None of 25 routine laboratory tests were clinically useful for diagnosing long COVID, despite some slight differences in results between patients with and without prior SARS-CoV-2 infection, according to an analysis of the RECOVER-Adult cohort.

Among participants with a post-acute sequelae of COVID-19 (PASC) index of 12 points or higher, there were no meaningful differences in mean laboratory values when compared with those with a PASC index of zero, reported Kristine Erlandson, MD, MSc, of the University of Colorado, Anschutz Medical Campus, in Aurora, and colleagues in the Annals of Internal Medicineopens in a new tab or window.

"While routine laboratory values should certainly be obtained to rule out other conditions that may contribute to long COVID symptoms, we don't expect these laboratory values to be abnormal, even among people with severe long COVID symptoms," Erlandson told MedPage Today.

"We were very surprised when none of the labs distinguished between those that had prior COVID or those that had higher values on the PASC index," Erlandson said, noting that the initial purpose of the analysis was to identify laboratory values that could be included in a revised version of the PASC index.

The routine laboratory tests included those for electrolyte levels; liver, renal, and thyroid function; lipid and hematology panels; and inflammatory markers.

"The new clinical knowledge gained is that none of these 25 routine clinical laboratory tests can aid in diagnosing long COVID," wrote Annukka Antar, MD, PhD, and Paul Auwaerter, MD, both of the Johns Hopkins University School of Medicine in Baltimore, in an accompanying editorialopens in a new tab or window.

These results were "somewhat surprising," they noted, given that a previous studyopens in a new tab or window identified several common abnormalities on routine lab tests after COVID-19 infection. In that study, which looked at a VA population with long COVID, the researchers found elevated hemoglobin A1C (HbA1C) levels, low hemoglobin levels, high total and low-density lipoprotein cholesterol levels, high triglyceride levels, and elevated platelet counts.

"Our findings do not rule out that there might be a biomarker or combination of biomarkers that do help understand the causes, identify risk factors for long COVID, or can be used to identify ideal treatments," Erlandson said.

An important limitation of the study was that pre-infection laboratory values were not available for most participants, so pre-and post-infection comparison of laboratory results was not possible and limited the researchers' ability to identify abnormalities resulting from infection.

Summary: New research uncovers how COVID-19 may cause neuroinflammation, leading to persistent neurological symptoms even after recovery.

The study found elevated levels of pro-inflammatory cytokines and significant changes in cerebrospinal fluid among hospitalized patients, highlighting the brain’s vulnerability to the virus.

These findings suggest that neuroinflammation could play a key role in the cognitive decline seen in “long COVID,” stressing the need for ongoing monitoring and targeted therapies for survivors.

Long COVID is a difficult therapeutic area to work in. It’s a scientifically challenging condition, but perhaps more critically, few want to fund new treatments. Private investors, Big Pharma, and government agencies alike see long COVID as too risky as long as its underlying mechanisms are so poorly understood. This dynamic has hampered the few biotechnology and pharmaceutical companies trying to develop new medicines. The lack of funding has frustrated people with long COVID, who have few options available to them. And crucially, it has snarled research and development, cutting drug development short.

Received 13 May 2024, Revised 2 July 2024, Accepted 8 September 2024, Available online 17 September 2024, Version of Record 17 September 2024.

Our findings are consistent with those of a population-based study in Scotland where prevalence of long COVID at least six-months after symptomatic infection varied from 6 %, when defining long COVID as not recovered from COVID-19, to 42 % when defining long COVID as partially recovered [32]. Although slightly higher, our unadjusted prevalence estimate for severe long COVID of 4.8 % is comparable to findings of a modeling study conducted by Tenforde et al. estimating activity-limiting long COVID >1 month after infection to be 1.2–1.9 % of the adult US population [5]. While broader prevalence estimates allow for the public health planning necessary to meet the needs of individuals with long COVID, it is this most severely impacted proportion of patients who are likely to require the most intensive resources. As the discussion around a case definition for long COVID continues, especially in the absence of an objective laboratory indicator, it is increasingly important to pilot and validate survey questions to assess long COVID [11,33].

Damage to the brainstem – the brain’s ‘control centre’ – is behind long-lasting physical and psychiatric effects of severe Covid-19 infection, a study suggests.

Using ultra-high-resolution scanners that can see the living brain in fine detail, researchers from the Universities of Cambridge and Oxford were able to observe the damaging effects Covid-19 can have on the brain.

The study team scanned the brains of 30 people who had been admitted to hospital with severe Covid-19 early in the pandemic, before vaccines were available. The researchers found that Covid-19 infection damages the region of the brainstem associated with breathlessness, fatigue and anxiety.

