Preprint: Prevalence, determinants, and impact on general health and working capacity of PASC 6-12 m after infection..., 2022, Peter, Kern et al

[Kalliope]

Prevalence, determinants, and impact on general health and working capacity of post-acute sequelae of COVID-19 six to 12 month after infection: a population-based retrospective cohort study from southern Germany
Peter, Kern et al

https://www.medrxiv.org/content/10.1101/2022.03.14.22272316v1 (preprint)

Abstract

Background: Post-acute sequelae of SARS-CoV-2 infection have commonly been described after COVID-19, but few population-based studies have examined symptoms six to 12 months after acute SARS-CoV-2 infection and their associations with general health recovery and working capacity.

Methods: This population-based retrospective cohort study in four geographically defined regions in southern Germany included persons aged 18-65 years with PCR confirmed SARS-CoV-2 infection between October 2020 and March 2021.

Symptom frequencies (six to 12 months after versus before acute infection, expressed as prevalence differences [PD] and ratios [PR]), symptom severity and clustering, risk factors and associations with general health recovery, and working capacity were analysed.

Findings: Among a total of 11,710 subjects (mean age 44.1 years, 59.8% females, 3.5% previously admitted with COVID-19, mean follow-up time 8.5 months) the most prevalent symptoms with PDs >20% and PRs >5% were rapid physical exhaustion, shortness of breath, concentration difficulties, chronic fatigue, memory disturbance, and altered sense of smell. Female sex and severity of the initial infection were the main risk factors.

Prevalence rates, however, appeared substantial among both men and women who had a mild course of acute infection, and PCS considerably affected also younger subjects.

Fatigue (PD 37.2%) and neurocognitive impairment (PD 31.3%) as symptom clusters contributed most to reduced health recovery and working capacity, but chest symptoms, anxiety/depression, headache/dizziness and pain syndromes were also prevalent and relevant for working capacity, with some differences according to sex and age.

When considering new symptoms with at least moderate impairment of daily life and ≤80% recovered general health or working capacity, the overall estimate for post-COVID syndrome was 28.5% (age- and sex-standardised rate 26.5%).

Interpretation The burden of self-reported post-acute symptoms and possible sequelae, notably fatigue and neurocognitive impairment, remains considerable six to 12 months after acute infection even among young and middle-aged adults after mild acute SARS-CoV-2 infection, and impacts general health and working capacity.

 

[Kalliope]

Spotted the paper in a tweet by professor Kunst who comments:
One of the largest population-based studies from Germany shows a high prevalence of #LongCovid also among younger adults with a history of mild acute infection. Considerably impaired general health and work capacity. Note: Pre-print, not peer-reviewed.

 

[rvallee]

rapid physical exhaustion, shortness of breath, concentration difficulties, chronic fatigue

Interesting that they differentiated fatigue from exhaustion, since when we say fatigue it's usually what we mean, rather than either of sleepy or a bit tired that people hear. Hard to say whether they basically mean PEM, since they've had plenty of time to get on with the basics and may simply be using a different term because it's not recognized.

 

[Jonathan Edwards]

Interesting that they differentiated fatigue from exhaustion,

I think what they mean by rapid physical exhaustion is the sort of thing you get with heart failure or respiratory failure (or my mother aged 100) - becoming unable to continue, with shortness of breath, after a minute or less of walking or climbing stairs. After ten minutes rest the problem has settled but will recur with further exercise. The exhaustion of ME sounds to me more like I have seen in people who have just recovered from septicaemia. They don't get 'rapidly exhausted' so much as being exhausted in the first place. PEM would be something different again though.

 

[Trish]

I think with ME it's both types of exhaustion. All the time, and rapid muscle fatiguability preventing ongoing activity after a short time.

 

[Hutan]

Some more of the more interesting bits

People with notified Covid-19 infections in south-western Germany were sent a questionnaire asking about 30 symptoms before infection, during infection and at the time of the survey (6-12 months after infection). Respondents could add other symptoms. For each symptom present, participants were asked to grade the level of impairment.



