tbuckley/cabot-search huggingface dataset:
FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury
Authors: Mi Zhou, Yang-Wu-Yue Liu, Yu-Hang He, Jing-Yu Zhang, Hao Guo, Hao Wang, Jia-Kui Ren, Yi-Xun Su, Teng Yang, Jia-Bo Li, Wen-Hui He, Peng-Jiao Ma, Man-Tian Mi, Shuang-Shuang Dai
Journal: Military Medical Research (2024)

Abstract Background Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood. Methods Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice. Results We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1 high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1 high neutrophils. In the chronic stage, the “FOXO1-transferrin receptor (TFRC)” mechanism contributes to FOXO1 high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI. Conclusions FOXO1 high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI.
Increase in invasive Streptococcus pyogenes M1 infections with close evolutionary genetic relationship, Iceland and Scotland, 2022 to 2023
Authors: Stephen B Beres, Randall J Olsen, S Wesley Long, Ross Langley, Thomas Williams, Helga Erlendsdottir, Andrew Smith, Karl G Kristinsson, James M Musser
Journal: Eurosurveillance (2024)

Group A Streptococcus isolates of the recently described M1 UK clade have emerged to cause human infections in several European countries and elsewhere. Full-genome sequence analysis of M1 isolates discovered a close genomic relationship between some isolates from Scotland and the majority of isolates from Iceland causing serious infections in 2022 and 2023. Phylogenetic analysis strongly suggests that an isolate from or related to Scotland was the precursor to an M1 UK variant responsible for almost all recent M1 infections in Iceland.
COVID-19 vaccine effectiveness against symptomatic infection with SARS-CoV-2 BA.1/BA.2 lineages among adults and adolescents in a multicentre primary care study, Europe, December 2021 to June 2022
Authors: Charlotte Lanièce Delaunay, Iván Martínez-Baz, Noémie Sève, Lisa Domegan, Clara Mazagatos, Silke Buda, Adam Meijer, Irina Kislaya, Catalina Pascu, AnnaSara Carnahan, Beatrix Oroszi, Maja Ilić, Marine Maurel, Aryse Melo, Virginia Sandonis Martín, Camino Trobajo-Sanmartín, Vincent Enouf, Adele McKenna, Gloria Pérez-Gimeno, Luise Goerlitz, Marit de Lange, Ana Paula Rodrigues, Mihaela Lazar, Neus Latorre-Margalef, Gergő Túri, Jesús Castilla, Alessandra Falchi, Charlene Bennett, Virtudes Gallardo, Ralf Dürrwald, Dirk Eggink, Raquel Guiomar, Rodica Popescu, Maximilian Riess, Judit Krisztina Horváth, Itziar Casado, Mª del Carmen García, Mariëtte Hooiveld, Ausenda Machado, Sabrina Bacci, Marlena Kaczmarek, Esther Kissling
Journal: Eurosurveillance (2024)

