Body

A comprehensive review into what we know about COVID-19 and the way it functions suggests the virus has a unique infectious profile, which explains why it can be so hard to treat and why some people experience so-called "long-COVID", struggling with significant health issues months after infection.

There is growing evidence that the virus infects both the upper and lower respiratory tracts - unlike "low pathogenic" human coronavirus sub-species, which typically settle in the upper respiratory tract and cause cold-like symptoms, or "high pathogenic" viruses such as those that cause SARS and ARDS, which typically settle in the lower respiratory tract.

Additionally, more frequent multi-organ impacts, and blood clots, and an unusual immune-inflammatory response not commonly associated with other, similar viruses, mean that COVID-19 has evolved a uniquely challenging set of characteristics.

While animal and experimental models imply an overly aggressive immune-inflammation response is a key driver, it seems things work differently in humans: although inflammation is a factor it is a unique dysregulation of the immune response that causes our bodies to mismanage the way they fight the virus.

This may explain why some people experience "long-COVID" and suffer severe lung damage after infection.

Ignacio Martin-Loeches, Clinical Professor in Trinity College Dublin's School of Medicine, and Consultant in Intensive Care Medicine at St James's Hospital, is a co-author of the review just published in leading medical journal, The Lancet. He said:

"The emergence of severe acute respiratory syndrome coronavirus two (SARS-CoV-2), which causes COVID-19, has resulted in a health crisis not witnessed since the 1918 Spanish flu pandemic. Tragically, millions around the world have died already.

"Despite international focus on the virus, we are only just beginning to understand its intricacies. Based on growing evidence we propose that COVID-19 should be perceived as a new entity with a previously unknown infectious profile. It has its own characteristics and distinct pathophysiology and we need to be aware of this when treating people.

"That doesn't mean we should abandon existing best-practice treatments that are based on our knowledge of other human coronaviruses, but an unbiased, gradual assembly of the key COVID-19 puzzle pieces for different patient cohorts - based on sex, age, ethnicity, pre-existing comorbidities - is what is need to modify the existing treatment guidelines, subsequently providing the most adequate care to COVID-19 patients."

The review article was produced by the European Group on Immunology of Sepsis (EGIS) in which Professor Martin-Loeches is one of the funding members. EGIS is a multidisciplinary group of scientists and doctors with special interest in severe infection in patients admitted to ICU.

Neonatal hypothermia -- which occurs when an infant's core body temperature falls below the normal range needed to maintain health -- contributes to approximately one million deaths each year, and countless cases of stunted growth, almost exclusively in low- and middle-income countries. To address this common but preventable condition, researchers from Boston Children's Hospital, engineers at Lawrence Berkeley National Laboratory, and colleagues in Rwanda developed the Dream Warmer, a low cost, reusable non-electric infant warmer to prevent and treat hypothermia. A new study from the team shows that infants who received treatment with the warmer had only an 11 percent rate of hypothermia compared to 29 percent of those who did not. Infant death rates also dropped, from 2.8 percent among infants who did not use the warmer to 0.9 percent of those who did. Results of the study were published in eClinicalMedicine from The Lancet.

"Infant hypothermia is a silent killer," says study leader Anne Hansen, MD, MPH of the Division of Newborn Medicine and Medical Director of the Neonatal Intensive Care Unit at Boston Children's, "but it's a modifiable risk factor, and this study shows that reducing it can have a large impact on survival and also likely on the long-term neurodevelopment of these babies."

Warmer was effective and safe

The primary aim of the study was to see if the warmer increased body temperatures in infants who are hypothermic or at risk of hypothermia due to prematurity or low birth weight compared to the standard of care in rural Rwandan hospitals.

Over the study period from November 2019 to July 2020, 464 infants at ten of the largest neonatal wards in Rwandan district hospitals used the warmer 892 times. Data was also collected on over a thousand patients on the neonatal ward who did not receive the warmer.

The study found that:

The rate of achieving a normal body temperature rose from 51 percent before introduction of the warmer to 67 percent after the warmer was introduced.

Use of the warmer did not lead to an increased rate of excessively high core temperatures.

The warmer caused no burns, rashes or other safety concerns, and no instances of incorrect warmer use were observed.

"This is a good option for treatment in setting where incubators are not the right solution, whether it is because they are too expensive, (about $100 compared with $5,000 for an incubator) require electricity, or require extensive training to correctly use and maintain," says Hansen, who adds that the warmer was specifically designed to complement skin-to-skin care, known as kangaroo mother care, either when it provides insufficient heat or if the mother needs to take a break. "And, the nurses needed only a couple minutes of training to prepare, use and clean it correctly because it is quite intuitive."

Ten years in the making

Dr. Hansen has been working in Rwanda for more than a decade to address these and other preventable causes of infant disease and death. She teamed up with engineers from Lawrence Berkeley National Lab at the University of California, Berkeley, to develop this low-cost, reusable infant warming mattress. The warmer contains 12 wax "candles" that are made of a material specially designed to melt at exactly skin temperature. When heated in boiled water, the candles melt and remain at body temperature for about six hours. Once they cool, the mattress can be cleaned and reused multiple times.

"The final design is a skin temperature heating pad that the infant can either lay on or be wrapped around the infant's back in addition to skin-to-skin care with the mother," says Hansen. Two smaller studies conducted by Hansen's team in Rwanda in 2016-2018 showed the warmer was effective, safe, and usable without needing an extensive training.

"Because treating neonatal hypothermia is relatively easy given the appropriate equipment, we hope this warmer can play a significant role in optimizing the health of these vulnerable infants in low- and middle-income countries," says Hansen, who is now partnering with others with the goal of distributing the infant warmer across Sub Saharan Africa as well as Haiti and Chiapas, Mexico.

