A Longitudinal Study of COVID-19 Sequelae and Immunity: Baseline Findings, 2022, Sneller et al

Abstract

Background:
A substantial proportion of persons who develop COVID-19 report persistent symptoms after acute illness. Various pathophysiologic mechanisms have been implicated in the pathogenesis of postacute sequelae of SARS-CoV-2 infection (PASC).

Objective:
To characterize medical sequelae and persistent symptoms after recovery from COVID-19 in a cohort of disease survivors and controls.

Design:
Cohort study. (ClinicalTrials.gov: NCT04411147)

Setting:
National Institutes of Health Clinical Center, Bethesda, Maryland.

Participants:
Self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of PASC. A control group comprised persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, recruited regardless of their current health status. Both groups were enrolled over the same period and from the same geographic area.

Measurements:
All participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset also underwent exploratory immunologic and virologic evaluations.

Results:
189 persons with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC.

Limitations:
Most participants with COVID-19 had mild to moderate acute illness that did not require hospitalization. The prevalence of reported PASC was likely overestimated in this cohort because persons with PASC may have been more motivated to enroll. The study did not capture PASC that resolved before enrollment.

Conclusion:
A high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19.


Primary Funding Source:
Division of Intramural Research, National Institute of Allergy and Infectious Diseases.

Full text

 

From the Discussion:

"For participants with PASC, an extensive diagnostic evaluation failed to reveal a cause of reported symptoms in most cases. Exploratory studies did not show evidence of abnormal systemic immune activation or persistent viral infection in participants with PASC. The constellation of subjective symptoms in the absence of objective abnormalities on diagnostic evaluation resembles what has been described with other illnesses, including chronic fatigue syndrome/myalgic encephalomyelitis (21), postinfection syndromes described after resolution of certain viral and bacterial infections (22–25), and mental health disorders such as depression and anxiety (26). The pathogenesis of PASC remains unclear and requires further study."

So they did a bunch of tests and didn't turn up anything.

 

Accompanying editorial, which highlights that the study didn't look at PEM and that the anxiety found may actually be autonomic issues.

 

"Depression and anxiety were assessed using the ultra-brief Patient Health Questionnaire-2 (PHQ-2) and the Generalized Anxiety Disorder-2 (GAD-2). Both questionnaires are validated and standardized assessments of anxiety and depression"

The PHQ-2 is

(click thumbnail to expand image)

and the GAD-2 is

(again, click to expand)

It looks like these are meant to be used as initial screens to highlight the need for further investigation and, unsurprisingly, will also pickup people who have typical symptoms of Long Covid and ME. So perhaps another benefit to science of the wave of Long Covid from the pandemic is that these 'validated' questionnaires will be revealed to many as being, in certain circumstances and use, deeply flawed.

 

And of course, commentators are now highlighting that
"Notably, post-COVID patients were much more likely to have high anxiety scores and depression scores, particularly anxiety with PASC."

 

David Lee MD comments:

 

Eric Topol comments:

 

Here is Gaffney’s wife. She says “a history” of anxiety, when in fact the questionnaire only asks about the past 2 weeks—quite a long history.* (see below, I think I am wrong here but don’t know how to do a strike through font)

https://twitter.com/user/status/1528859492275740673


Gaffney is doing a great job of psychologizing Covid-triggered MECFS—but he couches it in such caring sympathetic language. I *really* don’t like this guy.

ETA—I think I am wrong and Natalie is correct. The questionnaires asked about the past two weeks, but it seems at the initial screening they asked the patients if they had a history of anxiety. So if I’m understanding correctly, they asked about anxiety history AND they did a questionnaire about anxiety in the last two weeks.

 

Gaffney offers condescending pseudo-compassion while his wife seems to derive some sort of less diplomatic pleasure in framing this as hysteria. I believe I saw Gaffney mention that this study opens the door to functional neurological disorder explaining the symptoms, and moreover, using standard rehabilitative approaches to restore functioning. GET/CBT ideologues have to be in heaven over the free promotion provided via Gaffney.

 

One other thing. This paper, coupled with the Brigette Ranque missive surrounding beliefs of having Covid= higher incidence of long Covid, could prove catastrophic for patients. I hate to sound alarmist, but the playing field is decidedly uneven. Patients and their advocates need to produce incontrovertible proof of a definitive pathology. The deluge of discreet anomalous findings will never suffice, as it’s never sufficed for us. Those hoping to deem this hysteria only need a few references and a retinue of willing physicians clamoring to run with said narrative. They’re accumulating their references, and they already have their mouthpieces. I’m sorry, but this has really dampened my spirits.

