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1.
J Acquir Immune Defic Syndr ; 85(2): 123-126, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-1806747

ABSTRACT

BACKGROUND: COVID-19 disease has spread globally and was declared a pandemic on March 11, 2020, by the World Health Organization. On March 10, the State of Michigan confirmed its first 2 cases of COVID-19, and the number of confirmed cases has reached 47,182 as of May 11, 2020, with 4555 deaths. SETTING: Currently, little is known if patients living with HIV (PLWH) are at a higher risk of severe COVID-19 or if their antiretrovirals are protective. This study presents epidemiologic and clinical features of COVID-19 infected PLWH in Detroit, Michigan. METHODS: This is a case series that included 14 PLWH with laboratory-confirmed COVID-19 infection who were evaluated at Henry Ford Hospital in Detroit, Michigan, between March 20, 2020, and April 30, 2020. RESULTS: Fourteen PLWH were diagnosed with COVID-19. Twelve patients were men and 2 were women; 13 patients were virally suppressed. Eight patients were hospitalized, and 6 patients were told to self-quarantine at home after their diagnoses. Three patients who were admitted expired during their hospital stay. No patient required bilevel positive airway pressure or nebulizer use in the emergency department, and none developed acute respiratory distress syndrome, pulmonary embolism, deep venous thrombosis, or a cytokine storm while on therapy for COVID-19. CONCLUSION: Although the clinical spectrum of COVID-19 among PLWH cannot be fully ascertained by this report, it adds to the data that suggest that HIV-positive patients with SARS-CoV-2 infection are not at a greater risk of severe disease or death as compared to HIV-negative patients.


Subject(s)
Coronavirus Infections/complications , HIV Infections/complications , Pneumonia, Viral/complications , COVID-19 , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/ethnology , Female , HIV Infections/epidemiology , HIV Infections/ethnology , Hispanic or Latino , Humans , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/ethnology
2.
Clin Transl Sci ; 14(6): 2146-2151, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526353

ABSTRACT

Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We evaluated patients treated with tocilizumab for a SARS-CoV-2 infection who were admitted between March 13, 2020, and April 16, 2020. This was a multicenter study with data collected by chart review both retrospectively and concurrently. Parameters evaluated included age, sex, race, use of mechanical ventilation (MV), usage of steroids and vasopressors, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within 1 day of intubation. Late dosing was defined as a dose administered > 1 day after intubation. In the absence of MV, the timing of the dose was related to the patient's date of admission only. We evaluated 145 patients. The average age was 58.1 years, 64% were men, 68.3% had comorbidities, and 60% received steroid therapy. Disposition of patients was 48.3% discharged and 29.3% died, of which 43.9% were African American. MV was required in 55.9%, of which 34.5% died. Avoidance of MV (P = 0.002) and increased survival (P < 0.001) was statistically associated with early dosing. Tocilizumab therapy was effective at decreasing mortality and should be instituted early in the management of critically ill patients with coronavirus disease 2019) COVID-19).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , COVID-19/therapy , Cytokine Release Syndrome/therapy , Respiration, Artificial/statistics & numerical data , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Critical Illness/mortality , Critical Illness/therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Female , Hospital Mortality , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/immunology , Severity of Illness Index , Time Factors , Time-to-Treatment , Treatment Outcome
3.
Rheumatology (Oxford) ; 60(1): 399-407, 2021 01 05.
Article in English | MEDLINE | ID: covidwho-1388014

