Brain
on the brain
‘Those infected with the [SARS-CoV-2] virus are at increased risk of developing a range of neurological conditions in the first year after the infection. Such complications include strokes, cognitive and memory problems, depression, anxiety, and migraine headaches.’
Dr. Ziyad Al-Aly (2023)
❦ on the web of dementia
‘All subtypes of dementia, irrespective of patients’ previous dementia types, behaved like rapidly-progressive dementia following COVID-19.
Researchers also found that the characteristics of a particular type of dementia changed following COVID-19, and both degenerative and vascular dementias started behaving like mixed dementia both clinically and radiologically.
A rapidly and aggressively deteriorating course was observed in patients having insidious onset, slowly progressive dementia, and who were previously cognitively stable.’
IOS Press (2023)
❦ on neurodegenerative diseases
“The brains of people who died from COVID-19 were remarkably similar to the brains of people who die from neurodegenerative diseases such as Alzheimer’s and Parkinson’s, showing inflammation and disrupted circuitry.”
Tony Wyss-Coray, Professor of Neurology, Stanford University (2021)
❦ on acute and chronic neurological impacts
‘From mild anosmia [loss of smell] to severe ischemic stroke, the impact of SARS-CoV-2 on the central nervous system is still a great challenge to scientists and healthcare practitioners.
Besides the acute and severe neurological problems described, as encephalopathies, leptomeningitis, and stroke, the chronic impact observed during Long COVID or the post-acute sequelae of COVID-19 (PASC) greatly intrigues scientists worldwide.
Strikingly, even asymptomatic, and mild-diseased patients may evolve with important neurological and psychiatric symptoms such as confusion, memory loss, cognitive decline and chronic fatigue, associated or not with anxiety and depression.’
J.P.S Peron, Associate Professor of Neurology, University of Massachusetts (2023)
❦ on haemorrhage of human foetal cortex
‘Strikingly, the [foetal brain] haemorrhages are predominately found in the late first and early second trimester of gestation.
Specifically, the majority were between 12 and 14 PCW [post conception weeks], a critical window of human foetal brain development when the endothelial tight junctions increase to form the blood-brain barrier.
Our observations of disrupted foetal cerebral vasculature are consistent with reports of damage to the microvasculature of the adult brain in SARS-CoV-2 infected patients.’
Massimo et al / Brain (2023)
❦ on children, mental health issues and neurological problems
‘Children have largely been unaffected by severe COVID-19 [SARS-CoV-2 infection] compared to adults, but data suggest that they may have experienced new conditions after developing the disease.
We found significantly higher risks for some new conditions in exposed children, including mental health issues and neurological problems.
The overall excess risk for new-onset conditions after COVID-19 was 78% higher in the exposed than unexposed children.’
Di Chiara et al / Acta Paediatrica (2023)
❦ on catching a stroke in a café
“A bizarre recurring point of debate:
— “People die every day of lots of other things!”
True, but you don’t catch a stroke or cancer from other people in a restaurant.”
NHS Palliative Medicine Consultant (2023)
❦ fire and predisposition
“If someone is already pre-disposed to Parkinson’s, having COVID-19 could be like pouring more fuel on that ‘fire’ in the brain.
The same would apply for a predisposition for Alzheimer’s and other dementias that have been linked to inflammasomes.”
Trent Woodruff (NHMRC), Professor of Pharmacology, University of Queensland (2022)
❦ the brain & nervous system ~ further reading
❦ This study confirms everything that I have seen in the microscope over the last few years. The authors of the study use a technique called dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), an imaging technique that can measure the density, integrity, and leakiness of tissue vasculature. Comparing all individuals with previous COVID infection to unaffected controls revealed decreased general brain volume in patients with brain fog along with significantly reduced cerebral white matter volume in both hemispheres in the recovered and brain fog cohorts . Covid-19 induces brain volume loss and leaky blood-brain barrier in some patients. How can this be more clear? © 2024 Danielle Beckman. ➲ ❂ 📖 (22 Feb 2024 ~ Nature: Neuroscience) Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment ➤ 📖 (22 Feb 2024 ~ Nature: Neuroscience) Leaky blood–brain barrier in long-COVID-associated brain fog ➤ ➲ Layperson overview: 📖 (February 2024 ~ Genetic Engineering and Biotechnology News) Leaky Blood Vessels in the Brain Linked to Brain Fog in Long COVID Patients ➤ Related: 📖 (7 Feb 2022 ~ Nature: Cardiovascular Research) Blood–brain barrier link to human cognitive impairment and Alzheimer’s disease ➤ ❂ © 2024 Nature .
❦ ‘Although some studies have shown neuroimaging and neuropsychological alterations in post-COVID-19 patients, fewer combined neuroimaging and neuropsychology evaluations of individuals who presented a mild acute infection. Here we investigated cognitive dysfunction and brain changes in a group of mildly infected individuals. We conducted a cross-sectional study of 97 consecutive subjects ( median age of 41 years ) without current or history of psychiatric symptoms (including anxiety and depression) after a mild infection , with a median of 79 days (and mean of 97 days ) after diagnosis of COVID-19. We performed semi-structured interviews, neurological examinations, 3T-MRI scans, and neuropsychological assessments. The patients reported memory loss ( 36% ), fatigue ( 31% ) and headache ( 29% ). The quantitative analyses confirmed symptoms of fatigue ( 83% of participants), excessive somnolence ( 35% ), impaired phonemic verbal fluency ( 21% ), impaired verbal categorical fluency ( 13% ) and impaired logical memory immediate recall ( 16% ). Our group… presented higher rates of impairments in processing speed ( 11.7% in FDT- Reading and 10% in FDT- Counting ). The white matter (WM) analyses with DTI * revealed higher axial diffusivity values in post-infected patients compared to controls. * Diffusion tensor imaging tractography , or DTI tractography, is an MRI (magnetic resonance imaging) technique most commonly used to provide imaging of the brain. Our results suggest persistent cognitive impairment and subtle white matter abnormalities in individuals mildly infected , without anxiety or depression symptoms. One intriguing fact is that we observed a high proportion of low average performance in our sample of patients (which has a high average level of education ), including immediate and late verbal episodic memory, phonological and semantic verbal fluency, immediate visuospatial episodic memory, processing speed, and inhibitory control . Although most subjects did not present significant impaired scores compared with the normative data, we speculate that the low average performance affecting different domains may result in a negative impact in everyday life , especially in individuals with high levels of education and cognitive demands .’ ❂ ❦ Note how these findings might negatively affect daily activities that demand sustained cognitive attention and fast reaction times – such as driving a car or motorbike, or piloting a plane. Consider air-traffic control. Consider the impact on healthcare workers whose occupations combine long periods of intense concentration with a need for critical precision. ❂ 📖 (19 Jan 2024 ~ Nature: Scientific Reports) Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19 ➤ © 2024 Nature .
❦ ‘Alzheimer’s disease (AD) is acknowledged by the World Health Organisation (WHO) as a global public health concern. AD is the primary cause of dementia and accounts for 50–70% of cases. SARS-CoV-2 can damage the peripheral and the central nervous system (CNS) through both direct and indirect pathways, potentially leaving COVID-19 patients at higher risks for neurological difficulties, including depression, Parkinson’s disease, AD, etc., after recovering from severe symptoms. Patients who recovered from severe COVID-19 infection are more likely to acquire stable neuropsychiatric and neurocognitive conditions like depression, obsessive-compulsive disorder, psychosis, Parkinson’s disease, and Alzheimer’s disease. SARS-CoV-2 infection causes immune system dysfunction, which can lead to suppression of neurogenesis, synaptic damage, and neuronal death, all of which are associated with the aetiology of Alzheimer’s disease. Severe systemic inflammation caused by SARS-CoV-2 is predicted to have long-term negative consequences, such as cognitive impairment. Research has demonstrated that SARS-CoV-2-infected AD patients had a higher mortality rate. In a study from the Department of Neuroscience at the University of Madrid, 204 participants with Frontotemporal Dementia (FTD) and Alzheimer’s disease (AD) were enrolled. According to the study, 15.2% of these individuals had COVID-19 infection, and sadly, 41.9% of those who had the virus died as a result of their illness. COVID-19 causes a secondary effect on underlying brain pathologies, as SARS-CoV-2 has been shown to trigger or accelerate neurodegeneration processes that possibly explain long-term neurodegenerative effects in the elderly population. In response to the impact of COVID-19 in 2020, governments worldwide acted promptly by implementing various public health measures. During this period, people with cognitive impairments such as dementia or AD may have experienced greater stress and anxiety due to sudden changes in the environment and people’s behaviour. It is also significantly harder for AD patients to comprehend and execute defensive measures such as wearing face masks and sanitising frequently. ❂ COVID-19 has generated a worldwide outbreak, resulting in a slew of issues for humans, particularly those suffering from Alzheimer’s disease. Its ability to invade the central nervous system through the hematogenous and neural routes, besides attacking the respiratory system, has the potential to worsen cognitive decline in Alzheimer’s disease patients. The severity of this issue must be highlighted.’ ❂ 📖 (8 Jan 2024 ~ Frontiers in Aging Neuroscience) Unravelling the connection between COVID-19 and Alzheimer’s disease: a comprehensive review ➤ © 2024 Shajahan et al / Frontiers in Aging Neuroscience .
❦ Always Covid+ Colleague: — “One of the medical groups. One of the groups. One of the groups...” Moderator: — “Is there something you want to share?” Always Covid+ Colleague: — “I was asked something. I don’t know. It has something to do with something.” This is what Covid is doing to the brain. Unfortunately this is not an isolated incident – but something I’m witnessing all day long throughout the company. ❂ © 2023 Lady Chuan ➲
❦ ‘It is now well established that post-COVID syndrome ( PCS ) represents a serious complication in a substantial number of patients following SARS-CoV-2 infection. PCS is diagnosed when COVID-19-related symptoms persist for more than 3 months. It can occur even after an initially mild to moderate course of infection , and comprise a large variety of symptoms . Around 30% of PCS patients show neurological and neuropsychiatric sequelae , such as fatigue , depressive symptoms , and cognitive dysfunction . These are experienced as particularly debilitating, as they have detrimental effects on daily functioning in PCS patients and hamper a successful return to their jobs. Fatigue is a frequent and one of the most debilitating symptoms in post-COVID syndrome (PCS). Recently, we proposed that fatigue is caused by hypoactivity of the brain’s arousal network and reflected by a reduction of cognitive processing speed . Eighty-eight PCS patients with cognitive complaints and 50 matched healthy controls underwent neuropsychological assessment. Seventy-seven patients were subsequently assessed at 6-month follow-up. Patients showed cognitive slowing indicated by longer reaction times compared to control participants in a simple-response tonic alertness task and in all more complex tasks requiring speeded performance . Reduced alertness correlated with higher fatigue . Alertness dysfunction remained unchanged at 6-month follow-up and the same was true for most attention tasks and cognitive domains .’ ❂ 📖 (7 Nov 2023 ~ Journal of Neurology) Persistent cognitive slowing in post-COVID patients: longitudinal study over 6 months ➤ © 2023 Journal of Neurology .
➲ A layperson-level overview from New Atlas on how all variants of SARS-CoV-2 – the virus that causes COVID-19 – are ‘neuroinvasive’ , meaning that all can infect or enter the brain and the nervous system . ❂ ❦ ‘... We know COVID is associated with a variety of neurological symptoms , both short- and long-term, but it still isn’t entirely clear whether these cognitive issues are the result of the virus directly infecting brain cells or simply due to a broader systemic inflammatory response. Studies looking at human brain tissue have yielded contradictory results. Some have found direct traces of SARS-CoV-2 , while others report only inflammatory damage . Animal models certainly demonstrate it is possible for the virus to infect the brain, but human tissue samples are obviously taken after a patient dies – meaning researchers can only hypothesize what happens during an acute infection. Using a hamster model, the research compared infection with the original SARS-CoV-2 virus from 2020 to several subsequent variants including Gamma, Delta and Omicron/BA.1 variants. Interestingly, the findings confirmed epidemiological observations showing acute disease severity is reduced in Omicron infections – however, all [SARS-CoV-2] variants demonstrated similar neuroinvasive capabilities. And, most strikingly, all variants infected the brain’s olfactory regions regardless of whether symptoms of anosmia (the loss of sense of smell) were present or not. “This suggests that anosmia and neuronal infection are two unrelated phenomena. If we follow this line of reasoning, it is quite possible that even an asymptomatic infection is characterized by the spread of the virus in the nervous system.” The researchers conclude this suggests all SARS-CoV-2 variants have the capacity to infect the brain, via the olfactory pathway, regardless of clinical disease presentations. This means it is possible even mild infections can lead to the virus infiltrating the brain. “The next step will be to understand... whether the virus is able to persist in the brain beyond the acute [initial, short-term] phase of infection, and whether the presence of the virus can induce persistent inflammation and the symptoms described in cases of long COVID, such as anxiety, depression and brain fog” [brain damage].’ © 2023 Rich Haridy / New Atlas. ➲ Source © 2023 Institut Pasteur .
❦ Your brain is a vast city. The roads (myelin) in this city let cars move efficiently. Oligodendrocytes are the construction workers who maintain these roads. As we age, these workers slow down, causing traffic jams and slower thoughts. Enter SARS-CoV-2, the destructive rioter. It doesn’t just disrupt traffic; it damages the roads and chases away the construction crews. Weeks after the riot, the city still struggles to function, with long-lasting road damages and traffic jams. This is the ‘brain fog’ of post-COVID life. ❂ 📖 (24 Sep 2023 ~ Aging and Disease) Role of Microglia, Decreased Neurogenesis and Oligodendrocyte Depletion in Long COVID-Mediated Brain Impairments ➤ © 2023 Outbreak Updates ➲
❦ ‘We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone ( GnRH ), the master molecule regulating reproduction , and cognitive deficits during pathological aging , including Down syndrome and Alzheimer’s disease. Olfactory and cognitive alterations , which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline . We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin , favouring post-COVID cognitive or neurological symptoms , and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes . Furthermore, GnRH neurons themselves were dying in all patient brains studied , dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia , from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection . Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive , metabolic , and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups .’ ❂ 📖 (12 Sep 2023 ~ eBioMedicine: Lancet Discovery Science) Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death ➤ © 2023 eBioMedicine: Lancet Discovery Science .
❦ Children have largely been unaffected by severe COVID-19 compared to adults, but data suggest that they may have experienced new conditions after developing the disease. We compared 1656 exposed and 1656 unexposed children from 1 February 2020 to 30 November 2021. We found significantly higher risks for some new conditions in exposed children, including mental health issues and neurological problems . The overall excess risk for new-onset conditions after COVID-19 was 78% higher in the exposed than unexposed children. ❂ 📖 (9 Sep 2023 ~ Acta Paediatrica) Comparative study showed that children faced a 78% higher risk of new-onset conditions after they had COVID-19 ➤ © 2023 Di Chiara et al / Acta Paediatrica.
