COVID Lockdown Loneliness Linked to More Depressive Symptoms in Older Adults

Loneliness in adults aged 50 and over during the COVID-19 lockdown was linked to worsening depressive and other mental health symptoms, according to a large-scale online study.

Loneliness emerged as a key factor linked to worsening symptoms of depression and anxiety in a study of more than 3,000 people aged 50 or over led by the University of Exeter and King’s College London, and funded by The National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre (BRC).

Researchers had access to data going back to 2015 for participants of the PROTECT online study. They also found that a decrease in physical activity since the start of the pandemic was associated with worsening symptoms of depression and anxiety during the pandemic. Other factors included being female and being retired.

Dr Byron Creese, of the University of Exeter Medical School, who led the study, said: “Even before the pandemic, loneliness and physical activity levels were a huge issue in society, particularly among older people. Our study enabled us to compare mental health symptoms before and after COVID-19 in a large group of people aged 50 and over. We found that during lockdown, loneliness and decreased physical activity were associated with more symptoms of poor mental health, especially depression. It’s now crucial that we build on this data to find new ways to mitigate risk of worsening mental health during the pandemic.”

The study found that before the pandemic, lonely people would report an average of two symptoms of depression for at least several days over the previous last two weeks. During lockdown, lonely people reported either an increase in frequency of depressive symptoms, to more than half the days in the two week period, or a new symptom for at least several days in that timeframe. In people who were not lonely, levels of depressive symptoms were unaffected.

PROTECT began in 2011, and has 25,000 participants signed up. Designed to understand the factors involved in healthy ageing, the innovative study combines detailed lifestyle questionnaires with cognitive tests that assess aspects of brain function including memory, judgment and reasoning over time. In May, researchers included a new questionnaire designed to assess the impact of COVID-19 on health and wellbeing. Running from May 13 to June 8, the questionnaire was completed by 3,300 people, of which 1,900 were long-standing PROTECT participants. The study is continuing to run so that longer term outcomes can be assessed.

Zunera Khan, Research Portfolio Lead at Institute of Psychiatry, Psychology & Neuroscience said “We’ve found links between loneliness and a drop in physical exercise and worsening mental health symptoms. It should be within our power to find ways of keeping people socially engaged and active. Our online PROTECT platform ultimately aims to find new ways to engage people in their homes, however, technology can only be part of the picture. We need to ensure we can find new ways to help people stay active and social, whether they are online or not.”

Professor Clive Ballard, Executive Dean and Pro-Vice Chancellor of the University of Exeter Medical School, who leads PROTECT, said: “We are only just beginning to learn the impact that COVID-19 is having on the health and wellbeing of older people. For example, the effect of any economic impact may not yet have emerged. Our largescale study will span a number of years, and will help us understand some of the longer-term effects of COVID-19 on mental health and wellbeing, and ultimately, on whether this has any knock-on effect on aspects of ageing, such as brain function and memory. “

The study plans to conduct further analysis on groups at particularly high risk, such as people with cognitive impairment and those with caring roles.

Source: University of Exeter

Study: Exercise Doesn’t Boost Heart Health for Obese Individuals

The harmful effects of obesity on the heart can’t be undone by exercise, and it’s not possible to be “fat but healthy,” Spanish researchers warn.

“Exercise does not seem to compensate for the negative effects of excess weight,” said study author Alejandro Lucia, a professor of exercise physiology at European University in Madrid.

The study findings “refute the notion that a physically active lifestyle can completely negate the deleterious effects of overweight and obesity,” he said.

Lucia and his colleagues analyzed data from nearly 528,000 working adults in Spain. The participants’ average age was 42 and close to 7 out of 10 were men.

About 42% of these adults were normal weight; 41% were overweight, and 18% were obese. Most were inactive (63.5%); 12.3% got some but not enough exercise, and 24.2% were regularly active.

About 30% of participants had high cholesterol; 15% had high blood pressure, and 3% had diabetes.

No matter how active they were, however, overweight and obese people had a higher risk of heart disease than those whose weight was normal, according to the study, published in the European Journal of Preventive Cardiology.

Compared to active people of normal weight, active obese people were about twice as likely to have high cholesterol, four times more likely to have diabetes, and five times more likely to have high blood pressure.

“One cannot be ‘fat but healthy,’ ” Lucia warned in a journal news release.

But the researchers did not disregard the importance of exercise. In all weight categories, any physical activity was associated with a lower risk of diabetes, high blood pressure or high cholesterol, according to the findings. And the risk of diabetes and high blood pressure fell as physical activity rose.

“This tells us that everyone, irrespective of their body weight, should be physically active to safeguard their health,” Lucia said.

