Opinion Long COVID-19 and Peripheral Serotonin: A Commentary and Reconsideration, 2024, Anderson et al.

Long COVID-19 and Peripheral Serotonin: A Commentary and Reconsideration
George M Anderson; Edwin H Cook; Randy D Blakely; James S Sutcliffe; Jeremy Veenstra-VanderWeele

We believe there are serious problems with a recently published and highly publicized paper entitled “Serotonin reduction in post-acute sequelae of viral infection.” The blood centrifugation procedure reportedly used by Wong et al would produce plasma that is substantially (over 95%) depleted of platelets. Given this, their published mean plasma serotonin values of 1.2 uM and 2.4 uM for the control/contrast groups appear to be at least 30 to 60 times too high and should be disregarded. The plasma serotonin values reported for the long COVID and viremia patients also should be disregarded, as should any comparisons to the control/contrast groups. We also note that the plasma serotonin means for the two control/contrast groups are not in good agreement.

In the “Discussion” section, Wong et al state that their results tend to support the use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of COVID-19, and they encourage further clinical trials of SSRIs. While they state that, “Our animal models demonstrate that serotonin levels can be restored and memory impairment reversed by precursor supplementation or SSRI treatment”, it should be noted that no data are presented showing an increase or restoration in circulating serotonin with SSRI administration. In fact, one would expect a marked decline in platelet serotonin due to SSRIs’ effective inhibition of the platelet serotonin transporter.

Wong et al hypothesize that problems of long COVID arise from too little peripheral serotonin. However, given the frequent presence of a hyperaggregation state in long COVID, and the known augmenting effects of platelet serotonin on platelet aggregation, it is plausible to suggest that reductions in platelet serotonin might be associated with a lessening of the cardiovascular sequelae of COVID-19.

Link | PDF (Journal of Inflammation Research) [Open Access]

 

Commentary on Serotonin reduction in post-acute sequelae of viral infection (2023, Cell)

@Janna Moen PhD in case you haven't already seen this.

 

Very critical commentary, but it did seem quite surprising to see serotonin pop up as such a significant finding when it hadn't been before.

 

Interesting comment by a much smaller team than the original study team and largely consisting of psychiatrists.

Will be interesting to see if and how Wong et al reply to this, especially since the list of authors is ridiculously long and consists of names and teams that have gone very viral in the LC field (Peluso, Wherry, Henrich, Deeks, Cherry, Levy).