal in its scales. Photonic crystals are microscopic structures that can block the passage of some wavelengths of light while permitting the passage of others. The crystals are difficult to make in the laboratory, but many organisms grow them with ease: the structures are found in butterfly wings and give an emerald sheen to the Sternotomis callais beetle of Central Africa. Using scanning electron microscopy, a group took images at 17-nanometre intervals through a S. callais scale. The team used the images to reconstruct the scale’s 3D internal structure and found that it matches well with an ideal mathematical surface called I-WP, which looks a bit like a mixture of spheres and wide tunnels. At the size of the scale’s crystal, the structure should reflect green light, just as the beetle’s wings do. It is unclear how the beetle’s crystal, which differs markedly from the twisty labyrinthine structure found in butterflies, is formed:

https://www.nature.com/articles/d41586-021-03076-3

The scarcity and high radioactivity of the heaviest actinide elements, such as californium, make their study a formidable challenge. A landmark report describes the first structural characterization of a californium—carbon bond:

https://www.nature.com/articles/d41586-021-03385-7

Pet cats seem to be able to track their human companion’s every move — through sound. Domestic house cats (Felis catus) use visual cues to create a mental map of their environment and the whereabouts of any other creatures nearby. However, our feline familiars also have keen ears, which could assist with their mental cartography when their prey — or person — is out of sight. To investigate this, researchers attempted to hoodwink dozens of house cats through ‘impossible teleportation’ experiments. The researchers placed each cat in a room with two widely spaced audio speakers. First, one speaker played a recording of the cat’s owner calling its name. Then, the second speaker played the same recording after an interval that would be too short for a human to travel between the two locations. Video cameras recorded the cats’ reactions. The team found that house cats were noticeably surprised by auditory evidence that their people had been ‘teleported’. The cats’ astonishment suggests that they can keep mental notes of their humans’ presence and map that person’s location by voice:

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257611

Cold-loving creatures known as Pacific Ocean rockfishes have wildly varying lifespans. The species Sebastes minor lasts a mere 11 years; its cousin Sebastes aleutianus can live for more than 2 centuries. Scientists have now pinpointed genes linked to this remarkable range. To understand the variation in longevity, researchers examined the genomes of 88 rockfish species, most in the Sebastes genus. They discovered that the longest-lived rockfishes, a group that includes several species that can live for more than 105 years, have more genes linked to DNA maintenance and for sensing nutrients in the body than do their counterparts that live for less than 20 years. Some of those genes seemed to indirectly affect longevity by influencing a fish’s size and ability to adapt to different environments. The long-lived fish also have more copies of genes involved in dialing back the immune system, suggesting that these fish are more protected against the effects of ‘inflammaging’, an increase in inflammation throughout the body that occurs with age in many vertebrates, including humans:

https://www.nature.com/articles/d41586-021-03423-4

Analysis of immune cells shows that, unexpectedly, B cells secrete GABA, a molecule best known as a neurotransmitter. B-cell-derived GABA can modulate immune responses against tumours, raising the prospect of new therapies:

https://www.nature.com/articles/d41586-021-02953-1

As we age, we are more likely to develop ageing-related illnesses such as cardiovascular disease, cancer and type 2 diabetes. Yet centenarians — people who are more than 100 years old — are less susceptible to such conditions than are ageing individuals who do not live as long. For some centenarians, answers to this conundrum might lie in the gut. A team identify a previously unknown connection between healthy ageing in humans over the age of 100, and gut bacteria and bile acids:

https://www.nature.com/articles/d41586-021-02196-0

The US reached a grim milestone amid the ongoing pandemic with deaths caused by drug overdoses topping 100,000 for the first time, according to the CDC. In a 12-month period from May 2020 to April 2021, more than 100,300 people across the U.S. died of drug overdoses. The number was nearly 30% higher than the about 78,000 deaths reported by the CDC from May 2019 to April 2020. Nearly two-thirds of the deaths were caused by synthetic opioids, primarily fentanyl. Fentanyl can be as many as 100 times more potent than morphine and 50 times more potent than heroin, according to the Drug Enforcement Administration. Earlier this year, they warned that as little as two milligrams of the opioid, a dose small enough to fit on the tip of a pencil, can be lethal:

