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1.
Semin Respir Crit Care Med ; 42(5): 672-682, 2021 10.
Article in English | MEDLINE | ID: covidwho-1493295

ABSTRACT

While the use of vitamin C as a therapeutic agent has been investigated since the 1950s, there has been substantial recent interest in the role of vitamin C supplementation in critical illness and particularly, sepsis and septic shock. Humans cannot synthesize vitamin C and rely on exogenous intake to maintain a plasma concentration of approximately 70 to 80 µmol/L. Vitamin C, in healthy humans, is involved with antioxidant function, wound healing, endothelial function, and catecholamine synthesis. Its function in the human body informs the theoretical basis for why vitamin C supplementation may be beneficial in sepsis/septic shock.Critically ill patients can be vitamin C deficient due to low dietary intake, increased metabolic demands, inefficient recycling of vitamin C metabolites, and loss due to renal replacement therapy. Intravenous supplementation is required to achieve supraphysiologic serum levels of vitamin C. While some clinical studies of intravenous vitamin C supplementation in sepsis have shown improvements in secondary outcome measures, none of the randomized clinical trials have shown differences between vitamin C supplementation and standard of care and/or placebo in the primary outcome measures of the trials. There are some ongoing studies of high-dose vitamin C administration in patients with sepsis and coronavirus disease 2019; the majority of evidence so far does not support the routine supplementation of vitamin C in patients with sepsis or septic shock.


Subject(s)
Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , Shock, Septic/drug therapy , Vitamins/pharmacology , Vitamins/therapeutic use , Animals , Antioxidants/pharmacology , Ascorbic Acid/administration & dosage , Ascorbic Acid/adverse effects , Ascorbic Acid Deficiency/physiopathology , Clinical Trials as Topic , Critical Illness , Dose-Response Relationship, Drug , Glucocorticoids/pharmacology , Humans , Inflammation Mediators/metabolism , Vasoconstrictor Agents/pharmacology , Vitamins/administration & dosage , Vitamins/adverse effects
2.
Viruses ; 13(7)2021 07 20.
Article in English | MEDLINE | ID: covidwho-1325786

ABSTRACT

Treatment options for COVID-19, a disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, are currently severely limited. Therefore, antiviral drugs that efficiently reduce SARS-CoV-2 replication or alleviate COVID-19 symptoms are urgently needed. Inhaled glucocorticoids are currently being discussed in the context of treatment for COVID-19, partly based on a previous study that reported reduced recovery times in cases of mild COVID-19 after inhalative administration of the glucocorticoid budesonide. Given various reports that describe the potential antiviral activity of glucocorticoids against respiratory viruses, we aimed to analyze a potential antiviral activity of budesonide against SARS-CoV-2 and circulating variants of concern (VOC) B.1.1.7 (alpha) and B.1.351 (beta). We demonstrate a dose-dependent inhibition of SARS-CoV-2 that was comparable between all viral variants tested while cell viability remains unaffected. Our results are encouraging as they could indicate a multimodal mode of action of budesonide against SARS-CoV-2 and COVID-19, which could contribute to an improved clinical performance.


Subject(s)
Antiviral Agents/pharmacology , Budesonide/pharmacology , COVID-19/drug therapy , SARS-CoV-2/drug effects , Adrenal Cortex Hormones/pharmacology , Animals , Antiviral Agents/administration & dosage , Budesonide/administration & dosage , COVID-19/virology , Chlorocebus aethiops , Glucocorticoids/pharmacology , Humans , Vero Cells , Virus Replication/drug effects
3.
Eur J Pharmacol ; 908: 174374, 2021 Oct 05.
Article in English | MEDLINE | ID: covidwho-1322083

ABSTRACT

The efficacy of corticosteroids and its use for the treatment of SARS-CoV-2 infections is controversial. In this study, using data sets of SARS-CoV-2 infected lung tissues and nasopharyngeal swabs, as well as in vitro experiments, we show that SARS-CoV-2 infection significantly downregulates DUSP1 expression. This downregulation of DUSP1 could be the mechanism regulating the enhanced activation of MAPK pathway as well as the reported steroid resistance in SARS-CoV-2 infection. Moreover, chloroquine, an off labeled COVID-19 drug is able to induce DUSP1 and attenuate MAPK pathway; and is expected to improve sensitivity to steroid treatment. However, further mechanistic studies are required to confirm this effect.


