Forty percent of dementia cases could be prevented or delayed by targeting 12 risk factors throughout life

by Lancet

Credit: CC0 Public Domain

Modifying 12 risk factors over the lifecourse could delay or prevent 40% of dementia cases, according to an update to The Lancet Commission on dementia prevention, intervention, and care, which is being presented at the Alzheimer's Association International Conference (AAIC 2020).

30 july 2020--Combined, the three new risk factors are associated with 6% of all dementia cases—with an estimated 3% of cases attributable to head injuries in mid-life, 1% of cases to excessive alcohol consumption (of more than 21 units per week) in mid-life, and 2% to exposure to air pollution in later life.

The remaining risk factors are associated with 34% of all dementia cases. The factors associated with the greatest proportion of dementia cases in the population are less education in early life, hearing loss in mid-life, and smoking in later life (7%, 8%, and 5%, respectively).

Led by 28 world-leading dementia experts, the report builds on the 9 risk factors identified in the 2017 Lancet Commission, and provides an up-to-date analysis of the best evidence on the prevention of dementia. The new report calls for nations and individuals to be ambitious about preventing dementia and lays out a set of policies and lifestyle changes to help prevent dementia.

Worldwide around 50 million people live with dementia, and this number is projected to increase to 152 million by 2050, rising particularly in low-income and middle-income countries (LMIC) where around two-thirds of people with dementia live. Dementia affects individuals, their families, and the economy, with global costs estimated at about US$1 trillion annually.

In certain countries, however, the proportion of older people with dementia has fallen, probably due to improvements in education, nutrition, health care, and lifestyle changes, demonstrating the possibility of reducing dementia through preventative measures.

"Our report shows that it is within the power of policy-makers and individuals to prevent and delay a significant proportion of dementia, with opportunities to make an impact at each stage of a person's life," says lead author Professor Gill Livingston, University College London, UK. "Interventions are likely to have the biggest impact on those who are disproportionately affected by dementia risk factors, like those in low- and middle-income countries and vulnerable populations, including Black, Asian and Minority Ethnic communities."

Professor Livingston continues, "As societies, we need to think beyond promoting good health to prevent dementia, and begin tackling inequalities to improve the circumstances in which people live their lives. We can reduce risks by creating active and healthy environments for communities, where physical activity is the norm, better diet is accessible for all, and exposure to excessive alcohol is minimized."

To address dementia risk, the authors call for 9 ambitious recommendations to be undertaken by policymakers and by individuals:

• Aim to maintain systolic blood pressure of 130 mm Hg or less in midlife from around age 40 years.
• Encourage use of hearing aids for hearing loss and reduce hearing loss by protecting ears from high noise levels.
• Reduce exposure to air pollution and second-hand tobacco smoke.
• Prevent head injury (particularly by targeting high risk occupations and transport)
• Prevent alcohol misuse and limit drinking to less than 21 units per week.
• Stop smoking uptake and support individuals to stop smoking (which the authors stress is beneficial at any age).
• Provide all children with primary and secondary education.
• Lead an active life into mid, and possibly later life.
• Reduce obesity and diabetes.

These actions are especially important in LMICs where dementia rates are rising more rapidly than in high-income countries. This is a result of increasing life expectancy, and a higher frequency of certain dementia risk factors—such as lower rates of education; high rates of hypertension, obesity, and hearing loss, and rapidly growing rates of diabetes.

Modifying 12 risk factors over a lifetime could delay or prevent 40% of dementia cases. Credit: Keck Medicine of USC

Based on their past model including 9 risk factors, the authors estimated that many more cases of dementia could be prevented in LMICs, compared to globally. While globally the 9 risk factors were estimated to contribute to 35% of all dementia cases, in China they might account for 40% of cases, 41% in India and 56% in Latin America.

The authors warn that estimates could be even higher, as they used conservative estimates for the prevalence of these risk factors in these populations, and because they do not account for the three new risk factors. The authors also note that nearly all the evidence for dementia is from studies in high-income countries, so risks might differ for LMICs and interventions might require modifying to best support different cultures and environments.

The authors note that the modeling for their prevention estimates globally and in LMICs assumes that there is a causal relationship between risk factors and dementia, but were careful to only include risk factors with strong evidence for a causal link.

Report co-author, Professor Adesola Ogunniyi, University of Ibadan, Nigeria, says: "In low- and middle-income countries, the higher prevalence of dementia risk factors means an even greater proportion of dementia is potentially preventable than in "higher-income countries". In this context, national policies addressing dementia risk factors, like primary and secondary education for all and stopping smoking policies, might have the potential for large reductions in dementia and should be prioritized. We also need more dementia research coming from low- and middle-income countries, so we can better understand the risks particular to these settings."

In the final section of the report, the authors advocate for holistic and individualized evidence-based care that addresses physical and mental health, social care, and support that can accommodate complex needs. Keeping people with dementia physically healthy is important for their cognition but they often have other illnesses which they may struggle to manage on their own, resulting in potentially harmful preventable hospitalisations.

