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Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
@NickAnderegg
Aug 9, 2024 • 30 tweets • 12 min read • Read on X
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New interdisciplinary review was published on current Long COVID science, with a roadmap for science and policy!

It is written in plain language, so it's worth a read on its own, but I just want to pull out some highlights about what WE DO KNOW into a single thread...

1/many Published Aug 9, 2024 in Nature Medicine: "Long COVID science, research and policy" Abstract: "Long COVID represents the constellation of post-acute and long-term health effects caused by SARS-CoV-2 infection; it is a complex, multisystem disorder that can affect nearly every organ system and can be severely disabling. The cumulative global incidence of long COVID is around 400 million individuals, which is estimated to have an annual economic impact of approximately $1 trillion—equivalent to about 1% of the global economy. Several mechanistic pathways are implicated in long...
This is definitely the definition for Long COVID I'll be explicitly using from now on: Long COVID is "the constellation of post-acute and long-term health effects caused by SARS-CoV-2 infection."

2/ "Long COVID is best defined as the constellation of post-acute and long-term health effects caused by SARS-CoV-2 infection. Long COVID was initially reported by patients who coined the term and, through research and advocacy, drove much of the progress in understanding this condition over the past several years (Fig. 1)."
Long COVID "affects nearly every organ system, including the cardiovascular system, the nervous system, the endocrine system, the immune system, the reproductive system, and the gastrointestinal system."

It affects people regardless of age or pre-existing health status.

3/ "Long COVID is a complex, multisystem disorder that affects nearly every organ system, including the cardiovascular system, the nervous, the nervous system, the endocrine system", the immune system, the reproductive system and the gastrointestinal system. It affects people across the age spectrum (from children 6-18 to older adults), people of different race and ethnicities, sex and gender, and baseline health status. Cardinal manifestations include brain fog (or cognitive dysfunction), fatigue, dysautonomia (which commonly manifests as postural orthostatic tachycardia syndrome (P...
The specifics of the risk have varied over time (as the virus and medicine both evolve), but one thing is clear: The risk of Long COVID accumulates with each infection.

People with three infections are more at risk than people with two infection, for example.

4/ "The epidemiology of long COVID is influenced by various factors. The Omicron variant of SARS-CoV-2 is associated with less risk of long COVID than the Delta and pre-Delta variants. Vaccines (before infection) and antivirals (during the acute phase of infection) may reduce the risk of long COVID. Reinfection, on the other hand, is a risk factor for long COVID; even if individuals did not experience long COVID after a first SARS-CoV-2 infection, they remain at risk of developing it with subsequent infections. Reinfection can trigger de novo long COVID or exacerbate the severity of exist...
The *risk* of LC is correlated with the severity of acute COVID, but because most of the people around the world have had mild COVID, these "mild" cases "constitute more than 90% of people with long COVID, despite their lower relative risk..."

5/ "A unifying thread of evidence across most studies evaluating the risk of long COVID is the finding that the risk increases as the severity of acute infection increases. People who had severe COVID-19 that necessitated hospitalization exhibit a higher risk of long COVID than those with mild COVID-19. However, because most people around the globe had mild COVID-19, they constitute more than 90% of people with long COVID, despite their lower relative risk compared with that of people with severe COVID-19 (ref. 31)."
The specifics of Long COVID are unclear, simply because studies have not been consistent enough to be comparable.

One of the biggest problems is labeling "remission" as "recovery," especially when many manifestations "are chronic conditions that last a lifetime."

6/ "Studies evaluating recovery from long COVID are sparse and inconsistent; this is largely due to use of various definitions, incomplete accounting for all the manifestations of long COVID and misclassification of remission as 'recovery'. However, studies carefully evaluating individual manifestations show that recovery rates are generally low at 1 year34, and several studies show only 7-10% fully recovered at 2 years. Furthermore, some manifestations of long COVID, including heart disease, diabetes, myalgic encephalomyelitis and dysautonomia are chronic conditions that last a lifetime....
Simply put, we're facing a MASSIVE threat to global public health. This review looked at what is known—and what issues will have to be addressed going forward!

