Long COVID: major findings, mechanisms and recommendations, 2023, Davis, Topol et al

[Kalliope]

Nature reviews microbiology
Long COVID: major findings, mechanisms and recommendations

Abstract

Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.

More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily.

Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field.

In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations.

Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses.

Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process.

https://www.nature.com/articles/s41...qkinzI2fO5dBkWxCNAXBrOqUrl7Rq0MlHELfbmbRv-Nc=

 

[Hutan]

Hannah Davis
Lisa McCorkell
Julia Moore Vogel
Eric Topol

The most interesting thing for regular members here, I think, is that this is in 'nature reviews microbiology'. Good on the authors for taking the message to the readers of that journal.

At least 65 million individuals around the world have long COVID, based on a conservative estimated incidence of 10% of infected people and more than 651 million documented COVID-19 cases worldwide1; the number is likely much higher due to many undocumented cases.

I think we have to be careful about calculations like that. Just because 10% of people have persisting symptoms 6 months after the infection, it doesn't mean that the symptoms will be there forever. Incidence is not the same as prevalence.

We know that most people recover from post-infection conditions (e.g. the Dubbo study). I think a better guess would be around 1% - although who knows what the impact of repeated infections will be.

There are currently no validated effective treatments. There are likely multiple, potentially overlapping, causes of long COVID

Both important points

 

[Robert 1973]

Eric Topol Tweet:

“Below is our Table summarizing candidate treatment options for different components of #LongCovid
If you have any access issues, you can use this link
rdcu.be/c3m45”

 

[Hutan]

A higher prevalence of long Covid has been reported in certain ethnicities, including people with Hispanic or Latino heritage35

I hadn't heard that before.

35 CDC. Long COVID- household pulse survey - COVID-19. https://www.cdc.gov/nchs/covid19/pulse/long-covid.htm 2022

As part of an ongoing partnership with the Census Bureau, the National Center for Health Statistics (NCHS) recently added questions to assess the prevalence of post-COVID-19 conditions (long COVID), on the experimental Household Pulse Survey. This 20-minute online survey was designed to complement the ability of the federal statistical system to rapidly respond and provide relevant information about the impact of the coronavirus pandemic in the U.S. Data collection began on April 23, 2020.

Beginning in Phase 3.5 (on June 1, 2022), NCHS included questions about the presence of symptoms of COVID that lasted three months or longer. Beginning in Phase 3.6 (on September 14, 2022), NCHS included a question about whether long-term symptoms among those reporting symptoms lasting three months or longer reduced the ability to carry out day-to-day activities compared with the time before having COVID-19. Phase 3.6 will continue with a two-weeks on, two-weeks off collection and dissemination approach.

That survey is an interesting source of information, no doubt we have a thread on it already. If not, I'll make one.
Edit - Yep, thanks @LarsSG
US: Long Covid prevalence from Household Pulse Survey

 

[Trish]

I think we have to be careful about calculations like that. Just because 10% of people have persisting symptoms 6 months after the infection, it doesn't mean that the symptoms will be there forever. Incidence is not the same as prevalence.

But as a running percentage it may be accurate, given that the virus is still infecting vast numbers of people, so as some recover, others will get sick. And as some don't get better long term, the numbers are likely to increase overall until it reaches a plateau in overall numbers with people dying as fast as new cases starting.

 

[RedFox]

After all these years the only recommendation for PEM is pacing.

 

[Sean]

...similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field.

Nowhere near as much as it could and should have.

 

[Hutan]

I'm not sure that the authors fully understand how thin and unreliable the ME/CFS literature is - and the Long Covid literature is not looking to be substantially better yet. That 2015 Hornig paper (43), for example, has not been replicated and I don't think we have much certainty about what cytokines are doing in ME/CFS, early in the disease or otherwise. Nanoneedle diagnostic testing is noted as useful existing ME/CFS-related knowledge that can be built on.

That Klein, Iwasaki paper didn't find abnormal cortisol levels in the Long Covid patients, on average, just an average lower than the controls. Cortisol levels adjust quite quickly to physical activity - it is not at all surprising to find that cortisol levels were lower in the Long Covid patients. The literature on cortisol levels in ME/CFS in its entirety does not support a claim that levels are abnormally low.

It's great that the similarities between ME/CFS and a substantial portion of Long Covid are acknowledged, and that clinical trials are called for in a very robust way. It's great that the problems with exercise therapies are acknowledged and the potential for misdiagnoses of mental health conditions when inappropriate survey tools are used is highlighted. Wonderfully, this is a BPS free-zone, although the old HPA-axis dysfunction hypothesis still gets a whirl.

Despite the paper's comment that I noted in a post above (that there are no validated effective treatments for Long Covid), it is suggested that there are treatments for ME/CFS that can be useful in Long Covid. This is probably my biggest concern - the promotion of treatments that, as yet, are a long way from being proven as being of use in either ME/CFS or LC.

There are a lot of good things in the paper, including the call for more research funding and the establishment of an NIH national institution of Complex Chronic Conditions (just please don't use 'complex', and maybe Diseases would be better than conditions?).

 

[Robert 1973]

Despite the paper's comment that I noted in a post above (that there are no validated effective treatments for Long Covid), it is suggested that there are treatments for ME/CFS that can be useful in Long Covid. This is probably my biggest concern - the promotion of treatments that, as yet, are a long way from being proven as being of use in either ME/CFS or LC.

I only skimmed it but this was what concerned me. Overstating what is known is unhelpful in so many ways. In particular, it undermines the credibility of the valid arguments/assertions, and it may give patients false hope which may lead to them wasting time, energy and money on private medicine and therapies that don’t work.

