Evidence map›Paper›PMID 41568000›Full record

ArticleFrontiers in cellular and infection microbiology2025

Salivary cortisol in long COVID: a marker of broader stress system and circadian rhythm dysregulation.

Marta Camici, Marta Franco, Lorenzo Talamanca, Manuela Petino, Jessica Paulicelli, Liliana Scarnecchia, Lucia Ciavarella, Tiziana Orzilli, Francesca Balducelli, Valentina Mazzotta and 9 more

Abstract read
In one paragraph

Article in Frontiers in cellular and infection microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Marta CamiciClinical and Research Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
Marta FrancoEndocrinology Clinical Unit, San Camillo Forlanini Hospital, Rome, Italy.
Lorenzo TalamancaDepartment of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule Zürich (ETH Zürich), Zurich, Switzerland.
Manuela PetinoAzienda Sanitaria Locale ASL Roma 1, Rome, Italy.
Jessica PaulicelliClinical and Research Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
Liliana ScarnecchiaDepartment of Clinical Pathology, San Camillo Forlanini Hospital, Rome, Italy.
Lucia CiavarellaDepartment of Clinical Pathology, San Camillo Forlanini Hospital, Rome, Italy.
Tiziana OrzilliDepartment of Clinical Pathology, San Camillo Forlanini Hospital, Rome, Italy.
Francesca BalducelliDepartment of Clinical Pathology, San Camillo Forlanini Hospital, Rome, Italy.
Valentina MazzottaClinical and Research Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
Ilaria MastrorosaClinical and Research Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
Eleonora CiminiLaboratory of Cellular Immunology and Pharmacology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.
Eleonora TartagliaLaboratory of Cellular Immunology and Pharmacology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.
Stefania NotariLaboratory of Cellular Immunology and Pharmacology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.
Fabrizio MaggiLaboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.
Enrico GirardiScientific Direction, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.
Roberto BaldelliEndocrinology Clinical Unit, San Camillo Forlanini Hospital, Rome, Italy.
Paolo ZuppiOrdine di Malta Italia, Endocrinology Project, San Giovanni Battista Hospital, Rome, Italy.
Andrea AntinoriClinical and Research Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Long COVID (LC) has been associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction, although findings from blood cortisol measurements remain inconsistent. We hypothesized that LC patients exhibit a disrupted diurnal cortisol rhythm and that salivary cortisol (SC) profiling may provide a more accurate assessment of HPA activity. Methods: This prospective, single-center, case-control study was conducted at a Long COVID clinic in Rome between February 2023 and March 2024 and included 96 participants evaluated at least 28 days after confirmed SARS-CoV-2 infection. LC was defined as one or more new or persistent symptoms and classified as severe when four or more of the following were present: fatigue, cognitive impairment, exercise intolerance, dyspnea, arthralgia, or dysautonomia. SC was measured at 8:00 AM, 3:00 PM, and 11:00 PM. Results: The cohort (mean age 58.1 ± 14.8 years; 60% female; all White) included 83 LC patients (80% moderate, 20% severe) and 13 asymptomatic post-COVID (APC) individuals. Compared with healthy controls, both LC and APC groups showed reduced morning SC (p<0.01), flattened diurnal variation, and elevated evening SC, indicating loss of the normal morning peak and nocturnal decline. Blood cortisol levels did not differ among groups, but LC patients had higher ACTH than APC (26 pg/mL vs 13 pg/mL; p<0.01), suggesting compensatory HPA activation. One LC patient (1.2%) was diagnosed with adrenal insufficiency. Discussion: These exploratory findings suggest a disrupted circadian cortisol rhythm in individuals after COVID-19, with altered HPA axis dynamics that may be associated with disease severity.

Indexed as

Circadian RhythmCOVID-19HydrocortisoneSalivaAdultAgedBiomarkersCase-Control StudiesFemaleHumansHypothalamo-Hypophyseal SystemMaleMiddle AgedPituitary-Adrenal SystemPost-Acute COVID-19 SyndromeProspective StudiesBiomarkersHydrocortisonebiomarkerscircadian rhythm dysregulationfatigue assessment scalehypothalamic-pituitary-adrenal axis impairmentlong-COVIDlong-COVID hallmarkssalivary cortisol profile

Identifiers

PMID41568000
PMCPMC12816214

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.