❦ When someone shows a severe personality shift, there could be many reasons. One possibility? Their brain may have been affected by COVID-19. It’s crucial to approach with empathy, to consider all potential causes, and to consult healthcare professionals. Don’t jump to conclusions, but stay informed. © 2023 Dr. Sean Mullen . ➲
❦ Researchers at The University of Queensland have discovered viruses such as SARS-CoV-2 can cause brain cells to fuse, initiating malfunctions that lead to chronic neurological symptoms. SARS-CoV-2, the virus that causes COVID-19, has been detected in the brains of people with 'Long COVID' months after their initial infection. "We discovered COVID-19 causes neurons to undergo a cell fusion process, which has not been seen before," Professor Hilliard said. "After neuronal infection with SARS-CoV-2, the spike S protein becomes present in neurons, and once neurons fuse, they don't die." "They either start firing synchronously, or they stop functioning altogether." As an analogy, Professor Hilliard likened the role of neurons to that of wires connecting switches to the lights in a kitchen and a bathroom. "Once fusion takes place, each switch either turns on both the kitchen and bathroom lights at the same time, or neither of them," he said. "It's bad news for the two independent circuits." The discovery offers a potential explanation for persistent neurological effects after a viral infection. "In the current understanding of what happens when a virus enters the brain, there are two outcomes – either cell death or inflammation," Dr Martinez-Marmol said. "But we've shown a third possible outcome, which is neuronal fusion." Dr Martinez-Marmol said numerous viruses cause cell fusion in other tissues, but also infect the nervous system and could be causing the same problem there. "These viruses include HIV, rabies, Japanese encephalitis, measles, herpes simplex virus and Zika virus," he said. “Our research reveals a new mechanism for the neurological events that happen during a viral infection. “This is potentially a major cause of neurological diseases and clinical symptoms that is still unexplored.” ❂ 📖 (7 June 2023 ~ Science Advances) SARS-CoV-2 infection and viral fusogens cause neuronal and glial fusion that compromises neuronal activity ➤ 📖 (8 June 2023 ~ Queensland Brain Institute) COVID-19 can cause brain cells to 'fuse' ➤ © 2023 Martinez-Marmol & Hilliard / Queensland Brain Institute / University of Queensland.
❦ A bizarre recurring point of debate: “People die every day of lots of other things!” True, but you don’t catch a stroke or cancer from other people in a restaurant. © 2023 NHS Medical Consultant . ➲
❦ What if Covid has been causing mass cognitive impairment and we are all living in an increasingly stupid society? Mad things could happen with that: imagine if hospitals got rid of masks or people started to believe Covid was just a cold? I know that’s far-fetched, but imagine! ❂ © 2023 NHS Medical Consultant . ➲
❦ The results presented here reveal that at least 85% [of the 214 patients with post COVID-19 syndrome] exhibit deficits in one neuropsychological test . Also, the youngest patients were those who showed the most marked and heterogeneous cognitive impairment , while the oldest patients maintained their cognitive functions preserved to a greater extent with only a mild impairment in attention and speed processing. ❂ 📖 (19 Apr 2023 ~ Nature: Scientific Reports) Cognitive impairment in young adults with post COVID-19 syndrome ➤ © 2023 Herrera et al / Nature.
❦ The Linseman Laboratory is studying the long-term brain health effects of COVID-19 in individuals with and without traumatic brain injury (TBI). Preliminary data suggest that those with a history of both COVID-19 and TBI experience more severe Long COVID symptoms, a higher symptom burden , and more frequent symptoms . Those who reported having COVID-19 and TBI reported worse depressive symptoms , worse functional outcomes , and increased fatigue . ❂ 📖 (4 Apr 2023 ~ SciTechDaily) Researchers Discover Connection Between Traumatic Brain Injury and Long COVID ➤ © 2023 Linesman Laboratory / University of Denver / SciTechDaily.
❦ From mild anosmia to severe ischemic stroke , the impact of SARS-CoV-2 on the central nervous system is still a great challenge to scientists and healthcare practitioners. Besides the acute and severe neurological problems described, as encephalopathies , leptomeningitis , and stroke , the chronic impact observed during Long COVID or the post-acute sequelae of COVID-19 (PASC) greatly intrigues scientists worldwide. Strikingly, even asymptomatic , and mild-diseased patients may evolve with important neurological and psychiatric symptoms such as confusion , memory loss , cognitive decline and chronic fatigue , associated or not with anxiety and depression . ❂ 📖 (1 Apr 2023 ~ Human Genetics) Direct and indirect impact of SARS-CoV-2 on the brain ➤ © 2023 J.P.S Peron / Human Genetics.
❦ The possible neurological consequences of SARS-CoV-2 infection, associated with physical and cognitive frailty, could lead to a worsening of Parkinson’s disease (PD) in infected patients or – more rarely – to an increase in the Parkinsonian symptomatology . Parkinson’s disease (PD) or Parkinsonism has been described after infections with viruses , such as the Epstein-Barr virus , hepatitis C virus , HIV , influenza A virus , Japanese encephalitis virus , varicella zoster virus , or West Nile virus . Therefore, the hypothesis that SARS-CoV-2 may have even longer-term effects on the brain and lead to an increase in cases of Parkinson’s disease, as occurred in the years following the Spanish flu , has been put forward. ❂ 📖 (23 Mar 2023 ~ Brain Science) Parkinson’s Disease, SARS-CoV-2, and Frailty: Is There a Vicious Cycle Related to Hypovitaminosis D? ➤ © 2023 Palermo et al / Brain Science.
❦ It's no wonder that depression and PTSD rates ✢ are up in people living with Long COVID. ✢ Long COVID: major findings, mechanisms and recommendations ➤ There are no approved therapies for the physical or cognitive disabilities that now plague 65 million people around the world, a conservative estimate given the degree of undocumented cases. It is now clear from US and UK investigations of approximately 2,000 previously hospitalized Covid patients that six months later more than half have problems managing finances and paying bills as well as completing everyday activities like preparing meals, bathing, getting dressed, or walking across a room. But what exactly is going on inside the brains of these people from a biological and pathological perspective? Autopsy studies show that the virus can persist ✢ in some people for many months even though they have no symptoms and test negative for the virus. ✢ Persistent SARS-CoV-2 infection in patients seemingly recoveredfrom COVID-19 ➤ Brains donated by people who died of Covid-19 also show widespread problems in the cells lining the blood vessels and exaggerated clotting, supporting the idea of Covid-19 as a blood flow disorder ✢ that brings on brain disease. ✢ Neurovascular injury with complement activation and inflammation in COVID-19 ➤ Perhaps the most harrowing thing I have done in 30 years as a physician-scientist has been to ask family members I'd never met, often in the middle of the night via telephone during the height of the Covid surges, if I and my colleagues could study their loved one's brain. In a study we conducted of 20 of these priceless brain donations ✢ , we found brain swelling due to decreased blood flow and heightened activity in microglial cells, the so-called 'white matter' in brains that support the neurons that transmit thoughts and help store information. We saw this even in young previously healthy individuals. ✢ Brain autopsies of critically ill COVID-19 patients demonstrate heterogeneous profile of acute vascular injury, inflammation and age-linked chronic brain diseases ➤ A study from the National Institutes of Health of 44 complete autopsies ✢ mapped and quantified the distribution of SARS-CoV-2 and showed it was widely distributed throughout the body, including in the hypothalamus and cerebellum in the brain and neurons in the spinal cord. ✢ SARS-CoV-2 infection and persistence in the human body and brain at autopsy ➤ Especially relevant to Long Covid, viral fragments were detected in some of the brains of people who died many months after symptom onset. In Their Own Words Barbara Nivens, who retired from retail management at age 59, has been diagnosed by her neurologist as having rapid onset dementia due to Covid-19. An incredibly thorough medical work-up found no plausible causes for this dementia other than its onset following her Covid infection, which she contracted before the vaccine was available. Matt Fitzgerald, age 26, is a mechanical engineer who worked for Tesla and now designs surgical devices – when he can. Since recovering from his initial bout with Covid-19, he's developed a condition characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) known as post-exertional malaise, which is why even slight exertion leaves him and millions like him inexplicably incapacitated. ❦ Barbara Nivens: — “I walk down the hall and see dozens of pictures of family trips and feel like a ghost because I don't remember any of them. Now I'm trying to figure out who Barbara 2.0 is going to be.” (Her husband, tearing up as he listened to her, said softly, “I just want my wife back.”) ❦ Matt Fitzgerald: — “I feel like I'm underwater. When you talk to me, I can hear you, but my brain does not understand the words. I can't comprehend what you're saying. I have no intellectual capacity or energy to digest data. At work my brain is just begging for rest. I struggle with finding words and completing tasks in a timely manner. It's the worst. I'll be in a meeting and know exactly what I want to say before I say it. I'll start saying it and I'll get to a word, and I just cannot think of the word. I'll just be like, ‘Give me a moment,’ and I'll go through my brain cycling through words. This week it was 'consistent'. I couldn't think of the word 'consistent'. I kept thinking it was 'coincident' or 'concentric' or 'constant'.” Such problems in executive function, memory, and processing speed are what many people complain about in the Long COVID support groups. Science validates their injuries. A picture is emerging from animal models showing how on-going inflammation of glial cells disrupts the electrical conduction highways in the brain's white matter that link to and support the neurons in gray matter. It's as if the bridges (white matter) linking different territories of the brain have been blown up and the land itself (nerves in the cerebral cortex and hippocampus) becomes scorched, leaving people with Long COVID plagued by thinking and memory deficits. ❂ 📖 (16 Feb 2023 ~ Stat) The haunting brain science of Long COVID ➤ © 2023 E. Wesley Ely / Stat.
❦ Cognitive postscripts of COVID-19 , codenamed as ‘cognitive COVID' or ‘brain fog’, characterized by multi-domain cognitive impairments, are now being reckoned as the most devastating sequelae of COVID-19 . The rapid progression of dementia , the addition of further impairments/deterioration of cognitive abilities , and the increase or new appearance of white matter lesion burden suggest that previously compromised brains have little defense to withstand a new insult (i.e., a ‘second hit’-like infection/dysregulated immune response, and inflammation). ❂ 📖 Related: (4 Apr 2023 ~ Eurekalert) New study shows SARS-CoV-2 infection accelerates the progression of dementia ➤ ‘ All subtypes of dementia , irrespective of patients' previous dementia types, behaved like rapidly-progressive dementia following COVID-19 .’ 📖 Related: (4 Apr 2023 ~ NeuroscienceNews) COVID-19 Infection Accelerates the Progression of Dementia ➤ ‘A rapidly and aggressively deteriorating course was observed in patients having insidious-onset, slowly-progressive dementia, and who were previously cognitively stable .’ ❂ 📖 (14 Feb 2023 ~ Journal of Alzheimer's Disease Reports) The Effects of SARS-CoV-2 Infection on the Cognitive Functioning of Patients with Pre-Existing Dementia ➤ © 2023 Dubey et al / Journal of Alzheimer’s Disease Reports.
❦ ‘Acute ischemic stroke (AIS) is a fearful complication of Coronavirus Disease-2019 (COVID-19). SARS-CoV-2 infection seems to play a major role in endothelium activation and infarct volume extension during AIS.’ ❂ 📖 (10 Jan 2023 ~ Frontiers in Cardiovascular Medicine) SARS-CoV-2 infection predicts larger infarct volume in patients with acute ischemic stroke ➤ © 2023 Frontiers in Cardiovascular Medicine .
❦ Strikingly, the [foetal brain] haemorrhages are predominately found in the late first and early second trimester of gestation , a period of development in which the effect of the COVID-19 pandemic has not been thoroughly investigated. Specifically, the majority were between 12 and 14 pcw, a critical window of human foetal brain development when the endothelial tight junctions increase to form the blood-brain barrier . Our observations of disrupted foetal cerebral vasculature are consistent with reports of damage to the microvasculature of the adult brain in SARS-CoV-2 infected patients . ❂ 📖 (16 Jan 2023 ~ Brain) Haemorrhage of human foetal cortex associated with SARS-CoV-2 infection ➤ © 2023 Massimo et al / Brain.
❦ ‘The narrative that COVID-19 had only respiratory sequelae led to a delayed realization of the neurological, cardiovascular and other multi-system impacts of COVID-19. Long COVID is a multi-systemic illness encompassing ME / CFS , dysautonomia , impacts on multiple organ systems , and vascular and clotting abnormalities . Circulatory system disruption includes endothelial dysfunction and subsequent downstream effects, and increased risks of deep vein thrombosis , pulmonary embolism and bleeding events . Microclots detected in both acute COVID-19 and long COVID contribute to thrombosis.’ ✻ Endothelial dysfunction precedes atherosclerosis and is an independent predictor of cardiovascular events. Atherosclerosis is a condition where plaque , a sticky substance made up of fat, cholesterol, calcium, and other substances found in the blood, hardens and narrows the arteries , limiting the flow of oxygen-rich blood to the body . Deep vein thrombosis ( DVT ) is a blood clot that forms in a deep vein , usually in the pelvis , calf , or thigh . A pulmonary embolism [ PE ] is a blood clot that blocks and stops blood flow to an artery in the lung . Often the clot starts in a leg and travels to the lung. ‘Long-term changes to the size and stiffness of blood cells have also been found in long COVID, with the potential to affect oxygen delivery. A long-lasting reduction in vascular density , specifically affecting small capillaries, was found in patients with long COVID 18 months after infection . Long COVID has already debilitated millions of individuals worldwide, and that number is continuing to grow. On the basis of more than two years of research on Long COVID and decades of research on conditions such as ME/CFS, a significant proportion of individuals with Long COVID may have lifelong disabilities if no action is taken. Diagnostic and treatment options are currently insufficient , and many clinical trials are urgently needed to rigorously test treatments that address hypothesized underlying biological mechanisms, including viral persistence, neuroinflammation, excessive blood clotting and autoimmunity.’ ❂ 📖 (13 Jan 2023 ~ Nature Reviews: Microbiology) Long COVID: major findings, mechanisms and recommendations ➤ © 2023 Davis et al / Nature .
