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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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Could your oral health be affecting fertility?

Chronic oral inflammation may impair female fertility by triggering a systemic immune response that affects the ovaries. A new study shows this leads to oxidative damage, reduced egg quality, disrupted follicle development and reduced live birth rate. These findings point to a potential biological link between oral health and unexplained infertility, opening new directions for future treatments.

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A new study led by Prof. Michael Klutstein at the Hebrew University of Jerusalem and Prof. Asaf Wilensky at the Hebrew University-Hadassah Medical center and spearheaded by the students Dr. Paz Kles and Stephen Ameho has uncovered a striking biological link between chronic oral inflammation and female fertility, suggesting that conditions in the mouth may have far-reaching effects on reproductive health.

Published in the Journal of Dental Research, the study shows that persistent inflammation in the oral cavity can impair ovarian function, reduce egg quality, and ultimately lower fertility rates.

Researchers examined in a mouse model inflammation associated with dental implants, a common clinical scenario, and tracked how immune signals spread throughout the body. Their findings reveal that inflammation does not remain confined to the oral cavity but triggers a systemic immune response that reaches the ovaries.

The consequences were significant. Chronic oral inflammation in the animals was linked to increased levels of inflammatory cytokines in the ovaries, along with shifts in immune cell populations. This was accompanied by oxidative damage to ovarian tissue, impaired development of follicles, and reduced quality of oocytes.

These biological changes translated into measurable reproductive outcomes, with markedly reduced birth rates observed under inflammatory conditions in the animals.

The study also identified deeper cellular effects. Oocytes exhibited DNA damage and epigenetic alterations resembling those seen in reproductive aging, pointing to a possible mechanism by which inflammation accelerates the decline in fertility.

“Inflammation is often thought of as a localized response, but our findings show that it can have systemic consequences that extend as far as the reproductive system,” said Prof. Michael Klutstein. “This work suggests that chronic oral inflammation may be an underrecognized factor in female infertility, potentially contributing to cases that currently have no clear explanation.”

The findings add to growing evidence that oral health is closely linked to overall health. Chronic oral inflammatory conditions such as periodontitis are widespread and have already been associated with a range of systemic diseases.

The researchers note that further investigation in clinical settings will be essential to determine how these findings translate to patient care. If confirmed, the work could open new avenues for diagnosis and treatment, including the use of anti-inflammatory or antioxidant approaches to improve fertility outcomes.

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Maintaining a healthy heart may require regular doses of positivity

The findings of this study further point to the importance of attending to mental and behavioral health for cardiovascular disease prevention and cardiovascular health optimization.

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Positive psychology interventions such as mindfulness, gratitude journaling and optimism training can consistently improve blood pressure, inflammation markers and other cardiovascular disease risk factors within a matter of weeks, a recent study found. However, since these benefits are associated with lifestyle changes such as eating healthier and greater physical activity, the researchers suggested that ongoing reinforcements may be needed to stay on course long term.

Rosalba (Rose) Hernandez, a professor of social work at the University of Illinois Urbana-Champaign, led a team that analyzed the findings of 18 randomized controlled trials that used positive psychological and mindfulness interventions to enhance mental or physical health.

The programs that the team reviewed included individual methods — such as structured telephone sessions, journaling with brief check-ins and digital platforms such as apps and text messaging — and interactive in-person group sessions, as well as hybrid formats that blended these with online tools and virtual meetings. Most of the programs consisted of weekly sessions and at-home activities that reinforced the skills taught, with the majority of programs lasting from six to 12 weeks, the team found.

In general, the programs included 50-200 adults with elevated cardiovascular risk factors such as uncontrolled hypertension, heart failure or other conditions. Typically, the participants were in their late 50s to mid-60s, and women comprised 35-55% of the samples across those studies that reported their participants’ gender, according to the researchers.

“In hypertension and postacute coronary syndrome cohorts, mindfulness-based programs delivered over an eight-week period reduced systolic blood pressure and lowered inflammatory markers such as high-sensitivity C-reactive protein and fibrinogen,” said Hernandez, who is a Fellow of the American Heart Association. “A 12-week spirituality-based digital intervention achieved one of the largest reductions — reducing systolic blood pressure measured with a standard cuff by 7.6 points, and central systolic pressure — which is measured in the aorta as it leaves the heart — by 4.1 points.”

In prior research on positive psychology interventions, scientists seldom defined the dose that was needed to obtain the beneficial effects, Hernandez said. She and the team members sought to clarify the frequency and duration that was most likely to improve individuals’ cardiovascular health.

Programs that had more frequent contact with their participants yielded the most consistent physiological benefits, underscoring the opportunity to embed positive psychological strategies into long-term cardiovascular care, Hernandez said.

The team found that the strongest behavioral improvements were achieved by an eight-week program delivered over WhatsApp that combined weekly sessions with daily microtasks, motivating participants to engage in greater physical activity, eat a healthier diet and take their medication as prescribed. A program that included motivational interviewing succeeded in increasing cardiac patients’ levels of physical activity by 1,800 steps a day and their medication adherence, while the mindfulness programs improved participants’ activity levels and diets only, according to the study.