 

They report two different things, which people are mixing up:

1. People with Long Covid are more likely to have "anxiety" or "depression" according to their questionnaires, which may be the questionnaires capturing physiological LC symptoms as mental health symptoms, actual mental health symptoms as part of LC, or people being quite reasonably depressed or anxious due to their LC.
2. People who reported a history of anxiety disorder before Covid infection were 2.78 [CI, 1.35 to 5.98] times more likely to have LC.

While the problems with the first are obvious, I wonder if there are issues with the second as well. Two potential factors come to mind:

1. People with anxiety and LC might be more likely to enrol themselves in the NIH study than those without anxiety who have LC, leading to an overrepresentation of LC patients with a history of anxiety in their sample.
2. According to NIMH, 31% of adults experience anxiety disorder at some point in their lives, 19% in the past year. But in the NIH's study, only 17-18% of controls and Covid patients without LC reported a history of anxiety disorder. Maybe anxiety makes Covid patients without LC and controls less likely to enrol themselves.

 

There's something deeply ironic that the day after the NIH publishes this waste of a study, the CDC publishes a warning that 1/5 have significant health problems after getting Covid. It's just so all over the damn place. There's something deeply wrong with medicine here, it makes for an incredible mess that just turns people off from trusting experts. You hear one thing one day and the complete opposite the next, then back and forth. Everything is an opinion, pick and choose.

Modern propaganda is not at all built the way Orwell thought it would: there is no need to rewrite the record or torture people into accepting that new "official record". Instead it works by putting out multiple versions of the truth, all with ample true details and a different interpretation. What happens is that it destroys the very concept that there is knowable truth, that everyone lies, just differently.

This is what medicine is currently doing with Long Covid, just a stream of contradictory claims and framing. Honestly medicine is currently executing the most spectacular faceplant any profession has ever managed in all of human history, straight up destroying the very idea that credible experts are even worth paying attention to. It's hard to put into context just how bad this is, how massive the repercussions will be.

Just think how this will completely break everything the next pandemic happens. No one can trust anything they hear from authorities now, especially medical and public health authorities. Medicine is genuinely doing more damage to its image than the entire antivaccination movement. It's not without irony that medicine launched the antivaccination movement and perpetuates it in part by denying the real consequences of vaccines. What a time to be alive...

 

One of the authors is the Head of NIH Lyme research. A couple authors are from the Lyme team.

Moreover, one in five Covid patients walk away with persistent symptoms? Man, that 20% incidence rate keeps coming up in contentious areas. Wish I could think of where else...

Curious, though, that such high incidence infections seem to generate similar rates of persistence. Does it speak to genetics, or some other common mechanism, or something altogether different?

Edit to add: So they could find nothing to explain the sequelae? Self-reported symptoms aside, everything seems pretty much the same as healthy controls? If I read that right, the similarities don't stop with the 20% estimate. I've seen this movie before. I don't much care for where the NIH seems headed with this.

 

Moved post

Brian Vastag has published a series of tweets in last day or so on an article from NIH study
Cannot get link onto here nor do I tweet.
Will have another go and add it in an edit if I have any success.

eta: https://www.acpjournals.org/doi/10.7326/M21-4905. Focus is on medical sequelae following long covid.

 

Here's an interview from last year with the first author, Michael Sneller, that definitely shows some concerning attitudes and ideas. He also seems to favour PTSD as an explanation for post-Ebola symptoms in his previous work (see Discussion).

Here he is on NPR suggesting physical therapy and CBT:

"SNELLER: And clearly don't want to send a message that this is all not real and in people's heads and just go home and stop worrying about it. That's not the message.
STEIN: Instead, Sneller hopes his findings will help doctors understand what's not wrong and focus on what might help, like physical and cognitive behavioral therapy."

This seems bad.

 

I thought his name sounded familiar. As you say, he has been claiming that Long Covid was most likely just 'anxiety' for over a year.

It looks like he then set out to ensure that he found nothing but 'anxiety' in this study.

More on Sneller here.

 

@Sarah94 - I think you are wanting links to NIH study.