❦ Globally, millions of people have contracted COVID-19 over the past few years, and some have even caught the virus two or more times. Of more than 665 million cases worldwide, nearly one in two people with COVID-19 is at risk of developing Post-COVID-19 Neurological Syndrome (PCNS). Symptoms of Post-COVID-19 Neurological Syndrome (PCNS) mimic some of the symptoms we see after a stroke, and younger adults seem to be at particular risk. It’s worth noting that a link between brain health and Coronavirus infections has been known since 2006, so in this context the long-term impact of COVID-19 on the brain may arguably be the expectation rather than the exception. Nearly one in two people who have reportedly recovered from acute COVID-19 cite disabling fatigue – that is, fatigue lasting more than twelve weeks – coupled with a series of attention and cognitive deficits similar to persistent post-stroke neurological symptoms. We have already reported on the shared pathobiology between stroke and COVID-19 at a cellular level. So, it should not be surprising to see the long-term impact on the brain with a persistent inflammatory response (potentially due to viral persistence, immune dysregulation or autoimmunity). ❂ 📖 Related: (1 Jan 2023 ~ The Lancet) The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: A systematic review and meta-analysis ➤ 📖 Related: (7 Mar 2022 ~ Nature) SARS-CoV-2 is associated with changes in brain structure in UK Biobank ➤ 📖 Related: (12 Jan 2021 ~ Australian Journal of General Practice) COVID-19 and long-term neurological problems: Challenges ahead with Post-COVID-19 Neurological Syndrome ➤ 📖 Related: (1 Feb 2006 ~ Nature Reviews Microbiology) Coronavirus infection of the central nervous system: host-virus stand-off ➤ 📖 Related: (28 Jan 2021~ Frontiers in Neurology) COVID-19 Pathophysiology Predicts That Ischemic Stroke Occurrence Is an Expectation, Not an Exception - A Systematic Review ➤ ❂ 📖 (6 Jan 2023 ~ University of Melbourne) What we now know about long COVID and our brains ➤ © 2023 Wijeratne et al / University of Melbourne.
❦ ‘In 2021, SARS-CoV-2-related severe neurologic involvement in US hospitalized children and adolescents showed a potential increase in diagnoses of acute central nervous system infections / demyelination. In this case series of 2168 US patients younger than 21 years hospitalized for acute COVID-19 (34%) or multisystem inflammatory syndrome in children (66%), 476 (22%) had neurologic involvement. Of these, 42 (9%) had life-threatening conditions, with 23 (55%) having acute central nervous system (CNS) infections / demyelination; 18 of 42 (43%) died or had new neurologic deficits; and most vaccine-eligible patients were unvaccinated.’ ❂ 📖 (1 Jan 2023 ~ JAMA Network / Neurology) Changes in Distribution of Severe Neurologic Involvement in US Pediatric Inpatients With COVID-19 or Multisystem Inflammatory Syndrome in Children in 2021 vs 2020 ➤ 📖 Related: (5 Jan 2023 ~ Neurology Today) Nearly One-Fifth of Hospitalized Children and Adolescents with SARS-CoV-2 or MIS-C Have Persistent Neurologic Complications ➤ © 2023 LaRovere et al / JAMA: Neurology.
❦ COVID-19 is an acute respiratory disease often accompanied by neurological sequelae. Individuals with previous severe COVID-19 exhibit a 10-year average drop in their global cognitive performance , mimicking accelerated aging . Complementary studies combining neuroimaging and cognitive screening implicate COVID-19-induced impairment of the frontal cortex, a critical area for cognitive function. Our findings indicate that COVID-19 is associated with molecular signatures of brain aging . ❂ 📖 (5 Dec 2022 ~ Nature Aging) Severe COVID-19 is associated with molecular signatures of aging in the human brain ➤ © 2023 Mavrikaki et al / Nature: Aging.
❦ Research led by The University of Queensland has found COVID-19 activates the same inflammatory response in the brain as Parkinson’s disease. “We studied the effect of the virus on the brain’s immune cells, ‘microglia’ which are the key cells involved in the progression of brain diseases like Parkinson’s and Alzheimer’s,” Professor Woodruff said. “Our team grew human microglia in the laboratory and infected the cells with SARS-CoV-2, the virus that causes COVID-19. “We found the cells effectively became ‘angry’, activating the same pathway that Parkinson’s and Alzheimer’s proteins can activate in disease, the inflammasomes.” Dr Albornoz Balmaceda said triggering the inflammasome pathway sparked a ‘fire’ in the brain, which begins a chronic and sustained process of killing off neurons . “It’s kind of a silent killer , because you don’t see any outward symptoms for many years,” Dr Albornoz Balmaceda said. “It may explain why some people who’ve had COVID-19 are more vulnerable to developing neurological symptoms similar to Parkinson’s disease .” The researchers found the spike protein of the virus was enough to start the process and was further exacerbated when there were already proteins in the brain linked to Parkinson’s. “So if someone is already pre-disposed to Parkinson’s , having COVID-19 could be like pouring more fuel on that ‘fire’ in the brain,” Professor Woodruff said. “The same would apply for a predisposition for Alzheimer’s and other dementias that have been linked to inflammasomes.” ❂ 📖 (1 Nov 2022 ~ The University of Queensland, Australia) ‘ A silent killer’ – COVID-19 shown to trigger inflammation in the brain ➤ © 2022 Woodruff & Balmaceda / The University of Queensland, Australia.
❦ Our results show that in the postacute phase of COVID-19, there was increased risk of an array of incident neurologic sequelae including ischemic and hemorrhagic stroke , cognition and memory disorders , peripheral nervous system disorders , episodic disorders (for example, migraine and seizures ), extrapyramidal and movement disorders , mental health disorders , musculoskeletal disorders , sensory disorders , Guillain-Barré syndrome , and encephalitis or encephalopathy . ❂ 📖 Related: (22 Sep 2022 ~ Washington University School of Medicine in St. Louis) COVID-19 infections increase risk of long-term brain problems ➤ Those who have been infected with the [SARS-CoV-2] virus are at increased risk of developing a range of neurological conditions in the first year after the infection. Such complications include strokes, cognitive and memory problems, depression, anxiety and migraine headaches. Additionally, the post-COVID brain is associated with movement disorders, from tremors and involuntary muscle contractions to epileptic seizures, hearing and vision abnormalities, and balance and coordination difficulties as well as other symptoms similar to what is experienced with Parkinson’s disease. ❂ 📖 (22 Sep 2022 ~ Nature Medicine) Long-term neurologic outcomes of COVID-19 ➤ © 2022 Xu, Xie & Al-Aly / Nature: Medicine.
❦ ‘Older people who were infected with COVID-19 show a substantially higher risk – as much as 50% to 80% higher than a control group – of developing Alzheimer’s disease within a year, according to a study of more than 6 million patients 65 and older. In a study published today in the Journal of Alzheimer’s Disease, researchers report that people 65 and older who contracted COVID-19 were more prone to developing Alzheimer’s disease in the year following their COVID diagnosis. And the highest risk was observed in women at least 85 years old. The findings showed that the risk for developing Alzheimer’s disease in older people nearly doubled (0.35% to 0.68%) over a one-year period following infection with COVID. The researchers say it is unclear whether COVID-19 triggers new development of Alzheimer’s disease or accelerates its emergence. “The factors that play into the development of Alzheimer’s disease have been poorly understood, but two pieces considered important are prior infections, especially viral infections, and inflammation,” said Pamela Davis, Distinguished University Professor and The Arline H. and Curtis F. Garvin Research Professor at the Case Western Reserve School of Medicine, the study’s co-author. Previous COVID-related studies led by CWRU have found that people with dementia are twice as likely to contract COVID.’ 📖 (13 Sep 2022 ~ Science Daily / Case Western Reserve University) Risk factor for developing Alzheimer's disease increases by 50-80% in older adults who caught COVID-19 ➤ ❂ 📖 (13 Sep 2022 ~ Journal of Alzheimer’s Disease) Association of COVID-19 with New-Onset Alzheimer’s Disease ➤ © 2022 Journal of Alzheimer’s Disease / Science Daily .
❦ So, we want to ‘live with the virus’. Is there any evidence of this occurring successfully anywhere? Yes! In bats... and it has taken 64 million years of evolution ✢ to get there. 📖 (20 Jan 2021 ~ Nature) Lessons from the host defences of bats, a unique viral reservoir ➤ To ‘live with the virus’, bats have better host defences – they don’t overdo inflammation, and they can get rid of toxic compounds and deal with reactive oxygen species much better than humans. They literally live with the virus . For humans to ‘live with the virus’, we would need to have similar mechanisms to permit SARS-CoV-2 to be part of our biome – without causing all of the autoimmune disease and other damage. We would have to have fundamentally different biochemistry and immune systems. We can mimic this using therapeutics to some extent, and this may help us treat Long COVID. However, I don’t think that we will naturally become resilient to SARS-CoV-2 for a very long time. What I’m trying to say is that mass-infecting this generation of children is unlikely to result in them developing a bat-like immune system within their lifetimes. It’s ridiculous that the attempt was ever made. I genuinely think that putting ventilation upgrades into every building and wearing good-quality masks will be easier than building a genetically modified SARS-resistant human. I keep trying to give you the easy way out! The coronavirus is moving into our bodies and is attempting to stay there, just like it does in bats. The problem is that our bodies try to fight it. We fight it well enough to reduce detectable virus-shedding on our breath, but there is evidence (persistent spike RNA) that the virus is hiding somewhere else in our body anyway. So our bodies keep fighting it. The collateral damage is the problem. What are our choices? 1. Figure out how to change human physiology so that we don’t burn ourselves out fighting an elusive and persistent enemy. 2. Or figure out how we can stop transmission. The second is easier, and economically sound. The ability to completely clear coronavirus is also a potential goal – but again, therapeutics will be needed because we have places where, if the immune system is left to do it, it causes damage – and coronavirus has many tricks to help it hide from detection. Needless to say, coronavirus can evolve a lot faster than we can, so we need to use our brain cells in a different way to fight COVID-19. Instead of using microglia, we need to think ...
❦ ‘The prevalence of Long COVID in children and adolescents was 25.24% . The five most prevalent clinical manifestations were mood symptoms (16.50%), fatigue (9.66%), sleep disorders (8.42%), headache (7.84%), and respiratory symptoms (7.62%). Interestingly, many of the symptoms identified in these meta-analyses associated to Long COVID, such as mood, fatigue, sleep disorders, orthostatic intolerance, decreased concentration, confusion, memory loss, balance problems, exercise intolerance, hyperhidrosis, blurred vision, body temperature dysregulation, dysfunction on heart, rate variability and palpitations, constipation or diarrhea, and dysphagia, are commonly present in dysautonomia .’ ❂ 📖 (23 Jun 2022 ~ Nature Scientific Reports) Long COVID in children and adolescents: a systematic review and meta-analyses ➤ © 2022 Lopez-Leon et al / Nature.
❦ ‘In this analysis of 222 offspring of mothers infected with SARS-CoV-2, compared with the offspring of 7550 mothers in the control group (not infected) delivered during the same period, we observed neurodevelopmental diagnoses to be significantly more common among exposed offspring, particularly those exposed to third-trimester maternal infection . The majority of these diagnoses reflected developmental disorders of motor function or speech and language .’ ❂ 📖 (9 Jun 2022 ~ JAMA: Pediatrics) Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy ➤ © 2022 Edlow et al / JAMA: Pediatrics.
❦ ‘The authors performed a survey in children suffering from persistent symptoms since initial infection. A total of 510 children infected between January 2020 and January 2021 were included. Symptoms such as fatigue, headache, muscle and joint pain, rashes and heart palpitations and issues such as lack of concentration and short-term memory problems were particularly frequent and confirm previous observations, suggesting that they may characterize this condition.’ ❂ 📖 (1 Apr 2022 ~ Future Microbiology) Clinical characteristics, activity levels and mental health problems in children with long coronavirus disease: a survey of 510 children ➤ © 2022 Buonsenso et al / Future Microbiology.
❦ Headaches are one of the most common non-respiratory symptoms associated with SARS-CoV-2 and COVID-19. In fact, for most, a headache was the first initial symptom of the infection. For many, the headaches resolve after recovery from the acute infection. However, headaches are also one of the most common symptoms experienced by those with Long COVID. These migraine-like headaches can often last for weeks or even months, leaving many unable to perform routine daily activities. ❦ Headaches are a main symptom of acute COVID-19 While originally considered a respiratory virus, respiratory symptoms are not always the first indicator of a COVID infection. For example, for many, the first symptom is the loss of taste and/or smell ('anosmia'). Researchers believe that this may occur due to the virus entering the nasal cavity and crossing over into the brain. In this same way, many people often experience a severe headache in addition to the anosmia. ❦ How is a COVID headache different to a migraine? Many describe a COVID headache as crushing pain spread throughout the skull that can cause a pulsing or pressing pain. This pain typically worsens with physical activity or movement of the head. For this reason, many often refer to it as a migraine. However, a migraine is considered a primary headache. A COVID headache, on the other hand, is considered a secondary headache due to an underlying condition – in this case, the SARS-CoV-2 viral infection. While both types of headaches produce moderate to severe pain intensity, there are some differences between a traditional migraine and a COVID headache. COVID headache vs. migraine: ❦ Missing common additional symptoms ~ Migraines often come with nausea, vomiting, and a sensitivity to light and sound. In addition, many often experience an aura before headache onset. None of these symptoms typically accompany a COVID headache. ❦ Different pain ~ In many cases, migraines occur unilaterally, or on one side. COVID headaches are typically bilateral and affect the entire head. ❦ Do not respond to medication ~ If you have a history of migraines and take prescribed medication, you may find the COVID headache does not respond. In fact, a COVID headache is unlikely to respond to traditional headache medications in general, including over-the-counter pain medications such as acetaminophen or ibuprofen. Headaches continue with Long COVID Lingering headaches are not uncommon after viral infections, so it was no surprise to see headaches become a symptom associated with Long COVID. However, the persistence and severity of headaches with Long COVID has been different than with previous viral infections. While many of these headaches do improve on their own over time, many people continue to struggle with severe headaches that can last for weeks or months. In many cases, people will have a baseline headache that gets worse from time to time, along with other Long COVID symptoms. What is causing COVID headaches? [At the time of writing (24 Feb 2022)] the exact cause of these COVID headaches is unknown. However, researchers and clinicians have some theories. 1. Researchers propose that the trigeminal nerve endings in the nasal cavity may sustain direct viral damage that activates the trigeminovascular system, resulting in headaches, as well as other cognitive symptoms. 2. Studies are showing that many COVID patients are experiencing unusual microclots in their blood after recovering from the acute infection. These microclots can prevent adequate oxygen transportation throughout the body and contribute to Long COVID symptoms, including headaches. 3. Neurological damage has been seen in many COVID and Long COVID patients, but the exact cause of this damage is still unknown. Some theories believe that the virus may be able to cause direct damage to the brain by entering through the olfactory bulb or through the bloodstream or nerve endings. In addition, as your body fights the virus, your immune system often goes into overdrive, creating autoantibodies that attack healthy cells within the body and cause damage. 4. Jaw or dental concerns. ❂ 📖 Related: (19 July 2021 ~ Nature / Scientific Reports) Frequency and phenotype of headache in Covid-19: a study of 2194 patients ➤ 📖 Related: (15 May 2020 ~ Headache: The Journal of Head and Face Pain) COVID-19 is a Real Headache! ➤ 📖 Related: (9 May 2022 ~ Preprint) Combined triple treatment of fibrin amyloid microclots and platelet pathology in individuals with Long COVID / Post-Acute Sequelae of COVID-19 (PASC) can resolve their persistent symptoms ➤ ❂ 📖 (24 Feb 2022 ~ RTHM) Long COVID: Migraines and Headaches ➤ © 2022 RTHM.