The powerful MRI scanners used for the study, known as 7-Tesla or 7T scanners, can measure inflammation in the brain. Their results, published in the journal Brain, will help scientists and clinicians understand the long-term effects of Covid-19 on the brain and the rest of the body. Although the study was started before the long-term effects of Covid was recognised, it will help to better understand this condition.

The brainstem, which connects the brain to the spinal cord, is the control centre for many basic life functions and reflexes. Clusters of nerve cells in the brainstem, known as nuclei, are responsible for regulating and processing essential bodily functions such as breathing, heart rate, pain and blood pressure.

“Things happening in and around the brainstem are vital for quality of life, but it had been impossible to scan the inflammation of the brainstem nuclei in living people, because of their tiny size and difficult position.” said first author Dr Catarina Rua, from the Department of Clinical Neurosciences. “Usually, scientists only get a good look at the brainstem during post-mortem examinations.”

“The brainstem is the critical junction box between our conscious selves and what is happening in our bodies,” said Professor James Rowe, also from the Department of Clinical Neurosciences, who co-led the research. “The ability to see and understand how the brainstem changes in response to Covid-19 will help explain and treat the long term effects more effectively.”

In the early days of the Covid-19 pandemic, before effective vaccines were available, post-mortem studies of patients who had died from severe Covid-19 infections showed changes in their brainstems, including inflammation. Many of these changes were thought to result from a post-infection immune response, rather than direct virus invasion of the brain... continues

In the early days of the Covid-19 pandemic, before effective vaccines were available, post-mortem studies of patients who had died from severe Covid-19 infections showed changes in their brainstems, including inflammation. Many of these changes were thought to result from a post-infection immune response, rather than direct virus invasion of the brain.

World class discussion for the serious viewer. Professor Dalgleish informs us about several important topics: Problems encountered on his tour of Australia. Lessons learned from his research into cancer vaccines. The potential for ivermectin aid in cancer treatment. Vitamin D is essential in cancer treatment. Obvious mistakes in production of Covid vaccines. Evidence from virology for a lab leak of the covid virus. The existence of a simple bacterial preparation to treat sever cancers and infections which has been refused regulator approval.

Trust me, no one, even in public health or medicine, wants to talk or think about Covid-19. The trauma of those pandemic years is burnt into our minds. But, whether we want to deal with it or not, Covid-19 is still affecting all of us, and circulating at fairly high levels in Britain this month. While community surveys are no longer conducted by the Office for National Statistics to estimate overall cases, hospital data from England indicates that the weekly hospital admission rate for Covid-19 is at 4.64 for every 100,000 people, with the north-east region at 8.91.

These figures just cover people who are admitted to hospital and don’t reflect those suffering at home or attending GP clinics. While we were mainly fixated on death rates during the pandemic, the longer legacy concerns people who had and cleared the infection, but are still suffering – what is usually referred to as long Covid.

This chronic condition still has many questions hanging over it. We are still learning about its overall prevalence in the population (estimated at 5.5% of those infected in the UK in one study, and 15% in another study from the US), and there is continuing research on the underlying biology and immunology behind symptoms, including attempts to identify markers for diagnosis, as well as work towards promising treatments. Sufferers have had to fight first to have their condition recognised as “real” (instead of a figment of their imagination or a sign of mental weakness), and second for medical services to provide support and care.
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Patients with long COVID may have one or more symptoms such as cough, persistent fatigue, problems with taste or smell, sleep disturbance, concentration issues, memory changes, recurring headaches, shortness of breath, lightheadedness, bloating constipation, diarrhea, and more, as well as one or more diagnosable conditions such as anxiety, mood disorders, cognitive impairment, migraine, blood clots, stroke, cardiovascular disease, heart arrhythmia, fibromyalgia, diabetes, autoimmune disorders, and many more conditions, according to The New England Journal of Medicine (NEJM). Highlighted for emphasis by Doddie.

Personalized medicine, or precision medicine, considers a patient’s individual genetic, environmental, and lifestyle variability for the prevention and treatment of diseases. It is the exact opposite of the one-size-fits-all approach. A person’s observable traits, called phenotypes, are determined by a combination of their genetic makeup (genotype) and environmental factors. For example, weight is an observable trait or phenotype that may be impacted by diet, exercise, and other factors.

One of the aims of studying phenotyping for precision medicine is to understand the phenotypic abnormalities associated with a particular disease in order for clinicians to provide better diagnosis and treatment for the individual patient. Additionally, having knowledge of a disease’s full range of associated phenotypic abnormalities may help with early intervention and treatment for better outcomes.

