No reduced serum serotonin levels in patients with post-acute sequelae of COVID-19, 2024, Mathé et al.

No reduced serum serotonin levels in patients with post-acute sequelae of COVID-19
Mathé, Philipp; Götz, Veronika; Stete, Katarina; Walzer, Dietrich; Hilger, Hanna; Pfau, Stefanie; Hofmann, Maike; Rieg, Siegbert; Kern, Winfried V.

PURPOSE
Approximately 10–20% of patients previously infected with SARS-CoV-2 experience post-acute sequelae of COVID-19 (PASC), presenting with fatigue and neurocognitive dysfunction along various other symptoms. Recent studies suggested a possible role of a virally induced decrease in peripheral serotonin concentration in the pathogenesis of PASC. We set out to verify this finding in an independent and well-defined cohort of PASC patients from our post-COVID-19 outpatient clinic.

METHODS
We performed a retrospective case–control study including 34 confirmed PASC patients and 14 healthy controls. Clinical assessment encompassed physician examination as well as questionnaire based evaluation. Eligibility required ongoing symptoms for at least 6 months post-PCR-confirmed infection, relevant fatigue (CFS ≥ 4), and no other medical conditions. Serum serotonin was determined by LC–MS/MS technique.

RESULTS
Serum serotonin levels in PASC patients did not significantly differ from healthy controls. Most subjects had normal serotonin levels, with no subnormal readings. Subgroup analyses showed no significant differences in serotonin levels based according to predominant fatigue type, high overall fatigue score or depression severity.

CONCLUSIONS
We postulate that peripheral serotonin is no reliable biomarker for PASC and that it should not be used in routine diagnostic. Therapy of PASC with serotonin-reuptake inhibitors or tryptophane supplementation should not be based solely on the assumption of lowered serotonin levels.

Link | PDF (Infection) [Open Access]

 

Is measuring serotonin actually worth doing for anyone? Doctors dish out SSRIs to depressed patients without ever measuring serotonin. And I thought the idea that depression was caused by low levels of serotonin was outdated now. I was also under the impression that 90% of serotonin in the body was found in the gut rather than the brain. So is it really connected with fatigue?

 

I think it's based on past research that saw abnormalities in serotonin in ME/CFS. For example:

Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review, 2020, Shan et al

Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome, 2024, Walitt et al

 

Reduction in serotonin transporters in the brain wouldn't necessarily correlate with overall serotonin level in the blood?

 

No, but there's been some research on serotonin itself:

An Etiological Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2011, Jason et al

 

This looks like the main data with no reduction in the PASC group. A previous study reported reduced levels.