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1.
Vopr Virusol ; 67(2): 115-125, 2022 05 05.
Article in Russian | MEDLINE | ID: covidwho-1836596

ABSTRACT

By the end of 2021, about 200 studies on the effect of interferons (IFNs) on the incidence and course of the new coronavirus infection COVID-19 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus) have been reported worldwide, with the number of such studies steadily increasing. This review discusses the main issues of the use of IFN drugs in this disease. The literature search was carried out in the PubMed, Scopus, Cochrane Library, Web of Science, RSCI databases, as well as in the Google Scholar preprint database using the available search queries «MeSH for coronavirus¼, «SARS-CoV-2¼, «IFN drugs¼, and «COVID-19¼. Interferon therapy is indicated for early administration (within the first 5 days of patient admission) in cases of mild to moderate COVID-19 to take advantage of the narrow therapeutic window of IFNs action. Control and suppression of viral replication requires therapy with IFNs and other effective antiviral agents that inhibit the reproduction of SARS-CoV-2 and induce several interferon-stimulated genes (ISG). Type I IFNs (IFN-I) exhibit potent pro-inflammatory properties and activate a wide variety of different cell types that respond to IFNs stimulation and pathogen entry. IFN-III confer local mucosal antiviral immunity without inducing the strong systemic pro-inflammatory responses associated with IFN-I. The use of IFNs drugs in the therapy of new coronavirus infection requires a cautious and differentiated approach, because in severe cases they can aggravate viral pathogenesis by causing excessive intensity of inflammatory reactions. The unique biological properties of substances of this class allow us to consider them as therapeutic agents with significant potential for use in patients with COVID-19.


Subject(s)
COVID-19 , Coronaviridae , Interferon Type I , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Interferon Type I/pharmacology , Interferon Type I/therapeutic use , Interferons/therapeutic use , SARS-CoV-2
2.
Brain Behav Immun ; 87: 59-73, 2020 07.
Article in English | MEDLINE | ID: covidwho-1719339

ABSTRACT

As of April 15, 2020, the ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept through 213 countries and infected more than 1,870,000 individuals, posing an unprecedented threat to international health and the economy. There is currently no specific treatment available for patients with COVID-19 infection. The lessons learned from past management of respiratory viral infections have provided insights into treating COVID-19. Numerous potential therapies, including supportive intervention, immunomodulatory agents, antiviral therapy, and convalescent plasma transfusion, have been tentatively applied in clinical settings. A number of these therapies have provided substantially curative benefits in treating patients with COVID-19 infection. Furthermore, intensive research and clinical trials are underway to assess the efficacy of existing drugs and identify potential therapeutic targets to develop new drugs for treating COVID-19. Herein, we summarize the current potential therapeutic approaches for diseases related to COVID-19 infection and introduce their mechanisms of action, safety, and effectiveness.


Subject(s)
Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Adrenal Cortex Hormones/therapeutic use , Angiotensin-Converting Enzyme 2 , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Anticoagulants/therapeutic use , Antimalarials/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus , Bevacizumab/therapeutic use , COVID-19 , COVID-19 Vaccines , Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Interferons/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Killer Cells, Natural , Medicine, Chinese Traditional , Mesenchymal Stem Cell Transplantation , Nitric Oxide/therapeutic use , Pandemics , Peptidyl-Dipeptidase A , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Trace Elements/therapeutic use , Viral Vaccines/therapeutic use , Vitamins/therapeutic use , Zinc/therapeutic use
3.
Viruses ; 13(8)2021 08 12.
Article in English | MEDLINE | ID: covidwho-1436097

ABSTRACT

Type III interferons (lambda IFNs) are a quite new, small family of three closely related cytokines with interferon-like activity. Attention to IFN-λ is mainly focused on direct antiviral activity in which, as with IFN-α, viral genome replication is inhibited without the participation of immune system cells. The heterodimeric receptor for lambda interferons is exposed mainly on epithelial cells, which limits its possible action on other cells, thus reducing the likelihood of developing undesirable side effects compared to type I IFN. In this study, we examined the antiviral potential of exogenous human IFN-λ1 in cellular models of viral infection. To study the protective effects of IFN-λ1, three administration schemes were used: 'preventive' (pretreatment); 'preventive/therapeutic' (pre/post); and 'therapeutic' (post). Three IFN-λ1 concentrations (from 10 to 500 ng/mL) were used. We have shown that human IFN-λ1 restricts SARS-CoV-2 replication in Vero cells with all three treatment schemes. In addition, we have shown a decrease in the viral loads of CHIKV and IVA with the 'preventive' and 'preventive/therapeutic' regimes. No significant antiviral effect of IFN-λ1 against AdV was detected. Our study highlights the potential for using IFN-λ as a broad-spectrum therapeutic agent against respiratory RNA viruses.