Background Scarce European data in early 2021 suggested lower vaccine effectiveness (VE) against SARS-CoV-2 Omicron lineages than previous variants. Aim We aimed to estimate primary series (PS) and first booster VE against symptomatic BA.1/BA.2 infection and investigate potential biases. Methods This European test-negative multicentre study tested primary care patients with acute respiratory symptoms for SARS-CoV-2 in the BA.1/BA.2-dominant period. We estimated PS and booster VE among adults and adolescents (PS only) for all products combined and for Comirnaty alone, by time since vaccination, age and chronic condition. We investigated potential bias due to correlation between COVID-19 and influenza vaccination and explored effect modification and confounding by prior SARS-CoV-2 infection. Results Among adults, PS VE was 37% (95% CI: 24–47%) overall and 60% (95% CI: 44–72%), 43% (95% CI: 26–55%) and 29% (95% CI: 13–43%) &lt; 90, 90–179 and ≥ 180 days post vaccination, respectively. Booster VE was 42% (95% CI: 32–51%) overall and 56% (95% CI: 47–64%), 22% (95% CI: 2–38%) and 3% (95% CI: −78% to 48%), respectively. Primary series VE was similar among adolescents. Restricting analyses to Comirnaty had little impact. Vaccine effectiveness was higher among older adults. There was no signal of bias due to correlation between COVID-19 and influenza vaccination. Confounding by previous infection was low, but sample size precluded definite assessment of effect modification. Conclusion Primary series and booster VE against symptomatic infection with BA.1/BA.2 ranged from 37% to 42%, with similar waning post vaccination. Comprehensive data on previous SARS-CoV-2 infection would help disentangle vaccine- and infection-induced immunity.
[Ga68] DOTATATE PET/MRI-guided radiosurgical treatment planning and response assessment in meningiomas
Authors: Jana Ivanidze, Se Jung Chang, Arsalan Haghdel, Joon Tae Kim, Arindam Roy Choudhury, Alan Wu, Rohan Ramakrishna, Theodore H Schwartz, Babacar Cisse, Philip Stieg, Leland Muller, Joseph R Osborne, Rajiv S Magge, Nicolas A Karakatsanis, Michelle Roytman, Eaton Lin, Susan C Pannullo, Joshua D Palmer, Jonathan P S Knisely
Journal: Neuro-Oncology (2024)

Abstract Background Our purpose was to determine the utility of [68Ga]-DOTATATE PET/MRI in meningioma response assessment following radiosurgery. Methods Patients with meningioma prospectively underwent postoperative DOTATATE PET/MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI were employed for radiosurgery planning. Follow-up DOTATATE PET/MRI was performed at 6–12 months post-radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVRSSS) referencing superior sagittal sinus (SSS) blood pool were obtained. Size change was determined by Response Assessment in Neuro-Oncology (RANO) criteria. Association of SUVRSSS change magnitude and progression-free survival (PFS) was evaluated using Cox regression. Results Twenty-seven patients with 64 tumors (26% World Health Organization [WHO]-1, 41% WHO-2, 26% WHO-3, and 7% WHO-unknown) were prospectively followed post stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT; mean dose: 30 Gy, modal dose 35 Gy, mean of 5 fractions). Post-irradiation SUV and SUVRSSS decreased by 37.4% and 44.4%, respectively (P &amp;lt; .0001). Size product decreased by 8.9%, thus failing to reach the 25% significance threshold as determined by RANO guidelines. Mean follow-up time was 26 months (range: 6–44). Overall mean PFS was 83% and 100%/100%/54% in WHO-1/-2/-3 subcohorts, respectively, at 34 months. At maximum follow-up (42–44 months), PFS was 100%/83%/54% in WHO-1/-2/-3 subcohorts, respectively. Cox regression analyses revealed a hazard ratio of 0.48 for 10-unit reduction in SUVRSSS in the SRS cohort. Conclusions DOTATATE PET SUV and SUVRSSS demonstrated marked, significant decrease post-radiosurgery. Lesion size decrease was statistically significant; however, it was not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising imaging biomarker for response assessment in meningiomas treated with radiosurgery. ClinicalTrials.gov Identifier NCT04081701
The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models
Authors: Daniel de la Nava, Iker Ausejo-Mauleon, Virginia Laspidea, Marisol Gonzalez-Huarriz, Andrea Lacalle, Noelia Casares, Marta Zalacain, Lucía Marrodan, Marc García-Moure, Maria C Ochoa, Antonio Carlos Tallon-Cobos, Reyes Hernandez-Osuna, Javier Marco-Sanz, Laasya Dhandapani, Irati Hervás-Corpión, Oren J Becher, Javad Nazarian, Sabine Mueller, Timothy N Phoenix, Jasper van der Lugt, Mikel Hernaez, Elizabeth Guruceaga, Carl Koschmann, Sriram Venneti, Joshua E Allen, Matthew D Dun, Juan Fueyo, Candelaria Gomez-Manzano, Jaime Gallego Perez-Larraya, Ana Patiño-García, Sara Labiano, Marta M Alonso
Journal: Neuro-Oncology (2024)