ABSTRACT

OBJECTIVES: The Janus kinase (JAK) inhibitor baricitinib may block viral entry into pneumocytes and prevent cytokine storm in patients with SARS-CoV-2 pneumonia. We aimed to assess whether baricitinib improved pulmonary function in patients treated with high-dose corticosteroids for moderate to severe SARS-CoV-2 pneumonia. METHODS: This observational study enrolled patients with moderate to severe SARS-CoV-2 pneumonia [arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2) <200 mmHg] who received lopinavir/ritonavir and HCQ plus either corticosteroids (CS group, n = 50) or corticosteroids and baricitinib (BCT-CS group, n = 62). The primary end point was the change in oxygen saturation as measured by pulse oximetry (SpO2)/FiO2 from hospitalization to discharge. Secondary end points included the proportion of patients requiring supplemental oxygen at discharge and 1 month later. Statistics were adjusted by the inverse propensity score weighting (IPSW). RESULTS: A greater improvement in SpO2/FiO2 from hospitalization to discharge was observed in the BCT-CS vs CS group (mean differences adjusted for IPSW, 49; 95% CI: 22, 77; P < 0.001). A higher proportion of patients required supplemental oxygen both at discharge (62.0% vs 25.8%; reduction of the risk by 82%, OR adjusted for IPSW, 0.18; 95% CI: 0.08, 0.43; P < 0.001) and 1 month later (28.0% vs 12.9%, reduction of the risk by 69%, OR adjusted for IPSW, 0.31; 95% CI: 0.11, 0.86; P = 0.024) in the CS vs BCT-CS group. CONCLUSIONS: . In patients with moderate to severe SARS-CoV-2 pneumonia a combination of baricitinib with corticosteroids was associated with greater improvement in pulmonary function when compared with corticosteroids alone. TRIAL REGISTRATION: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, ENCEPP (EUPAS34966, http://www.encepp.eu/encepp/viewResource.htm? id = 34967).


Subject(s)
Azetidines/therapeutic use , COVID-19/drug therapy , Glucocorticoids/therapeutic use , Hypoxia/therapy , Janus Kinase Inhibitors/therapeutic use , Methylprednisolone/therapeutic use , Oxygen Inhalation Therapy/statistics & numerical data , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Aged , Antiviral Agents/therapeutic use , COVID-19/metabolism , COVID-19/physiopathology , Cohort Studies , Drug Combinations , Drug Therapy, Combination , Endothelium, Vascular , Enzyme Inhibitors/therapeutic use , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Interferon beta-1b/therapeutic use , Lopinavir/therapeutic use , Lung/blood supply , Male , Middle Aged , Oximetry , Prospective Studies , Ritonavir/therapeutic use , SARS-CoV-2 , Severity of Illness Index
4.
Cytometry A ; 97(9): 887-890, 2020 09.
Article in English | MEDLINE | ID: covidwho-1384155

ABSTRACT

In patients with severe SARS-CoV-2 infection, the development of cytokine storm induces extensive lung damage, and monocytes play a role in this pathological process. Non-classical (NC) and intermediate (INT) monocytes are known to be involved during viral and bacterial infections. In this study, 30 patients with different manifestations of acute SARS-CoV-2 infection were investigated with a flow cytometric study of NC, INT, and classical (CL) monocytes. Significantly reduced NC and INT monocytes and a downregulated HLA-DR were found in acute patients with severe SARS-CoV-2 symptoms. Conversely in patients with moderate symptoms NC and INT monocytes and CD11b expression were increased. © 2020 International Society for Advancement of Cytometry.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Monocytes/immunology , Pneumonia, Viral/immunology , Aged , Betacoronavirus/pathogenicity , Biomarkers/analysis , CD11b Antigen/analysis , COVID-19 , Cell Separation , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Female , Flow Cytometry , Host Microbial Interactions , Humans , Leukocytes , Male , Middle Aged , Monocytes/virology , Pandemics , Phenotype , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index
5.
Pharmacol Res ; 157: 104854, 2020 07.
Article in English | MEDLINE | ID: covidwho-1318928

ABSTRACT

SARS-CoV-2 is a novel strain, causing a global pandemic since the end of 2019. The majority of patients showed nonspecific symptoms such as fever, dry cough, and fatigue. Most patients have a good prognosis while some with severe conditions could rapidly progress to acute respiratory distress syndrome, septic shock, metabolic acidosis, coagulation dysfunction, and even die. The exacerbation of the patient's condition may be due to a cytokine storm in the body. Effective targeted therapies including antiviral and immunization are urgently needed. Although many clinical trials are already underway and the majority of patients have received antiviral therapy based on medication experience with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and preliminary results from some clinical trials, there are no antiviral drugs proven to be effective currently. We summarize the current therapeutic medicines used in the clinic, hope to be able to provide some implications for clinical medication.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Betacoronavirus/drug effects , COVID-19 , China , Humans , Pandemics , SARS-CoV-2
6.
Cureus ; 13(6): e15604, 2021 Jun 11.
Article in English | MEDLINE | ID: covidwho-1271055

