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Fatigue, headache among top lingering symptoms months after COVID

Fatigue and headache were the most common symptoms reported by individuals an average of more than four months out from having COVID-19, investigators report.

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Fatigue and headache were the most common symptoms reported by individuals an average of more than four months out from having COVID-19, investigators report.

Muscle aches, cough, changes in smell and taste, fever, chills and nasal congestion were next in the long line of lingering symptoms.

“Our results support the growing evidence that there are chronic neuropsychiatric symptoms following COVID-19 infections,” Medical College of Georgia investigators write in the journal ScienceDirect

“There are a lot of symptoms that we did not know early on in the pandemic what to make of them, but now it’s clear there is a long COVID syndrome and that a lot of people are affected,” says Dr. Elizabeth Rutkowski, MCG neurologist and the study’s corresponding author.

The published study reports on preliminary findings from the first visit of the first 200 patients enrolled in the COVID-19 Neurological and Molecular Prospective Cohort Study in Georgia, or CONGA, who were recruited on average about 125 days after testing positive for the COVID-19 virus.

CONGA was established at MCG early in the pandemic in 2020 to examine the severity and longevity of neurological problems and began enrolling participants in March 2020 with the ultimate goal of recruiting 500 over five years.

Eighty percent of the first 200 participants reported neurological symptoms with fatigue, the most common symptom, reported by 68.5%, and headache close behind at 66.5%. Just over half reported changes in smell (54.5%) and taste (54%) and nearly half the participants (47%) met the criteria for mild cognitive impairment, with 30% demonstrating impaired vocabulary and 32% having impaired working memory.

Twenty-one percent reported confusion, and hypertension was the most common medical condition reported by participants in addition to their bout with COVID-19.

No participants reported having a stroke, weakness or inability to control muscles involved with speaking, and coordination problems were some of the less frequently reported symptoms.

Twenty-five percent met the criteria for depression, and diabetes, obesity, sleep apnea and a history of depression were associated with those who met the criteria. Anemia and a history of depression were associated with the 18% who met the objective criteria for anxiety.

While the findings to date are not surprising and are consistent with what other investigators are finding, Rutkowski says the fact that symptoms reported by participants often didn’t match what objective testing indicated, was surprising. And, it was bidirectional.

For example, the majority of participants reported taste and smell changes, but objective testing of both these senses did not always line up with what they reported. In fact, a higher percentage of those who did not report the changes actually had evidence of impaired function based on objective measures, the investigators write. While the reasons are not certain, part of the discrepancy may be a change in the quality of their taste and smell rather than pure impaired ability, Rutkowski says.

“They eat a chicken sandwich and it tastes like smoke or candles or some weird other thing but our taste strips are trying to depict specific tastes like salty and sweet,” Rutkowski says. Others, for example, may rely on these senses more, even when they are preparing the food, and may be apt to notice even a slight change, she says.

Either way, their data and others suggest a persistent loss of taste and smell following COVID-19, Rutkowski and her colleagues write.

Many earlier reports have been based on these kinds of self-reports, and the discrepancies they are finding indicate that approach may not reflect objective dysfunction, the investigators write.

On the other hand, cognitive testing may overestimate impairment in disadvantaged populations, they report.

The first enrollees were largely female, 35.5% were male. They were an average of 44.6 years old, nearly 40% were Black and 7% had been hospitalized because of COVID-19. Black participants were generally disproportionately affected, the investigators say.

Seventy-five percent of Black participants and 23.4% of white participants met criteria for mild cognitive impairment. The findings likely indicate that cognitive tests assess different ethnic groups differently. And, socioeconomic, psychosocial (issues like family problems, depression and sexual abuse) and physical health factors generally may disproportionately affect Black individuals, the investigators write. It also could mean that cognitive testing may overestimate clinical impairment in disadvantaged populations, they write.

Black and Hispanic individuals are considered twice as likely to be hospitalized by COVID-19 and ethnic and racial minorities are more likely to live in areas with higher rates of infection. Genetics also is a likely factor for their increased risk for increased impact from COVID, much like being at higher risk for hypertension and heart disease early and more severely in life.

A focus of CONGA is to try to better understand how increased risk and effects from COVID-19 impact Blacks, who comprise about 33% of the state’s population.

A reason fatigue appears to be such a major factor among those who had COVID-19 is potentially because of levels of inflammation, the body’s natural response to an infection, remain elevated in some individuals. For example, blood samples taken at the initial visit and again on follow up showed some inflammatory markers were up and stayed up in some individuals.

These findings and others indicate that even though the antibodies to the virus itself may wain, persistent inflammation is contributing to some of the symptoms like fatigue, she says. She notes patients with conditions like multiple sclerosis and rheumatoid arthritis, both considered autoimmune conditions that consequently also have high levels of inflammation, also include fatigue as a top symptom.

