Month: November 2020

“Elegant Chemo” Uses CRISPR Tools to Target Tumours

New research from Tel Aviv University led by Prof Dan Peer, has developed a new system to directly slice DNA in cancer cells, effectively “deleting” them with molecular “scissors”, leaving no side effects, it is claimed. 

“This is the first study in the world to prove that the CRISPR genome editing system, which works by cutting DNA, can effectively be used to treat cancer in an animal,” said Peer.

The treatment increased survival by 30% for mice with gliboglioblastoma, one of the deadliest cancers, and 80% in disseminated ovarian tumours. 

When adapted for humans, the treatment would have to be customised for each individual based on a biopsy and then injected, either into the tumour or generally.

Peer explained that the injection consists of three components: a nanoparticle made from lipids, messenger RNA which “encodes” the “tiny scissor function” for cutting the DNA, and a system which “recognises” cancerous cells.   

Peer said, “When we first spoke of treatments with messenger RNA twelve years ago, people thought it was science fiction. I believe that in the near future, we will see many personalized treatments based on genetic messengers, for cancer and various genetic diseases.”

Source: Times of Israel

COVID and Vaping Lung Injuries can be Confused

Three recent case studies show that breathing problems in teens could be a result of vaping or COVID, according to a UC Davis Health paediatric team.

Known as e-cigarette, or vaping, product use-associated lung injury (EVALI), it is present in large numbers. As of February 2020, 2758 cases of EVALI were hospitalised, with 64 deaths in the United States, and over half of those hospitalised were under 25 years old.

“EVALI and COVID-19 share many symptoms but have very different treatment plans,” said lead author Kiran Nandalike, associate professor of paediatrics. “For this reason, providers caring for pediatric patients with unexplained respiratory failure should consider EVALI and ask for relevant smoking/vaping history.”

EVALI and COVID patients often present with fever, cough, nausea, abdominal pain and diarrhoea. Bilateral ground glass opacities are seen in chest imaging in both conditions.

Adolescents often use vaping with marijuana obtained through friends, family and unlicenced dealers, with products often containing vitamin E acetate, an additive which is strongly associated with lung injury. Isolation and stress as a result of the COVID pandemic increased usage.

In the case studies, all of the patients had fever, nausea and cough, as well as a high heart rate, rapid breathing and low blood oxygen levels. Laboratory results showed higher white blood cells (WBC) count and elevated inflammation, pointing to COVID inflammation. Chest imaging revealed nonspecific ground glass opacities. Despite all other findings indicating COVID, SARS-CoV-2 testing was negative. The patients were successfully treated with steroids, a potentially life-saving treatment for EVALI.

“To help reduce risk of EVALI recurrence, providers would recommend vaping cessation counseling to patients and close outpatient monitoring,” advised Nandalike.

Source: Medical Xpress

Gut Microbiome is Linked to Pulmonary Disease

A link has been shown between the gut microbiome and chronic obstructive pulmonary disease (COPD), a lung disease with an often poor prognosis.

Senior author Prof Phil Hansbro, Director of the Centenary University of Technology Sydney Centre for Inflammation, said, “It’s already known that the lung microbiome is a contributing factor in COPD. We wanted to see if the gut environment was also somehow involved–to determine whether the gut could act as a reliable indicator of COPD or if it was connected in some way to the development of the disease.”

Stool samples of COPD patients showed elevated levels of the bacteria Streptococcus and Lachnospiraceae. Additionally a unique metabolite signature was identified in individuals with COPD, created by the chemical by-products of the metabolic process.

First author Dr Kate Bowerman from the University of Queensland said, “Our research indicates that the gut of COPD patients is notably different from healthy individuals. This suggests that stool sampling and analysis could be used to non-invasively diagnose and monitor for COPD,” she said.
“The ‘gut-lung axis’ describes the common immune system of the lung and gastrointestinal tract. This means that activity in the gut can impact activity in the lung. Our COPD findings suggest that the gut microbiome should now also be considered when looking for new therapeutic targets to help treat lung disease,” Prof Hansbro said.

Source: Medical Xpress

Long-term HIV Immunisation in Mice with Gene Technology

While some COVID vaccines are entering the final phases of approval less than a year before the disease was first identified, HIV still has no vaccine after decades of research.

Now, engineered immune cells have elicited a response against HIV in mice, presenting an important first step forward in the quest for a vaccine. These broadly neutralising antibodies (bnabs) are effective against a variety of viruses and neutralise the glycan protecting HIV’s proteins.

