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The following papers will be presented at a Lancet journals' session at ECCVID 2020, organised by European Society of Clinical Microbiology and Infectious Diseases. The conference will take place online on Wednesday 23rd to Friday 25th September 2020, the society's first online conference focussing exclusively on COVID-19.

Contact details for corresponding authors are provided should you wish to arrange an interview the authors. Funding information is listed on the first page of each Article.

Timely preventive measures against COVID-19 such as providing hotel room accommodation for homeless people in the UK are estimated to have prevented hundreds of deaths in this vulnerable population, according to research presented at this week's ESCMID Conference on Coronavirus Disease (ECCVID, held online 23-25 September) and published in The Lancet Respiratory Medicine ahead of a special conference session featuring The Lancet journals.

On March 26, 2020, the UK Government instructed local authorities to provide accommodation for people sleeping rough during the pandemic. Dormitory-style night shelters were subsequently closed, and special accommodation referred to as COVID-PROTECT was established, focusing on people sleeping in these facilities and those sleeping rough. This system was in fact designed, very rapidly, by some of the co-authors of this study.

"COVID-PROTECT accommodation has mainly been in commercial hotels that have been left otherwise vacant during the pandemic. Most people who were living in homeless hostels before the pandemic have stayed in their existing location, with increased infection control," explain the authors, who include Dan Lewer of the University College London (UCL) Collaborative Centre for Inclusion Health, London, UK, and colleagues.

In this study - the first study to model SARS-CoV-2 transmission in a homeless population - the researchers used computer modelling capable of assessing multiple possible scenarios to come to their estimates. It explored the effect of the pandemic on 46565 individuals experiencing homelessness: some 35817 living in 1065 hostels for homeless people, 3616 sleeping in 143 night shelters, and 7132 sleeping outside.

They ran the model under scenarios looking at the effect of a 'second wave' and prevention measures that protect homeless people: specialist hotel accommodation, infection control in homeless settings, and reduced mixing with the general population.

The authors used data from charities that support homeless people and information provided by hostels to estimate that 4% of the homeless population had acquired SARS-CoV-2 by May 31, 2020, based on surveillance data from hostels and also further data provided by the St Mungo's homeless charity, UK. The model estimated that 24 deaths actually occurred among homeless people in the first wave in England. However, it also estimated that the preventative measures imposed might have avoided over 21,000 infections, 266 deaths, 1164 hospital admissions and 338 ICU admissions among the homeless population.

If preventative measures are continued as they were during the first wave, the authors project a relatively small number of additional cases between June 1, 2020, and Jan 31, 2021, with over 1,700 new infections, 31 deaths, 122 hospital admissions, and 35 ICU admissions with a second wave in the general population.

However, if preventative measures are lifted, outbreaks in homeless settings might lead to larger numbers of infections and deaths, even with low incidence in the general population. In a scenario with no second wave and relaxed measures in homeless settings in England (effectively a return to the system homeless people experienced pre-pandemic), the model projects more than 12,000 new infections, 184 deaths, 733 hospital admissions, and 213 ICU admissions between June 1, 2020, and Jan 31, 2021.

The researchers did not model what they called the true nightmare scenario - a second wave and less preventive measures, because further surges of COVID-19 (as are currently happening in the UK) will lead to more intensive preventive measures in the general population.

The authors say: "During the first wave of COVID-19 in England, our modelling suggests that people experiencing homelessness were protected by interventions in the general population, infection control in hostels, and closing of dormitory-style accommodation."

They add: "In England, homeless people living in hostels or in COVID-PROTECT have been offered testing when symptomatic, and occasionally mass screening exercises have been undertaken. We are not aware of any outbreaks in these settings to date. The results of our model suggest that closing of dormitory-style accommodation and increased infection control in single-room accommodation might have contributed to the absence of outbreaks."

They conclude*: "The two main implications for practice are that night shelters should not be re-opened while there is sustained transmission of SARS-CoV-2 in the community, and that heightened infection control measures in hostels should be continued even when incidence of COVID-19 is low in the general population. While there is uncertainty in the impact of COVID-19 on people experiencing homelessness, there is clear potential for outbreaks in hostels and night shelters. A large number of deaths can be avoided by maintaining the additional support that has so far been provided in England. Relaxing these measures would be risky."

Co-author Dr Alistair Story, also of the University College London (UCL) Collaborative Centre for Inclusion Health, London, UK, adds**: "COVID-19 cases are surging again. Our work demonstrates that safe single room accommodation for homeless people is life-saving and must be scaled and sustained to meet need. As the winter months approach, homeless people cannot face a choice between freezing to death or risking infection in crowded emergency night shelters. This is not an acceptable choice in a civilised society."

DALLAS (September 23, 2020) - Researchers at Center for BrainHealth®, part of The University of Texas at Dallas, recently examined how cells in the brains of people at risk for developing Alzheimer's disease make and use energy. Relationships between the brain's energy metabolism and the risk of Alzheimer's disease have been reported previously. But this is the first study to clearly distinguish different energy molecules in the brain using high-powered imaging called magnetic resonance spectroscopy (MRS) at 7-Tesla. The findings from this study could help the development of tests for the earlier detection and treatment of Alzheimer's disease.

The study was published in Frontiers in Aging Neuroscience (August 2020) by Center for BrainHealth researchers Sandra Bond Chapman, PhD, chief director; Namrata Das, MD, MPH, a research neuroscientist in Alzheimer's Disease and the study's lead author; Jeffrey Spence, PhD, director of biostatistics; Audette Rackley, head of special programs; and Jimin Ren, PhD, a researcher at UT-Southwestern Medical Center.