“They have body fatigue where they feel short of breath, they go to get the dishes done and they are feeling palpitations, they immediately have to sit down and they feel muscle soreness like they just ran a mile or more,” Rutkowski says.

“There is probably some degree of neurologic fatigue as well because patients also have brain fog, they say it hurts to think, to read even a single email and that their brain is just wiped out,” she says. Some studies have even shown shrinkage of brain volume as a result of even mild to moderate disease. 

These multisystem, ongoing concerns are why some health care facilities have established long COVID clinics where physicians with expertise in the myriad of problems they are experiencing gather to see each patient.

CONGA participants who reported more symptoms and problems tended to have depression and anxiety. Problems like these as well as mild cognitive impairment and even impaired vocabulary may also reflect the long-term isolation COVID-19 produced for many individuals, Rutkowski says.

“You are not doing what you would normally do, like hanging out with your friends, the things that bring most people joy,” Rutkowski says. “On top of that, you may be dealing with physical ailments, lost friends and family members and loss of your job.”

For CONGA, participants self-report symptoms and answer questions about their general state of health like whether they smoked, drank alcohol, exercised, and any known preexisting medical conditions. But they also receive an extensive neurological exam that looks at fundamentals like mental status, reflexes and motor function. They also take established tests to assess cognitive function with results being age adjusted. They also do at-home extensive testing where they are asked to identify odors and the ability to taste sweet, sour, bitter, salty, brothy or no taste. They also have blood analysis done to look for indicators of lingering infection like those inflammatory markers and oxidative stress.

Neuropsychiatric symptoms are observed in the acute phase of infection, but there is a need for accurate characterization of how symptoms evolve over time, the investigators write.

And particularly for some individuals, symptoms definitely linger. Even some previously high-functioning individuals, who normally worked 80 hours a week and exercised daily, may find themselves only able to function about an hour a day and be in the bed the remainder, Rutkowski says.

The investigators are searching for answers to why and how, and while Rutkowski says she cannot yet answer all their questions, she can tell them with certainty that they are not alone or “crazy.”  

One of the best things everyone can do moving forward is to remain diligent about avoiding infection, including getting vaccinated or boosted to help protect your brain and body from long COVID symptoms and help protect others from infection, Rutkowski says. There is evidence that the more times you are infected, the higher the risk of ongoing problems.

Rutkowski notes that their study findings may be somewhat biased toward high percentages of ongoing symptoms because the study likely is attracting a high percentage of individuals with concerns about ongoing problems.

SARS-CoV-2 is thought to have first infected people in late 2019 and is a member of the larger group of coronaviruses, which have been a source of upper respiratory tract infections, like the common cold, in people for years.

At least part of the reason SARS-CoV-2 is believed to have such a wide-ranging impact is that the virus is known to attach to angiotensin-converting enzyme-2, or ACE2, which is pervasive in the body. ACE2 has a key role in functions like regulating blood pressure and inflammation. It’s found on neurons, cells lining the nose, mouth, lungs and blood vessels, as well as the heart, kidneys and gastrointestinal tract. The virus attaches directly to the ACE2 receptor on the surface of cells, which functions much like a door to let the virus inside.

Experience and study since COVID-19 started both indicate immediate neurological impact can include loss of taste and smell, brain infection, headaches and, less commonly, seizures, stroke and damage or death of nerves. As time has passed, there is increasing evidence that problems like loss of taste and smell, can become chronic, as well as problems like brain fog, extreme fatigue, depression, anxiety and insomnia, the investigators write. Persistent conditions including these and others are now referenced as “long Covid.”

The research was supported by funding from the National Institute of Neurological Disorders and Stroke and philanthropic support from the TR Reddy Family Fund.

Read the full study.

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Cancer risk is significantly higher for adults who never married, large study finds

Adults who were never married had substantially higher rates of developing cancer compared with those who were or had been married. For some cancers, the association was even stronger: adult men who were never married had approximately five times the rate of anal cancer compared with married men.

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Adults who have never been married face a significantly higher risk of developing cancer than those who have been married, according to a study of more than 4 million cases.

The increased risk spans nearly every major cancer type and is especially pronounced for preventable cancers—those linked to infections, smoking and reproductive factors. Led by researchers at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, the study appears in the April 8 issue of Cancer Research Communications.

link to the article is here.

“These findings suggest that social factors such as marital status may serve as important markers of cancer risk at the population level,” said Paulo Pinheiro, Ph.D., study co-author and a Sylvester physician-scientist whose lab conducts population-based cancer epidemiology.

The novel observation does not mean that getting married prevents cancer or that people need to get married.

“It means that if you’re not married, you should be paying extra attention to cancer risk factors, getting any screenings you may need, and staying up to date on health care,” said Frank Penedo, Ph.D., associate director for population sciences and director of the Sylvester Survivorship and Supportive Care Institute (SSCI).

