The Frequency of Neuropsychiatric Sequelae After Traumatic Brain Injury in the Global South: A systematic review and meta-analysis.

This study aimed to assess the prevalence of neuropsychiatric sequelae following traumatic brain injury (TBI) among the Western Asian, South Asian and African regions of the global south. All studies on psychiatric disturbances or cognitive impairment following TBI conducted (until August 2021) in the 83 countries that constitute the aforementioned regions were reviewed; 6 databases were selected for the literature search. After evaluating the articles using the Joanna Briggs Institute guidelines, the random effects model was used to estimate the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD), TBI-related sleep disturbance (TBI-SD), obsessive-compulsive disorder (OCD) and cognitive impairment. Of 56 non-duplicated studies identified in the initial search, 27 were eligible for systematic review and 23 for meta-analysis. The pooled prevalence of depression in 1,882 samples was 35.35%, that of anxiety in 1,211 samples was 28.64%, that of PTSD in 426 samples was 19.94%, that of OCD in 313 samples was 19.48%, that of TBI-SD in 562 samples was 26.67% and that of cognitive impairment in 941 samples was 49.10%. To date, this is the first critical review to examine the spectrum of post-TBI neuropsychiatric sequelae in the specified regions. Although existing studies lack homogeneous data due to variability in the diagnostic tools and outcome measures utilised, the reported prevalence rates are significant and comparable to statistics from the global north.

Retrospective study on the emotional status of healthcare workers in a COVID-19 field hospital in Oman.

Overview: To combat the overwhelming demand for medical services and care during the COVID-19 Pandemic, the Sultanate of Oman launched the COVID-19 Field Hospital in 2020, designed to respond and alleviate the burden on the medical infrastructure. Several studies globally and from the Middle East suggested that frontline healthcare workers (HCW) were at risk of developing markers of psychological distress. It was further understood through research findings that HCW were resilient during times of crisis. However, there is a dearth in studies evaluating the emotional status of frontline HCW posted in the COVID-19 field hospitals in Gulf Countries, including Oman. This study attempts to shed light on the emotional status of HCW that were on the frontlines in the field hospital in the Sultanate of Oman. Aim: This study aims to quantify and evaluate the emotional status of HCW in the frontline field hospital by screening for symptoms of depression, anxiety, and sleep quality. Method: The data was collected by a local private mental healthcare facility as part of digital feedback to design and implement supportive strategies. Data was collected between September 2021 and October 2021 from 121 HCW in the COVID-19 Field hospital in Oman via 'WhatsApp'. Results: Chi square and binary logistic regression tests were administered to evaluate the data. The participants comprised of 63.6% females and 79.3% were between 30 and 39 years of age. Majority of the participants (65.2%) described themselves as 'financially unstable' and possess an average of 7.5 years of work experience. Of the participants 73.6% of the HCW were based solely in the field hospital for 6-9 months at the time of the survey. Majority of the participants denied the presence of emotional distress expressed through depression (92.6%), anxiety (92.6%) and poor quality of sleep (59.5%). Conclusion: The findings of the present study reflect the HCW ability to cope during challenging situations likely owing to a variety of environmental, social and personal protective factors. The findings of this study can translate into further research on identifying and addressing stressors and targeting the enhancement of protective factors to safeguard the well-being of HCW.

Systematic Review and Meta-analysis of the Impact of Metabolic Surgery on Hepatic Stiffness.

BACKGROUND: Bariatric surgery is one of the effective therapeutic options for people with obesity and obesity-related co-morbidities. In addition to weight-related co-morbid diseases, including diabetes, hypertension, and hypercholesterolemia, non-alcoholic fatty liver disease (NAFLD) is common in patients with morbid obesity. Bariatric surgery is one of the therapeutic options in the management of NAFLD. Hence, this review focused on the potential role of bariatric surgery on hepatic elasticity measured through shear wave elastography. METHODS: A systematic literature search was performed, and the studies regarding heterogeneity were evaluated using the random-effects model. RESULTS: The meta-analysis on 6 trials (3-12 months follow-up) including 350 participants showed a significant reduction of liver elasticity after surgery (WMD: -1.149, 95% CI: -1.767, -0.532, p < 0.001; I2:81.55%). CONCLUSION: Bariatric surgery is associated with decreased liver elasticity. This improvement could be related to weight loss or other mechanisms of bariatric surgery.