This imaging technique allows scientists to look at how the human brain makes and uses energy at the cellular level. Other techniques are invasive, which is why until now most research on the brain's energy metabolism has been conducted in deceased patients or in model organisms like mice.

"The biggest finding is that the peaks from the MRS scan could be separated to look at the brain's energy. It's almost like seeing a heartbeat for the first time," said Chapman.

The findings add a methodology for studying the early pathological biomarkers for Alzheimer's disease in patients with amnestic mild cognitive impairment, a condition that sometimes leads to the development of the disease. Participants with higher brain energy metabolisms in their parieto-occipital lobes had poorer memory and attention skills.

Energy use and production are the core of all cells' biological mechanism, especially in the brain due to its high energy requirements. The brain's extraordinary energy requirements may lead to the dangerous buildup of beta-amyloid and tau proteins seen in patients with Alzheimer's disease.

"We want to look at how the brain energy metabolism differs between healthy participants, participants with amnestic mild cognitive impairment, and those with Alzheimer's disease," said Dr. Das. "Later on, we want to understand if energy abnormalities upstream trigger or aggravate the amyloid, tau, and glucose metabolism abnormalities in the brain." The earlier that Alzheimer's disease is detected and treated, the better the patients' outcomes.

Two nationwide COVID-19 antibody seroprevalence studies from Brazil show that many cities along the Amazon were hit hardest at the beginning of the epidemic in May and June, along with poorer and Indigenous communities. The research is presented at this week's ESCMID Conference on Coronavirus Disease (ECCVID, held online 23-25 September) and published in The Lancet Global Health, as part of a special conference session featuring The Lancet journals.

"Brazil has become a global hotspot for the COVID-19 pandemic in terms of reported cases and deaths," explains lead author Professor Cesar Victora, Federal University of Pelotas, Pelotas, Brazil. "Existing seroprevalence studies in Brazil have focused on the more developed parts of the country, represented by the southern and southeastern regions. So it is vital that we have more accurate data on the national situation."

The researchers did two household surveys in the most populous cities in all 133 so called 'mesoregions' - regional hubs used by the Brazilian Institute of Geography and Statistics to report on demographic and socioeconomic data across Brazil, covering 26 states and the Federal District. The studies included more than 25000 participants in the period May 14-21 and over 32000 in June 4-7. At each location, the researchers randomly selected households and randomly selected one individual from all household members to test for COVID-19 antibodies.

Participants also answered short questionnaires on sociodemographic information (sex, age, education, ethnicity, household size, and household assets) and compliance with physical distancing measures.

For the 83 (62%) of cities with sample sizes of more than 200 participants in both surveys, the pooled seroprevalence increased by more than 50%, from 1·9% to 3·1%, from the first survey to the second survey. City-level prevalence ranged from 0% to 25·4% in both surveys. 11 (69%) of 16 cities with a prevalence above 2.0% in the first survey were located along a 2000 km stretch of the Amazon river in the northern region, including well-known cities such as Belem, Manaus and Macapa, which are all state capitals located along the Amazon.

In the second survey, the authors found 34 cities with prevalence above 2.0%, which included the same 11 Amazon cities plus 14 from the northeast region, where prevalence was increasing rapidly. Prevalence levels were lower in the south and centre-west, and intermediate in the southeast, where the highest level was found in Rio de Janeiro (7·5%).

In the second survey, prevalence was similar in men and women, but an increased prevalence was observed in participants aged 20-59 years compared to younger or older persons, and in those living in crowded conditions (4·4% for those living with households with six or more people). Prevalence generally increased the more individuals there were per household.

Prevalence among Indigenous people, at 6.4%, was more than four times higher than that found among White people (1.4%). The poorest 20% of the population had a seroprevalence of 3.7%, more than double the 1·7% found in the wealthiest 20%.

The authors say: "Our most remarkable finding was the cluster of high prevalence in 11 cities along the Amazon River, with levels that were among the highest ever reported in population-based studies. This finding of high prevalence in a tropical region contradicts common wisdom that continents such as Africa might be protected against COVID-19 because of high ambient temperature."

The authors believe the high rates of seroprevalence in Indigenous Brazilians are due to a cluster of factors, geographical region, household size (usually overcrowded living conditions), and poverty. Mortality rates for most medical conditions are higher in Indigenous Brazilians, and this population was largely left behind during Brazil's rapid economic and health advances that began in the 1990s.

Overall, the authors say: "Our results must be interpreted in terms of the controversial management of the pandemic by the national government. Testing was restricted to individuals with severe symptoms during the early stages of the pandemic and contact tracing was virtually non-existent. Two consecutive health ministers were either dismissed or resigned in less than 1 month because of their opposition to the president's stance regarding physical distancing and the use of hydroxychloroquine to treat COVID-19, and since May 15, the country has not had a health minister... The controversial handling of the epidemic by the federal government is likely to have contributed to the rapid spread of COVID-19 in the country's most susceptible populations."

While initially many state governors were supportive of social distancing measures and some form of lockdown, the country has now gradually reopened, despite the persisting high incidence of new cases and deaths.

The authors conclude: "The effect of relaxing these measures is still too early to assess, but further waves of serological surveys will allow monitoring of the progression of the pandemic and help assess the effectiveness of policy changes."

