ecbe37e6e0db506a795c5d08f4353c0a pmc_10968573.pdf 7fcbc5c5c77c1b0180926020be7b1d7fbffda047 pmc_10968573.pdf ddb9634caa431fbf7ed4cbe7e4cc63f4ca496f211493af8b98e80db1e5003103 pmc_10968573.pdf Title: Pituitary–Adrenal Axis and Peripheral Immune Cell Profile in Long COVID Subject: In Long COVID, dysfunction in the pituitary–adrenal axis and alterations in immune cells and inflammatory status are warned against. We performed a prospective study in a cohort of 42 patients who suffered COVID-19 at least 6 months before attending the Long COVID unit at Althaia Hospital. Based on Post-COVID Functional Status, 29 patients were diagnosed with Long COVID, while 13 were deemed as recovered. The hormones of the pituitary–adrenal axis, adrenocorticotropin stimulation test, and immune cell profiles and inflammatory markers were examined. Patients with Long COVID had significantly lower EuroQol and higher mMRC scores compared to the recovered individuals. Their symptoms included fatigue, myalgia, arthralgia, persistent coughing, a persistent sore throat, dyspnoea, a lack of concentration, and anxiety. We observed the physiological levels of cortisol and adrenocorticotropin in individuals with or without Long COVID. The results of the adrenocorticotropin stimulation test were similar between both groups. The absolute number of neutrophils was lower in the Long COVID patients compared to recovered individuals (p < 0.05). The total count of B lymphocytes remained consistent, but Long COVID patients had a higher percentage of mature B cells compared to recovered participants (p < 0.05) and exhibited a higher percentage of circulating resident memory CD8+ T cells (p < 0.05) and Treg-expressing exonucleases (p < 0.05). Our findings did not identify adrenal dysfunction related to Long COVID, nor an association between adrenal function and clinical symptoms. The data indicated a dysregulation in certain immune cells, pointing to immune activation. No overt hyperinflammation was observed in the Long COVID group. Keywords: Long COVID; fatigue; dyspnea; cortisol; adrenal insufficiency; immune cells; inflammation Author: Jaume Alijotas-Reig, Ariadna Anunciacion-Llunell, Enrique Esteve-Valverde, Stephanie Morales-Pérez, Sergio Rivero-Santana, Jaume Trapé, Laura González-García, Domingo Ruiz, Joana Marques-Soares and Francesc Miro-Mur Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Mar 5 16:40:44 2024 CET ModDate: Tue Mar 5 16:50:15 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2034673 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- IOJCNK+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 DRUFMR+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 NBNGJS+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 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2024-04-03 02:33:02 CEST Size: 2034673 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 508 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Inclusion Criteria for Patients Destination: subsection.2.1 Item: Title: Health-Related Quality-of-Life Tests Destination: subsection.2.2 Item: Title: Adrenal Function Destination: subsection.2.3 Item: Title: Flow Cytometry Destination: subsection.2.4 Item: Title: Cytokine Assessment Destination: subsection.2.5 Item: Title: Statistical Analysis Destination: subsection.2.6 Item: Title: Results Destination: section.3 Children: Item: Title: Long COVID Assessment Destination: subsection.3.1 Item: Title: Preclinical and Acute COVID-19 Profiles Destination: subsection.3.2 Item: Title: Symptom Evaluation and Quality of Life Destination: subsection.3.3 Item: Title: Vaccination and Seropositivity for SARS-CoV2, CMV and EBV Antibodies Destination: subsection.3.4 Item: Title: Clinical Laboratory Parameters in Long COVID Destination: subsection.3.5 Item: Title: Long COVID Symptomatology Destination: subsection.3.6 Item: Title: Pituitary Adrenal Axis Function in Long COVID Destination: subsection.3.7 Item: Title: Immune Profile in Long COVID Patients Destination: subsection.3.8 Item: Title: Cytokine Evaluation Destination: subsection.3.9 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Pituitary Adrenal Axis and Peripheral Immune Cell Profile in Long COVID Author: Jaume Alijotas-Reig, Ariadna Anunciacion-Llunell, Enrique Esteve-Valverde, Stephanie Morales-Pérez, Sergio Rivero-Santana, Jaume Trapé, Laura González-García, Domingo Ruiz, Joana Marques-Soares and Francesc Miro-Mur Subject: In Long COVID, dysfunction in the pituitary adrenal axis and alterations in immune cells and inflammatory status are warned against. We performed a prospective study in a cohort of 42 patients who suffered COVID-19 at least 6 months before attending the Long COVID unit at Althaia Hospital. Based on Post-COVID Functional Status, 29 patients were diagnosed with Long COVID, while 13 were deemed as recovered. The hormones of the pituitary adrenal axis, adrenocorticotropin stimulation test, and immune cell profiles and inflammatory markers were examined. Patients with Long COVID had significantly lower EuroQol and higher mMRC scores compared to the recovered individuals. Their symptoms included fatigue, myalgia, arthralgia, persistent coughing, a persistent sore throat, dyspnoea, a lack of concentration, and anxiety. We observed the physiological levels of cortisol and adrenocorticotropin in individuals with or without Long COVID. The results of the adrenocorticotropin stimulation test were similar between both groups. The absolute number of neutrophils was lower in the Long COVID patients compared to recovered individuals (p < 0.05). The total count of B lymphocytes remained consistent, but Long COVID patients had a higher percentage of mature B cells compared to recovered participants (p < 0.05) and exhibited a higher percentage of circulating resident memory CD8+ T cells (p < 0.05) and Treg-expressing exonucleases (p < 0.05). Our findings did not identify adrenal dysfunction related to Long COVID, nor an association between adrenal function and clinical symptoms. The data indicated a dysregulation in certain immune cells, pointing to immune activation. No overt hyperinflammation was observed in the Long COVID group. 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