Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 31
Filter
1.
Acta Pharmacol Sin ; 42(11): 1913-1920, 2021 11.
Article in English | MEDLINE | ID: covidwho-1437673

ABSTRACT

Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.


Subject(s)
COVID-19 , Colitis, Ulcerative , Disulfiram/pharmacokinetics , Lactoferrin , Systemic Inflammatory Response Syndrome , Acetaldehyde Dehydrogenase Inhibitors/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Biomimetic Materials/pharmacology , COVID-19/drug therapy , COVID-19/immunology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/immunology , Disease Models, Animal , Disulfiram/pharmacology , Drug Carriers/pharmacology , Humans , Immunosuppressive Agents/pharmacology , Lactoferrin/metabolism , Lactoferrin/pharmacology , Lipopolysaccharides/immunology , Macrophages/drug effects , Macrophages/immunology , Mice , Mice, Inbred C57BL , Nanoparticles/therapeutic use , Pyroptosis/drug effects , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/metabolism , Treatment Outcome
2.
Ann Hematol ; 100(11): 2805-2812, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1432514

ABSTRACT

Rituximab is associated with prolonged B-cell depletion and secondary hypogammaglobulinemia and is associated with a dampened humoral response and increased infectious complications. To describe the potential impact of prior rituximab therapy on clinical outcomes from SARS-CoV-2 infection and development of COVID-19 antibodies, we conducted a retrospective study of adults across the Mount Sinai Health System diagnosed with COVID-19 who received rituximab for any indication from February 2019 to October 2020. Patients' baseline characteristics, markers of disease severity, clinical outcomes, and antibody development were examined. Of the 49 patients included in the analysis, 63.2% required hospitalization for COVID-19, 24.5% required an ICU admission, and 32.7% died. Proximity of last rituximab infusion and COVID-19 diagnosis did not affect rates of hospitalization, admission to intensive care units or death. Over half (51.7%) of those whose antibodies were checked developed neutralizing anti-spike protein antibodies. The median time between rituximab administration and COVID-19 diagnosis was not significantly different between those who developed antibodies and those who did not (p = .323). Of the 14 patients with documented negative COVID-19 antibody titers, 11 of them survived SARS-CoV-2 infection, indicating that development of neutralizing antibodies may not be necessary for recovery from COVID-19.


Subject(s)
COVID-19/epidemiology , Immunosuppressive Agents/pharmacology , Rituximab/pharmacology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , COVID-19/therapy , Comorbidity , Female , Hospitalization , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Intensive Care Units , Male , Middle Aged , Retrospective Studies , Risk Factors , Rituximab/adverse effects , Rituximab/therapeutic use , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Treatment Outcome
3.
J Neuroimmunol ; 359: 577696, 2021 10 15.
Article in English | MEDLINE | ID: covidwho-1356324

ABSTRACT

AIM: To determine the influence of high-efficacy disease modifying therapy (DMT) on the development of IgG SARS-CoV-2 antibody response in COVID-19 convalescent people with multiple sclerosis (pwMS). METHODS: Seventy-four pwMS taking high-efficacy DMTs (specifically natalizumab, fingolimod, alemtuzumab, ocrelizumab, cladribine and ublituximab) and diagnosed with COVID-19 and 44 healthy persons (HC) were enrolled. SARS-CoV2 antibodies were tested with Elecsys® Anti-SARSCoV-2 S assay. RESULTS: pwMS taking high-efficacy DMTs had a significantly higher chance of having negative titer of SARS-CoV2 antibodies compared to healthy controls (33 negative pwMS [44.6%] compared to one negative HC [2.3%], p < 0.001). pwMS taking B-cell depleting therapy (ocrelizumab and ublituximab) had a significantly higher chance of having negative titer of SARS-CoV2 antibodies compared to pwMS on all other DMTs (29 negative pwMS on B-cell therapy [64.4%] compared to four negative pwMS on all other DMTs [13.8%], p < 0.001). Out of other DMTs, two (33.3%) pwMS taking fingolimod and two (16.7%) pwMS taking cladribine failed to develop IgG SARS-COV-2 antibodies. B-cell depleting therapy independently predicted negative titer of IgG SARS-CoV-2 antibody (Exp[B] =0.014, 95%CI 0.002-0.110, p < 0.001). CONCLUSIONS: A significant proportion of convalescent COVID-19 pwMS on high-efficacy DMTs will not develop IgG SARS-CoV-2 antibodies. B-cell depleting therapies independently predict negative and low titer of IgG SARS-CoV-2 antibody.