The authors have also carried out two additional seroprevalence surveys* since the two reported in this paper, with an average prevalence of 3.8% in the third study from June 21-24, followed by a sharp decline to 1.4% in the last survey round that was carried out from August 27-30, after an interval of 66 days. This surprised the researchers, since they were expecting cumulative seroprevalence to continue rising (seroprevalence measures the proportion of individuals who have had the infection at some point, not the proportion who are currently infected).

Professor Victora says*: "We don't know what this says about immunity. Even though circulating antibodies, especially those that are neutralising, can quickly decay, the immune system may retain a memory of the infection. In the case of new contact with the virus, B and T cells will then be rapidly activated to produce antibody and cellular protection. All we know so far, for sure, is that so called 'herd immunity' should not be solely assessed on the basis of circulating antibody levels. The full picture is much more complex."

New Rochelle, NY, September 23, 2020 - Forensic DNA analysis enables new and increasingly sophisticated technology for solving cold cases. Through advances in DNA sequencing and bioinformatics, this relatively new and urgent field is enabling a broad range of cold cases, including homicides and other violent crimes, to be solved. The first issue of Forensic Genomics has just been published. Click here to read the issue now.

"Advances in forensic genomics and genealogy have helped solve an unprecedented number of cold cases in the past few years. Forensic Genomics will document and facilitate continued innovation in the field and drive validation and adoption of this exciting new technology for forensics professionals," says Editor-in-Chief David Mittelman, PhD, Founder & Chief Executive Officer, Othram, Inc.

Incorporating robotics and automation into forensic workflows can help reduce casework backlogs in crime laboratories. An article by Kevin Miller PhD, Hamilton Company, and coauthors, describes the "Validation of a High-Throughput Automated Liquid Handling DNA Extraction System to Maximize Efficiency in Forensic Casework."

An article by William Thomas, moderator of Mind Over Murder Podcast, provides a first-hand view of what it is like to suffer the unsolved murder of a loved one. Important insights for the future of the field are put forth.

The News section highlights new forensic DNA methods that are helping to solve cold cases. It focuses on the emergence of DNA sequencing as a more accurate method for collecting genetic information from challenging forensic evidence and also covers database tools for turning the genetic information into meaningful results.

New research presented at this week's ESCMID Conference on Coronavirus Disease (ECCVID, online 23-25 September) confirms that men with COVID-19 have worse outcomes than women, possibly related to them experiencing higher levels of inflammation. The study is by Dr Frank Hanses, University Hospital Regensburg, Germany, and colleagues, and shows that men have a 62% increased risk of COVID-19 associated death compared with women, after adjustment for various factors. (see figure 2 of poster).

Increasing evidence suggests a gender difference in SARS-CoV-2 infections. In most cohorts, men are overrepresented and previously published data show a higher incidence of severe courses of COVID-19 in men. To collect clinical data from the pandemic, the international multicenter Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) registry was established.

The German Society of Infectious Diseases (DGI) sponsored this registry aiming to provide scientists and doctors with reliable clinical data to enable them to answer numerous urgent questions, such as when do COVID-19 patients develop severe symptoms? What is the best possible treatment? Which measures have been successful up to now? Under the new initiative, it is planned to make the collected data available to the scientific community for use in crowd-based analyses.

In this study, the authors present a first analysis of the LEOSS dataset on the impact of sex in COVID-19. They retrospectively assessed 3,129 adult patients with COVID-19, enrolled between March and July 2020. Baseline characteristics include socio-demographics and comorbidities according to the Charlson Comorbidity Index (number of pre-existing conditions) (CCI).

Clinical manifestation of COVID-19 was described in four phases: uncomplicated (asymptomatic/mild symptoms), complicated (need for oxygen supplementation), critical (need for critical care) and recovery. Symptoms, vital signs, inflammatory markers and therapeutic interventions were analysed over all phases as was clinical outcome.

The male:female ratio in this mostly hospital-based cohort was 1.48 with a male predominance in all age groups. Male predominance was even more pronounced in the age groups >65 years and >75 years. Mean CCI and most comorbidities did not differ significantly between men and women, while coronary artery disease (18% vs 10%) and smoking rates were higher in male patients (14.5 vs 10.5%) than female patients.

Progression to a critical phase (generally reflecting ICU admission) was seen more often in men than in women (30.6% vs 17.2%). Mean hospital length of stay was longer in male patients (15.4 vs 13.3 days).

Both crude mortality (19.2% vs 12.9%) and COVID-19 attributable mortality (17.1% vs 10.3%, figure 1, e-poster), were significantly higher in men. Being male proved to be an independent risk factor for a 62% increased risk of COVID-19 associated death in an analysis adjusted for various factors.

While most laboratory parameters were comparable between male and female patients with COVID-19, men had significantly higher inflammatory markers (IL-6, CRP, PCT, ferritin) across all phases of disease (figure 3, e-poster).

The authors conclude: "Men are more likely to progress to critical phases of COVID-19. Men have higher death rates as well as more frequent ICU admissions and longer hospital stays, that are all associated with higher inflammatory parameters during all phases of COVID-19. In our cohort, this effect was not explained by differences in comorbidities, age or BMI between male and female patients."

"We need further studies on what exactly makes men more vulnerable to COVID-19", concludes Dr Hanses. "We do not yet know which biological or possibly social factors lead to these marked differences."

A US study from the city of Detroit, presented at this week's ESCMID Conference on Coronavirus Disease (ECCMID, online 23-25 September) shows that the initial SARS-CoV-2 viral load in nasopharyngeal samples has been decreasing as the pandemic progressed. The authors also observed that the decline in viral load was associated with a decrease in death rate. The study is by Dr Said El Zein, Wayne State University/ Detroit Medical Center, Detroit, MI, USA, and colleagues.