ABSTRACT

Coronavirus disease 2019 (COVID-19) is associated with various cardiovascular manifestations, including myocarditis, myocardial infarction, and arrhythmias. A prothrombotic state is the primary underlying pathogenic mechanism. While cardiac arrhythmias manifest more commonly amongst critically ill COVID-19 populations, ventricular arrhythmias have been reported only in few cases. This report describes a case of a 95-year-old African American man with COVID-19, who developed sustained monomorphic ventricular tachycardia, which progressed to an electrical storm. The case highlights the importance of high clinical suspicion, early recognition of electrical abnormalities in patients with active COVID-19 infection, and its ability to precipitate fatal ventricular arrhythmia. Also, we provide a literature review on the electrical storm in COVID-19 patients, highlighting the pathophysiologic mechanisms and the management of this deadly arrhythmia.

7.
Brief Bioinform ; 22(6)2021 11 05.
Article in English | MEDLINE | ID: covidwho-1266105

ABSTRACT

Recent studies have demonstrated that the excessive inflammatory response is an important factor of death in coronavirus disease 2019 (COVID-19) patients. In this study, we propose a deep representation on heterogeneous drug networks, termed DeepR2cov, to discover potential agents for treating the excessive inflammatory response in COVID-19 patients. This work explores the multi-hub characteristic of a heterogeneous drug network integrating eight unique networks. Inspired by the multi-hub characteristic, we design 3 billion special meta paths to train a deep representation model for learning low-dimensional vectors that integrate long-range structure dependency and complex semantic relation among network nodes. Based on the representation vectors and transcriptomics data, we predict 22 drugs that bind to tumor necrosis factor-α or interleukin-6, whose therapeutic associations with the inflammation storm in COVID-19 patients, and molecular binding model are further validated via data from PubMed publications, ongoing clinical trials and a docking program. In addition, the results on five biomedical applications suggest that DeepR2cov significantly outperforms five existing representation approaches. In summary, DeepR2cov is a powerful network representation approach and holds the potential to accelerate treatment of the inflammatory responses in COVID-19 patients. The source code and data can be downloaded from https://github.com/pengsl-lab/DeepR2cov.git.


Subject(s)
COVID-19/drug therapy , Drug Repositioning , Inflammation/drug therapy , SARS-CoV-2/drug effects , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , COVID-19/genetics , COVID-19/virology , Computational Biology , Deep Learning , Humans , Inflammation/complications , Inflammation/genetics , Inflammation/virology , Neural Networks, Computer , SARS-CoV-2/pathogenicity , Software , Transcriptome/drug effects , Transcriptome/genetics
8.
FASEB J ; 35(6): e21666, 2021 06.
Article in English | MEDLINE | ID: covidwho-1242109

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 is responsible for coronavirus disease 2019 (COVID-19). While COVID-19 is often benign, a subset of patients develops severe multilobar pneumonia that can progress to an acute respiratory distress syndrome. There is no cure for severe COVID-19 and few treatments significantly improved clinical outcome. Dexamethasone and possibly aspirin, which directly/indirectly target the biosynthesis/effects of numerous lipid mediators are among those options. Our objective was to define if severe COVID-19 patients were characterized by increased bioactive lipids modulating lung inflammation. A targeted lipidomic analysis of bronchoalveolar lavages (BALs) by tandem mass spectrometry was done on 25 healthy controls and 33 COVID-19 patients requiring mechanical ventilation. BALs from severe COVID-19 patients were characterized by increased fatty acids and inflammatory lipid mediators. There was a predominance of thromboxane and prostaglandins. Leukotrienes were also increased, notably LTB4 , LTE4 , and eoxin E4 . Monohydroxylated 15-lipoxygenase metabolites derived from linoleate, arachidonate, eicosapentaenoate, and docosahexaenoate were also increased. Finally yet importantly, specialized pro-resolving mediators, notably lipoxin A4 and the D-series resolvins, were also increased, underscoring that the lipid mediator storm occurring in severe COVID-19 involves pro- and anti-inflammatory lipids. Our data unmask the lipid mediator storm occurring in the lungs of patients afflicted with severe COVID-19. We discuss which clinically available drugs could be helpful at modulating the lipidome we observed in the hope of minimizing the deleterious effects of pro-inflammatory lipids and enhancing the effects of anti-inflammatory and/or pro-resolving lipid mediators.