❦ It has long been suspected by scientists that the flu (influenza) might play a role in developing Parkinson’s disease (PD) later in life. Compared to those who were not diagnosed with the flu, there was a 90% higher risk of PD for those who had the flu 15 or more years earlier. Inflammation is clearly a factor in PD – and influenza is known to trigger an extreme inflammatory response in the body. In light of the COVID-19 pandemic, and its known neurological consequences such as brain fog and loss of smell, continued robust research into how inflammation impacts the brain is warranted. ❂ 📖 (22 Feb 2022 ~ Parkinson's Foundation) The Flu Factor: Is There a Link to Parkinson's? ➤ © 2022 Parkinson’s Foundation.
❦ SARS-CoV-2 infection in pregnancy is known to confer a risk of increased morbidity and mortality for the mother. Placental and fetal infection with SARS-CoV-2 have been rare to date; SARS-CoV-2 infection in pregnancy appears most likely to impact fetal brain development via maternal and placental immune activation. Maternal and placental immune activation may impact the placenta and developing fetal brain via induction of immune activation and proinflammatory cytokine production, dysregulation of serotonin/other neurotransmitter signaling, and increased oxidative stress. ❂ 📖 (13 Feb 2022 ~ Trends in Molecular Medicine) COVID-19 in pregnancy: implications for fetal brain development ➤ © 2022 Shook et al / Trends in Molecular Medicine.
❦ SARS-CoV-2 infection, moderated in severity by age-, sex-, and race/ethnicity-dependent factors, initiates a disease progression that has the potential to promote cognitive decline and exacerbate pre-existing dementia. The damage cascade of COVID-19 is multi-faceted and interdependent, with multiple pathways that could lead to cognitive hazard mechanisms. One such cognitive hazard mechanism, cerebral direct infection, is possible with the SARS-CoV-2 virus, exhibiting neuroinvasive and neurotropic characteristics with neurovirulent potential. The greatest cognitive risk though may be from immune-mediated damage originating as cytokine storms that have far-reaching consequences for multiple organ systems, including the brain. Damage to organ systems and detrimental immune response, across the disease progression of COVID-19, may affect cognition via cerebral ischemia, hypoxia/acidosis, and neuroinflammation. The initiation of a coagulation cascade, from excessive immune response, which can generate micro-/macro-thromboemboli also poses significant risk. While long-term cognitive outcomes have not been fully evaluated, emerging reports indicate high rates of long-term symptoms and cognitive alterations in recovered COVID-19 patients. Due to these plausible COVID-19 cognitive decline pathways, evidence of prevalent neurological symptoms in patients, and long-term symptoms in recovered individuals, our conclusion is that COVID-19 represents a credible risk for cognitive decline and has the potential to exacerbate pre-existing dementia. For those at higher baseline dementia risk, older adults, those with cardiovascular risk factors, and people of color, COVID-19 may not only increase the risk of cognitive decline but also interact in a synergistic way with pre-existing dementia risk factors to disproportionately increase this dementia risk. ❂ 📖 (28 Jul 2021 ~ Neurodegenerative Diseases) The Impact of the COVID-19 Pandemic on Dementia Risk: Potential Pathways to Cognitive Decline ➤ © 2021 Pyne and Brickman / Neurodegenerative Diseases.
❦ The brains of people who died from COVID-19 were remarkably similar to the brains of people who die from neurodegenerative diseases such as Alzheimer’s and Parkinson’s , showing inflammation and disrupted circuitry . — “The brains of patients who died from severe COVID-19 showed profound molecular markers of inflammation , even though those patients didn’t have any reported clinical signs of neurological impairment,” said study co-senior author Tony Wyss-Coray, a professor of neurology and neurological sciences at Stanford University. His team analyzed brain tissue from eight people who died of COVID-19 and 14 people who died of other causes. About one-third of hospitalized COVID-19 patients report neurological symptoms such as fuzzy thinking , forgetfulness , difficulty concentrating and depression , Wyss-Coray noted. These problems can persist as part of what’s called Long COVID, a lingering condition that sometimes affects patients after they recover from the original infection. ❂ 📖 (21 Jun 2021 ~ Nature) Dysregulation of brain and choroid plexus cell types in severe COVID-19 ➤ 📖 (22 Jun 2021 ~ MedicalXpress) Autopsy study shows how COVID harms the brain ➤ © 2021 MedicalXpress.
❦ ‘Coronavirus disease 2019 (COVID-19), which resulted from the bpandemic outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a massive inflammatory cytokine storm leading to multi-organ damage including that of the brain and testes . While the lungs , heart , and brain are identified as the main targets of SARS-CoV-2 -mediated pathogenesis, reports on its testicular infections have been a subject of debate. The brain and testes are physiologically synchronized by the action of gonadotropins and sex steroid hormones. Though the evidence for the presence of the viral particles in the testicular biopsies and semen samples from COVID-19 patients are highly limited, the occurrence of testicular pathology due to abrupt inflammatory responses and hyperthermia has increasingly been evident. The reduced level of testosterone production in COVID-19 is associated with altered secretion of gonadotropins . Moreover, hypothalamic pathology which results from SARS-CoV-2 infection of the brain is also evident in COVID-19 cases. This article revisits and supports the key reports on testicular abnormalities and pathological signatures in the hypothalamus of COVID-19 patients and emphasizes that testicular pathology resulting from inflammation and oxidative stress might lead to infertility in a significant portion of COVID-19 survivors.’ ❂ 📖 (07 Jan 2021 ~ Reproductive Sciences) Testicular Atrophy and Hypothalamic Pathology in COVID-19: Possibility of the Incidence of Male Infertility and HPG Axis Abnormalities ➤ © 2021 Reproductive Sciences .
C-19 Blog:
brain & nerves
❦ This study confirms everything that I have seen in the microscope over the last few years. The authors of the study use a technique called dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), an imaging technique that can measure the density, integrity, and leakiness of tissue vasculature. Comparing all individuals with previous COVID infection to unaffected controls revealed decreased general brain volume in patients with brain fog along with significantly reduced cerebral white matter volume in both hemispheres in the recovered and brain fog cohorts . Covid-19 induces brain volume loss and leaky blood-brain barrier in some patients. How can this be more clear? © 2024 Danielle Beckman. ➲ ❂ 📖 (22 Feb 2024 ~ Nature: Neuroscience) Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment ➤ 📖 (22 Feb 2024 ~ Nature: Neuroscience) Leaky blood–brain barrier in long-COVID-associated brain fog ➤ ➲ Layperson overview: 📖 (February 2024 ~ Genetic Engineering and Biotechnology News) Leaky Blood Vessels in the Brain Linked to Brain Fog in Long COVID Patients ➤ Related: 📖 (7 Feb 2022 ~ Nature: Cardiovascular Research) Blood–brain barrier link to human cognitive impairment and Alzheimer’s disease ➤ ❂ © 2024 Nature .
❦ ‘Although some studies have shown neuroimaging and neuropsychological alterations in post-COVID-19 patients, fewer combined neuroimaging and neuropsychology evaluations of individuals who presented a mild acute infection. Here we investigated cognitive dysfunction and brain changes in a group of mildly infected individuals. We conducted a cross-sectional study of 97 consecutive subjects ( median age of 41 years ) without current or history of psychiatric symptoms (including anxiety and depression) after a mild infection , with a median of 79 days (and mean of 97 days ) after diagnosis of COVID-19. We performed semi-structured interviews, neurological examinations, 3T-MRI scans, and neuropsychological assessments. The patients reported memory loss ( 36% ), fatigue ( 31% ) and headache ( 29% ). The quantitative analyses confirmed symptoms of fatigue ( 83% of participants), excessive somnolence ( 35% ), impaired phonemic verbal fluency ( 21% ), impaired verbal categorical fluency ( 13% ) and impaired logical memory immediate recall ( 16% ). Our group… presented higher rates of impairments in processing speed ( 11.7% in FDT- Reading and 10% in FDT- Counting ). The white matter (WM) analyses with DTI * revealed higher axial diffusivity values in post-infected patients compared to controls. * Diffusion tensor imaging tractography , or DTI tractography, is an MRI (magnetic resonance imaging) technique most commonly used to provide imaging of the brain. Our results suggest persistent cognitive impairment and subtle white matter abnormalities in individuals mildly infected , without anxiety or depression symptoms. One intriguing fact is that we observed a high proportion of low average performance in our sample of patients (which has a high average level of education ), including immediate and late verbal episodic memory, phonological and semantic verbal fluency, immediate visuospatial episodic memory, processing speed, and inhibitory control . Although most subjects did not present significant impaired scores compared with the normative data, we speculate that the low average performance affecting different domains may result in a negative impact in everyday life , especially in individuals with high levels of education and cognitive demands .’ ❂ ❦ Note how these findings might negatively affect daily activities that demand sustained cognitive attention and fast reaction times – such as driving a car or motorbike, or piloting a plane. Consider air-traffic control. Consider the impact on healthcare workers whose occupations combine long periods of intense concentration with a need for critical precision. ❂ 📖 (19 Jan 2024 ~ Nature: Scientific Reports) Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19 ➤ © 2024 Nature .
❦ ‘Alzheimer’s disease (AD) is acknowledged by the World Health Organisation (WHO) as a global public health concern. AD is the primary cause of dementia and accounts for 50–70% of cases. SARS-CoV-2 can damage the peripheral and the central nervous system (CNS) through both direct and indirect pathways, potentially leaving COVID-19 patients at higher risks for neurological difficulties, including depression, Parkinson’s disease, AD, etc., after recovering from severe symptoms. Patients who recovered from severe COVID-19 infection are more likely to acquire stable neuropsychiatric and neurocognitive conditions like depression, obsessive-compulsive disorder, psychosis, Parkinson’s disease, and Alzheimer’s disease. SARS-CoV-2 infection causes immune system dysfunction, which can lead to suppression of neurogenesis, synaptic damage, and neuronal death, all of which are associated with the aetiology of Alzheimer’s disease. Severe systemic inflammation caused by SARS-CoV-2 is predicted to have long-term negative consequences, such as cognitive impairment. Research has demonstrated that SARS-CoV-2-infected AD patients had a higher mortality rate. In a study from the Department of Neuroscience at the University of Madrid, 204 participants with Frontotemporal Dementia (FTD) and Alzheimer’s disease (AD) were enrolled. According to the study, 15.2% of these individuals had COVID-19 infection, and sadly, 41.9% of those who had the virus died as a result of their illness. COVID-19 causes a secondary effect on underlying brain pathologies, as SARS-CoV-2 has been shown to trigger or accelerate neurodegeneration processes that possibly explain long-term neurodegenerative effects in the elderly population. In response to the impact of COVID-19 in 2020, governments worldwide acted promptly by implementing various public health measures. During this period, people with cognitive impairments such as dementia or AD may have experienced greater stress and anxiety due to sudden changes in the environment and people’s behaviour. It is also significantly harder for AD patients to comprehend and execute defensive measures such as wearing face masks and sanitising frequently. ❂ COVID-19 has generated a worldwide outbreak, resulting in a slew of issues for humans, particularly those suffering from Alzheimer’s disease. Its ability to invade the central nervous system through the hematogenous and neural routes, besides attacking the respiratory system, has the potential to worsen cognitive decline in Alzheimer’s disease patients. The severity of this issue must be highlighted.’ ❂ 📖 (8 Jan 2024 ~ Frontiers in Aging Neuroscience) Unravelling the connection between COVID-19 and Alzheimer’s disease: a comprehensive review ➤ © 2024 Shajahan et al / Frontiers in Aging Neuroscience .
❦ Always Covid+ Colleague: — “One of the medical groups. One of the groups. One of the groups...” Moderator: — “Is there something you want to share?” Always Covid+ Colleague: — “I was asked something. I don’t know. It has something to do with something.” This is what Covid is doing to the brain. Unfortunately this is not an isolated incident – but something I’m witnessing all day long throughout the company. ❂ © 2023 Lady Chuan ➲
❦ ‘It is now well established that post-COVID syndrome ( PCS ) represents a serious complication in a substantial number of patients following SARS-CoV-2 infection. PCS is diagnosed when COVID-19-related symptoms persist for more than 3 months. It can occur even after an initially mild to moderate course of infection , and comprise a large variety of symptoms . Around 30% of PCS patients show neurological and neuropsychiatric sequelae , such as fatigue , depressive symptoms , and cognitive dysfunction . These are experienced as particularly debilitating, as they have detrimental effects on daily functioning in PCS patients and hamper a successful return to their jobs. Fatigue is a frequent and one of the most debilitating symptoms in post-COVID syndrome (PCS). Recently, we proposed that fatigue is caused by hypoactivity of the brain’s arousal network and reflected by a reduction of cognitive processing speed . Eighty-eight PCS patients with cognitive complaints and 50 matched healthy controls underwent neuropsychological assessment. Seventy-seven patients were subsequently assessed at 6-month follow-up. Patients showed cognitive slowing indicated by longer reaction times compared to control participants in a simple-response tonic alertness task and in all more complex tasks requiring speeded performance . Reduced alertness correlated with higher fatigue . Alertness dysfunction remained unchanged at 6-month follow-up and the same was true for most attention tasks and cognitive domains .’ ❂ 📖 (7 Nov 2023 ~ Journal of Neurology) Persistent cognitive slowing in post-COVID patients: longitudinal study over 6 months ➤ © 2023 Journal of Neurology .
