Largest COVID-19 contact-tracing finds children key to spread, evidence of superspreaders

A study of more than a half-million people in India who were exposed to the novel coronavirus SARS-CoV-2, or COVID-19, suggests that the virus' continued spread is driven by only a small percentage of those who become infected. 

Furthermore, children and young adults were found to be potentially much more important to transmitting the virus—especially within households—than previous studies have identified, according to a paper by researchers from the United States and India published Sept. 30 in the journal Science.

Researchers from the Princeton Environmental Institute (PEI), Johns Hopkins University and the University of California-Berkeley worked with public health officials in the southeast Indian states of Tamil Nadu and Andhra Pradesh to track the infection pathways and mortality rate of 575,071 individuals who were exposed to 84,965 confirmed cases of SARS-CoV-2. It is the largest contact-tracing study—which is the process of identifying people who came into contact with an infected person—conducted in the world for any disease.

Lead researcher Ramanan Laxminarayan, a senior research scholar in PEI, said that the paper is the first large study to capture the extraordinary extent to which COVID-19 hinges on "superspreading," in which a small percentage of the infected population passes the virus on to more people. The researchers found that 71% of infected individuals did not infect any of their contacts, while a mere 8% of infected individuals accounted for 60% of new infections.

"Our study presents the largest empirical demonstration of superspreading that we are aware of in any infectious disease," Laxminarayan said. "Superspreading events are the rule rather than the exception when one is looking at the spread of COVID-19, both in India and likely in all affected places."

The findings provide extensive insight into the spread and deadliness of COVID-19 in countries such as India—which has experienced more than 96,000 deaths from COVID-19—that have a high incidence of resource-limited populations, the researchers reported. They found that coronavirus-related deaths in India occurred, on average, six days after hospitalization compared to an average of 13 days in the United States. Also, deaths from coronavirus in India have been concentrated among people aged 50-64, which is slightly younger than the 60-plus at-risk population in the United States.

The researchers also reported, however, the first large-scale evidence that the implementation of a country-wide shutdown in India led to substantial reductions in coronavirus transmission.

The researchers found that the chances of a person with coronavirus, regardless of their age, passing it on to a close contact ranged from 2.6% in the community to 9% in the household. The researchers found that children and young adults—who made up one-third of COVID cases—were especially key to transmitting the virus in resource-limited populations.

"Kids are very efficient transmitters in this setting, which is something that hasn't been firmly established in previous studies," Laxminarayan said. "We found that reported cases and deaths have been more concentrated in younger cohorts than we expected based on observations in higher-income countries."

Children and young adults were much more likely to contract coronavirus from patients their own age, the study found. In general, same-age contacts across all age groups greatly increased the chance of infection, with the probability of catching coronavirus from low- to high-risk contacts ranging from 4.7-10.7%, respectively. 

More information: "Epidemiology and transmission dynamics of COVID-19 in two Indian states," Science (2020). science.sciencemag.org/cgi/doi … 1126/science.abd7672

https://medicalxpress.com/news/2020-09-largest-covid-contact-tracing-children-key.html

Pathogens in the mouth induce oral cancer

Pathogens found in tissues that surround the teeth contribute to a highly aggressive type of oral cancer, according to a study published 1st October in the open-access journal PLOS Pathogens by Yvonne Kapila of the University of California, San Francisco, and colleagues. In addition, the study showed that oral cancer formation mediated by the pathogens is inhibited by a bacteriocin—an antimicrobial and probiotic peptide that is produced by bacteria.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide. Oral squamous cell carcinoma (OSCC), a subset of HNSCC, accounts for 90% of all oral malignancies, and it has a poor five-year survival rate that has not changed in decades. Risk factors, including smoking, alcohol consumption and human papilloma virus infection, alone have not been sufficient to explain the incidence and aggressive nature of OSCC. Other factors such as oral pathogens may play an important role in OSCC tumor development, progression and metastasis, yet this has not been well explored. Kapila and her collaborators tested whether OSCC is promoted by periodontal pathogens (i.e., those affecting the structures surrounding and supporting the teeth).

They found that three types of periodontal pathogens (Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum) enhanced OSCC cell migration, invasion, and tumor formation in mice. These effects were mediated by interactions between two signaling pathways: integrin/FAK and TLR/MyDD88. The pathogen-mediated processes were inhibited by treatment with nisin—a bacteriocin and a commonly used food preservative. According to the authors, this study offers the first direct evidence that a bacteriocin inhibits oral cancer formation mediated by periodontal pathogens. Moreover, the findings suggest that nisin could have broad therapeutic potential as an antimicrobial and anticancer agent, and as an inhibitor of pathogen-mediated cancer formation.