The dynamics of the SARS-CoV-2 viral load (VL) on a population level remain poorly characterised. In this study, the authors present data describing the downward trend in the initial SARS-CoV-2 VL in nasopharyngeal swab samples of hospitalised patients in Detroit, Michigan during the period of April 4- June 5, 2020.

They conducted a retrospective study that included all hospitalised patients who had initial nasopharyngeal swab samples analysed at the Detroit Medical Center, that returned positive for SARS-CoV-2 by PCR testing between April 4 and June 5, 2020. To estimate the viral load, the authors used the so-called cycle threshold (Ct) value provided by the test for each sample - a higher Ct indicates a lower viral load. Based on their studies, the authors designated high, intermediate, and low VL samples to have a Ct value of 25 or under, 26-36, and 37 or over, respectively.

During the first week of the study (week of April 4, 2020), 49% of the initial VL samples were in the intermediate group, compared to 25.5% each in the low and high VL categories respectively. Thereafter, there was a progressive decline in the percentage of samples in the high and intermediate VL categories with a concomitant rise in the percentage of samples in the low VL category.

By week five of the study, 70% of the positive samples had an initial low VL. This trend in initial VL coincided with a decrease in the percent of deaths (see figure 1 in abstract). Almost half of the patients in the high VL group died (45%) compared to 32% and 14 % of the intermediate and low VL categories respectively (Figure 2).

The authors concldue: : "During the April-June 2020 period of the COVID-19 pandemic, the initial SARS-CoV-2 load steadily declined among hospitalised patients with a corresponding decrease in the percent of deaths over time.Though confounding variables have not been evaluated, this suggests an association between initial viral load and mortality."

Dr El Zein adds: "Exact reasons for a decrease in initial viral load over time are unclear. A downward trend in the initial VL may reflect a reduction in the severity of the pandemic and trends in the viral load values over time may represent a marker to assess the progress of the pandemic. Rapid implementation of social distancing measures, lockdown and widespread use of facemasks may have contributed to a decrease in the exposure to the virus."

New research presented at this week's ESCMID Conference on Coronavirus Disease (ECCVID, online 23-25 September) suggests that, as lockdown took effect and case numbers dropped, the amount of virus patients were exposed to (viral load) fell, and this could be linked to lower proportions of patients requiring intensive care and dying. The study is by Dr Chiara Piubelli, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy, and colleagues.

In March 2020, Italy was one of the countries most severely hit by the SARS-CoV-2 (COVID-19). Then, the burden of cases gradually decreased until the end of May. The aim of this work was the evaluation of a possible association between the severity of clinical manifestations and viral load over time, during the epidemiological transition from high to low transmission setting.

The authors analysed 373 cases of COVID-19 diagnosed at the emergency room of the IRCCS Sacro Cuore Don Calabria Hospital, and obtained the proportion of patients admitted to the intensive care unit. To estimate viral load, the estimated the so-called cycle theshold (Ct) for each sample - a higher cycle threshold indicates a lower viral load.

The proportion of patients requiring intensive care significantly reduced from 6.7% in March, to 1.1% in April, and to zero in May. For viral load, they observed a trend of Ct increasing from 24 to 34 (median values) (indicating decreasing viral load) between March and May, with a statistically significant difference between March and April.

The authors conclude: "We observed a reduction over time of the proportion of patients with COVID-19 requiring intensive care, along with decreasing median values of viral load. As the epidemiological context changed from high to low transmission setting, people were presumably exposed to a lower viral load, which has been previously associated with less severe clinical manifestations."

There are no Food and Drug Administration (FDA)-approved treatments for COVID-19, the pandemic infection caused by a novel coronavirus. While several therapies are being tested in clinical trials, current standard of care involves providing patients with fluids and fever-reducing medications. To speed the search for new COVID-19 therapies, researchers are testing repurposed drugs -- medicines already known to be safe for human use because they are FDA-approved for other conditions -- for their abilities to mitigate the virus.

UC San Diego Health researchers recently reported that statins -- widely used cholesterol-lowering medications -- are associated with reduced risk of developing severe COVID-19 disease, as well as faster recovery times. A second research team at UC San Diego School of Medicine has uncovered evidence that helps explains why: In short, removing cholesterol from cell membranes prevents the coronavirus from getting in.

The clinical study, published September 15, 2020 in American Journal of Cardiology, was led by Lori Daniels, MD, professor and director of the Cardiovascular Intensive Care Unit at UC San Diego Health, and Karen Messer, PhD, professor and chief of the Division of Biostatics and Bioinformatics in the Department of Family Medicine and Public Health.

The mechanistic study, published September 18, 2020 in The EMBO Journal, was led by Tariq Rana, PhD, professor and chief of the Division of Genetics in the Department of Pediatrics at UC San Diego School of Medicine and Moores Cancer Center.

Patients with COVID-19 who took statins fared better

A molecule known as ACE2 sits like a doorknob on the outer surfaces of many human cells, where it helps regulate and lower blood pressure. ACE2 can be affected by prescription statins and other medications used for cardiovascular disease.

But, in January 2020, researchers discovered a new role for ACE2: SARS-CoV-2, the coronavirus that causes COVID-19, primarily uses the receptor to enter lung cells and establish respiratory infections.

