Long COVID patients continue to experience significant symptoms at 12 months and factors associated with improvement: France PERSICOR, 2023, Salmon et

Long COVID patients continue to experience significant symptoms at 12 months and factors associated with improvement: a prospective cohort study in France PERSICOR
Salmon; Slama; Linard; Dumesges; Lebaut; Hakim; Oustric; Seyrat; Thoreux; Marshall

Objectives
This study examines long COVID symptoms course over 12-months, their impact on daily life, and associated factors for symptom relief.

Methods
A prospective cohort study included 231 participants with long COVID at 12-months follow-up. Data on characteristics, symptom course and remission were collected using questionnaire and a remission scale. Poisson regression models were used to estimate the prevalence rate ratio (PRR) and 95% confidence intervals (CIs) for factors associated with symptom improvement.

Results
Of the 231 participants, 63.2% developed SARS-CoV-2 antibodies before COVID-19 vaccination. At 12-months, only 8.7% (95% CI: 5.4%-13.1%). reported complete remission, while 28.6% noted significant improvement. Most symptoms remained prevalent: asthenia (83.1%), neurocognitive/neurological (93.9%), cardiothoracic (77.9%), Musculoskeletal (78.8%). During long COVID, 62.2% stopped working, and only 32.5% resumed full-time professional activities. Presence of SARSCoV-2 antibodies before vaccination increased the probability of improvement (aPRR: 1.60, p=0.028), while ageusia at initial long COVID phase decreased the probability (aPRR: 0.38, p=0.007).

Conclusions
Long-COVID symptoms persisted in the majority of participants after 12-months, with significant impacts on daily life and work. SARS-CoV-2 antibodies were associated with better prognosis, while persistent ageusia indicated a lower probability of improvement. These findings highlight the need for ongoing support and care for individuals with long-COVID.

Highlights

• Long COVID patients tend to have persistent symptoms at 12-month

• At 12-month only 8.7% of Long COVID patients are in complete remission

• There is profound impact on daily life, work and daily activities

• SARS-CoV-2 antibodies prior to vaccination appears to be linked with better recovery

• Ageusia is associated with reduced chances of improvement at 12 months

Link | PDF (International Journal of Infectious Diseases)

 

This is relatively commonly described in our local FB support group, where people had recovered completely from a mild infection and a few weeks later started developing symptoms of fatigue, exertion and orthostatic intolerance etc.

This matches my own experience. I first noticed cardiorespiratory abnormalities in mid Jan 2021, but in retrospect was showing evidence of exertion intolerance from early Nov/Dec 2020 (which I didn't recognise at the time). There was zero community transmission of Covid in NZ over those months, so the latest I could have sustained an asymptomatic infection was the tail end of a (modest) wave in Aug/Sep 2020.

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Speculatively and purely looking at the muscle fibre and capillary findings being reported in LC, perhaps the sequence is as follows. Some form of immunometabolic dysfunction is set up (TBA). Capillary flow is impaired, in association with abnormal macrophage infiltration, with damaged and regenerating capillaries that lead to increased basement membrane thickness as a feature. Oxygen diffusion to muscle mitochondria is impaired. Initially metabolically compensated, this leads to increased mitochondrial defects over time that are then symptomatic.

(Perhaps HIF-1⍺ inducing WASF3 could be part of this mechanistic progression. HIF1A induces expression of the WASF3 metastasis-associated gene under hypoxic conditions (2012, International Journal of Cancer))

 

It also matches what I've heard amongst patients in the ME/CFS and neurocognitive subset of LC patients and it is the exact same thing that happened to me. I also always fully recovered from the acute Covid phase and only later developed symptoms of LC/ME/CFS. Retrospectively one might say that there were some mild lingering symptoms, but IMO that is incorrect since it suffers from a lot of bias confirmation if one later develops an illness and in the time between acute Covid and onset of LC/ME/CFS I would have always considered myself fully recovered and also was so based on all available data (working full time, doing sports daily etc). At least for me and those that I've talked to, this had nothing to with taking some time off or something similar.

Nath also discussed these 2 distinct patterns in the recent Advancing ME/CFS Research: Identifying Targets for Intervention and Learning from Long COVID conference (https://videocast.nih.gov/watch=52631). This picture summarises the situation well.



Belonging to the second pattern I'm naturally somewhat biased, but I think research has far to heavily focused on the first pattern and should have explored the second pattern much more. The second pattern automatically excludes the whole PICS, organ damage, pre-existing health anxiety, a continuing cough, anosmia, self-resolving fatigue or similar symptomology that isn't related to what one actually wants to study when studying LC or long-term health outcomes. Compared to the first pattern, there might be a somewhat bigger risk that studying the second pattern also includes some people who have developed problems that could have developed independently of Covid, however choosing previously very healthy people would reduce this risk substantially and the noise reduction of this cohort is well worth it receiving far more attention.

It is quite interesting that people have "brain fog" during acute Covid, then have no problems whatsoever for a number of weeks, and then practically develop "brain fog" overnight a few weeks later. The neurological symptoms of Long-Covid, as well as other symptoms which are considered to be long-lasting on average also begin weeks after the acute phase (there's a couple of studies that explored this for instance https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00299-6/fulltext# and https://www.bmj.com/content/380/bmj-2022-072529).

One beautiful aspect of the second pattern is that it completely falsifies the BPS narrative of "these people have illness beliefs caused by an acute infection and then perpetuated by some mind-body connection", because in fact the acute infection was never a problem, there was no anxiety about the acute infection or mind-body manifestation of it and they fully recovered from it.

If not more focus is placed on this second pattern in the future, then I at least hope that future studies would account for these patterns as part of their data when they recruit their patients.

I don't have much knowledge on something like autoimmunity or different immunological processes, but from what I've understood it is almost impossible that these develops within a day or 2 (which some people in the first pattern or those with post-vacc describe) and certainly seems to be far better matched in the second pattern which Nath describes.