The authors conclude, "Since a probiotic bacteriocin peptide, nisin, rescues this pathogen-mediated carcinogenesis, these findings could advance treatment for oral cancer and establish a novel paradigm for cancer treatment focused on antimicrobial-based therapies." 

More information: Kamarajan P, Ateia I, Shin JM, Fenno JC, Le C, Zhan L, et al. (2020) Periodontal pathogens promote cancer aggressivity via TLR/MyD88 triggered activation of Integrin/FAK signaling that is therapeutically reversible by a probiotic bacteriocin. PLoS Pathog 16(10): e1008881. doi.org/10.1371/journal.ppat.1008881

https://medicalxpress.com/news/2020-10-pathogens-mouth-oral-cancer.html

Why writing by hand makes kids smarter

New brain research shows that writing by hand helps children learn more and remember better. At the same time, schools are becoming more and more digital, and a European survey shows that Norwegian children spend the most time online of 19 countries in the EU. 

Professor Audrey van der Meer at NTNU believes that national guidelines should be put into place to ensure that children receive at least a minimum of handwriting training.

Results from several studies have shown that both children and adults learn more and remember better when writing by hand.

Now another study confirms the same: choosing handwriting over keyboard use yields the best learning and memory.

"When you write your shopping list or lecture notes by hand, you simply remember the content better afterwards," Van der Meer says.

Captures the brain's electricity

Van der Meer and her colleagues have investigated this several times, first in 2017 and now in 2020.

In 2017, she examined the brain activity of 20 students. She has now published a study in which she examined brain activity in twelve young adults and twelve children.

This is the first time that children have participated in such a study.

Both studies were conducted using an EEG to track and record brain wave activity. The participants wore a hood with over 250 electrodes attached.

The brain produces electrical impulses when it is active. The sensors in the electrodes are very sensitive and pick up the electrical activity that takes place in the brain.

Handwriting gives the brain more hooks to hang memories on

Each examination took 45 minutes per person, and the researchers received 500 data points per second.

The results showed that the brain in both young adults and children is much more active when writing by hand than when typing on a keyboard.

"The use of pen and paper gives the brain more 'hooks' to hang your memories on. Writing by hand creates much more activity in the sensorimotor parts of the brain. A lot of senses are activated by pressing the pen on paper, seeing the letters you write and hearing the sound you make while writing. These sense experiences create contact between different parts of the brain and open the brain up for learning. We both learn better and remember better," says Van der Meer.

Digital reality a big part of European children's lives

She believes that her own and others' studies emphasize the importance of children being challenged to draw and write at an early age, especially at school.

Today's digital reality is that typing, tapping and screen time are a big part of children's and adolescents' everyday lives.

A survey of 19 countries in the EU shows that Norwegian children and teens spend the most time online. The smartphone is a constant companion, followed closely by PCs and tablets.

The survey shows that Norwegian children ages 9 to16 spend almost four hours online every day, double the amount since 2010.

Kids' leisure time spent in front of a screen is now amplified by schools' increasing emphasis on digital learning.

Van der Meer thinks digital learning has many positive aspects, but urges handwriting training.

National guidelines needed

"Given the development of the last several years, we risk having one or more generations lose the ability to write by hand. Our research and that of others show that this would be a very unfortunate consequence" of increased digital activity, says Meer.

She believes that national guidelines should be put in place that ensure children receive at least a minimum of handwriting training.

"Some schools in Norway have become completely digital and skip handwriting training altogether. Finnish schools are even more digitized than in Norway. Very few schools offer any handwriting training at all," says Van der Meer.

In the debate about handwriting or keyboard use in school, some teachers believe that keyboards create less frustration for children. They point out that children can write longer texts earlier, and are more motivated to write because they experience greater mastery with a keyboard.

Important to be outside in all kinds of weather

"Learning to write by hand is a bit slower process, but it's important for children to go through the tiring phase of learning to write by hand. The intricate hand movements and the shaping of letters are beneficial in several ways. If you use a keyboard, you use the same movement for each letter. Writing by hand requires control of your fine motor skills and senses. It's important to put the brain in a learning state as often as possible. I would use a keyboard to write an essay, but I'd take notes by hand during a lecture," says Van der Meer.

Writing by hand challenges the brain, as do many other experiences and activities.