“More activity is better, so walking 30 minutes per day is better than walking 15 minutes a day,” he noted.

Lucia said it’s equally important to fight obesity and inactivity. “Weight loss should remain a primary target for health policies together with promoting active lifestyles,” he concluded.

Source: HealthDay

Study: Commonly Used Blood Pressure Medications Safe for COVID-19 Patients

Medications to treat high blood pressure did not affect outcomes among patients hospitalized with COVID-19, found an international team led by researchers in the Perelman School of Medicine at the University of Pennsylvania. The study, published in The Lancet Respiratory Medicine, is the first randomized controlled trial to show there is no risk for patients continuing these medications while hospitalized for COVID-19.

As part of the REPLACE COVID trial, investigators examined whether ACE inhibitors (ACEIs) or Angiotensin Receptor Blockers (ARBs) — two classes of medications to treat high blood pressure — could help mitigate complications or lead to more severe symptoms. More than 49 million U.S. adults take medication to treat hypertension, and among those, about 83 percent (41 million) take an ACEI or ARB, according to the Centers for Disease Control and Prevention.

Early during the pandemic, a concern arose regarding the use of ACEIs or ARBs in the setting of COVID-19, since some studies had suggested that these medications could upregulate cellular receptors for the SARS-CoV-2 virus potentially aiding viral replication. However, it was also considered that some effects of these medications could be protective against the virus.

“Observational studies were rapidly done, but randomized trials are important to establish a definitive answer regarding the potential impact of these commonly used blood pressure medications in the setting of COVID-19,” said study corresponding and senior author Julio A. Chirinos, MD, PhD, an associate professor of Cardiovascular Medicine in the Perelman School of Medicine. “Our trial results importantly show that these medications can be safely continued for patients hospitalized with COVID-19.”

ACEIs and ARBs are among the most commonly prescribed medications in the world, and a potential link between those medications and COVID-19 outcomes has large global health implications, the authors say. Several observational studies suggested no association between outpatient ACEI or ARB use and risk of COVID-19 hospitalization, but high-quality randomized trial evidence was lacking, until now.

For the trial, investigators enrolled 152 participants across several countries between March 31 and August 20, 2020, who were hospitalized with COVID-19 and already using one of the medications. The participants were randomly assigned to either stop or continue taking their prescribed medication and closely monitored to evaluate the effect of temporarily stopping the therapy.

Investigators developed an innovative global rank score to classify patient outcomes based on four factors: time to death, length of time supported by mechanical ventilation or extracorporeal membrane oxygenation (ECMO), length of time on renal replacement therapy, and a modified sequential organ failure assessment score. Through analyzing the patient outcome data, the team found discontinuation of ACEIs and ARBs compared with continuation of these medications had no effect on the global rank score.

This evidence supports international society recommendations for continuing ACEI and ARB therapy in patients admitted to the hospital with COVID-19, unless there is a clear, alternate medical issue with ongoing therapy.

“At the start of the pandemic, patients were worried about perceived harm based on limited and incomplete information, and unfortunately, some insisted on stopping their medications. However, stopping these medications unnecessarily can increase the risk for severe complications, including heart attack and stroke,” said first author Jordana B. Cohen, MD, MSCE, an assistant professor in the division of Renal-Electrolyte and Hypertension, and a co-principal investigator with Chirinos. “Now we have high quality evidence to support our recommendation that patients continue to take these medications as prescribed.”

Currently, trials are underway to determine if use of these medications is effective for the treatment of COVID-19.

Source: Penn Medicine

Most Patients Hospitalised with COVID-19 Have at least One Symptom Sx Months After Falling Ill

More than three quarters of COVID-19 patients have at least one ongoing symptom six months after initially becoming unwell, according to research published in The Lancet.

The cohort study, looking at long-term effects of COVID-19 infection on people hospitalised in Wuhan, China, reveals that the most common symptom to persist is fatigue or muscle weakness (63% of patients), with patients also frequently experiencing sleep difficulties (26%). Anxiety or depression was reported among 23% of patients.

Patients who were severely ill in hospital more often had impaired lung function and abnormalities detected in chest imaging – which could indicate organ damage – six months after symptom onset.

Levels of neutralising antibodies fell by more than half (52.5%) after six months in 94 patients whose immune response was tested at the peak of the infection, raising concerns about the possibility of being re-infected by the virus.

Little is known about the long-term health effects of COVID-19 as few follow-up studies have so far been carried out. Those that have been conducted looked only at a small number of cases over a short follow-up period (typically around three months after discharge).