Subject(s)
COVID-19/drug therapy , COVID-19/immunology , Immunity, Humoral/immunology , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , SARS-CoV-2/immunology , Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , Case-Control Studies , Female , Humans , Immunity, Humoral/drug effects , Immunologic Factors/pharmacology , Immunosuppressive Agents/pharmacology , Male , Middle Aged , SARS-CoV-2/metabolism , Treatment Outcome
5.
Cells ; 10(5)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1274611

ABSTRACT

Th17 cells are recognized as indispensable in inducing protective immunity against bacteria and fungi, as they promote the integrity of mucosal epithelial barriers. It is believed that Th17 cells also play a central role in the induction of autoimmune diseases. Recent advances have evaluated Th17 effector functions during viral infections, including their critical role in the production and induction of pro-inflammatory cytokines and in the recruitment and activation of other immune cells. Thus, Th17 is involved in the induction both of pathogenicity and immunoprotective mechanisms seen in the host's immune response against viruses. However, certain Th17 cells can also modulate immune responses, since they can secrete immunosuppressive factors, such as IL-10; these cells are called non-pathogenic Th17 cells. Here, we present a brief review of Th17 cells and highlight their involvement in some virus infections. We cover these notions by highlighting the role of Th17 cells in regulating the protective and pathogenic immune response in the context of viral infections. In addition, we will be describing myocarditis and multiple sclerosis as examples of immune diseases triggered by viral infections, in which we will discuss further the roles of Th17 cells in the induction of tissue damage.


Subject(s)
Myocarditis/immunology , Th17 Cells/metabolism , Virus Diseases/immunology , Adenoviridae , Animals , Autoimmune Diseases/immunology , Chikungunya virus , Cytokines/immunology , Dengue Virus , Humans , Immune System , Immunosuppressive Agents/pharmacology , Inflammation , Interleukin-10/biosynthesis , Lymphocytes/cytology , Multiple Sclerosis/immunology , Multiple Sclerosis/metabolism , Multiple Sclerosis/virology , Myocarditis/metabolism , Myocarditis/virology , Orthomyxoviridae , SARS-CoV-2 , Simplexvirus , Th1 Cells/cytology , Th2 Cells/cytology , Virus Diseases/drug therapy , Virus Diseases/metabolism , Zika Virus
6.
Sci Rep ; 11(1): 11462, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1253984

ABSTRACT

An excessive immune response known as cytokine storm is the hallmark of severe COVID-19. The cause of this cytokine rampage is yet not known. Based on recent epidemiological evidence, we hypothesized that CD80/86 signaling is essential for this hyperinflammation, and that blocking this proinflammatory axis could be an effective therapeutic approach to protect against severe COVID-19. Here we provide exploratory evidence that abatacept, a drug that blocks CD80/86 co-stimulation, produces changes at the systemic level that are highly antagonistic of the proinflammatory processes elicited by COVID-19. Using RNA-seq from blood samples from a longitudinal cohort of n = 38 rheumatic patients treated with abatacept, we determined the immunological processes that are significantly regulated by this treatment. We then analyzed available blood RNA-seq from two COVID19 patient cohorts, a very early cohort from the epicenter of the pandemic in China (n = 3 COVID-19 cases and n = 3 controls), and a recent and larger cohort from the USA (n = 49 severe and n = 51 mild COVD-19 patients). We found a highly significant antagonism between SARS-CoV-2 infection and COVID-19 severity with the systemic response to abatacept. Analysis of previous single-cell RNA-seq data from bronchoalveolar lavage fluid from mild and severe COVID-19 patients and controls, reinforce the implication of the CD80/86 proinflammatory axis. Our functional results further support abatacept as a candidate therapeutic approach to prevent severe COVID-19.