Previous research had engineered B cells that produced the same antibodies as seen in rare HIV patients who are able to produce bnabs against HIV after many years. Now, this research has shown that it was possible to mature these into memory and plasma cells, conferring long-lasting protection and even showing improved antibodies can be produced, as in the immunisation process.

Principal investigator James Voss, PhD, of Scripps Research said, “This is the first time it has been shown that modified B cells can create a durable engineered antibody response in a relevant animal model.”

Currently it appears it would be an expensive therapy and a great barrier to many of the 38 million living with HIV around the world. A blood draw would be taken to the lab to engineer a vaccine for the patient, but Voss says that his team is looking to make the procedure inexpensive.

“People think of cell therapies as being very expensive,” Voss said. “We’re doing a lot of work towards trying to make the technology affordable as a preventative HIV vaccine or functional cure that would replace daily antiviral therapy.”

Source: Science Daily

COVID Most Infectious Early On, Says New Review

According to a meta-analysis of COVID research published in The Lancet, individuals with COVID are most infectious early on.

In a meta-analysis of 79 studies from around the world, they examined viral load dynamics, duration of viral RNA shedding, and viable virus shedding for SARS-CoV-2, and for comparison, 8 studies on MERS-CoV and 11 on SARS-CoV. The study only looked at symptomatic individuals.

For SARS-CoV-2, the average duration of viral RNA shedding was 17 days in the upper respiratory tract and 14.6 days in the lower respiratory tract. Similar durations were found for stool (17.2 days) and serum samples (16.6 days). 

The maximum duration of viral RNA shedding was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract and 126 days in stools.  No role could be discerned for faecal shedding. Average shedding duration was positively correlated with age. No studies detected live virus after 9 days.

The viral load in the upper respiratory tract reached a peak in the first week of illness, which was shorter than SARS-CoV (peaking at days 10-14) and MERS-CoV (days 7-10). Most studies indicated faster viral load clearing in asymptomatic versus symptomatic SARS-CoV-2 carriers.

In view of these findings, the researchers suggest that repeat testing may not be necessary for patients no longer deemed infectious, and that isolation could be set for 10 days after the onset of symptoms.

The researchers concluded that early containment was key in fighting the spread of COVID, especially with regard to acting on atypical symptoms that might appear before other symptoms. Still, this could prove challenging to effect in practice. 

Source: The Lancet

T-cells can detect HIV-1

A new study reported by News 24 shows that T-cells can detect HIV-1 in patients years after commencing antiretroviral therapy (ART): 

In the HIV-1 proteome (the entire set of proteins expressed by the virus) for each participant, the team identified T-cell epitopes (regions of proteins that trigger an immune response). They sequenced HIV-1 ‘outgrowth’ viruses from resting CD4+ T cells and tested mutations in T-cell epitopes for their effect on the size of the T-cell response.

These strategies revealed that the majority (68%) of T-cell epitopes did not harbour any detectable escape mutations, meaning they could be recognised by circulating T cells.

“Our findings show that the majority of HIV-1-specific T cells in people on ART can detect HIV viruses that have the capacity to rebound following treatment interruption,” concludes senior author Nilu Goonetilleke, a faculty member at the Department of Microbiology and Immunology, University of North Carolina at Chapel Hill.

Controversial Study: Cloth Masks Don’t Prevent Catching COVID

In a controversial result, researchers in Denmark have shown real-world evidence that masks do not protect against becoming infected with COVID.

4860 participants completed the study in Denmark, which at the time had a 2% infection rate. Half received surgical masks and were told to wear them outside while the other half were told not to wear masks. The researchers had hoped to see the masks halving the infection rate among wearers, but 1.8% of mask wearers became infected with COVID vs 2.1% of non-mask wearers.

“Our study gives an indication of how much you gain from wearing a mask,” said lead author Dr Henning Bundgaard, a cardiologist at the University of Copenhagen. “Not a lot.”

The results were met with scepticism by some, and noted that the lower prevalence of COVID in Denmark at the time made differences hard to detect.

Dr Thomas Frieden, chief executive of Resolve to Save Lives, an advocacy group, and former director of the CDC outlined the limitations of the study, saying, “There is absolutely no doubt that masks work as source control. The question this study was designed to answer is: Do they work as personal protection?” Frieden said that the answer to those questions lay in the amount of virus exposure and the nature of the masks involved.