Subject(s)
COVID-19 , Leukotriene B4/metabolism , Leukotriene E4/analogs & derivatives , Leukotriene E4/metabolism , Lipoxins/metabolism , Lung , SARS-CoV-2/metabolism , Adult , COVID-19/metabolism , COVID-19/pathology , COVID-19/therapy , Female , Humans , Lung/metabolism , Lung/pathology , Lung/virology , Male , Middle Aged
9.
J Med Virol ; 93(1): 8-19, 2021 01.
Article in English | MEDLINE | ID: covidwho-1196413

ABSTRACT

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has led to the elaboration of multiple studies to increase knowledge and understanding, hence, having the ability to accomplish an adequate and timely diagnosis and give an optimal treatment according to the patient's condition. The clinical manifestations of COVID-19 pose a series of challenges both in understanding and delimiting the disease secondary to the SARS-CoV-2 infection. This is due to the fact that the main axis of this disease is the endothelial compromise and the production of a "cytokine storm," triggering multiple organ failure and death. Given that a complete understanding of its pathophysiology and clinical behavior has not yet been achieved, we wondered if coinfection with other respiratory viruses modifies its performance and outcomes described so far. A literature search was performed, obtaining 68 articles, of which 25 were analyzed. The analysis showed us that there is a high variety both in the types of associated infections and in the clinical behavior of patients and their outcomes. Therefore, we consider that the search for other infections should be performed exhaustively, especially in those cases that may be susceptible to treatment such as Influenza A, human immunodeficiency virus, or bacterial infections. As well as optimize the analysis of these cases and establish if there are characteristics that allow establishing the possibility of carrying an additional infection to that of SARS-CoV-2 and the implications for the management and prognosis of the patient.


Subject(s)
Bacterial Infections/complications , COVID-19/complications , Coinfection/virology , HIV Infections/complications , Influenza, Human/complications , SARS-CoV-2 , Humans
10.
Clin Infect Dis ; 72(7): 1247-1250, 2021 04 08.
Article in English | MEDLINE | ID: covidwho-1174886

ABSTRACT

Hyperinflammation is associated with increased mortality in coronavirus disease 2019 (COVID-19). In this retrospective, uncontrolled patient cohort with moderate -severe COVID-19, treatment with baricitinib plus hydroxychloroquine was associated with recovery in 11 of 15 patients. Baricitinib for the treatment of COVID-19 should be further investigated in randomized, controlled clinical trials.


Subject(s)
COVID-19 , Antiviral Agents/therapeutic use , Azetidines , COVID-19/drug therapy , Humans , Purines , Pyrazoles , Retrospective Studies , SARS-CoV-2 , Sulfonamides , Treatment Outcome
11.
Curr Stem Cell Res Ther ; 16(2): 105-108, 2021.
Article in English | MEDLINE | ID: covidwho-1136354

ABSTRACT

A novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) has emerged in Wuhan, China since the end of December 2019 and has quickly spread all over the world in a matter of two months. To date, no specific treatment has been proven to be effective for coronavirus (COVID-19). With the rapid increase of infected patients and deaths, it is vital to explore an effective treatment for COVID-19. Current studies suggest that there exists cytokine storm in SARS-CoV-2-infected patients; some of the them will develop acute respiratory distress syndrome (ARDS) and multiple organ dysfunction, and even death. Mesenchymal stem cells (MSCs) possess the property of immunomodulation. Given the previous preclinical and clinical studies, MSCs therapy has shown safety and efficacy in the treatment of respiratory failure or ARDS. Based on similar principles, MSCs therapy may also be an effective therapy in the treatment of COVID-19. In this study, we summarized the clinical outcomes of MSCs for ARDS patients in some preclinical and clinical studies and discussed the application of MSCs for patients with COVID-19 in China and the related important issues with MSCs used during the outbreak.