They note that people with dementia are particularly at risk from COVID-19 (due to age and having pre-existing illnesses, such as hypertension), and that physical-distancing measures can be challenging for dementia patients, who may find it difficult to adhere to the guidelines or distressing to be unable to have contact with carers and family. The authors call for people with unknown COVID-19 status to not be admitted to care homes to protect the existing residents, regular testing of staff and asymptomatic as well as symptomatic residents when there is exposure, not moving staff or residents between homes, and more research into how to protect dementia patients during the current pandemic and future public health emergencies.

More information: Gill Livingston et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet. Published:July 30, 2020 DOI: doi.org/10.1016/S0140-6736(20)30367-6

Can you get the coronavirus twice?

by The Associated Press

AP Illustration/Peter Hamlin

Can you get the coronavirus twice?

28 july 2020--Scientists don't know for sure yet, but they believe it's unlikely.

Health experts think people who had COVID-19 will have some immunity against a repeat infection. But they don't know how much protection or how long it would last.

There have been reports of people testing positive for the virus weeks after they were believed to have recovered, leading some to think they may have been reinfected. More likely, experts say people were suffering from the same illness or the tests detected remnants of the original infection. There's also the chance tests could have been false positives.

Scientists say there has been no documented instance of a patient spreading the virus to others after retesting positive.

With similar viruses, studies have shown that people could fall sick again three months to a year after their first infections. It's still too early to know whether that's also possible with the coronavirus.

"It's very much emerging science," said Dr. Philip Landrigan, director of the global public health program at Boston College.

A small U.S. study published last week also found the antibodies that fight the coronavirus may only last a few months in people with mild illness, suggesting people could become susceptible again. But antibodies aren't the only defense against a virus, and the other parts of the immune system could also help provide protection.

Settling the question of whether reinfection is possible is important. If it can occur, that could undermine the idea of "immunity passports" for returning back to workplaces. And it would not bode well for hopes of getting a long-lasting vaccine.

The Associated Press. 

How COVID-19 causes smell loss

by Harvard Medical School

Credit: Unsplash/CC0 Public Domain

Temporary loss of smell, or anosmia, is the main neurological symptom and one of the earliest and most commonly reported indicators of COVID-19. Studies suggest it better predicts the disease than other well-known symptoms such as fever and cough, but the underlying mechanisms for loss of smell in patients with COVID-19 have been unclear.

27 july 2020--Now, an international team of researchers led by neuroscientists at Harvard Medical School has identified the olfactory cell types most vulnerable to infection by SARS-CoV-2, the virus that causes COVID-19.

Surprisingly, sensory neurons that detect and transmit the sense of smell to the brain are not among the vulnerable cell types.

Reporting in Science Advances on July 24, the research team found that olfactory sensory neurons do not express the gene that encodes the ACE2 receptor protein, which SARS-CoV-2 uses to enter human cells. Instead, ACE2 is expressed in cells that provide metabolic and structural support to olfactory sensory neurons, as well as certain populations of stem cells and blood vessel cells.

The findings suggest that infection of nonneuronal cell types may be responsible for anosmia in COVID-19 patients and help inform efforts to better understand the progression of the disease.

"Our findings indicate that the novel coronavirus changes the sense of smell in patients not by directly infecting neurons but by affecting the function of supporting cells," said senior study author Sandeep Robert Datta, associate professor of neurobiology in the Blavatnik Institute at HMS.

This implies that in most cases, SARS-CoV-2 infection is unlikely to permanently damage olfactory neural circuits and lead to persistent anosmia, Datta added, a condition that is associated with a variety of mental and social health issues, particularly depression and anxiety.

"I think it's good news, because once the infection clears, olfactory neurons don't appear to need to be replaced or rebuilt from scratch," he said. "But we need more data and a better understanding of the underlying mechanisms to confirm this conclusion."

A majority of COVID-19 patients experience some level of anosmia, most often temporary, according to emerging data. Analyses of electronic health records indicate that COVID-19 patients are 27 times more likely to have smell loss but are only around 2.2 to 2.6 times more likely to have fever, cough or respiratory difficulty, compared to patients without COVID-19.

Some studies have hinted that anosmia in COVID-19 differs from anosmia caused by other viral infections, including by other coronaviruses.

For example, COVID-19 patients typically recover their sense of smell over the course of weeks—much faster than the months it can take to recover from anosmia caused by a subset of viral infections known to directly damage olfactory sensory neurons. In addition, many viruses cause temporary loss of smell by triggering upper respiratory issues such as stuffy nose. Some COVID-19 patients, however, experience anosmia without any nasal obstruction.

Pinpointing vulnerability

In the current study, Datta and colleagues set out to better understand how sense of smell is altered in COVID-19 patients by pinpointing cell types most vulnerable to SARS-CoV-2 infection.

They began by analyzing existing single-cell sequencing datasets that in total catalogued the genes expressed by hundreds of thousands of individual cells in the upper nasal cavities of humans, mice and nonhuman primates.

The team focused on the gene ACE2, widely found in cells of the human respiratory tract, which encodes the main receptor protein that SARS-CoV-2 targets to gain entry into human cells. They also looked at another gene, TMPRSS2, which encodes an enzyme thought to be important for SARS-CoV-2 entry into the cell.

The analyses revealed that both ACE2 and TMPRSS2 are expressed by cells in the olfactory epithelium—a specialized tissue in the roof of the nasal cavity responsible for odor detection that houses olfactory sensory neurons and a variety of supporting cells.