Subject(s)
COVID-19/drug therapy , Chloroquine/pharmacology , Dual Specificity Phosphatase 1/genetics , Glucocorticoids/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolism , Adult , Aged , COVID-19/pathology , COVID-19/virology , Case-Control Studies , Cells, Cultured , Chloroquine/therapeutic use , Datasets as Topic , Down-Regulation/drug effects , Drug Resistance/drug effects , Drug Resistance/genetics , Drug Synergism , Dual Specificity Phosphatase 1/metabolism , Fibroblasts , Glucocorticoids/therapeutic use , Healthy Volunteers , Humans , Lung/cytology , Lung/pathology , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/genetics , Middle Aged , Nasopharynx/virology , Off-Label Use , Primary Cell Culture , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity
4.
Transplant Proc ; 53(4): 1224-1226, 2021 May.
Article in English | MEDLINE | ID: covidwho-1203315

ABSTRACT

The cardiac effects of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include myocarditis, takotsubo cardiomyopathy, pericardial effusion, and cardioembolic events in the general population. The effects of SARS-CoV-2 in heart transplant patients are unclear. We describe a case of myocarditis in the transplanted heart that responded to methylprednisolone.


Subject(s)
COVID-19/diagnosis , Heart Transplantation , Myocarditis/diagnosis , Aged , COVID-19/complications , COVID-19/virology , Glucocorticoids/pharmacology , Glucocorticoids/therapeutic use , Heart Failure/complications , Heart Failure/therapy , Humans , Male , Methylprednisolone/pharmacology , Methylprednisolone/therapeutic use , Myocarditis/drug therapy , SARS-CoV-2/isolation & purification , Transplantation, Homologous , Ventricular Function, Left/drug effects
5.
Bioorg Med Chem Lett ; 43: 128052, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1196690

ABSTRACT

Ciclesonide is an inhaled corticosteroid used to treat asthma and is currently undergoing clinical trials for treatment of coronavirus disease 2019 (COVID-19). An active metabolite of ciclesonide, Cic2, was recently reported to repress severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomic RNA replication. Herein, we designed and synthesized a few types of ciclesonide analogues. Cic4 (bearing an azide group) and Cic6 (bearing a chloro group) potently decreased SARS-CoV-2 viral replication and had low cytotoxicity compared with Cic2 (bearing a hydroxy group). These compounds are promising as novel therapeutic agents for COVID-19 that show significant antiviral activity.


Subject(s)
COVID-19/drug therapy , Pregnenediones/pharmacology , RNA, Viral/antagonists & inhibitors , SARS-CoV-2/drug effects , COVID-19/virology , Glucocorticoids/pharmacology , Humans , RNA, Viral/genetics , SARS-CoV-2/genetics , Virus Replication/genetics
6.
PLoS Comput Biol ; 17(1): e1008223, 2021 01.
Article in English | MEDLINE | ID: covidwho-1088652

ABSTRACT

Gene regulatory network inference is essential to uncover complex relationships among gene pathways and inform downstream experiments, ultimately enabling regulatory network re-engineering. Network inference from transcriptional time-series data requires accurate, interpretable, and efficient determination of causal relationships among thousands of genes. Here, we develop Bootstrap Elastic net regression from Time Series (BETS), a statistical framework based on Granger causality for the recovery of a directed gene network from transcriptional time-series data. BETS uses elastic net regression and stability selection from bootstrapped samples to infer causal relationships among genes. BETS is highly parallelized, enabling efficient analysis of large transcriptional data sets. We show competitive accuracy on a community benchmark, the DREAM4 100-gene network inference challenge, where BETS is one of the fastest among methods of similar performance and additionally infers whether causal effects are activating or inhibitory. We apply BETS to transcriptional time-series data of differentially-expressed genes from A549 cells exposed to glucocorticoids over a period of 12 hours. We identify a network of 2768 genes and 31,945 directed edges (FDR ≤ 0.2). We validate inferred causal network edges using two external data sources: Overexpression experiments on the same glucocorticoid system, and genetic variants associated with inferred edges in primary lung tissue in the Genotype-Tissue Expression (GTEx) v6 project. BETS is available as an open source software package at https://github.com/lujonathanh/BETS.