Subject(s)
COVID-19/therapy , COVID-19/virology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , SARS-CoV-2/physiology , Animals , COVID-19/epidemiology , China/epidemiology , Clinical Trials as Topic , Humans , Pandemics
12.
Dermatol Ther (Heidelb) ; 11(2): 339-345, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1083623

ABSTRACT

INTRODUCTION: The inflammation storm involved in coronavirus disease 2019 (COVID-19) infection and worsening and the psychological stress derived from current quarantine conditions can affect the course of many skin and scalp conditions. This study examined the possible effects of COVID-19 on alopecia areata (AA) relapse in patients suffering from these scalp conditions during the pandemic. METHODS: The study was carried out in the form of an observational cross-sectional type using a questionnaire sent by mail to a cohort of patients affected by AA during the pandemic from March 2020 to October 2020. RESULTS: During the pandemic, AA relapse was reported in 42.5% of the participants who also declared COVID-19 infection, confirmed by nasopharyngeal swab or hematological analysis. The relapse was reported about 2 months later COVID-19 infection (median of 2.14 months) and 74.0% of these participants continue to experience AA symptoms when the survey was proposed. Only 12.5% of participants reported AA relapse in the absence of COVID-19 infection. CONCLUSIONS: The present study reported a significant relapse in patients suffering from AA and infected by COVID-19. This phenomenon could be attributed to the inflammation storm typical of COVID-19 infection and the psychological stress derived from quarantine conditions.

13.
Chest ; 159(3): 933-948, 2021 03.
Article in English | MEDLINE | ID: covidwho-1064923

ABSTRACT

BACKGROUND: Cytokine storm is a marker of coronavirus disease 2019 (COVID-19) illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes. RESEARCH QUESTION: Do immunomodulatory therapies improve survival in patients with COVID-19 cytokine storm (CCS)? STUDY DESIGN AND METHODS: We conducted a retrospective analysis of electronic health records across the Northwell Health system. COVID-19 patients hospitalized between March 1, 2020, and April 24, 2020, were included. CCS was defined by inflammatory markers: ferritin, > 700 ng/mL; C-reactive protein (CRP), > 30 mg/dL; or lactate dehydrogenase (LDH), > 300 U/L. Patients were subdivided into six groups: no immunomodulatory treatment (standard of care) and five groups that received either corticosteroids, anti-IL-6 antibody (tocilizumab), or anti-IL-1 therapy (anakinra) alone or in combination with corticosteroids. The primary outcome was hospital mortality. RESULTS: Five thousand seven hundred seventy-six patients met the inclusion criteria. The most common comorbidities were hypertension (44%-59%), diabetes (32%-46%), and cardiovascular disease (5%-14%). Patients most frequently met criteria with high LDH (76.2%) alone or in combination, followed by ferritin (63.2%) and CRP (8.4%). More than 80% of patients showed an elevated D-dimer. Patients treated with corticosteroids and tocilizumab combination showed lower mortality compared with patients receiving standard-of-care (SoC) treatment (hazard ratio [HR], 0.44; 95% CI, 0.35-0.55; P < .0001) and with patients treated with corticosteroids alone (HR, 0.66; 95% CI, 0.53-0.83; P = .004) or in combination with anakinra (HR, 0.64; 95% CI, 0.50-0.81; P = .003). Corticosteroids when administered alone (HR, 0.66; 95% CI, 0.57-0.76; P < .0001) or in combination with tocilizumab (HR, 0.43; 95% CI, 0.35-0.55; P < .0001) or anakinra (HR, 0.68; 95% CI, 0.57-0.81; P < .0001) improved hospital survival compared with SoC treatment. INTERPRETATION: The combination of corticosteroids with tocilizumab showed superior survival outcome when compared with SoC treatment as well as treatment with corticosteroids alone or in combination with anakinra. Furthermore, corticosteroid use either alone or in combination with tocilizumab or anakinra was associated with reduced hospital mortality for patients with CCS compared with patients receiving SoC treatment.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19 , Cytokine Release Syndrome , Immunomodulation , Interleukin 1 Receptor Antagonist Protein/administration & dosage , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Cytokine Release Syndrome/virology , Drug Repositioning , Drug Therapy, Combination/methods , Electronic Health Records/statistics & numerical data , Humans , Immunosuppressive Agents/administration & dosage , Medication Therapy Management/statistics & numerical data , Middle Aged , Outcome and Process Assessment, Health Care , Retrospective Studies , SARS-CoV-2/immunology , Severity of Illness Index , Survival Analysis , United States/epidemiology
14.
Adv Ther ; 38(1): 782-791, 2021 01.
Article in English | MEDLINE | ID: covidwho-1064616