Why can’t authors just be honest about how little we know instead of claiming we know more than we do?

It’s disappointing that the peer-review process has failed to iron out these issues.

 

[CRG]

I really don't know what this paper is - there are massive claims based on pretty thin evidence. I'm not encouraged by the author qualifications - superstar academics like Topol too often come to rely on appeal to their own authority (and too often get a peer review pass) Moore Vogel who works at the Scripps Research Institute (run by Topol), is a Mathematician with a Phd in Computational Biology and Medicine. Davis and McCorkell are from the Long Covid advocacy org the Patient-Led Research Collaborative, Davis is a machine learning artist, and McCorkell has a Masters in Public Policy and a BA in Political Science.

The lack of any epidemiologist input is a serious concern, no matter the capabilities, competences and insights of the other authors. I think it leaves the paper more of a manifesto than science.

 

[belbyr]

This should at least help fight all the 'pace pushers' and 'CBT'ers' that there is physical evidence of things gone awry.

 

[Charles B.]

I expect the PACE crowd to articulate the same defenses as always regarding these physiological abnormalities. They’ll assert that they’re likely downstream consequences of prolonged inactivity; they haven’t been sufficiently replicated; differences are too negligible to explain clinical presentation; similar findings in a host of neuropsychiatric conditions; etc.

 

[Hutan]

I expect the PACE crowd to articulate the same defenses as always regarding these physiological abnormalities. They’ll assert that they’re likely downstream consequences of prolonged inactivity; they haven’t been sufficiently replicated; differences are too negligible to explain clinical presentation; similar findings in a host of neuropsychiatric conditions; etc.

And they may not be wrong to do that about a lot of the findings, especially the 'not replicated' argument. Which is why it's best not to make claims that reach beyond the evidence.

 

[Kalliope]

The Sydney Morning Herald
´We're all vulnerable': One in 10 people will end up with long COVID, new study says

quotes:

The report’s researchers believe there are significant similarities between long COVID and some chronic health conditions, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia, a disorder of the autonomic nervous system.

Around half of the people living with long COVID meet the criteria for ME/CFS, the report says.

...

Victoria’s chief health officer, Brett Sutton, called the research “incredibly important” and hoped the review would raise awareness and progress research into chronic conditions such as ME/CFS and postural tachycardia syndrome (PoTS).


Crabb said doctors should believe patients who present with long COVID because “the accuracy with which somebody self-reports is tremendous”.

“Long COVID is not some vague mysterious thing that you can palm off as psychosomatic, though many do. It is a very clear clinical illness with a biochemical and cellular underpinning,” he said.

 

[rvallee]

Victoria’s chief health officer, Brett Sutton, called the research “incredibly important” and hoped the review would raise awareness and progress research into chronic conditions such as ME/CFS and postural tachycardia syndrome (PoTS).

If only there were some sort of, person, with a, responsibility of sorts, and a platform to do so, hell even an entire office with staff and resources and stuff, could do more than raise awareness and actually do something.

Some sort of... I don't know... health officer, maybe? Hell, make it a chief officer, or something, sounds so much more official. Nah that's clearly unrealistic, it's the natural burden of patients to have to do not only all the work but all the awareness while the paid people to do exactly that just sit on their ass hoping someone would do the job they aren't doing.

 

[Hutan]

Although, I don't know this Brett Sutton. I'm happy to give him the benefit of the doubt for a while, and look forward to concrete action from the Victorian government to improve the situation of people with LC and ME/CFS.

 

[oldtimer]

The Victorian Chief Health Officer is responsible for providing advice to the state government about anything and everything to do with public health and well-being. The government can take this advice or not. It can assign the CHO powers and take them away as it wants.

Brett Sutton was given the power to make the state's covid lockdown decisions until the government's need to open up again would have clashed with Sutton's views, at which point his emergency powers were rescinded.

He is a great CHO in my opinion and cannot be expected to do more than he is authorised to do. Like it or not, elected politicians are where the focus should be and I don't doubt he advises the health minister about long covid.

 

[Sean]

Sutton is one of the senior health professionals in Oz who has handled Covid well.

 

[Kalliope]

RNZ Risk of debilitating illness from long Covid could grow - epidemiologist Michael Baker

quote:

"It basically results in a vast array of different symptoms," University of Otago epidemiologist Michael Baker told Morning Report on Tuesday.

"Weakness and fatigue, neurological symptoms - people talk about brain fade and so on, and haze; and the other area of course is respiratory problems - being chronically short of breath.

"Many people have this effect, this post-Covid syndrome, that resembles ME (myalgic encephalomyelitis) and chronic fatigue syndrome, which are very well-known post-viral illnesses. And they, we know from past experience, can result in quite debilitating illness that can last for many years, and is in many cases permanent."

 

[rvallee]

Medicine is failing Long Covid not because it's new, but precisely because it's familiar and decades of mocking and dismissing this are too embarrassing to walk back. This is the simple truth: medicine is choosing, consciously or not, to continue failing rather than admitting to have done harm and cease doing so. In doing so, the profession is choosing to do more harm, knowing it has done so much harm already.

At the start of #LongCovid, everyone was so adamant we needed prevalence numbers to get the attention of policymakers and researchers, despite us getting some attention without that. So, I & many other advocates put a ton of effort into getting the HPS data and other surveys..

Once we got those, then the response was, "well that's inflated; that will never convince people," despite evidence they are *underestimating* prevalence. Meanwhile we're still getting meetings with CDC, HHS, NIH, etc.

Being in those rooms, the issue is not this disbelief in prevalence. It's political. It's budget related. It's steeped in a history of neglect of infection-onset illness.