Subject(s)
Abatacept/pharmacology , COVID-19/drug therapy , Cytokine Release Syndrome/prevention & control , Immunosuppressive Agents/pharmacology , SARS-CoV-2/immunology , Signal Transduction/drug effects , Abatacept/therapeutic use , Aged , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , B7-1 Antigen/metabolism , B7-2 Antigen/metabolism , Bronchoalveolar Lavage Fluid/cytology , COVID-19/blood , COVID-19/complications , COVID-19/immunology , China , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Observational Studies as Topic , RNA-Seq , Severity of Illness Index , Signal Transduction/immunology , Single-Cell Analysis , Spain , United States , Up-Regulation/drug effects , Up-Regulation/immunology
7.
Int Immunopharmacol ; 96: 107761, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1253056

ABSTRACT

Since the discovery of lymphocytes with immunosuppressive activity, increasing interest has arisen in their possible influence on the immune response induced by vaccines. Regulatory T cells (Tregs) are essential for maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammatory diseases. However, they also limit beneficial immune responses by suppressing anti-infectious and anti-tumor immunity. Mounting evidence suggests that Tregs are involved, at least in part, in the low effectiveness of immunization against various diseases where it has been difficult to obtain protective vaccines. Interestingly, increased activity of Tregs is associated with aging, suggesting a key role for these cells in the lower vaccine effectiveness observed in older people. In this review, we analyze the impact of Tregs on vaccination, with a focus on older adults. Finally, we address an overview of current strategies for Tregs modulation with potential application to improve the effectiveness of future vaccines targeting older populations.


Subject(s)
Autoimmune Diseases/therapy , Chronic Disease/therapy , Inflammation/therapy , T-Lymphocytes, Regulatory/physiology , Vaccines/immunology , Age Factors , Aged , Aged, 80 and over , Animals , Autoimmune Diseases/immunology , Humans , Immunologic Factors/pharmacology , Immunomodulation/physiology , Immunosuppressive Agents/pharmacology , Inflammation/immunology , Membrane Proteins/metabolism , Middle Aged , Vaccination
8.
Transplantation ; 105(9): 2119-2123, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1240980

ABSTRACT

BACKGROUND: Belatacept may impair humoral immunity, impacting the effectiveness of SARS-CoV-2 mRNA vaccines in transplant recipients. We investigated immunogenicity after SARS-CoV-2 mRNA vaccines in kidney transplant recipients who are and are not taking belatacept. METHODS: Participants were recruited between December 9, 2020, and April 1, 2021. Blood samples were collected after dose 1 and dose 2 (D1, D2) and analyzed using either an anti-SARS-CoV-2 enzyme immunoassay against the S1 domain of the SARS-CoV-2 spike protein or immunoassay against the receptor-binding domain of the SARS-CoV-2 spike protein. Stabilized inverse probability of treatment weights was used to compare immunogenicity, and a weighted logistics regression was used to calculate fold change of positive response. RESULTS: Among the 609 participants studied, 24 (4%) were taking belatacept. After dose 1, 0/24 (0%) belatacept patients had detectable antibodies, compared with 77 of 568 (14%) among the equivalent nonbelatacept population (P = 0.06). After dose 2, 1/19 (5%) belatacept patients had detectable antibodies, compared with 190/381 (50%) among the equivalent nonbelatacept population (P < 0.001). Belatacept use was associated with 16.7-fold lower odds of having a positive post-D2 titer result (P < 0.01). CONCLUSIONS: Additional measures need to be explored to protect kidney transplant recipients taking belatacept. Best safety practices should be continued despite vaccination among this population.


Subject(s)
Abatacept/pharmacology , COVID-19/epidemiology , Graft Rejection/immunology , Immunity, Humoral , Kidney Transplantation/adverse effects , RNA, Viral/analysis , Renal Insufficiency/surgery , Aged , Antibodies, Viral/blood , Comorbidity , Female , Follow-Up Studies , Graft Rejection/drug therapy , Humans , Immunosuppressive Agents/pharmacology , Male , Middle Aged , Pandemics , Renal Insufficiency/epidemiology , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/immunology
9.
Drugs ; 81(5): 605-610, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1159706

ABSTRACT

Voclosporin (Lupkynis™) is an oral calcineurin inhibitor immunosuppressant that is being developed by Aurinia Pharmaceuticals. In January 2021, based on positive results from the pivotal phases II and III trials, oral voclosporin received its first approval in the USA for use in combination with a background immunosuppressive therapy regimen for adults with active lupus nephritis. Voclosporin is also being explored for the novel coronavirus disease 2019 (COVID-19) in kidney transplant recipients. This article summarizes the milestones in the development of voclosporin leading to this first approval for lupus nephritis.