ABSTRACT

INTRODUCTION: The COVID-19 global pandemic caused by the novel coronavirus, SARS-CoV-2, and the consequent morbidity and mortality attributable to progressive hypoxemia and subsequent respiratory failure threaten to overrun hospital critical care units globally. New agents that address the hyperinflammatory "cytokine storm" and hypercoagulable pathology seen in these patients may be a promising approach to treat patients, minimize hospital stays, and ensure hospital wards and critical care units are able to operate effectively. Dociparstat sodium (DSTAT) is a glycosaminoglycan derivative of heparin with robust anti-inflammatory properties, with the potential to address underlying causes of coagulation disorders with substantially reduced risk of bleeding compared to commercially available heparin. METHODS: This study is a randomized, double-blind, placebo-controlled, phase 2/3 trial to determine the safety and efficacy of DSTAT added to standard of care in hospitalized adults with COVID-19 who require supplemental oxygen. Phase 2 will enroll 12 participants in each of two dose-escalating cohorts to confirm the safety of DSTAT in this population. Following review of the data, an additional 50 participants will be enrolled. Contingent upon positive results, phase 3 will enroll approximately 450 participants randomized to DSTAT or placebo. The primary endpoint is the proportion of participants who survive and do not require mechanical ventilation through day 28. DISCUSSION: Advances in standard of care, recent emergency use authorizations, and positive data with dexamethasone have likely contributed to an increasing proportion of patients who are surviving without the need for mechanical ventilation. Therefore, examining the time to improvement in the NIAID score will be essential to provide a measure of drug effect on recovery. Analysis of additional endpoints, including supportive biomarkers (e.g., IL-6, HMGB1, soluble-RAGE, D-dimer), will be performed to further define the effect of DSTAT in patients with COVID-19 infection. TRIAL REGISTRATION: ClinicalTrials.gov identifier; NCT04389840, Registered 13 May 2020.


Subject(s)
Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Heparin/therapeutic use , Respiratory Insufficiency/drug therapy , Acute Lung Injury/etiology , Adult , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Male , Middle Aged , Respiratory Insufficiency/etiology , SARS-CoV-2/drug effects , Treatment Outcome
15.
iScience ; 23(10): 101611, 2020 Oct 23.
Article in English | MEDLINE | ID: covidwho-1065230

ABSTRACT

The molecular mechanisms of cytokine storm in patients with severe COVID-19 infections are poorly understood. To uncover these events, we performed transcriptome analyses of lung biopsies from patients with COVID-19, revealing a gene enrichment pattern similar to that of PPARγ-knockout macrophages. Single-cell gene expression analysis of bronchoalveolar lavage fluids revealed a characteristic trajectory of PPARγ-related disturbance in the CD14+/CD16+ cells. We identified a correlation with the disease severity and the reduced expression of several members of the PPARγ complex such as EP300, RXRA, RARA, SUMO1, NR3C1, and CCDC88A. ChIP-seq analyses confirmed repression of the PPARγ-RXRA-NR3C1 cistrome in COVID-19 lung samples. Further analysis of protein-protein networks highlighted an interaction between the PPARγ-associated protein SUMO1 and a nucleoprotein of the SARS virus. Overall, these results demonstrate for the first time the involvement of the PPARγ complex in severe COVID-19 lung disease and suggest strongly its role in the major monocyte/macrophage-mediated inflammatory storm.

