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1.
J Investig Med High Impact Case Rep ; 10: 23247096211051928, 2022.
Article in English | MEDLINE | ID: covidwho-1714632

ABSTRACT

A 49-year-old man with no significant past medical history received dexamethasone as part of his treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Less than 3 weeks later, the patient developed acute respiratory distress syndrome. Radiological and serological testing led to a diagnosis of acute hypoxic miliary coccidioidomycosis. A 52-year-old man with a past medical history of chronic kidney disease (CKD) was treated with prednisone for focal segmental glomerulosclerosis (FSGS). Within 2 weeks, this patient developed bilateral lower extremity weakness. Radiology, serology, and lumbar puncture proved a diagnosis of reactivated coccidioidomycosis with miliary pattern and coccidioidomycosis meningoencephalitis with arachnoiditis. Whether treatment with glucocorticoids caused reactivation of coccidioidomycosis is discussed in this case series.


Subject(s)
COVID-19 , Coccidioidomycosis , Respiratory Distress Syndrome , COVID-19/drug therapy , Coccidioidomycosis/diagnosis , Coccidioidomycosis/drug therapy , Glucocorticoids/adverse effects , Humans , Male , Middle Aged , Respiratory Distress Syndrome/chemically induced , SARS-CoV-2
2.
Dis Markers ; 2022: 2639470, 2022.
Article in English | MEDLINE | ID: covidwho-1699232

ABSTRACT

Background: Steroid-induced osteonecrosis of the femoral head (SONFH) has produced a substantial burden of medical and social experience. However, the current diagnosis is still limited. Thus, this study is aimed at identifying potential biomarkers in the peripheral serum of patients with SONFH. Methods: The expression profile data of SONFH (number: GSE123568) was acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in SONFH were identified and used for weighted gene coexpression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the biological functions. The protein-protein interaction (PPI) network and machine learning algorithms were employed to screen for potential biomarkers. Gene set enrichment analysis (GSEA), transcription factor (TF) enrichment analysis, and competing endogenous RNA (ceRNA) network were used to determine the biological functions and regulatory mechanisms of the potential biomarkers. Results: A total of 562 DEGs, including 318 upregulated and 244 downregulated genes, were identified between SONFH and control samples, and 94 target genes were screened based on WGCNA. Moreover, biological function analysis suggested that target genes were mainly involved in erythrocyte differentiation, homeostasis and development, and myeloid cell homeostasis and development. Furthermore, GYPA, TMCC2, and BPGM were identified as potential biomarkers in the peripheral serum of patients with SONFH based on machine learning algorithms and showed good diagnostic values. GSEA revealed that GYPA, TMCC2, and BPGM were mainly involved in immune-related biological processes (BPs) and signaling pathways. Finally, we found that GYPA might be regulated by hsa-miR-3137 and that BPGM might be regulated by hsa-miR-340-3p. Conclusion: GYPA, TMCC2, and BPGM are potential biomarkers in the peripheral serum of patients with SONFH and might affect SONFH by regulating erythrocytes and immunity.


Subject(s)
Algorithms , Femur Head Necrosis/blood , Femur Head Necrosis/genetics , Gene Regulatory Networks , Glucocorticoids/adverse effects , Machine Learning , Biomarkers/blood , Femur Head Necrosis/chemically induced , Humans
4.
Ann Rheum Dis ; 81(3): 422-432, 2022 03.
Article in English | MEDLINE | ID: covidwho-1560917

