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Int J Mol Sci ; 22(21)2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1480799


The hypothalamus-pituitary-adrenal (HPA) axis was described as the principal component of the stress response 85 years ago, along with the acute-phase reaction, and the defense response at the tissue level. The orchestration of these processes is essential since systemic inflammation is a double-edged sword; whereas inflammation that is timely and of appropriate magnitude is beneficial, exuberant systemic inflammation incites tissue damage with potentially devastating consequences. Apart from its beneficial cardiovascular and metabolic effects, cortisol exerts a significant immunoregulatory role, a major attribute being that it restrains the excessive inflammatory reaction, thereby preventing unwanted tissue damage. In this review, we will discuss the role of the HPA axis in the normal stress response and in critical illness, especially in critically ill patients with coronavirus disease 2019 (COVID-19). Finally, a chapter will be dedicated to the findings from clinical studies in critical illness and COVID-19 on the expression of the mediator of glucocorticoid actions, the glucocorticoid receptor (GCR).

COVID-19/metabolism , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/virology , Pituitary-Adrenal System/metabolism , Pituitary-Adrenal System/virology , Receptors, Glucocorticoid/metabolism , Critical Illness , Glucocorticoids/metabolism , Humans , Stress, Physiological
Reprod Sci ; 28(10): 2735-2742, 2021 10.
Article in English | MEDLINE | ID: covidwho-1014275


Coronavirus disease 2019 (COVID-19), which resulted from the pandemic outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a massive inflammatory cytokine storm leading to multi-organ damage including that of the brain and testes. While the lungs, heart, and brain are identified as the main targets of SARS-CoV-2-mediated pathogenesis, reports on its testicular infections have been a subject of debate. The brain and testes are physiologically synchronized by the action of gonadotropins and sex steroid hormones. Though the evidence for the presence of the viral particles in the testicular biopsies and semen samples from COVID-19 patients are highly limited, the occurrence of testicular pathology due to abrupt inflammatory responses and hyperthermia has incresingly been evident. The reduced level of testosterone production in COVID-19 is associated with altered secretion of gonadotropins. Moreover, hypothalamic pathology which results from SARS-CoV-2 infection of the brain is also evident in COVID-19 cases. This article revisits and supports the key reports on testicular abnormalities and pathological signatures in the hypothalamus of COVID-19 patients and emphasizes that testicular pathology resulting from inflammation and oxidative stress might lead to infertility in a significant portion of COVID-19 survivors. Further investigations are required to monitor the reproductive health parameters and HPG axis abnormalities related to secondary pathological complications in COVID-19 patients and survivors.

COVID-19/epidemiology , Fertility , Hypothalamus/pathology , Infertility, Male/epidemiology , SARS-CoV-2/pathogenicity , Testis/pathology , Animals , Atrophy , COVID-19/diagnosis , COVID-19/virology , Gonadotropins/metabolism , Host-Pathogen Interactions , Humans , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/pathology , Hypothalamo-Hypophyseal System/physiopathology , Hypothalamo-Hypophyseal System/virology , Hypothalamus/metabolism , Hypothalamus/physiopathology , Hypothalamus/virology , Incidence , Infertility, Male/pathology , Infertility, Male/physiopathology , Infertility, Male/virology , Male , Testis/metabolism , Testis/physiopathology , Testis/virology , Testosterone/metabolism
ACS Chem Neurosci ; 11(13): 1868-1870, 2020 07 01.
Article in English | MEDLINE | ID: covidwho-606648


Cytokine storm in COVID-19 is characterized by an excessive inflammatory response to SARS-CoV-2 that is caused by a dysregulated immune system of the host. We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.

Betacoronavirus/metabolism , Coronavirus Infections/metabolism , Cytokines/metabolism , Pneumonia, Viral/metabolism , Solitary Nucleus/metabolism , Axons/immunology , Axons/metabolism , Axons/virology , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/immunology , Cranial Nerves/immunology , Cranial Nerves/metabolism , Cranial Nerves/virology , Cytokines/immunology , Humans , Hypothalamo-Hypophyseal System/immunology , Hypothalamo-Hypophyseal System/metabolism , Hypothalamo-Hypophyseal System/virology , Inflammation Mediators/immunology , Inflammation Mediators/metabolism , Pandemics , Pituitary-Adrenal System/immunology , Pituitary-Adrenal System/metabolism , Pituitary-Adrenal System/virology , Pneumonia, Viral/immunology , SARS-CoV-2 , Solitary Nucleus/immunology , Solitary Nucleus/virology