“For prevention efforts, our findings point to the importance of targeting cancer risk awareness and prevention strategies with attention to marital status,” he added.

Marriage is already associated with earlier cancer diagnosis and better survival. Married individuals often, but not always, have stronger support systems, greater economic stability and are more likely to adhere to cancer treatment regimens.

But previous work on the links between marriage and cancer focused almost entirely on what happens at and after diagnosis. Only a few small, older studies explored whether marriage affects the odds of getting cancer in the first place.

“We wanted to know who is more likely to get cancer: married people or unmarried people?” Pinheiro said.

To find out, the researchers analyzed a large dataset covering 12 states that included demographic and cancer data from more than 4 million cancer cases in a population of more than 100 million people, collected between 2015 and 2022. They examined cases of malignant cancers diagnosed at age 30 or older and compared rates of various cancers by marital status, further broken down by sex and race and adjusted for age.

The researchers categorized marital status into two groups: those who were or had been married, including married, divorced and widowed individuals, and those who had never been married. The study began in 2015 because that year, the U.S. Supreme Court legalized gay marriage, allowing same-sex couples to be included in the married category. One in five adults in the study had never married.

Pinheiro expected to see some associations, given established relationships between marriage and lifestyle factors such as smoking, routine medical care and having children. But the strength of some findings surprised him.

Adults who were never married had substantially higher rates of developing cancer compared with those who were or had been married. For some cancers, the association was even stronger: adult men who were never married had approximately five times the rate of anal cancer compared with married men. Adult women who were never married had nearly three times the rate of cervical cancer compared with women who were or had been married.

Both anal and cervical cancers are strongly related to HPV infection, so these differences likely reflect variation in exposure, and for cervical cancer, also differences in screening and prevention. In contrast, for cancers such as endometrial and ovarian, differences by marital status may partly reflect the protective effect of parity, which is more common among married individuals.

“It’s a clear and powerful signal that some individuals are at a greater risk,” Penedo said.

Men and women showed slightly different patterns. Men who were never married were about 70% more likely to develop cancer than married men, while women who never married were about 85% more likely to develop cancer than women who were or had been married.

This represents a small but noteworthy reversal of a broader trend: Men often benefit more from marriage than women in terms of health and social factors. In this case, women appeared to benefit slightly more from marriage than men.

The strongest associations between marriage and cancer were seen for cancers related to infection, smoking or alcohol use, and, for women, cancers related to reproduction, such as ovarian and endometrial cancer.

The researchers found weaker associations for cancers with robust screening programs, including breast, thyroid and prostate cancers.

They also observed patterns across race and marital status. Black men who were never married had the highest overall cancer rates. However, married Black men had lower cancer rates than married White men, indicating a strong protective association with marriage in that group.

The study has limitations. People who smoke less, drink less, take better care of themselves and are more socially integrated may also be more likely to get married.

Still, the researchers found that associations between marriage and cancer were stronger in adults older than 50, suggesting that as people age and accumulate cancer risk exposures, the benefits associated with marriage may become more pronounced.

The study also excluded individuals who are unmarried but in committed partnerships. That group is likely small relative to the size of the dataset, Pinheiro said, but worth exploring in future research.

Future studies could further subdivide the married category into married, divorced and widowed individuals and follow people over decades to better understand how marital transitions affect cancer risk.

Overall, getting married does not magically prevent cancer, both authors stressed.

“But the association between marriage status and cancer risk is an interesting, new observation that deserves more research,” Pinheiro said.

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Social support, sleep, pain management linked to mental health in later life

Older people who are socially connected, physically healthy, and spiritually engaged are significantly more likely to experience complete mental health.

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Older people who are socially connected, physically healthy, and spiritually engaged are significantly more likely to experience complete mental health.

This is according to a new study, “Flourishing older Canadians: What characteristics are associated with complete mental health?”, that was published in PLOS One.

Using data from 2,024 respondents in Statistics Canada’s 2022 Mental Health and Access to Care Survey (MHACS), researchers examined factors associated with both the absence of psychiatric disorder (APD) and complete mental health (CMH), a broader measure that combines freedom from mental illness with high emotional, psychological, and social well-being.

“Our findings shift the conversation away from mental illness alone and toward understanding what helps older adults truly flourish,” said first author Daniyal Rahim, PhD Candidate, Ontario Institute for Studies in Education, University of Toronto. “Complete mental health reflects not just the absence of disorders, but the presence of meaning, satisfaction, and strong social connections.”

The study found that older adults were more likely to experience APD and CMH if they were married or in a common-law relationship, had strong social support, rated their physical health as fair or better, and reported no chronic pain, sleep problems, or limitations in daily activities. Social support emerged as one of the strongest predictors, more than doubling the odds of achieving complete mental health.

