Neuroinflammation in Long Covid

[Pyrrhus]

Cerebrospinal fluid in Long Covid

As mentioned before, the brain and the cerebrospinal fluid (CSF) are separated by a part of the blood-brain-barrier, so looking for clues in the cerebrospinal fluid will only work if the blood-brain-barrier is damaged or compromised, as in acute encephalitis. Here's a diagram to clarify:

This fundamental problem with looking in the cerebrospinal fluid, for acute COVID patients, was noted in these two review articles:

Evidence of central nervous system infection and neuroinvasive routes, as well as neurological involvement, in the lethality of SARS-CoV-2 infection (Liu et al., 2020)
https://doi.org/10.1002/jmv.26570

Among the published data, only 1.28% COVID-19 patients who underwent cerebrospinal fluid (CSF) tests were positive for SARS-CoV-2 in CSF. However, this does not mean the absence of CNS infection in most COVID-19 patients because postmortem studies revealed that some patients with CNS infection showed negative results in CSF tests for SARS-CoV-2.

What can cerebrospinal fluid testing and brain autopsies tell us about viral neuroinvasion of SARS-CoV-2 (Li et al., 2021)
https://doi.org/10.1002/jmv.26943

In total, we identified 28 autopsy studies. [...] Among 202 patients, 108 (108/202, 53.5%) were further tested for SARS-CoV-2 in the neural tissues. [...] Among all patients who underwent viral detection, SARS-CoV-2 RNA was detected in the brain in 56 (51.9%) of 108 tested patients, while viral proteins were detected in the brain in 25 (29.4%) of 85 tested patients. [...] We identified 97 relevant papers and found the presence of SARS-CoV-2 in the CSF in 30 (6.4%) of 468 patients who underwent CSF testing.

Now, here's a case study that found low levels of virus in the cerebrospinal fluid of a patient with Long Covid:

SARS-CoV-2 RNA in the Cerebrospinal Fluid of a Patient with Long COVID (Viszlayova et al., 2021)
https://journals.sagepub.com/doi/full/10.1177/20499361211048572

We describe a long COVID patient with SARS-CoV-2 RNA in the cerebrospinal fluid, which seems important, specifically due to recent reports of gray matter volume loss in COVID-19 patients. Further studies of SARS-CoV2 RNA, markers of inflammation, and neuronal damage in the CSF of patients with long COVID would be useful and should address whether the CNS can serve as a reservoir of SARS-CoV-2, clarify the pathway by which COVID-19 contributes to CNS dysfunction, and how best to therapeutically address it.

Here's a larger case study that looked in the cerebrospinal fluid of 20 Long Covid patients and found no virus:

Cerebrospinal Fluid Analysis Post–COVID-19 Is Not Suggestive of Persistent Central Nervous System Infection (Schweitzer et al., 2021)
https://doi.org/10.1002/ana.26262

Cerebrospinal fluid was assessed between days 1 and 30 (n = 12), between days 31 and 90 (n = 8), or later than 90 days (post–COVID-19, n = 20) after COVID-19 diagnosis. SARS-CoV-2 RNA was absent in all patients, and in none of the 20 patients with post–COVID-19 syndrome were intrathecally produced anti–SARS-CoV-2 antibodies detected.

Finally, here's a study that found abnormalities, such as elevated CSF protein or abnormal oligoclonal banding, in the cerebrospinal fluid of 77% of Long Covid (PASC) patients, but no abnormalities in people without Long Covid:

Risk factors and abnormal cerebrospinal fluid associate with cognitive symptoms after mild COVID-19 (Apple et al., 2022)
https://forums.phoenixrising.me/thr...d-offers-clues-to-post-covid-brain-fog.86749/

We evaluated 22 adults reporting cognitive [Long Covid (PASC)] and 10 not reporting cognitive symptoms after mild SARS-CoV-2 infection through structured interviews, neuropsychological testing, and optional cerebrospinal fluid (CSF) evaluations (53%). [...] [Lumbar punctures (LP)] were performed a median of 9.7 months (IQR: 6.9–13.9) after first COVID-19 symptom. Overall, 77% (10/13) of participants with cognitive PASC had a CSF abnormality compared with 0% (0/4) of cognitive controls (p = 0.01). Two participants with cognitive PASC displayed elevated CSF protein without other explainable cause (59 and 76 mg/dL; reference range 15–45 mg/dL). [...] Abnormal oligoclonal banding (OCB) patterns were identified in 69% (9/13) of participants with cognitive PASC compared to 0% of cognitive controls (p = 0.03).