7/ "The impact of long COVID is not limited to the health and wellbeing of individual patients and their communities. Owing to its prevalence and the breadth of its clinical manifestations, it represents , it represents a major public health crisis; it strains health systems and national economies, and threatens progress on global health, including the Sustainable Development Goals (SDGs). In this interdisciplinary review, we provide a brief synthesis of the current state of scientific evidence on long COVID, including knowns, unknowns and the key controversies. We provide an assessment ...
Fundamentally, one of the biggest problems with grasping the nature of Long COVID is the "dynamic nature of the pandemic itself, which gave rise to many variants and subvariants, each yielding potentially different rates of long COVID"

8/ "State of the science on long COVID The global burden Estimating the global burden of long COVID presents substantial challenges due to the variability in study designs and populations, follow-up times, choice of control groups (for example, whether studies evaluated people with negative SARS-CoV-2 tests or no known SARS-CoV-2 infection as controls), assessment of baseline health before the infection (to ascertain emergence of a true new health condition) and definitions of what constitutes 'long COVID'. Variation in risk estimates also reflects the dynamic nature of the pandemic itse...
But you know what is really interesting? If we stick to the absolute bare-minimum definition (having one of three clusters of symptoms three months after infection), we consistently see that AT LEAST *7% of the population* is impacted.

9/ "Data from the US Centers for Disease Control and Prevention (CDC)'s National Health Interview Survey show that in 2022, 6.9% of US adults° and 1.3% of children" ever had long COVID. Data from the Medical Expenditure Panel Surveya nationally representative survey of US adults-found that 6.9% of adults had ever had long COVID as of early 2023 (ref. 52). Estimates from the CDC's Household Pulse Survey show that prevalence of current long COVID in US adults was around 6.7% in March 2024 (ref. 53)." "Also important are estimates of the incidence of long COVID, which can be ...
The global count of people affected by Long COVID is jarring: even only accounting for symptomatic cases and the most-likely outcomes, they "estimated a cumulative global incidence of long COVID by the end of 2023 of approximately 400 million."

400 MILLION.

10/
"We estimated the global incidence of long COVID on the basis of meta-regression studies that pool together all the available evidence 31 (Fig. 2). Incorporating a number of assumptions, including the Institute for Health Metrics and Evaluation's annual estimates of SARS-CoV-2 infections, a proportion symptomatic cases among infections of 65% (ref. 31), and a reduction in the risk of long COVID for 2022 and 2023 to account for the putative lower severity of the Omicron variant and the effect of vaccination, we estimated a cumulative global incidence of long COVID by the end of 2023 of ...
"Year Fig. 2| Estimated global cumulative incidence of long COVID. We estimated the global incidence of long COVID on the basis of meta regression estimates that pool together all the available evidence. Considering the Institute for Health Metrics and Evaluation's annual estimates of SARS-CoV-2 infections and assuming the lower risk estimate of 6.2% for long COVID at 3 months after infection, a proportion symptomatic cases among infections of 65% (ref. 31), and a reduction in the risk of long COVID for 2022 and 2023 (to account for the combination of the putative lower severity of the...
And you know what else makes it challenging to estimate the global incidence of Long COVID? We don't yet know what risks "are not yet manifest and may emerge years or decades after infection."

This is a pressing global health issue.

11/ "Furthermore, the estimates do not account for the added burden of long COVID due to reinfection" and the possibility of latent risks (that is, risks that are not vet manifest and may emerge vears or decades after infection). The emergence of new variants, changes in public health measures and changes in the effectiveness and uptake of vaccination may also substantially influence these estimates in the future. While it is challenging to provide estimates of new cases with high precision, the current evidence makes it compellingly clear that long COVID represents a substantial and ...
What causes Long COVID? Why does it occur?

Well, the specifics are still being figured out. There's not yet a clean answer to that question. All we do know is that it can involve many different systems, and many different variables affect outcomes.

