Our study investigated the circulating levels of factors involved in immune-inflammatory-endocrine-metabolic responses in patients with tuberculosis with the aim of uncovering a relation between certain immune and hormonal patterns, their clinical status and in vitro immune response. The concentration of leptin, adiponectin, IL-6, IL-1β, ghrelin, C-reactive protein (CRP), cortisol and dehydroepiandrosterone (DHEA), and the in vitro immune response (lymphoproliferation and IFN-γ production) was evaluated in 53 patients with active untreated tuberculosis, 27 household contacts and 25 healthy controls, without significant age- or sex-related differences. Patients had a lower body mass index (BMI), reduced levels of leptin and DHEA, and increased concentrations of CRP, IL-6, cortisol, IL-1β and nearly significant adiponectin values than household contacts and controls. Within tuberculosis patients the BMI and leptin levels were positively correlated and decreased with increasing disease severity, whereas higher concentrations of IL-6, CRP, IL-1β, cortisol, and ghrelin were seen in cases with moderate to severe tuberculosis. Household contacts had lower DHEA and higher IL-6 levels than controls. Group classification by means of discriminant analysis and the k-nearest neighbor method showed that tuberculosis patients were clearly different from the other groups, having higher levels of CRP and lower DHEA concentration and BMI. Furthermore, plasma leptin levels were positively associated with the basal in vitro IFN-γ production and the ConA-driven proliferation of cells from tuberculosis patients. Present alterations in the communication between the neuro-endocrine and immune systems in tuberculosis may contribute to disease worsening.

The SARS-CoV-2, a newly identified β-coronavirus, is the causative agent of the third large-scale pandemic from the last two decades. The outbreak started in December 2019 in Wuhan City, Hubei province in China. The patients presented clinical symptoms of dry cough, fever, dyspnea, and bilateral lung infiltrates on imaging. By February 2020, The World Health Organization (WHO) named the disease as Coronavirus Disease 2019 (COVID-19). The Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses (ICTV) recognized and designated this virus as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 uses the same host receptor, angiotensin-converting enzyme 2 (ACE2), used by SARS-CoV to infect humans. One hypothesis of SARSCoV-2 origin indicates that it is likely that bats serve as reservoir hosts for SARSCoV-2, being the intermediate host not yet determined. The predominant route of transmission of SARS-CoV-2 is from human to human. As of May 10th 2020, the number of worldwide confirmed COVID-19 cases is over 4 million, while the number of global deaths is around 279.000 people. The United States of America (USA) has the highest number of COVID-19 cases with over 1.3 million cases followed by Spain,

Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS.

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Tuberculosis (TB) caused by Mycobacterium tuberculosis is a health problem worldwide. Patients with pulmonary TB show a neuro-immune-endocrine imbalance characterized by an impaired cellular immunity together with increased plasma levels of cortisol, pro- and anti-inflammatory cytokines and markedly decreased dehydroepiandrosterone (DHEA) levels. Extending these findings, we now investigated the immune-endocrine profile of TB patients undergoing specific treatment. Patients (n = 24) were bled at diagnosis (T0), 2, 4, 6 months after treatment initiation and 3 months following its completion. At T0, TB patients showed increased plasma levels of interleukin-6 (IL-6), C reactive protein, interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-β). These mediators decreased during treatment, reaching levels similar to those from healthy controls (n = 26). Specific treatment led to an increased lymphoproliferative response along with clinical improvement. Newly diagnosed patients had low levels of DHEA, with increased cortisol amounts and cortisol/DHEA ratio, which normalized upon specific treatment. As regards glucocorticoid receptors (GR), TB patients at diagnosis presented a reduced mRNA GRα/GRβ ratio in their peripheral blood mononuclear cells. Furthermore, multivariate analysis showed that cortisol/DHEA ratio was positively associated with inflammatory mediators for which this ratio may constitute a disease biomarker. Anti-mycobacterial treatment results in a better immune-endocrine scenario for the control of physiopathological processes accompanying disease development and hence implied in clinical recovery.