 

[Pyrrhus]

Animal models of Long Covid

As mentioned before, in order to develop an animal model of a disease you must first have a clear understanding of the underlying pathology of the disease that you are trying to model. If you don't, then the animal model may turn out to be useless, or even worse - misleading.

For acute COVID infections, it is fairly straightforward to make an animal model. First pick an animal that has a similar physiology and immune system as humans, as well as similar viral receptors as humans, and then infect the animal with the coronavirus. Monkeys are usually the best choice, but hamsters turn out to be a decent choice as well. Mice turn out to make poor animal models of acute COVID.

Unfortunately, for Long Covid, it's not that simple. Since we don't yet have a clear understanding of the underlying pathology of Long Covid, we simply don't yet know how to develop an animal model of Long Covid that accurately captures this underlying pathology of Long Covid.


Here's a study that infected monkeys with the coronavirus, and then looked for any lingering pathology 5-6 weeks after infection. It found evidence of viral persistence 5-6 weeks after infection, but did not look in the brain:

The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues (Böszörményi et al., 2021)
https://doi.org/10.3390/v13081673

The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (Macaca mulatta) and cynomolgus macaques. [...] Even after the alleged resolution of the infection, computed tomography (CT) and positron emission tomography (PET)-CT revealed pulmonary lesions and activated tracheobronchial lymph nodes in all animals. [...] However, 5–6 weeks after SARS-CoV-2 exposure, upon necropsy, viral RNA was still detectable in a wide range of tissue samples in 50% of the macaques and included amongst others the heart, the respiratory tract and surrounding lymph nodes, salivary gland, and conjunctiva. Subgenomic messenger RNA was detected in the lungs and tracheobronchial lymph nodes, indicative of ongoing virus replication during the post-acute phase.

And here's a paper that tried to propose a hamster model of Long Covid. They infected hamsters with the coronavirus and then followed the hamsters for up to a month, looking primarily for organ damage and signs of persisting inflammation. They found viral RNA in the brain a few days after infection, but not after that point. However, it must be noted that the investigators neglected to use any RNA stabilizer at the time of sample collection.

SARS-CoV-2 infection results in lasting and systemic perturbations post recovery (Frere et al., 2022) (pre-print)
https://www.biorxiv.org/content/10.1101/2022.01.18.476786v1.full.pdf

A growing body of evidence suggests that in a subset of individuals, SARS-CoV-2 infection results in prolonged complications including shortness of breath, persistent fevers, fatigue, depression, anxiety, and a state of chronic impairment of memory and concentration known colloquially as “brain fog”. The direct cause of these impairments, known collectively as “long COVID” or post acute sequelae of COVID-19 (PASC), is currently unknown. [...] Brain regions from [hamsters 3 days post infection (3dpi)] were surveyed for the presence of viral RNA. [...] Within the SARS-CoV-2-infected hamster cohort, viral reads were readily detectable in the nervous system in a subset of animals, consistent with the findings of others (de Melo et al., 2021). Of note, in one hamster, SARS-CoV-2 reads were detectable in all surveyed regions of the nervous system (Figure 4B). Mapping of these reads to the SARS-CoV-2 genome revealed that most reads aligned to the nucleocapsid (N) transcript. [...] To further characterize the appearance of SARS-CoV-2 genetic material in the brains of infected hamsters, a time course was conducted in which geographically distinct regions of the brain were sampled on days 1, 4, 7, and 14 post-infection. [...] In the olfactory bulb, a low level of [viral RNA] at 1dpi increased to a more prominent level at 4dpi in two of three hamsters before dissipating over the next seven days. [...] At [1 day post-infect (1dpi)], SARS-CoV-2-infected hamsters demonstrated [viral RNA] in one out of three tested striatum sections and in all of the cerebellum samples. Beyond this early time point, however, no cerebellum or striatum sections demonstrated [viral RNA].

 

[Pyrrhus]

Autopsies of Long Covid patients

Since all the indirect methods of examining viral persistence in the brain come with significant limitations, we must return to the idea of directly examining the brains of people with Long Covid. Obviously, this can only be done at autopsy.