ABSTRACT

OBJECTIVES: Perform a systematic literature review (SLR) on risk and prognosis of SARS-CoV-2 infection and vaccination against SARS-CoV-2 in patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: Literature was searched up to 31 May 2021, including (randomised) controlled trials and observational studies with patients with RMD. Pending quality assessment, data extraction was performed and risk of bias (RoB) was assessed. Quality assessment required provision of (1) an appropriate COVID-19 case definition, and (2a) a base incidence (for incidence data) or (2b) a comparator, >10 cases with the outcome and risk estimates minimally adjusted for age, sex and comorbidities (for risk factor data). RESULTS: Of 5165 records, 208 were included, of which 90 passed quality assessment and data were extracted for incidence (n=42), risk factor (n=42) or vaccination (n=14). Most studies had unclear/high RoB. Generally, patients with RMDs do not face more risk of contracting SARS-CoV-2 (n=26 studies) or worse prognosis of COVID-19 (n=14) than individuals without RMDs. No consistent differences in risk of developing (severe) COVID-19 were found between different RMDs (n=19). Disease activity is associated with worse COVID-19 prognosis (n=2), possibly explaining the increased risk seen for glucocorticoid use (n=13). Rituximab is associated with worse COVID-19 prognosis (n=7) and possibly Janus kinase inhibitors (n=3). Vaccination is generally immunogenic, though antibody responses are lower than in controls. Vaccine immunogenicity is negatively associated with older age, rituximab and mycophenolate. CONCLUSION: This SLR informed the July 2021 update of the European Alliance of Associations for Rheumatology recommendations for the management of RMDs in the context of SARS-CoV-2.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/mortality , Musculoskeletal Diseases/virology , Rheumatic Diseases/virology , SARS-CoV-2/immunology , Adult , COVID-19/immunology , COVID-19/prevention & control , Female , Glucocorticoids/adverse effects , Humans , Immunogenicity, Vaccine/drug effects , Immunosuppressive Agents/adverse effects , Incidence , Janus Kinase Inhibitors/adverse effects , Male , Middle Aged , Musculoskeletal Diseases/drug therapy , Prognosis , Rheumatic Diseases/drug therapy , Risk Factors , Rituximab/adverse effects
5.
JAMA ; 326(18): 1807-1817, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1527380

ABSTRACT

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.


Subject(s)
COVID-19/drug therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Life Support Care , Aged , COVID-19/complications , COVID-19/mortality , Dexamethasone/adverse effects , Dose-Response Relationship, Drug , Female , Glucocorticoids/adverse effects , Humans , Hypoxia/etiology , Hypoxia/therapy , Male , Middle Aged , Mycoses/etiology , Respiration, Artificial , Shock, Septic/etiology , Single-Blind Method
6.
Intern Emerg Med ; 17(2): 329-338, 2022 03.
Article in English | MEDLINE | ID: covidwho-1491358

ABSTRACT

Since the publication of the RECOVERY trial, the use of glucocorticoid drugs (GC) has spread for the treatment of severe COVID-19 worldwide. However, the benefit of dexamethasone was largest in patients who received mechanical ventilation or supplemental oxygen therapy, while no benefit was found among patients without hypoxemia. In addition, a positive outcome was found in patients who received dexamethasone after several days of symptoms, while possible harm could exist if administered early. The right time interval for GC administration is still a matter of debate. Previous studies showed that an early GC use during the first phase of the disease, when viral replication peaks, may negatively affect the innate immune response through several mechanisms, such as the inhibition of pro-inflammatory and antiviral cytokine production and signaling pathway, including type I interferon, that is fundamental to counteract the virus and that was found to be impaired in several patients with life-threatening COVID-19. The GC misuse can lead to a more severe disease even in patients who do not have the established risk factors, such as obesity and cardiovascular diseases. In our focused review, we describe the role of immune response in viral infections, especially SARS-CoV-2, and discuss the potential harms of GC misuse in COVID-19.


Subject(s)
COVID-19 , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Glucocorticoids/adverse effects , Humans , Pharmaceutical Preparations , SARS-CoV-2
7.
Front Endocrinol (Lausanne) ; 12: 711612, 2021.
Article in English | MEDLINE | ID: covidwho-1485047

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic forced a change in the way we provide medical treatment. Endocrinology in the era of COVID-19 had to transform and reduce its vast potential to the absolute necessities. Medical professionals needed to update their clinical practice to provide their patients as much support and as little harm as possible in these increasingly difficult times. International expert statements were published to offer guidance regarding proper care. It was suggested to simplify the diagnostic scheme of hypercortisolemia and to modify the approach to treatment. Hypercortisolemic patients with COVID-19 and iatrogenic hypercortisolemia due to glucocorticoid use are important clinical scenarios - we aimed to provide a cohesive summary of issues to consider.