https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm

Although fear is important for survival, it is maladaptive if it is either too strong, as in anxiety disorders, or too weak, as in exaggerated risk taking. Working in mice, a group observed that the insular cortex has an unparalleled dual role in either enhancing or weakening the extinction of fear, depending on the internal fear state of the animal (see the Perspective by Christianson). This insula function helps to maintain fear within a homeostatic range and depends on bodily feedback signals: Fear-induced freezing behavior is associated with a slowed heart rate, which in turn dampens fear-evoked activity of the insular cortex. Two opposite signals, prediction of threat by fear-associated cues and negative feedback signals from the body, are thus integrated within the insular cortex:

https://www.science.org/doi/10.1126/science.abj8817

Repeated exposures to the black-legged tick, Ixodes scapularis, can lead to acquired resistance against ticks. To bypass the need for repeated exposures, a group developed a messenger RNA vaccine that encoded for 19 I. scapularis salivary proteins. Vaccinated hamsters developed erythema at the site of tick attachment, a feature of acquired tick resistance. The immunization also led to poor tick feeding and reduced transmission of a tick-borne bacterial pathogen:

https://www.science.org/doi/10.1126/scitranslmed.abj9827

Covid papers:

Concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines. Concomitant vaccination with both COVID-19 and influenza vaccines over the next immunisation season should reduce the burden on health-care services for vaccine delivery, allowing for timely vaccine administration and protection from COVID-19 and influenza for those in need:

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02329-1/fulltext

Researchers performed a meta-analysis including 24 published studies on neutralisation of ancestral SARS-CoV-2 and integrated the results into a statistical model that was previously developed to estimate vaccine efficacy against variants. They found that neutralisation titres remained a correlate of protection from variants of concern and by modelling the effects of waning immunity, they predicted a loss of protection to the variants after vaccination that could be reversed by a vaccine booster dose. The work might be useful to predict the efficacy of novel vaccines against new variants and inform the optimal development of the next generation of vaccines. While reassuring that current variants of concern are susceptible to the vaccines in use, it's good to have tools to predict vaccines protection and guide the development of new vaccines against possibly escaping variants in the future:

https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00267-6/fulltext?

Research on the long-term effects of Covid-19 (PASC, post-acute sequelae of COVID) found that at least 50% of people who survive infection experience a variety of physical and psychological health issues for six months or more after their recovery. The research was based on data from 250,351 adults and children and found that over half experience a decline in general well-being, resulting in weight loss, fatigue, fever, or pain. “About 20% have decreased mobility, 25% have trouble thinking or concentrating (called “brain fog”), 30% develop an anxiety disorder, 25% have breathing problems, and 20% have hair loss or skin rashes. Cardiovascular issues — chest pain and palpitations — are common, as are stomach and gastrointestinal problems.” Those who suffer with longer term symptoms include anyone who had Covid-19, even if they had no symptoms initially or just mild ones:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784918?

Researchers asked are persons vaccinated after SARS-CoV-2 infection better protected against breakthrough infection than those vaccinated without prior infection? In this cohort study of 1,531,736 mRNA-vaccinated individuals in Qatar, prior SARS-CoV-2 infection was associated with a statistically significant reduced hazard of breakthrough infection among recipients of both the BNT162b2 (Pfizer-BioNTech) (adjusted hazard ratio, 0.62) and the mRNA-1273 (Moderna) vaccines (adjusted hazard ratio, 0.40). Prior SARS-CoV-2 infection was associated with a lower risk for breakthrough infection among persons receiving the SARS-CoV-2 mRNA vaccines; however, the observational study design precludes direct comparison of infection risk between the 2 vaccines:

https://jamanetwork.com/journals/jama/fullarticle/2785918

Researchers asked how does human milk antibody composition and neutralization activity differ between lactating parents with COVID-19 infection vs those with COVID-19 messenger RNA vaccination? In this cohort study of a convenience sample of 47 lactating parents with infection and 30 lactating parents who were vaccinated, antibody response in milk after infection was IgA dominant and highly variable while vaccination was associated with a robust IgG response, which began to decline by 90 days after the second vaccine dose. Milk from both groups showed neutralization activity against live SARS-CoV-2 virus, which can be attributed to IgA and IgG SARS-CoV-2 antibodies. COVID-19 infection and vaccination may result in significant antibodies in human milk that exhibit different temporal patterns, but both neutralize live SARS-CoV-2 virus:

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2786219

Routine testing for asymptomatic SARS-COV-2 infection among health care personnel (HCP) who have not been vaccinated against COVID-19 can reduce transmission to the residents of long-term care (LTC) facilities. However, the utility of surveillance testing for LTC HCP who have been vaccinated against COVID-19 is unclear. Although rates of positive results among HCP who are vaccinated are extremely low, breakthrough infections and transmission still occur. The Veterans Health Administration (VHA) implemented routine surveillance of HCP and residents of LTC units in April 2020. Surveillance was intensified in January 2021, coincident with a national surge of cases and first vaccine availability. This cohort study found that frequent, mandatory surveillance of HCP in a LTC setting was effective in detecting SARS-CoV-2 infection in HCP. The yield of positive test results was much higher in HCP who were unvaccinated than those who were vaccinated, consistent with an evolving literature that suggests full vaccination status reduces asymptomatic SARS-CoV-2 infection in HCP. The observation that surveillance was primarily beneficial in HCP who were unvaccinated during periods of high community transmission is consistent with recent guidance from the CDC and presents a quandary regarding how to identify and differentially test HCP who are unvaccinated in the absence of mandatory vaccination policy. The detection of asymptomatic SARS-CoV-2 infection decreased in parallel with community prevalence. As case rates decrease, the proportion of tests with positive results that are false positives will increase, even in HCP who are unvaccinated, sometimes leading to unnecessary quarantine of essential HCP. Hence, the utility of frequent surveillance will vary as a function of the rate and trend of community transmission, vaccination status of HCP and residents, and the transmissibility of variant strains of SARS-CoV-2:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2785925

Are sleep-disordered breathing and sleep-related hypoxia associated with SARS-CoV-2 infection and COVID-19 outcomes? In this case-control study of 5402 patients in a large integrated health system, sleep-disordered breathing and sleep-related hypoxia were not associated with an increased likelihood of contracting SARS-CoV-2. After accounting for confounding factors including cardiopulmonary disease, cancer, and smoking exposure, sleep-related hypoxia indices were associated with more severe COVID-19 clinical outcomes, including hospitalization and mortality, in time-to-event analyses. These results suggest that baseline sleep-related hypoxia may portend worse clinical prognosis in COVID-19:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2785921

We know that Covid-19 has disproportionately affected people of color. They are more likely to hold down essential jobs that increase exposure to Covid. More likely to be infected, their disease is more severe. A meta-analysis of more than 4 million patients in 68 studies teases out the socioeconomic factors behind these disparities. After accounting for underlying medical conditions, the researchers factored in a deprivation index based on such measures as income, education, housing, insurance, and access to medical care. They found that African American and Hispanic people were almost twice as likely to test positive for Covid-19 as white individuals, followed by Asian Americans. “Public health policies should address socioeconomic and racial disparities to reduce exposure to and fatality from Covid-19 in underrepresented populations,” the researchers write:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2785980?

Researchers asked has the COVID-19 pandemic been associated with differences in careers and mental health between physician mothers and fathers? In this cohort study of 276 physicians during the COVID-19 pandemic, mothers were more likely than fathers to be responsible for childcare or schooling and household tasks, to work primarily from home, to reduce their work hours, and to experience work-to-family conflict, family-to-work conflict, and depressive and anxiety symptoms. A gender difference in depressive symptoms was observed among physician parents during the COVID-19 pandemic that was not present before the pandemic. This study suggests that pandemic conditions are associated with an increase in gender inequalities within medicine and signals the importance of further attention and resources to mitigate the potential adverse consequences for the careers and well-being of physician mothers:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786027

Given the higher COVID-19–related mortality rate observed among men than among women, is androgen deprivation therapy associated with decreased rate of 30-day mortality from COVID-19 among patients with prostate cancer? In this cohort study of 1106 patients, no statistically significant difference was found in the rates of all cause 30-day mortality following COVID-19 infection among men with prostate cancer receiving androgen deprivation therapy (15%) vs those not receiving androgen deprivation therapy (14%). The findings of this cohort study do not support an association between androgen deprivation therapy and 30-day mortality among patients with COVID-19 infection:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786026