Furthermore, the body must be immediately frozen or processed right after death, and tissues must be immediately treated with an RNA stabilizer, as viral RNA degrades very rapidly, in a matter of hours. Unfortunately, many studies neglect to do these two simple things, and as a result the viral RNA degrades completely before the researchers even have a chance to test for the presence of viral RNA.

Additional problems with the standard techniques for detecting viral RNA were noted in this review article on autopsies of acute COVID patients:

What can cerebrospinal fluid testing and brain autopsies tell us about viral neuroinvasion of SARS-CoV-2 (Li et al., 2021)
https://doi.org/10.1002/jmv.26943

Postmortem examination is known as the most definitive mean to assess viral neuroinvasion in patients with COVID-19. [...] Because neurotropic viruses usually infect some neurons only in specific brain regions, a sample homogenate containing uninfected neuronal and glial cells may have extremely low viral RNA, leading to false-negative results by PCR assays.
[...]
Noteworthily, Matschke et al. found that the presence of SARS-CoV-2 in the brain was not associated with the severity of [inflammation]. At first sight, this finding seems surprising, but it may be consistent with the characteristics of neurotropic viruses as they can hide in neurons from the surveillance of the immune system. Therefore, the immune response will not be effectively activated in the infected areas unless the initially infected neurons have been significantly damaged.
[...]
Due to technical or ethical factors, complete brain removal was difficult or even was not permitted in some studies. However, incomplete or random sampling of brain tissue is not suitable for the study of CNS infection caused by neurotropic viruses, because these viruses usually only infect the brain regions with neural connections to the peripheral invasion sites.
[...]
As compared with the number of patients who underwent viral testing in the CNS, the number of patients with positive results seems very small. However, it should not be simply concluded that the neuroinvasion of SARS-CoV-2 is rare in COVID-19 patients because the detection methods or sampling procedures in some studies may not be suitable or sufficient to reveal the CNS infection induced by neurotropic viruses. [...] Given the complex pathophysiology of COVID-19 and the characteristics of neurotropic viruses, it is understandable that any study of the CNS infection may inevitably have limitations.

Although autopsy data from Long Covid patients can be hard to come by, we do have the following study on COVID patients which found virus persisting in the brain for months after infection. This is one of the very few studies that correctly froze the bodies right after death and correctly treated the tissues with an RNA stabilizer.

SARS-CoV-2 infection and persistence throughout the human body and brain (Chertow et al., 2021) (pre-print)
https://doi.org/10.21203/rs.3.rs-1139035/v1

We performed complete autopsies on 44 patients with COVID-19 to map and quantify SARS-CoV-2 distribution, replication, and cell-type specificity across the human body, including brain, from acute infection through over seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, even among patients who died with asymptomatic to mild COVID-19, and that virus replication is present in multiple extrapulmonary tissues early in infection. Further, we detected SARS-CoV-2 RNA in multiple anatomic sites, including regions throughout the brain, for up to 230 days following symptom onset. Despite extensive distribution of SARS-CoV-2 in the body, we observed a paucity of inflammation or direct viral cytopathology outside of the lungs. Our data prove that SARS-CoV-2 causes systemic infection and can persist in the body for months.
[...]
Our focus on short post-mortem intervals, comprehensive approach to tissue collection, and preservation techniques – RNAlater and flash freezing of fresh tissue – allowed us to detect and quantify viral levels with high sensitivity by ddPCR and ISH, as well as culture virus, which are notable differences compared to other studies.

(emphasis added)


Understandably, this study has caused some real waves:

https://twitter.com/i/web/status/1473686914960171020

https://twitter.com/i/web/status/1473655530786725891

https://twitter.com/i/web/status/1473495885933916170

https://twitter.com/i/web/status/1473721448342687754

 

[WinterWren]

@Pyrrhus thanks for collecting and posting so much about this topic.

So as far as ideas go about what might be happening in the covid infected brain… There’s the two FDG-PET studies you posted about a hypometabolism in multiple parts of the brain, there’s the Olivarria paper that demonstrated in mice that microglia don’t restrict covid replication in the brain, and there’s the two Yale studies that found that infected neurons remained intact and entered into a hypermetabolic state, using intracellular antiviral strategies which may have been using up key nutrients in the areas around the infected neurons…

Sorry I gave up trying to use the quote function for all that…

The Yale studies make me wonder about possible methods to support the neurons “intracellular antiviral strategies” and whether that hypermetabolic state could be tied to the brains hypometabolic state found in the other studies?