Pediatric high-grade gliomas (pHGGs), including diffuse midline gliomas (DMGs), are aggressive pediatric tumors with one of the poorest prognoses. Delta-24-RGD and ONC201 have shown promising efficacy as single agents for these tumors. However, the combination of both agents has not been evaluated.
OCaR1 endows exocytic vesicles with autoregulatory competence by preventing uncontrolled Ca2+ release, exocytosis, and pancreatic tissue damage
Authors: Volodymyr Tsvilovskyy, Roger Ottenheijm, Ulrich Kriebs, Aline Schütz, Kalliope Nina Diakopoulos, Archana Jha, Wolfgang Bildl, Angela Wirth, Julia Böck, Dawid Jaślan, Irene Ferro, Francisco J. Taberner, Olga Kalinina, Staffan Hildebrand, Ulrich Wissenbach, Petra Weissgerber, Dominik Vogt, Carola Eberhagen, Stefanie Mannebach, Michael Berlin, Vladimir Kuryshev, Dagmar Schumacher, Koenraad Philippaert, Juan E. Camacho-Londoño, Ilka Mathar, Christoph Dieterich, Norbert Klugbauer, Martin Biel, Christian Wahl-Schott, Peter Lipp, Veit Flockerzi, Hans Zischka, Hana Algül, Stefan G. Lechner, Marina Lesina, Christian Grimm, Bernd Fakler, Uwe Schulte, Shmuel Muallem, Marc Freichel
Journal: Journal of Clinical Investigation (2024)

Regulated exocytosis is initiated by increased Ca2+ concentrations in close spatial proximity to secretory granules, which is effectively prevented when the cell is at rest. Here we showed that exocytosis of zymogen granules in acinar cells was driven by Ca2+ directly released from acidic Ca2+ stores including secretory granules through NAADP-activated two-pore channels (TPCs). We identified OCaR1 (encoded by Tmem63a) as an organellar Ca2+ regulator protein integral to the membrane of secretory granules that controlled Ca2+ release via inhibition of TPC1 and TPC2 currents. Deletion of OCaR1 led to extensive Ca2+ release from NAADP-responsive granules under basal conditions as well as upon stimulation of GPCR receptors. Moreover, OCaR1 deletion exacerbated the disease phenotype in murine models of severe and chronic pancreatitis. Our findings showed OCaR1 as a gatekeeper of Ca2+ release that endows NAADP-sensitive secretory granules with an autoregulatory mechanism preventing uncontrolled exocytosis and pancreatic tissue damage.
Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia
Authors: Han Xie, Yanyi Jiang, Yufei Xiang, Baoming Wu, Jiajia Zhao, Ruixiang Huang, Mengting Wang, Yunlong Wang, Jun Liu, Dejun Wu, Dasheng Tian, Erbao Bian
Journal: Neuro-Oncology (2024)

The mesenchymal (MES) subtype of glioblastoma (GBM) is believed to be influenced by both cancer cell-intrinsic alterations and extrinsic cellular interactions, yet the underlying mechanisms remain unexplored.
Surviving without BRCA2: MLH1 gets R-looped in to curtail genomic instability
Authors: Neil Johnson
Journal: Journal of Clinical Investigation (2024)