Neither gene, however, was expressed by olfactory sensory neurons. By contrast, these neurons did express genes associated with the ability of other coronaviruses to enter cells.

The researchers found that two specific cell types in the olfactory epithelium expressed ACE2 at similar levels to what has been observed in cells of the lower respiratory tract, the most common targets of SARS-CoV-2, suggesting a vulnerability to infection.

These included sustentacular cells, which wrap around sensory neurons and are thought to provide structural and metabolic support, and basal cells, which act as stem cells that regenerate the olfactory epithelium after damage. The presence of proteins encoded by both genes in these cells was confirmed by immunostaining.

In additional experiments, the researchers found that olfactory epithelium stem cells expressed ACE2 protein at higher levels after artificially induced damage, compared with resting stem cells. This may suggest additional SARS-CoV-2 vulnerability, but it remains unclear whether or how this is important to the clinical course of anosmia in patients with COVID-19, the authors said.

Datta and colleagues also analyzed gene expression in nearly 50,000 individual cells in the mouse olfactory bulb, the structure in the forebrain that receives signals from olfactory sensory neurons and is responsible for initial odor processing.

Neurons in the olfactory bulb did not express ACE2. The gene and associated protein were present only in blood vessel cells, particularly pericytes, which are involved in blood pressure regulation, blood-brain barrier maintenance and inflammatory responses. No cell types in the olfactory bulb expressed the TMPRSS2 gene.

Smell loss clue

Together, these data suggest that COVID-19-related anosmia may arise from a temporary loss of function of supporting cells in the olfactory epithelium, which indirectly causes changes to olfactory sensory neurons, the authors said.

"We don't fully understand what those changes are yet, however," Datta said. "Sustentacular cells have largely been ignored, and it looks like we need to pay attention to them, similar to how we have a growing appreciation of the critical role that glial cells play in the brain."

The findings also offer intriguing clues into COVID-19-associated neurological issues. The observations are consistent with hypotheses that SARS-CoV-2 does not directly infect neurons but may instead interfere with brain function by affecting vascular cells in the nervous system, the authors said. This requires further investigation to verify, they added.

The study results now help accelerate efforts to better understand smell loss in patients with COVID-19, which could in turn lead to treatments for anosmia and the development of improved smell-based diagnostics for the disease.

"Anosmia seems like a curious phenomenon, but it can be devastating for the small fraction of people in whom it's persistent," Datta said. "It can have serious psychological consequences and could be a major public health problem if we have a growing population with permanent loss of smell."

The team also hope the data can help pave inroads for questions on disease progression such as whether the nose acts as a reservoir for SARS-CoV-2. Such efforts will require studies in facilities that allow experiments with live coronavirus and analyses of human autopsy data, the authors said, which are still difficult to come by. However, the collaborative spirit of pandemic-era scientific research calls for optimism.

"We initiated this work because my lab had a couple of datasets ready to analyze when the pandemic hit, and we published an initial preprint," Datta said. "What happened after that was amazing, researchers across the globe offered to share and merge their data with us in a kind of impromptu global consortium. This was a real collaborative achievement."

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More information: David H. Brann et al. Non-neuronal expression of SARS-CoV-2 entry genes in the olfaory system suggests mechanisms underlying COVID-19-associated anosmia, Science Advances (2020). DOI: 10.1126/sciadv.abc5801

Plant-based diets shown to lower blood pressure even with limited meat and dairy

by Peter Thorley, University of Warwick

Consuming a plant-based diet can lower blood pressure even if small amounts of meat and dairy are consumed too, according to new research from the University of Warwick.

26 july 2020--Published online by a team from Warwick Medical School in the Journal of Hypertension today (25 July), they argue that any effort to increase plant-based foods in your diet and limit animal products is likely to benefit your blood pressure and reduce your risk of heart attacks, strokes and cardiovascular disease. They conducted a systematic review of previous research from controlled clinical trials to compare seven plant-based diets, several of which included animal products in small amounts, to a standardised control diet and the impact that these had on individuals' blood pressure.

Plant-based diets support high consumption of fruits, vegetables, whole grains, legumes, nuts and seeds, limiting the consumption of most or all animal products (mainly meat and diary). (See Notes to Editors for further details)

High blood pressure is the leading risk factor globally for heart attacks, strokes and other cardiovascular diseases. A reduction in blood pressure has important health benefits both for individuals and for populations. Unhealthy diets are responsible for more deaths and disabilities globally than tobacco use, high alcohol intake, drug use and unsafe sex put together. An increased consumption of whole grains, vegetables, nuts and seeds, and fruit, as achieved in plant-based diets, could avert up to 1.7, 1.8, 2.5 and 4.9 million deaths globally respectively every year according to previous research.

Vegetarian and vegan diets with complete absence of animal products are already known to lower blood pressure compared to omnivorous diets. Their feasibility and sustainability are, however, limited. Until now, it has not been known whether a complete absence of animal products is necessary in plant-based dietary patterns to achieve a significant beneficial effect on blood pressure.