MELBOURNE, Nov 11: Nearly five years into the pandemic, COVID is feeling less central to our daily lives.
But the virus, SARS-CoV-2, is still around, and for many people the effects of an infection can be long-lasting. When symptoms persist for more than three months after the initial COVID infection, this is generally referred to as long COVID.
In September, Grammy-winning Brazilian musician Sérgio Mendes died aged 83 after reportedly having long COVID.
Australian data show 196 deaths were due to the long-term effects of COVID from the beginning of the pandemic up to the end of July 2023.
In the United States, the Centers for Disease Control and Prevention reported 3,544 long-COVID-related deaths from the start of the pandemic up to the end of June 2022.
The symptoms of long COVID – such as fatigue, shortness of breath and “brain fog” – can be debilitating. But can you die from long COVID? The answer is not so simple.

How could long COVID lead to death?

There’s still a lot we don’t understand about what causes long COVID. A popular theory is that “zombie” virus fragments may linger in the body and cause inflammation even after the virus has gone, resulting in long-term health problems. Recent research suggests a reservoir of SARS-CoV-2 proteins in the blood might explain why some people experience ongoing symptoms.
We know a serious COVID infection can damage multiple organs. For example, severe COVID can lead to permanent lung dysfunction, persistent heart inflammation, neurological damage and long-term kidney disease.
These issues can in some cases lead to death, either immediately or months or years down the track. But is death beyond the acute phase of infection from one of these causes the direct result of COVID, long COVID, or something else? Whether long COVID can directly cause death continues to be a topic of debate.
Of the 3,544 deaths related to long COVID in the US up to June 2022, the most commonly recorded underlying cause was COVID itself (67.5%). This could mean they died as a result of one of the long-term effects of a COVID infection, such as those mentioned above.
COVID infection was followed by heart disease (8.6%), cancer (2.9%), Alzheimer’s disease (2.7%), lung disease (2.5%), diabetes (2%) and stroke (1.8%). Adults aged 75–84 had the highest rate of death related to long COVID (28.8%).
These findings suggest many of these people died “with” long COVID, rather than from the condition. In other words, long COVID may not be a direct driver of death, but rather a contributor, likely exacerbating existing conditions.

‘Cause of death’ is difficult to define

Long COVID is a relatively recent phenomenon, so mortality data for people with this condition are limited.
However, we can draw some insights from the experiences of people with post-viral conditions that have been studied for longer, such as myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS).
Like long COVID, ME/CFS is a complex condition which can have significant and varied effects on a person’s physical fitness, nutritional status, social engagement, mental health and quality of life.
Some research indicates people with ME/CFS are at increased risk of dying from causes including heart conditions, infections and suicide, that may be triggered or compounded by the debilitating nature of the syndrome.

So what is the emerging data on long COVID telling us about the potential increased risk of death?

Research from 2023 has suggested adults in the US with long COVID were at greater risk of developing heart disease, stroke, lung disease and asthma.
Research has also found long COVID is associated with a higher risk of suicidal ideation (thinking about or planning suicide). This may reflect common symptoms and consequences of long COVID such as sleep problems, fatigue, chronic pain and emotional distress.
But long COVID is more likely to occur in people who have existing health conditions. This makes it challenging to accurately determine how much long COVID contributes to a person’s death.
Research has long revealed reliability issues in cause-of-death reporting, particularly for people with chronic illness.

So what can we conclude?

Ultimately, long COVID is a chronic condition that can significantly affect quality of life, mental wellbeing and overall health.
While long COVID is not usually immediately or directly life-threatening, it’s possible it could exacerbate existing conditions, and play a role in a person’s death in this way.
Importantly, many people with long COVID around the world lack access to appropriate support. We need to develop models of care for the optimal management of people with long COVID with a focus on multidisciplinary care

Encephalitis lethargica is a neurological syndrome that spread across Europe and then the world beginning in the winter of 1916–17, and continuing into the 1930s. Although the exact number of people afflicted with encephalitis lethargica during the epidemic period is unknown, it is estimated to be more than one million worldwide (Ravenholt and Foege, 1982). Those who survived were sometimes left with lingering and permanent neurological sequelae that rendered them nearly akinetic. Although 100 years have elapsed since the beginning of the epidemic period, many questions remain about this mysterious illness: What causes it? How is it transmitted? Could an epidemic happen again?

The hyperkinetic form presented with an initial manic phase during which the patient experienced chorea, vocalizations, myoclonic twitches, and myorhythmia of the ocular and masticatory muscles. (Oculomasticatory myorhythmia is also indicative of Whipple’s disease, but it is not known whether the movement disorder seen in the hyperkinetic form of encephalitis lethargica is the same or different from that seen in Whipple’s disease). The manic phase was followed by generalized restlessness, weakness, and fatigue that persisted for days. During this hypomanic phase, patients experienced neuralgic pain in the face and limbs, visual and tactile hallucinations, and day-night sleep cycle reversal Edited for emphasis

Around 5–10% of people with COVID infections go on to experience long COVID, with symptoms lasting three months or more.

