Serotonin reduction in post-acute sequelae of viral infection

被引：205

作者：

Wong, Andrea C. ^{[1
,2
]}

Devason, Ashwarya S. ^{[1
,2
,3
]}

Umana, Iboro C. ^{[1
,2
,3
]}

Cox, Timothy O. ^{[1
,2
,3
]}

Dohnalova, Lenka ^{[1
,2
,3
,4
]}

Litichevskiy, Lev ^{[1
,2
,3
]}

Perla, Jonathan ^{[1
,2
]}

Lundgren, Patrick ^{[1
,2
,3
]}

Etwebi, Zienab ^{[5
]}

Izzo, Luke T. ^{[6
,7
]}

Kim, Jihee ^{[1
,2
,3
]}

Tetlak, Monika ^{[1
,2
,3
]}

Descamps, Helene C. ^{[1
,2
,3
]}

Park, Simone L. ^{[2
,8
]}

Wisser, Stephen ^{[1
,2
,3
]}

McKnight, Aaron D. ^{[1
,2
,3
]}

Pardy, Ryan D. ^{[9
]}

Kim, Junwon ^{[1
,2
,3
]}

Blank, Niklas ^{[1
,2
,3
]}

Patel, Shaan ^{[1
,2
,3
]}

Thum, Katharina ^{[1
,2
,3
]}

Mason, Sydney ^{[1
,2
,3
]}

Beltra, Jean-Christophe ^{[2
,8
,10
]}

Michieletto, Michael F. ^{[2
,5
,11
]}

Ngiow, Shin Foong ^{[2
,8
,10
]}

Miller, Brittany M. ^{[1
,2
]}

Liou, Megan J. ^{[1
,2
,3
]}

Madhu, Bhoomi ^{[1
,2
]}

Dmitrieva-Posocco, Oxana ^{[1
,2
]}

Huber, Alex S. ^{[5
]}

Hewins, Peter ^{[1
]}

Petucci, Christopher ^{[12
]}

Chu, Candice P. ^{[9
]}

Baraniecki-Zwil, Gwen ^{[13
]}

Giron, Leila B. ^{[14
]}

Baxter, Amy E. ^{[2
,8
]}

Greenplate, Allison R. ^{[2
,8
]}

Kearns, Charlotte ^{[5
]}

Montone, Kathleen ^{[5
]}

Litzky, Leslie A. ^{[5
]}

Feldman, Michael ^{[5
]}

Henao-Mejia, Jorge ^{[2
,5
,11
]}

Striepen, Boris ^{[9
]}

Ramage, Holly ^{[15
]}

Jurado, Kellie A. ^{[1
]}

Wellen, Kathryn E. ^{[6
,7
]}

O'Doherty, Una ^{[5
]}

Abdel-Mohsen, Mohamed ^{[14
]}

Landay, Alan L. ^{[16
]}

Keshavarzian, Ali ^{[16
,17
]}

机构：

[1] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Inst Immunol & Immune Hlth, Philadelphia, PA 19104 USA

[3] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA

[4] Goethe Univ Frankfurt, Inst Mol Bio Sci, Frankfurt, Germany

[5] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[6] Univ Penn, Perelman Sch Med, Dept Canc Biol, Philadelphia, PA USA

[7] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

[8] Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA USA

[9] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA USA

[10] Univ Penn, Parker Inst Canc Immunotherapy, Perelman Sch Med, Philadelphia, PA USA

[11] Univ Penn, Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Div Protect Immun, Philadelphia, PA USA

[12] Univ Penn, Penn Cardiovasc Inst, Metabol Core, Philadelphia, PA USA

[13] Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA

[14] Wistar Inst Anat & Biol, Philadelphia, PA USA

[15] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Microbiol & Immunol, Philadelphia, PA USA

[16] Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL USA

[17] Rush Ctr Integrated Microbiome & Chronobiol Res, Chicago, IL USA

[18] Univ Calif San Francisco, Div Expt Med, San Francisco, CA USA

[19] Univ Calif San Francisco, Dept Med, Div HIV Infect Dis & Global Med, San Francisco, CA USA

[20] Univ Penn, Perelman Sch Med, Div Pulm & Crit Care Med, Philadelphia, PA USA

来源：

CELL | 2023年 / 186卷 / 22期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

TOLL-LIKE RECEPTOR-3; FATIGUE-SYNDROME; COVID-19; SARS-COV-2; ACID; ACE2; EXPRESSION; RATS;

D O I：

10.1016/j.cell.2023.09.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hy-percoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are asso-ciated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated se-rotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocog-nitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes.

引用

页码：4851 / +

页数：38

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