Lead author Joshua Gibbs, a student in the University of Warwick School of Life Sciences, said: "We reviewed 41 studies involving 8,416 participants, in which the effects of seven different plant-based diets (including DASH, Mediterranean, Vegetarian, Vegan, Nordic, high fibre and high fruit and vegetables) on blood pressure were studied in controlled clinical trials. A systematic review and meta-analysis of these studies showed that most of these diets lowered blood pressure. The DASH diet had the largest effect reducing blood pressure by 5.53/3.79 mmHg compared to a control diet, and by 8.74/6.05 mmHg when compared to a 'usual' diet.

"A blood pressure reduction of the scale caused by a higher consumption of plant-based diets, even with limited animal products would result in a 14% reduction in strokes, a 9% reduction in heart attacks and a 7% reduction in overall mortality.

"This is a significant finding as it highlights that complete eradication of animal products is not necessary to produce reductions and improvements in blood pressure. Essentially, any shift towards a plant-based diet is a good one."

Senior author Professor Francesco Cappuccio of Warwick Medical School said: "The adoption of plant-based dietary patterns would also play a role in global food sustainability and security. They would contribute to a reduction in land use due to human activities, to global water conservation and to a significant reduction in global greenhouse gas emission.

"The study shows the efficacy of a plant-based diet on blood pressure. However, the translation of this knowledge into real benefits to people, i.e. its effectiveness, depends on a variety of factors related to both individual choices and to governments' policy decisions. For example, for an individual, the ability to adopt a plant-based diet would be influenced by socio-economic factors (costs, availability, access), perceived benefits and difficulties, resistance to change, age, health status, low adherence due to palatability and acceptance.

"To overcome these barriers, we ought to formulate strategies to influence beliefs about plant-based diets, plant food availability and costs, multisectoral actions to foster policy changes focusing on environmental sustainability of food production, science gathering and health consequences."

More information: The effect of plant-based dietary patterns on blood pressure: a systematic review and meta-analysis of controlled intervention trials, Journal of Hypertension 2020; 38: in press. DOI: 10.1097/HJH0000000000002604

Provided by University of Warwick 

Genetic mutations predispose individuals to severe COVID-19

by Radboud University

Credit: CC0 Public Domain

Current observations suggest that the coronavirus SARS-CoV-2 causes severe symptoms mainly in elderly patients with chronic disease. However when two pairs of previously healthy young brothers from two families required mechanical ventilation at the intensive care unit in rapid succession, doctors and researchers at Radboud University Medical Center were inclined to consider that genetic factors had a key role in compromising their immune system. Their research identified the gene TLR7 as an essential player in the immune response against SARS-CoV-2. A finding with potentially major consequences for understanding and possibly treatment of COVID-19.

26 july 2020--During the wave of COVID-19 patients that flooded Dutch hospitals in the first half of 2020, two young brothers became seriously ill with the SARS-CoV-2 virus and had to be mechanically ventilated in the ICU. One of them died from the consequences of the infection, the other recovered. The severe course of disease in otherwise healthy young brothers was a relatively rare occurrence, especially because the virus mainly affects the elderly. This observation triggered the curiosity of an attentive physician from the MUMC+ department of clinical genetics. She contacted her colleagues in Nijmegen who then investigated why these two young brothers were so severely affected.

Genetic factors

"In such a case, you immediately wonder whether genetic factors could play a role," says geneticist Alexander Hoischen. "Getting sick from an infection is always an interplay between—in this case—the virus and the human immune system. It may be a mere coincidence that two brothers from the same family become so severely ill. But it is also possible that an inborn error of the immune system has played an important role. We investigated this possibility, together with our multidisciplinary team at Radboudumc."

One X-chromosome

All genes (collectively called the exome) of both brothers were sequenced, after which the investigators combed through the data searching for a possible shared cause. Cas van der Made, Ph.D. student and resident at the department of Internal Medicine: "We mainly looked at genes that play a role in the immune system. We know that several of these genes are located on the X-chromosome, and with two brother pairs affected X-chromosomal genes were most suspicious. Women carry two X-chromosomes, while men possess a Y-chromosome apart from the X. Therefore, men have only one copy of the X-chromosomal genes. In case men have a defect in such a gene, there is no second gene that can take over that role, as in women."

Gene identification

That search quickly revealed mutations in the gene encoding for the Toll-like receptor 7, TLR7 for short. There are multiple TLR-genes, which belong to a family of receptors with an important role in the recognition of pathogens (such as bacteria and viruses) and the activation of the immune system. Hoischen: "A few letters were missing in the genetic code of the TLR7 gene. As a result, the code cannot be read properly and hardly any TLR7 protein is produced. TLR7 function has so far never been associated with an inborn error of immunity. But unexpectedly we now have an indication that TLR7 is essential for protection from this coronavirus. So it seems that the virus can replicate undisturbed because the immune system does not get a message that the virus has invaded. Because TLR7, which must identify the intruder and subsequently activate the defense, is hardly present. That could be the reason for the severity of the disease in these brothers."

Additional confirmation

Then, quite unexpectedly, the doctors and researchers at Radboudumc come across another pair of brothers who have fallen seriously ill with COVID-19. Again, they are both under 35 years of age. Both of them were also in the ICU for mechanical ventilation. "Then the question of the role of genetics became even more obvious." says Hoischen. "We also investigated the genetic code of these two brothers, again via the 'rapid-clinical exome' method. This time we saw no deletion, no loss of letters, but a single spelling mistake of one DNA-letter of the TRL7 gene. The effect on the gene is the same, however, because these brothers also do not make sufficient functional TLR7 protein. Suddenly we had four young people with a defect in the same gene, all of whom had fallen seriously ill from the SARS-CoV-2 virus."

