Highly recommend this review from Oba et al. on the current status of Long COVID research & treatment -- worth a read!

Here, the authors outline the major hypotheses for the root causes of LC. The research community has largely been coalescing around these ideas in the last 1-2 years.

These root causes of LC include:

👉 persistent viral infection,
👉 latent virus reactivation,
👉 immune dysregulation,
👉 autoimmunity,
👉 gut microbiota alterations,
👉mitochondrial dysfunction,
👉 endothelial injury
👉 coagulation abnormalities

The Long COVID community will likely be familiar with these hypotheses.

However, these authors do a great job of explaining mechanistic insights for how and why these phenomena may be occurring - with info you may not have heard before.

Of particular interest was their section on why the SARS-CoV-2 interest may persist - believed by many, including our team, to be the leading root cause of Long COVID.

Let's take a look at what they said!

1/ Possible reasons why SARS-CoV-2 may persist in the human body:

1) Viral persistence has also been reported after infections with other single-stranded RNA viruses, such as Ebola. Ebola RNA has been found throughout the human body months and years after acute infection - and SARS-CoV-2 may be persisting for a similar reason.

2) SARS-CoV-2 possesses multiple immune evasion mechanisms, where it suppresses our own human responses to infection. Its proteins NSP1 and ORF6, inhibit the production of Interferon, which is an important chemical signal our bodies normally produce to fight viruses.

Meanwhile, its ORF8 protein downregulates MHC-1 expression, which is a mechanism our body normally uses to tell the immune system which of our cells are infected by a virus, so it can kill them. When MHC-1 is inhibited, the SARS-CoV-2 virus can remain in our cells, undetected.

2/

✨What causes Brain Fog in Long COVID?🧠

Thanks @MensHealthMag for this great article on new research towards our understanding of brain fog!

In a new study published in Brain Communications, researchers identified a major possible cause of brain fog in Long COVID.

They used PET-scan imaging to compare the brains of Long COVID patients to healthy controls.

They found that the Long COVID patients had increased numbers of a particular type of receptor within the brain, called AMPA receptors.🧐

1/ AMPA receptors help brain cells communicate with one another.

These receptors are crucial for processes like learning new things and storing new memories.

The brain learns and stores new information by forming connections between neurons.🧠

When the number of AMPA receptors has increased, it strongly suggests that something has gone wrong in this process.

2/

Here it is: the long-awaited recap of yesterday's space with @rd108 and @MichaelPelusoMD!

Dr. Peluso is an infectious diseases specialist, and HIV and Long Covid researcher at @UCSF Medical School. He is a member of the @Polybio research consortium, as well as the UCSF LIINC team specifically focusing on Long Covid.

Dr. Peluso shared his insights on the root causes of Long Covid, what's been holding research back, and how to move it forward!

To start with, he had some words of hope for LC sufferers.

He explained that while LC sufferers frequently express concern about being left behind as the media stops talking about Covid, he said nothing could be furfher from the truth!

His words:

“I want everyone know that there is a large group of scientists and clinicians who have been working in this field for five years now…. we are all-in in our efforts to try to figure this out.

We really want to see this through and get answers for the millions of people dealing with this debilitating disease.”

1/ Dr. Peluso shared some key insighrs with us from his years on the frontlines studying Long Covid.

Dr. Peluso explained one of the major problems with RECOVER - which as LC suffered know, blew through its initial $1 billion in funding with little to show for it.

A key shortcoming of RECOVER’s initial phase was that it stratified patients into different groups based on symptoms. This meant that, even if patients’ underlying symptoms were all caused by a common cause, such as viral persistence, it became harder to see what was truly going on underneath the surface.

That’s part of why it took the @NIH nearly five years from the start of the pandemic to identify viral persistence as their top hypothesis (as @NIHDirector announced this past spring).

Now, we’re in a situation where LC patients have been left to suffer with no formal treatments. Rohan and Dr Peluso talked about how to move trials forward as quickly as possible.

2/

People aren’t talking about this enough.

It’s hard to see; it’s hard to measure.

There are still no FDA-approved tests for Long Covid.

Yet a recent article in Nature Medicine estimates that the impact of Long Covid on the workforce is 1 TRILLION dollars.

1/ #LongCovid According to this recent study from @YaleMedicine, up to 14% of 3,500 Long COVID patients surveyed in the US had not returned to work three months after getting sick. 2/

yalemedicine.org/news/long-covi…