Subject(s)
COVID-19/drug therapy , Calcineurin Inhibitors/therapeutic use , Cyclosporine/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Animals , COVID-19/complications , Calcineurin Inhibitors/pharmacokinetics , Calcineurin Inhibitors/pharmacology , Cyclosporine/pharmacokinetics , Cyclosporine/pharmacology , Drug Approval , Humans , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/pharmacology , Lupus Nephritis/drug therapy
10.
Ann Transplant ; 26: e929279, 2021 Mar 12.
Article in English | MEDLINE | ID: covidwho-1154830

ABSTRACT

Coronavirus disease 19 (COVID-19) has been an ongoing pandemic since December 2019. Unfortunately, kidney transplant recipients are a high-risk group during the disease course, and scientific data are still limited in this patient group. Beyond the dosage of immunosuppressive drugs, pharmacological immunosuppression may also alter the infection response in the COVID-19 course. The effects of immunosuppressive agents on the development and process of infection should not be decided only by determining how potent they are and how much they suppress the immune system; it is also thought that the direct effect of the virus, increased oxidative stress, and cytokine storm play a role in the pathogenesis of COVID-19 disease. There are data about immunosuppressive drugs like calcineurin inhibitors (CNI) or mammalian target of rapamycin inhibitors (mTORi) therapy related to their beneficial effects during any infection course. Limited data suggest that the use of CNI or mTORi may have beneficial effects on the process. In this hypothetical review, the probable impacts of CNI and mTORi on the pathogenesis of the COVID-19 were investigated.


Subject(s)
COVID-19/immunology , Calcineurin Inhibitors/therapeutic use , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Postoperative Complications/immunology , Protein Kinase Inhibitors/therapeutic use , Adaptive Immunity/drug effects , COVID-19/diagnosis , Calcineurin Inhibitors/pharmacology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/prevention & control , Cytokine Release Syndrome/virology , Graft Rejection/immunology , Humans , Immunity, Innate/drug effects , Immunocompromised Host , Immunosuppressive Agents/pharmacology , Oxidative Stress/drug effects , Oxidative Stress/immunology , Postoperative Complications/diagnosis , Postoperative Complications/virology , Protein Kinase Inhibitors/pharmacology , TOR Serine-Threonine Kinases/antagonists & inhibitors
11.
Rev Neurol ; 72(7): 250-260, 2021 04 01.
Article in Spanish | MEDLINE | ID: covidwho-1151140

ABSTRACT

INTRODUCTION: The recent availability of SARS-CoV-2 vaccines has raised concerns in certain patient groups, such as those with multiple sclerosis. However, there are currently few publications that provide information on this issue. We pooled the information available on the safety and efficacy of vaccination against SARS-CoV-2 in patients with multiple sclerosis, with and without disease-modifying therapy. DEVELOPMENT: The study consisted in a literature search focused on the types of SARS-CoV-2 vaccines, the current status of their approval, and the data available on the safety and efficacy of vaccines in patients with multiple sclerosis, including the new COVID-19 vaccines. Based on this search, the document has been designed taking into account current evidence and expert recommendations. There are no data on the safety and efficacy of SARS-CoV-2 vaccines in patients with multiple sclerosis. However, evidence does exist to suggest that messenger RNA (mRNA) vaccines against SARS-CoV-2 are as safe in these patients as in other individuals. Some therapies with immunosuppressants might reduce the effectiveness of these vaccines and require the scheduling of their administration, preferably before the start of treatment if possible. CONCLUSION: The data available make it possible to recommend mRNA vaccines against SARS-CoV-2 in patients with multiple sclerosis. In patients on fingolimod, cladribine, alemtuzumab, ocrelizumab and rituximab, vaccination prior to the initiation of medication administration would be recommendable whenever possible.