Essential role in the defense

Van der Made and colleagues have investigated the consequences of improper functioning of the TLR7 receptor. "Once activated, TLR7 triggers the production of so-called interferons, signaling proteins that are essential in the defense against virus infections," says van der Made. "This immune response is perhaps all the more important in the fight against the SARS-CoV-2 virus, because we know from the literature that the virus has tricks to reduce the production of interferons by immune cells. When we mimic an infection with the coronavirus, we see that immune cells of the patients without properly functioning TLR7 hardly respond, and that minimal amounts of interferons are produced. These tests make it clear that the virus appears to have free rein in people without properly functioning TLR7 because it [the virus] is not recognized by the immune system."

Consequences

"Due to the serious illness of four brothers in two families, so serious that it cost one of the young men his life, we have discovered this condition," says Hoischen. "It seems to be a very specific abnormality, an immunodeficiency, which is mainly related to this coronavirus. None of the four men have previously suffered from immune-related diseases. It is the first time that we can connect a clinical phenomenon so strongly with TLR7."

"This discovery not only provides us with more insight into the fundamental workings of the immune system, but it may also have important consequences for the treatment of severely ill COVID-19 patients," says Frank van de Veerdonk, immunologist and infectiologist. "The substance interferon can be given as a therapy. It is currently being investigated whether administering interferon in COVID-19 can indeed help."

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More information: Caspar I. van der Made et al, Presence of Genetic Variants Among Young Men With Severe COVID-19, JAMA (2020). DOI: 10.1001/jama.2020.13719

Journal information: Journal of the American Medical Association 

Simple test helps to predict and prevent falls

by Staffordshire University

Designed by Staffordshire University Cartoon and Comic Arts student Josh Thomas who won a competition to illustrate the study. Credit: Staffordshire University/Josh Thomas

The "enhanced paper grip test" validated by researchers from the Centre for Biomechanics and Rehabilitation Technologies (CBRT) at Staffordshire University involves pulling a small card from underneath the participant's foot while asking them to grip with their big toe (Hallux).

25 july 2020--The proposed test can potentially be used to monitor muscle weakness in clinics for better falls-risk assessment in patients with diabetes.

Dr Aoife Healy, Associate Professor of Human Movement Biomechanics at CBRT, said: "The paper grip test is a simple, clinically applicable test to detect muscle weakness in the foot. The current paper builds on our previous work and shows its usefulness in assessing strength and balance in this group of vulnerable patients."

The experiment involved assessing twenty healthy volunteers at Staffordshire University's specialist Biomechanics labs and ten people with diabetes at a diabetic foot clinic in India.

Hallux grip force was previously found to be strongly linked to the strength of all muscle groups of the foot and ankle and to the ability to maintain balance. The latest results published in Gait and Posture on a modified test shows the reliability and validity of Hallux grip force during clinical assessment.

Dr Lakshmi Sundar, a co-author in this study and a diabetic foot specialist from Chennai in India, added: "This type of simple clinical assessment is extremely valuable in low resource settings and helps in providing effective clinical advice."

Dr Panagiotis Chatzistergos, Associate Professor in Orthopaedic and Rehabilitation Biomechanics, who led this study highlighted: "The original version of the paper grip test was shown to be effective in detecting foot muscle-weakening but its outcome is operator-dependent. To overcome this limitation, we have developed this enhanced test that replaces the pass/fail outcome with a continuous measurement of the pulling force that is needed to remove the card."

This latest study is part of the Centre for Biomechanics and Rehabilitation Technologies' wider work in the area of diabetic foot management which includes research to help prevent life-threatening foot ulcers and amputations.

Professor Nachi Chockalingam, Director of the Centre for Biomechanics and Rehabilitation Technologies, said: "Falls and fear of falling are a major issue in the management of older adults. Also, falling for the first time sets in motion a cycle of increased fear of falling, reduced activity and loss of strength. This leads to a higher risk for further falls. So, it is important to identify individuals who might fall and preventing the first fall is extremely important."

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More information: Panagiotis E. Chatzistergos et al, Reliability and validity of an enhanced paper grip test; a simple clinical test for assessing lower limb strength, Gait & Posture (2020). DOI: 10.1016/j.gaitpost.2020.07.011

Infected with the coronavirus but not showing symptoms? A physician answers 5 questions about asymptomatic COVID-19

by William Petri, The Conversation

Credit: CC0 Public Domain

Blood tests that check for exposure to the coronavirus are starting to come online, and preliminary findings suggest that many people have been infected without knowing it. Even people who do eventually experience the common symptoms of COVID-19 don't start coughing and spiking fevers the moment they're infected.

23 july 2020--William Petri is a professor of medicine and microbiology at the University of Virginia who specializes in infectious diseases. Here, he runs through what's known and what isn't about asymptomatic cases of COVID-19.

How common is it for people to contract and fight off viruses without knowing it?

In general, having an infection without any symptoms is common. Perhaps the most infamous example was Typhoid Mary, who spread typhoid fever to other people without having any symptoms herself in the early 1900s.