Nearly 1 in 5 adults with high blood pressure, a leading risk factor for heart disease and stroke, also take a medicine that could be elevating their blood pressure, according to new research presented at the American College of Cardiology's 70th Annual Scientific Session. The results underscore the need for patients to routinely review all of the medications they take with their care team, including those available over the counter, to make sure none could be interfering with blood pressure lowering efforts.

Which are the most likely culprits? Based on the study findings, the three most common classes of medications were antidepressants; nonsteroidal anti-inflammatory drugs (NSAIDs) that include ibuprofen and naproxen; and oral steroids used to treat conditions such as gout, lupus, rheumatoid arthritis or after an organ transplant. These medications were reported by 9%, 7% and 2% of participants, respectively. Other medications associated with blood pressure elevation were also reported, including antipsychotics, certain oral contraceptives and popular decongestants.

Researchers said these findings raise concerns, especially as nearly half of Americans diagnosed with high blood pressure do not have it sufficiently controlled. Dr. Vitarello explained the goal blood pressure for hypertension patients is a reading of less than 130 mmHg over 80 mmHg, based on the 2017 American College of Cardiology/American Heart Association (ACC/AHA) Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults.

"These are medications that we commonly take--both over-the-counter and prescribed medications--that may have the unintended side effect of raising blood pressure and could have adverse effects on our heart health," said John Vitarello, MD, an internal medicine resident at Beth Israel Deaconess Medical Center in Boston and the study's lead author. "We know that high blood pressure leads to cardiovascular disease, stroke and death and even small increases in blood pressure can have meaningful impacts on cardiovascular disease. Based on our findings, we need to be more aware of polypharmacy (the use of multiple medications by a single patient) in older adults who also have the highest burden of high blood pressure."

The study examined data from 27,599 participants in the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2018. Of these, about half (49%) had hypertension (average age 55 years, 48% female), which was defined in the study as having a blood pressure reading of ?130 mmHg (systolic, the top number) or ?80 mmHg (diastolic, the bottom number) or ever having been told they have high blood pressure. Researchers identified medications associated with blood pressure elevation based on those listed in the ACC/AHA guideline and examined use of these medications by adults with hypertension above and below recommended blood pressure goals.

Among participants with high blood pressure, 19% reported using one or more blood pressure raising medications and 4% reported using multiple. Nearly one-quarter (24%) of women with high blood pressure reported using a blood pressure raising medication compared with 14% of men. Older adults were more likely to be using blood pressure raising medications than younger adults (19% of participants over age 65 vs. 18% of participants under age 65).

Vitarello said the findings suggest that, in some cases, rather than treating high blood pressure with more medications, there may be opportunities to lower blood pressure by deprescribing or substituting safer medications. For example, there may be other classes of medications to treat the same condition that have less impact on blood pressure. Nevertheless, there are some patients who may not have another medication option, so it's advisable to keep a closer eye on their blood pressure and talk with their care team before stopping or starting medications.

Additionally, the study authors estimate that if half of U.S. adults with hypertension who are taking blood pressure raising medications were to discontinue one of these medications, 560,000 to 2.2 million patients could be able to achieve their blood pressure goals without additional medications. But Vitarello said this analysis is only preliminary and individual responses to stopping blood pressure medications are likely to vary, thus the real-world benefit and tradeoffs of stopping these medications need to be further studied.

The study is limited in that it relies on participants' self-report of having high blood pressure and an accurate accounting of all the medications they take. The study was funded by the National Institute on Aging and an ACC Fellows Career Development Award.

New research from the University of Virginia School of Medicine reveals why sleep can put people with epilepsy at increased risk of sudden death.

Both sleep and seizures work together to slow the heart rate, the researchers found. Seizures also disrupt the body's natural regulation of sleep-related changes. Together, in some instances, this can prove deadly, causing Sudden Unexpected Death in Epilepsy, or SUDEP.

"We have been trying to better understand the cardiac changes around the time of a seizure in patients with epilepsy. When we looked at the heart rates for patients with epilepsy admitted to the hospital, many of them develop tachycardia [a fast heart rate] following a seizure, but a subset of patients have a decreased heart rate. This decline was more pronounced when the patients were asleep," said Andrew Schomer, MD, of UVA's Department of Neurology and the UVA Brain Institute. "The mechanism of SUDEP, or Sudden Unexpected Death in Epilepsy, is still not fully understood. We know there is an increased risk during sleep and if seizures are poorly controlled. Hopefully with further study we can try to identify individuals who are at an increased risk and work to prevent this devastating outcome."

Understanding SUDEP in Sleep

Doctors have been unsure how seizures in sleep can cause death, such as was the case with young Disney Channel star Cameron Boyce in 2019. He died of SUDEP while sleeping at age 20. (While SUDEP can occur when patients with epilepsy are awake, the majority of cases occur during sleep.)

To better understand the effect of sleep seizures, UVA researchers led by Schomer and Mark Quigg, MD, MSc, monitored the brain and heart activity of people with epilepsy as they slept. The patients were admitted to the UVA Epilepsy Monitoring Unit between February 2018 and August 2019, and all were 17 or older.

In total, the researchers evaluated 101 sleep seizures in 41 patients, with a median age of 40.5. The participants were, on average, diagnosed more than 20 years previously.

The researchers monitored how deeply the patients were sleeping when the seizures occurred. Some seizures caused heart rates to increase. But the greater sleep depth prior to a seizure, the slower the patient's heart rate was likely to become, the scientists found.