➲ A layperson-level overview from New Atlas on how all variants of SARS-CoV-2 – the virus that causes COVID-19 – are ‘neuroinvasive’ , meaning that all can infect or enter the brain and the nervous system . ❂ ❦ ‘... We know COVID is associated with a variety of neurological symptoms , both short- and long-term, but it still isn’t entirely clear whether these cognitive issues are the result of the virus directly infecting brain cells or simply due to a broader systemic inflammatory response. Studies looking at human brain tissue have yielded contradictory results. Some have found direct traces of SARS-CoV-2 , while others report only inflammatory damage . Animal models certainly demonstrate it is possible for the virus to infect the brain, but human tissue samples are obviously taken after a patient dies – meaning researchers can only hypothesize what happens during an acute infection. Using a hamster model, the research compared infection with the original SARS-CoV-2 virus from 2020 to several subsequent variants including Gamma, Delta and Omicron/BA.1 variants. Interestingly, the findings confirmed epidemiological observations showing acute disease severity is reduced in Omicron infections – however, all [SARS-CoV-2] variants demonstrated similar neuroinvasive capabilities. And, most strikingly, all variants infected the brain’s olfactory regions regardless of whether symptoms of anosmia (the loss of sense of smell) were present or not. “This suggests that anosmia and neuronal infection are two unrelated phenomena. If we follow this line of reasoning, it is quite possible that even an asymptomatic infection is characterized by the spread of the virus in the nervous system.” The researchers conclude this suggests all SARS-CoV-2 variants have the capacity to infect the brain, via the olfactory pathway, regardless of clinical disease presentations. This means it is possible even mild infections can lead to the virus infiltrating the brain. “The next step will be to understand... whether the virus is able to persist in the brain beyond the acute [initial, short-term] phase of infection, and whether the presence of the virus can induce persistent inflammation and the symptoms described in cases of long COVID, such as anxiety, depression and brain fog” [brain damage].’ © 2023 Rich Haridy / New Atlas. ➲ Source © 2023 Institut Pasteur .
❦ Your brain is a vast city. The roads (myelin) in this city let cars move efficiently. Oligodendrocytes are the construction workers who maintain these roads. As we age, these workers slow down, causing traffic jams and slower thoughts. Enter SARS-CoV-2, the destructive rioter. It doesn’t just disrupt traffic; it damages the roads and chases away the construction crews. Weeks after the riot, the city still struggles to function, with long-lasting road damages and traffic jams. This is the ‘brain fog’ of post-COVID life. ❂ 📖 (24 Sep 2023 ~ Aging and Disease) Role of Microglia, Decreased Neurogenesis and Oligodendrocyte Depletion in Long COVID-Mediated Brain Impairments ➤ © 2023 Outbreak Updates ➲
❦ ‘We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone ( GnRH ), the master molecule regulating reproduction , and cognitive deficits during pathological aging , including Down syndrome and Alzheimer’s disease. Olfactory and cognitive alterations , which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline . We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin , favouring post-COVID cognitive or neurological symptoms , and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes . Furthermore, GnRH neurons themselves were dying in all patient brains studied , dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia , from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection . Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive , metabolic , and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups .’ ❂ 📖 (12 Sep 2023 ~ eBioMedicine: Lancet Discovery Science) Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death ➤ © 2023 eBioMedicine: Lancet Discovery Science .
❦ Children have largely been unaffected by severe COVID-19 compared to adults, but data suggest that they may have experienced new conditions after developing the disease. We compared 1656 exposed and 1656 unexposed children from 1 February 2020 to 30 November 2021. We found significantly higher risks for some new conditions in exposed children, including mental health issues and neurological problems . The overall excess risk for new-onset conditions after COVID-19 was 78% higher in the exposed than unexposed children. ❂ 📖 (9 Sep 2023 ~ Acta Paediatrica) Comparative study showed that children faced a 78% higher risk of new-onset conditions after they had COVID-19 ➤ © 2023 Di Chiara et al / Acta Paediatrica.
❦ When someone shows a severe personality shift, there could be many reasons. One possibility? Their brain may have been affected by COVID-19. It’s crucial to approach with empathy, to consider all potential causes, and to consult healthcare professionals. Don’t jump to conclusions, but stay informed. © 2023 Dr. Sean Mullen . ➲
❦ Researchers at The University of Queensland have discovered viruses such as SARS-CoV-2 can cause brain cells to fuse, initiating malfunctions that lead to chronic neurological symptoms. SARS-CoV-2, the virus that causes COVID-19, has been detected in the brains of people with 'Long COVID' months after their initial infection. "We discovered COVID-19 causes neurons to undergo a cell fusion process, which has not been seen before," Professor Hilliard said. "After neuronal infection with SARS-CoV-2, the spike S protein becomes present in neurons, and once neurons fuse, they don't die." "They either start firing synchronously, or they stop functioning altogether." As an analogy, Professor Hilliard likened the role of neurons to that of wires connecting switches to the lights in a kitchen and a bathroom. "Once fusion takes place, each switch either turns on both the kitchen and bathroom lights at the same time, or neither of them," he said. "It's bad news for the two independent circuits." The discovery offers a potential explanation for persistent neurological effects after a viral infection. "In the current understanding of what happens when a virus enters the brain, there are two outcomes – either cell death or inflammation," Dr Martinez-Marmol said. "But we've shown a third possible outcome, which is neuronal fusion." Dr Martinez-Marmol said numerous viruses cause cell fusion in other tissues, but also infect the nervous system and could be causing the same problem there. "These viruses include HIV, rabies, Japanese encephalitis, measles, herpes simplex virus and Zika virus," he said. “Our research reveals a new mechanism for the neurological events that happen during a viral infection. “This is potentially a major cause of neurological diseases and clinical symptoms that is still unexplored.” ❂ 📖 (7 June 2023 ~ Science Advances) SARS-CoV-2 infection and viral fusogens cause neuronal and glial fusion that compromises neuronal activity ➤ 📖 (8 June 2023 ~ Queensland Brain Institute) COVID-19 can cause brain cells to 'fuse' ➤ © 2023 Martinez-Marmol & Hilliard / Queensland Brain Institute / University of Queensland.
❦ A bizarre recurring point of debate: “People die every day of lots of other things!” True, but you don’t catch a stroke or cancer from other people in a restaurant. © 2023 NHS Medical Consultant . ➲
❦ What if Covid has been causing mass cognitive impairment and we are all living in an increasingly stupid society? Mad things could happen with that: imagine if hospitals got rid of masks or people started to believe Covid was just a cold? I know that’s far-fetched, but imagine! ❂ © 2023 NHS Medical Consultant . ➲
❦ The results presented here reveal that at least 85% [of the 214 patients with post COVID-19 syndrome] exhibit deficits in one neuropsychological test . Also, the youngest patients were those who showed the most marked and heterogeneous cognitive impairment , while the oldest patients maintained their cognitive functions preserved to a greater extent with only a mild impairment in attention and speed processing. ❂ 📖 (19 Apr 2023 ~ Nature: Scientific Reports) Cognitive impairment in young adults with post COVID-19 syndrome ➤ © 2023 Herrera et al / Nature.
❦ The Linseman Laboratory is studying the long-term brain health effects of COVID-19 in individuals with and without traumatic brain injury (TBI). Preliminary data suggest that those with a history of both COVID-19 and TBI experience more severe Long COVID symptoms, a higher symptom burden , and more frequent symptoms . Those who reported having COVID-19 and TBI reported worse depressive symptoms , worse functional outcomes , and increased fatigue . ❂ 📖 (4 Apr 2023 ~ SciTechDaily) Researchers Discover Connection Between Traumatic Brain Injury and Long COVID ➤ © 2023 Linesman Laboratory / University of Denver / SciTechDaily.
❦ From mild anosmia to severe ischemic stroke , the impact of SARS-CoV-2 on the central nervous system is still a great challenge to scientists and healthcare practitioners. Besides the acute and severe neurological problems described, as encephalopathies , leptomeningitis , and stroke , the chronic impact observed during Long COVID or the post-acute sequelae of COVID-19 (PASC) greatly intrigues scientists worldwide. Strikingly, even asymptomatic , and mild-diseased patients may evolve with important neurological and psychiatric symptoms such as confusion , memory loss , cognitive decline and chronic fatigue , associated or not with anxiety and depression . ❂ 📖 (1 Apr 2023 ~ Human Genetics) Direct and indirect impact of SARS-CoV-2 on the brain ➤ © 2023 J.P.S Peron / Human Genetics.
❦ The possible neurological consequences of SARS-CoV-2 infection, associated with physical and cognitive frailty, could lead to a worsening of Parkinson’s disease (PD) in infected patients or – more rarely – to an increase in the Parkinsonian symptomatology . Parkinson’s disease (PD) or Parkinsonism has been described after infections with viruses , such as the Epstein-Barr virus , hepatitis C virus , HIV , influenza A virus , Japanese encephalitis virus , varicella zoster virus , or West Nile virus . Therefore, the hypothesis that SARS-CoV-2 may have even longer-term effects on the brain and lead to an increase in cases of Parkinson’s disease, as occurred in the years following the Spanish flu , has been put forward. ❂ 📖 (23 Mar 2023 ~ Brain Science) Parkinson’s Disease, SARS-CoV-2, and Frailty: Is There a Vicious Cycle Related to Hypovitaminosis D? ➤ © 2023 Palermo et al / Brain Science.
❦ It's no wonder that depression and PTSD rates ✢ are up in people living with Long COVID. ✢ Long COVID: major findings, mechanisms and recommendations ➤ There are no approved therapies for the physical or cognitive disabilities that now plague 65 million people around the world, a conservative estimate given the degree of undocumented cases. It is now clear from US and UK investigations of approximately 2,000 previously hospitalized Covid patients that six months later more than half have problems managing finances and paying bills as well as completing everyday activities like preparing meals, bathing, getting dressed, or walking across a room. But what exactly is going on inside the brains of these people from a biological and pathological perspective? Autopsy studies show that the virus can persist ✢ in some people for many months even though they have no symptoms and test negative for the virus. ✢ Persistent SARS-CoV-2 infection in patients seemingly recoveredfrom COVID-19 ➤ Brains donated by people who died of Covid-19 also show widespread problems in the cells lining the blood vessels and exaggerated clotting, supporting the idea of Covid-19 as a blood flow disorder ✢ that brings on brain disease. ✢ Neurovascular injury with complement activation and inflammation in COVID-19 ➤ Perhaps the most harrowing thing I have done in 30 years as a physician-scientist has been to ask family members I'd never met, often in the middle of the night via telephone during the height of the Covid surges, if I and my colleagues could study their loved one's brain. In a study we conducted of 20 of these priceless brain donations ✢ , we found brain swelling due to decreased blood flow and heightened activity in microglial cells, the so-called 'white matter' in brains that support the neurons that transmit thoughts and help store information. We saw this even in young previously healthy individuals. ✢ Brain autopsies of critically ill COVID-19 patients demonstrate heterogeneous profile of acute vascular injury, inflammation and age-linked chronic brain diseases ➤ A study from the National Institutes of Health of 44 complete autopsies ✢ mapped and quantified the distribution of SARS-CoV-2 and showed it was widely distributed throughout the body, including in the hypothalamus and cerebellum in the brain and neurons in the spinal cord. ✢ SARS-CoV-2 infection and persistence in the human body and brain at autopsy ➤ Especially relevant to Long Covid, viral fragments were detected in some of the brains of people who died many months after symptom onset. In Their Own Words Barbara Nivens, who retired from retail management at age 59, has been diagnosed by her neurologist as having rapid onset dementia due to Covid-19. An incredibly thorough medical work-up found no plausible causes for this dementia other than its onset following her Covid infection, which she contracted before the vaccine was available. Matt Fitzgerald, age 26, is a mechanical engineer who worked for Tesla and now designs surgical devices – when he can. Since recovering from his initial bout with Covid-19, he's developed a condition characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) known as post-exertional malaise, which is why even slight exertion leaves him and millions like him inexplicably incapacitated. ❦ Barbara Nivens: — “I walk down the hall and see dozens of pictures of family trips and feel like a ghost because I don't remember any of them. Now I'm trying to figure out who Barbara 2.0 is going to be.” (Her husband, tearing up as he listened to her, said softly, “I just want my wife back.”) ❦ Matt Fitzgerald: — “I feel like I'm underwater. When you talk to me, I can hear you, but my brain does not understand the words. I can't comprehend what you're saying. I have no intellectual capacity or energy to digest data. At work my brain is just begging for rest. I struggle with finding words and completing tasks in a timely manner. It's the worst. I'll be in a meeting and know exactly what I want to say before I say it. I'll start saying it and I'll get to a word, and I just cannot think of the word. I'll just be like, ‘Give me a moment,’ and I'll go through my brain cycling through words. This week it was 'consistent'. I couldn't think of the word 'consistent'. I kept thinking it was 'coincident' or 'concentric' or 'constant'.” Such problems in executive function, memory, and processing speed are what many people complain about in the Long COVID support groups. Science validates their injuries. A picture is emerging from animal models showing how on-going inflammation of glial cells disrupts the electrical conduction highways in the brain's white matter that link to and support the neurons in gray matter. It's as if the bridges (white matter) linking different territories of the brain have been blown up and the land itself (nerves in the cerebral cortex and hippocampus) becomes scorched, leaving people with Long COVID plagued by thinking and memory deficits. ❂ 📖 (16 Feb 2023 ~ Stat) The haunting brain science of Long COVID ➤ © 2023 E. Wesley Ely / Stat.
❦ Cognitive postscripts of COVID-19 , codenamed as ‘cognitive COVID' or ‘brain fog’, characterized by multi-domain cognitive impairments, are now being reckoned as the most devastating sequelae of COVID-19 . The rapid progression of dementia , the addition of further impairments/deterioration of cognitive abilities , and the increase or new appearance of white matter lesion burden suggest that previously compromised brains have little defense to withstand a new insult (i.e., a ‘second hit’-like infection/dysregulated immune response, and inflammation). ❂ 📖 Related: (4 Apr 2023 ~ Eurekalert) New study shows SARS-CoV-2 infection accelerates the progression of dementia ➤ ‘ All subtypes of dementia , irrespective of patients' previous dementia types, behaved like rapidly-progressive dementia following COVID-19 .’ 📖 Related: (4 Apr 2023 ~ NeuroscienceNews) COVID-19 Infection Accelerates the Progression of Dementia ➤ ‘A rapidly and aggressively deteriorating course was observed in patients having insidious-onset, slowly-progressive dementia, and who were previously cognitively stable .’ ❂ 📖 (14 Feb 2023 ~ Journal of Alzheimer's Disease Reports) The Effects of SARS-CoV-2 Infection on the Cognitive Functioning of Patients with Pre-Existing Dementia ➤ © 2023 Dubey et al / Journal of Alzheimer’s Disease Reports.
❦ ‘Acute ischemic stroke (AIS) is a fearful complication of Coronavirus Disease-2019 (COVID-19). SARS-CoV-2 infection seems to play a major role in endothelium activation and infarct volume extension during AIS.’ ❂ 📖 (10 Jan 2023 ~ Frontiers in Cardiovascular Medicine) SARS-CoV-2 infection predicts larger infarct volume in patients with acute ischemic stroke ➤ © 2023 Frontiers in Cardiovascular Medicine .