Impact of bariatric surgery on circulating irisin levels: a systematic review and meta­analysis.

This systematic review and meta-analysis evaluated changes in circulating irisin levels after bariatric surgery. A systematic search was performed across Embase, Scopus, PubMed, and Web of Science for this study. The meta-analysis was conducted using Comprehensive Meta-Analysis (CMA) V4 software. The overall effect size was depicted through a random-effects meta-analysis and the leave-one-out method. The meta-analysis, which included 13 studies with a total of 407 participants, showed a statistically non-significant reduction in circulating irisin levels following bariatric surgery (SMD: - 0.089, 95% CI - 0.281, 0.102, 95% PI: - 0.790, 0.611, p = 0.360; I2:70.56). Our research found no significant change in irisin levels after bariatric surgery. Moreover, these findings were not associated with the type of surgery or the duration of follow-up.

Metabolic dysfunction-associated fatty liver disease: current therapeutic strategies.

The definition of "Metabolic Associated Fatty Liver Disease - MAFLD" has replaced the previous definition of Nonalcoholic Fatty Liver Disease (NAFLD), because cardiometabolic criteria have been added for the prevention of cardiological risk in these patients. This definition leads to an in-depth study of the bidirectional relationships between hepatic steatosis, Type 2 Diabetes Mellitus (T2DM), Cardiovascular Disease (CVD) and/or their complications. Lifestyle modification, which includes correct nutrition combined with regular physical activity, represents the therapeutic cornerstone of MAFLD. When therapy is required, there is not clear accord on how to proceed in an optimal way with nutraceutical or pharmacological therapy. Numerous studies have attempted to identify nutraceuticals with a significant benefit on metabolic alterations and which contribute to the improvement of hepatic steatosis. Several evidences are supporting the use of silymarin, berberine, curcumin, Nigella sativa, Ascophyllum nodosum, and Fucus vesiculosus, vitamin E, coenzyme Q10 and Omega-3. However, more evidence regarding the long-term efficacy and safety of these compounds are required. There is numerous evidence that highlights the use of therapies such as incretins or the use of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors or other similar therapies which, by assisting existing therapies for pathologies such as diabetes, hypertension, insulin resistance, have given a breakthrough in prevention and the reduction of cardiometabolic risk. This review gave an overview of the current therapeutic strategies that are expected to aid in the treatment and prevention of MAFLD.

Identification of Critical Genes Differentiating Stable and Unstable Atherosclerotic Plaques: A Bioinformatic and Computational Analysis.

BACKGROUND: Identification of biomarkers to distinguish between stable and unstable plaque formation would be very useful to predict plaque vulnerability. METHODS: We downloaded microarray profiles of gene set enrichment (GSE) accession numbers including GSE71226 and GSE20680 (group A: containing healthy vs stable plaque samples) and GSE62646 and GSE34822 (group B: containing stable vs unstable plaque samples) from Gene expression omnibus (GEO) database. Differentially expressed genes were compared in both data sets of each group. RESULTS: Ten and 12 key genes were screened in groups A and B, respectively. Gene Ontology (GO) enrichment was applied by the plugin "BiNGO" (Biological networks gene ontology tool) of the Cytoscape. The key genes were mostly enriched in the biological process of positive regulation of the cellular process. The protein-protein interaction and co-expression network were analyzed by the STRING (search tool for the retrieval of interacting genes/proteins) and GeneMANIA (gene multiple association network integration algorithm) plugin of Cytoscape, respectively, which showed that Epidermal growth factor (EGF), Heparin-binding EGF like growth factor (HBEGF), and Matrix metalloproteinase 9 (MMP9) were at the core of the network. Further validation of key genes using two datasets showed that Phosphodiesterase 5A (PDE5A) and Protein S (PROS1) were decreased in unstable plaques, while Suppressor of cytokine signaling (SOCS3), HBEGF, and Leukocyte immunoglobulin-like receptor B4 (LILRB4) were increased. CONCLUSION: The present study used several datasets to identify key genes associated with stable and unstable atherosclerotic plaque.