Subject(s)
Adrenocortical Hyperfunction/therapy , COVID-19/complications , COVID-19/therapy , Adrenocortical Hyperfunction/chemically induced , Adrenocortical Hyperfunction/complications , Cushing Syndrome/complications , Cushing Syndrome/therapy , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Humans , Hydrocortisone/blood , Pandemics , Pituitary ACTH Hypersecretion/complications , Pituitary ACTH Hypersecretion/therapy
8.
JAMA ; 326(18): 1807-1817, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1482066

ABSTRACT

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.


Subject(s)
COVID-19/drug therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Life Support Care , Aged , COVID-19/complications , COVID-19/mortality , Dexamethasone/adverse effects , Dose-Response Relationship, Drug , Female , Glucocorticoids/adverse effects , Humans , Hypoxia/etiology , Hypoxia/therapy , Male , Middle Aged , Mycoses/etiology , Respiration, Artificial , Shock, Septic/etiology , Single-Blind Method
9.
PLoS One ; 16(9): e0256682, 2021.
Article in English | MEDLINE | ID: covidwho-1416872

ABSTRACT

BACKGROUND: Glucocorticoid (GC)-exacerbated hyperglycemia is prevalent in hospitalized patients with diabetes mellitus (DM) but evidence-based insulin guidelines in inpatient settings are lacking. METHODS AND FINDINGS: Retrospective cohort study with capillary blood glucose (CBG) readings and insulin use, dosed with 50% basal (glargine)-50% bolus (lispro) insulin, analyzed in hospitalized patients with insulin-treated DM given GC and matched controls without GC (n = 131 pairs). GC group (median daily prednisone-equivalent dose: 53.36 mg (IQR 30.00, 80.04)) had greatest CBG differences compared to controls at dinner (254±69 vs. 184±63 mg/dL, P<0.001) and bedtime (260±72 vs. 182±55 mg/dL, P<0.001). In GC group, dinner CBG was 30% higher than lunch (254±69 vs. 199±77 mg/dL, P<0.001) when similar lispro to controls given at lunch. Bedtime CBG not different from dinner when 20% more lispro given at dinner (0.12 units/kg (IQR 0.08, 0.17) vs. 0.10 units/kg (0.06, 0.14), P<0.01). Despite receiving more lispro, bedtime hypoglycemic events were lower in GC group (0.0% vs. 5.9%, P = 0.03). CONCLUSIONS: Since equal bolus doses inadequately treat large dinner and bedtime GC-exacerbated glycemic excursions, initiating higher bolus insulin at lunch and dinner with additional enhanced GC-specific insulin supplemental scale may be needed as initial insulin doses in setting of high-dose GC.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus , Glucocorticoids/adverse effects , Hyperglycemia/chemically induced , Hypoglycemic Agents/adverse effects , Insulin , Aged , Chicago/epidemiology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/epidemiology , Drug Administration Schedule , Female , Humans , Insulin/administration & dosage , Insulin/blood , Male , Middle Aged , Retrospective Studies
10.
Respir Res ; 22(1): 245, 2021 Sep 15.
Article in English | MEDLINE | ID: covidwho-1412433

