@longcovidlabs.bsky.social
Non-profit accelerating a cure for 100M+ people with Long COVID. Longcovidlabs.org
Good to know!
24.10.2025 19:11 — 👍 1 🔁 0 💬 0 📌 0Thank you for the kind words!
24.10.2025 18:58 — 👍 1 🔁 0 💬 1 📌 0.... ongoing efforts to address persistent viral reservoirs, immune dysregulation, and multisystem injury are driving the exploration of targeted interventions."
Long COVID research is in a very different place than it was a few years ago.
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Moving forward, the authors explain:
"Advances in understanding the complex biological mechanisms underlying Long COVID have opened promising avenues for therapeutic development. While management currently remains largely supportive...
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Moving forward, the authors explain:
"Advances in understanding the complex biological mechanisms underlying Long COVID have opened promising avenues for therapeutic development. While management currently remains largely supportive...
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If this organ is damaged, and unable to produce adequate numbers of new immune cells, that can lead to issues fighting off the acute infection, as well as future reinfections. 🦠
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If the acute infection kills off too many of these cells, they may be able to fully fight it - meaning some amount of virus will remain.
6) Acute infections can damage the thymus
The thymus gland is responsible for producing naive T cells - it's the bedrock of our immune system.
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5) The immune system may have been damaged during acute COVID-19 infection - leaving it unable to clear persistent virus.
Acute COVID-19 has been shown to deplete numbers of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, which are critical for viral clearance.
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4) The virus may have gotten into immunologically-privileged sites in the body.
There are certain places in the body, such as the GI tract, the eyes, and the reproductive organs, where the immune system doesn't attack.
Unfortunately, these can be the perfect places for SARS-CoV-2 to hide.
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3) Chronic inflammation may lead to immune exhaustion—particularly of CD8+ T cells and NK cells.
These are two types of immune cells our body uses to kill virally-infected cells. During chronic infections, they can become "exhausted" - no longer able to do their job.
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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.
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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.
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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. Ebola RNA has been found throughout the body months - years after acute infection - and SARS-CoV-2 may be similarly persisting.
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The authors do a great job of explaining mechanistic insights for how why the SARS-CoV-2 interest may persist.
Let's take a look at what they said!
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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.
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These root causes of LC include:
👉 persistent viral infection,
👉 latent virus reactivation,
👉 immune dysregulation,
👉 autoimmunity,
👉 gut microbiota alterations,
👉mitochondrial dysfunction,
👉 endothelial injury
👉 coagulation abnormalities
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Screenshot of article title, author info, and abstract from this paper: https://www.tandfonline.com/doi/full/10.1080/25785826.2025.2570902#d1e608 Titled: "Long COVID: mechanisms of disease, multisystem sequelae, and prospects for treatment"
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. 📊
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LONG COVID LABS is very excited to study antivirals such as Paxlovid and Ensitrelvir - both in their own right, as well as in combination with other treatments such as monoclonal antibodies.
Stay tuned for more! ✨
Study 🔗 www.thelancet.com/journals/lan...
Having another option may increase the likelihood that COVID patients will be able to complete their full antiviral treatment.
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The researchers write that the availability of Ensitrelvir is a welcome development, as the side effect profile of the two drugs is very different.
👉Specifically, ensitrelvir does not carry the same side effect of dysgeusia (where patients taste a horrible or metallic taste in their mouth).
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The median estimated viral clearance half-lives under the linear model were:
👉5.2 hours with ritonavir-boosted nirmatrelvir
👉5.9 hours with ensitrelvir, and
👉11.6 hours in the no-treatment group
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Compared to no-treatment, the rates of viral clearance up to Day 5 of infection were:
👉82% faster with ensitrelvir, and
👉116% faster with ritonavir-boosted nirmaltrelvir
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Each day, researchers then measured the presence of the SARS-CoV-2 virus using oropharyngeal (back of the throat) swabs. 🦠
They found that both drugs sped up the time to symptom resolution, compared to the no-treatment group.
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Figure 4B from the paper - graph showing viral clearance rates over 7 days. Ritonavir- boosted nirmaltrelvir decreases the most sharply, to just over 50% of patients with symptoms at 7 days, while ensitlrevr's recovery rates remain slightly higher. The no-treatment group persistently maintains a higher % of symptoms. Paper here: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00482-7/fulltext
📣 New Clinical Trial Compares Efficacy of Paxlovid vs. Ensitrelvir
Researchers in Thailand and Laos compared the rates of recovery from acute SARS-CoV-2 infection while patients were taking these two antiviral drugs:
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Importantly, there is so much great work on the horizon, and we thank the authors of this paper for their important findings! 🙏
Check out the study here: frontiersin.org/journals/cel...
As long as the virus is mutating and creating new strains, our current vaccines and monoclonal antibodies will only be playing catch-up.
We need to develop new therapies to target all strains of the virus, and also to prevent forward transmission & new cases.
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There is so much more we need to know about this virus:
👉How and why does it persist in the human body?
👉 How can we identify which patients have it?
👉 Which treatments will most effectively clear it?
👉 And how can we prevent forward transmission
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What does this mean?
COVID is not over. Multiple papers all over the world are pointing to the conclusion that the SARS-CoV-2 virus can persist in the human body. This includes Long COVID patients, immunocompromised patients, and - some studies even suggest- even the healthy controls.
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They explain that their paper adds to the growing body of work suggesting that least some variants of concern, including alpha and omicron, initially involved in patients with chronic infection before escaping into the general population.
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The team ran an in-depth analysis and concluded that the patient's variant was unlikely to have been acquired in the local community, as it was not a close enough to match to any circulating variants at the time.
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