New-Onset Diabetes Mellitus in COVID-19: A Scoping Review.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic became superimposed on the pre-existing obesity and diabetes mellitus (DM) pandemics. Since COVID-19 infection alters the metabolic equilibrium, it may induce pathophysiologic mechanisms that potentiate new-onset DM, and we evaluated this issue. METHOD: A systematic review of the literature published from the 1 January 2020 until the 20 July 2023 was performed (PROSPERO registration number CRD42022341638). We included only full-text articles of both human clinical and randomized controlled trials published in English and enrolling adults (age > 18 years old) with ongoing or preceding COVID-19 in whom hyperglycemia was detected. The search was based on the following criteria: "(new-onset diabetes mellitus OR new-onset DM) AND (COVID-19) AND adults". RESULTS: Articles on MEDLINE (n = 70) and the Web of Science database (n = 16) were included and analyzed by two researchers who selected 20 relevant articles. We found evidence of a bidirectional relationship between COVID-19 and DM. CONCLUSIONS: This link operates as a pathophysiological mechanism supported by epidemiological data and also by the clinical and biological findings obtained from the affected individuals. The COVID-19 pandemic raised the incidence of DM through different pathophysiological and psychosocial factors.

Improvement of Triglyceride-Glucose Index Following Bariatric Surgery: a Systematic Review and Meta-analysis.

BACKGROUND: Bariatric surgery is an effective intervention for the management of severe obesity and its associated comorbidities, including metabolic abnormalities. This meta-analysis aimed to evaluate the impact of bariatric surgery on the triglyceride-glucose (TyG) index, a novel marker of insulin resistance and metabolic syndrome. METHODS: A systematic search was conducted in Embase, PubMed, Web of Science, and Scopus. The meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V4 software. The overall effect size was determined by a random-effects meta-analysis and the leave-one-out approach. RESULTS: A total of 9 trials including 1620 individuals confirmed a significant reduction in TyG following bariatric surgery (weighted mean difference (WMD) - 0.770, 95% CI - 1.006, - 0.534, p < 0.001). In a sub-analysis according to the type of bariatric surgery there was a significant reduction in TyG index for Roux-en-Y gastric bypass (WMD - 0.775, 95% CI - 1.000, - 0.550, p < 0.001), and sleeve gastrectomy (WMD - 0.920, 95% CI - 1.368, - 0.473, p < 0.001). In a sub-analysis according to the follow-up duration there was similarly a significant reduction in TyG index for both < 12 months (WMD - 1.645, 95% CI - 2.123, - 1.167, p < 0.001), and ≥ 12 months follow-up (WMD - 0.954, 95% CI - 1.606, - 0.303, p < 0.001). CONCLUSION: The results of this meta-analysis demonstrated a significant reduction in the TyG index following bariatric surgery, indicating improved insulin sensitivity and metabolic health. These findings highlight the potential of bariatric surgery as a valuable therapeutic option for individuals with obesity and its metabolic consequences.

Statins and portal hypertension: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Statins are primarily used to decrease elevated LDL-cholesterol and thus prevent atherosclerotic cardiovascular disease. Portal hypertension is one of the most important complications of chronic liver disease. Several studies indicated that statins might be beneficial for portal hypertension as well but there is still no clear answer whether this is true or not. METHODS: A literature search of the major databases was performed to find eligible randomized controlled trials (RCTs) analyzing the effect of statins on portal hypertension from inception to February 5th, 2021. Six RCTs with 442 patients who received statin or statin plus carvedilol were finally included. Meta-analysis was performed using the Comprehensive Meta-Analysis V2 software. RESULTS: Reduction of portal hypertension after statin treatment was not significant (WMD: -0.494, 95% CI: -1.239, 0.252, p=0.194; I2:0%). The reduction of portal hypertension was robust in the leave-one-out sensitivity analysis. CONCLUSION: Treatment with statins did not decrease significantly portal hypertension.