ABSTRACT

BACKGROUND: We performed a multicenter, randomized open-label trial in patients with moderate to severe Covid-19 treated with a range of possible treatment regimens. METHODS: Patients were randomly assigned to one of three regimen groups at a ratio of 1:1:1. The primary outcome of this study was admission to the intensive care unit. Secondary outcomes were intubation, in-hospital mortality, time to clinical recovery, and length of hospital stay (LOS). Between April 13 and August 9, 2020, a total of 336 patients were randomly assigned to receive one of the 3 treatment regimens including group I (hydroxychloroquine stat, prednisolone, azithromycin and naproxen; 120 patients), group II (hydroxychloroquine stat, azithromycin and naproxen; 116 patients), and group III (hydroxychloroquine and lopinavir/ritonavir (116 patients). The mean LOS in patients receiving prednisolone was 5.5 in the modified intention-to-treat (mITT) population and 4.4 days in the per-protocol (PP) population compared with 6.4 days (mITT population) and 5.8 days (PP population) in patients treated with Lopinavir/Ritonavir. RESULTS: The mean LOS was significantly lower in the mITT and PP populations who received prednisolone compared with populations treated with Lopinavir/Ritonavir (p = 0.028; p = 0.0007). We observed no significant differences in the number of deaths, ICU admission, and need for mechanical ventilation between the Modified ITT and per-protocol populations treated with prednisolone and Lopinavir/Ritonavir, although these outcomes were better in the arm treated with prednisolone. The time to clinical recovery was similar in the modified ITT and per-protocol populations treated with prednisolone, lopinavir/ritonavir, and azithromycin (P = 0.335; P = 0.055; p = 0.291; p = 0.098). CONCLUSION: The results of the present study show that therapeutic regimen (regimen I) with low dose prednisolone was superior to other regimens in shortening the length of hospital stay in patients with moderate to severe COVID-19. The steroid sparing effect may be utilized to increase the effectiveness of corticosteroids in the management of diabetic patients by decreasing the dosage.


Subject(s)
COVID-19/drug therapy , Glucocorticoids/therapeutic use , Prednisolone/therapeutic use , Adult , Aged , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Drug Therapy, Combination , Female , Glucocorticoids/adverse effects , Hospital Mortality , Humans , Intensive Care Units , Intubation, Intratracheal , Iran , Length of Stay , Male , Middle Aged , Prednisolone/adverse effects , Severity of Illness Index , Time Factors , Treatment Outcome
11.
Clin Exp Nephrol ; 26(1): 75-85, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1372798

ABSTRACT

BACKGROUND: Critical coronavirus disease 2019 (COVID-19) has a high fatality rate, especially in hemodialysis (HD) patients, with this poor prognosis being caused by systemic hyperinflammation; cytokine storms. Steroid pulse therapy or tocilizumab (TCZ) have insufficient inhibitory effects against cytokine storms in critical cases. This study evaluated the clinical effects and safety of combining steroid pulse therapy and TCZ. METHODS: From September 2020 to May 2021, 201 patients with COVID-19 were admitted to our hospital. Before February 2021, patients with an oxygen demand exceeding 8 L/min were intubated and treated with standard therapy (dexamethasone and antiviral therapy). After February 2021, patients underwent high-flow nasal cannula oxygen therapy and were treated with TCZ (8 mg/kg) and methylprednisolone (mPSL) (500 mg/day [≤ 75 kg], 1000 mg/day [> 75 kg]) for 3 days. We compared background characteristics, laboratory findings, and prognosis between non-HD and HD patients and between patients who received and did not receive TCZ and mPSL pulse therapy. RESULTS: Among non-HD patients, the TCZ + mPSL pulse group had significantly higher survival rates and lower secondary infection rates (p < 0.05), than the standard therapy group. All HD patients in the standard therapy group with oxygen demand exceeding 8 L/min died. Contrastingly, all patients in the TCZ + mPSL pulse group survived, with their oxygen demand decreasing to 0-1 L/min within 3 weeks post-administration. CONCLUSION: TCZ combined with mPSL pulse therapy improved the survival rate without significant adverse events in critical HD and non-HD patients with COVID-19 by strongly suppressing systemic hyperinflammation.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/prevention & control , Glucocorticoids/administration & dosage , Kidney Diseases/therapy , Methylprednisolone/administration & dosage , Renal Dialysis , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/diagnosis , COVID-19/immunology , COVID-19/mortality , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Drug Therapy, Combination , Female , Glucocorticoids/adverse effects , Humans , Kidney Diseases/diagnosis , Kidney Diseases/immunology , Kidney Diseases/mortality , Male , Methylprednisolone/adverse effects , Middle Aged , Pulse Therapy, Drug , Renal Dialysis/adverse effects , Renal Dialysis/mortality , Retrospective Studies , Time Factors , Treatment Outcome
13.
Drug Dev Res ; 82(7): 880-882, 2021 11.
Article in English | MEDLINE | ID: covidwho-1330313