While breast cancer 2 (BRCA2) loss of heterozygosity (LOH) promotes cancer initiation, it can also induce death in nontransformed cells. In contrast, mismatch repair gene mutL homolog 1 (MLH1) is a tumor-suppressor gene that protects cells from cancer development through repairing mismatched base pairs during DNA mismatch repair (MMR). Sengodan et al., in this issue of the JCI, reveal an interplay between the 2 genes: MLH1 promoted the survival of BRCA2-deficient cells independently of its MMR function. MLH1 protected replication forks from degradation, while also resolving R-loops, thereby reducing genomic instability. Moreover, MLH1 expression was regulated directly by estrogen, shedding light into the hormone-responsive nature of many BRCA2 mutant breast cancers. These results provide important insight into the genetics that drive the initiation of BRCA2-mutated breast cancers.
Hepatocyte-specific CCAAT/enhancer binding protein α restricts liver fibrosis progression
Authors: Tingting Yan, Nana Yan, Yangliu Xia, Vorthon Sawaswong, Xinxin Zhu, Henrique Bregolin Dias, Daisuke Aibara, Shogo Takahashi, Keisuke Hamada, Yoshifumi Saito, Guangming Li, Hui Liu, Hualong Yan, Thomas J Velenosi, Kristopher W Krausz, Jing Huang, Shioko Kimura, Yaron Rotman, Aijuan Qu, Haiping Hao, Frank J Gonzalez
Journal: Journal of Clinical Investigation (2024)

Metabolic dysfunction-associated steatohepatitis (MASH) - previously described as nonalcoholic steatohepatitis (NASH) - is a major driver of liver fibrosis in humans, while liver fibrosis is a key determinant of all-cause mortality in liver disease independent of MASH occurrence. CCAAT/enhancer binding protein α (CEBPA), as a versatile ligand-independent transcriptional factor, has an important function in myeloid cells, and is under clinical evaluation for cancer therapy. CEBPA is also expressed in hepatocytes and regulates glucolipid homeostasis; however, the role of hepatocyte-specific CEBPA in modulating liver fibrosis progression is largely unknown. Here, hepatic CEBPA expression was found to be decreased during MASH progression both in humans and mice, and hepatic CEBPA mRNA was negatively correlated with MASH fibrosis in the human liver. CebpaΔHep mice had markedly enhanced liver fibrosis induced by a high-fat, high-cholesterol, high-fructose diet or carbon tetrachloride. Temporal and spatial hepatocyte-specific CEBPA loss at the progressive stage of MASH in CebpaΔHep,ERT2 mice functionally promoted liver fibrosis. Mechanistically, hepatocyte CEBPA directly repressed Spp1 transactivation to reduce the secretion of osteopontin, a fibrogenesis inducer of hepatic stellate cells. Forced hepatocyte-specific CEBPA expression reduced MASH-associated liver fibrosis. These results demonstrate an important role for hepatocyte-specific CEBPA in liver fibrosis progression, and may help guide the therapeutic discoveries targeting hepatocyte CEBPA for the treatment of liver fibrosis.
IL-6–mediated endothelial injury impairs antiviral humoral immunity after bone marrow transplantation
Authors: Ping Zhang, Peter Fleming, Christopher E. Andoniou, Olivia G. Waltner, Shruti S. Bhise, Jose Paulo Martins, Benjamin A. McEnroe, Valentina Voigt, Sheridan Daly, Rachel D. Kuns, Adaeze P. Ekwe, Andrea S. Henden, Alda Saldan, Stuart Olver, Antiopi Varelias, Corey Smith, Christine R. Schmidt, Kathleen S. Ensbey, Samuel R.W. Legg, Tomoko Sekiguchi, Simone A. Minnie, Mark Gradwell, Irma Wagenaar, Andrew D. Clouston, Motoko Koyama, Scott N. Furlan, Glen A. Kennedy, E Sally Ward, Mariapia A. Degli-Esposti, Geoffrey R. Hill, Siok-Keen Tey
Journal: Journal of Clinical Investigation (2024)