International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia.

This contemporary, international, evidence-informed guidance aims to achieve the greatest good for the greatest number of people with familial hypercholesterolaemia (FH) across different countries. FH, a family of monogenic defects in the hepatic LDL clearance pathway, is a preventable cause of premature coronary artery disease and death. Worldwide, 35 million people have FH, but most remain undiagnosed or undertreated. Current FH care is guided by a useful and diverse group of evidence-based guidelines, with some primarily directed at cholesterol management and some that are country-specific. However, none of these guidelines provides a comprehensive overview of FH care that includes both the lifelong components of clinical practice and strategies for implementation. Therefore, a group of international experts systematically developed this guidance to compile clinical strategies from existing evidence-based guidelines for the detection (screening, diagnosis, genetic testing and counselling) and management (risk stratification, treatment of adults or children with heterozygous or homozygous FH, therapy during pregnancy and use of apheresis) of patients with FH, update evidence-informed clinical recommendations, and develop and integrate consensus-based implementation strategies at the patient, provider and health-care system levels, with the aim of maximizing the potential benefit for at-risk patients and their families worldwide.

Telemedicine for diabetes management during COVID-19: what we have learnt, what and how to implement.

The past two decades have witnessed telemedicine becoming a crucial part of health care as a method to facilitate doctor-patient interaction. Due to technological developments and the incremental acquisition of experience in its use, telemedicine's advantages and cost-effectiveness has led to it being recognised as specifically relevant to diabetology. However, the pandemic created new challenges for healthcare systems and the rate of development of digital services started to grow exponentially. It was soon discovered that COVID-19-infected patients with diabetes had an increased risk of both mortality and debilitating sequelae. In addition, it was observed that this higher risk could be attenuated primarily by maintaining optimal control of the patient's glucose metabolism. As opportunities for actual physical doctor-patient visits became restricted, telemedicine provided the most convenient opportunity to communicate with patients and maintain delivery of care. The wide range of experiences of health care provision during the pandemic has led to the development of several excellent strategies regarding the applicability of telemedicine across the whole spectrum of diabetes care. The continuation of these strategies is likely to benefit clinical practice even after the pandemic crisis is over.

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance.

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy-both pharmacologic intervention and lipoprotein apheresis (LA)-is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide.

Glucometabolic Perturbations in Type 2 Diabetes Mellitus and Coronavirus Disease 2019: Causes, Consequences, and How to Counter Them Using Novel Antidiabetic Drugs - The CAPISCO International Expert Panel.

The growing amount of evidence suggests the existence of a bidirectional relation between coronavirus disease 2019 (COVID-19) and type 2 diabetes mellitus (T2DM), as these two conditions exacerbate each other, causing a significant healthcare and socioeconomic burden. The alterations in innate and adaptive cellular immunity, adipose tissue, alveolar and endothelial dysfunction, hypercoagulation, the propensity to an increased viral load, and chronic diabetic complications are all associated with glucometabolic perturbations of T2DM patients that predispose them to severe forms of COVID-19 and mortality. Severe acute respiratory syndrome coronavirus 2 infection negatively impacts glucose homeostasis due to its effects on insulin sensitivity and ß-cell function, further aggravating the preexisting glucometabolic perturbations in individuals with T2DM. Thus, the most effective ways are urgently needed for countering these glucometabolic disturbances occurring during acute COVID-19 illness in T2DM patients. The novel classes of antidiabetic medications (dipeptidyl peptidase 4 inhibitors (DPP-4is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are considered candidate drugs for this purpose. This review article summarizes current knowledge regarding glucometabolic disturbances during acute COVID-19 illness in T2DM patients and the potential ways to tackle them using novel antidiabetic medications. Recent observational data suggest that preadmission use of GLP-1 RAs and SGLT-2is are associated with decreased patient mortality, while DPP-4is is associated with increased in-hospital mortality of T2DM patients with COVID-19. Although these results provide further evidence for the widespread use of these two classes of medications in this COVID-19 era, dedicated randomized controlled trials analyzing the effects of in-hospital use of novel antidiabetic agents in T2DM patients with COVID-19 are needed.