Subject(s)
Glucocorticoids/pharmacology , Models, Statistical , Transcriptome/drug effects , A549 Cells , Algorithms , Computational Biology , Humans , Lung/chemistry , Lung/metabolism , Machine Learning , Software , Transcriptome/genetics
7.
Int J Mol Sci ; 21(23)2020 Dec 03.
Article in English | MEDLINE | ID: covidwho-965280

ABSTRACT

Glucocorticoids are drugs of choice in Duchenne muscular dystrophy (DMD), prolonging patients' ambulation. Their mode of action at the protein level is not completely understood. In DMD, muscle tissue is replaced by fibrotic tissue produced by fibroblasts, reducing mobility. Nuclear factor of activated T-cells 5 (NFAT5) is involved in fibroblast proliferation. By treating one DMD fibroblast cell culture and one of unaffected skeletal muscle fibroblasts with methylprednisolone (MP) or hydrocortisone (HC) for 24 h or 12 d, the antiproliferative properties of glucocorticoids could be unraveled. NFAT5 localization and expression was explored by immunocytochemistry (ICC), Western blotting (WB) and RT-qPCR. NFAT5 and glucocorticoid receptor (GR) colocalization was measured by ImageJ. GR siRNA was used, evaluating GR's influence on NFAT5 expression during MP and HC treatment. Cell proliferation was monitored by IncuCyte ZOOM. In DMD fibroblasts, treatment with MP for 24 h induced dots (ICC) positive for NFAT5 and colocalizing with GR. After 12 d of MP or HC in DMD fibroblasts, NFAT5 expression was decreased (RT-qPCR and WB) and growth arrest was observed (Incucyte ZOOM), whereas NFAT5 expression and cell growth remained unchanged in unaffected skeletal muscle fibroblasts. This study may help understand the antiproliferative properties of glucocorticoids in DMD fibroblasts.


Subject(s)
Fibroblasts/drug effects , Fibroblasts/metabolism , Glucocorticoids/pharmacology , Receptors, Glucocorticoid/metabolism , Transcription Factors/metabolism , Cell Proliferation/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Fluorescent Antibody Technique , Humans , Hydrocortisone/pharmacology , Methylprednisolone/pharmacology , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/metabolism , Protein Binding
8.
Eur J Pharmacol ; 882: 173328, 2020 Sep 05.
Article in English | MEDLINE | ID: covidwho-959744

ABSTRACT

The novel coronavirus, later identified as SARS-CoV-2, originating from Wuhan in China in November 2019, quickly spread around the world becoming a pandemic. Despite the knowledge of previous coronaviruses, such as those responsible for the SARS and MERS-CoV epidemic, there is no drug or prophylaxis treatment to this day. The rapid succession of scientific findings on SARS-CoV-2 provides a significant number of potential drug targets. Nevertheless, at the same time, the high quantity of clinical data, generated by a large number of rapidly infected people, require accurate tests regarding effective medical treatments. Several in vitro and in vivo studies were rapidly initiated after the outbreak of the pandemic COVID-19. Initial clinical studies revealed the promising potential of remdesivir that demonstrated a powerful and specific in vitro antiviral activity for COVID-19. Promising effects appear to be attributable to hydroxychloroquine. Remdesivir and hydroxychloroquine are being tested in ongoing randomized trials. In contrast, oseltamivir was not effective and corticosteroids are not currently recommended. However, few data from ongoing clinical trials are identifying low molecular weight heparins, innate immune system stimulating agents, and inflammatory modulating agents as potential effective agents. The authors assume that the current pandemic will determine the need for a systematic approach based on big data analysis for identifying effective drugs to defeat SARS-Cov-2. This work is aimed to be a general reference point and to provide an overview as comprehensive as possible regarding the main clinical trials in progress at the moment.


