Journal of Inflammation Research (Apr 2024)
Long COVID-19 and Peripheral Serotonin: A Commentary and Reconsideration
Abstract
George M Anderson,1,2 Edwin H Cook,3 Randy D Blakely,4 James S Sutcliffe,5,6 Jeremy Veenstra-VanderWeele7,8 1Yale Child Study Center, Yale University School of Medicine, New Haven, CT, USA; 2Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA; 3Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 4FAU Stiles-Nicholson Brain Institute, Department of Biomedical Science, Florida Atlantic University, Jupiter, FL, USA; 5Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN, USA; 6Department of Psychiatry & Behavioral Sciences, Vanderbilt University, Nashville, TN, USA; 7Department of Psychiatry, College of Medicine, Columbia University, New York, NY, USA; 8New York State Psychiatric Institute, Columbia University, New York, NY, USACorrespondence: George M Anderson, Yale Child Study Center, 230 S. Frontage Road, New Haven, CT, USA, Email [email protected]: 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.Keywords: serotonin, COVID-19, plasma, platelets, long COVID, viral infection