Post-COVID syndrome, inflammation, and diabetes.

The raging COVID-19 pandemic is in its third year of global impact. The SARS CoV 2 virus has a high rate of spread, protean manifestations, and a high morbidity and mortality in individuals with predisposing risk factors. The pathophysiologic mechanisms involve a heightened systemic inflammatory state, cardiometabolic derangements, and varying degrees of glucose intolerance. The latter can be evident as significant hyperglycemia leading to new-onset diabetes or worsening of preexisting disease. Unfortunately, the clinical course beyond the acute phase of the illness may persist in the form of a variety of symptoms that together form the so-called "Long COVID" or "Post-COVID Syndrome". It is thought that a chronic, low-grade inflammatory and immunologic state persists during this phase, which may last for weeks or months. Although numerous insights have been gained into COVID-related hyperglycemia and diabetes, its prediction, course, and management remain to be fully elucidated.

Effect of Bariatric Surgery on Intima Media Thickness: A Systematic Review and Meta-Analysis.

BACKGROUND: Obesity, and in particular extreme obesity, as a global health problem is an important risk factor for many diseases, including atherosclerotic cardiovascular disease (ACVD). Bariatric surgery might stop or slow atherogenesis by decreasing excessive weight in the early stages of atherogenesis, by suppressing low-grade systemic inflammation as well as by inhibiting oxidative stress and endothelial dysfunction. The aim of this meta-analysis was to provide an answer to whether bariatric surgery has a significant effect on intima-media thickness (IMT) which is a surrogate marker of early atherosclerosis and has a good correlation with atherosclerotic coronary heart disease. METHODS: A systematic literature search in PubMed, Scopus, Embase, and Web of Science as well as grey literature was performed from inception to 1 July 2022. The meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V3 software. Overall, the estimate of effect size was measured by a random effects meta-analysis. To account for the heterogeneity of studies regarding study design, characteristics of the populations, and treatment duration, a random-effects model (using the DerSimonian-Laird method) and the generic inverse variance weighting approach were used. To assess the existence of publication bias in the meta-analysis, the funnel plot, Begg's rank correlation, and Egger's weighted regression tests were used. RESULTS: The meta-analysis of 30 trials, including 1488 subjects, demonstrated a significant decrease in IMT after bariatric surgery. The reduction in IMT was also robust in the leave-one-out sensitivity analysis. It must be stressed that the results of the random-effects meta-regression did not suggest any relationship between the changes in IMT and delta body mass index (BMI) or duration of follow-up after the bariatric surgery. However, the subgroup analyses showed a better IMT reduction after laparoscopic sleeve gastrectomy (LSG) when compared to Roux-en-Y gastric bypass (RYGB). Within a year, the IMT follow-up values showed a further improvement. CONCLUSIONS: Bariatric surgery significantly reduced IMT. Significant associations were found between the surgery type and IMT changes, as well as a significant effect of follow-up duration on the changes of IMT after bariatric surgery.

Molecular and pro-inflammatory aspects of COVID-19: The impact on cardiometabolic health.