The results suggest that seizures during sleep are more likely to lead to dangerously slow heart rate. The effect of the seizure is secondary to the natural slowing of the heart rate during sleep, the researchers believe, but the two together can, in some instances, prove deadly.

More study is needed to better understand the variables involved and to better determine what is occurring in individual patients, the researchers say. But the findings represent an important advance in the effort to prevent SUDEP during sleep.

"People with poorly controlled seizures have the greatest risk of SUDEP, and seizures during sleep may hold the higher risk," said Quigg, of UVA's Department of Neurology and the UVA Brain Institute. "Our findings can direct further research to determine how the heart's and lung's control systems fail during sleep-related seizures in order to help prevent SUDEP."

Determining safe yet effective drug dosages for children is an ongoing challenge for pharmaceutical companies and medical doctors alike. A new drug is usually first tested on adults, and results from these trials are used to select doses for pediatric trials. The underlying assumption is typically that children are like adults, just smaller, which often holds true, but may also overlook differences that arise from the fact that children's organs are still developing.

Compounding the problem, pediatric trials don't always shed light on other differences that can affect recommendations for drug doses. There are many factors that limit children's participation in drug trials - for instance, some diseases simply are rarer in children - and consequently, the generated datasets tend to be very sparse.

To make drugs and their development safer for children, researchers at Aalto University and the pharmaceutical company Novartis have developed a method that makes better use of available data.

'This is a method that could help determine safe drug doses more quickly and with less observations than before,' says co-author Aki Vehtari, an associate professor of computer science at Aalto University and the Finnish Center for Artificial Intelligence FCAI.

In their study, the research team created a model that improves our understanding of how organs develop.

'The size of an organ is not necessarily the only thing that affects its performance. Kids' organs are simply not as efficient as those of adults. In drug modeling, if we assume that size is the only thing that matters, we might end up giving too large of doses,' explains Eero Siivola, first author of the study and doctoral student at Aalto University.

Whereas the standard approach of assessing pediatric data relies on subjective evaluations of model diagnostics, the new approach, based on Gaussian process regression, is more data-driven and consequently less prone to bias. It is also better at handling small sample sizes as uncertainties are accounted for.

The research comes out of FCAI's research programme on Agile and probabilistic AI, offering a great example of a method that makes the best out of even very scarce datasets.

In the study, the researchers demonstrate their approach by re-analyzing a pediatric trial investigating Everolimus, a drug used to prevent the rejection of organ transplants. But the possible benefits of their method are far reaching.

'It works for any drug whose concentration we want to examine,' Vehtari says, like allergy and pain medication.

The approach could be particularly useful for situations where a new drug is tested on a completely new group -- of children or adults -- which is small in size, potentially making the trial phase much more efficient than it currently is. Another promising application relates to extending use of an existing drug to other symptoms or diseases; the method could support this process more effectively than current practices.

Half of the Danish population have overweight, while 17 percent live with obesity. Worldwide, almost 40 procent have overweight and 13 procent live with obesity.

The condition is associated with increased risk for early death, as well as sequelae such as Type 2 diabetes, cardiovascular diseases, cancer, and infertility.

Weight regain after an initial successful weight loss in people with obesity, constitutes an important and unsolved problem. Until now, no well-documented study on which treatment method is best for maintaining a healthy weight loss has been available.

Researchers at University of Copenhagen and Hvidovre Hospital have completed a new, sensational study, which is being published in the world's most quoted medical journal, The New England Journal of Medicine. By testing four different types of treatment following a diet-induced weight loss, the researchers demonstrate for the first time how it is possible for people with obesity to maintain long-term weight loss, says Professor Signe Torekov at the Department of Biomedical Sciences.

In a randomized clinical trial, the group of researchers has demonstrated a highly effective treatment after a diet-induced weight loss, by combining moderate to vigorous-intensive exercise with appetite-inhibiting obesity medication, an analogue to the appetite-inhibiting hormone GLP-1.

"This is new knowledge for doctors, dietitians and physical therapists to use in practice. This is evidence that we have been missing," explains Signe Torekov, who has been heading the study.

"The problem is that people are fighting against strong biological forces when losing weight. The appetite increases simultaneously with decreased energy consumption, and this counteracts weight loss maintenance. We have an appetite-stimulating hormone, which increases dramatically when we lose weight, and simultaneously the level of appetite-suppressing hormones drops dramatically. In addition, a weight loss can provoke loss of muscle mass, while the body reduces the energy consumption. Thus, when the focus in obesity treatment has been on how to obtain a weight loss - rather than how to maintain a weight loss - it is really difficult to do something about your situation," says Signe Torekov.

Highly efficient when combining treatments

215 Danes with obesity and low fitness ratings participated in the study. The participants initially followed a low calorie diet over eight weeks, where they each lost approximately 13 kg, which brought significant improvements to their health with a drop in blood sugar level and blood pressure.

The participants were then randomly divided into four groups. Two of the groups received placebo medication, while the two other groups received obesity medication. Among the two placebo groups, one group followed an exercise program of minimum 150 minutes of physical activity at moderate intensity or 75 minutes at vigorous-intensity during the week or a combination of the two, while the other group maintained their current level of physical activity. The two groups receiving obesity medication were similarly divided into one group with and one group without an exercise program.

All participants in the study were weighed monthly and received nutritional and diet counseling with the focus on healthy weight loss according to the guidelines from the Danish health and food administrations.

After one year, the group with exercise alone and the group with obesity medication alone maintained the weight loss of 13 kg and health improvements. The placebo group gained half of the weight back with deterioration of all risk factors, for example for development of Type 2 diabetes and cardiovascular disease.