12/ "Mechanisms of long COVID The pathophysiological mechanisms of long COVID are still being elucidated, and it is unlikely that a single mechanism can explain the broad and heterogeneous set of symptoms and diseases spanning various organ systems. Long COVID likely represents a disease with many subtypes; each may have their own risk factors, biological mechanisms and disease trajectory, and may respond differently to treatments. Multiple pathological pathways may be engaged depending on various factors, including prior environmental exposures, genetic makeup, age, sex, prior health, mi...
There are, however, some more-salient pathways that have been proposed, "including viral persistence, immune dysregulation, mitochondrial dysfunction, complement dysregulation, prothrombotic inflammation and microbiome dysbiosis"

13/ "Initial triggers include viral persistence in tissue reservoirs (or immune-privileged sites) and possible replication of SARS-CoV-2 leading to the generation of viral antigens and RNA, which stimulates adaptive and innate immune cells, respectively. This can lead to immune cell activation, cytokine secretion, T cell exhaustion, antibody secretion against SARS-CoV-2 antigens and complement activation. Innate recognition of viral RNA by myeloid cells can lead to enhanced phagocytosis and cytokine secretion and inflammasome activation (bottom yellow box). These events can trigger autoimm...
Viral persistence is of particular concern, because persistence of "either replicating virus or viral RNA or protein fragments" in certain tissues "may be common" and "may trigger chronic low-grade inflammation and tissue injury."

14/ "Several mechanistic pathways have been proposed for long COVID, including viral persistence, immune dysregulation, mitochondrial dysfunction, complement dysregulation, prothrombotic inflammation and microbiome dysbiosis (Fig. 3). Viral persistence (either replicating virus or viral RNA or protein fragments)-which may be common —in immune-privileged sites may trigger chronic low-grade inflammation and tissue injury, and may correlate with long COVID symptomatology."
Viral persistence is of particular note for further investigation, because studies "have demonstrated persistence of the virus in extrapulmonary sites, including the brain and coronary arteries, of individuals with severe COVID-19."

15/ "Studies have demonstrated persistence of the virus in extrapulmonary sites, including the brain and coronary arteries, of individuals with severe COVID-19 (refs. 68,74). Studies in human and mouse brain organoids showed that SARS-CoV-2 infection induces fusion between neurons and between neurons and glial cells, which may progressively lead to formation of multicellular syncytia compromising neuronal activity. Neuroimaging studies performed in humans 10 months after they 'recovered' from mild-to-moderate SARS-CoV-2 infection showed significant alterations (commensurate with 7 'years o...
But here's the thing: Even if SARS-CoV-2 *isn't* directly infecting the brain, we DO know that "a transient respiratory infection with SARS-CoV-2 induces prolonged neuroinflammatory responses" and *brain fog* is associated with "disrupted blood-brain barriers."

NOT GOOD.

16/ "Even in the absence of direct infection in the brain, a transient respiratory infection with SARS-CoV-2 induces prolonged neuroinflammatory responses, activation of microglial cells and impaired neurogenesis. In addition to neuroinflammation, people with brain fog due to long COVID were shown to have disrupted blood-brain barriers."
When it comes to the immune system "abnormalities in the immune system have been documented in" pwLC, including a heightened antibody response to various herpesviruses, "exhausted T cell responses," uncoordinated adaptive immunity, and autoimmune responses.

17/ "Abnormalities in the immune system have been documented in people with long COVID, including increased humoral responses directed against SARS-CoV-2; higher antibody responses against Epstein-Barr virus (EBV), varicella zoster virus (VZV)% and cytomegalovirus (suggesting possible reactivation of herpesviruses 0); exhausted T cell responses; and uncoordinated cross-talk between the cellular and humoral adaptive immunity. Autoimmune responses triggered by SARS-CoV-2 infection may underlie long COVID symptoms. Passive transfer of IgG antibodies from patients with long COVID to healthy mi...
Note that some of the vascular, endocrine, and GI impacts of LC can also have a DIRECT impact on nervous system and brain function.

(IMO, LC is primarily neurological, with the overarching condition being triggered by dysregulation in these other areas.)