Endothelial function and integrity are compromised after allogeneic bone marrow transplantation (BMT), but how this affects immune responses broadly remains unknown. Using a preclinical model of CMV reactivation after BMT, we found compromised antiviral humoral responses induced by IL-6 signaling. IL-6 signaling in T cells maintained Th1 cells, resulting in sustained IFN-γ secretion, which promoted endothelial cell (EC) injury, loss of the neonatal Fc receptor (FcRn) responsible for IgG recycling, and rapid IgG loss. T cell-specific deletion of IL-6R led to persistence of recipient-derived, CMV-specific IgG and inhibited CMV reactivation. Deletion of IFN-γ in donor T cells also eliminated EC injury and FcRn loss. In a phase III clinical trial, blockade of IL-6R with tocilizumab promoted CMV-specific IgG persistence and significantly attenuated early HCMV reactivation. In sum, IL-6 invoked IFN-γ-dependent EC injury and consequent IgG loss, leading to CMV reactivation. Hence, cytokine inhibition represents a logical strategy to prevent endothelial injury, thereby preserving humoral immunity after immunotherapy.
Anti–PD-1 chimeric antigen receptor T cells efficiently target SIV-infected CD4+ T cells in germinal centers
Authors: Karsten Eichholz, Yoshinori Fukazawa, Christopher W Peterson, Francoise Haeseleer, Manuel Medina, Shelby Hoffmeister, Derick M Duell, Benjamin D Varco-Merth, Sandra Dross, Haesun Park, Caralyn S Labriola, Michael K Axthelm, Robert D Murnane, Jeremy V Smedley, Lei Jin, Jiaxin Gong, Blake J Rust, Deborah H Fuller, Hans-Peter Kiem, Louis J Picker, Afam A Okoye, Lawrence Corey
Journal: Journal of Clinical Investigation (2024)

Programmed cell death protein 1 (PD-1) is an immune checkpoint marker commonly expressed on memory T cells and enriched in latently HIV-infected CD4+ T cells. We engineered an anti-PD-1 chimeric antigen receptor (CAR) to assess the impact of PD-1 depletion on viral reservoirs and rebound dynamics in SIVmac239-infected rhesus macaques (RMs). Adoptive transfer of anti-PD-1 CAR T cells was done in 2 SIV-naive and 4 SIV-infected RMs on antiretroviral therapy (ART). In 3 of 6 RMs, anti-PD-1 CAR T cells expanded and persisted for up to 100 days concomitant with the depletion of PD-1+ memory T cells in blood and tissues, including lymph node CD4+ follicular helper T (TFH) cells. Loss of TFH cells was associated with depletion of detectable SIV RNA from the germinal center (GC). However, following CAR T infusion and ART interruption, there was a marked increase in SIV replication in extrafollicular portions of lymph nodes, a 2-log higher plasma viremia relative to controls, and accelerated disease progression associated with the depletion of CD8+ memory T cells. These data indicate anti-PD-1 CAR T cells depleted PD-1+ T cells, including GC TFH cells, and eradicated SIV from this immunological sanctuary.
Protective hepatocyte signals restrain liver fibrosis in metabolic dysfunction–associated steatohepatitis
Authors: Marcella Steffani, Yana Geng, Utpal B Pajvani, Robert F Schwabe
Journal: Journal of Clinical Investigation (2024)

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects nearly 40% of the global adult population and may progress to metabolic dysfunction-associated steatohepatitis (MASH), and MASH-associated liver fibrosis and cirrhosis. Despite numerous studies unraveling the mechanism of hepatic fibrogenesis, there are still no approved antifibrotic therapies. The development of MASLD and liver fibrosis results from complex cell-cell interactions that often initiate within hepatocytes but remain incompletely understood. In this issue of the JCI, Yan and colleagues describe an ATF3/HES1/CEBPA/OPN pathway that links hepatocyte signals to fibrogenic activation of hepatic stellate cells and may provide new perspectives on therapeutic options for MASLD-induced liver fibrosis.
Increasing histone acetylation improves sociability and restores learning and memory in KAT6B-haploinsufficient mice
Authors: Maria I Bergamasco, Hannah K Vanyai, Alexandra L Garnham, Niall D Geoghegan, Adam P Vogel, Samantha Eccles, Kelly L Rogers, Gordon K Smyth, Marnie E Blewitt, Anthony J Hannan, Tim Thomas, Anne K Voss
Journal: Journal of Clinical Investigation (2024)