Also the Olivarria study might suggest that microglia inhibitors could help? Like the ones they’re studying for MS, where if I understand it right, they also don’t know if microglia are stuck “on” or serving a purpose (being necessary to clear debris, fight a virus…). But trials are looking promising I think.

 

[Pyrrhus]

There’s the two FDG-PET studies you posted about a hypometabolism in multiple parts of the brain, there’s the Olivarria paper that demonstrated in mice that microglia don’t restrict covid replication in the brain, and there’s the two Yale studies that found that infected neurons remained intact and entered into a hypermetabolic state, using intracellular antiviral strategies which may have been using up key nutrients in the areas around the infected neurons…

The Yale studies make me wonder about possible methods to support the neurons “intracellular antiviral strategies” and the whether that hypermetabolic state could be tied to the brains hypometabolic state found in the other studies?

Great synthesis of ideas!

I wonder the exact same things myself...

 

[Pyrrhus]

Related discussions:

Scientists set out to connect the dots on long COVID (Marx, 2021)
https://forums.phoenixrising.me/thr...na-viruses-is-deadly-real.83408/#post-2336196

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms (Proal and VanElzakker, 2021)
https://forums.phoenixrising.me/thr...te-to-persistent-symptoms-polybio-2021.84761/

Persistent coronaviral particles in the gut
https://forums.phoenixrising.me/threads/persistent-viral-particles-in-the-gut.84272/

Covid 19 persistence for over a year - confirmed case in immunocompromised patient
https://forums.phoenixrising.me/thr...rmed-case-in-immunocompromised-patient.85952/

Persistence of SARS-CoV-2 Spike Protein in Long Covid up to 15 Months Post-Infection (Patterson et al., 2022)
https://forums.phoenixrising.me/thr...hs-post-infection-patterson-et-al-2022.86657/

Possibility of coronaviral persistence in testicles
https://forums.phoenixrising.me/thr...cells-in-human-testes-costa-et-al-2022.86946/

 

[heapsreal]

Sorry if you have written about this before but have they done much research on reactivation of secondary bacterial infections especially common ones involved in cfs like mycoplasma??
I believe this was the reasoning behind giving azithromycin to covid pts, to minimize secondary bacterial infections, which are very common in viral infections like influenza etc.

 

[Pyrrhus]

Sorry if you have written about this before but have they done much research on reactivation of secondary bacterial infections especially common ones involved in cfs like mycoplasma??
I believe this was the reasoning behind giving azithromycin to covid pts, to minimize secondary bacterial infections, which are very common in viral infections like influenza etc.

I'm afraid I don't know. But it's a very interesting question!

 

[heapsreal]

I'm afraid I don't know. But it's a very interesting question!

The way i think about it is most people have mycoplasma but its controlled by their own immune system. A big hit like covid could potentially lower ones general immunity and infections like mycoplasma which are very common in chest infections, could run wild. I just wonder if running an antibiotic like azithro or doxy prophylactically, it may prevent these secondary infections and seriousness of this virus especially in reguards to the lungs and pts needing ventilation. Im guessing once a pt is on ventilation they would be treated with a broad spectrum antibiotic?? But prevention would be a better option for these secondary bacterial infections.

As ive written above is one big reason why many infections have been implicated in cfsme. The initial infection whatever it was has done some damage and lowered our immunity and this has allowed dormant infections to reactivate and run wild. The hit and run theory has damaged the immune system and hpa axis and now we have become a favourable breeding ground for a certain bug or bugs. Reasonable theory for long covid and fits into the neuroimmune disease bracket.

 

[Pyrrhus]

Here's a new preprint that raises the possibility of SARS-CoV-2 inducing neuroinflammation with an "Alzheimers-like pathology":

SARS-CoV-2 invades cognitive centers of the brain and induces Alzheimer's-like neuropathology (Shen et al., 2022) (pre-print)
https://www.biorxiv.org/content/10.1101/2022.01.31.478476v1

Here, we show that SARS-CoV-2 invades the brains of five patients with COVID-19 and Alzheimers, autism, frontotemporal dementia or no underlying condition by infecting neurons and other cells in the cortex. SARS-CoV-2 induces or enhances Alzheimers-like neuropathology with manifestations of beta-amyloid aggregation and plaque formation, tauopathy, neuroinflammation and cell death.
[...]
In this study, we sought to test whether SARS-CoV-2 is neurotropic and infects neural cells in the cognitive center in five patients with Alzheimer’s disease, autism, frontotemporal dementia and no underlying condition, respectively.
[...]
We found that SARS-CoV-2 invades the cognitive centers of all five COVID-19 patients, leading to Alzheimer’s-like neuropathology or Alzheimer’s neuropathology exacerbation.