“The therapeutic dose that was most consistently linked with improvements in blood pressure, inflammation and endothelial function was daily practice reinforced by weekly sessions over eight to 12-week periods,” Hernandez said. “Therapeutic dosing typically involved high-frequency dosing over this time period to obtain short-term physiologic benefits, while ongoing less-intensive contact may be needed to sustain behavioral change.”

Published in the journal Cardiology Clinics, the study was co-written by University of South Florida social work professor Soonhyung Kwon; Alyssa M. Vela, a professor of surgery and of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine; and Katharine S. Edwards, a professor of cardiovascular medicine and of psychiatry and behavioral medicine at Stanford Medicine.

“The findings of this study further point to the importance of attending to mental and behavioral health for cardiovascular disease prevention and cardiovascular health optimization,” Vela said. “This speaks to the need for routine screening and integration of cardiac behavioral medicine to allow for access to important interventions.”

The current study adds to a growing body of research linking psychological well-being — including traits such as optimism, positive affect and gratitude — with cardioprotective benefits.

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Heart disease risk may start in the womb, study finds

Young adults whose mothers had high blood pressure during pregnancy — either pregnancy-associated hypertension, pre-eclampsia or eclampsia — had more signs of early arterial injury, higher blood pressure, higher body mass index and higher blood sugar than peers.

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A child’s future heart health may be partially shaped before they are born, reports a new Northwestern Medicine study that found pregnancy complications are linked to poorer cardiovascular health in offspring more than 20 years later.

The study found that young adults whose mothers had high blood pressure during pregnancy — either pregnancy-associated hypertension, pre-eclampsia or eclampsia — had more signs of early arterial injury, higher blood pressure, higher body mass index and higher blood sugar than peers.

The authors said the study adds to growing evidence that cardiovascular risk may be transmitted across generations through a combination of biological, environmental and behavioral factors.

“That means we must make sure people maintain good health from childhood into young adulthood, so that if or when someone becomes a parent, they pass on the best opportunity for good health to their children,” said study senior author Dr. Nilay Shah, assistant professor of medicine in the division of cardiology at Northwestern University Feinberg School of Medicine.

How the study was conducted

Shah and colleagues evaluated nearly 1,350 mother-child pairs from the Future of Families and Child Well-Being Study, which enrolled mothers and children at birth between 1998 and 2000 across 20 U.S. cities. The children were then followed into adulthood.

Using delivery hospitalization records, the Northwestern scientists first identified whether mothers experienced pregnancy complications, including high blood pressure during pregnancy, gestational diabetes (high blood sugar during pregnancy) or preterm birth (before 37 weeks of pregnancy).

The three pregnancy complications are on the rise, and affect almost one in four pregnancies in the U.S.

The research team then analyzed cardiovascular health of offspring at age 22, using blood pressure measurements, blood testing, body mass index assessments and carotid artery ultrasounds to look for signs of artery injury.

Finally, the scientists compared participants with and without exposure to each pregnancy complication and adjusted for factors like income, education, difference in birth weight and smoking during pregnancy.

Key findings

At around age 22, participants whose mothers had high blood pressure during pregnancy had:

  • Higher body mass index (+2.8 BMI points)
  • Higher diastolic blood pressure (+2.3 mm Hg)
  • Higher blood sugar levels (+0.2% HbA1c)
  • Thicker artery walls (~0.02 mm)

While the difference in artery wall thickness may seem small, the study authors said it corresponds to roughly three to five years of additional vascular aging. That means arteries looked older and less healthy than expected, which raises the risk of future heart disease.

Other pregnancy complications also showed some long-term effect:

  • Exposure to gestational diabetes was linked to worse blood pressure and some evidence of artery thickening
  • Being born preterm was associated with higher blood sugar levels

‘Most heart disease is preventable’

With pregnancy complications on the rise in the U.S., Shah said the study provides compelling evidence that improving health before and during pregnancy could help reduce heart disease risk in the next generation.

“There is evidence that both parents’ health at the time of conception and during pregnancy influences a child’s health,” he said. “So, promoting health from an early age, like exercising regularly, eating healthfully, never smoking and getting enough sleep, is not just meant for an individual, but doing so may help future generations be healthier, too.”

Shah also emphasizes that risk is not destiny.

“The good news is that most heart disease is preventable,” he said. “If you experienced high blood pressure or high blood sugar during pregnancy, or your child was born early, it does not absolutely mean that your child will have worse health as adults. But I would encourage you to pay attention now to your child’s health behaviors.

“What children learn in childhood sets the stage for their health across their lives. If you are wondering whether your children’s behaviors are healthy, or are considering making a change, please speak with your child’s pediatrician for advice and guidance.”

Other Northwestern co-authors include Emily Lam, Abigail Gauen, Dr. Sadiya Khan, Alexa Freedman and Norrina Allen.

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