16.
Can J Respir Ther ; 56: 25-31, 2020.
Article in English | MEDLINE | ID: covidwho-1060415

ABSTRACT

The global pandemic COVID-19 is a contagious disease and its mortality rates ranging from 1% to 5% are likely due to acute respiratory distress syndrome (ARDS), and cytokine storm. A significant proportion of patients who require intubation succumb to the disease, despite the availability of ventilators and the best treatment practices. Researchers worldwide are in search of anti-inflammatory medicines in the hope of finding a cure for COVID-19. Low-level laser therapy (LLLT) has strong, anti-inflammatory effects confirmed by meta-analyses, and it may be therapeutic to ARDS. LLLT has been used for pain management, wound healing, and other health conditions by physicians, physiotherapists, and nurses worldwide for decades. In addition, it has been used in veterinary medicine for respiratory tract disease such as pneumonia. Laser light with low-power intensity is applied to the surface of the skin to produce local and systemic effects. Based on the clinical experience, peer-reviewed studies, and solid laboratory data in experimental animal models, LLLT attenuates cytokine storm at multiple levels and reduces the major inflammatory metabolites. LLLT is a safe, effective, low-cost modality without any side-effects that may be combined with conventional treatment of ARDS. We summarize the effects of LLLT on pulmonary inflammation and we provide a protocol for augmenting medical treatment in COVID-19 patients. LLLT combined with conventional medical therapy has the potential to prevent the progression of COVID-19, minimize the length of time needed on a ventilator, enhance the healing process, and shorten recovery time.

17.
J Clin Med ; 9(9)2020 Sep 14.
Article in English | MEDLINE | ID: covidwho-1021973

ABSTRACT

The repurposing of colchicine for the treatment of COVID-19 was suggested based in its immunomodulatory, anti-inflammatory, and anti-viral properties. We performed a single-center propensity score matched cohort study, including all consecutive COVID-19 patients admitted to a community hospital between 1 March 2020 and 30 May 2020. Patients were stratified according to the receipt of colchicine. The primary endpoint was defined as in-hospital death within 28-days follow-up. Secondary endpoints included favorable change in the Ordinal Scale for Clinical Improvement on days 14 and 28 versus baseline, proportion of patients not requiring supplemental oxygen on days 14 and 28, and proportion of patients discharged by day 28. In total data for 303 PCR positive COVID-19 patients were extracted and 66 patients were included in the 1:1 matched cohort study. At the end of the 28 day follow-up, patients receiving colchicine were approximately five times more likely to be discharged (odds ratio, 5.0; 95% confidence interval, 1.25-20.1; p = 0.023) and when comparing mortality, there were 3 deaths (9.1%) in patients receiving colchicine versus 11 deaths (33.3%) in the groups receiving standard of care (odds ratio, 0.20; 95% confidence interval, 0.05-0.80; p = 0.023). These observations warrant further investigation in large controlled clinical trials.

18.
Br J Pharmacol ; 177(21): 4873-4886, 2020 11.
Article in English | MEDLINE | ID: covidwho-998831

ABSTRACT

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overwhelmed healthcare systems requiring the rapid development of treatments, at least, to reduce COVID-19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID-19 patients based on evidence that they may target virus receptors, replication, degradation, and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could modulate virus entry, acting on the SARS-CoV-2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well-known anti-inflammatory properties of statins, by blocking several molecular mechanisms, including NF-κB and NLRP3 inflammasomes, could limit the "cytokine storm" in severe COVID-19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improving COVID-19 outcomes. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.


Subject(s)
Coronavirus Infections/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Pneumonia, Viral/drug therapy , Animals , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokines/immunology , Drug Repositioning , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Virus Internalization/drug effects
19.
J Zhejiang Univ Sci B ; 21(12): 921-939, 2020.
Article in English | MEDLINE | ID: covidwho-999888

ABSTRACT

The coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a matter of months, this highly contagious novel virus has led to a global outbreak and is still spreading rapidly across continents. In patients with COVID-19, underlying chronic diseases and comorbidities are associated with dismal treatment outcomes. Owing to their immunosuppressive status, patients with hematological malignancies (HMs) are at an increased risk of infection and have a worse prognosis than patients without HMs. Accordingly, intensive attention should be paid to this cohort. In this review, we summarize and analyze specific clinical manifestations for patients with coexisting COVID-19 and HMs. Furthermore, we briefly describe customized management strategies and interventions for this susceptible cohort. This review is intended to guide clinical practice.