My colleagues and I have found that many infections are fought off by the body without the person even knowing it. For example, when we carefully followed children for infection by the parasite Cryptosporidia, one of the major causes of diarrhea, almost half of those with infections showed no symptoms at all.

In the case of the flu, estimates are that anywhere from 5% to 25% of infections occur with no symptoms.

For the most part, symptoms are actually a side effect of fighting off an infection. It takes a little time for the immune system to rally that defense, so some cases are more aptly considered presymptomatic rather than asymptomatic.

How can someone spread coronavirus if they aren't coughing and sneezing?

Everyone is on guard against the droplets that spray out from a coronavirus patient's cough or sneeze. They're a big reason public health officials have suggested everyone should wear masks.

But the virus also spreads through normal exhalations that can carry tiny droplets containing the virus. A regular breath may spread the virus several feet or more.

Spread could also come from fomites—surfaces, such as a doorknob or a grocery cart handle, that are contaminated with the coronavirus by an infected person's touch.What's known about how contagious an asymptomatic person might be?

No matter what, if you've been exposed to someone with COVID-19, you should self-quarantine for the entire 14-day incubation period. Even if you feel fine, you're still at risk of spreading the coronavirus to others.

Most recently it has been shown that high levels of the virus are present in respiratory secretions during the "presymptomatic" period that can last days to more than a week prior to the fever and cough characteristic of COVID-19. This ability of the virus to be transmitted by people without symptoms is a major reason for the pandemic.

After an asymptomatic infection, would someone still have antibodies against SARS-CoV-2 in their blood?

Most people are developing antibodies after recovery from COVID-19, likely even those without symptoms. It is a reasonable assumption, from what scientists know about other coronaviruses, that those antibodies will offer some measure of protection from reinfection. But nothing is known for sure yet.

Recent serosurveys in New York City that check people's blood for antibodies against SARS-CoV-2 indicate that as many as one in five residents may have been previously infected with COVID-19. Their immune systems had fought off the coronavirus, whether they'd known they were infected or not—and many apparently didn't.

How widespread is asymptomatic COVID-19 infection?

No one knows for sure, and for the moment lots of the evidence is anecdotal.

For a small example, consider the nursing home in Washington where many residents became infected. Twenty-three tested positive. Ten of them were already sick. Ten more eventually developed symptoms. But three people who tested positive never came down with the illness.

When doctors tested 397 people staying at a homeless shelter in Boston, 36% came up positive for COVID-19 – and none of them had complained of any symptoms.

In the case of Japanese citizens evacuated from Wuhan, China and tested for COVID-19, fully 30% of those infected were aymptomatic.

An Italian pre-print study that has not yet been peer-reviewed found that 43% of people who tested positive for COVID-19 showed no symptoms. Of concern: The researchers found no difference in how potentially contagious those with and without symptoms were, based on how much of the virus the test found in indiduals' samples.

The antibody serosurveys getting underway in different parts of the country add further evidence that a good number—possibly anywhere from around 10% to 40% – of those infected might not experience symptoms.

Asymptomatic SARS-CoV-2 infection appears to be common—and will continue to complicate efforts to get the pandemic under control.

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Provided by The Conversation 

Coronavirus: B cells and T cells explained

by Raj Thaker, The Conversation

To develop effective drugs, we need a good understanding of how the immune system responds to the novel coronavirus. Credit: Video_Creative/Shutterstock

To get the upper hand on the coronavirus, we first need to understand how our immune system reacts to it. Understanding this will lead to better treatments, effective vaccines and knowing how near we are to herd immunity—and if it's even achievable.

21 july 2020--Every day, new research adds to this knowledge and is widely reported in the media. To follow the discussion, you need to know about two very important cells: B cells and T cells. Here is a quick primer to get you up to speed.

The immune system is a network of intricately connected cells to protect the body from internal and external threats. It is broadly classified into two sub-types: innate (or natural) and adaptive (or acquired). The key differences between the two are the specificity and agility of the responses generated towards a perceived threat.

The innate system is the first line of defense, capable of detecting many common infectious agents, such as viruses and bacteria, as soon as they find their way into the body. Although it may respond quickly, the innate system cannot always eliminate infectious organisms and it doesn't recognize all the pathogens.

Because of the intricate nature of the immune system, the innate system also provides cues in the forms of chemical signals (cytokines) or degraded products of infectious organisms (antigens) to activate the adaptive immune system, using a process known as "antigen presentation." Without these cues, the adaptive immune system cannot be activated.

The adaptive immune system has evolved to provide a more versatile and highly target-specific defense with an ability to distinguish very subtle differences in the make-up of infectious agents. But the adaptive immune system is slow and can take several days before two key cell types—B cells and T cells—are brought into play.

T cells are further grouped into two sub-types, CD4+ and CD8+ cells. CD4+ are helper T cells that help the activity of other immune cells by releasing cytokines. The cytokines prime the maturation of B cells, which become plasma cells and produce antibodies to neutralize the pathogen. CD8+ cytotoxic T cells, on the other hand, directly kill infected cells.