Mutations in genes encoding chromatin modifiers are enriched among mutations causing intellectual disability. The continuing development of the brain postnatally, coupled with the inherent reversibility of chromatin modifications, may afford an opportunity for therapeutic intervention following a genetic diagnosis. Development of treatments requires an understanding of protein function and models of the disease. Here, we provide a mouse model of Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) (OMIM 603736) and demonstrate proof-of-principle efficacy of postnatal treatment. SBBYSS results from heterozygous mutations in the KAT6B (MYST4/MORF/QFK) gene and is characterized by intellectual disability and autism-like behaviors. Using human cells carrying SBBYSS-specific KAT6B mutations and Kat6b heterozygous mice (Kat6b+/-), we showed that KAT6B deficiency caused a reduction in histone H3 lysine 9 acetylation. Kat6b+/- mice displayed learning, memory, and social deficits, mirroring SBBYSS individuals. Treatment with a histone deacetylase inhibitor, valproic acid, or an acetyl donor, acetyl-carnitine (ALCAR), elevated histone acetylation levels in the human cells with SBBYSS mutations and in brain and blood cells of Kat6b+/- mice and partially reversed gene expression changes in Kat6b+/- cortical neurons. Both compounds improved sociability in Kat6b+/- mice, and ALCAR treatment restored learning and memory. These data suggest that a subset of SBBYSS individuals may benefit from postnatal therapeutic interventions.
Soluble immune-checkpoint factors: a potential immunotherapy biomarker
Authors: Aaron C Tan, Sarah L Cook, Mustafa Khasraw
Journal: Journal of Clinical Investigation (2024)

There is unmet need for additional biomarkers to better select patients with non-small cell lung cancer (NSCLC) that are likely to benefit from immunotherapy in order to improve patient outcomes, reduce patient toxicity, and relieve the growing burden of healthcare costs. In this issue of the JCI, Hayashi and colleagues evaluated soluble forms of the immune checkpoint molecules PD-L1, PD-1, and CTLA-4 in the plasma of patients with advanced NSCLC who had been treated with anti-PD-1/L1 therapy. The findings suggest that these soluble immune-checkpoint factors may provide a complementary biomarker to PD-L1 IHC, although application into the clinic may not be straightforward.
Serial direct sodium removal in patients with heart failure and diuretic resistance
Authors: Veena S. Rao, Juan B. Ivey‐Miranda, Zachary L. Cox, Julieta Moreno‐Villagomez, Daniela Ramos‐Mastache, Daniel Neville, Natasha Balkcom, Jennifer L. Asher, Lavanya Bellumkonda, Tamar Bigvava, Tamaz Shaburishvili, Jozef Bartunek, F. Perry Wilson, Fredrick Finkelstein, Christopher Maulion, Jeffrey M. Turner, Jeffrey M. Testani
Journal: European Journal of Heart Failure (2024)
Serotonin signaling: a new player and therapeutic target beyond Long‐haul coronavirus disease
Authors: Lan Bai, Fangfang Zhou, Long Zhang
Journal: MedComm (2024)

During the coronavirus disease 2019 (COVID-19) pandemic, a subset of individuals continues to suffer from symptoms including fatigue, post-exertional malaise, dyspnea, bone loss, and memory and neurocognitive dysfunction for months and even years after infection. This clinical phenomenon has been labeled 'Long-haul COVID' or 'post-acute sequelae of COVID-19 (PASC)'; however, the underlying pathophysiological mechanisms remain unclear. In a recent study published in Cell, Wong et al. revealed that viral infection and type I interferon-driven reduction of peripheral serotonin impaired hippocampal responses and short-term memory through vagal neurons in patients with PASC. Therefore, the study provided novel insights into how serotonin links persistent viral inflammation with the neurocognitive symptoms of Long-haul COVID and actionable therapeutic targets for patients with PASC.