18/ "In the heart, SARS-CoV-2 infects coronary vessels, preferentially targeting coronary artery plaque macrophages and inducing plaque inflammation. Vascular disease in long COVID is likely triggered by complement activation, red blood cell lysis, platelet activation and thromboinflammation-leading to altered coagulation and tissue injury. Dysfunctional hypothalamic-pituitary-adrenal response with inappropriately low levels of cortisol may mediate some of the symptomatology observed in long COVID (including fatigue, sleep abnormalities and metabolic derangements), and has been seen in tho...
How can LC be prevented? The best way to avoid Long COVID is to avoid SARS-CoV-2 infection.

Masking and ventilation "can reduce the risk of SARS-CoV-2 infection and... the risk of long COVID."

Vaccines ALSO reduce the risk of (but don't entirely *prevent*) LC.

19/ "Prevention, treatment and care models Non-pharmaceutical interventions (for example, masking, improved indoor air quality) can reduce the risk of SARS-CoV-2 infection and consequently reduce the risk of long COVID. COVID-19 vaccines may partially reduce the risk of long COVID in adults by 15-70% (mean, ~40%); they may also partially reduce the risk of long COVID in children. In nonhospitalized individuals (mild-to-moderate COVID-19) who have at least one risk factor for the development of severe COVID19, use of the SARS-CoV-2 antivirals (ritonavir-boosted nirmatrelvir and molnupiravir...
There are some drugs in the works that have been shown to be useful in acute COVID, but it's still not entirely clear if they have a significant impact on the risk of Long COVID.

The best thing you can do for yourself is to not have anymore SARS-CoV-2 infections.

20/ "Simnotrelvir-a new SARS-CoV-2 antiviral available in China -resulted in earlier reduction in viral load and faster resolution of acute symptoms (than placebo) but its effectiveness against long COVID has not yet been evaluated. Exploratory analyses showed that another new SARS-CoV-2 antiviral, ensitrelvir (currently available in Japan), reduced the risk of long COVID when initiated in the acute phase of COVID-19 (refs. 101,102). Furthermore, metformin (initiated within 7 days of SARS-CoV-2 infection) has been shown to reduce the risk of long COVID in a randomized controlled trial."
What about treatments? There is nothing yet, other than a few promising leads.

Current treatment for Long COVID is based on evidence for "treating similar symptomatology from other conditions," including ME/CFS and Gulf War illness.

So, nothing specific yet.

21/ "Evidence for long COVID treatments is beginning to emerge, but it is still limited. A randomized, double-blind, placebo-controlled trial showed that treatment with a synbiotic preparation (a gut microbiome modulator) alleviated multiple symptoms of long COVID-highlighting the need to further explore microbiome modulators as potential therapeutics in this setting. Another randomized, controlled trial showed that a 15-day course of ritonavir-boosted nirmatrelvir did not reduce the burden of long COVID symptoms in comparison to ritonavir with placebo. Due to near-total absence of evidenc...
All of these issues are compounded by "lack of widespread recognition and understanding of long COVID among medical professionals" and a "general pervasive pandemic fatigue with an urge to 'move on'."

Unfortunately, the virus is unaware the pandemic was DECLARED "over".

22/ "Care for people with long COVID varies widely across settings and practitioners. It is often challenged by lack of widespread recognition and understanding of long COVID among medical professionals, constrained resources and competing demands on healthcare systems still recovering from the shock of the pandemic, lack of standardized care pathways, lack of definitive diagnostic and treatment tools, and a general pervasive pandemic fatigue with an urge to 'move on'. Much of the global burden of long COVID remains undiagnosed, particularly in low-resource settings, and in many instances ...
The impacts have been SIGNIFICANT.

- 1 in 4 pwLC have to "limit activities outside work in order to continue working."
- The increased demand created by LC "exacerbates existing pressures on health systems."
- There are "wide and deep ramifications on national economies."