TITLE: Vacunación frente al SARS-CoV-2 en pacientes con esclerosis múltiple.Introducción. La reciente disponibilidad de vacunas contra el SARS-CoV-2 ha suscitado dudas en determinados colectivos de pacientes, como los que padecen esclerosis múltiple. Sin embargo, en la actualidad hay pocas publicaciones que ofrezcan información en este sentido. Se recopila la información disponible sobre la seguridad y la eficacia de la vacunación contra el SARS-CoV-2 en pacientes con esclerosis múltiple, con y sin tratamiento modificador de la enfermedad. Desarrollo. Búsqueda bibliográfica enfocada en los tipos de vacunas contra el SARS-CoV-2, la situación actual de su aprobación, y los datos disponibles sobre la eficacia y la seguridad de las vacunas en pacientes con esclerosis múltiple, incluidas las nuevas vacunas frente a la COVID-19. A partir de esta búsqueda, se ha diseñado el documento recogiendo la evidencia actual y las recomendaciones de expertos. No existen datos sobre la seguridad y la eficacia de las vacunas contra el SARS-CoV-2 en pacientes con esclerosis múltiple. Sin embargo, los datos disponibles permiten prever que las vacunas de tipo ARN mensajero (ARNm) frente al SARS-CoV-2 son tan seguras en ellos como en el resto de los individuos. Algunos de los tratamientos inmunosupresores podrían reducir la efectividad de las vacunas y requerir la planificación del momento de su administración, preferentemente antes del inicio del tratamiento en caso de ser posible. Conclusión. Los datos disponibles permiten recomendar las vacunas de tipo ARNm frente al SARS-CoV-2 en los pacientes con esclerosis múltiple. En los pacientes con fingolimod, cladribina, alemtuzumab, ocrelizumab y rituximab, sería recomendable la vacunación previa al inicio de la medicación cuando sea posible.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Immunosuppressive Agents/adverse effects , Multiple Sclerosis/immunology , SARS-CoV-2/immunology , Vaccination , Antibodies, Viral/biosynthesis , Antibody Formation/drug effects , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Communicable Disease Control/methods , Humans , Immunization Schedule , Immunocompromised Host , Immunogenicity, Vaccine , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Influenza Vaccines/administration & dosage , Masks , Multiple Sclerosis/drug therapy , Vaccination/adverse effects
12.
ACS Chem Neurosci ; 12(5): 930-944, 2021 03 03.
Article in English | MEDLINE | ID: covidwho-1091527

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 represents a global public health emergency. The entry of SARS-CoV-2 into host cells requires the activation of its spike protein by host cell proteases. The serine protease, TMPRSS2, and cysteine proteases, Cathepsins B/L, activate spike protein and enable SARS-CoV-2 entry to the host cell through two completely different and independent pathways. Therefore, inhibiting either TMPRSS2 or cathepsin B/L may not sufficiently block the virus entry. We here hypothesized that simultaneous targeting of both the entry pathways would be more efficient to block the virus entry rather than targeting the entry pathways individually. To this end, we utilized the network-based drug repurposing analyses to identify the possible common drugs that can target both the entry pathways. This study, for the first time, reports the molecules like cyclosporine, calcitriol, and estradiol as candidate drugs with the binding ability to the host proteases, TMPRSS2, and cathepsin B/L. Next, we analyzed drug-gene and gene-gene interaction networks using 332 human targets of SARS-CoV-2 proteins. The network results indicate that, out of 332 human proteins, cyclosporine interacts with 216 (65%) proteins. Furthermore, we performed molecular docking and all-atom molecular dynamics (MD) simulations to explore the binding of drug with TMPRSS2 and cathepsin L. The molecular docking and MD simulation results showed strong and stable binding of cyclosporine A (CsA) with TMPRSS2 and CTSL genes. The above results indicate cyclosporine as a potential drug molecule, as apart from interacting with SARS-CoV-2 entry receptors, it also interacts with most of SARS-CoV-2 target host genes; thus it could potentially interfere with functions of SARS-CoV-2 proteins in human cells. We here also suggest that these antiviral drugs alone or in combination can simultaneously target both the entry pathways and thus can be considered as a potential treatment option for COVID-19.


