scRNA-seq reveals persistent aberrant differentiation of nasal epithelium driven by TNFα and TGFβ in post-COVID syndrome, 2025, Reddy et al.

[Hutan]

On the participants:

We selected 33 patients (whose entire metadata was available) recruited from the NAPKON study cohort (n = 1270). Using the PCS questionnaire developed previously8, these 33 participants were clas-si ed into mild (n = 4), moderate (n = 11), and severe (n = 18) PCS based on long-term symptom complexes. Supplementary Fig. S1 contains a breakdown of the number of samples selected from the NAPKON cohort.

The threshold for each PCS group classi cation was deter-mined at mild PCS < 10.75, moderate 10.75–25.25, and severe PCS >25.25. Using a curette, the nasal epithelium was collected from the anterior and medial heads of the middle turbinate (Fig. 1).

All patient groups had a comparable age, with no sex imbalance between the moderate and severe PCS groups. Severe PCS patients reported more joint and muscle pain, and skin complaints compared to moderate PCS patients. Notably, severe PCS patients also present with higher rates of breathing problems and symptoms of infections (Supplementary Table S1). This indicates an apparent increased disruption of respira-tory function in severe PCS.

Ref 8 for the PCS questionnaire is
Bahmer, T. et al. Severity, predictors and clinical correlates of Post-COVID syndrome (PCS) in Germany: a prospective, multi-centre, population-based cohort study. EClinicalMedicine 51,101549 (2022).

The development of a PCS score was based upon the binary indicators of 12 non-overlapping long-term symptom complexes of COVID-19, chosen a priori to cover the likely spectrum of infection-related health complications (Table 1).

1 Chemosensory deficits (taste, smell) 3.5
2 Fatigue 7
3 Exercise intolerance (shortness of breath, reduced exercise capacity) 4
4 Joint or muscle pain 6.5
5 Ear-Nose-Throat (ENT) ailments (hoarseness, sore throat, running nose) 5.5
6 Coughing, wheezing 7
7 Chest pain 3.5
8 Gastrointestinal ailments (stomach pain, diarrhoea, vomiting, nausea) 5
9 Neurological ailments (confusion, vertigo, headache, motor deficits, sensory deficits, numbness, tremor, deficits of concentration, cognition or speech) 6.5
10 Dermatological ailments (Hair loss, rash, itchiness) 2
11 Infection signs (chills, fever, general sickness/flu-like symptoms) 3.5
12 Sleeping disturbance (insomnia, unrestful sleep) 5

The work was done on three cohorts of people with PCS. Females accounted for 56.5%, 52.1% and 55.8% of the cohorts.
Weightings were given to each symptom cluster depending on how relevant it was found to be to overall disease severity. (The weightings are the numbers in red above.) For an individual, their PCS score depends on whether the symptom cluster is present or not. If a symptom cluster is present, no matter whether it is mild or severe, they get the symptom cluster score. The sum of the symptom cluster scores produces the individual's PCS score.

Less than 10.75 = Mild PCS
10.75- 26.25 = Moderate PCS
More than 26.5 = Severe PCS

So, someone could have fatigue, chest pain, coughing and wheezing and shortness of breath on exercising and score 7+3.5+7+4 =21.5
Someone could have fatigue, PEM, brain fog and unrestful sleep and be housebound and score 7+4+6.5+5=22.5.
Someone could have problems with their sense of smell, an occasional headache and mild insomnia, but otherwise be well 3.5+6.5+5 =15
These people could have completely different pathologies, but they all would be classified as 'Moderate PCS'.

In addition, partici-pants with higher PCS scores had been hospitalised more often during the acute phase (none/mild: 8, 4.2%; moderate: 30, 10.8%; severe: 17, 15.6%; p = 0¢0022) and had experienced a greater number of, as well as more severe, acute symptoms (both p < 0¢0001). Further-more, pre-existing respiratory, cardiovascular, neuro-logic, psychiatric, rheumatologic/immunologic, and allergic comorbidities were more frequent in Kiel-I cohort members with high PCS scores (all p < 0¢05; see Supplementary Table 3). While all functional measure-ments taken during the site visit were within non-patho-logical reference ranges, resting heart rate as well as some lung function and echocardiography parameters were different between PCS score-defined classes (Table 4).

The paper notes that people who had a more severe acute illness are more likely to have a severe PCS score. I still haven't looked at this nasal epithelium paper yet. But, unless the authors applied additional criteria, then I think the 'moderate PCS' and 'severe PCS' groupings are too heterogeneous to be useful. And I think our suspicion that the findings are more related to the severity of the acute illness than anything particularly related to ME/CFS is warranted.

(cross post with SNT Gatchaman)