The most dramatic improvements occurred in the combination group, which followed the exercise program and received obesity medication. The researchers observed additional weight loss in this group, and the total weight loss was approximately 16 kg over one year. The health benefits were also double that of each of the single treatments, i.e., twice the loss of fat mass while preserving muscle mass, higher fitness ratings, reduced blood sugar and improved quality of life.

The two groups that exercised increased their fitness rating, lost fat mass, and gained muscle mass. This could indicate a healthier weight loss than for people, who had only lost fat mass without increasing the fitness rating.

"It is an important aspect to highlight, as you do not necessarily get a healthier body from losing weight if, at the same time, you lose a lot of muscle mass," says Signe Torekov.

"It is great news for public health that a significant weight loss can be maintained with exercise for approximately 115 minute per week performed mostly at vigorous-intensity, such as cycling. And that by combining exercise with obesity medication, the effect is twice as good as each of the individual treatments"."

With the study, the researchers now hope people with obesity, together with their care provider, can create a useful framework for maintaining the weight loss.

Fundamental lifestyle change

Signe Torekov points out that many people with obesity have tried to lose weight before, only to regain the weight. This happens, because the general advice is to eat healthier and exercise more.

"Without a follow-up on whether people actually have support to perform exercise, the treatment will not be enough. Therefore, we also followed up with the participants on an ongoing basis to ensure that they received the support they needed in order to exercise. That is necessary, because maintaining weight loss is extremely hard. People need to understand this. Once you have lost weight, you are not "cured". "The ongoing exercise and effort will likely need to continue for many years," says Signe Torekov.

"Our study also demonstrates that without a structured treatment plan, there is a high risk of gaining the weight back. There were 12 individual consultations over the course of a year, including weighing and diet advice from Danish authorities according to guidelines for healthy weight maintenance. This was just not enough for the placebo group without exercise program, in this group all health benefits gained by weight loss during the eight week program were gone after one year, despite frequent weighing and diet and nutritional counseling based on official guidelines". Torekov says.

According to Signe Torekov, this underscores the importance of participating in a mutual weight maintenance program based on feedback when starting a weight loss programme.

"Therefore, it is important that there is a system for supporting people with obesity in maintaining the lifestyle change. Our study can help with this, because we can say this actually works to doctors, dietitians and municipalities, if they create a structured, joint treatment plan with the individual using ongoing follow-ups," says Torekov.

Research conducted by the University of Birmingham shows in order to have an effective Covid-19 vaccination rollout it has to be widely accepted by the entire population.

The study, conducted in collaboration with the NIHR Clinical Research Network West Midlands and The Royal Wolverhampton NHS Trust was published in the journal Trials involved an anonymous cross-sectional online survey across the UK involving 4884 participants of which 9.44% were Black Asian Minority Ethnic (BAME). Overall, 2020 (41.4%) respondents were interested in participating in vaccine trials, while 27.6% of the respondents were not interested and 31.1% were unsure. The most interested groups were male, graduates the 40-49 and 50-59 age groups and those with no health issues. The least interested groups were BAME those from villages and small towns and those aged 70 and above.

Currently, the UK registry has a very low trial participant uptake on the elderly and BAME participants which are two high-risk priority groups. The study concludes there is a need to design interventional and public health strategies to engage and encourage trial participation from these specific demographic groups as the research data provides unique insights into participation interest geographically and can be used to target ongoing and future campaigns in rural and core inner city populations.

Dr Anandadeep Mandal, lecturer in finance from the Birmingham Business School and one the lead authors who carried out the research design involving enhanced text mining and non-linear estimations said: "This study has key importance with COVID-19 mutant (VOC) B117 acquiring mutant E484 and the need for continual trials. The study examines the various factors affecting participation in trials, including geographical locations in England. The results indicate the lack of interest in trial participation among the BAME community even though they score high on importance of vaccine trials. Further, respondents from small town and villages fail to address the need for vaccine trials. Therefore, a joint effort is required engage various ethnic communities and people from different geographical locations to participate in vaccine trials to help the society in need."

Even though 50% of the UK population has the first dose of the vaccination current COVID-19 vaccination trials are not adequately representing a diverse participant population in terms of age, ethnicity and backgrounds which is becoming a challenge in clinical trial management. The study highlights how it is crucial to recruit patients which are representative of the target population which can help in drug development. The aim of this study was to provide possible interventions to increase the uptake for COVID-19 vaccine trial participations with the overall goal to acquire a safe and effective vaccine. This can provide useful in future trials that will continue on for 2021, such as human challenge trials, phase 3 trials and non-inferiority COVID-19 vaccine studies.

The study could not ascertain the reasons to why people did not want to partake in vaccination trials but they were to deduce their general perception towards COVID-19 and vaccines, as well as extracting demographic and geographical data. Being able to understand the key reasons would be beneficial in targeting educational campaigns to tackle specific barriers to trial recruitment.

UNIVERSITY PARK, Pa. -- Social media has become a platform for new mothers to openly share their experiences of the joys and challenges of parenthood. Researchers at Penn State and Dalhousie University have unraveled the sentiments in nursing mothers' tweets to better understand the factors influencing breastfeeding behaviors. They hope the findings can inform policies and interventions to support and improve resources for nursing mothers, such as breastfeeding support, workplace accommodations and technological aids such as apps.

"We are getting the raw sentiment of nursing mothers without putting them in a controlled experiment environment where their views could become biased," said Richard Lomotey, assistant professor of information sciences and technology at Penn State Beaver. "We are getting the real frustrations and joys experienced by these lactating mothers, which can help us to really explore the questions on the ground and the interventions that can be proposed to assist in this regard."