Subject(s)
COVID-19/virology , Cyclosporine/pharmacology , Immunosuppressive Agents/pharmacology , SARS-CoV-2/drug effects , Virus Internalization/drug effects , Antiviral Agents/pharmacology , Cathepsin B/metabolism , Cathepsin L/metabolism , Drug Repositioning , Humans , Models, Molecular , Molecular Docking Simulation , Molecular Dynamics Simulation , Pandemics , Serine Endopeptidases/metabolism
13.
Biomed Pharmacother ; 135: 111233, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1009323

ABSTRACT

Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, has led to the ongoing global pandemic. Although most patients experience no or only mild symptoms, some patients can develop severe illness, such as progressive pneumonia, acute respiratory distress syndrome, secondary hemophagocytic lymphohistiocytosis and multiple organ failure caused by cytokine release syndrome. A majority of COVID-19 patients also develop gastrointestinal symptoms. These can present special challenges to the management of patients with inflammatory bowel disease (IBD) due to potential interactions between the immune response related to SARS-CoV-2 infection and dysregulated immunity associated with IBD. In this context, the pathogenesis of COVID-19 is reviewed in order to address these questions regarding immune interactions between COVID-19 and IBD.


Subject(s)
COVID-19/epidemiology , COVID-19/physiopathology , Immunity/physiology , Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/physiopathology , Angiotensin-Converting Enzyme 2/drug effects , Angiotensin-Converting Enzyme 2/immunology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/physiopathology , Humans , Immunity/drug effects , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/immunology
14.
Clin Neurol Neurosurg ; 201: 106451, 2021 02.
Article in English | MEDLINE | ID: covidwho-1002417

ABSTRACT

At the end of 2019, the COVID-19 pandemic began, which at the time of writing continues to be a serious problem for many areas of medicine, including neurology. Since patients with multiple sclerosis (MS) often exhibit motor disability and receive disease-modifying therapy (DMT), which has an immunosuppressive effect, it is plausible that this will affect the susceptibility of MS patients to COVID-19, as well as the course of this disease. However, current data indicate that the use of DMT does not cause negative prognosis in COVID-19 sufferers, but the motor disability progression associated with MS does. In this study, we present the case reports of 4 patients with relapsing-remitting MS, who developed COVID-19, and despite the use of DMT the course of the disease was mild. Two patients were treated with dimethyl fumarate, one with Interferon ß1b and one with glatiramer acetate. One of the patients using dimethyl fumarate had lymphopenia. All patients had symptoms of COVID-19 from the nervous system, the most frequent being headache, which occurred in all patients. The aim of this article is to present a case series of four patients with MS and COVID-19, and to discuss the available literature on COVID-19 in patients with MS, with particular consideration of the impact of DMT.


Subject(s)
COVID-19/complications , COVID-19/drug therapy , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/complications , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Adult , COVID-19/diagnostic imaging , Female , Humans , Immunosuppressive Agents/pharmacology , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging
15.
Theranostics ; 11(1): 316-329, 2021.
Article in English | MEDLINE | ID: covidwho-922935

ABSTRACT

Severe coronavirus disease 2019 (COVID-19) is characterized by systemic hyper-inflammation, acute respiratory distress syndrome, and multiple organ failure. Cytokine storm refers to a set of clinical conditions caused by excessive immune reactions and has been recognized as a leading cause of severe COVID-19. While comparisons have been made between COVID-19 cytokine storm and other kinds of cytokine storm such as hemophagocytic lymphohistiocytosis and cytokine release syndrome, the pathogenesis of cytokine storm has not been clearly elucidated yet. Recent studies have shown that impaired response of type-1 IFNs in early stage of COVID-19 infection played a major role in the development of cytokine storm, and various cytokines such as IL-6 and IL-1 were involved in severe COVID-19. Furthermore, many clinical evidences have indicated the importance of anti-inflammatory therapy in severe COVID-19. Several approaches are currently being used to treat the observed cytokine storm associated with COVID-19, and expectations are especially high for new cytokine-targeted therapies, such as tocilizumab, anakinra, and baricitinib. Although a number of studies have been conducted on anti-inflammatory treatments for severe COVID-19, no specific recommendations have been made on which drugs should be used for which patients and when. In this review, we provide an overview of cytokine storm in COVID-19 and treatments currently being used to address it. In addition, we discuss the potential therapeutic role of extracorporeal cytokine removal to treat the cytokine storm associated with COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , Cytokine Release Syndrome/immunology , Cytokines/metabolism , Immunosuppressive Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Azetidines/pharmacology , Azetidines/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Clinical Trials as Topic , Cytokine Release Syndrome/drug therapy , Cytokines/antagonists & inhibitors , Cytokines/immunology , Humans , Immunosuppressive Agents/pharmacology , Interleukin 1 Receptor Antagonist Protein/pharmacology , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Janus Kinases/antagonists & inhibitors , Janus Kinases/metabolism , Purines/pharmacology , Purines/therapeutic use , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , SARS-CoV-2/immunology , STAT Transcription Factors/antagonists & inhibitors , STAT Transcription Factors/metabolism , Severity of Illness Index , Signal Transduction/drug effects , Signal Transduction/immunology , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Treatment Outcome
16.
Biochemistry (Mosc) ; 85(7): 833-837, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-772260