❦ Strikingly, the [foetal brain] haemorrhages are predominately found in the late first and early second trimester of gestation , a period of development in which the effect of the COVID-19 pandemic has not been thoroughly investigated. Specifically, the majority were between 12 and 14 pcw, a critical window of human foetal brain development when the endothelial tight junctions increase to form the blood-brain barrier . Our observations of disrupted foetal cerebral vasculature are consistent with reports of damage to the microvasculature of the adult brain in SARS-CoV-2 infected patients . ❂ 📖 (16 Jan 2023 ~ Brain) Haemorrhage of human foetal cortex associated with SARS-CoV-2 infection ➤ © 2023 Massimo et al / Brain.
❦ ‘The narrative that COVID-19 had only respiratory sequelae led to a delayed realization of the neurological, cardiovascular and other multi-system impacts of COVID-19. Long COVID is a multi-systemic illness encompassing ME / CFS , dysautonomia , impacts on multiple organ systems , and vascular and clotting abnormalities . Circulatory system disruption includes endothelial dysfunction and subsequent downstream effects, and increased risks of deep vein thrombosis , pulmonary embolism and bleeding events . Microclots detected in both acute COVID-19 and long COVID contribute to thrombosis.’ ✻ Endothelial dysfunction precedes atherosclerosis and is an independent predictor of cardiovascular events. Atherosclerosis is a condition where plaque , a sticky substance made up of fat, cholesterol, calcium, and other substances found in the blood, hardens and narrows the arteries , limiting the flow of oxygen-rich blood to the body . Deep vein thrombosis ( DVT ) is a blood clot that forms in a deep vein , usually in the pelvis , calf , or thigh . A pulmonary embolism [ PE ] is a blood clot that blocks and stops blood flow to an artery in the lung . Often the clot starts in a leg and travels to the lung. ‘Long-term changes to the size and stiffness of blood cells have also been found in long COVID, with the potential to affect oxygen delivery. A long-lasting reduction in vascular density , specifically affecting small capillaries, was found in patients with long COVID 18 months after infection . Long COVID has already debilitated millions of individuals worldwide, and that number is continuing to grow. On the basis of more than two years of research on Long COVID and decades of research on conditions such as ME/CFS, a significant proportion of individuals with Long COVID may have lifelong disabilities if no action is taken. Diagnostic and treatment options are currently insufficient , and many clinical trials are urgently needed to rigorously test treatments that address hypothesized underlying biological mechanisms, including viral persistence, neuroinflammation, excessive blood clotting and autoimmunity.’ ❂ 📖 (13 Jan 2023 ~ Nature Reviews: Microbiology) Long COVID: major findings, mechanisms and recommendations ➤ © 2023 Davis et al / Nature .
❦ Globally, millions of people have contracted COVID-19 over the past few years, and some have even caught the virus two or more times. Of more than 665 million cases worldwide, nearly one in two people with COVID-19 is at risk of developing Post-COVID-19 Neurological Syndrome (PCNS). Symptoms of Post-COVID-19 Neurological Syndrome (PCNS) mimic some of the symptoms we see after a stroke, and younger adults seem to be at particular risk. It’s worth noting that a link between brain health and Coronavirus infections has been known since 2006, so in this context the long-term impact of COVID-19 on the brain may arguably be the expectation rather than the exception. Nearly one in two people who have reportedly recovered from acute COVID-19 cite disabling fatigue – that is, fatigue lasting more than twelve weeks – coupled with a series of attention and cognitive deficits similar to persistent post-stroke neurological symptoms. We have already reported on the shared pathobiology between stroke and COVID-19 at a cellular level. So, it should not be surprising to see the long-term impact on the brain with a persistent inflammatory response (potentially due to viral persistence, immune dysregulation or autoimmunity). ❂ 📖 Related: (1 Jan 2023 ~ The Lancet) The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: A systematic review and meta-analysis ➤ 📖 Related: (7 Mar 2022 ~ Nature) SARS-CoV-2 is associated with changes in brain structure in UK Biobank ➤ 📖 Related: (12 Jan 2021 ~ Australian Journal of General Practice) COVID-19 and long-term neurological problems: Challenges ahead with Post-COVID-19 Neurological Syndrome ➤ 📖 Related: (1 Feb 2006 ~ Nature Reviews Microbiology) Coronavirus infection of the central nervous system: host-virus stand-off ➤ 📖 Related: (28 Jan 2021~ Frontiers in Neurology) COVID-19 Pathophysiology Predicts That Ischemic Stroke Occurrence Is an Expectation, Not an Exception - A Systematic Review ➤ ❂ 📖 (6 Jan 2023 ~ University of Melbourne) What we now know about long COVID and our brains ➤ © 2023 Wijeratne et al / University of Melbourne.
❦ ‘In 2021, SARS-CoV-2-related severe neurologic involvement in US hospitalized children and adolescents showed a potential increase in diagnoses of acute central nervous system infections / demyelination. In this case series of 2168 US patients younger than 21 years hospitalized for acute COVID-19 (34%) or multisystem inflammatory syndrome in children (66%), 476 (22%) had neurologic involvement. Of these, 42 (9%) had life-threatening conditions, with 23 (55%) having acute central nervous system (CNS) infections / demyelination; 18 of 42 (43%) died or had new neurologic deficits; and most vaccine-eligible patients were unvaccinated.’ ❂ 📖 (1 Jan 2023 ~ JAMA Network / Neurology) Changes in Distribution of Severe Neurologic Involvement in US Pediatric Inpatients With COVID-19 or Multisystem Inflammatory Syndrome in Children in 2021 vs 2020 ➤ 📖 Related: (5 Jan 2023 ~ Neurology Today) Nearly One-Fifth of Hospitalized Children and Adolescents with SARS-CoV-2 or MIS-C Have Persistent Neurologic Complications ➤ © 2023 LaRovere et al / JAMA: Neurology.
❦ COVID-19 is an acute respiratory disease often accompanied by neurological sequelae. Individuals with previous severe COVID-19 exhibit a 10-year average drop in their global cognitive performance , mimicking accelerated aging . Complementary studies combining neuroimaging and cognitive screening implicate COVID-19-induced impairment of the frontal cortex, a critical area for cognitive function. Our findings indicate that COVID-19 is associated with molecular signatures of brain aging . ❂ 📖 (5 Dec 2022 ~ Nature Aging) Severe COVID-19 is associated with molecular signatures of aging in the human brain ➤ © 2023 Mavrikaki et al / Nature: Aging.
❦ Research led by The University of Queensland has found COVID-19 activates the same inflammatory response in the brain as Parkinson’s disease. “We studied the effect of the virus on the brain’s immune cells, ‘microglia’ which are the key cells involved in the progression of brain diseases like Parkinson’s and Alzheimer’s,” Professor Woodruff said. “Our team grew human microglia in the laboratory and infected the cells with SARS-CoV-2, the virus that causes COVID-19. “We found the cells effectively became ‘angry’, activating the same pathway that Parkinson’s and Alzheimer’s proteins can activate in disease, the inflammasomes.” Dr Albornoz Balmaceda said triggering the inflammasome pathway sparked a ‘fire’ in the brain, which begins a chronic and sustained process of killing off neurons . “It’s kind of a silent killer , because you don’t see any outward symptoms for many years,” Dr Albornoz Balmaceda said. “It may explain why some people who’ve had COVID-19 are more vulnerable to developing neurological symptoms similar to Parkinson’s disease .” The researchers found the spike protein of the virus was enough to start the process and was further exacerbated when there were already proteins in the brain linked to Parkinson’s. “So if someone is already pre-disposed to Parkinson’s , having COVID-19 could be like pouring more fuel on that ‘fire’ in the brain,” Professor Woodruff said. “The same would apply for a predisposition for Alzheimer’s and other dementias that have been linked to inflammasomes.” ❂ 📖 (1 Nov 2022 ~ The University of Queensland, Australia) ‘ A silent killer’ – COVID-19 shown to trigger inflammation in the brain ➤ © 2022 Woodruff & Balmaceda / The University of Queensland, Australia.
❦ Our results show that in the postacute phase of COVID-19, there was increased risk of an array of incident neurologic sequelae including ischemic and hemorrhagic stroke , cognition and memory disorders , peripheral nervous system disorders , episodic disorders (for example, migraine and seizures ), extrapyramidal and movement disorders , mental health disorders , musculoskeletal disorders , sensory disorders , Guillain-Barré syndrome , and encephalitis or encephalopathy . ❂ 📖 Related: (22 Sep 2022 ~ Washington University School of Medicine in St. Louis) COVID-19 infections increase risk of long-term brain problems ➤ Those who have been infected with the [SARS-CoV-2] virus are at increased risk of developing a range of neurological conditions in the first year after the infection. Such complications include strokes, cognitive and memory problems, depression, anxiety and migraine headaches. Additionally, the post-COVID brain is associated with movement disorders, from tremors and involuntary muscle contractions to epileptic seizures, hearing and vision abnormalities, and balance and coordination difficulties as well as other symptoms similar to what is experienced with Parkinson’s disease. ❂ 📖 (22 Sep 2022 ~ Nature Medicine) Long-term neurologic outcomes of COVID-19 ➤ © 2022 Xu, Xie & Al-Aly / Nature: Medicine.
❦ ‘Older people who were infected with COVID-19 show a substantially higher risk – as much as 50% to 80% higher than a control group – of developing Alzheimer’s disease within a year, according to a study of more than 6 million patients 65 and older. In a study published today in the Journal of Alzheimer’s Disease, researchers report that people 65 and older who contracted COVID-19 were more prone to developing Alzheimer’s disease in the year following their COVID diagnosis. And the highest risk was observed in women at least 85 years old. The findings showed that the risk for developing Alzheimer’s disease in older people nearly doubled (0.35% to 0.68%) over a one-year period following infection with COVID. The researchers say it is unclear whether COVID-19 triggers new development of Alzheimer’s disease or accelerates its emergence. “The factors that play into the development of Alzheimer’s disease have been poorly understood, but two pieces considered important are prior infections, especially viral infections, and inflammation,” said Pamela Davis, Distinguished University Professor and The Arline H. and Curtis F. Garvin Research Professor at the Case Western Reserve School of Medicine, the study’s co-author. Previous COVID-related studies led by CWRU have found that people with dementia are twice as likely to contract COVID.’ 📖 (13 Sep 2022 ~ Science Daily / Case Western Reserve University) Risk factor for developing Alzheimer's disease increases by 50-80% in older adults who caught COVID-19 ➤ ❂ 📖 (13 Sep 2022 ~ Journal of Alzheimer’s Disease) Association of COVID-19 with New-Onset Alzheimer’s Disease ➤ © 2022 Journal of Alzheimer’s Disease / Science Daily .
❦ So, we want to ‘live with the virus’. Is there any evidence of this occurring successfully anywhere? Yes! In bats... and it has taken 64 million years of evolution ✢ to get there. 📖 (20 Jan 2021 ~ Nature) Lessons from the host defences of bats, a unique viral reservoir ➤ To ‘live with the virus’, bats have better host defences – they don’t overdo inflammation, and they can get rid of toxic compounds and deal with reactive oxygen species much better than humans. They literally live with the virus . For humans to ‘live with the virus’, we would need to have similar mechanisms to permit SARS-CoV-2 to be part of our biome – without causing all of the autoimmune disease and other damage. We would have to have fundamentally different biochemistry and immune systems. We can mimic this using therapeutics to some extent, and this may help us treat Long COVID. However, I don’t think that we will naturally become resilient to SARS-CoV-2 for a very long time. What I’m trying to say is that mass-infecting this generation of children is unlikely to result in them developing a bat-like immune system within their lifetimes. It’s ridiculous that the attempt was ever made. I genuinely think that putting ventilation upgrades into every building and wearing good-quality masks will be easier than building a genetically modified SARS-resistant human. I keep trying to give you the easy way out! The coronavirus is moving into our bodies and is attempting to stay there, just like it does in bats. The problem is that our bodies try to fight it. We fight it well enough to reduce detectable virus-shedding on our breath, but there is evidence (persistent spike RNA) that the virus is hiding somewhere else in our body anyway. So our bodies keep fighting it. The collateral damage is the problem. What are our choices? 1. Figure out how to change human physiology so that we don’t burn ourselves out fighting an elusive and persistent enemy. 2. Or figure out how we can stop transmission. The second is easier, and economically sound. The ability to completely clear coronavirus is also a potential goal – but again, therapeutics will be needed because we have places where, if the immune system is left to do it, it causes damage – and coronavirus has many tricks to help it hide from detection. Needless to say, coronavirus can evolve a lot faster than we can, so we need to use our brain cells in a different way to fight COVID-19. Instead of using microglia, we need to think ...
❦ ‘The prevalence of Long COVID in children and adolescents was 25.24% . The five most prevalent clinical manifestations were mood symptoms (16.50%), fatigue (9.66%), sleep disorders (8.42%), headache (7.84%), and respiratory symptoms (7.62%). Interestingly, many of the symptoms identified in these meta-analyses associated to Long COVID, such as mood, fatigue, sleep disorders, orthostatic intolerance, decreased concentration, confusion, memory loss, balance problems, exercise intolerance, hyperhidrosis, blurred vision, body temperature dysregulation, dysfunction on heart, rate variability and palpitations, constipation or diarrhea, and dysphagia, are commonly present in dysautonomia .’ ❂ 📖 (23 Jun 2022 ~ Nature Scientific Reports) Long COVID in children and adolescents: a systematic review and meta-analyses ➤ © 2022 Lopez-Leon et al / Nature.
❦ ‘In this analysis of 222 offspring of mothers infected with SARS-CoV-2, compared with the offspring of 7550 mothers in the control group (not infected) delivered during the same period, we observed neurodevelopmental diagnoses to be significantly more common among exposed offspring, particularly those exposed to third-trimester maternal infection . The majority of these diagnoses reflected developmental disorders of motor function or speech and language .’ ❂ 📖 (9 Jun 2022 ~ JAMA: Pediatrics) Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy ➤ © 2022 Edlow et al / JAMA: Pediatrics.
❦ ‘The authors performed a survey in children suffering from persistent symptoms since initial infection. A total of 510 children infected between January 2020 and January 2021 were included. Symptoms such as fatigue, headache, muscle and joint pain, rashes and heart palpitations and issues such as lack of concentration and short-term memory problems were particularly frequent and confirm previous observations, suggesting that they may characterize this condition.’ ❂ 📖 (1 Apr 2022 ~ Future Microbiology) Clinical characteristics, activity levels and mental health problems in children with long coronavirus disease: a survey of 510 children ➤ © 2022 Buonsenso et al / Future Microbiology.