 

[Pyrrhus]

There are many other people, all around the world, who have also been reviewing these and other coronavirus studies which examine ideas of neuroinflammation or viral persistence:

https://twitter.com/i/web/status/1407611399593996288

https://twitter.com/i/web/status/1461418168379924480

https://twitter.com/i/web/status/1489597152003305473

 

[antares4141]

I have alot of intense eye inflammation with ME, and my right eye experiences alot of- variation in symptoms...that I notice tracks my overall condition pretty closely. My right side is much more sick than my left.

I thought maybe my going to a real eye doctor would lead to insights into this situation, but alas. Nah.

Really wondering about this whole "main route for lymph drainage"..may mean. Thats Newsworthy here. I figure my right side being more ill is tied to lymph issues, chronic EppsteinB of some type, and the liver is : on that side.

I have had that issue with my eyes periodically over the years. Feels like when I used to grind fiberglass and sometimes would get a spec of it in my eye.

 

[Pyrrhus]

A blood-based biomarker for neurological Long COVID?

SARS-CoV-2 and Mitochondrial Proteins in Neural-Derived Exosomes of COVID-19 (Peluso et al., 2022)
https://doi.org/10.1002/ana.26350

A recent paper that found significantly more coronaviral proteins in neuron-derived extracellular vesicles from patients with neurological Long COVID, when compared to recovered COVID patients without Long COVID. (in blood samples collected 2 months after infection)

Excerpt:

As SARS-CoV-2 is known to invade neural cell mitochondria, a plasma system for quantifying central nervous system proteins in living humans was used to investigate neuropathogenic mechanisms of long-COVID-19.
[...]
Comparing protein S1 levels [in neuron-derived extracellular vesicles] revealed a significant difference only between convalescent COVID-19 w/o [Long COVID] and [neurological Long COVID] (p = 0.0172).
[...]
Comparing protein N levels [in neuron-derived extracellular vesicles] revealed significant differences between [...] COVID-19 w/o [Long COVID] and both [neurological Long COVID] (p = 0.0109) and [severe neurological Long COVID] (p = 0.0212).

 

[Pyrrhus]

Although autopsy data from Long Covid patients can be hard to come by, we do have the following study on COVID patients which found virus persisting in the brain for months after infection. This is one of the very few studies that correctly froze the bodies right after death and correctly treated the tissues with an RNA stabilizer.

SARS-CoV-2 infection and persistence throughout the human body and brain (Chertow et al., 2021) (pre-print)
https://doi.org/10.21203/rs.3.rs-1139035/v1

The authors discuss this study in an hour-long NIH video cast here:
https://videocast.nih.gov/watch=45296

Air date: Thursday, May 19, 2022

Description: This will be an NIH–FDA COVID-19 SIG lecture concerning findings from the NIH COVID-19 Autopsy Consortium. Daniel Chertow is a tenure-track investigator in the Critical Care Medicine Department at the NIH Clinical Center and in the Laboratory of Immunoregulation at the National Institute of Allergy and Infectious Diseases.

 

[Pyrrhus]

Well, there it is.

Long COVID is associated with extensive in-vivo neuroinflammation on [18F]DPA-714 PET (Visser et al., 2022) (pre-print)
https://www.medrxiv.org/content/10.1101/2022.06.02.22275916v1

Excerpt:

A significant number of COVID-19 patients develop 'long COVID', a condition defined by long-lasting debilitating, often neurological, symptoms. The pathophysiology of long COVID is unknown.

Here we present in-vivo evidence of widespread neuroinflammation in long COVID, using a quantitative assessment, [18F]DPA-714 PET, in two long COVID patients. We reanalyzed historical data from three matched healthy control subjects, for comparison purposes.