“Social relationships appear to be a cornerstone of mental well-being in later life,” said coauthor Shannon Halls, Research Coordinator, Institute for Life Course & Aging, University of Toronto. “Having people to rely on during stressful times may buffer against psychological distress and promote resilience, happiness, and a sense of purpose.”

Spirituality was also strongly associated with mental well-being. Older adults who reported that religion or spirituality was important in their daily lives had significantly higher odds of both APD and CMH.

“Spiritual beliefs may help older adults cope with adversity by providing meaning, hope, and a sense of community,” said co-author Ying Jiang, a senior epidemiologist in the Applied Research Division, Centre for Surveillance and Applied Research, Public Health Agency of Canada. “These factors can be particularly relevant during periods of declining health or life transitions.”

Physical health factors played a critical role. Freedom from chronic pain, sleep problems, and limitations in instrumental activities of daily living was consistently associated with better mental health outcomes. Conversely, living in a large urban center was linked to lower odds of complete mental health compared to rural living.

“These findings underscore that mental health in aging is shaped by a complex interplay of social, physical, and environmental factors,” said senior author Esme Fuller-Thomson, Director, Institute for Life Course & Aging, University of Toronto, Factor-Inwentash Faculty of Social Work, University of Toronto. “Public health strategies that strengthen social support, address pain and sleep problems, and promote meaningful engagement could substantially improve well-being among older adults.”

The authors emphasize that many of the identified factors are modifiable, suggesting opportunities for targeted interventions, including social programming, pain management, sleep treatment, and community-based supports to help more older Canadians achieve complete mental health.

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Healthier plant-based diet associated with lower risk of Alzheimer’s, other dementias

Eating a higher quality plant-based diet is associated with a lower risk of Alzheimer’s disease and other related dementias compared to eating a lower quality plant-based diet.

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Eating a higher quality plant-based diet is associated with a lower risk of Alzheimer’s disease and other related dementias compared to eating a lower quality plant-based diet.

This is according to a study published in Neurology, the medical journal of the American Academy of Neurology.

While the study shows an association based on observations, it does not prove that a higher quality plant-based diet causes a lower risk of dementia.

Researchers looked at three plant-based diets. The overall plant-based diet prioritizes eating more plant foods than animal products like meat, milk and eggs, without looking at quality. The healthful plant-based diet prioritizes healthy plant foods like whole grains, fruits, vegetables, vegetable oils, nuts, legumes and tea and coffee. The unhealthful plant-based diet includes less healthy plant foods like refined grains, fruit juices, potatoes and added sugars. Researchers did not look at vegetarian or vegan diets.

“Plant-based diets have been shown to be beneficial in reducing the risk of diseases like diabetes and high blood pressure, but less is known about the risk of Alzheimer’s disease and other dementias,” said study author Song-Yi Park, PhD, of the University of Hawaii at Manoa’s Cancer Center in Honolulu. “Our study found that the quality of a plant-based diet mattered, with a higher quality diet associated with a reduced risk, and a lower quality diet associated with an increased risk.”

The study involved 92,849 people with an average age of 59 at the start of the study. It included African American, Japanese American, Latino, Native Hawaiian and white participants. They were followed for an average of 11 years. During that time, 21,478 people developed Alzheimer’s disease or another related dementia.

Participants completed food questionnaires at the start of the study. Researchers determined how well people’s diets resembled the overall plant-based diet, the healthful plant-based diet and the unhealthful plant-based diet, by reviewing how many healthy and less healthy plant foods they ate, as well as animal fats, meat, dairy, eggs, fish and seafood. Participants were each given three scores based on how closely they followed the three plant-based diets.

Researchers then ranked the participants into five subgroups for each of the three diet scores.

After adjusting for factors like age, physical activity and diabetes, researchers found that when comparing people based on their score for the overall plant-based diet, the top subgroup who ate the most plant foods had a 12% lower risk of dementia compared to the lowest subgroup.

When people were compared based on their score for the healthful plant-based diet, the top subgroup had a 7% lower risk compared to the lowest subgroup. And when compared based on their score for the unhealthful plant-based diet, the top subgroup who ate the most unhealthy plant foods had a 6% higher risk of dementia than the lowest subgroup.

Among a smaller group of 45,065 participants who reported their diet again after 10 years, 8,360 participants later developed dementia. Researchers looked at diet changes over time. When compared to people whose diets didn’t change, people whose diets changed the most toward following an unhealthful diet had a 25% higher risk of dementia while those whose diets changed the most away from following an unhealthful diet had an 11% lower risk.

“We found that adopting a plant-based diet, even starting at an older age, and refraining from low-quality plant-based diets were associated with a lower risk of Alzheimer’s and other dementias,” said Park. “Our findings highlight that it is important not only to follow a plant-based diet, but also to ensure that the diet is of high quality.”

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