ABSTRACT

COVID-19's second wave had a significant impact on India, on May 7, 2021, the largest daily recorded case count was a little more than 4 million, and it has since fallen. Although the number of new cases reported has dropped, during the third week of May 2021, India accounted for about 45% of new cases identified globally and around 34% of deaths. As India maintains its present level of stability, a new urgent threat has emerged in the form of coronavirus-associated mucormycosis. Mucormycosis, an acute and deadly fungal infection caused by Mucorales-related fungal species, is a fungal emergency with a particularly aggressive propensity for contiguous spread, associated with a poor prognosis if not properly and immediately identified, and treated. Mucormycosis, sometimes referred to as the "black fungus," has increased more rapidly in India during the second wave of COVID-19 than during the first wave, with at least 14,872 cases as of May 28, 2021. Uncontrolled diabetic mellitus (DM) and other immunosuppressive diseases such as neutropenia and corticosteroid treatment have traditionally been identified as risk factors for mucormycosis. Therefore, the use of glucocorticoids or high doses of glucocorticoids in mild COVID-19 cases (without hypoxemia) should be avoided. In addition, drugs that target the immune pathway, such as tocilizumab, are not recommended without clear benefits.


Subject(s)
Anti-Bacterial Agents/adverse effects , COVID-19/complications , Mucormycosis/epidemiology , Mucormycosis/etiology , Prescription Drug Misuse , Anti-Bacterial Agents/therapeutic use , COVID-19/drug therapy , Emergency Medical Services , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Humans , India , Pandemics , Prognosis , Risk Factors
14.
Rev Endocr Metab Disord ; 23(2): 233-250, 2022 04.
Article in English | MEDLINE | ID: covidwho-1303352

ABSTRACT

Patients with endogenous or exogenous glucocorticoid (GC) excess exhibit a range of side effects, including an increased risk of infections. Via both mechanism, immune impairments and cardiometabolic concomitant diseases, patients with GC excess could be at increased risk for COVID-19. The impact on incidence and outcome of a SARS-CoV-2 infection in this population are not yet completely clear. This review aims to compile the data available to date and to discuss the existing literature on this topic. Further we highlight potential effects of SARS-CoV-2 on the hypothalamic-pituitary-adrenal axis as well as the influence of endogenous or exogenous GC excess on SARS-CoV-2 mRNA vaccination. There is growing evidence suggesting an increased risk of infection and severe outcome in patients with high-dose GC therapy after contracting SARS-CoV-2. The few data and case reports on patients with endogenous GC excess and SARS-CoV-2 infection point in a similar direction: chronic GC excess seems to be associated with an unfavorable course of COVID-19. Whether this is mainly a primary immune-mediated effect, or also triggered by the many GC-associated comorbidities in this population, is not yet fully understood. Patients with endogenous or exogenous GC excess should be considered as a vulnerable group during the SARS-CoV-2 pandemic. Regardless of the cause, vaccination and consistent surveillance and control of associated comorbidities are recommended.


Subject(s)
COVID-19 , Glucocorticoids , Glucocorticoids/adverse effects , Humans , Hypothalamo-Hypophyseal System , Pituitary-Adrenal System , Risk Factors , SARS-CoV-2
15.
Cell Metab ; 33(8): 1592-1609.e7, 2021 08 03.
Article in English | MEDLINE | ID: covidwho-1300705

ABSTRACT

Glucocorticoids (GCs) are widely used as anti-inflammatory drugs, but their long-term use has severe metabolic side effects. Here, by treating multiple individual adipose stem cell-derived adipocytes and induced pluripotent stem cell-derived hepatocytes with the potent GC dexamethasone (Dex), we uncovered cell-type-specific and individual-specific GC-dependent transcriptomes and glucocorticoid receptor (GR) cistromes. Individual-specific GR binding could be traced to single-nucleotide polymorphisms (SNPs) that altered the binding motifs of GR or its cooperating factors. We also discovered another set of genetic variants that modulated Dex response through affecting chromatin accessibility or chromatin architecture. Several SNPs that altered Dex-regulated GR binding and gene expression controlled Dex-driven metabolic perturbations. Remarkably, these genetic variations were highly associated with increases in serum glucose, lipids, and body mass in subjects on GC therapy. Knowledge of the genetic variants that predispose individuals to metabolic side effects allows for a precision medicine approach to the use of clinically relevant GCs.