Subject(s)
Adjuvants, Immunologic/pharmacology , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Inflammation Mediators/pharmacology , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Adjuvants, Immunologic/therapeutic use , Alanine/analogs & derivatives , Alanine/pharmacology , Alanine/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Clinical Trials as Topic , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Glucocorticoids/pharmacology , Glucocorticoids/therapeutic use , Heparin, Low-Molecular-Weight/pharmacology , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Hydroxychloroquine/pharmacology , Hydroxychloroquine/therapeutic use , Immunity, Innate/drug effects , Inflammation Mediators/therapeutic use , Oseltamivir/pharmacology , Oseltamivir/therapeutic use , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2 , Treatment Outcome
9.
Chest ; 159(3): 1019-1040, 2021 03.
Article in English | MEDLINE | ID: covidwho-959674

ABSTRACT

BACKGROUND: Since its appearance in late 2019, infections caused by severe acute respiratory syndrome coronavirus 2 have created unprecedented challenges for health systems worldwide. Multiple therapeutic options have been explored, including corticosteroids. Preliminary results of corticosteroids in coronavirus disease 2019 (COVID-19) are encouraging; however, the role of corticosteroids remains controversial. RESEARCH QUESTION: What is the impact of corticosteroids in mortality, ICU admission, mechanical ventilation, and viral shedding in COVID-19 patients? STUDY DESIGN AND METHODS: We conducted a systematic review of literature on corticosteroids and COVID-19 in major databases (PubMed, MEDLINE, and EMBASE) of published literature through July 22, 2020, that report outcomes of interest in COVID-19 patients receiving corticosteroids with a comparative group. RESULTS: A total of 73 studies with 21,350 COVID-19 patients were identified. Corticosteroid use was reported widely in mechanically ventilated patients (35.3%), ICU patients (51.3%), and severe COVID-19 patients (40%). Corticosteroids showed mortality benefit in severelly ill COVID-19 patients (OR, 0.65; 95% CI, 0.51-0.83; P = .0006); however, no beneficial or harmful effects were noted among high-dose or low-dose corticosteroid regimens. Emerging evidence shows that low-dose corticosteroids do not have a significant impact in the duration of SARS-CoV-2 viral shedding. The analysis was limited by highly heterogeneous literature for high-dose and low-dose corticosteroids regimens. INTERPRETATION: Our results showed evidence of mortality benefit in severely ill COVID-19 patients treated with corticosteroids. Corticosteroids are used widely in COVID-19 patients worldwide, and a rapidly developing global pandemic warrants further high-quality clinical trials to define the most beneficial timing and dosing for corticosteroids.


Subject(s)
COVID-19 , Glucocorticoids/pharmacology , SARS-CoV-2/drug effects , COVID-19/drug therapy , COVID-19/epidemiology , Dose-Response Relationship, Drug , Humans , Mortality , SARS-CoV-2/physiology , Virus Shedding/drug effects
10.
Allergy ; 76(3): 789-803, 2021 03.
Article in English | MEDLINE | ID: covidwho-933959

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. However, the association between SARS-CoV-2 and nasal inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been investigated. We thus investigated the expression of SARS-CoV-2 entry factors in nasal tissues of CRSwNP patients, and their associations with inflammatory endotypes of CRSwNP. METHODS: The expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated. RESULTS: ACE2 expression was significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects, and positively correlated with the expression of IFN-γ, but negatively correlated with tissue infiltrated eosinophils, and expression of IL5 and IL13. IFN-γ up-regulated ACE2 expression while glucocorticoid attenuated this increase in cultured nasal epithelial cells. Genes co-expressed with ACE2 were enriched in pathways relating to defence response to virus in nasal tissue. TMPRSS2 expression was decreased in nasal tissues of CRSwNP patients compared to control subjects and not correlated with the inflammatory endotypes of CRSwNP. Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected. CONCLUSION: These findings indicate that ACE2 expression, regulated by IFN-γ, is increased in nasal tissues of nonECRSwNP patients and positively correlates with type 1 inflammation.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/etiology , Nasal Polyps/enzymology , Receptors, Coronavirus/genetics , Rhinitis/enzymology , Sinusitis/enzymology , Adult , Cells, Cultured , Chronic Disease , Female , Gene Expression Regulation, Enzymologic , Glucocorticoids/pharmacology , Humans , Male , Middle Aged , Nasal Polyps/immunology , Rhinitis/immunology , Serine Endopeptidases/genetics , Sinusitis/immunology
11.
Cell Mol Immunol ; 18(2): 269-278, 2021 02.
Article in English | MEDLINE | ID: covidwho-738750