"When faced with this novel virus at the beginning of the pandemic, there was a lot of speculation surrounding certain medications that affect ACE2, including statins, and if they may influence COVID-19 risk," Daniels said. "We needed to confirm whether or not the use of statins has an impact on a person's severity of SARS-CoV-2 infection and determine if it was safe for our patients to continue with their medications."

To do this, Daniels, Messer and team retrospectively analyzed the electronic medical records of 170 patients with COVID-19 and 5,281 COVID-negative control patients hospitalized at UC San Diego Health between February and June 2020. They collected anonymized data that included the patients' disease severity, length of hospital stay, outcome, and use of statins, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) within 30 days prior to hospital admission.

Among the patients with COVID-19, 27 percent were actively taking statins on admission, while 21 percent were on an ACE inhibitor and 12 percent on an ARB. The median length of hospital stay was 9.7 days for patients with COVID-19.

The researchers found that statin use prior to hospital admission for COVID-19 was associated with a more than 50 percent reduction in risk of developing severe COVID-19, compared to those with COVID-19 but not taking statins. Patients with COVID-19 who were taking statins prior to hospitalization also recovered faster than those not taking the cholesterol-lowering medication.

"We found that statins are not only safe but potentially protective against a severe COVID-19 infection," said Daniels. "Statins specifically may inhibit SARS-CoV-2 infection through its known anti-inflammatory effects and binding capabilities as that could potentially stop progression of the virus."

This initial study was relatively small and focused on a single health system. Moving forward, Daniels is partnering with the American Heart Association to analyze thousands of patients all over the country to corroborate the data she's developed locally.

"I tell my patients who are on statins, ACE inhibitors or other ARBs to keep taking them," she said. "Fears of COVID-19 should not be a reason to stop, if anything our research findings should be incentive to continue with their medication."

Draining cholesterol from cell membranes blocks SARS-CoV-2 entry

Statins weren't yet on Rana's radar when they began their EMBO Journal study approximately six months ago. At first, his team was simply curious to see which genes are switched "on" in human lung cells in response to SARS-CoV-2 infection.

A gene called CH25H was "blazing hot," Rana said. CH25H encodes an enzyme that modifies cholesterol. "I got excited because with HIV, Zika, and a few others, we know that CH25H blocks the virus' ability to enter human cells."

Here's what's happening inside our cells: CH25H's enzymatic activity produces a modified form of cholesterol called 25-hydroxycholesterol (25HC). In turn, 25HC activates another enzyme called ACAT, found inside cells in the endoplasmic reticulum. ACAT then depletes accessible cholesterol on the cell's membrane. It's a normally occurring process that gets kicked into high gear during some viral infections.

The team quickly got to work examining 25HC in the context of SARS-CoV-2 from several angles. They explored what happens to human lung cells in the lab with and without 25HC treatment when they are exposed to first a noninfectious virus that carries the SARS-CoV-2 spike protein (its key to cell entry) or to live SARS-CoV-2 virus itself.

No matter which way they came at it, added 25HC inhibited the ability of the virus to enter cells -- blocking infection almost completely.

"The difference between untreated cells and those treated with 25HC was like day and night," Rana said.

While SARS-CoV-2 uses the ACE2 receptor to initially dock on a cell, Rana's study suggests that the virus also needs cholesterol (normally found in cell membranes) in order to fuse with and enter the cell. 25HC takes away a lot of that membrane cholesterol, preventing viral entry.

In a similar way, statins are likely beneficial in preventing or reducing the severity of SARS-CoV-2 infection because, while intended to remove cholesterol from blood vessels, they are also removing cholesterol from cell membranes. As a result, the coronavirus can't get in.

"This is already happening in our bodies on a regular basis, so perhaps we just need to give it a boost, with statins or by other means, to better resist some viruses," Rana said. "It's not unlike cancer immunotherapy -- the idea that sometimes instead of attacking a tumor directly, it's better to arm a patient's immune system to do a better job of clearing away tumors on its own."

If it can be developed into a therapeutic, 25HC might work even better as an antiviral than statins, Rana said. That's because it works specifically on cholesterol in cell membranes, rather than cholesterol throughout the body. Like all medications, statins can cause negative side effects, including digestive problems and muscle pains, and may not be an option for many people with COVID-19. What's more, while some previous studies suggested statins may also elevate ACE2 levels, which could allow more viral entry, Rana's team did not see an increase in the receptor in response to 25HC.

Statins are FDA-approved for human use, but 25HC is a natural product currently available only for laboratory work. Rana and team plan to continue optimizing 25HC as a potential antiviral agent. Many steps remain before it might be tested in human clinical trials.

AMHERST, Mass. - In a new climate modeling study that looked at the impacts of accelerated ice melt from the Antarctic Ice Sheet (AIS) on future climate, a team of climate scientists reports that future ice-sheet melt is expected to have significant effects on global climate.

First author and graduate student Shaina Sadai at the University of Massachusetts Amherst, with Alan Condron of the Woods Hole Oceanographic Institution, Rob DeConto at UMass Amherst and David Pollard at Pennsylvania State University, present details this week in Science Advances.

Their study predicts how future climate conditions could change under high- and low-greenhouse gas emissions scenarios, while accounting for accelerated melting of the AIS.

Scientists have long recognized that future meltwater input from the Antarctic will affect the Southern Ocean and global climate, but ice-sheet processes are not now included in most state-of-the-art climate prediction simulations, Sadai says. She and colleagues report that their modeling with the added ice melt information reveals interacting processes.

For this work, Sadai's task was to add accelerated AIS melting and icebergs into simulations of Earth's future climate. One important step was to include the details of where and when the meltwater will go into the ocean.