Researchers characterized Illinois unintentional opioid overdose deaths from July 2017 through June 2020 using the CDC State Unintentional Drug Overdose Reporting System (SUDORS). Illinois SUDORS includes 42 counties, representing 91% of the state’s overdose deaths; trained abstractors enter data using death certificates, medical examiner and autopsy reports, and postmortem toxicology testing. There were 6058 opioid overdose deaths from July 2017 to June 2020. Deaths and hospitalizations were stable from July 2017 to June 2019 and increased from July 2019 to June 2020. Decedents were increasingly Black and Hispanic over time and exceeded White decedents by January to June 2020; decedents were also increasingly aged 60 years or older. In January to June 2020, 174 (13.5%) had a recent touchpoint encounter compared with 133 (11.8%) in July to December 2019. Toxicology testing results were increasingly positive for fentanyl, reaching 1056 (82.1%) by January to June 2020; prescription opioid positivity remained stable. During the January to June 2020 period coinciding with COVID-19, most overdose deaths occurred in the decedent’s home (787 [61.2%]) with bystanders present (647 [50.3%]), similar to preceding periods. Some death scene characteristics were marginally lower in January to June 2020 compared with July to December 2019: bystander cardiopulmonary resuscitation (93 [14.4%] vs 92 [16.1%]), ED transportation (306 [23.8%] vs 319 [28.3%]), and naloxone administration (465 [31.8%] vs 449 [34.0%]), although these rates were not dissimilar to earlier periods:

https://jamanetwork.com/journals/jama-health-forum/fullarticle/2786178

US technologist has released a huge online index of 355 billion words and short phrases contained in >100 million journal articles — including many paywalled papers. This ‘General Index’, which was just made public and is free to use, holds tables of words and sentence fragments listed next to the articles in which they appear. It is an effort to help scientists use software to glean insights from published work even if they have no legal access to the underlying papers, says creator Carl Malamud. Malamud says that because the index doesn’t contain the full text of articles, but only snippets up to five words long, releasing it does not breach publishers’ copyright restrictions on the reuse of paywalled articles. Some researchers who have had early access to the index say that it has helped them to search the literature with software — a procedure known as text mining:

https://archive.org/details/GeneralIndex

Individuals with potential exposure to SARS-CoV-2 do not necessarily develop PCR or antibody positivity, suggesting some may clear sub-clinical infection before seroconversion. T-cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections. A group hypothesised that pre-existing memory T-cell responses, with cross-protective potential against SARS-CoV-2, would expand in vivo to support rapid viral control, aborting infection. They measured SARS-CoV-2-reactive T-cells, including those against the early transcribed replication transcription complex (RTC), in intensively monitored healthcare workers (HCW) remaining repeatedly negative by PCR, antibody binding, and neutralisation (seronegative HCW, SN-HCW). SN-HCW had stronger, more multispecific memory T-cells than an unexposed pre-pandemic cohort, and more frequently directed against the RTC than the structural protein-dominated responses seen post-detectable infection (matched concurrent cohort). SN-HCW with the strongest RTC-specific T-cells had an increase in IFI27, a robust early innate signature of SARS-CoV-2, suggesting abortive infection. RNA-polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA-polymerase was preferentially targeted (amongst regions tested) by T-cells from pre-pandemic cohorts and SN-HCW. RTC epitope-specific T-cells cross-recognising HCoV variants were identified in SN-HCW. Enriched pre-existing RNA-polymerase-specific T-cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Their data highlight RTC-specific T-cells as targets for vaccines against endemic and emerging Coronaviridae:

https://www.nature.com/articles/s41586-021-04186-8

A paper used 37 upper-middle and high income countries or regions with reliable and complete mortality data. Reduction in life expectancy in men and women was observed in all the countries studied except New Zealand, Taiwan, and Norway, where there was a gain in life expectancy in 2020. No evidence was found of a change in life expectancy in Denmark, Iceland, and South Korea. The highest reduction in life expectancy was observed in Russia (men: −2.33), the United States (men: −2.27; women: −1.61), Bulgaria (men: −1.96; women: −1.37), Lithuania (men: −1.83; women: −1.21), Chile (men: −1.64; women: −0.88), and Spain (men: −1.35; women: −1.13). Years of life lost in 2020 were higher than expected in all countries except Taiwan, New Zealand, Norway, Iceland, Denmark, and South Korea. In the remaining 31 countries, more than 222 million years of life were lost in 2020, which is 28.1 million (95% confidence interval 26.8m to 29.5m) years of life lost more than expected (17.3 million (16.8m to 17.8m) in men and 10.8 million (10.4m to 11.3m) in women). The highest excess years of life lost per 100 000 population were observed in Bulgaria (men: 7260; women: 3730), Russia (men: 7020; women: 4760), Lithuania (men: 5430; women: 2640), the US (men: 4350; women: 2430), Poland (men: 3830; women: 1830), and Hungary (men: 2770; women: 1920). The excess years of life lost were relatively low in people younger than 65 years, except in Russia, Bulgaria, Lithuania, and the US where the excess years of life lost was >2000 per 100 000. More than 28 million excess years of life were lost in 2020 in 31 countries, with a higher rate in men than women. Excess years of life lost associated with the covid-19 pandemic in 2020 were more than five times higher than those associated with the seasonal influenza epidemic in 2015:

https://www.bmj.com/content/375/bmj-2021-066768

Researchers asked what was the prevalence of unidentified SARS-CoV-2 infection in April 2021 after 3 major pandemic waves in Hong Kong, a city without complete lockdown? In this cross-sectional study of 4198 participants of the general public in Hong Kong, 6 were identified as positive for anti-SARS-CoV-2 IgG after 3 major waves of COVID-19. The adjusted prevalence of unidentified infection was 0.15%, with fewer than 1.9 unidentified infections for every recorded case. The findings suggest that stringent isolation and quarantine policies even without complete city lockdown are successful in minimizing SARS-CoV transmission:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786137

Researchers asked are anti-depressants, notably selective serotonin reuptake inhibitors (SSRIs), specifically fluoxetine hydrochloride, associated with a lower mortality risk among patients with COVID-19? In this multicentre cohort study analysing electronic health records of 83,584 patients diagnosed with COVID-19, including 3401 patients who were prescribed SSRIs, a reduced relative risk of mortality was found to be associated with the use of SSRIs, specifically fluoxetine, compared with patients who were not prescribed SSRIs. These findings suggest that SSRI use may reduce mortality among patients with COVID-19, although they may be subject to unaccounted confounding variables; further investigation via large, randomized clinical trials is needed:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786136

Researchers asked is the low COVID-19–related mortality reported in Bangladesh for 2020 associated with massive undercounting? This repeated survey study including households from a sample of 135 villages in rural Bangladesh found that all-cause mortality in the surveyed was lower in 2020 compared with 2019, but measures to control the COVID-19 pandemic were associated with a reduction in rural income and food availability. These findings suggest that government restrictions designed to curb the spread of COVID-19 may have been effective in 2020 but needed to be accompanied by expanded welfare support:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786144

The pandemic could cost an extra 300,000 lives in Europe (corresponding they say to my surprise to just 900k cases), according to a study of the number of people in 19 countries who have been neither infected nor vaccinated. The study’s models also predict that the pandemic could lead to roughly one million hospitalisations in Europe, some of which would contribute to the projected death toll. But the authors of the analysis point out that their estimates are maximum numbers, which assume that all anti-infection restrictions are lifted and contacts between individuals have returned to their pre-pandemic levels:

https://www.medrxiv.org/content/10.1101/2021.11.10.21266166v1.full.pdf

In more pandemic fallout, the number of people hospitalised for eating disorders doubled in 2020 from the year before, spanning anorexia, bulimia, and other diagnoses found in health insurance records. The median length of hospital stays also grew, from 9 to 12 days. The researchers mention some possible reasons why disordered eating might have increased: i) a focus on obesity as a risk factor for bad Covid outcomes could lead to unhealthy dieting, ii) a fear of contagion during grocery shopping could mean fewer trips, so buying and eating too much, iii) families could have noticed eating problems in college-age children living at home again:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786185?

It is not yet known whether breakthrough infections increase risk of long COVID (otherwise known as post-acute sequelae of COVID-19 or PASC), a constellation of debilitating and lingering symptoms following infection. These symptoms can lead to physiologic disruption of multiple organ systems, substantial disruption of daily life, employment, and mental health, and a higher burden on the healthcare system. Long COVID has been observed as a consequence of both mild and severe infection, raising the possibility that survivors of breakthrough infections may also be at risk for long COVID. Therefore, prevention of breakthrough infections may avoid the overwhelming, long-term consequences of long COVID due to widespread infection:

https://www.science.org/doi/10.1126/science.abm0620

In patients with ST-segment elevation myocardial infarction (STEMI, an ‘old fashioned’ heart attack), is a concomitant diagnosis of COVID-19 associated with differences in clinical outcome? In this retrospective cohort study that included 80,449 patients, the rates of in-hospital mortality for patients with vs without a concomitant diagnosis of COVID-19 were 15.2% vs 11.2% among those with out-of-hospital STEMI and 78.5% vs 46.1% among those with in-hospital STEMI; both differences were statistically significant. Among patients with STEMI, a concomitant diagnosis of COVID-19 was associated with significantly higher rates of in-hospital mortality:

https://jamanetwork.com/journals/jama/fullarticle/2785893

In a randomised, single-blind trial, researchers assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titre of antibodies against SARS-CoV-2 or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. A total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titre of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups. The administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression:

https://www.nejm.org/doi/full/10.1056/NEJMoa2103784?query=featured_home

Next, researchers performed a case–control study with data from Norwegian registries on first-trimester pregnancies, Covid-19 vaccination, background characteristics, and underlying health conditions. Among 13,956 women with ongoing pregnancies (of whom 5.5% were vaccinated) and 4521 women with miscarriages (of whom 5.1% were vaccinated), the median number of days between vaccination and miscarriage or confirmation of ongoing pregnancy was 19. Among women with miscarriages, the adjusted odds ratios for Covid-19 vaccination were 0.91 for vaccination in the previous 3 weeks and 0.81 for vaccination in the previous 5 weeks. The results were similar in an analysis that included all available vaccine types, in an analysis stratified according to the number of doses received (one or two), and in sensitivity analyses limited to health care personnel (for whom vaccination was routinely recommended other than in the first trimester) or women with at least 8 weeks of follow-up after confirmed pregnancy (to exclude subsequent pregnancy loss). Most recognized miscarriages are known to occur between pregnancy weeks 6 and 10, a period that is similar to the gestational ages at which women in Norway consult a physician to confirm pregnancy. Also, only approximately 40% of women in Norway have a primary care appointment to confirm pregnancy, but the characteristics of these women appear to be similar to those of women who do not have a registered pregnancy confirmation. This study found no evidence of an increased risk for early pregnancy loss after Covid-19 vaccination and adds to the findings from other reports supporting Covid-19 vaccination during pregnancy:

https://www.nejm.org/doi/full/10.1056/NEJMc2114466?query=featured_home 

Sotrovimab is a pan-sarbecovirus monoclonal antibody that was designed to prevent progression of Covid-19 in high-risk patients early in the course of disease. In this prespecified interim analysis, which included an intention-to-treat population of 583 patients (291 in the sotrovimab group and 292 in the placebo group), 3 patients (1%) in the sotrovimab group, as compared with 21 patients (7%) in the placebo group, had disease progression leading to hospitalisation or death (relative risk reduction, 85%; 97.24% confidence interval, 44 to 96; P=0.002). In the placebo group, 5 patients were admitted to the intensive care unit, including 1 who died by day 29. Safety was assessed in 868 patients (430 in the sotrovimab group and 438 in the placebo group). Adverse events were reported by 17% of the patients in the sotrovimab group and 19% of those in the placebo group; serious adverse events were less common with sotrovimab than with placebo (in 2% and 6% of the patients, respectively). Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression. No safety signals were identified:

https://www.nejm.org/doi/full/10.1056/NEJMoa2107934?query=featured_home

T-cell responses were assessed by CD4+ and CD8+ intracellular cytokine-staining assays that used pooled S peptides for stimulation. At 8 months, the median CD8+ T-cell responses were 0.016% with the BNT162b2 vaccine, 0.017% with the mRNA-1273 vaccine, and 0.12% with the Ad26.COV2.S vaccine. With all three vaccines, T-cell responses showed broad cross-reactivity against SARS-CoV-2 variants. These data show differential kinetics of immune responses induced by the mRNA and Ad26.COV2.S vaccines over an 8-month follow-up period. As shown in previous studies, the BNT162b2 and mRNA-1273 vaccines were characterized by high peak antibody responses that declined sharply by 6 months; these responses declined further by 8 months. Antibody titres in recipients of the mRNA-1273 vaccine were generally higher than those in recipients of the BNT162b2 vaccine. The Ad26.COV2.S vaccine induced lower initial antibody responses, but these responses were relatively stable over the 8-month follow-up period, with minimal-to-no evidence of decline. These findings have important implications for waning vaccine immunity, although correlates of protection from SARS-CoV-2 are not yet defined:

https://www.nejm.org/doi/full/10.1056/NEJMc2115596?query=featured_secondary

 


Justin Stebbing
Managing Director

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