ABSTRACT

Glucocorticoids (GCs) are endogenous hormones that are crucial for the homeostasis of the organism and adaptation to the external environment. Because of their anti-inflammatory effects, synthetic GCs are also extensively used in clinical practice. However, almost all cells in the body are sensitive to GC regulation. As a result, these mediators have pleiotropic effects, which may be undesirable or detrimental to human health. Here, we summarize the recent findings that contribute to deciphering the molecular mechanisms downstream of glucocorticoid receptor activation. We also discuss the complex role of GCs in infectious diseases such as sepsis and COVID-19, in which the balance between pathogen elimination and protection against excessive inflammation and immunopathology needs to be tightly regulated. An understanding of the cell type- and context-specific actions of GCs from the molecular to the organismal level would help to optimize their therapeutic use.


Subject(s)
Glucocorticoids/pharmacology , Organ Specificity/drug effects , Animals , COVID-19/metabolism , Humans , Inflammation/pathology , Receptors, Glucocorticoid/metabolism , Signal Transduction/drug effects
12.
Cardiovasc Revasc Med ; 23: 107-113, 2021 02.
Article in English | MEDLINE | ID: covidwho-718669

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also referred to as COVID-19, was declared a pandemic by the World Health Organization in March 2020. The manifestations of COVID-19 are widely variable and range from asymptomatic infection to multi-organ failure and death. Like other viral illnesses, acute myocarditis has been reported to be associated with COVID-19 infection. However, guidelines for the diagnosis of COVID-19 myocarditis have not been established. METHODS: Using a combination of search terms in the PubMed/Medline, Ovid Medline and the Cochrane Library databases and manual searches on Google Scholar and the bibliographies of articles identified, we reviewed all cases reported in the English language citing myocarditis associated with COVID-19 infection. RESULTS: Fourteen records comprising a total of fourteen cases that report myocarditis/myopericarditis secondary to COVID-19 infection were identified. There was a male predominance (58%), with the median age of the cases described being 50.4 years. The majority of patients did not have a previously identified comorbid condition (50%), but of those with a past medical history, hypertension was most prevalent (33%). Electrocardiogram findings were variable, and troponin was elevated in 91% of cases. Echocardiography was performed in 83% of cases reduced function was identified in 60%. Endotracheal intubation was performed in the majority of cases. Glucocorticoids were most commonly used in treatment of myocarditis (58%). Majority of patients survived to discharge (81%) and 85% of those that received steroids survived to discharge. CONCLUSION: Guidelines for diagnosis and management of COVID-19 myocarditis have not been established and our knowledge on management is rapidly changing. The use of glucocorticoids and other agents including IL-6 inhibitors, IVIG and colchicine in COVID-19 myocarditis is debatable. In our review, there appears to be favorable outcomes related to myocarditis treated with steroid therapy. However, until larger scale studies are conducted, treatment approaches have to be made on an individualized case-by-case basis.


Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , COVID-19/drug therapy , Myocarditis/complications , Myocarditis/drug therapy , SARS-CoV-2/drug effects , Adult , Aged , COVID-19/complications , COVID-19/virology , Female , Glucocorticoids/pharmacology , Humans , Male , Middle Aged , Myocarditis/virology , SARS-CoV-2/pathogenicity , Young Adult
13.
Sci Rep ; 10(1): 13689, 2020 08 13.
Article in English | MEDLINE | ID: covidwho-711912