She says, "We found that future melt water coming off Antarctica leads to huge amounts of thick sea ice around the continent. With higher greenhouse gas emissions, the ice sheet melts faster, which in turn leads to more freshwater flowing into the ocean and more sea ice production."

All this additional meltwater and sea ice production dramatically slows the pace of future warming around Antarctica, the researchers report - seemingly welcome news. And remarkably, the climate impacts are not just restricted to the Antarctic. Condron, previously at UMass Amherst, points out that the cooling effects are felt worldwide.

But ,he adds, "All that said, it's important to note that this is not a global 'cooling' scenario - average global temperatures would still be roughly 3 degrees Celsius warmer than today due to human greenhouse gas emissions, even with the cooling effects of this melt water on climate."

That is not the end of the story. Even though atmospheric warming slows, the deep sea waters around Antarctica actually warm faster in their model. This is because, Condron explains, the new sea ice stops heat from escaping from the deeper waters to the atmosphere. "The subsurface ocean waters warm by as much as one degree Celsius, which can increase melting below parts of the ice sheet. This could make the ice sheet more unstable and accelerate rates of sea level rise beyond current projections."

Overall, Sadai says, "Our results demonstrate a need to accurately account for meltwater input from ice sheets if we are to make confident climate predictions." She emphasizes that the delayed future warming they found in the new simulations may sound like good news, but it is important to keep in mind that serious warming and sea level rise will still occur with unabated greenhouse gas emissions, which will affect coastal communities and ecosystems worldwide.

DeConto and Pollard add that the future stability of the AIS and future sea-level rise will be governed by which process wins out - ocean warming or atmospheric cooling. Answering this question is the target of the team's ongoing research.

During pregnancy in mice, the billions of bacteria and other microbes that live in a mother's intestines regulate key metabolites, small molecules that are important for healthy fetal brain development, UCLA biologists report Sept. 23 in the journal Nature.

While the maternal gut microbiota has been associated with abnormalities in the brain function and behavior of offspring -- often in response to factors like infection, a high-fat diet or stress during pregnancy -- scientists had not known until now whether it influenced brain development during critical prenatal periods and in the absence of such environmental challenges.

To test the impact the gut microbiata has on the metabolites and other biochemicals that circulate in maternal blood and nurture the rapidly developing fetal brain, the researchers raised mice that were treated with antibiotics to kill gut bacteria, as well as mice that were bred microbe-free in a laboratory.

"Depleting the maternal gut microbiota, using both methods, similarly disrupted fetal brain development," said the study's lead author, Helen Vuong, a postdoctoral scholar in laboratory of UCLA's Elaine Hsiao.

Depleting the maternal gut microbiota altered which genes were turned on in the brains of developing offspring, including many genes involved in forming new axons within neurons, Vuong said. Axons are tiny fibers that link brain cells and enable them to communicate.

In particular, axons that connect the brain's thalamus to its cortex were reduced in number and in length, the researchers found.

"These axons are particularly important for the ability to sense the environment," Vuong said. "Consistent with this, offspring from mothers lacking a gut microbiota had impairments in particular sensory behaviors."

The findings indicate that the maternal gut microbiota can promote healthy fetal brain development by regulating metabolites that enter the fetal brain itself, Vuong said.

"When we measured the types and levels of molecules in the maternal blood, fetal blood and fetal brain, we found that particular metabolites were commonly decreased or missing when the mother was lacking a gut microbiota during pregnancy," she said.

The biologists then grew neurons in the presence of these key metabolites. They also introduced these metabolites into the microbiata-depleted pregnant mice.

"When we grew neurons in the presence of these metabolites, they developed longer axons and greater numbers of axons," Vuong said. "And when we supplemented the pregnant mice with key metabolites that were decreased or missing when the microbiata was depleted, levels of those metabolites were restored in the fetal brain and the impairments in axon development and in offspring behavior were prevented.

"The gut microbiota has the incredible capability to regulate many biochemicals not only in the pregnant mother but also in the developing fetus and fetal brains," Vuong said. "Our findings also pinpoint select metabolites that promote axon growth."

The results suggest that interactions between the microbiota and nervous system begin prenatally through the influence of the maternal gut microbiota on the fetal brain, at least in mice.

The applicability of the findings to humans is still unclear, said the study's senior author, Elaine Hsiao, a UCLA associate professor of integrative biology and physiology, and of microbiology, immunology and molecular genetics in the UCLA College.

"We don't know whether and how the findings may apply to humans," said Hsiao, who is also an associate professor of digestive diseases at the David Geffen School of Medicine at UCLA. "However, there are many neurodevelopmental disorders that are believed to be caused by both genetic and environmental risk factors experienced during pregnancy. Our study suggests that maternal gut microbiota during pregnancy should also be considered and further studied as a factor that could potentially influence not only the health of the mother but the health of the developing offspring as well."

Hsiao, Vuong and colleagues reported in 2019 that serotonin and drugs that target serotonin, such as antidepressants, can have a major effect on the gut's microbiota. In 2018, Hsiao and her team established a causal link between seizure susceptibility and gut microbiota and identified specific gut bacteria that play an essential role in the anti-seizure effects of the ketogenic diet.

A neighborhood's overall socioeconomic status, including income and education level, may influence its residents' risk of chronic kidney disease, according to a study recently published in SSM Population Health by researchers from Drexel University's Dornsife School of Public Health.