A potentially large response bias, limiting what we can do with the prevalence rates found.

A total of 50,457 adults with confirmed SARS-CoV-2 infection were invited to participate in the study, of whom 12,053 (24%) subjects responded, and 11,710 provided at least information on age and sex (see study flow-chart in the appendix, figure S1).

On the sex ratio:

Further prevalence measures according to age categories and stratified to sex are shown in the appendix, figure S2. Interestingly, symptoms prior to the acute infection and – more so – post- acute were reported more frequently by women, with PDs for hair loss, headache and nausea differing by a factor greater than two between sexes.

We noted differences between current symptoms regarding the grade of impairment, showing higher grades of impairment for women for most symptoms (see appendix, figure S3).

Smell and taste disorder wasn't well correlated with other symptoms; fatigue was correlated wth neurocognitive impairment and chest symptoms.

Although a variety of long-lasting complaints was reported, few symptoms and symptom clusters drove this burden, and fatigue, neurocognitive impairment, and chest symptoms (e.g. shortness of breath) appeared to be the key health problems.

estimated prevalence differences of 23% for fatigue, 15% for self-reported neurocognitive impairment, and 14% for chest symptoms, respectively, or a prevalence of 41·5% for any at least moderate symptom.

Neurocognitive impairment had a significantly stronger effect on loss of working capacity than on loss of health. They found a good correlation of Heath Related Quality of Life with the SF-12 physical subscore.

Almost one-third of the respondents (30·4%) reported their health recovery to be ≤80%, and 26·6% of the respondents reported ≤80% working capacity recovered in comparison to the situation before acute infection. If such reduced health or working capacity was combined with reporting (any) new symptom of moderate or strong impairment of daily life, we estimated a prevalence of 28·5% (corresponding to an age and sex-standardised prevalence of 26·5%).

Use of the FAS to assess fatigue. They believe the FAS instrument "assesses fatigue largely distinct from depressive symptoms, anxiety and neuroticism.

For the evaluation of fatigue (already included in the list of symptoms), we additionally used the 10-item Fatigue Assessment Scale (FAS).11 A threshold score of ≥22 is used for determining the presence of substantial fatigue, and a threshold score of ≥35 for extreme fatigue. To assess working capacity we adapted questions from the short form of the work ability index.12 Participants assessed their current general health recovery and current working capacity compared with the situation before the acute SARS-CoV-2 infection on a 10-point Likert scale (10% steps from 0% to 100%). To evaluate the current health-related quality of life (HRQoL), we used the SF-12 (short form-12) questionnaire assessing physical and mental health-related quality of life components (https://www.rand.org/health-care/surveys_tools/mos/12-item- short-form.html).

There's mention of ME/CFS - they seem to associate ME/CFS with anxiety, depression and sleep disorders. I guess at least they use the term ME/CFS and have noted an overlap.

fatigue was frequently accompanied by other prevalent symptom clusters such as chest pain and neurocognitive impairment, but also co-occurred with anxiety/depression as a symptom cluster including sleep disorders, and with many other complaints such as pain syndromes – similar to observations elsewhere.14,21-24 This may indicate some overlap of PCS with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) which may include similar sometimes relapsing symptoms and usually persists for years rather than for months. Further investigations are needed to address such a possible overlap.25,26

They conclude:

Roughly one out of four patients had new symptoms that at least moderately impaired daily life and activities and were associated with reduced health recovery or working capacity. Given the individual and societal burden of post-COVID sequelae, the underlying biologic abnormalities and causes need urgent clarification to define adequate treatment options and develop effective rehabilitation measures.

It's a decent study, and apart from the association of ME/CFS with anxiety/depression, it's remarkably free from psychologising. I think it would be really helpful if people with a good knowledge of ME/CFS collaborated with these researchers.