23/

"Impact on individuals and communities Long COVID drastically affects patients' well-being and sense of self, as well as their ability to work, socialize, care for others, manage chores and engage in community activities-which also affects patients' families, caregivers and their communities. Over three quarters of people with long COVID report a moderate or severe impact on general well-being. The high rates of cognitive and physical symptoms also affect individuals' identity and sense of self. One in four people with long COVID limit activities outside work in order to continue work...
"Impact on health systems ...Patients with long COVID frequently require ongoing medical care and multiple specialist consultations to manage their complex symptoms. This increased demand exacerbates existing pressures on health systems, leading to longer wait times, potential delays in essential care and increased costs. In the United States, people with long COVID are more likely to report unmet healthcare needs in the past year because of costs and difficulties finding a clinician and getting an appointment when needed. These issues are exacerbated in low-and middle-income countrie...
"Impact on economies Long COVID strains individual financial health and has wide and deep ramifications on national economies. In addition to the substantial direct healthcare costs, there is also financial strain on support services and disability benefits. In addition, long COVID affects labor participation, employment and productivity of impacted individuals and their caregivers - resulting in depleted savings, food and housing insecurity and negative impact on labor supply, thereby fueling labor shortages. Studies indicate a significant percentage of individuals with long COVID ex...
The economic losses in the United States alone are "on par with the global 2008 Great Recession," incurring financial losses of around $11,000 per capita.

And this is with the assumption that, for those who develop Long COVID, it will only last five years.

24/ "Quantitative estimates of the total economic impact of long COVID remain preliminary. A study in 2022 estimated the economic cost of three key parameters in the United States, including lost quality of life ($2,195 billion), cost of lost earning ($997 billion) and spending on healthcare ($528 billion), for up to a total cost of $3.7 trillion - this amounts to $11,000 per capita or 17% of the 2019 gross domestic product (GDP). These economic losses are on par with the global 2008 Great Recession. Assumptions included in these estimates are that burden of disability from long COVID is o...
So... what do we do?

The rest of the paper lays out detailed research and policy roadmaps we can follow to navigate this crisis, and it's worth a read:

The path forward isn't easy, but this is not a problem that CANNOT be ignored.

25/25 nature.com/articles/s4159…



"Research and policy roadmaps Substantial work lies ahead to address the broad and multifaceted challenges posed by long COVID-including preventing further increase in the number of people with long COVID and addressing the care needs of people already impacted. Responding to these challenges will require coordinated, long-term policy response and visionary research strategies, guided by the principles of health equity and patient centeredness. We developed the following research and policy roadmaps on the basis of our assessment of the evidence and policy gaps, as well as our own cli...
See Table 2 in the paper for full text. This table is way too extensive to try to condense into alt text!
Image
Image
*This is a problem that CANNOT be ignored.

One of my absolute worst habits is rephrasing a sentence without making sure I removed all the redundant words. 🤦‍♂️

26/25
Agreed! It seems likely to be an underestimate.

I think they were aiming to define the bare minimum scope of what is actually known fairly definitively, and based on that the floor of the estimate is 400 million. It’s a good strategy from a policy advocacy perspective!

27/25
Here is the entire thread summarizing the paper on one page: readwise.io/reader/shared/…
Note that they found an apparent disparity between LC in adults (6-7%) and children (~1%)!

HOWEVER, I do think this disparity may represent a significant underreporting of LC symptoms in children. Why?

While the severe ME/CFS phenotype of LC has very overt symptoms,…

28/25
…if a child’s symptoms manifest as moderate cognitive impairment and fatigue, they may not even realize something is wrong.

An adult realizes the issue when they’re no longer able to do their job. How many kids think school just becomes MUCH more challenging with age?

29/25

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More from @NickAnderegg

Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Feb 1
Many people are asking for recommendations about what storage media to buy, so here's a buying guide from an experienced data hoarder (me)

The MOST IMPORTANT thing to know is that SOLID-STATE MEDIA IS NOT DURABLE. Flash drives, SSDs, SD cards, etc. are NOT long-term storage.

1/
That's not to say that it's impossible to use solid-state media for long-term storage. It's just that anything with durability guarantees gets prohibitively expensive quickly. Spinning hard drives—as well as DVDs and Blu-ray discs!—are your friend.

2/
- The way data is stored in solid-state media makes it much more susceptible to bit rot than other media.
- In a spinning hard drive, the moving parts are the most common point of failure.
- When you burn a DVD, that shit is fairly permanent.