Obesity, type 2 diabetes (T2DM), hypertension (HTN), and Cardiovascular Disease (CVD) often cluster together as "Cardiometabolic Disease" (CMD). Just under 50% of patients with CMD increased the risk of morbidity and mortality right from the beginning of the COVID-19 pandemic as it has been reported in most countries affected by the SARS-CoV2 virus. One of the pathophysiological hallmarks of COVID-19 is the overactivation of the immune system with a prominent IL-6 response, resulting in severe and systemic damage involving also cytokines such as IL2, IL4, IL8, IL10, and interferon-gamma were considered strong predictors of COVID-19 severity. Thus, in this mini-review, we try to describe the inflammatory state, the alteration of the adipokine profile, and cytokine production in the obese state of infected and not infected patients by SARS-CoV2 with the final aim to find possible influences of COVID-19 on CMD and CVD. The immunological-based discussion of the molecular processes could inspire the study of promising targets for managing CMD patients and its complications during COVID-19.

A Comprehensive Neuropsychological Study of Familial Hypercholesterolemia and Its Relationship with Psychosocial Functioning: A Biopsychosocial Approach.

BACKGROUND: Over the past few years, there has been an increasing interest in viewing the diagnosis of familial hypercholesterolemia (FH) through the lens of the biopsychosocial model. However, other than a few epidemiological surveys, there is a dearth of studies from emerging economies that have examined FH using the biological, psychological, and socio-environmental facets of the aforementioned model. AIM. The three aims of the current study were as follows: (i) to examine the psychosocial status among patients with genetically confirmed FH, (ii) to compare their intellectual capacity and cognitive outcomes with a reference group, and (iii) to examine the relationship between health literacy and cognitive functioning. METHOD: Consecutive FH patients referred to the lipid clinic at a tertiary care center for an expert opinion were recruited into this study conducted from September 2019 to March 2020. Information regarding psychosocial functioning, health literacy, quality of life, and affective ranges was surveyed. Indices of current reasoning ability and cognition (attention and concentration, memory, and executive functioning) were compared with a socio-demographically-matched reference group. The current hypothesis also explored the impact of FH on health literacy and cognition. RESULT: A total of 70 participants out of 106 (response rate: 66.0%) initially agreed to participate. However, 18 out of 70 dropped out of the study, yielding a final total of 52 FH patients. With 27 (51.9%) males and 25 (48.1%) females, the mean participant age stood at 37.2 years (SD = 9.2), ranging from 21 to 52 years of age. In the psychosocial data, thirty-two percent (n = 17) of them had anxiety (HADS ≥ 8), and twenty-five percent (n = 13) had depressive symptoms (HADS ≥ 8). The performance of the FH patients was significantly impaired compared to the control group on the indices of current reasoning ability and all domains of cognitive functioning. In the univariate analysis conducted to compare cognitive functioning with health literacy status, only indices of attention and concentration emerged as being significant. CONCLUSION: The current study indicates that the FH population is marked with impediments in biopsychosocial functioning, including indices tapping into the integrity of health literacy, quality of life, affective ranges, and higher functioning such as cognition and current reasoning ability when compared with a socio-demographically-matched reference group. The present results support the hypothesis that chronic diseases vis-à-vis the sequelae of coronary artery disease can potentially impede biopsychosocial functioning.

The Dual Pandemics of COVID-19 and Obesity: Bidirectional Impact.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, has been shown to disrupt many organ systems in the human body. Though several medical disorders have been affected by this infection, a few illnesses in addition may also play a role in determining the outcome of COVID-19. Obesity is one such disease which is not only affected by the occurrence of COVID-19 but can also result in a worse clinical outcome of COVID-19 infection. This manuscript summarizes the most recent evidence supporting the bidirectional impact of COVID-19 and obesity. It highlights how the presence of obesity can be detrimental to the outcome of COVID-19 in a given patient because of the mechanical limitations in lung compliance and also by the activation of several thrombo-inflammatory pathways. The sociodemographic changes brought about by the pandemic in turn have facilitated the already increasing prevalence of obesity. This manuscript highlights the importance of recognizing these pathways which may further help in policy changes that facilitate appropriate measures to prevent the further worsening of these two pandemics.

The Relationship between COVID-19 and Hypothalamic-Pituitary-Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess-The CAPISCO International Expert Panel.

Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic-pituitary-adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.