"The brain has evolved over thousands of years. It has evolved to be able to take action and navigate appropriate behavior. In order for the brain to develop in the best possible way, we need to use it for what it's best at. We need to live an authentic life. We have to use all our senses, be outside, experience all kinds of weather and meet other people. If we don't challenge our brain, it can't reach its full potential. And that can impact school performance," says Van der Meer.

More information: Eva Ose Askvik et al. The Importance of Cursive Handwriting Over Typewriting for Learning in the Classroom: A High-Density EEG Study of 12-Year-Old Children and Young Adults, Frontiers in Psychology (2020). DOI: 10.3389/fpsyg.2020.01810

https://medicalxpress.com/news/2020-10-kids-smarter.html

UK scientists trial Humira biosimilar for COVID-19 in care homes

Researchers at the University of Oxford in the UK have started a trial of TNF inhibitor adalimumab for COVID-19 patients in care homes and other community settings.

Adalimumab – sold by AbbVie as Humira as well as in biosimilar form by companies including Novartis’ Sandoz unit, Amgen and Biogen/Samsung joint venture Bioepis – will be used in the phase 2 AVID-CC study to see if it can prevent progression to respiratory failure in people with coronavirus infections.

Sandoz is providing the adalimumab to be used in the trial, which will be carried out at care homes around the UK and is due to get underway later this month. The main readout of the study is whether adalimumab can prevent progression to respiratory failure or death due to COVID-19.

Meanwhile, with the country entering a new phase of social distancing and restrictions, the study will use digital tools for remote symptom data collection and analytics provided by Sensyne Health.

Those tools will collect additional information on patients’ symptoms, vital signs and activities of daily living through an app called CVm-Health, which was launched earlier this year.

Care home residents were particularly hard hit by the first wave of COVID-19 earlier this year, often experiencing severe symptoms including acute respiratory distress syndrome (ARDS).

In July, data published by the Office of National Statistics (ONS) suggested that almost 30,000 more care home residents in England and Wales died during the coronavirus outbreak than during the same period in 2019.

While some drugs like dexamethasone have been shown to help patients within hospitals, so far no therapies have emerged that work in community care settings, and the Oxford trial aims to see whether adalimumab could fulfil that role.

The anti-TNF drug has been used for more than two decades to treat conditions like rheumatoid arthritis and inflammatory bowel disease, and it is hoped that it could also interrupt the runaway inflammation that occurs in some patients with COVID-19.

There is some evidence that people already taking anti-TNF drugs for other illnesses are less likely to be admitted to hospital with COVID-19 – something that hasn’t been seen with other anti-inflammatory drugs, according to the university.

According to one of the trial investigators – Prof Dan Lasserson of the University of Warwick – AVID-CC is the first drug trial designed for acute ‘hospital at home’ services as an alternative to inpatient care.

“We need to determine the best treatments for COVID-19 that can be given to older people with frailty who are in care homes or living in their own homes,” he said, adding that it could also “help the development nationally of acute hospital at home services.”

AVID-CC is funded by the COVID-19 Therapeutics Accelerator, an initiative set up by Wellcome, the Bill and Melinda Gates Foundation and Mastercard in March.

https://pharmaphorum.com/news/uk-scientists-trial-anti-tnf-drug-for-covid-19-in-care-homes/

Many ventilation systems may increase risk of COVID-19 exposure

Ventilation systems in many modern office buildings, which are designed to keep temperatures comfortable and increase energy efficiency, may increase the risk of exposure to the coronavirus, particularly during the coming winter, according to research published in the Journal of Fluid Mechanics.

A team from the University of Cambridge found that widely-used ‘mixing ventilation’ systems, which are designed to keep conditions uniform in all parts of the room, disperse airborne contaminants evenly throughout the space. These contaminants may include droplets and aerosols, potentially containing viruses.

The research has highlighted the importance of good ventilation and mask-wearing in keeping the contaminant concentration to a minimum level and hence mitigating the risk of transmission of SARS-CoV-2, the virus that causes COVID-19.

The evidence increasingly indicates that the virus is spread primarily through larger droplets and smaller aerosols, which are expelled when we cough, sneeze, laugh, talk or breathe. In addition, the data available so far indicate that indoor transmission is far more common than outdoor transmission, which is likely due to increased exposure times and decreased dispersion rates for droplets and aerosols.

