Growth Differentiation Factor-15 Is Considered a Predictive Biomarker of Long COVID in Non-hospitalized Patients, 2024, Ono et al.

[SNT Gatchaman]

Growth Differentiation Factor-15 Is Considered a Predictive Biomarker of Long COVID in Non-hospitalized Patients
Rie Ono; Shin Takayama; Michiaki Abe; Ryutaro Arita; Takaaki Abe; Tadashi Ishii; Rie Ono; Shin Takayama Sr.; Michiaki Abe; Ryutaro Arita; Takaaki Abe; Tadashi Ishii

Mitochondrial dysfunction is associated with various diseases. Mitochondria plays a regulatory role during infection. The association between mitokines and subsequent COVID progression has not been previously studied. The retrospective cohort study aimed to investigate the potential of serum mitokines as long COVID biomarkers in non-hospitalized patients.

Patients with confirmed SARS-CoV-2 infection and blood test reports between January 2021 and April 2023 were included. Patients were categorized into two groups, the recovered and long COVID groups, based on fatigue, decline in focus, and pain. Serum levels of growth differentiation factor 15 (GDF-15) and fibroblast growth factor-21 (FGF-21), which are affected by mitochondrial function, along with inflammatory and vascular endothelium markers, were measured using enzyme-linked immunosorbent assays (ELISA). A receiver operating characteristic curve was used to screen the biomarkers.

The threshold value of GDF-15 in the acute phase was 965 pg/mL (sensitivity: 71.4%, specificity: 83.3%), indicating that GDF-15 may be associated with the presence of symptoms three months post onset. No association with inflammatory markers and vascular structures was observed. Therefore, elevated GDF-15 levels in the acute phase may act as a predictive biomarker of long COVID.

Link | PDF (Cureus) [Open Access]

 

[EndME]

"Considered" biomarker no. 1012152.

 

[Hutan]

In this retrospective study, we aimed to investigate whether serum GDF-15 and FGF-21 may predict the onset and prognosis of long COVID in non-hospitalized patients with mild or moderate symptoms in the acute phase.

This retrospective cohort study included patients who had medical treatment in the isolation facilities for COVID-19 in Miyagi Prefecture between January 2021 and April 2023 and needed medical checks for residual symptoms over three months post onset. The exclusion criteria were unconfirmed to SARS-CoV-2, requiring oxygenation, hospitalization, and pregnancy.

We categorized patients into two groups based on the VAS scores for fatigue, decline in focus, and pain: the recovered and long COVID groups. Patients in the recovered group were asymptomatic, with VAS scores for the aforementioned symptoms at zero, Conversely, patients in the long COVID group continued to experience any of these symptoms three months post onset.

Blood samples were centrifuged and stored at -80 ℃ at the Tohoku University Medical Megabank Organization. We analyzed serum samples from the acute phase and approximately three months post onset. We measured GDF-15 and FGF-21 as indicators of mitochondrial function. Additionally, we identified several potential biomarkers for comparison with GDF-15 and FGF-21: inflammation markers IL-6, TNF-α, and IL-8; anti-inflammation marker IL-10; and endothelium markers vascular cell adhesion molecule-1 (VCAM-1) and syndecan-1.

Consent for the study and blood samples was obtained from 197 cases during the acute phase. Subsequently, blood samples from 13 cases (6.6%) were collected after three months. In 13 cases, seven cases (53.8%) were categorized into the long COVID group. Table 1lists the background characteristics of the patients. The patient age ranged from 31 to 75 years, and eight patients (57.1%) were women.

That's what I was looking for - how many people? Turns out they looked at 13 cases at the three month mark, 7 of which were categorised as long COVID. So, 7 Long Covid; 6 controls to make this biomarker.

Mean age: controls 44.5; long COVID 56 years
Female percentage: controls 50%; long COVID 71.4%
body mass index range: controls 17.4 -30; long COVID 18.4 -25.1

I should really stop there.

 

[butter.]

I doubt that GDF15 will be a good predictor/biomarker for LC and ME/CFS, but the study design (not in terms of how many patients were used!) is what we need much more of, we need to get a better grip of acute vs sub-acute vs chronic disease vs recovery (the PVFS subgroup,in case it really exists) in IACCs.

 

[butter.]

What's pretty insane about this, apart from the study population size, is that GDF15 is fully expected to be higher in an older population.

 

[Hutan]

A is GDF-15; B is FGF-21 - levels in the acute phase disease

It's just too small a sample and too confounded to tell us anything.


GDF-15

No significant difference was observed between the median acute phase GDF-15 level (610 pg/mL; range: 320-1,610 pg/mL) of the recovered group and that (1,120 pg/mL; range: 320-1,680 pg/mL) of the long COVID group (p = 0.23). However, there was variation in the distribution of values between the two groups during the acute phase. The AUC of the ROC curve (Figure 1C) was 0.71, indicating a moderate predictive ability. The threshold value was 965 pg/mL (sensitivity: 71.4%, specificity: 83.3%). Of the patients with GDF-15 levels of 965 pg/mL or higher, five out of six (83.3%) exhibited symptoms, compared to two out of seven (28.6%) with levels below 965 pg/mL. Although not statistically significant (Fisher's exact test, p = 0.08), many patients with serum GDF-15 levels of 965 pg/mL or higher experienced symptoms. After three months, serum GDF-15 levels were 535 pg/mL (range: 470-1,100) in the recovered group and 590 pg/mL (range: 220-1,430) in the long COVID group (p = 0.66).

Limitations

This study has some limitations. Serum GDF-15 and FGF-21 levels are affected by age, which is also a long-term risk factor for COVID; therefore, age could have interfered with the conclusions regarding the potential of mitokines as biomarkers. The small sample size posed another limitation. This study was conducted using stored samples, thus limiting the number of samples available.

In this study, blood samples were collected from 197 patients during the acute phase, but only 13 patients required medical treatment for more than three months. In other words, the incidence of patients with residual symptoms was 6.7%, resulting in a small sample size for this study.

So it sounds as though the 6 controls required medical treatment for more than three months.