Subject(s)
COVID-19/complications , Hematologic Neoplasms/complications , COVID-19/diagnosis , COVID-19/prevention & control , Diagnosis, Differential , Disease Management , Hematologic Neoplasms/diagnosis , Hematologic Neoplasms/virology , Hospitalization , Humans , Immunocompromised Host , Risk Factors
20.
Orv Hetil ; 161(50): 2099-2103, 2020 12 13.
Article in Hungarian | MEDLINE | ID: covidwho-992775

ABSTRACT

Összefoglaló. Bevezetés: Egy új, számítógép által segített betegminta-asszociációs analízis eredménye szerint a COVID-19 tüneteinek kialakításában kiemelt tényezoként jelenik meg a bradikinin. Eszerint a bradikinin lebontása lelassul az angiotenzinkonvertáló enzim aktivitásának csökkenése miatt, ami jelentosen megemelkedo bradikininszinthez vezet a tüdoben. Nem merült fel azonban a véralvadási faktorok lehetséges szerepe a "bradikininviharban", annak ellenére, hogy az idosebb cardiovascularis betegekben aktiválódó XII-es faktor és a C1-észteráz-inhibitor (C1INH) alacsony szintje nagy mennyiségu bradikinin képzodéséhez vezethet. Módszer: Átfogó irodalmi áttekintés. Eredmények: 1) A vírus által fertozött, sérült endotheliumsejtek felülete az a hely, amellyel érintkezve elindulhat a XII-es véralvadási faktor aktivációja - ez serkenti a prekallikrein/kallikrein/kinin rendszert, és bradikininképzodést okoz. Ez a folyamat megtörténik a súlyos vese- és tüdokárosodást okozó hantavírus-fertozésekben. 2) Idos betegekben az atherosclerosis miatt többszörösen sérült, merev, "stiff" erek endotheliumfelszínein jóval magasabb lehet a XII-es faktor kontakt úton történo aktivációja, mint a fiatal egyének ereiben. Ez a tény egyik oka lehet az idos, cardiovascularis betegek körében tapasztalt magasabb halálozásnak. Következtetés: Az aktivált XII-es véralvadási faktor célzott gátlása újabb gyógyítási lehetoség lehet a SARS-CoV-2-fertozött idos betegekben. Jelenleg már hatásosnak bizonyult a bradikininképzést gátló C1INH-nak, továbbá a bradikininreceptor-gátlóknak az adása is. Orv Hetil. 2020; 161(50): 2099-2103. INTRODUCTION: Bradykinin was implicated in a new complex model of pathomechanism leading to the symptoms of COVID-19 created by a computer-assisted association analysis. According to this model, the decrease in angiotensin-converting enzyme expression leads to impaired bradykinin elimination and subsequent enrichment in the lungs. However, there is no mentioning of the importance of blood coagulation factor XII in increased bradykinin production, in spite of its age-dependent activation and the lower level of C1-esterase inhibitor (C1INH). Activated factor XII may be an important contributor to the "bradykinin storm" in elder cardiovascular patients. METHOD: Literature review. RESULTS: 1) Activation of the coagulation factor XII on the surface of SARS-CoV-2 infected endothelial cells may trigger the prekallikrein/kallikrein/kinin system producing bradykinin. Such process is taking place in hantavirus infections causing severe lung and kidney damages. 2) The endothelial system is dysregulated in elderly patients, resulting in potentially higher factor XII activities on the surface of damaged endothelial cells in the stiffened arteries. This can contribute to the higher mortality rates in the elderly. CONCLUSION: The targeted inhibition of activated blood coagulation factor XII may represent a new therapeutic target for COVID-19, especially for elder patients. Recently, beneficial results have already been observed by the clinical applications of recombinant C1INH and bradykinin receptor antagonists. Orv Hetil. 2020; 161(50): 2099-2103.


Subject(s)
Betacoronavirus , Bradykinin , Factor XIIa , Age Factors , Aged , Angiotensin-Converting Enzyme Inhibitors , COVID-19 , Complement C1 Inhibitor Protein , Endothelial Cells , Humans , SARS-CoV-2
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