Professor Bin Cao, from National Center for Respiratory Medicine, China-Japan Friendship Hospital and Capital Medical University, said: “Because COVID-19 is such a new disease, we are only beginning to understand some of its long-term effects on patients’ health. Our analysis indicates that most patients continue to live with at least some of the effects of the virus after leaving hospital, and highlights a need for post-discharge care, particularly for those who experience severe infections. Our work also underscores the importance of conducting longer follow-up studies in larger populations in order to understand the full spectrum of effects that COVID-19 can have on people.” [1]

The new study included 1,733 COVID-19 patients who were discharged from Jin Yin-tan Hospital in Wuhan, China, between January 7th and May 29th 2020. Patients had a median age of 57 years. Follow-up visits were done from June 16th to September 3rd, 2020, and the median follow-up time was 186 days.

All patients were interviewed face-to-face using questionnaires to evaluate their symptoms and health-related quality of life. They also underwent physical examinations, lab tests, and a six-minute walking test to gauge patients’ endurance levels. 390 patients had further tests, including an assessment of their lung function. In addition, 94 patients whose blood antibody levels were recorded at the height of the infection as part of another trial received a follow-up test.

At follow-up, 76% of patients (1,265/1,655) reported at least one ongoing symptom. Fatigue or muscle weakness was reported by 63% (1,038/1,655), while 26% (437/1,655) had sleep difficulties and 23% (367/1,733) experienced anxiety or depression.

Of the 390 patients who underwent additional testing, 349 completed the lung function test (41 were unable to complete the test due to poor compliance). Patients with more severe illness commonly had reduced lung function, with 56% (48/86) of those at severity scale 5-6 (who required ventilation) experiencing diffusion impairment – reduced flow of oxygen from the lungs to the bloodstream. For patients at severity scale 4 (who required oxygen therapy) and those at scale 3 (who did not require oxygen therapy) the figures were 29% (48/165) and 22% (18/83), respectively.

Patients with more severe disease performed worse in the six-minute walking test (which measures the distance covered in six minutes), with 29% of those at severity scale 5-6 walking less than the lower limit of the normal range, compared with 24% for those at scale 3, and 22% for scale 4.

The authors also found that some patients went on to develop kidney problems post-discharge. As well as the lungs, COVID-19 is known to affect other organs, including the kidney. Lab tests revealed that 13% (107/822) of patients whose kidney function was normal while in hospital had reduced kidney function in follow-up.

Follow-up blood antibody tests from 94 patients after six months revealed that levels of neutralising antibodies were 52.5% lower than at the height of infection. The authors say this raises concerns about the possibility of COVID-19 re-infection.

As the number of participants with antibody test results both at acute phase and follow-up was limited, larger samples are needed in future to clarify how levels of antibodies against the virus change over time. Further work is also needed to compare differences in outcomes between inpatients and outpatients, as patients with mild COVID-19 symptoms who stayed in temporary Fangcang shelter hospitals were not included in the study.

Impaired lung function and exercise capacity observed in the study cannot be directly attributed to COVID-19 as baseline data for these are unavailable. Due to the way the data was analysed, it also was not possible to determine if symptoms reported during follow-up were persistent following the infection, worsened after recovery, or occurred post-discharge.

Writing in a linked Comment, Monica Cortinovis, Norberto Perico, and Giuseppe Remuzzi, from the Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Italy, who were not involved in the study, remark on the uncertainty regarding the possible long-term impacts of COVID-19 on health, saying: “Unfortunately, there are few reports on the clinical picture of the aftermath of COVID-19. The study by Huang and colleagues in The Lancet is therefore relevant and timely.”

Echoing the study authors’ calls for further research, they add: “Even though the study offers a comprehensive clinical picture of the aftermath of COVID-19 in hospitalised patients, only 4% were admitted to an intensive care unit (ICU), rendering the information about the long-term consequences in this particular cohort inconclusive. Nonetheless, previous research on patient outcomes after ICU stays suggests that several COVID-19 patients who were critically ill while hospitalised will subsequently face impairments regarding their cognitive and mental health and/or physical function far beyond their hospital discharge.”

Source: EurekAlert!

Study: COVID-19 Severity Affected by Proportion of Antibodies Targeting Crucial Viral Protein

Krista Conger wrote . . . . . . . . .

A comprehensive study of immune responses to SARS-CoV-2 associates mild disease with comparatively high levels of antibodies that target the viral spike protein. But all antibodies wane within months.

COVID-19 antibodies preferentially target a different part of the virus in mild cases of COVID-19 than they do in severe cases, and wane significantly within several months of infection, according to a new study by researchers at Stanford Medicine.