In the study, the researchers collected more than 19,000 breastfeeding-related tweets. Using existing lexicon-based tools and new machine learning classifiers that they developed, they classified the data to predict the sentiment polarity -- whether the text was positive or negative -- of the behavior described in each tweet.

The negative issues tweeted about by nursing mothers run the gamut, from latching problems and low milk supply, to postpartum depression and lack of support, to criticism over public breastfeeding. Positive tweets highlighted perceived benefits of breastfeeding, such as mother-child bonding, nutritional value and access to breastfeeding resources.

In all, 29 negative themes and 21 positive themes were identified. While the majority of the factors affecting breastfeeding behaviors negatively have been reported in existing literature -- such as latching problems and short maternity leave -- the researchers' analysis uncovered some new factors that have not previously been studied, including the deliberate decision to not breastfeed and fear of biting.

"Breastfeeding is a very popular issue, but you don't see public health officials and policy makers discussing it publicly or public engagement on this topic," said Lomotey. "Yet, it's a very important issue from a health perspective. So that's one of the driving factors in this project, to explore these issues that are being swept under the carpet and certainly considered a public taboo in some regions."

The researchers then placed the themes they identified into four negative categories of health-related issues, social factors, psychological factors and situational factors; and four positive categories of perceived benefits, maternal self-efficacy, social support, and education and training support.

"We highlighted a lot of issues that impact breastfeeding women, and we're not going to be able to address them all," said Rita Orji, associate professor of computer science at Dalhousie University. "But we want to put this out there so that policymakers and leaders at workplaces and schools can begin to engage with these topics and begin to highlight the issues that exist that impact women, as well as possible solutions."

In their paper, the researchers also propose various interventions that address the negative factors to propose positive breastfeeding behaviors. For example, mothers facing social factors such as lack of lactation rooms at work could benefit from technological interventions for delivering public awareness and sensitization programs designed to increase employer's awareness on the need to create a breastfeeding-friendly workplace.

"Many mothers have conflicting interests of a baby and a career, and this is something that fundamentally needs to be addressed," said Orji. "We want to create a strong workforce that accommodates women and empowers them to succeed -- especially while they're breastfeeding, which is a right and a natural phenomenon in a woman's life."

While this study focused solely on issues that breastfeeding mothers face, the researchers say that the methodology they applied could be used across a number of societal issues that people talk about on social media.

(Boston)-- The global spread of COVID-19 has raised serious concern for patients with chronic disease. A correlation has been identified between the severity of COVID-19 and a patient's preexisting comorbidities. Although COVID-19 primarily involves the respiratory system, dysfunction in multiple organ systems is common, particularly in the cardiovascular, gastrointestinal, immune, renal, and nervous systems. Patients with transthyretin amyloidosis (ATTR) (a disease caused by an abnormal misfolded protein that causes buildup of amyloid deposits in the heart, peripheral nervous system including the autonomic nervous system, or other organs) represent a population particularly vulnerable to COVID-19 morbidity due to the multisystem nature of ATTR amyloidosis.

Early on in the pandemic, an expert roundtable of international clinicians and investigators who specialize in ATTR amyloidosis was convened to discuss the impact of the pandemic on the ATTR patient population, ongoing clinical trials, and access to care. Since ATTR amyloidosis causes multi-system disease, as does COVID-19, they reviewed how the two diseases could overlap in presentation and how ATTR patients could be particularly vulnerable to advanced COVID complications.

In a position statement currently online in the Orphanet Journal of Rare Diseases, this panel concluded that patients with ATTR amyloidosis who develop COVID-19 have a higher risk of mortality, due to age, the organ system dysfunction caused by ATTR amyloid disease, and other comorbidities such as hypertension and diabetes, necessitating additional precautions and specialized management including:

Older patients with ATTR amyloidosis are at increased risk for developing severe COVID-19, requiring more careful social distancing, use of protective masks, and frequent hand washing

Many older patients with ATTR amyloidosis share comorbidities known to increase morbidity and mortality risk in COVID-19. Patients with cardiac ATTR amyloidosis should be aware of their predisposition to complications if they develop COVID-19, particularly stroke, congestive heart failure, and other cardiac-related issues

Differential access to care and the utilization of telehealth may more greatly impact older individuals with ATTR amyloidosis

Limitations of in-person evaluations and performing diagnostic evaluation during the COVID-19 pandemic limits the ability to diagnose and follow progression of patients with ATTR amyloidosis

Laboratory test results, such as elevated cardiac biomarkers, may be seen in both ATTR amyloidosis and COVID-19, confusing interpretation

"Patients with ATTR amyloidosis are at increased risk for COVID complications, so recognition of ATTR in undiagnosed patients as well as specialized care in diagnosed ATTR patients who contract COVID is warranted," explained corresponding author Frederick Ruberg, MD, associate professor of medicine and radiology at Boston University School of Medicine.

While other medical systems across the country failed to maintain HIV screening volumes throughout the COVID-19 pandemic, the University of Chicago Medicine maintained screening volumes by including universal HIV screening alongside COVID-19 testing in its busy emergency department, according to a new report published April 12 in JAMA Internal Medicine. Through targeted efforts to maintain infrastructure and enthusiasm for HIV screening, the number of HIV tests remained at pre-pandemic levels while the rate of acute HIV diagnoses actually increased.

Widespread screening to diagnose individuals newly infected with HIV is a key part of Centers for Disease Control and Prevention's (CDC) plan to end the HIV epidemic in America. However, the COVID-19 pandemic presented a challenge, because changes to the logistics of running emergency departments during a pandemic led to reduced HIV screening across the country.

"At UChicago Medicine, we successfully maintained our screening volume because we implemented infrastructure to facilitate continued routine HIV screening alongside COVID-19 testing in our emergency department," said first author Kim Stanford, MD, MPH, Assistant Professor of Medicine.