 

[ME/CFS Skeptic]

It's a decent study,

Some major limitations: It's retrospective, asking patients how they felt before infection when they already had the infection. It had no control group without infection and only 1 in 4 people contacted responded.

I'm a bit frustrated that we still haven't got a decent prospective study that follows up patients and a control group for a long period of time (more than a year) to see if COVID-19 increases the incidence of ME/CFS and other conditions or not. I'm beginning to worry if we will ever see one.

 

[Kalliope]

I'm a bit frustrated that we still haven't got a decent prospective study that follows up patients and a control group for a long period of time (more than a year) to see if COVID-19 increases the incidence of ME/CFS and other conditions or not. I'm beginning to worry if we will ever see one.

I thought dr. Avindra Nath talked about that and that NIH was going to do this? Following lots of Covid-19 patients over time and investigating differences in people who go back to normal compared with those who don't. But I don't know of any concrete research projects.

 

[Peter T]

I'm a bit frustrated that we still haven't got a decent prospective study that follows up patients and a control group for a long period of time (more than a year) to see if COVID-19 increases the incidence of ME/CFS and other conditions or not. I'm beginning to worry if we will ever see one.

I echo your frustration, given the horror of Covid-19 it was a hopefully unique opportunity to undertake prospective studies on the full range of post viral conditions, including ME, but so far we have largely seen a total failure to learn from previous poor ME research.

 

[rvallee]

I think what they mean by rapid physical exhaustion is the sort of thing you get with heart failure or respiratory failure (or my mother aged 100) - becoming unable to continue, with shortness of breath, after a minute or less of walking or climbing stairs. After ten minutes rest the problem has settled but will recur with further exercise. The exhaustion of ME sounds to me more like I have seen in people who have just recovered from septicaemia. They don't get 'rapidly exhausted' so much as being exhausted in the first place. PEM would be something different again though.

I don't think I'm typical in that but the first description applies to me perfectly so it applies to ME to some degree (and I've read several from pwLC but the delayed response is more typical). There's a lot of emphasis on delayed symptoms but I have basically a few seconds to maybe a few minutes before I get like this. Rapid exhaustion is a good description, but not just physical, cognitive does the same. Like an electrical machine with a drained battery. High heart rate, shortness of breath and just complete physical, uh, molasses.

Not always though. Which is absolutely ideal when trying to figure it out...

 

[Hutan]

I'm a bit frustrated that we still haven't got a decent prospective study that follows up patients and a control group for a long period of time (more than a year) to see if COVID-19 increases the incidence of ME/CFS and other conditions or not. I'm beginning to worry if we will ever see one.

Yes. But these researchers seemed better than many we have seen, and seem to understand the significance of Long Covid, which is why I suggested people who understand ME/CFS contact them. The researchers themselves call for more study of this and I think they might be open to being assisted to make a better study.

This may indicate some overlap of PCS with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) which may include similar sometimes relapsing symptoms and usually persists for years rather than for months. Further investigations are needed to address such a possible overlap

Some major limitations: It's retrospective, asking patients how they felt before infection when they already had the infection. It had no control group without infection and only 1 in 4 people contacted responded.

Yes, these are significant problems that severely limit what can be done with the results. But, at least they asked participants about their symptoms prior to Covid-19 and made adjustments for that - many studies haven't. The size of the study was good. Rather than just ask about the presence of a small number of symptoms, they asked about the presence of many symptoms. Importantly, they asked about severity/impact on life which is better than surveys that simply ask, for example, 'Do you have headaches?'.

Roughly one out of four patients had new symptoms that at least moderately impaired daily life and activities and were associated with reduced health recovery or working capacity.

 

[Snow Leopard]

Importantly, they asked about severity/impact on life which is better than surveys that simply ask, for example, 'Do you have headaches now?'.

Yes, this is a key point that many of the prior "studies" lacked.