Subject(s)
Epigenomics , Glucocorticoids , Adipocytes/metabolism , Anti-Inflammatory Agents , Dexamethasone/adverse effects , Glucocorticoids/adverse effects , Humans , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolism
16.
Front Endocrinol (Lausanne) ; 12: 649405, 2021.
Article in English | MEDLINE | ID: covidwho-1295631

ABSTRACT

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness.


Subject(s)
COVID-19/drug therapy , Glucocorticoids/adverse effects , Insulin/therapeutic use , Metabolic Diseases/chemically induced , Metabolic Diseases/prevention & control , COVID-19/complications , Critical Care/methods , Critical Illness/therapy , Dexamethasone/adverse effects , Dexamethasone/therapeutic use , Diabetes Complications/diagnosis , Diabetes Complications/drug therapy , Diabetes Complications/mortality , Diabetes Mellitus/drug therapy , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Glucocorticoids/therapeutic use , Humans , Hyperglycemia/complications , Hyperglycemia/drug therapy , Hyperglycemia/mortality , Metabolic Diseases/etiology , Obesity/complications , Obesity/drug therapy , Obesity/mortality , SARS-CoV-2/physiology , Treatment Outcome
17.
Int J Hematol ; 114(6): 719-724, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1274955

ABSTRACT

Patients with cancer are considered at high risk of acquiring coronavirus disease (COVID-19). To identify patients who are likely to be diagnosed with severe COVID-19, we analyzed the risk factors for mortality in patients admitted to the hematology department at our institute. The mortality rate of all patients was as high as 62% (21 of the 34 patients), and most of these patients had malignant malignancies. Patients before an achievement of remission had a 10.8-fold higher risk of death than those in remission. The group receiving chemotherapy with steroids had a shorter survival time and had an 8.3-fold higher risk of death than that receiving chemotherapy without steroids. During the COVID-19 pandemic, it is necessary to carefully monitor or follow-up patients with active diseases and patients receiving steroid-containing chemotherapy.


Subject(s)
COVID-19 , Cross Infection , Glucocorticoids/adverse effects , Hematologic Diseases , COVID-19/complications , Cross Infection/complications , Female , Glucocorticoids/therapeutic use , Hematologic Diseases/complications , Hematologic Diseases/drug therapy , Hematologic Diseases/mortality , Humans , Japan , Male , Risk Factors , Severity of Illness Index , Survival Rate
18.
Epilepsy Res ; 174: 106675, 2021 08.
Article in English | MEDLINE | ID: covidwho-1233420

ABSTRACT

In regard to the global pandemic of COVID-19, it seems that persons with epilepsy (PWE) are not more vulnerable to get infected by SARS-CoV-2, nor are they more susceptible to a critical course of the disease. However, management of acute seizures in patients with COVID-19 as well as management of PWE and COVID-19 needs to consider potential drug-drug interactions between antiseizure drugs and candidate drugs currently assessed as therapeutic options for COVID-19. Repurposing of several licensed and investigational drugs is discussed for therapeutic management of COVID-19. While for none of these approaches, efficacy and tolerability has been confirmed yet in sufficiently powered and controlled clinical studies, testing is ongoing with multiple clinical trials worldwide. Here, we have summarized the possible mechanisms of action of drugs currently considered as potential therapeutic options for COVID-19 management along with possible and confirmed drug-drug interactions that should be considered for a combination of antiseizure drugs and COVID-19 candidate drugs. Our review suggests that potential drug-drug interactions should be taken into account with drugs such as chloroquine/hydroxychloroquine and lopinavir/ritonavir while remdesivir and tocilizumab may be less prone to clinically relevant interactions with ASMs.