Although previous studies have shown an association between individual socioeconomic status and chronic kidney disease, less is known about how the characteristics of an individual's neighborhood, such as overall socioeconomic status, walkability, violent crime and availability of healthy food, may influence the risk of chronic kidney disease, poor blood sugar control (A1c over or equal to 6.5 percent) and uncontrolled high blood pressure (at least one instance of systolic blood pressure greater than 140 mm Hg and/or diastolic blood pressure greater than 90 mm Hg), especially in urban areas.

In a study of 23,692 adult Philadelphians, all seen in a primary care practice in 2016 or 2017, the authors found that those living in low socioeconomic status neighborhoods (factoring in neighborhood income, educational attainment and occupation), were more likely to have kidney disease than those living in higher socioeconomic status neighborhoods. Also, poor neighborhood walkability, as measured by Walkscore®, was associated with poor blood sugar control in chronic kidney disease patients and poor blood pressure control in those without chronic kidney disease. The authors adjusted for individual age, race, sex and insurance type.

"Our finding, that people who are living in neighborhoods with the fewest resources are at highest risk for kidney disease, should be a call to health providers to integrate knowledge about their patients' environments in their care processes, and to policymakers to allocate resources to at-risk communities that will promote health," said senior author Meera Harhay, MD, an associate professor of Medicine at Drexel's College of Medicine and Dornsife School of Public Health. "Our results also show that neighborhood environments that promote physical activity are protective when it comes to blood pressure and blood sugar management, whereas less walkable neighborhoods might exacerbate conditions that are risk factors for kidney disease."

Chronic kidney disease is characterized by damaged kidneys that are unable to adequately filter waste and excess fluids out of blood. Without early detection and management of blood pressure and blood glucose, this damage can lead to kidney failure and dialysis or a kidney transplant as the remaining options. An estimated 37 million -- 15% -- of U.S. adults are estimated to suffer from chronic kidney disease, and nine out of 10 of those cases go undiagnosed. The findings of this research are valuable to the U.S. Department of Health and Human Services' Advancing American Kidney Health Initiative, whose goals include reducing the number of Americans in end-stage renal disease by 25% by 2030.

"This study offers tools to help identify communities at higher risk of kidney disease at earlier stages so their condition can be managed to prevent end-stage kidney disease from developing," Harhay said. "Health providers should consider incorporating knowledge about neighborhood-level social determinants of health when they are assessing their patients."

The authors note that future studies should look at what neighborhood characteristics might contribute to progression of chronic kidney disease, and whether socioeconomic status might be a marker for lower access to health-promoting resources, such as information on self-care and chronic disease management, that might help prevent chronic kidney disease.

Researchers at the University of Alberta have discovered a novel, second mechanism of action by the antiviral drug remdesivir against SARS-CoV-2, according to findings published today in the Journal of Biological Chemistry.

The research team previously demonstrated how remdesivir inhibits the COVID-19 virus’s polymerase or replication machinery in a test tube. 

Matthias Götte, chair of medical microbiology and immunology in the Faculty of Medicine & Dentistry, likened the polymerase to the engine of the virus. He said the first mechanism the team identified is like putting diesel fuel into an engine that needs regular gasoline. 

“You can imagine that if you give it more and more diesel, you will go slower and slower and slower,” he said.

The newly identified mechanism is more like a roadblock, “so if you want to go from A to B with the wrong fuel and terrible road conditions, you either never reach B or you arrive extremely late,” Götte said.

“Remdesivir stops or heavily delays replication of the virus, which in turn reduces propagation and spread.”

Benchmark drug against COVID-19

Götte said it is not common for antiviral drugs to have more than one mechanism of action. The first mechanism his team uncovered affects what is known as the “primer strand” of RNA or the first copy the virus makes of the viral genome as it infects a cell. The second mechanism affects the “template strand” which is repeated over and over as the virus spreads.

Clinical trials of remdesivir in COVID-19 patients are underway around the world, including one run by the U.S. National Institutes of Health which reported preliminary results showing the average recovery time for treated patients was shortened to 11 days compared with 15 days for the placebo group. 

Götte said it is important to know how remdesivir works because it is the only direct-acting antiviral currently approved for conditional and/or emergency use as a COVID-19 treatment in several countries, including Canada and the U.S. 

“That means remdesivir is a benchmark that we need to understand in great detail in order to build on it and to improve therapies in the future,” Götte said.

Next steps for human trials and laboratory studies

Götte said that while remdesivir looks promising in laboratory tests and in cell cultures, he is anxious to see more results from human clinical trials, in particular how remdesivir affects the “viral load” or amount of virus in patients. 

“Is there a difference as to whether somebody has a low viral load from the beginning or a high viral load? We don’t know that yet,” he pointed out.

He said laboratory results can differ from human trials because there could be reservoirs of the virus in the human body that the drug does not reach. SARS-CoV-2 may also develop resistance to the drug, although he thinks this will be difficult based on what is known about how remdesivir interacts with other coronaviruses.

“We need these data to help us to better understand which patients will benefit from remdesivir,” he said. 

Götte’s lab will continue trying to understand more about how remdesivir and other polymerase inhibitors work against SARS-CoV-2 to aid drug discovery and development. 

University of Houston researchers have found that during early pregnancy, the mix of alcohol and nicotine significantly alters the gene regulatory pathways of the developing fetus, which can lead to major deficiencies in brain development. Metin Akay, founding chair and John S. Dunn Endowed Chair Professor of biomedical engineering is reporting the findings, the first study of its kind, in the Nature journal Scientific Reports.

