[Preprint] Post-acute symptoms 4 months after SARS-CoV-2 ... during the Omicron period: a ... Danish ... study, Spiliopoulos et al (2022)

Full title: [Preprint] Post-acute symptoms four months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study, Spiliopoulos et al (2022)

Participants 44,004 individuals aged 15 years or older with either a SARS-CoV-2 RT-PCR positive test result from the period of Delta dominance (July to November 2021), or a positive or negative RT-PCR test result from the period of Omicron dominance (December 2021 to January 2022).

Methods A questionnaire based cohort study with outcomes on post-acute physical, fatigue, cognitive, mental health symptoms, and new-onset general health problems, four months after testing. Risk differences (RDs) were estimated by comparing cases and controls during the Omicron period, cases during the Delta and Omicron periods, and vaccinated cases with two and three doses during the Omicron period, adjusted for age, sex, BMI, self-reported chronic diseases, Charlson comorbidity index, healthcare occupation and vaccination status.

Results Four months after testing for SARS-CoV-2 during the Omicron period, cases experienced higher risk of 18 out of 26 post-acute symptoms and five out of five new-onset general health problems, compared to controls. Cases during the Omicron period experienced lower risks of 8 of the 18 symptoms and of all five new-onset general health problems, compared to Delta cases. The most prominent RDs estimated when comparing Omicron cases to controls were: memory issues (RD=5.4%, 95% CI 4.8 to 6.1), post-exertional malaise (RD=5.3%, 95% CI 3.1 to 7.7), fatigue/exhaustion (RD=5.2%, 95% CI 3.7 to 6.9), substantial fatigue (RD=5.0%, 95% CI 2.7 to 7.5), and dyspnea (RD=4.8%, 95% CI 3.8 to 5.9). Compared to cases from the Delta period, Omicron cases reported reduced risks of post-acute altered/reduced sense of smell (dysosmia) (RD=−15.1%, 95% CI −17.0 to −12.9) and −taste (dysgeusia) (RD=−11.6%, 95% CI −13.6 to −9.7). Cases vaccinated with three doses prior to Omicron infection reported reduced risk of 13 of the 26 post-acute symptoms and of three of the five new-onset general health problems, compared to those vaccinated with two doses.

Conclusions A considerable amount of cases infected during the Omicron period experienced post-acute symptoms and new-onset health problems, four months after testing, although milder compared to Delta cases. During the Omicron period, a booster vaccination dose was associated with fewer post-acute symptoms and new-onset health problems, four months after infection, compared to two doses of COVID-19 vaccine."

https://www.medrxiv.org/content/10.1101/2022.10.12.22280990v1.full-text

 

Hm. So they used the DePaul Symptom Questionnaire to assess PEM. And somehow found 30% of the controls reported PEM (vs 34-35% of cases, depending on virus variant, shown in figure 1).

What went wrong here? DSQ unfit for purpose? DSQ somehow badly implemented? Or were the controls with PEM actually Long Covid cases but weren't counted as such due to the study's design?

As far as I can make out cases were defined by having a confirmed infection during two defined study periods whereas controls did not have a confirmed infection during those same two periods. It's not clear to me if they could have been infected before and/or between those periods.

Edited to highlight it's 30% of controls who supposedly have PEM as assessed by the DSQ.

 

We really need to figure out the issue here. Nobody will take us seriously if they think 30% of healthy people experience PEM.

 

Here's a simple table of what they found between Omicron and Delta. It looks like they're comparing people who get acute Delta vs. Omicron, rather than people who get LC from Delta vs. Omicron, so this considers both the differences in what LC symptoms are most common, as well as the overall difference in the risk of LC.

Long Covid symptoms more common from Omicron than Delta:

• Anxiety

More common from Delta:

• Fatigue/exhaustion
• Dyspnea (breathlessness)
  
• Dysosmia (trouble smelling things)
• Headache
• Dysguesia (trouble with taste)
• Sore throat
• Chills

Similar in severity:

• Arms/legs falling asleep
• Runny nose
• Dizziness
• Weakness
• Red runny eyes
• Hot flashes/sweating
• Cough
• Chest pain
• Abdominal pain
• Nausea
• Diarrhea
• Muscle/joint pain
• Fever
• Reduced appetite
• Depression
• PEM
• Fatigue (evaluated using a different method)
  
• Cognitive issues

 

The also use the Hospital Anxiety and Depression scale to evaluate mental health, which only asks about emotions, not tiredness or autonomic symptoms.

 

That's why I posted the study. The lack of understanding of what PEM really is worries me. This team didn't even realise that something must have gone wrong if you find 30% of controls reporting a phenomenon considered extremely rare to non-existent outside ME and LC.

 

The questions and scoring of them can be seen here, A Brief Questionnaire to Assess Post-Exertional Malaise 2018 Cotler, Jason et al

I know that it can be challenging for a questionnaire to capture the experience of patients and achieve a particular aim but, for me, as an assessment of PEM this doesn't come close enough. Too many of the questions could be answered honestly by people who don't experience PEM and yet be rated as suffering from PEM, as seems to be the case in this paper.