Subject(s)
Adenoviruses, Human/drug effects , Chikungunya virus/drug effects , Influenza A virus/drug effects , Interferons/pharmacology , SARS-CoV-2/drug effects , A549 Cells , Adenoviruses, Human/physiology , Animals , Chikungunya virus/physiology , Chlorocebus aethiops , Dose-Response Relationship, Drug , Gene Expression Regulation , Humans , Influenza A virus/physiology , Interferons/therapeutic use , Interleukins , RNA Virus Infections/drug therapy , RNA Virus Infections/prevention & control , Recombinant Proteins/pharmacology , SARS-CoV-2/physiology , Vero Cells , Viral Load/drug effects , Virus Replication/drug effects
4.
JCI Insight ; 6(18)2021 09 22.
Article in English | MEDLINE | ID: covidwho-1435141

ABSTRACT

Cell lines are the mainstay in understanding the biology of COVID-19 infection but do not recapitulate many of the complexities of human infection. The use of human lung tissue is one solution for the study of such novel respiratory pathogens. We hypothesized that a cryopreserved bank of human lung tissue would allow for the ex vivo study of the interindividual heterogeneity of host response to SARS-CoV-2, thus providing a bridge between studies with cell lines and studies in animal models. We generated a cryobank of tissues from 21 donors, many of whom had clinical risk factors for severe COVID-19. Cryopreserved tissues preserved 90% cell viability and contained heterogenous populations of metabolically active epithelial, endothelial, and immune cell subsets of the human lung. Samples were readily infected with HCoV-OC43 and SARS-CoV-2 and demonstrated comparable susceptibility to infection. In contrast, we observed a marked donor-dependent heterogeneity in the expression of IL6, CXCL8, and IFNB1 in response to SARS-CoV-2. Treatment of tissues with dexamethasone and the experimental drug N-hydroxycytidine suppressed viral growth in all samples, whereas chloroquine and remdesivir had no detectable effect. Metformin and sirolimus, molecules with predicted but unproven antiviral activity, each suppressed viral replication in tissues from a subset of donors. In summary, we developed a system for the ex vivo study of human SARS-CoV-2 infection using primary human lung tissue from a library of donor tissues. This model may be useful for drug screening and for understanding basic mechanisms of COVID-19 pathogenesis.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Immunity, Innate/immunology , Interferons/therapeutic use , Lung/pathology , SARS-CoV-2 , Aged , COVID-19/immunology , Cell Line , Female , Humans , Lung/immunology , Male , Middle Aged
5.
Eur J Pharmacol ; 906: 174248, 2021 Sep 05.
Article in English | MEDLINE | ID: covidwho-1267662

ABSTRACT

Concern regarding coronavirus (CoV) outbreaks has stayed relevant to global health in the last decades. Emerging COVID-19 infection, caused by the novel SARS-CoV2, is now a pandemic, bringing a substantial burden to human health. Interferon (IFN), combined with other antivirals and various treatments, has been used to treat and prevent MERS-CoV, SARS-CoV, and SARS-CoV2 infections. We aimed to assess the clinical efficacy of IFN-based treatments and combinational therapy with antivirals, corticosteroids, traditional medicine, and other treatments. Major healthcare databases and grey literature were investigated. A three-stage screening was utilized, and included studies were checked against the protocol eligibility criteria. Risk of bias assessment and data extraction were performed, followed by narrative data synthesis. Fifty-five distinct studies of SARS-CoV2, MERS-CoV, and SARS-CoV were spotted. Our narrative synthesis showed a possible benefit in the use of IFN. A good quality cohort showed lower CRP levels in Arbidol (ARB) + IFN group vs. IFN only group. Another study reported a significantly shorter chest X-ray (CXR) resolution in IFN-Alfacon-1 + corticosteroid group compared with the corticosteroid only group in SARS-CoV patients. In a COVID-19 trial, total adverse drug events (ADEs) were much lower in the Favipiravir (FPV) + IFN-α group compared with the LPV/RTV arm (P = 0.001). Also, nausea in patients receiving FPV + IFN-α regimen was significantly lower (P = 0.03). Quantitative analysis of mortality did not show a conclusive effect for IFN/RBV treatment in six moderately heterogeneous MERS-CoV studies (log OR = -0.05, 95% CI: (-0.71,0.62), I2 = 44.71%). A meta-analysis of three COVID-19 studies did not show a conclusive nor meaningful relation between receiving IFN and COVID-19 severity (log OR = -0.44, 95% CI: (-1.13,0.25), I2 = 31.42%). A lack of high-quality cohorts and controlled trials was observed. Evidence suggests the potential efficacy of several combination IFN therapies such as lower ADEs, quicker resolution of CXR, or a decrease in inflammatory cytokines; Still, these options must possibly be further explored before being recommended in public guidelines. For all major CoVs, our results may indicate a lack of a definitive effect of IFN treatment on mortality. We recommend such therapeutics be administered with extreme caution until further investigation uncovers high-quality evidence in favor of IFN or combination therapy with IFN.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Coronavirus Infections/drug therapy , Interferons/therapeutic use , Severe Acute Respiratory Syndrome/drug therapy , Antiviral Agents/adverse effects , COVID-19/diagnostic imaging , COVID-19/mortality , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/mortality , Humans , Interferons/adverse effects , Severe Acute Respiratory Syndrome/diagnostic imaging , Severe Acute Respiratory Syndrome/mortality
6.
Aging (Albany NY) ; 12(12): 11224-11237, 2020 06 17.
Article in English | MEDLINE | ID: covidwho-1251837