“As winter approaches in the northern hemisphere and people start spending more time inside, understanding the role of ventilation is critical to estimating the risk of contracting the virus and helping slow its spread,” said Professor Paul Linden from Cambridge’s Department of Applied Mathematics and Theoretical Physics (DAMTP), who led the research.

“While direct monitoring of droplets and aerosols in indoor spaces is difficult, we exhale carbon dioxide that can easily be measured and used as an indicator of the risk of infection. Small respiratory aerosols containing the virus are transported along with the carbon dioxide produced by breathing, and are carried around a room by ventilation flows. Insufficient ventilation can lead to high carbon dioxide concentration, which in turn could increase the risk of exposure to the virus.”

The team showed that airflow in rooms is complex and depends on the placement of vents, windows and doors, and on convective flows generated by heat emitted by people and equipment in a building. Other variables, such as people moving or talking, doors opening or closing, or changes in outdoor conditions for naturally ventilated buildings, affect these flows and consequently influence the risk of exposure to the virus.

Ventilation, whether driven by wind or heat generated within the building or by mechanical systems, works in one of two main modes. Mixing ventilation is the most common, where vents are placed to keep the air in a space well mixed so that temperature and contaminant concentrations are kept uniform throughout the space.

The second mode, displacement ventilation, has vents placed at the bottom and the top of a room, creating a cooler lower zone and a warmer upper zone, and warm air is extracted through the top part of the room. As our exhaled breath is also warm, most of it accumulates in the upper zone. Provided the interface between the zones is high enough, contaminated air can be extracted by the ventilation system rather than breathed in by someone else. The study suggests that when designed properly, displacement ventilation could reduce the risk of mixing and cross-contamination of breath, thereby mitigating the risk of exposure.

As climate change has accelerated since the middle of the last century, buildings have been built with energy efficiency in mind. Along with improved construction standards, this has led to buildings that are more airtight and more comfortable for the occupants. In the past few years however, reducing indoor air pollution levels has become the primary concern for designers of ventilation systems.

“These two concerns are related, but different, and there is tension between them, which has been highlighted during the pandemic,” said Dr Rajesh Bhagat, also from DAMTP. “Maximising ventilation, while at the same time keeping temperatures at a comfortable level without excessive energy consumption is a difficult balance to strike.”

In light of this, the Cambridge researchers took some of their earlier work on ventilation for efficiency and reinterpreted it for air quality, in order to determine the effects of ventilation on the distribution of airborne contaminants in a space.

“In order to model how the coronavirus or similar viruses spread indoors, you need to know where people’s breath goes when they exhale, and how that changes depending on ventilation,” said Linden. “Using these data, we can estimate the risk of catching the virus while indoors.”

The researchers explored a range of different modes of exhalation: nasal breathing, speaking and laughing, each both with and without a mask. By imaging the heat associated with the exhaled breath, they could see how it moves through the space in each case. If the person was moving around the room, the distribution of exhaled breath was markedly different as it became captured in their wake.

“You can see the change in temperature and density when someone breathes out warm air – it refracts the light and you can measure it,” said Bhagat. “When sitting still, humans give off heat, and since hot air rises, when you exhale, the breath rises and accumulates near the ceiling.”

Their results show that room flows are turbulent and can change dramatically depending on the movement of the occupants, the type of ventilation, the opening and closing of doors and, for naturally ventilated spaces, changes in outdoor conditions.

The researchers found that masks are effective at reducing the spread of exhaled breath, and therefore droplets.

“One thing we could clearly see is that one of the ways that masks work is by stopping the breath’s momentum,” said Linden. “While pretty much all masks will have a certain amount of leakage through the top and sides, it doesn’t matter that much, because slowing the momentum of any exhaled contaminants reduces the chance of any direct exchange of aerosols and droplets as the breath remains in the body’s thermal plume and is carried upwards towards the ceiling. Additionally, masks stop larger droplets, and a three-layered mask decreases the amount of those contaminants that are recirculated through the room by ventilation.”

The researchers found that laughing, in particular, creates a large disturbance, suggesting that if an infected person without a mask was laughing indoors, it would greatly increase the risk of transmission.

“Keep windows open and wear a mask appears to be the best advice,” said Linden. “Clearly that’s less of a problem in the summer months, but it’s a cause for concern in the winter months.”

The team are now working with the Department for Transport looking at the impacts of ventilation on aerosol transport in trains and with the Department for Education to assess risks in schools this coming winter.

https://www.cam.ac.uk/research/news/many-ventilation-systems-may-increase-risk-of-covid-19-exposure-study-suggests