ABSTRACT

Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages. Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the inflammatory cytokines in macrophages. Critically ill patients with COVID-19 infection often present signs of high oxidative stress and systemic inflammation - the leading causes of mortality. This article suggests rationale for the use of Nrf2 inducers to prevent development of an excessive inflammatory response in COVID-19 patients.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/metabolism , Cytokines/antagonists & inhibitors , Cytokines/metabolism , Molecular Targeted Therapy/methods , NF-E2-Related Factor 2/metabolism , Pneumonia, Viral/drug therapy , Pneumonia, Viral/metabolism , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , COVID-19 , Catechin/analogs & derivatives , Catechin/pharmacology , Catechin/therapeutic use , Coronavirus Infections/virology , Dimethyl Fumarate/pharmacology , Dimethyl Fumarate/therapeutic use , Female , Humans , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Inflammation/metabolism , Isothiocyanates/pharmacology , Isothiocyanates/therapeutic use , Male , Mice , Oxidative Stress/drug effects , Pandemics , Pneumonia, Viral/virology , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/virology , Resveratrol/pharmacology , Resveratrol/therapeutic use , SARS-CoV-2 , Signal Transduction/drug effects , Sulfoxides , Thiosulfates/pharmacology , Thiosulfates/therapeutic use
17.
Mult Scler Relat Disord ; 46: 102516, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-765424

ABSTRACT

OBJECTIVE: Patients with Multiple Sclerosis (MS) and on disease modifying therapies (DMTs) that can be immunosuppressive or immunomodulatory form a special group where risk of continuation of DMT needs to be taken into account with risk of contracting Covid-19. This concept can pose a degree of anxiety for patients as well as neurologists. We aimed to evaluate patient perspectives regarding the use of Natalizumab and anti-CD20 therapies (Rituximab and Ocrelizumab) in the context of the COVID-19 pandemic. METHODS: cross-sectional study conducted via voluntary survey filled in by patients with MS and related disorders receiving their infusional treatment in one MS centre in Australia, exploring their concerns regarding their therapy, their therapy and COVID-19, precautions undertaken in response to the pandemic, and factors impacting their decision-making. RESULTS: 170 patients completed the survey. Of patients on Natalizumab, the majority had either no or mild concern regarding their DMT and COVID-19, and of patients on B-cell depleting therapies, again, the majority had no or mild concern, though a slightly higher proportion had a moderate level of concern. Asked to delineate their concerns, an increased risk of contracting COVID-19 was more commonly conveyed than MS-specific factors or poor outcomes pertaining to COVID-19 if contracted, by patients in both groups. Conversely, being invited to specifically consider the possibility of contracting COVID-19 or experience a relapse of MS, almost half of the cohort rated both of equal of concern. More than half of the cohort were self-isolating more stringently than general government advice and government-related resources followed by information provided by patient's neurologist where the commonest means of information to guide decision making. CONCLUSIONS: Whilst a large proportion of patients had some concern regarding the impact of their DMT on COVID-19, whether on their risk of contracting COVID-19 or a theoretical risk for more severe disease, the overall level of concern in most cases was at most mild. Patients on B-cell depleting therapies were more inclined to express a higher level of concern. A similar concern was ascribed to a risk of a relapse or worsening MS symptoms compared to the risk of contracting COVID-19. Such attitudes may underscore a willingness of patients to continue their DMT where benefits outweigh risks during future phases of the COVID-19 pandemic.