“An N95 mask is better than a surgical mask,” he said. “A surgical mask is better than most cloth masks. A cloth mask is better than nothing.”

Dr Christine Laine, editor in chief of the Annals of Internal Medicine, characterised the evidence that masks were protective of wearers as weak.

“These studies cannot differentiate between source control and personal protection of the mask wearer,” she said. 

She added that the new study reinforced the need for other methods, such as social distancing. Masks “are not a magic bullet,” she said. “There are people who say, ‘I’m fine, I’m wearing a mask.’ They need to realise they are not invulnerable to infection.”

Source: Japan Times

Activists to Pressure SA Government over COVID Vaccine

With the recent news that Pfizer’s and Moderna’s vaccines both have over a 90% efficacy, and air cargo carriers are standing ready to transport them, concerns are mounting that South Africa, with no deals to access vaccines, will be left out in the scramble by richer countries to secure vaccines.

Mark Heywood, executive director of Section27 and a veteran activist, said: “Now that vaccines are becoming available, our government must use all its powers to ensure that people in South Africa have equal access. Neither price nor patents should be an obstacle, and government must start now to think about the systems that will be needed to ensure the smooth distribution of the vaccine, starting for those with the highest risk of Covid-19.”

Dr Anthonet Koen, principal investigator at a COVID vaccine trial site, said: “It’s important that we get a vaccine that’s right, especially for South Africa. We often get overseen and get left behind when it comes to life-saving treatments. If you think about HIV, we were last in line to get access to antiretrovirals, and we don’t want that to happen.”
Koen dispelled any possibility of a vaccine being available before the year is out. “We need to be realistic about this… but hopefully within the first quarter of 2021 we will have something.”

Health Minister Zweli Mkhizi reiterated that there was no vaccine for now, “so we need to adhere to containment measures”.

Not only the vaccine’s acquisition but its logistics for distribution must be taken into account. Economist Mike Schussler said, “The entire supply chain will have to be considered. What we know is that if we had to do half of the South African population it would cost about R40  billion, and that’s highly problematic and unaffordable so we have to think strategically about this.”

Source: IOL

HIV Death Rates in Men Far Exceed Women in SA

At a virtual conference on Tuesday, the South African National AIDS Council (Sanac) showcased their updated Thembisa model, which is the definitive model for HIV prevalence and incidence in the country.

Between 2000 and 2019, there was a 57% drop in incidence, or new infections, which falls short of the UN target of 75% reduction.  Antiretroviral therapy (ART) coverage is 71% of those infected with HIV.

About 13% of South Africans are currently living with HIV, which is partly a result of longer life expectancy thanks to ART. Among female sex workers, the prevalence is 55%. Due to biological and social factors, the prevalence rate is higher among women but the death rate from HIV is higher in men, due to less ART coverage than in women.

The new Thembisa model also showed the country’s progress towards UNAIDS 90-90-90 model (90% knowing their HIV status, 90% on ART, 90% viral suppression). Although 94% of women and 91% of men knew their statuses, only 74% of women and 71% of men were on ART. Fortunately, 92% of both sexes achieved viral suppression. 

SA’s National Strategic Plan for HIV, TB and STIs is due to be renewed in 2022.

Source: Daily Maverick

Tinnitus Severity Measured with Non-invasive Brain Imaging

Tinnitus, experienced by about 20% of people, has long been a complaint without any overt signs to measure. Recent bran imaging techniques showed that tinnitus was related to increased neural firing and changes in connectivity in certain brain regions.

Using functional near-infrared spectroscopy (fNIRS), researchers in 2014 were able to map anomalous activity in the right auditory cortex of tinnitus sufferers, and in 2018, researchers showed that signals there were related to both the presence and intensity of the tinnitus.

fNIRS measures the absorption of near-infrared light shining into the head to measure oxy- and deoxyhaemoglobin levels, which are associated with cerebral activity.

Using machine learning which compared 25 patients with tinnitus to 21 healthy patients, the researchers were able to isolate two distinct areas of 

The algorithms were able to diagnose tinnitus with 78% accuracy and gauge intensity with 87% accuracy.

The imaging showed higher connectivity in the temporal-frontal lobe, linked to tinnitus duration and stress, and higher connectivity in the temporal-occipital lobe, which is linked to sound intensity. It opens the possibility of measuring both loudness and annoyance with fNIRS, and also supports preliminary research showing that by making the brain process other information, the tinnitus intensity can be reduced.

Source: Science Alert