ABSTRACT

With the outbreak of coronavirus disease-19 (COVID-19), Changsha faced an increasing burden of treating the Wuhan migrants and their infected patients. This study is a retrospective, single-center case series of the 238 consecutive hospitalized patients with confirmed COVID-19 at the First Hospital of Changsha city, China, from 01/21 to 02/14, 2020; the final date of follow-up was 02/27, 2020. Of 238 patients 43.7% visited Wuhan, 58.4% got in touch with Wuhan people, and 47.5% had contacted with diagnosed patients. 37.8% patients had family members infected. 190 cases had mild / general disease, and 48 cases had severe / critical disease. Compared to mild or general patients, more severe or critical patients visited Wuhan (59.6% vs 40.2%; P=0.02) and contacted with Wuhan people (74.5% vs 55.0%; P=0.02). All patients received antiviral treatment, including Lopinavir / Ritonavir (29.3%), Interferon (14.6%) and their combination (40.6%), Arbidol (6.7%), Xuebijing (7.1%) and Chloroquine phosphate (1.3%). Severe and critical patients received glucocorticoid, Gamma-globulin and oxygen inhalation. Some received mechanic ventilation support. As of 02/27, 161 patients discharged. The median length of hospital stay was 13 days. The 10-, 14-, 20- and 28-day discharge rate was 19.1%, 42.8%, 65.0% and 76.4%, respectively. No hospital-related transmission was observed.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Respiration, Artificial , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , COVID-19 , China/epidemiology , Chloroquine/analogs & derivatives , Chloroquine/therapeutic use , Drug Combinations , Drugs, Chinese Herbal/therapeutic use , Female , Glucocorticoids/therapeutic use , Hospitalization , Humans , Immunologic Factors/therapeutic use , Indoles/therapeutic use , Interferons/therapeutic use , Lopinavir/therapeutic use , Male , Middle Aged , Oxygen/therapeutic use , Pandemics , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2 , gamma-Globulins/therapeutic use
7.
Cell Host Microbe ; 29(7): 1052-1062, 2021 07 14.
Article in English | MEDLINE | ID: covidwho-1230406

ABSTRACT

COVID-19 can result in severe disease characterized by significant immunopathology that is spurred by an exuberant, yet dysregulated, innate immune response with a poor adaptive response. A limited and delayed interferon I (IFN-I) and IFN-III response results in exacerbated proinflammatory cytokine production and in extensive cellular infiltrates in the respiratory tract, resulting in lung pathology. The development of effective therapeutics for patients with severe COVID-19 depends on our understanding of the pathological elements of this unbalanced innate immune response. Here, we review the mechanisms by which SARS-CoV-2 both activates and antagonizes the IFN and inflammatory response following infection, how a dysregulated cytokine and cellular response contributes to immune-mediated pathology in COVID-19, and therapeutic strategies that target elements of the innate response.