❦ Headaches are one of the most common non-respiratory symptoms associated with SARS-CoV-2 and COVID-19. In fact, for most, a headache was the first initial symptom of the infection. For many, the headaches resolve after recovery from the acute infection. However, headaches are also one of the most common symptoms experienced by those with Long COVID. These migraine-like headaches can often last for weeks or even months, leaving many unable to perform routine daily activities. ❦ Headaches are a main symptom of acute COVID-19 While originally considered a respiratory virus, respiratory symptoms are not always the first indicator of a COVID infection. For example, for many, the first symptom is the loss of taste and/or smell ('anosmia'). Researchers believe that this may occur due to the virus entering the nasal cavity and crossing over into the brain. In this same way, many people often experience a severe headache in addition to the anosmia. ❦ How is a COVID headache different to a migraine? Many describe a COVID headache as crushing pain spread throughout the skull that can cause a pulsing or pressing pain. This pain typically worsens with physical activity or movement of the head. For this reason, many often refer to it as a migraine. However, a migraine is considered a primary headache. A COVID headache, on the other hand, is considered a secondary headache due to an underlying condition – in this case, the SARS-CoV-2 viral infection. While both types of headaches produce moderate to severe pain intensity, there are some differences between a traditional migraine and a COVID headache. COVID headache vs. migraine: ❦ Missing common additional symptoms ~ Migraines often come with nausea, vomiting, and a sensitivity to light and sound. In addition, many often experience an aura before headache onset. None of these symptoms typically accompany a COVID headache. ❦ Different pain ~ In many cases, migraines occur unilaterally, or on one side. COVID headaches are typically bilateral and affect the entire head. ❦ Do not respond to medication ~ If you have a history of migraines and take prescribed medication, you may find the COVID headache does not respond. In fact, a COVID headache is unlikely to respond to traditional headache medications in general, including over-the-counter pain medications such as acetaminophen or ibuprofen. Headaches continue with Long COVID Lingering headaches are not uncommon after viral infections, so it was no surprise to see headaches become a symptom associated with Long COVID. However, the persistence and severity of headaches with Long COVID has been different than with previous viral infections. While many of these headaches do improve on their own over time, many people continue to struggle with severe headaches that can last for weeks or months. In many cases, people will have a baseline headache that gets worse from time to time, along with other Long COVID symptoms. What is causing COVID headaches? [At the time of writing (24 Feb 2022)] the exact cause of these COVID headaches is unknown. However, researchers and clinicians have some theories. 1. Researchers propose that the trigeminal nerve endings in the nasal cavity may sustain direct viral damage that activates the trigeminovascular system, resulting in headaches, as well as other cognitive symptoms. 2. Studies are showing that many COVID patients are experiencing unusual microclots in their blood after recovering from the acute infection. These microclots can prevent adequate oxygen transportation throughout the body and contribute to Long COVID symptoms, including headaches. 3. Neurological damage has been seen in many COVID and Long COVID patients, but the exact cause of this damage is still unknown. Some theories believe that the virus may be able to cause direct damage to the brain by entering through the olfactory bulb or through the bloodstream or nerve endings. In addition, as your body fights the virus, your immune system often goes into overdrive, creating autoantibodies that attack healthy cells within the body and cause damage. 4. Jaw or dental concerns. ❂ 📖 Related: (19 July 2021 ~ Nature / Scientific Reports) Frequency and phenotype of headache in Covid-19: a study of 2194 patients ➤ 📖 Related: (15 May 2020 ~ Headache: The Journal of Head and Face Pain) COVID-19 is a Real Headache! ➤ 📖 Related: (9 May 2022 ~ Preprint) Combined triple treatment of fibrin amyloid microclots and platelet pathology in individuals with Long COVID / Post-Acute Sequelae of COVID-19 (PASC) can resolve their persistent symptoms ➤ ❂ 📖 (24 Feb 2022 ~ RTHM) Long COVID: Migraines and Headaches ➤ © 2022 RTHM.
❦ It has long been suspected by scientists that the flu (influenza) might play a role in developing Parkinson’s disease (PD) later in life. Compared to those who were not diagnosed with the flu, there was a 90% higher risk of PD for those who had the flu 15 or more years earlier. Inflammation is clearly a factor in PD – and influenza is known to trigger an extreme inflammatory response in the body. In light of the COVID-19 pandemic, and its known neurological consequences such as brain fog and loss of smell, continued robust research into how inflammation impacts the brain is warranted. ❂ 📖 (22 Feb 2022 ~ Parkinson's Foundation) The Flu Factor: Is There a Link to Parkinson's? ➤ © 2022 Parkinson’s Foundation.
❦ SARS-CoV-2 infection in pregnancy is known to confer a risk of increased morbidity and mortality for the mother. Placental and fetal infection with SARS-CoV-2 have been rare to date; SARS-CoV-2 infection in pregnancy appears most likely to impact fetal brain development via maternal and placental immune activation. Maternal and placental immune activation may impact the placenta and developing fetal brain via induction of immune activation and proinflammatory cytokine production, dysregulation of serotonin/other neurotransmitter signaling, and increased oxidative stress. ❂ 📖 (13 Feb 2022 ~ Trends in Molecular Medicine) COVID-19 in pregnancy: implications for fetal brain development ➤ © 2022 Shook et al / Trends in Molecular Medicine.
❦ SARS-CoV-2 infection, moderated in severity by age-, sex-, and race/ethnicity-dependent factors, initiates a disease progression that has the potential to promote cognitive decline and exacerbate pre-existing dementia. The damage cascade of COVID-19 is multi-faceted and interdependent, with multiple pathways that could lead to cognitive hazard mechanisms. One such cognitive hazard mechanism, cerebral direct infection, is possible with the SARS-CoV-2 virus, exhibiting neuroinvasive and neurotropic characteristics with neurovirulent potential. The greatest cognitive risk though may be from immune-mediated damage originating as cytokine storms that have far-reaching consequences for multiple organ systems, including the brain. Damage to organ systems and detrimental immune response, across the disease progression of COVID-19, may affect cognition via cerebral ischemia, hypoxia/acidosis, and neuroinflammation. The initiation of a coagulation cascade, from excessive immune response, which can generate micro-/macro-thromboemboli also poses significant risk. While long-term cognitive outcomes have not been fully evaluated, emerging reports indicate high rates of long-term symptoms and cognitive alterations in recovered COVID-19 patients. Due to these plausible COVID-19 cognitive decline pathways, evidence of prevalent neurological symptoms in patients, and long-term symptoms in recovered individuals, our conclusion is that COVID-19 represents a credible risk for cognitive decline and has the potential to exacerbate pre-existing dementia. For those at higher baseline dementia risk, older adults, those with cardiovascular risk factors, and people of color, COVID-19 may not only increase the risk of cognitive decline but also interact in a synergistic way with pre-existing dementia risk factors to disproportionately increase this dementia risk. ❂ 📖 (28 Jul 2021 ~ Neurodegenerative Diseases) The Impact of the COVID-19 Pandemic on Dementia Risk: Potential Pathways to Cognitive Decline ➤ © 2021 Pyne and Brickman / Neurodegenerative Diseases.
❦ The brains of people who died from COVID-19 were remarkably similar to the brains of people who die from neurodegenerative diseases such as Alzheimer’s and Parkinson’s , showing inflammation and disrupted circuitry . — “The brains of patients who died from severe COVID-19 showed profound molecular markers of inflammation , even though those patients didn’t have any reported clinical signs of neurological impairment,” said study co-senior author Tony Wyss-Coray, a professor of neurology and neurological sciences at Stanford University. His team analyzed brain tissue from eight people who died of COVID-19 and 14 people who died of other causes. About one-third of hospitalized COVID-19 patients report neurological symptoms such as fuzzy thinking , forgetfulness , difficulty concentrating and depression , Wyss-Coray noted. These problems can persist as part of what’s called Long COVID, a lingering condition that sometimes affects patients after they recover from the original infection. ❂ 📖 (21 Jun 2021 ~ Nature) Dysregulation of brain and choroid plexus cell types in severe COVID-19 ➤ 📖 (22 Jun 2021 ~ MedicalXpress) Autopsy study shows how COVID harms the brain ➤ © 2021 MedicalXpress.
❦ ‘Coronavirus disease 2019 (COVID-19), which resulted from the bpandemic outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a massive inflammatory cytokine storm leading to multi-organ damage including that of the brain and testes . While the lungs , heart , and brain are identified as the main targets of SARS-CoV-2 -mediated pathogenesis, reports on its testicular infections have been a subject of debate. The brain and testes are physiologically synchronized by the action of gonadotropins and sex steroid hormones. Though the evidence for the presence of the viral particles in the testicular biopsies and semen samples from COVID-19 patients are highly limited, the occurrence of testicular pathology due to abrupt inflammatory responses and hyperthermia has increasingly been evident. The reduced level of testosterone production in COVID-19 is associated with altered secretion of gonadotropins . Moreover, hypothalamic pathology which results from SARS-CoV-2 infection of the brain is also evident in COVID-19 cases. This article revisits and supports the key reports on testicular abnormalities and pathological signatures in the hypothalamus of COVID-19 patients and emphasizes that testicular pathology resulting from inflammation and oxidative stress might lead to infertility in a significant portion of COVID-19 survivors.’ ❂ 📖 (07 Jan 2021 ~ Reproductive Sciences) Testicular Atrophy and Hypothalamic Pathology in COVID-19: Possibility of the Incidence of Male Infertility and HPG Axis Abnormalities ➤ © 2021 Reproductive Sciences .
❦ the brain & neurological system: scientific papers & media articles
✒ 2024
📖 (19 Jan 2024 ~ Nature: Scientific Reports)
Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19 ➤
❂
✒ 2023
📖 (7 Nov 2023 ~ Journal of Neurology) Persistent cognitive slowing in post-COVID patients: longitudinal study over 6 months ➤
❂
📖 (19 Sep 2023 ~ PNAS Nexus) Severe acute respiratory syndrome coronavirus 2 infection leads to Tau pathological signature in neurons ➤
❂
📖 (12 Sep 2023 ~ eBioMedicine: Lancet Discovery Science) Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death ➤
❂
📖 (1 Sep 2023 ~ Pre-print) SARS-CoV-2 Spike amyloid fibrils specifically and selectively accelerates amyloid fibril formation of human prion protein and the amyloid β peptide ➤
❂
📖 (8 June 2023 ~ Queensland Brain Institute) COVID-19 can cause brain cells to 'fuse' ➤
❂
📖 (7 June 2023 ~ Science Advances) SARS-CoV-2 infection and viral fusogens cause neuronal and glial fusion that compromises neuronal activity ➤
❂
📖 (1 May 2023 ~ Patient Care) Persistent Changes in Brain Function Observed in Persons with Long COVID ➤
➲ 'The greater activity occurred outside of the normal working memory brain network. We often see such changes in patients with a brain injury: deficits in the default mode network of the brain leads to an increase in activity in other regions to help maintain brain function.'
✢ Related: (26 Apr 2023 ~ Neurology) Changes in Brain Activation Pattern During Working Memory Tasks in People With Post-COVID Condition and Persistent Neuropsychiatric Symptoms ➤
➲ 'Post-Covid Condition (PCC) participants with neuropsychiatric symptoms demonstrated compensatory neural processes with greater usage of alternate brain regions, and reorganized networks, to maintain normal performance during working memory tasks.'
❂
📖 (19 Apr 2023 ~ Nature / Scientific Reports) Cognitive impairment in young adults with post COVID-19 syndrome ➤
➲ 'The results presented here reveal that at least 85% [of the 214 patients with post COVID-19 syndrome] exhibit deficits in one neuropsychological test.
Also, the youngest patients were those who showed the most marked and heterogeneous cognitive impairment, while the oldest patients maintained their cognitive functions preserved to a greater extent with only a mild impairment in attention and speed processing.'
❂
📖 (10 Apr 2023 ~ Nature / Scientific Reports) Cerebral hypoperfusion in post-COVID-19 cognitively impaired subjects revealed by arterial spin labeling MRI ➤
➲ 'The most frequent neurological manifestations of post-COVID-19 include increased fatigue, diffuse myalgia, ageusia, anosmia, headache, sleep disturbances, dysautonomia and cognitive impairment.
Particularly, cognitive impairment has been increasingly recognised as a long-term sequela of COVID-19.
Recent follow-up investigations reported prevalence of cognitive deficits in 36% of patients at 3 months and 10 months after infection.'
❂
📖 (4 Apr 2023 ~ SciTechDaily) Researchers Discover Connection Between Traumatic Brain Injury and Long COVID ➤
➲ 'The Linseman Laboratory is studying the long-term brain health effects of COVID-19 in individuals with and without traumatic brain injury (TBI).
Preliminary data suggest that those with a history of both COVID-19 and TBI experience more severe Long COVID symptoms, a higher symptom burden, and more frequent symptoms.
Those who reported having COVID-19 and TBI reported worse depressive symptoms, worse functional outcomes, and increased fatigue.'
❂
📖 (1 Apr 2023 ~ Human Genetics) Direct and indirect impact of SARS-CoV-2 on the brain ➤
➲ 'From mild anosmia to severe ischemic stroke, the impact of SARS-CoV-2 on the central nervous system is still a great challenge to scientists and healthcare practitioners.
Besides the acute and severe neurological problems described, as encephalopathies, leptomeningitis, and stroke, the chronic impact observed during Long COVID or the post-acute sequelae of COVID-19 (PASC) greatly intrigues scientists worldwide.
Strikingly, even asymptomatic, and mild-diseased patients may evolve with important neurological and psychiatric symptoms such as confusion, memory loss, cognitive decline and chronic fatigue, associated or not with anxiety and depression.'
❂
📖 (23 Mar 2023 ~ Brain Science) Parkinson's Disease, SARS-CoV-2, and Frailty: Is There a Vicious Cycle Related to Hypovitaminosis D? ➤
➲ 'The possible neurological consequences of SARS-CoV-2 infection, associated with physical and cognitive frailty, could lead to a worsening of Parkinson's disease (PD) in infected patients or – more rarely – to an increase in the Parkinsonian symptomatology.
Parkinson's disease (PD) or Parkinsonism has been described after infections with viruses, such as the Epstein-Barr virus, hepatitis C virus, HIV, influenza A virus, Japanese encephalitis virus, varicella zoster virus, or West Nile virus.
Therefore, the hypothesis that SARS-CoV-2 may have even longer-term effects on the brain and lead to an increase in cases of Parkinson's disease, as occurred in the years following the Spanish flu, has been put forward.'
❂
📖 (23 Mar 2023 ~ Frontiers in Neurology) Headache in long COVID as disabling condition: A clinical approach ➤
➲ 'The major late neurological manifestations [of Long COVID syndrome] include hyposmia, hypogeusia, dizziness, insomnia, and headache characterized by intense and frequent chronic pain that is resistant to easily accessible drugs.