"The alterations of these pathways are crucial since they are involved in neural network formation, cell development and communication," reports Akay. "Among pathways in which many genes and miRNAs were significantly altered in response to perinatal nicotine/alcohol co-exposure are dopamine cell growth, neuronal migration, neuronal axon guidance, neurotrophin signaling and glutamatergic synapse."

Addictive substances act on the brain's reward system by triggering the release of the dopamine hormone through the activation of the mesocorticolimbic DA system, also known as the reward circuitry in the brain.

"A characteristic structure of dopamine neurons are the long axons that project to different regions of the brain to build functional networks, which results in pathways such as the mesocorticolimbic DA system," said Akay. "It is highly likely that axon guidance is modulated in the newborn after perinatal substance abuse and may cause faulty assembly of the network."

The alterations in this pathway cause interruptions in cellular communication and development, and finally, lead to synaptic rearrangements in the plasticity and neurological disorders.

It's no small problem.

Maternal substance abuse (drinking and smoking) during pregnancy increases health risks, including cognitive impairments, lower academic achievement, attention deficit hyperactivity disorder (ADHD), the likelihood of substance abuse in newborns, and may even lead sudden infant death syndrome (SIDS). Despite these harmful effects, more than 10% of pregnant women drink and smoke, according to the Centers for Disease Control.

Following alcohol treatment, 1,257 unique genes were found to be differentially upregulated and 330 were differentially downregulated. Following perinatal nicotine-alcohol treatment contrasted against the alcohol group, 2,113 genes were upregulated and 1,836 were downregulated.

"A more comprehensive treatment needs to be developed for the perinatal co-exposure since more pathways and gene expressions were significantly altered, suggesting the involvement of several addiction pathways in newborns," said Akay.

"Until now, the influence of maternal alcohol and nicotine co-exposure on the brain development of newborns has not been investigated at the multi scale from molecular, to cellular and to systemic levels," said Yasemin Akay, instructional associate professor of biomedical engineering and the co-lead investigator on the project. "Our group has focused on the integration of molecular, cellular and systemic data - using a custom-made implantable dopamine probe and artificial intelligence - to better understand the addiction mechanism and develop effective therapeutics," she said.

PHILADELPHIA -- A recent study published in the journal Nature Medicine, led by researchers James Riley, PhD, a professor of Microbiology at the Perelman School of Medicine at the University of Pennsylvania, and Todd Allen, PhD, a professor of Medicine at Harvard Medical School and Group Leader at the Ragon Institute of MGH, MIT and Harvard, describes a new Dual CAR T cell immunotherapy that can help fight HIV infection. The paper's first authors are Colby Maldini, a graduate student at the University of Pennsylvania and Daniel Claiborne, PhD, a research fellow at the Ragon Institute.

"This study highlights how relatively straightforward alterations to the way T cells are engineered can lead to dramatic changes in their potency and durability," Riley said. "This finding has significant implications for using engineered T cells to fight both HIV and cancer."

The global HIV epidemic impacts more than 35 million people around the world. Antiretroviral therapy (ART) is a daily treatment that can control, but not cure, HIV infection. However, access and lifelong adherence to a daily regimen is a significant barrier for many people living with HIV. A major hurdle to HIV cure is the viral reservoir, copies of HIV hidden away in the genome of infected cells. If ART treatment is stopped, the virus is able to rapidly make new copies of itself, ultimately leading to the development of AIDS.

CAR T cells are a powerful immunotherapy, currently used in cancer treatments, in which a patient's own immune T cells are engineered to express Chimeric Antigen Receptors (CARs). These CARs re-program the T cells to recognize and eliminate specific diseased or infected cells, such as cancer cells or, potentially, HIV-infected cells.

Allen's and Riley's research groups worked together to design a new HIV-specific CAR T cell. They needed to design a CAR T cell that would be able to target and quickly eliminate HIV-infected cells, survive and reproduce once in the body, and resist infection by HIV itself, since HIV's primary target is these very same T cells.

"By using a stepwise approach to solve each issue as it arose, we developed protected Dual CAR T cells, which provided a strong, long-lasting response against HIV-infection while being resistant to the virus itself," Allen said.

This Dual CAR T cell, a new type of CAR T cell, was made by engineering two CARs into a single T cell. Each CAR had a CD4 protein that allowed it to target HIV-infected cells and a costimulatory domain, which signaled the CAR T cell to increase its immune functions. The first CAR contained the 4-1BB co-stimulatory domain, which stimulates cell proliferation and persistence, while the second has the CD28 co-stimulatory domain, which increases its ability to kill infected cells.

Since HIV frequently infects T cells, they also added in a protein called C34-CXCR4, developed in the lab of James Hoxie, MD, a professor of Hematology-Oncology at Penn. C34-CXCR4 prevents HIV from attaching to and then infecting the cell. The final CAR T cell was long-lived, replicated in response to HIV infection, killed infected cells effectively, and was partially resistant to HIV infection.

When the protected Dual CAR T cells were given to HIV-infected mice, the team saw slower HIV replication and fewer HIV infected cells than in untreated animals. They also saw reduced amounts of virus and preservation of CD4+ T cells, HIV's preferred target, in the blood of these animals. In addition, when they combined Dual CAR T cells with ART in HIV-infected mice, the virus was suppressed faster, which led to a smaller viral reservoir than in mice who were only treated with ART.

"The ability of these protected Dual CAR T cells to reduce the HIV burden in a variety of tissues and cell types, including long-lived memory CD4+ T cells, we believe supports the approach of using CAR T cell therapy as a new tool to target the HIV reservoir towards a functional cure for HIV," said Allen.