"We wanted to test as many people as possible in the emergency department, and Kim's team was unique in having the foresight to include phlebotomy for HIV testing in evaluation of people who were otherwise being seen for COVID-19," said senior author David Pitrak, MD, Professor of Medicine.

The investigators found that the diagnosis rate of acute HIV infection at UChicago Medicine actually rose during the pandemic compared to the previous four years. Other emergency departments that did not implement HIV screening as a part of COVID-19 testing saw a reduction in their HIV diagnoses.

While UChicago Medicine did see a rise in the rate of new HIV diagnoses, which has large implications for public health, it is as of yet unclear what drove this increase.

"It's possible that through screening during a COVID-19 test, we are just detecting more infections than we would have otherwise, and there isn't actually more widespread transmission," said Pitrak "It's also possible that the pressures of social isolation and drop offs in routine visits for HIV care led people to engage in more high-risk behaviors, and that community transmission is actually up. We don't know yet, but finding that out will be important for strategizing how to continue to stem further HIV transmission."

The CDC recommends HIV screening as a part of emergency department visits, yet only about 2% of these visits nationally are actually associated with a test.

"Emergency departments really are the places in the medical center with the highest prevalence of undiagnosed HIV infection," said Pitrak.

According to Stanford, screening for HIV during emergency department visits is especially critical for people in low-resource settings, since they may be at elevated risk for HIV infection and may not undergo routine screening. That means an emergency department visit is a critical opportunity to diagnose new infections.

Both Pitrak and Stanford emphasized how critical it is for a HIV testing program to have strong advocates in both the emergency and infectious disease departments.

"You need a strong partnership between these two parts of the medical system for this type of screening program to succeed. Our teams have been able to work well together to implement this program," said Stanford.

"Many doctors think there are these barriers that prevent them from ordering testing: 'What do I do if the test comes back positive? How am I going to help these patients get care? How am I going to answer all of their questions?'" said Pitrak. "Here at UChicago Medicine, we have a strong program to link patients to care and make sure they can access needed resources, so doctors don't need to worry about any of these questions. It's all streamlined and handled for them."

Both Pitrak and Stanford see the strength of this program in both the ability to diagnose individuals who may not normally be screened and its use as a model for other screenings during emergency department visits.

"Some of these patients normally wouldn't have come in for testing, and only received a diagnosis because they visited the emergency department because they were concerned about having COVID-19," said Stanford.

The results of the HIV screening program also suggest that other screenings as part of emergency room visits may be similarly useful.

"Diabetes screenings would be especially useful here at UChicago Medicine, for example, given the high rates in our community," said Stanford. "This could be extremely valuable for helping patients with little access to resources get a proper diagnosis and get connected with necessary treatment before their condition becomes severe."

On the HIV front, UChicago Medicine is continuing to move forward. "We are building a plan to work with other emergency departments in Chicago to implement both HIV and Hepatitis C screening," said Pitrak. "This really has the potential to help patients across the region. It's very exciting."

Asthma attacks account for almost 50 percent of the cost of asthma care which totals $80 billion each year in the United States. Asthma is more severe in Black and Hispanic/Latinx patients, with double the rates of attacks and hospitalizations as the general population.

When the COVID-19 pandemic swept over the United States, a series of reports suggested that fewer people were coming to emergency departments for all sorts of medical problems, including asthma attacks and even heart attacks. In the case of asthma, it was not clear if the drop was due to people avoiding emergency services or due to better asthma control. A new analysis from investigators at Brigham and Women's Hospital shines new light on this question. In a report of data collected as part of a trial in Black and Hispanic/Latinx patients with asthma that began before COVID-19 hit the U.S., they found total asthma attacks decreased by greater than 40 percent with the onset of the pandemic. Results are published in the Journal of Allergy & Clinical Immunology: In Practice.

"We found a substantial decrease in asthma exacerbation -- on the order of what we see for biologic therapies for severe asthma," said lead author Justin Salciccioli, MBBS, MA, a fellow in the Division of Pulmonary and Critical Care Medicine at the Brigham. "Although we don't know for sure who in the cohort changed their behavior, it's likely that decreased exposure to environmental or viral triggers contributed to our findings."

While no single change is likely to account for the large decrease in asthma attacks, Salciccioli and colleagues note that decreased exposure to allergens such as pollen, dust mites and mold, as well as viruses like influenza, are most likely to account for the decrease in asthma attacks. During the pandemic, measures to decrease exposure to the virus that causes COVID-19, including wearing masks, physical distancing and more, may have also decreased exposure to triggers of asthma.

Salciccioli and colleagues analyzed data collected as part of the PREPARE (The PeRson EmPowered Asthma Relief) Trial. The PREPARE Trial, led by Elliot Israel, MD, the Gloria M. and Anthony C. Simboli Distinguished Chair in Asthma Research and director of Clinical Research in the Brigham's Pulmonary and Critical Care Division, is a national randomized trial examining interventions to reduce asthma attacks in Black and Hispanic/Latinx adults with moderate-to-severe asthma supported by PCORI (The Patient Centered Outcome Research Institute). As part of the study, its nearly 1,200 participants completed monthly questionnaires remotely for 15 months, either online, by phone or by mail.

"Since patients participated remotely once they were enrolled, they could tell us about the condition of their asthma separate from any concerns about leaving the house or having contact with health care providers" said Israel.

This allowed the team to assess the impact of the COVID-19 pandemic independent of hesitancy to utilize health care.