Once the adaptive immune system has vanquished the invader, a pool of long-lived memory T and B cells are made. These memory lymphocytes remain dormant until the next time they encounter the same pathogen. This time, though, they produce a much faster and stronger immune reaction. Memory is the key feature of the adaptive immune system, enabling long-term protection.

T cells and B cells in COVID-19

Since most people have not been exposed to the novel coronavirus, it can safely be assumed that uninfected people have no memory T and B cells and therefore no protection from a COVID-19 infection. Technically speaking, as with any other infection, COVID-19 should generate an immune response, priming the proliferation of anti-COVID T and B cells.

Around 8.3 million people have recovered from COVID, yet evidence of exactly how the adaptive immune system responds to the novel coronavirus has, so far, been scarce. But new information is emerging all the time.

A recent study from the US showed that infected people are able to generate COVID-specific T cells and B cells. This study also showed that even some uninfected people had T cells to COVID-19, suggesting an overlap with the response to previous coronavirus infections—so-called cross-reactivity. (Coronaviruses also cause SARS, Mers and some cases of the common cold.)

Also, recent research from the Karolinska Institute in Sweden showed that several COVID patients with mild to no symptoms had generated T cells against the virus. This was even the case in patients who had no detectable levels of antibodies against the virus. More importantly, the researchers also found evidence of memory T cells in convalescent patients. This suggests that COVID elicits a robust memory T cell response, which could prevent recurrent episodes of severe COVID.

Disappearing antibodies

How long antibodies stick around for varies from one pathogen to another. For example, we know that antibodies to other coronaviruses diminish over time (12 to 52 weeks from the time of infection). Some studies suggest that COVID-19 antibodies can be detected for seven weeks in recovered patients. But given the huge variability of symptoms and immune responses among patients, the precise timeline is unclear.

Another recent study comparing groups of symptomatic with asymptomatic people showed that asymptomatic people had much lower antibody levels. And follow-up monitoring showed that about 40% of asymptomatic people had no detectable antibodies after eight weeks.

This suggests that antibodies to COVID may not last very long. But this does not exclude the existence of memory T and B cells, capable of re-emerging from their dormant states to protect against re-infection. In other words, the antibodies that B cells make during initial exposure disappear in a few weeks, but the memory cells generated as a consequence of this persist for much longer.

But there is still a lot we don't know. And without a deep understanding of the immune system role in COVID, designing effective therapies is going to be difficult.

Provided by The Conversation 

5G networks have few health impacts, study finds

by Oregon State University

Adult zebrafish in the lab of Robyn Tanguay. Credit: Lynn Ketchum

Fifth generation or 5G wireless technology, which began being deployed worldwide in 2019, provides faster connectivity and more bandwidth, meaning higher download speeds.

19 july 2020--But because 5G technology is so new, little is known about the potential health effects from its radiofrequency radiation, which is higher than the current industry standard 4G. The Oregon State study begins to change that.

"Based on our study, we don't think 5G radiation is that harmful," said Subham Dasgupta, a postdoctoral fellow working in the lab of Robyn Tanguay at Oregon State. "It's predominately benign."

Researchers conducted the research using embryonic zebrafish, a model organism often used to discover interactions between environmental stressors and biological systems. Zebrafish and humans have similar developmental processes and are similar on a genomic level, meaning zebrafish research can easily be applied to humans.

In the study, published July 9 in the journal PLOS ONE, the researchers exposed embryonic zebrafish for two days to 3.5 GHz radiofrequency radiation, the frequency typically used by 5G-enabled cell phones.

They found no significant impacts on mortality, how the embryos formed or the embryos' behavioral response to light. They did find a modest impact on a test that measures the embryos' response to a sudden sound that they will investigate further.

Experimental set up used in the 5G zebrafish model research. Credit: Subham Dasgupta

Future research will look at the 5G radiation effects on the same zebrafish used in the study at a gene level and as they develop from embryos to adults, Dasgupta said. The researchers also would like to study the impacts of higher frequencies and higher exposure levels on zebrafish to keep pace with the changing cell phone industry.

The future research will use the same standardized experimental set up used in this study. It involves a box made of copper. The zebrafish embryos are placed on plates, which are put inside the box. The radiation enters the box through an antennae and the copper keeps it inside the box.

Provided by Oregon State University 

A simple laboratory test can aid in early recognition of COVID-19 in patients

by Aoa Media Team, American Osteopathic Association

Credit: CC0 Public Domain

A rapid laboratory test, the eosinophil count, readily obtained from a routine complete blood cell count (CBC) can aid in the early recognition of COVID-19 in patients, as well as provide prognostic information, according to new research in The Journal of the American Osteopathic Association.

17 july 2020--Current testing, which relies on diagnosis of COVID-19 by nasopharyngeal swab PCR assay, remains unreliable due to variable turnaround time and a high false-negative rate.

"We found that the absence of eosinophils on presentation can aid in early diagnosis, and in general, a persistent low count correlated with a poor prognosis for the patient," said Muhammad M. Zaman, MD, an infectious disease specialist affiliated with Coney Island Hospital in Brooklyn. "Review of the eosinophil count can be a useful tool in deciding whether to promptly isolate someone and initiate specific therapies while waiting for confirmatory test results."

