Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
1.
Int J Mol Sci ; 22(13)2021 Jun 23.
Article in English | MEDLINE | ID: covidwho-1282517

ABSTRACT

The coronavirus disease 2019 (COVID-19) caused by infection of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) significantly impacted human society. Recently, the synthetic pure glucocorticoid dexamethasone was identified as an effective compound for treatment of severe COVID-19. However, glucocorticoids are generally harmful for infectious diseases, such as bacterial sepsis and severe influenza pneumonia, which can develop respiratory failure and systemic inflammation similar to COVID-19. This apparent inconsistency suggests the presence of pathologic mechanism(s) unique to COVID-19 that renders this steroid effective. We review plausible mechanisms and advance the hypothesis that SARS-CoV-2 infection is accompanied by infected cell-specific glucocorticoid insensitivity as reported for some other viruses. This alteration in local glucocorticoid actions interferes with undesired glucocorticoid to facilitate viral replication but does not affect desired anti-inflammatory properties in non-infected organs/tissues. We postulate that the virus coincidentally causes glucocorticoid insensitivity in the process of modulating host cell activities for promoting its replication in infected cells. We explore this tenet focusing on SARS-CoV-2-encoding proteins and potential molecular mechanisms supporting this hypothetical glucocorticoid insensitivity unique to COVID-19 but not characteristic of other life-threatening viral diseases, probably due to a difference in specific virally-encoded molecules and host cell activities modulated by them.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Dexamethasone/pharmacology , Hypothalamo-Hypophyseal System/physiology , Inflammation/drug therapy , Host Microbial Interactions , Humans , Immunity, Innate , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Severity of Illness Index , Virus Replication/drug effects
2.
Cell ; 184(11): 2797-2801, 2021 05 27.
Article in English | MEDLINE | ID: covidwho-1241746

ABSTRACT

The COVID-19 pandemic has highlighted structural inequalities and racism promoting health disparities among communities of color. Taking cardiovascular disease as an example, we provide a framework for multidisciplinary efforts leveraging translational and epidemiologic approaches to decode the biological impacts of inequalities and racism and develop targeted interventions that promote health equity.


Subject(s)
COVID-19/epidemiology , Health Equity , Health Promotion/methods , Racism , Stress, Physiological/immunology , COVID-19/immunology , COVID-19/metabolism , COVID-19/psychology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/immunology , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/psychology , Gene Expression Regulation/genetics , Gene Expression Regulation/immunology , Gene Expression Regulation/physiology , Humans , Hypothalamo-Hypophyseal System/immunology , Hypothalamo-Hypophyseal System/physiology , Racism/psychology , Risk Factors , Sympathetic Nervous System/immunology , Sympathetic Nervous System/physiology
3.
Int J Surg ; 81: 47-54, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-684306

ABSTRACT

Globally, a staggering 310 million major surgeries are performed each year; around 40 to 50 million in USA and 20 million in Europe. It is estimated that 1-4% of these patients will die, up to 15% will have serious postoperative morbidity, and 5-15% will be readmitted within 30 days. An annual global mortality of around 8 million patients places major surgery comparable with the leading causes of death from cardiovascular disease and stroke, cancer and injury. If surgical complications were classified as a pandemic, like HIV/AIDS or coronavirus (COVID-19), developed countries would work together and devise an immediate action plan and allocate resources to address it. Seeking to reduce preventable deaths and post-surgical complications would save billions of dollars in healthcare costs. Part of the global problem resides in differences in institutional practice patterns in high- and low-income countries, and part from a lack of effective perioperative drug therapies to protect the patient from surgical stress. We briefly review the history of surgical stress and provide a path forward from a systems-based approach. Key to progress is recognizing that the anesthetized brain is still physiologically 'awake' and responsive to the sterile stressors of surgery. New intravenous drug therapies are urgently required after anesthesia and before the first incision to prevent the brain from switching to sympathetic overdrive and activating secondary injury progression such as hyperinflammation, coagulopathy, immune activation and metabolic dysfunction. A systems-based approach targeting central nervous system-mitochondrial coupling may help drive research to improve outcomes following major surgery in civilian and military medicine.


Subject(s)
Postoperative Complications/etiology , Surgical Procedures, Operative/mortality , Global Health , Glycocalyx/physiology , Humans , Hypothalamo-Hypophyseal System/physiology , Mitochondria/physiology , Pituitary-Adrenal System/physiology , Postoperative Complications/prevention & control , Stress, Physiological , Surgical Procedures, Operative/adverse effects
4.
Endocr Relat Cancer ; 27(9): R281-R292, 2020 09.
Article in English | MEDLINE | ID: covidwho-577793

ABSTRACT

The current pandemic (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health challenge with active development of antiviral drugs and vaccines seeking to reduce its significant disease burden. Early reports have confirmed that transmembrane serine protease 2 (TMPRSS2) and angiotensin converting enzyme 2 (ACE2) are critical targets of SARS-CoV-2 that facilitate viral entry into host cells. TMPRSS2 and ACE2 are expressed in multiple human tissues beyond the lung including the testes where predisposition to SARS-CoV-2 infection may exist. TMPRSS2 is an androgen-responsive gene and its fusion represents one of the most frequent alterations in prostate cancer. Androgen suppression by androgen deprivation therapy and androgen receptor signaling inhibitors form the foundation of prostate cancer treatment. In this review, we highlight the growing evidence in support of androgen regulation of TMPRSS2 and ACE2 and the potential clinical implications of using androgen suppression to downregulate TMPRSS2 to target SARS-CoV-2. We also discuss the future directions and controversies that need to be addressed in order to establish the viability of targeting TMPRSS2 and/or ACE2 through androgen signaling regulation for COVID-19 treatment, particularly its relevance in the context of prostate cancer management.


Subject(s)
Androgen Antagonists/therapeutic use , Betacoronavirus , Coronavirus Infections/etiology , Pneumonia, Viral/etiology , Prostatic Neoplasms/drug therapy , Androgens/physiology , Angiotensin-Converting Enzyme 2 , COVID-19 , Coronavirus Infections/drug therapy , Humans , Hypothalamo-Hypophyseal System/physiology , Male , Pandemics , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Serine Endopeptidases/physiology
SELECTION OF CITATIONS
SEARCH DETAIL