Long COVID-19 and Peripheral Serotonin: A Commentary and Reconsideration

Area of Science:

• Biochemistry
• Virology
• Pharmacology

Background:

• A recent paper, "Serotonin reduction in post-acute sequelae of viral infection," reported significant findings.
• The paper suggested a link between reduced serotonin and long COVID, proposing selective serotonin reuptake inhibitors (SSRIs) as a treatment.
• Concerns exist regarding the methodology and interpretation of results in the original study.

Purpose of the Study:

• To critically evaluate the methodology and conclusions of a published paper on serotonin levels in viral infections and long COVID.
• To address potential inaccuracies in reported plasma serotonin concentrations.
• To re-evaluate the proposed link between serotonin and long COVID sequelae, including cardiovascular issues.

Main Methods:

• Analysis of the blood centrifugation procedure described by Wong et al.
• Assessment of the impact of platelet depletion on reported plasma serotonin concentrations.
• Review of the data presented regarding SSRI treatment and serotonin restoration.

Main Results:

• The centrifugation method likely results in over 95% platelet depletion, rendering reported plasma serotonin levels significantly overestimated (30-60 times too high).
• Reported plasma serotonin values for control, long COVID, and viremia groups are deemed unreliable and should be disregarded.
• No data were presented to support claims of serotonin restoration with SSRI administration; SSRIs are expected to decrease platelet serotonin.

Conclusions:

• The original study's findings and conclusions regarding serotonin reduction in viral infections and long COVID are invalidated by methodological flaws.
• The proposed use of SSRIs for long COVID treatment based on this study is not supported by the presented evidence.
• Reduced platelet serotonin, rather than peripheral serotonin, may be more relevant to long COVID, potentially mitigating cardiovascular sequelae due to decreased platelet aggregation.