Researchers have proposed several biological mechanisms to explain long COVID. However, in a perspective article published in the latest Medical Journal of Australia, we argue that much, if not all, long COVID appears to be driven by the virus itself persisting in the body.

Since relatively early in the pandemic, there has been a recognition that in some people, SARS-CoV-2 – or at least remnants of the virus – could stay in various tissues and organs for extended periods. This theory is known as "viral persistence".

While the long-term presence of residual viral fragments in some people's bodies is now well established, what remains less certain is whether live virus itself, not just old bits of virus, is lingering – and if so, whether this is what causes long COVID.

This distinction is crucial because live virus can be targeted by specific antiviral approaches in ways that "dead" viral fragments cannot.

Viral persistence has two significant implications:

1. when it occurs in some highly immunocompromised people, it is thought to be the source of new and substantially different-looking variants, such as JN.1

2. it has the potential to continue to cause symptoms in many people in the wider population long beyond the acute illness. In other words, long COVID could be caused by a long infection.

What does the research say?

While there remains no single study that confirms that persistent virus is the cause of long COVID, collectively several recent key papers make a compelling case.

In February, a study in Nature found a high number of people with mild COVID symptoms had extended periods of shedding the genetic material of the virus, so-called viral RNA, from their respiratory tract.

Those with persistent shedding of this viral RNA – which almost certainly represents the presence of live virus – were at higher risk of long COVID.

Other key papers detected replicating viral RNA and proteins in blood fluid of patients years after their initial infection, a sign that the virus is likely replicating for long periods in some hidden reservoirs in the body, perhaps including blood cells.

Another study detected viral RNA in ten different tissue sites and blood samples 1–4 months after acute infection. This study found the risk of long COVID (measured four months following infection) was higher in those with persistently positive viral RNA.

The same study also gave clues about where in the body the persisting virus resides. The gastrointestinal tract is one site of considerable interest as a long-term viral hideout.

Earlier this week, further evidence of persistent virus increasing likelihood of long COVID has been published as part of the RECOVER initiative, a collaborative research project that aims to address the impacts of long COVID.

However, formal proof that virus capable of replicating can last for years in the body remains elusive. This is because isolating the live virus from reservoirs inside the body where the virus "hides" is technically challenging.

In its absence, we and other scientists argue the cumulative evidence is now sufficiently compelling to galvanise action.

What needs to happen next?

The obvious response to this is to fast-track trials of known antivirals for prevention and cure of long COVID.

This should include more left-field therapies such as the diabetes drug metformin. This has possible dual benefits in the context of long COVID:

* its antiviral properties, which have demonstrated surprising efficacy against long COVID

* as a potential therapeutic in treating impairments related to fatigue.

However, another major thrust should be the development of new drugs and the establishment of clinical trial platforms for rapid testing.

Science has uncovered exciting therapeutic options. But translating these into forms usable in the clinic is a large hurdle that requires support and investment from governments.

Demystify and preventing long COVID

The notion of "long infection" as a contributor or even the driver of long COVID is a powerful message. It could help demystify the condition in the eyes of the wider community and increase awareness among the general public as well as medical professionals.

It should help raise awareness in the community of the importance of reducing rates of re-infection. It is not just your first infection, but each subsequent COVID infection carries a risk of long COVID.

Long COVID is common and isn't restricted to those at high risk of severe acute disease but affects all age groups. In one study, the highest impact was in those aged 30 to 49 years.

So, for now, we all need to reduce our exposure to the virus with the tools available, a combination of:

* clean indoor air approaches. In its simplest form, this means being conscious of the importance of well-ventilated indoor spaces, opening the windows and improving airflow as COVID spreads through air. More sophisticated ways of ensuring indoor air is safe involve monitoring quality and filtering air in spaces that cannot be easily naturally ventilated

* using high-quality masks (that are well-fitting and don't let air in easily, such as N95-type masks) in settings where you don't have confidence of the quality of the indoor air and/or that are crowded

* testing, so you know when you're positive. Then, if you're eligible, you can get treatment. And you can be vigilant about protecting those around you with masks, staying at home where possible, and ventilating spaces

* staying up to date with COVID booster doses. Vaccines reduce long COVID and other post-COVID complications.

Hopefully one day there will be better treatments and even a cure for long COVID.

But in the meantime, increased awareness of the biomedical basis of long COVID should prompt clinicians to take patients more seriously as they attempt to access the treatments and services that already exist.

Brendan Crabb, Director and CEO, Burnet Institute; Gabriela Khoury, Theme Leader, Antiviral Immunity, Burnet Institute, and Michelle Scoullar, Senior Research Fellow, Burnet Institute

This article is republished from The Conversation under a Creative Commons license. Read the original article.