In the study, eosinopenia correlated with diagnosis of COVID-19, and its persistence correlated with high disease severity and low rates of recovery. Low eosinophil count, or eosinopenia, is defined as having < 100 cells/microliter. A healthy range is typically between 100-400 cells/microliter.

"The trend of the eosinophil count has been known to correlate with viral infections, but we did not know the correlation was so significant in the case of COVID-19," says Dr. Zaman.

Actionable clinical information

Coney Island Hospital, part of the New York City Health and Hospitals system, serves a diverse population in Brooklyn, New York. The site experienced a sharp incline in COVID-19 cases during March and April 2020, when the study data was collected.

Researchers compared the eosinophil results of routine CBC from the first 50 admitted COVID-19-positive patients with the eosinophil results of 50 patients with confirmed influenza infection at the time of presentation to the emergency department at Coney Island Hospital in Brooklyn.

Of the patients with COVID-19, 60% had zero eosinophils at presentation, compared to 16% of influenza patients. An additional 28% of COVID-19 patients had zero eosinophils within 48 hours of admission, thus a total of 88% had zero eosinophils during hospitalization.

"In COVID-19, a disease that has substantial symptom overlap with influenza, eosinopenia could help to distinguish which patients likely have COVID-19," said Dr. Zaman.

A total of 23 of the 50 patients in the COVID-19 group (46%) passed away. Eighteen out of 21 (86%) deceased patients in the COVID-19 group who initially presented with eosinopenia remained eosinopenic versus 13 out of 26 (50%) survivors who had eosinopenia on presentation.

"As you can see from the data, continued low counts of eosinophils trended with mortality rates," said Dr. Zaman. "Patients whose eosinophil count rose tended to have better disease outcomes."

Existing testing is challenging

The clinical diagnosis of COVID-19 is confirmed by laboratory testing with a reverse-transcription polymerase chain reaction (RT-PCR) assay, which remains a challenge due to limited test availability, variable turnaround time, and low sensitivity of RT-PCR. In many hospitals, test results may take days to return.

"If a patient comes in on the first day of symptom onset, typically day five after exposure, the false-negative rate is as high as 38%," says Dr. Zaman. "This means a high number of potentially infectious patients are being misinformed of their true diagnosis—and a simple blood test could dramatically lower that number and the subsequent spread of disease."

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More information: Fahmina Tanni et al. Eosinopenia and COVID-19. The Journal of the American Osteopathic Association. Published Online First on July 16, 2020. doi:doi.org/10.7556/jaoa.2020.091

All the Zoom calls and screen time are bad for your eyes. Here are ways to protect your eyesight

by Milan Polk

Credit: CC0 Public Domain

Long meetings are a necessary evil in most careers. Now that so many people are working from home, meetings have transitioned from in-person to online video calls. Hours and hours spent staring at your screen can strain your eyes. Every device emits blue light, which the sun also emits.

13 JULY 2020--"Blue light is actually important. It's actually healthy for us; it wakes us up. There are a lot of beneficial properties. But these devices operate heavily on these wavelengths," said Dr. Robert Steinmetz, an optometrist at Solo Eye Care in Chicago. "The blue light on our devices is much less intense than the sun, but we also aren't 25 inches away from the sun for eight hours a day."

There's not enough data on the long-term effects of staring at our screens for hours, but it does significantly reduce how often people blink per minute, which can dry out your eyes. Looking at your phone all night can also create sleeping problems, messing with your circadian rhythm, the body's internal clock.

Here are five tips on how to protect your eyesight.

Abide by the 20-20-20 rule

It's important to take breaks. Steinmetz recommends the 20-20-20 rule. "Every 20 minutes on the computer, you need to look at something 20 feet away for 20 seconds," said Steinmetz. "And this is shown to help alleviate eye strain and reduce stress on your ... system. That's an important one, especially for kids."

Watch out for your kids

Kids could be learning from home right alongside working parents. Increased screen time means making sure they're getting enough sleep since blue light can keep us awake.

"All of us that have children are just experiencing what it's like to have e-learning," said Steinmetz. "The most important thing as a parent is to make sure your child gets adequate sleep. We know that these devices operate in a blue-light range that can suppress melatonin. If you're going to suppress melatonin, that's been shown to give you poorer quality sleep."

Night mode really helps

As it gets later in the day, switching to a device's night mode can help. "That gives your phone a warmer hue. So it blocks out that blue light and allows for that more comfortable experience," said Steinmetz.

Night mode can work on your phone as well as your computer. It can also be set for specific times of the day, so it's a seamless transition from morning to evening. Steinmetz also recommends his patients use a free program called f.lux if it's not installed on their devices already. It adapts the screen hue to the time of day.

Use eye drops

In terms of tools to reduce the strain of all those long video calls, Steinmetz points to eye drops. Eye strain can come from dry eyes, so drops are great for people who stare at screens for eight to 12 hours a day.

Get glasses for staring at screens

Blue light protective lenses are readily available. But some glasses offered online might have yellow or orange tints, which might not look right on a Zoom call.

"What we need is to maximize your vision by giving you a single-vision pair of glasses to maximize the height of the letters that you're looking at, comforts of that screen," said Steinmetz. "We need to get a specific prescription just for the computer that has blue light protection and an anti-reflecting coating on the front. They're inexpensive."

Prices range from $100 to $200, but insurance can often cover most of the cost.