The findings identify new links between the course of the disease and a patient’s immune response. They also raise concerns about whether people can be re-infected, whether antibody tests to detect prior infection may underestimate the breadth of the pandemic and whether vaccinations may need to be repeated at regular intervals to maintain a protective immune response.

“This is one of the most comprehensive studies to date of the antibody immune response to SARS-CoV-2 in people across the entire spectrum of disease severity, from asymptomatic to fatal,” said Scott Boyd, MD, PhD, associate professor of pathology. “We assessed multiple time points and sample types, and also analyzed levels of viral RNA in patient nasopharyngeal swabs and blood samples. It’s one of the first big-picture looks at this illness.”

The study found that people with severe COVID-19 have a lower proportion of antibodies targeting the spike protein used by the virus to enter human cells than of antibodies targeting proteins of the virus’s inner shell.

Boyd is a senior author of the study, which was published in Science Immunology.

Virus binds to ACE2 receptor

The researchers studied 254 people with asymptomatic, mild or severe COVID-19 who were identified either through routine testing or occupational health screening at Stanford Health Care or who came to a Stanford Health Care clinic with symptoms of COVID-19. Of the people with symptoms, 25 were treated as outpatients, 42 were hospitalized outside the intensive care unit and 37 were treated in the intensive care unit. Twenty-five people in the study died of the disease.

SARS-CoV-2 binds to human cells via a structure on its surface called the spike protein. This protein binds to a receptor on human cells called ACE2. The binding allows the virus to enter and infect the cell. Once inside, the virus sheds its outer coat to reveal an inner shell encasing its genetic material. Soon, the virus co-opts the cell’s protein-making machinery to churn out more viral particles, which are then released to infect other cells.

Antibodies that recognize and bind to the spike protein block its ability to bind to ACE2, preventing the virus from infecting the cells, whereas antibodies that recognize other viral components are unlikely to prevent viral spread. Current vaccine candidates use portions of the spike protein to stimulate an immune response.

Boyd and his colleagues analyzed the levels of three types of antibodies — IgG, IgM and IgA — and the proportions that targeted the viral spike protein or the virus’s inner shell as the disease progressed and patients either recovered or grew sicker. They also measured the levels of viral genetic material in nasopharyngeal samples and blood from the patients. Finally, they assessed the effectiveness of the antibodies in preventing the spike protein from binding to ACE2 in a laboratory dish.

“Although previous studies have assessed the overall antibody response to infection, we compared the viral proteins targeted by these antibodies,” Boyd said. “We found that the severity of the illness correlates with the ratio of antibodies recognizing domains of the spike protein compared with other nonprotective viral targets. Those people with mild illness tended to have a higher proportion of anti-spike antibodies, and those who died from their disease had more antibodies that recognized other parts of the virus.”

Substantial variability in immune response

The researchers caution, however, that although the study identified trends among a group of patients, there is still substantial variability in the immune response mounted by individual patients, particularly those with severe disease.

“Antibody responses are not likely to be the sole determinant of someone’s outcome,” Boyd said. “Among people with severe disease, some die and some recover. Some of these patients mount a vigorous immune response, and others have a more moderate response. So, there are a lot of other things going on. There are also other branches of the immune system involved. It’s important to note that our results identify correlations but don’t prove causation.”

As in other studies, the researchers found that people with asymptomatic and mild illness had lower levels of antibodies overall than did those with severe disease. After recovery, the levels of IgM and IgA decreased steadily to low or undetectable levels in most patients over a period of about one to four months after symptom onset or estimated infection date, and IgG levels dropped significantly.

“This is quite consistent with what has been seen with other coronaviruses that regularly circulate in our communities to cause the common cold,” Boyd said. “It’s not uncommon for someone to get re-infected within a year or sometimes sooner. It remains to be seen whether the immune response to SARS-CoV-2 vaccination is stronger, or persists longer, than that caused by natural infection. It’s quite possible it could be better. But there are a lot of questions that still need to be answered.”

Boyd is a co-chair of the National Cancer Institute’s SeroNet Serological Sciences Network, one of the nation’s largest coordinated research efforts to study the immune response to COVID-19. He is the principal investigator of Center of Excellence in SeroNet at Stanford, which is tackling critical questions about the mechanisms and duration of immunity to SARS-CoV-2.

“For example, if someone has already been infected, should they get the vaccine? If so, how should they be prioritized?” Boyd said. “How can we adapt seroprevalence studies in vaccinated populations? How will immunity from vaccination differ from that caused by natural infection? And how long might a vaccine be protective? These are all very interesting, important questions.”

Source: Stanford Medicine