Subject(s)
COVID-19/drug therapy , Multiple Sclerosis/drug therapy , Natalizumab/therapeutic use , Rituximab/therapeutic use , SARS-CoV-2/pathogenicity , Adult , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Australia , Female , Humans , Immunosuppressive Agents/pharmacology , Male , Middle Aged , Multiple Sclerosis/epidemiology , Multiple Sclerosis/virology
18.
Mult Scler Relat Disord ; 46: 102482, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-741441

ABSTRACT

Since 2019, a new coronavirus infection (COVID-19) due to an agent called SARS-CoV-2 spread rapidly worldwide. Patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMO-SD) are often treated with immunosuppressants. Beyond their effect on the risk of COVID-19 infection, the consequences on the long-term immune response against the coronavirus remain unknown. Among 13 MS or NMOSD patients with confirmed COVID-19 included, all 5 patients treated with anti-CD20 therapies had a negative SARS-CoV-2 serology. To date, maximal precautions to prevent coronavirus infection should be maintained in MS/NMOSD patients already exposed to COVID-19 during anti-CD20 therapy.


Subject(s)
Antigens, CD20/immunology , COVID-19/drug therapy , Multiple Sclerosis/drug therapy , Neuromyelitis Optica/drug therapy , SARS-CoV-2/pathogenicity , Adult , COVID-19/immunology , COVID-19/virology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/virology , Female , Humans , Immunosuppressive Agents/pharmacology , Male , Multiple Sclerosis/complications , Multiple Sclerosis/virology , Neuromyelitis Optica/epidemiology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , SARS-CoV-2/drug effects
19.
Expert Opin Biol Ther ; 21(2): 219-228, 2021 02.
Article in English | MEDLINE | ID: covidwho-735642

ABSTRACT

INTRODUCTION: SARS-CoV-2 is a novel coronavirus that was first isolated from a group of patients hospitalized with pneumonia in China at the end of 2019, and, in February 2020, the syndrome it caused was named coronavirus disease 2019 (COVID-19) by the World Health Organization. In the absence of specific antiviral treatments capable of neutralizing the etiological agent, one therapeutic approach is to control the cytokine storm responsible for the most severe forms of the disease. The characteristic cytokine profile of severely affected patients is increased levels of interleukin (IL)-1ß, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor alpha (TNF-α). AREAS COVERED: This article discusses the pathogenesis of COVID-19 as a rationale for using the biological and targeted synthetic drugs used in rheumatology (anti-TNF, anti-IL-1 and anti-IL-6 agents and baricitinib) to treat the disease, and provides key information concerning their potential benefits and adverse effects. EXPERT OPINION: Interleukin inhibition seems to be a promising means of treating COVID-19 patients when respiratory function declines (or even earlier) if there are laboratory data indicating the presence of a cytokine storm because the interleukins are key drivers of inflammation. However, it is important to consider the risks and benefits of biological agents carefully, and critically analyze the evidence concerning their use in COVID-19 patients.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19/drug therapy , Cytokines/antagonists & inhibitors , Rheumatology/methods , SARS-CoV-2/drug effects , Antirheumatic Agents/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Azetidines/pharmacology , Azetidines/therapeutic use , COVID-19/epidemiology , COVID-19/metabolism , China/epidemiology , Clinical Trials as Topic/methods , Cytokines/metabolism , Humans , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Purines/pharmacology , Purines/therapeutic use , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , SARS-CoV-2/metabolism , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism
20.
Mult Scler Relat Disord ; 46: 102476, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-733681

ABSTRACT

Cladribine is a highly effective, recently available treatment in multiple sclerosis. This case report describes a patient with COVID-19 infection during second year treatment with cladribine. The infection was mild and she was able to mount an adequate immune response with detectable antibodies three months later.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation/immunology , COVID-19/drug therapy , Cladribine/pharmacology , SARS-CoV-2/drug effects , COVID-19/immunology , Female , Humans , Immunosuppressive Agents/pharmacology , Multiple Sclerosis/complications , Multiple Sclerosis/drug therapy , Multiple Sclerosis/virology , SARS-CoV-2/pathogenicity
SELECTION OF CITATIONS
SEARCH DETAIL