Subject(s)
Anti-Inflammatory Agents/adverse effects , Anticonvulsants/adverse effects , Antiviral Agents/adverse effects , COVID-19/drug therapy , Enzyme Inhibitors/adverse effects , Epilepsy/drug therapy , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Alanine/adverse effects , Alanine/analogs & derivatives , Amides/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/complications , Chloroquine/adverse effects , Cytochrome P-450 CYP3A Inducers/adverse effects , Dexamethasone/adverse effects , Drug Combinations , Drug Interactions , Epilepsy/complications , Glucocorticoids/adverse effects , Humans , Hydroxychloroquine/adverse effects , Interleukin 1 Receptor Antagonist Protein/adverse effects , Ivermectin/adverse effects , Lopinavir , Pyrazines/adverse effects , Ritonavir , SARS-CoV-2
19.
Clin Infect Dis ; 72(10): 1830-1833, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1232178

ABSTRACT

Use of high-dose glucocorticoids for COVID-19 (caused by SARS-CoV-2) is controversial because of safety concerns. We examined the long-term consequences of glucocorticoid use in severe acute respiratory syndrome (caused by SARS-CoV-1) survivors. Results showed that high-dose glucocorticoids greatly increased the long-term risk of avascular necrosis but not other major diseases.


Subject(s)
COVID-19 , Glucocorticoids , Follow-Up Studies , Glucocorticoids/adverse effects , Humans , SARS-CoV-2 , Survivors
20.
Front Immunol ; 12: 651715, 2021.
Article in English | MEDLINE | ID: covidwho-1211813

ABSTRACT

BACKGROUND: The course of novel coronavirus disease 2019 (COVID-19) has been of special concern in patients with inflammatory rheumatic diseases (IRDs) due to the immune dysregulation that may be associated with these diseases and the medications used for IRDs, that may affect innate immune responses. OBJECTIVE: In this cohort study, we aimed to report the disease characteristics and variables associated with COVID-19 outcome among Turkish patients with IRDs. METHODS: Between April and June, 2020, 167 adult IRD patients with COVID-19 were registered from 31 centers in 14 cities in Turkey. Disease outcome was classified in 4 categories; (i) outpatient management, (ii) hospitalization without oxygen requirement, (iii) hospitalization with oxygen requirement, and (iv) intensive care unit (ICU) admission or death. Multivariable ordinal logistic regression analysis was conducted to determine variables associated with a worse outcome. RESULTS: 165 patients (mean age: 50 ± 15.6 years, 58.2% female) were included. Twenty-four patients (14.5%) recovered under outpatient management, 141 (85.5%) were hospitalized, 49 (30%) required inpatient oxygen support, 22 (13%) were treated in the ICU (17 received invasive mechanic ventilation) and 16 (10%) died. Glucocorticoid use (OR: 4.53, 95%CI 1.65-12.76), chronic kidney disease (OR: 12.8, 95%CI 2.25-103.5), pulmonary disease (OR: 2.66, 95%CI 1.08-6.61) and obesity (OR: 3.7, 95%CI 1.01-13.87) were associated with a worse outcome. Biologic disease-modifying antirheumatic drugs (DMARDs) do not seem to affect COVID-19 outcome while conventional synthetic DMARDs may have a protective effect (OR: 0.36, 95%CI 0.17-0.75). Estimates for the associations between IRD diagnoses and outcome were inconclusive. CONCLUSIONS: Among IRD patients with COVID-19, comorbidities and glucocorticoid use were associated with a worse outcome, while biologic DMARDs do not seem to be associated with a worse outcome.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19/complications , Glucocorticoids/adverse effects , Rheumatic Diseases/immunology , Adult , Aged , Ambulatory Care , Antirheumatic Agents/adverse effects , COVID-19/immunology , COVID-19/mortality , COVID-19/physiopathology , Cohort Studies , Comorbidity , Critical Care , Female , Glucocorticoids/therapeutic use , Hospitalization , Humans , Male , Middle Aged , Multivariate Analysis , Oxygen Inhalation Therapy , Regression Analysis , Rheumatic Diseases/complications , Rheumatic Diseases/mortality , Rheumatic Diseases/physiopathology , Turkey
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