3/
Read 42 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jan 9
I wish people would understand that insurance underwriters have armies of actuaries calculating risks, and if an insurance company drops you, it's because things have changed in such a way that insuring you will take more out of the financial pool than you're putting in

1/
It sucks, but it's a direct result of the fact that humans are widely inhabiting locations that are rapidly becoming impossible to inhabit safely. If you can't find insurance for your home, it means there's a high likelihood you'll need to move soon anyway.

2/
You get insurance so that you can replace all of your stuff in the event of a disaster. When the insurance company effectively says "the risk of disaster is so high that insuring you would almost certainly cause us to lose a lot of money," it ALSO means your life is in danger

3/
Read 7 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jan 5
So here’s the thing about some of the subtle neuro damage related to SARS-CoV-2 infection that I think a lot of people miss: some of the known deficits are correlated with things like impulsiveness and poor emotional control, so we might expect to see deficits there are well

1/
Consider how impatient people seem to be on the road in the last couple years relative to the 2010s, and I think we have a perfect example of where this is LIKELY already manifesting.

2/
This impact is particularly insidious for the person experiencing it, because poor impulse control, by definition, doesn’t really come on gradually. My biggest concern is how interactions under these circumstances will play out if this impact continues to become more common

3/
Read 15 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jan 3
Let's review some major points in the Nukit controversy, since some people are unclear:

- Someone criticized someone's use of Nukit lanterns.
- Nukit attacked the critic because, as noted, this is how they market
- Nukit now demands "mediation" with the community (how??)

1/ @marigoldglitter: "these tools should be used for people who must be in public despite the dangers, not for white men who want to eat in restaurants and maintain the status quo. if this is what you're gonna use these for, give them to a disabled person who can't go to the doctor b/c of risk." Nukit: ""White man" in this case is buying those products from non-white small businesses who are focused on providing the community with effective, tested mitigations at far, far lower costs than anyone else." OP: "Like why are you coming at me with this aggressive...
Nukit: "If you are in the US, and would like to purchase Far-UVC products, we cannot help you at this time. We tried to resolve the issues there, but the US COVID-Aware community was uninterested in mediation or intercession. As a result of that disinterest, a great deal of harm was done. When stock is finished, we will not be selling our products to the Us anymore. If you are in the US and want Nukit products, would like 333 million Americans, many disabled or immune compromised, to be able to access the most affordable Far-UVC on the market, kindly address the people who made it unsa...
So let's look at this a bit more critically. Here is the "evidence" Nukit provided that the didn't say anything racist. First of all, these aren't the comments in question, but it's worth a look anyway.

2/ Ok, I get that "evidence," "citations," and "personal accountability" are going to be called racist, but since people insist on just spewing lie after lie without any pushback- here's what actually happened. @marigoldglitter- a white woman attacked a Nukit customer who was supporting us by showing our products. This is something we rely on to fund research and donations. If our customers do not do this, that money goes to paid advertising. So yes, attacking our customers is attacking our company and directly harming marginalized folks who receive our products. ...
Seems to be framed this way because Nukit knows it's not an adequate explanation, so they're acting like anyone who criticizes them is in the wrong. --- A bigoted comment is a bigoted comment, even if it's not directed at someone who might be personally offended. Of course, Nukit didn't include the comments people actually call racist! --- Nukit is explicitly saying here that they view any criticism as an "attack," because criticisms can potentially hurt their business goals. Fundamentally, Nukit is angry that this usage of their products are being criticized. --- After Nuki...
Let's be clear about what happened here: Someone lamented the unequal access to protective measures and criticized someone who seems to be using a certain device to *maintain the status quo*, and the manufacturer of the device found it unacceptable.

3/
Read 16 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Oct 9, 2024
NEW STUDY! This exploratory study identifies a SPECIFIC PHENOTYPE OF LONG COVID that appears related to NEUROMUSCULAR DISTURBANCE rather than lung damage—and they've termed it Complex Ventilatory Dysfunction!

Breakdown of the paper (thread written for a general audience!)...