ABSTRACT

To describe the epidemiological and clinical characteristics of patients with Corona Virus Disease 2019 (COVID-19) in Beijing. To analyze the application of corticosteroids in patients with severe pneumonia. We collected information on demographic characteristics, exposure history, clinical characteristics, corticosteroids use, and outcomes of the 65 confirmed cases of COVID-19 at Fifth Medical Center of PLA General Hospital from Jan 20 to Feb 23, 2020. The final follow-up date observed was April 15th, 2020. The number of patients with mild, general, severe, and critical type were 10 (15.38%), 32 (49.23%), 8 (12.31%), and 15 (23.08%), respectively. The median incubation period was 6 days. Notable outliers were 1 patient at 16 days and 1 patient at 21 days. In lymphocyte subgroup analysis, decreases in total, T, CD4, and CD8 lymphocytes were more common as the disease worsened (All P < 0.05). Methylprednisolone (mPSL) was applied to 31 (47.69%) patients with pneumonia, including 10 (31.25%) general, 8 (100%) severe, and 13 (86.67%) critical patients, respectively. Corticosteroids inhibited Interleukin-6(IL-6) production (P = 0.0215) but did not affect T lymphocyte (P = 0.0796). There was no significant difference between patients using lower dose (≤ 2 mg/kg day) and higher dose (> 2 mg/kg day) mPSL in inhibiting IL-6 production (P = 0.5856). Thirty of 31 patients (96.77%) had stopped mPSL due to improvement of pneumonia. Virus RNA clearance time lengthened with disease progression (P = 0.0001). In general type, there was no significant difference in virus clearance time between patients with (15, 12-19 days) and without (14.5, 11-18 days) (P = 0.7372) mPSL use. Lymphocyte, especially T lymphocyte, in severe and critical patients showed a dramatic decrease. Application of lower dose corticosteroids (≤ 2 mg/kg day) could inhibit IL-6 production (a representative of cytokines) as effectively as a higher dose. Proper use corticosteroids in general type patients did not delay virus clearance.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Glucocorticoids/therapeutic use , Methylprednisolone/therapeutic use , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Beijing/epidemiology , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , COVID-19 , Child , Child, Preschool , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Female , Follow-Up Studies , Glucocorticoids/administration & dosage , Glucocorticoids/pharmacology , Humans , Interleukin-6/antagonists & inhibitors , Lymphocyte Count , Male , Methylprednisolone/administration & dosage , Methylprednisolone/pharmacology , Middle Aged , Pandemics , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , RNA, Viral/drug effects , SARS-CoV-2 , Treatment Outcome , Young Adult
14.
Obstet Gynecol ; 136(4): 823-826, 2020 10.
Article in English | MEDLINE | ID: covidwho-706939

ABSTRACT

Recent evidence supports the use of an early, short course of glucocorticoids in patients with COVID-19 who require mechanical ventilation or oxygen support. As the number of coronavirus disease 2019 (COVID-19) cases continues to increase, the number of pregnant women with the disease is very likely to increase as well. Because pregnant women are at increased risk for hospitalization, intensive care unit admission, and mechanical ventilation support, obstetricians will be facing the dilemma of initiating maternal corticosteroid therapy while weighing its potential adverse effects on the fetus (or neonate if the patient is postpartum and breastfeeding). Our objective is to summarize the current evidence supporting steroid therapy in the management of patients with acute respiratory distress syndrome and COVID-19 and to elaborate on key modifications for the pregnant patient.


Subject(s)
Coronavirus Infections , Critical Care/methods , Glucocorticoids , Medication Therapy Management/standards , Pandemics , Pneumonia, Viral , Pregnancy Complications, Infectious , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Drug Monitoring/methods , Female , Fetal Organ Maturity/drug effects , Glucocorticoids/classification , Glucocorticoids/pharmacology , Humans , Infant, Newborn , Oxygen Inhalation Therapy/methods , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/therapy , Pregnancy Complications, Infectious/virology , Respiration, Artificial/methods , Risk Assessment , SARS-CoV-2
15.
J Zhejiang Univ Sci B ; 21(8): 628-636, 2020.
Article in English | MEDLINE | ID: covidwho-694091

ABSTRACT

BACKGROUND: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development. METHODS: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors. RESULTS: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206). CONCLUSIONS: IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.