To better understand how the pandemic may have affected people with asthma, the research team compared asthma exacerbation rates between the winter and spring of 2019 with those from 2020. There was a 40 percent decrease between the winter (Jan. 1 to March 31) and spring (April 1 to June 30) for 2020 compared to 2019. Participants who worked outside of the home when they first enrolled in the study had a 65 percent decrease. Decreases were also greatest for individuals with a less "allergic type" of asthma known as "TH2-low" asthma -- a type of asthma that might be triggered by environmental irritants such as pollution, smoke, or ozone, as opposed to exposure to allergens such as dust mite or mold.

While this study included only Black and Hispanic/Latinx participants, those groups are among the most impacted by asthma.

"This is the first study to assess asthma exacerbation before and after the COVID-19 pandemic using data that are unlikely to be affected by patients avoiding the health care system," said Salciccioli. "Because this was part of a prospective trial that started before the pandemic and was planned to be remote, it gave us a unique window into how changes during the pandemic may have led to a dramatic decrease in asthma exacerbation."

Vaccination dramatically reduced COVID-19 symptomatic and asymptomatic infections in St. Jude Children's Research Hospital employees compared with their unvaccinated peers, according to a research letter that appears today in the Journal of the American Medical Association.

The study is among the first to show an association between COVID-19 vaccination and fewer asymptomatic infections. When the Pfizer-BioNTech BNT162b2 vaccine was authorized for use in the U.S., the vaccine was reported to be highly effective at preventing laboratory-confirmed COVID-19. Clinical trial data suggested that the two-dose regimen reduced symptomatic disease, including hospitalization and death. But an association with reduced asymptomatic infection was unclear.

"While further research is needed, by preventing infections, including in people who have no symptoms, there is a high possibility that vaccination will decrease transmission of SARS-CoV-2," said Diego Hijano, M.D., of the St. Jude Department of Infectious Diseases. He and Li Tang, Ph.D., of St. Jude Biostatistics, are the first authors of the report. Tang is also the corresponding author.

The study involved 5,217 St. Jude employees who were eligible under Tennessee state guidelines for vaccination between Dec. 17, 2020, and March 20, 2021. More than 58% of employees were vaccinated during that period. Most workers received both doses.

Overall, vaccination reduced the risk of asymptomatic and symptomatic SARS-CoV-2 infection by 79% in vaccinated employees compared with their unvaccinated colleagues. An analysis of asymptomatic infections alone found vaccination reduced the risk by 72%.

Protection was even greater for employees who completed two doses. A week or more after receiving the second dose, vaccinated employees were 96% less likely than unvaccinated workers to become infected with SARS-CoV-2. When researchers looked just at asymptomatic infections, vaccination reduced the risk by 90%.

Finding SARS-CoV-2 infections

The research stems from a program that St. Jude leaders began in March 2020 to protect patients and employees from the pandemic virus.

The effort included targeted testing for employees with COVID-19 symptoms or known exposure to the pandemic virus. The plan also involved routine, laboratory testing of asymptomatic employees. Nasal swabs were collected at least weekly from self-reported asymptomatic on-campus workers to perform polymerase chain reaction to detect asymptomatic SARS-CoV-2 infection.

"This study was possible because St. Jude invested in resources to determine how best to control the disease and protect our patients and employees," Tang said. "Few places then or now provide such broad asymptomatic testing."

Hijano said, "Testing has been invaluable to the institutional COVID-19 mitigation plan. In the end, the testing also serves as a unique tool that helps to fill in critical knowledge gaps."

Results by the numbers

During the study, 236 of the 5,217 employees included in the analysis tested positive for SARS-CoV-2. They included 185 unvaccinated employees and 51 of the 3,052 workers who had received at least one dose of the vaccine.

Almost half of the positive cases, 108, reported no symptoms upon testing. The asymptomatic cases included 20 employees who had received one vaccine dose and three who tested positive within seven days of the second dose. "The results are a reminder of the many hidden cases in the population, which makes containing the virus a big challenge," Tang said.

The study group included a cross-section of employees in regard to race and gender. More than 80% of employees were younger than 65 years old. The vaccinated group included a higher percentage of health care staff, 47%, than the unvaccinated employees, 25.7%.

In a study published today in the Journal of the American Medical Association (JAMA), Johns Hopkins Medicine researchers show that although two doses of a vaccine against SARS-CoV-2 -- the virus that causes COVID 19 -- confers some protection for people who have received solid organ transplants, it's still not enough to enable them to dispense with masks, physical distancing and other safety measures.

This is a follow-up study to an earlier one published in March in JAMA, in which the researchers reported that only 17% of the participating transplant recipients produced sufficient antibodies after just one dose of a two-dose COVID-19 vaccine regimen.

"While there was an increase in those with detectable antibodies -- 54% overall -- after the second shot, the number of transplant recipients in our second study whose antibody levels reached high enough levels to ward off a SARS-CoV-2 infection was still well below what's typically seen in people with healthy immune systems," says study lead author Brian Boyarsky, M.D., a surgery resident at the Johns Hopkins University School of Medicine.

"Based on our findings, we recommend that transplant recipients and other immunocompromised patients continue to practice strict COVID-19 safety precautions, even after vaccination," Boyarsky says.

People who receive solid organ transplants (such as hearts, lungs and kidneys) often must take drugs to suppress their immune systems and prevent rejection. Such regimens may interfere with a transplant recipient's ability to make antibodies to foreign substances, including the protective ones produced in response to vaccines.

The new study evaluated this immunogenic response following the second dose of either of the two messenger RNA (mRNA) vaccines -- made by Moderna and Pfizer-BioNTech -- for 658 transplant recipients, none of whom had a prior diagnosis of COVID-19. The participants completed their two-dose regimen between Dec. 16, 2020, and March 13, 2021.