Headache is a disabling condition in patients with Long COVID-19, exacerbating the conditions of those with headaches prior to contracting COVID-19.'
❂
📖 (March 2023 ~ European Neuropsychopharmacology) Brain correlates of subjective cognitive complaints in COVID-19 survivors: A multimodal magnetic resonance imaging study ➤
❂
📖 (March 2023 ~ Science Direct: Brain, Behavior, & Immunity) Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies ➤
❂
📖 (6 Mar 2023 ~ Cells) Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics ➤
❂
📖 (1 Mar 2023 ~ Scientific American) Long COVID Now Looks like a Neurological Disease, Helping Doctors to Focus Treatments ➤
❂
📖 (1 Mar 2023 ~ Business Standard) Long Covid cuts brain oxygen, worsens cognitive problems, depression ➤
❂
📖 (1 Mar 2023 ~ University of Waterloo) Long COVID linked to lower brain oxygen levels, cognitive problems and psychiatric symptoms ➤
❂
📖 (March 2023 ~ Brain, Behavior, & Immunity: Health) Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies ➤
❂
📖 (27 Feb 2023 ~ Lancet / eClinicalMedicine) Structural brain changes in patients with post-COVID fatigue: a prospective observational study ➤
❂
📖 (23 Feb 2023 ~ Journal of Neurology) Patterns of acute ischemic stroke and intracranial hemorrhage in patients with COVID-19 ➤
❂
📖 (20 Feb 2023 ~ Journal of Clinical Medicine) COVID-19-Related Neuropathic Pain: A Systematic Review and Meta-Analysis ➤
❂
📖 (14 Feb 2023 ~ Journal of Alzheimer's Disease Reports) The Effects of SARS-CoV-2 Infection on the Cognitive Functioning of Patients with Pre-Existing Dementia ➤
➲ 'Cognitive postscripts of COVID-19, codenamed as 'cognitive COVID' or 'brain fog,' characterized by multi-domain cognitive impairments, are now being reckoned as the most devastating sequelae of COVID-19.
The rapid progression of dementia, the addition of further impairments / deterioration of cognitive abilities, and the increase or new appearance of white matter lesion burden suggest that previously compromised brains have little defense to withstand a new insult (i.e., a 'second hit'-like infection / dysregulated immune response, and inflammation).'
✢ Related: (4 Apr 2023 ~ Eurekalert) New study shows SARS-CoV-2 infection accelerates the progression of dementia ➤
'All subtypes of dementia, irrespective of patients' previous dementia types, behaved like rapidly-progressive dementia following COVID-19.'
✢ Related: (4 Apr 2023 ~ NeuroscienceNews) COVID-19 Infection Accelerates the Progression of Dementia ➤
'A rapidly and aggressively deteriorating course was observed in patients having insidious-onset, slowly-progressive dementia, and who were previously cognitively stable.'
❂
📖 (13 Feb 2023 ~ NPJ Parkinson's Disease) Detection of SARS-CoV-2 viral proteins and genomic sequences in human brainstem nuclei ➤
❂
📖 (2 Feb 2023 ~ Brain) Neuropsychiatric disorders following SARS-CoV-2 infection ➤
❂
📖 (February 2023 ~ Leadership) Japan: Over 10% Of Kids With COVID-related Brain Disease Died In Japan – Survey ➤
❂
📖 (28 Jan 2023 ~ NeuroImage: Clinical) Brain diffusion alterations in patients with COVID-19 pathology and neurological manifestations ➤
❂
📖 (26 Jan 2023 ~ Plos Blogs: DNA Science) COVID Virus Ventures Beyond the Lungs, Often Lodging in the Brain ➤
❂
📖 (23 Jan 2023 ~ Journal of Neurology) Brain positron emission tomography (PET) and cognitive abnormalities one year after COVID-19 ➤
❂
📖 (19 Jan 2023 ~ Neuron) Virus exposure and neurodegenerative disease risk across national biobanks ➤
❂
📖 (18 Jan 2023 ~ Journal of Clinical Medicine) Cognitive Deficits in the Acute Phase of COVID-19: A Review and Meta-Analysis ➤
❂
📖 (17 Jan 2023 ~ BMC Neurology) Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 "long haulers" ➤
❂
📖 (16 Jan 2023 ~ Brain) Haemorrhage of human foetal cortex associated with SARS-CoV-2 infection ➤
➲ 'Strikingly, the [foetal brain] haemorrhages are predominately found in the late first and early second trimester of gestation, a period of development in which the effect of the COVID-19 pandemic has not been thoroughly investigated.
Specifically, the majority were between 12 and 14 pcw, a critical window of human foetal brain development when the endothelial tight junctions increase to form the blood-brain barrier.
Our observations of disrupted foetal cerebral vasculature are consistent with reports of damage to the microvasculature of the adult brain in SARS-CoV-2 infected patients.'
❂
📖 (14 Jan 2023 ~ Acta Neuropathologica Communications) Reduced T-cell densities in cranial nerves of patients who died with SARS-CoV-2 infection ➤
❂
✒ 2022
📖 (17 Dec 2022 ~ Acta Neuropathologica Communications) Brain autopsies of critically ill COVID-19 patients demonstrate heterogeneous profile of acute vascular injury, inflammation and age-linked chronic brain diseases ➤
❂
📖 (14 Dec 2022 ~ Nature) SARS-CoV-2 infection and persistence in the human body and brain at autopsy ➤
❂
📖 (12 Dec 2022 ~ Yale School of Medicine) Potential New Treatment for "Brain Fog" in Long COVID Patients ➤
❂
📖 (5 Dec 2022 ~ Nature Aging) Severe COVID-19 is associated with molecular signatures of aging in the human brain ➤
➲ 'COVID-19 is an acute respiratory disease often accompanied by neurological sequelae.
Individuals with previous severe COVID-19 exhibit a 10-year average drop in their global cognitive performance, mimicking accelerated aging.
Complementary studies combining neuroimaging and cognitive screening implicate COVID-19-induced impairment of the frontal cortex, a critical area for cognitive function.
Our findings indicate that COVID-19 is associated with molecular signatures of brain aging.'
❂
📖 (5 Dec 2022 ~ New Atlas) Harvard study links severe COVID with genetic signs of brain aging ➤
❂
📖 (30 Nov 2022 ~ Revue Neurologie) Cerebrospinal fluid biomarkers in SARS-CoV-2 patients with acute neurological syndromes ➤
❂
📖 (30 Nov 2022 ~ Psychiatry Research)
Two-year follow-up of brain structural changes in patients who recovered from COVID-19: A prospective study ➤
❂
📖 (10 Nov 2022 ~ Nature Medicine) Acute and postacute sequelae associated with SARS-CoV-2 reinfection ➤
❂
📖 (10 Nov 2022 ~ Journal of Neuropathology & Experimental Neurology) Neuropathological findings in COVID-19: an autopsy cohort ➤
❂
📖 (1 Nov 2022 ~ The University of Queensland, Australia) 'A silent killer' – COVID-19 shown to trigger inflammation in the brain ➤
➲ 'Research led by The University of Queensland has found COVID-19 activates the same inflammatory response in the brain as Parkinson's disease.
The discovery identified a potential future risk for neurodegenerative conditions in people who've had COVID-19, but also a possible treatment.
"It may explain why some people who've had COVID-19 are more vulnerable to developing neurological symptoms similar to Parkinson's disease."
The researchers found the spike protein of the virus was enough to start the process [of triggering the inflammasome pathway], and was further exacerbated when there were already proteins in the brain linked to Parkinson's.
"So if someone is already pre-disposed to Parkinson's, having COVID-19 could be like pouring more fuel on that 'fire' in the brain."
"The same would apply for a predisposition for Alzheimer's and other dementias that have been linked to inflammasomes."
❂
📖 (1 Nov 2022 ~ Nature Molecular Psychiatry) SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein ➤
❂
📖 (6 Oct 2022 ~ Neuron) The neurobiology of long COVID ➤
❂
📖 (28 Sep 2022 ~ The Tyee) The Coming COVID Brain Wreck? ➤
➲ 'A new study adds to concerns about the severity and scope of neurological damage the virus can cause.'
❂
📖 (27 Sep 2022 ~ Frontiers in Neuroscience) SARS-CoV-2, long COVID, prion disease and neurodegeneration ➤
❂
📖 (23 Sep 2022 ~ CTV News/Canada) COVID raises risk of long-term brain injury, large U.S. study finds ➤
❂
📖 (22 Sep 2022 ~ Nature Medicine) Long-term neurologic outcomes of COVID-19 ➤
➲ 'Our results show that in the postacute phase of COVID-19, there was increased risk of an array of incident neurologic sequelae including ischemic and hemorrhagic stroke, cognition and memory disorders, peripheral nervous system disorders, episodic disorders (for example, migraine and seizures), extrapyramidal and movement disorders, mental health disorders, musculoskeletal disorders, sensory disorders, Guillain-Barré syndrome, and encephalitis or encephalopathy.'
✢ Related: (22 Sep 2022 ~ Washington University School of Medicine in St. Louis) COVID-19 infections increase risk of long-term brain problems ➤
➲ 'Those who have been infected with the [SARS-CoV-2] virus are at increased risk of developing a range of neurological conditions in the first year after the infection.
Such complications include strokes, cognitive and memory problems, depression, anxiety and migraine headaches.
Additionally, the post-COVID brain is associated with movement disorders, from tremors and involuntary muscle contractions to epileptic seizures, hearing and vision abnormalities, and balance and coordination difficulties as well as other symptoms similar to what is experienced with Parkinson's disease.'
❂
📖 (11 Sep 2022 ~ BMC Translational Neurodegeneration) The COVID-19 pandemic and Alzheimer's disease: mutual risks and mechanisms ➤
❂
📖 (6 Sep 2022 ~ International Review of Neurobiology) Chapter Five - Smell deficits in COVID-19 and possible links with Parkinson's disease ➤
❂
📖 (Sep 2022 ~ Ageing Research Reviews) SARS-CoV-2 and the central nervous system: Emerging insights into hemorrhage-associated neurological consequences and therapeutic considerations ➤
❂
📖 (11 Aug 2022 ~ PNAS) Morphological, cellular, and molecular basis of brain infection in COVID-19 patients ➤
❂
📖 (29 Jul 2022 ~ Brain) Neurovascular injury with complement activation and inflammation in COVID-19 ➤
❂
📖 (29 Jul 2022 ~ Brain: Editorial) How COVID-19 affects microvessels in the brain ➤
❂
📖 (7 Jul 2022 ~ Nature) COVID and the brain: researchers zero in on how damage occurs ➤
❂
📖 (July 2022 ~ Brain) Neurovascular injury with complement activation and inflammation in COVID-19 ➤
❂
📖 (30 Jun 2022 ~ News Medical Life Sciences) Ischemic stroke risk may be higher after COVID-19 compared to flu or bacterial pneumonia ➤
❂
📖 (May 2022 ~ Brain) Persistent white matter changes in recovered COVID-19 patients at the 1-year follow-up ➤
❂
📖 (22 Apr 2022 ~ Frontiers in Neuroscience) Brain Imaging Changes in Patients Recovered From COVID-19: A Narrative Review ➤
❂
📖 (1 Apr 2022 ~ Nature) Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates ➤
❂
📖 (7 Mar 2022 ~ Nature) SARS-CoV-2 is associated with changes in brain structure in UK Biobank ➤
❂
📖 (22 Feb 2022 ~ Parkinson's Foundation) The Flu Factor: Is There a Link to Parkinson's? ➤
➲ 'It has long been suspected by scientists that the flu (influenza) might play a role in developing Parkinson's disease (PD) later in life.
Compared to those who were not diagnosed with the flu, there was a 90% higher risk of PD for those who had the flu 15 or more years earlier.
Inflammation is clearly a factor in PD – and influenza is known to trigger an extreme inflammatory response in the body.
In light of the COVID-19 pandemic, and its known neurological consequences such as brain fog and loss of smell, continued robust research into how inflammation impacts the brain is warranted.'
❂
📖 (12 Jan 2022 ~ UConn Today) COVID is Not Just a Respiratory Illness – It Can Cause Strokes Too ➤
❂
✒ 2021
📖 (1 Dec 2021 ~ JAMA Neurology) Long-term Risk of Parkinson Disease Following Influenza and Other Infections ➤
➲ 'Influenza has been associated with the risk of developing Parkinson disease, but the association is controversial.
In this case-control study, influenza was associated with diagnoses of Parkinson disease more than 10 years after infection.'
❂
📖 (30 Sep 2021 ~ Translational Psychiatry) Neuropsychiatric manifestations of COVID-19, potential neurotropic mechanisms, and therapeutic interventions ➤
❂
📖 (22 Jun 2021 ~ Medical Xpress) Autopsy study shows how COVID harms the brain ➤
❂
📖 (21 Jun 2021 ~ Nature) Dysregulation of brain and choroid plexus cell types in severe COVID-19 ➤
❂
📖 (June 2021 ~ Brain Hemorrhages) COVID-19 and stroke: A review ➤
➲ 'COVID-19 patients have presented with a wide range of neurological disorders, among which stroke is the most devastating.
SARS-CoV-2 infection induces coagulopathy, disrupts endothelial function, and promotes hypercoagulative state. Severe COVID-19 infection renders patients bedridden, and in certain cases requiring instrumental support.'
❂
📖 (8 Apr 2021 ~ St. Luke's Health) Connections Between COVID-19 and Stroke You Need to Know ➤
❂
📖 (23 Mar 2021 ~ Annals of Clinical and Translational Neurology) Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 "long haulers" ➤
❂
📖 (1 Mar 2021 ~ Hospital Practice) SARS-CoV-2 invasion of the central nervous: a brief review ➤
❂
📖 (15 Jan 2021 ~ European Journal of Nuclear Medicine) The cerebral network of COVID-19-related encephalopathy: a longitudinal voxel-based 18F-FDG-PET study ➤
❂
📖 (07 Jan 2021 ~ Reproductive Sciences) Testicular Atrophy and Hypothalamic Pathology in COVID-19: Possibility of the Incidence of Male Infertility and HPG Axis Abnormalities ➤
❂
✒ 2020
📖 (10 Sep 2020 ~ BMC / Fluids and Barriers of the CNS) The potential role of microvascular pathology in the neurological manifestations of coronavirus infection ➤
❂
📖 (20 Aug 2020 ~ NPJ Parkinson's Disease) COVID-19 and possible links with Parkinson's disease and parkinsonism: from bench to bedside ➤
❂
📖 (13 Mar 2020 ~ ACS Chemical Neuroscience) Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms ➤
❂
