Acute serum protein biomarker profile and prevalence of persistent [...] neuropsychiatric symptoms in [SARS-CoV-2+] [...], 2025, Niekerk et al

Acute serum protein biomarker profile and prevalence of persistent (>6 months) neuropsychiatric symptoms in a cohort of SARS-CoV-2 PCR positive patients in Cape Town, South Africa

Inette van Niekerk, Monica Panieri, Talitha Müller, Lovemore Mapahla, Sonwa Dzanibe, Cascia Day, Dan J. Stein, Jonny Peter

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Highlights
• Neither systemic inflammatory, cardiovascular, nor renin-angiotensin-system (RAS) biomarkers or antibody responses performed during the peak of illness or on a recovery sample at least three months after disease resolution, could predict persistent post-infection longer term (>6months) neuropsychiatric symptom outcomes
• More than half of participants from this South African post COVID-19 cohort (median 45 years old) were affected by neuropsychiatric symptoms of anxiety, fatigue, memory and cognitive impairment across the spectrum of disease severity (from asymptomatic to critical).

Background
SARS-CoV-2 is a neurotrophic and pro-inflammatory virus, with several acute and more persistent neuropsychiatric sequelae reported. There are limited data from African cohorts and few acute illness biomarkers of persistent neuropsychiatric symptoms.

Objectives
To examine the association of neuropsychiatric outcomes with clinical illness severity, systemic inflammation, cardiovascular and renin-angiotensin-system (RAS) biomarkers. Second, to determine the prevalence of neuropsychiatric symptoms in a cohort of South African SARS-CoV-2 PCR positive patients at least six months following infection/hospitalization.

Methodology
SARS-CoV-2 PCR positive patients were recruited prospectively from Cape Town, South Africa, including hospitalized patients from ancestral, beta and delta-dominant COVID-19 waves (pre-vaccine rollout); and asymptomatic/mild SARS-CoV-2 positive patients. The 96-protein O-link inflammation and cardiovascular panels, RAS fingerprinting, and antibody responses were measured in serum samples collected at peak severity and recovery (>3 months post-infection).

Telephonic interviews were conducted at least six months post infection/hospitalization. Validated measures employed were: WHO Self-Report Questionnaire (SRQ-20), Generalized Anxiety Disorder Scale (GAD-7), Chalder Fatigue Scale (CFS-11) and Telephonic Montreal Cognitive Assessment (T-MoCA).

Results
Ninety-seven participants completed telephonic interviews. The median (IQR) age was 48(37-59) years, and 54% were female.

There were no significant associations between neuropsychiatric outcomes and illness severity, systemic inflammation, cardiovascular and/or renin-angiotensin-system (RAS) biomarkers from either peak illness or recovery samples.

More than half of this SA COVID-19 cohort had one or more persistent neuropsychiatric symptoms >6 months post vaccine-naïve infection. On the T-MoCA, 44% of participants showed evidence of cognitive and/or memory impairments.

Conclusion
The high prevalence of persistent neuropsychiatric symptoms in this African cohort supports ongoing attention to long COVID. Acute and early serum protein biomarkers were not associated with persistent neuropsychiatric outcomes post-COVD-19.

Link | PDF (Brain, Behavior, & Immunity - Health) [Open Access, Press Pre-proof]

 

Is it just me and I'm not understanding? Does that sequence of words actually make sense? What is the "acute" referring to? And how can serum protein be "acute".

Why do researchers - particularly the ones keen on finding psychiatric problems - never test for anemia after illness? Every major surgery I've ever had has left me with iron deficiency or iron deficiency anaemia. And that causes fatigue. I have similar results from some serious illnesses. I got Covid badly twice and ended up low in iron after it.

It seems to me that psychologists are rubbing their hands in glee because they find patients with anxiety or fatigue or depression after illness. But you can't replace low vitamins and minerals with CBT or GET.

 

I think they just mean proteins measured during the acute illness.

 

I’m assuming they just mean cytokines in the blood here?

 

Thanks. That makes sense. It was still a poorly worded title in my opinion!

 

A recent LC paper I co-authored also used the serum O-link assay. One of the models we tested was for predicting cognitive impairment as measured by the PROMIS cognitive function scale. Tldr, we couldn't get a model with any predictive power from it--the only one with strong enough signal was for the PROMIS physical function scale.

I suspect that whatever drives cognitive dysfunction in LC, the markers of it aren't very detectable in the blood.