Subject(s)
Coronavirus Infections/drug therapy , Interferon alpha-2/administration & dosage , Nasal Sprays , Pneumonia, Viral/drug therapy , Virus Shedding/drug effects , Albumins/analysis , Antiviral Agents/administration & dosage , Betacoronavirus , C-Reactive Protein/analysis , COVID-19 , Case-Control Studies , China , Glucocorticoids/pharmacology , Hospitalization , Humans , Pandemics , Propensity Score , Retrospective Studies , SARS-CoV-2 , Sodium/blood
16.
Gastroenterol Hepatol ; 43(8): 457-463, 2020 Oct.
Article in English, Spanish | MEDLINE | ID: covidwho-639589

ABSTRACT

SARS-CoV-2 infection has produced a pandemic with serious consequences for our health care system. Although liver transplant patients represent only a minority of the population, the hepatologists who follow these patients have tried to coordinate efforts to produce a protocol the management of immunosuppression during SARS-CoV-2 infection. Although there are no solid studies to support general recommendations, experiences with other viral infections (hepatitis C, cytomegalovirus) suggest that management of immunosuppression without mycophenolate mofetil or m-Tor inhibitors (drugs that are also associated with leukopenia and lymphopenia) may be beneficial. It is also important to pay attention to possible drug interactions, especially in the case of tacrolimus, with some of the treatments with antiviral effect given in the context of COVID 19 (lopinavir/ritonavir, azithromycin). Finally, the immunosuppressive effect of immunomodulating drugs (tocilizumab and similar) administered to patients with severe lung disease should be taken into account. The mechanisms of action of the different immunosuppressive drugs are reviewed in this article, as well as their potential effect on SARS-CoV-2 infection, and suggests guidelines for the management of immunosuppression.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Immunosuppressive Agents/adverse effects , Liver Transplantation , Pandemics , Pneumonia, Viral/epidemiology , Adaptive Immunity , Antiviral Agents/pharmacology , Betacoronavirus/immunology , Betacoronavirus/physiology , COVID-19 , Calcineurin Inhibitors/adverse effects , Calcineurin Inhibitors/pharmacology , Calcineurin Inhibitors/therapeutic use , Contraindications, Drug , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Disease Susceptibility , Drug Interactions , Everolimus/adverse effects , Everolimus/pharmacology , Everolimus/therapeutic use , Glucocorticoids/adverse effects , Glucocorticoids/pharmacology , Glucocorticoids/therapeutic use , Humans , Immunity, Innate , Immunocompromised Host , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/adverse effects , Mycophenolic Acid/pharmacology , Mycophenolic Acid/therapeutic use , Pneumonia, Viral/immunology , Postoperative Complications/immunology , Postoperative Complications/prevention & control , SARS-CoV-2 , Sirolimus/adverse effects , Sirolimus/pharmacology , Sirolimus/therapeutic use , TOR Serine-Threonine Kinases/antagonists & inhibitors
18.
J Allergy Clin Immunol ; 146(2): 330-331, 2020 08.
Article in English | MEDLINE | ID: covidwho-597639
19.
Respir Med ; 170: 106045, 2020.
Article in English | MEDLINE | ID: covidwho-378076

ABSTRACT

The potential detrimental effects of steroids on the immune system to fight viral infections had always been a concern for patients on long term steroids in chronic conditions. A recent warning from WHO on systemic corticosteroid use amid COVID-19 raised suspicion among public and healthcare professionals regarding the safety of steroid use during the SARS-CoV-2 pandemic. The corticosteroids (inhaled and oral) are commonly prescribed in the management of asthma and COPD patients and any unsolicited changes in medications use may lead to potentially severe exacerbations and may risk patient lives. This article provides a critical review of clinical evidence and offers a detailed discussion on the safety and efficacy of corticosteroids in asthma and COPD patients, both with and without COVID-19.


Subject(s)
Asthma/drug therapy , Coronavirus Infections , Glucocorticoids/pharmacology , Pandemics , Pneumonia, Viral , Pulmonary Disease, Chronic Obstructive/drug therapy , Asthma/epidemiology , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Drug Administration Routes , Humans , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , SARS-CoV-2 , Treatment Outcome
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