In the most recent study, the researchers found that only 98 of the 658 study participants -- 15% -- had detectable antibodies to SARS-CoV-2 at 21 days after the first vaccine dose. This was comparable to the 17% reported in the March study looking at immune response after only one vaccine dose.

At 29 days following the second dose, the number of participants with detectable antibodies rose to 357 out of 658 -- 54%. After both vaccine doses were administered, 301 out of 658 participants -- 46% -- had no detectable antibody at all while 259 -- 39% -- only produced antibodies after the second shot.

The researchers also found that among the participants, the most likely to develop an antibody response were younger, did not take immunosuppressive regimens including anti-metabolite drugs and received the Moderna vaccine. These were similar to the associations seen in the March single-dose study.

"Given these observations, transplant recipients should not assume that two vaccine doses guarantee sufficient immunity against SARS-CoV-2 any more than it did after just one dose," says study co-author Dorry Segev, M.D., Ph.D., the Marjory K. and Thomas Pozefsky Professor of Surgery and Epidemiology and director of the Epidemiology Research Group in Organ Transplantation at the Johns Hopkins University School of Medicine.

Segev says that future studies should seek to improve COVID-19 vaccine responses in this population, including additional booster doses or modulating the use of immunosuppressive medications so that sufficient antibody levels are achieved.

How can scientists predict a covid-19 outbreak? There's an app for that.

Media Contact: Rachel Butch; rbutch1@jhmi.edu

"COVID Control" using self-reported virus symptom information could predict next outbreak.

A mobile app that uses crowd-sourced data on COVID-19 symptoms can accurately identify where local coronavirus outbreaks will appear, according to Johns Hopkins Medicine scientists who developed the app.

The Johns Hopkins team launched the "COVID Control" app in May 2020 and have been studying how user-reported COVID-19 symptoms can predict potential outbreaks of the virus, enabling public health leaders to enact measures to contain the virus' spread. Results of the researchers' findings were published February 25, in Nature Scientific Reports.

"It's a really promising example of how we can use public participation and the ubiquity of technology like cell phones to track disease," says Robert Stevens, M.D., director of anesthesiology and critical care precision medicine at the Johns Hopkins University School of Medicine. "It's not limited to infectious diseases. This could be used to track the epidemiology of a number of prevalent health conditions, such as heart disease, cancer and diabetes."

Available via Google Play and Apple's App Store, COVID Control enables users to anonymously report symptoms associated with COVID-19, such as fever, loss of taste/smell, nausea and other symptoms to create a publicly viewable map showing clusters of people experiencing those symptoms. Since its launch, more than 19,000 users in 1,019 counties in every state across the U.S. have logged more than 174,000 data entries.

The study focused on Baltimore City and Baltimore County and showed that nine clusters of symptoms logged by COVID Control users correlated with locations of increased coronavirus prevalence reported by the Baltimore City Department of Health. New loss of taste or smell showed the strongest correlation between symptom reporting and confirmed COVID-19 cases, predicting the spike in cases an average of five days before the city's Department of Health confirmed a coronavirus outbreak.

As state and federal authorities decide whether to continue reimbursing for telehealth services that were suddenly adopted last spring in response to the coronavirus pandemic, a new study out of UC San Francisco has found that clinicians in the San Francisco Health Network (SFHN) overwhelmingly support using these services for outpatient primary care and specialty care visits.

The results surprised the research team, which includes a number of clinicians at Zuckerberg San Francisco General Hospital and Trauma Center (ZSFG), since they witnessed firsthand the difficulties that many of their colleagues and patients experienced when they had to turn to telehealth overnight. ZSFG is part of the San Francisco Health Network, where the survey was conducted, which also includes clinics run by the San Francisco Department of Public Health.

"That transition was so painful for many people: to find a new way to provide medical care," said Anjana Sharma, MD, MAS, assistant professor of family and community medicine at UCSF and first author of the paper, published in the Journal of Health Care for the Poor and Underserved. "We were surprised to see that 9 out of 10 clinicians expressed comfort with providing care by phone and video."

She said the team was also surprised at the concerns that providers expressed over whether they could accurately diagnose patients remotely. Almost 60 percent of those surveyed questioned the diagnostic safety of providing health care services over the telephone, and 35 percent had those concerns about diagnosing on video.

And there were other problems. Some 44 percent of clinicians reported that speech, hearing and cognitive barriers made telephone visits impractical. Significant portions also reported having patients who either did not have access to video (39 percent) or had no phone at all (38 percent), while 40 percent reported seeing patients who had trouble setting up video access because of language or educational barriers, and 35 percent reported patients without Internet.

Still, more than 90 percent of the clinicians surveyed said they planned to continue using phone and video to care for their patients after the COVID-19 pandemic ended.

For patients who can utilize the technology, particularly for follow-up care after a diagnosis has already been made, the benefits of telehealth are overwhelming. It saves time and money, especially for people who cannot easily get time off work to see the doctor or who may have childcare responsibilities. And, for those with access to video at home, the technology can make it easier to include other family members.

"People have been talking about telemedicine forever, but this transformation would have never happened if not for the pandemic," Sharma said. "It's the reimbursement flexibility that drove this to be possible."

State and federal authorities are currently debating whether to lower or potentially eliminate payments for video and telephone visits that have been reimbursed at near similar levels to in-person visits throughout the public health emergency.

"We do believe that video visits are higher quality and are probably safer for patients," Sharma said. "But we don't want to leave anyone behind. We're trying to say, 'both/and.' It makes sense to improve our video capacity for patients. But if telephone reimbursement goes away, that will be devastating for our patients."