Both patients with long COVID had widespread increases in [18F]DPA-714 binding throughout the brain. Quantitative measures of binding (BPND values) were increased on average by 121% and 76%, respectively. This implicates profound neuroinflammation in the pathophysiology of long COVID.
[...]
The first patient with long COVID included in our study was a Dutch woman, in her late fifties. She was healthy, worked full-time, and led a fulfilling life prior to developing a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. She was first infected in December 2020 (polymerase chain reaction (PCR)-test confirmed). During the acute phase of the infection, she was not hospitalized and did not need treatment.

However, since the infection, she has suffered from severe fatigue, concentration deficits, anosmia and parosmia, headaches, and some visual complaints. Her symptoms prevent her from working. Her medical history consisted of preexistent fibromyalgia (with subtle fatigue related complaints, that did not interfere with her work or daily functioning) and high cholesterol, which was at normal levels and stable with treatment. Her pre-existent fatigue-related complaints increased severely after infection with SARS-CoV-2. [...] Her symptoms remain present until this day, 15 months after infection.

The second patient with long COVID included in our study was a Dutch male in his mid-sixties, who was healthy, fully functioning and worked full-time prior to the SARS-CoV-2 infection. He was infected in March 2020 (PCR-confirmed). During the acute phase of SARS-CoV-2 infection, he was hospitalized on a nursing ward for a total of 15 days.
[...]
Since the infection, he has suffered from severe fatigue and concentration deficits, and he was declared partially unfit for work for 75 %. He had no relevant past medical history. [...] Although there has been some improvement, his symptoms remain present until this day, 24 months after infection.
[...]
In this study, we report widespread and large increases in [18F]DPA-714 binding throughout the brain in the first two patients included in our in-vivo study of neuroinflammation. Although far from definitive, these findings are striking in extent and magnitude.
[...]
As can be visually appreciated, we found high binding in the thalamus for both patients. [...] The thalamus is considered an important regulator, in relation to fatigue and cognitive functioning (13, 14) and may offer a clue towards the etiology of these symptoms in long COVID.
[...]
However, this study also has several limitations. First and foremost, we included only two patients with long COVID. These were the first two patients with long COVID included in this study, and we felt these data were too important not to publish at this stage. However, that does not negate that these remarkable findings will need to be replicated in a larger number of patients.

(emphasis and spacing added)

 

[Insomniac]

I don't know if this is related. My brain is too tired to listen and understand this video

Dr John Campbell on Long Covid

 

[almost]

What does the virus do to the terrain that it leaves behind inflammation?

And then, how do we fix it?

Did you get answers to your questions? Please share if you did.

This thread has a LOT of great info, thanks to @Pyrrhus for putting it together. Right now, absorbing two years of papers is way more than I can digest. What I really want to know is, what can I do about it? Do I need different antivirals?

 

[Violeta]

Did you get answers to your questions? Please share if you did.

This thread has a LOT of great info, thanks to @Pyrrhus for putting it together. Right now, absorbing two years of papers is way more than I can digest. What I really want to know is, what can I do about it? Do I need different antivirals?

The only thing I've found so far is that there is oxidative stress involved.

Do you know which virus you are dealing with? I don't know anything about medicines, only herbal remedies.

For example, here's a study about berberine being good for herpesviruses.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320912/

 

[almost]

Do you know which virus you are dealing with? I don't know anything about medicines, only herbal remedies.

Thank you for the reply. That's a good question. On the face of it, I would say SARS-CoV2 since is suspect I may be dealing with 'long Covid.' But, as I'm also dealing with CFS, who knows if there is another lurking in the shadows as well.

So, I'm looking at what my options may be. I didn't like how I felt with Paxlovid, so I don't want to go there again, and my Garmin watch data shows definite deterioration of sleep, HRV and 'body battery' data beginning almost to the day I started it for treatment of the SARS infection. I'm looking to see if there are other antivirals, natural/herbal or pharmacological that may help clean up remaining infection. I prefer natural/herbal, but would consider pharmacological.

Before this latest insult, I was dealing with a good bit of neuro-inflammation, and had plenty of oxidative stress. I bet I have more now.

 

[Violeta]

I edited in to my most recent post before I saw that you had already responded a link to a study about berberine.

I know what you mean about not knowing what virus could be involved with ME/CFS.

The study says berberine might be helpful for Sars, too.

I've had berberine on hand but just today I was having a flare and thought I would try it and it seems to be helping. I have taken one capsule a day for a couple of days but for this flare I have already taken two in the past couple of hours. I am going to try taking 3 capsules a day and see if it helps with fatigue, too.