1/ Published Oct 7, 2024: "A new phenotype of patients with post-COVID-19 condition is characterised by a pattern of complex ventilatory dysfunction, neuromuscular disturbance and fatigue symptoms" Abstract: Background Patients with post-COVID-19 condition frequently suffer from chronic dyspnoea. The causes and mechanism for dyspnoea in these patients without evidence of structural lung disease are unclear. ... Results ... A pattern of reduced forced vital capacity (FVC), but normal total lung capacity (TLC), termed complex ventilatory dysfunction ... was observed and occurred mo...
Broadly speaking, there are two groups of acute covid outcomes involving dyspnea (shortness of breath) as a long-term symptom:

- Severe cases that may have physical lung damage
- "Mild" cases that now have ME/CFS-like features, but who have no evidence of lung damage!

2/ "Current evidence suggests that cellular damage, a robust innate immune response with inflammatory cytokine production and a procoagulant state induced by SARS-CoV-2 infection are factors potentially contributing to post-COVID-19 sequelae such as dyspnoea, fatigue, and cognitive and mental disturbances... Dyspnoea has been well characterised as a major clinical symptom of post-COVID condition after severe and critical COVID-19 and is correlated with impaired lung function in terms of pulmonary restriction, and with reduced diffusion capacity as a possible consequence of pulmonary remod...
In this study, they explored this distinction further and identified a distinct subset of patients with a pattern of breathing abnormality that they have termed complex ventilatory dysfunction (CVD).

So how did they arrive at this conclusion? Let's dig in!

3/16 "We hypothesise that patients suffering from post-COVID-19 condition who have fatigue and exertional intolerance also have a reduction in respiratory muscle strength, causing a dysfunctional breathing pattern which is distinct from typical pulmonary sequelae after COVID-19 such as obstruction, restriction or impaired diffusion capacity. Based on clinical observations, we describe a new breathing abnormality termed complex ventilatory dysfunction (CVD), defined as total lung capacity (TLC) - forced vital capacity (FVC) >10% predicted value and absence of restriction (TLC ≥ lower limit o...
Read 16 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Sep 22, 2024
NEW STUDY! It VERY thoroughly supports the hypothesis that SARS-CoV-2 emerged as a zoonotic spillover event in the Huanan Seafood Wholesale Market—using multiple methods!

Breakdown of the paper (written for a general audience!)...

1/many (but it's worth it, I promise!) Published Sep 19, 2024 in Cell: "Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic" Highlights: - Common ancestor of SARS-CoV-2 linked to Huanan market matches the global common ancestor - Wildlife mitochondrial DNA identified in samples from stalls positive for SARS-CoV-2 Abstract: "... We demonstrate that market-linked severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversity is consistent with market emergence and find increased SARS-CoV-2 positivity near and within a wildlife stall. We identify wildlife DNA in...
This paper reanalyzes the same data from the April 2023 paper in Nature that cast doubt on the Huanan Market hypothesis (pictured).

In the new paper published in Cell this week, another group conducted far more detailed (and statistically sound) analyses!

2/
Original paper that analyzed this same data: "Surveillance ofSARS-CoV-2 at the Huanan Seafood Market" "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019, emerged in December 2019. Its origins remain uncertain. It has been reported that a number of the early human cases of coronavirus disease 2019 had a history of contact with the Huanan Seafood Market...."
"...It should be noted that the selection of shops for sampling was biased because shops selling wildlife as well as shops linked to early cases were prioritized for sampling. The origin of the virus cannot be determined from the analyses available so far. Although gene barcode analysis of animal species in the study suggested that Myotis, Nyctereutes and Melogale-species that have been recognized as potential host species of sarbecoviruses-were present at the market, these barcodes were mostly detected within the SARS-CoV-2 RT-qPCR-negative samples from the environment. It remains pos...
This new paper starts by reviewing the evidence supporting the Huanan Market hypothesis, and some of the details are FASCINATING!

To begin with, of the 174 COVID cases identified with an onset of December 2019, 32% had a link to the Huanan Market.

In a city of 12 million.

3/ "INTRODUCTION Many of the earliest known cases of COVID-19 worked at or visited the Huanan Seafood Wholesale Market ("Huanan market") in the city of Wuhan, a link first made by clinicians at different hospitals throughout the city. Retrospective review of early COVID-19 cases identified 174 patients with onset in December 2019, 32% of whom had an ascertained link to this location, within a city of over 12 million."
Read 24 tweets

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