Subject(s)
COVID-19/immunology , Immunity, Innate/immunology , Interferons/therapeutic use , SARS-CoV-2/immunology , Animals , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Cytokines/metabolism , Disease Models, Animal , Humans , Immune Evasion , Interferon Type I/metabolism , Interferons/metabolism , Kinetics
8.
Hum Vaccin Immunother ; 17(6): 1650-1661, 2021 06 03.
Article in English | MEDLINE | ID: covidwho-1214420

ABSTRACT

No proven remedy is identified for COVID-19 yet. SARS-CoV-2, the viral agent, is recognized by some endosomal and cytosolic receptors following cell entry, entailing innate and adaptive immunity stimulation, notably through interferon induction. Impairment in immunity activation in some patients, mostly elderlies, leads to high mortalities; thus, promoting immune responses may help. BCG vaccine is under investigation to prevent COVID-19 due to its non-specific effects on the immune system. However, other complementary immune-induction methods at early stages of the disease may be needed. Here, the potentially preventive immunologic effects of BCG and influenza vaccination are compared with the immune response defects caused by aging and COVID-19. BCG co-administration with interferon-α/-ß, or influenza vaccine is suggested to overcome its shortcomings in interferon signaling against COVID-19. However, further studies are highly recommended to assess the outcomes of such interventions considering their probable adverse effects especially augmented innate immune responses and overproduction of proinflammatory mediators.


Subject(s)
BCG Vaccine/therapeutic use , COVID-19/prevention & control , Influenza Vaccines/therapeutic use , Clinical Trials as Topic , Humans , Immunity, Innate , Interferons/therapeutic use , Pandemics , Prospective Studies
9.
Food Chem Toxicol ; 150: 112087, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1188569

ABSTRACT

Coronavirus disease-19 (COVID-19) is a complex disease that causes illness ranging from mild to severe respiratory problems. It is caused by a novel coronavirus SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) that is an enveloped positive-sense single-stranded RNA (+ssRNA) virus belongs to coronavirus CoV family. It has a fast-spreading potential worldwide, which leads to high mortality regardless of lows death rates. Now some vaccines or a specific drug are approved but not available for every country for disease prevention and/or treatment. Therefore, it is a high demand to identify the known drugs and test them as a possible therapeutic approach. In this critical situation, one or more of these drugs may represent the only option to treat or reduce the severity of the disease, until some specific drugs or vaccines will be developed and/or approved for everyone in this pandemic. In this updated review, the available repurpose immunotherapeutic treatment strategies are highlighted, elucidating the crosstalk between the immune system and SARS-CoV-2. Despite the reasonable data availability, the effectiveness and safety of these drugs against SARS-CoV-2 needs further studies and validations aiming for a better clinical outcome.


Subject(s)
Antiviral Agents/pharmacology , Inflammation/etiology , SARS-CoV-2/drug effects , Adrenal Cortex Hormones/pharmacology , Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Cytokines/metabolism , Humans , Inflammation/drug therapy , Inflammation/immunology , Interferons/pharmacology , Interferons/therapeutic use , Janus Kinase Inhibitors/pharmacology , Janus Kinase Inhibitors/therapeutic use , SARS-CoV-2/immunology
10.
Cytokine Growth Factor Rev ; 60: 28-45, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1184922

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicits an interferon (IFN) deficiency state, which aggravates the type I interferon deficiency and slow IFN responses, which associate with e.g. aging and obesity. Additionally, SARS-CoV-2 may also elicit a cytokine storm, which accounts for disease progression and ultimately the urgent need of ventilator support. Based upon several reports, it has been argued that early treatment with IFN-alpha2 or IFN-beta, preferentially in the early disease stage, may prohibit disease progression. Similarly, preliminary studies have shown that JAK1/2 inhibitor treatment with ruxolitinib or baricitinib may decrease mortality by dampening the deadly cytokine storm, which - in addition to the virus itself - also contributes to multi-organ thrombosis and multi-organ failure. Herein, we describe the rationale for treatment with IFNs (alpha2 or beta) and ruxolitinib emphasizing the urgent need to explore these agents in the treatment of SARS-CoV-2 - both as monotherapies and in combination. In this context, we take advantage of several safety and efficacy studies in patients with the chronic myeloproliferative blood cancers (essential thrombocythemia, polycythemia vera and myelofibrosis) (MPNs), in whom IFN-alpha2 and ruxolitinib have been used successfully for the last 10 (ruxolitinib) to 30 years (IFN) as monotherapies and most recently in combination as well. In the context of these agents being highly immunomodulating (IFN boosting immune cells and JAK1/2 inhibitors being highly immunosuppressive and anti-inflammatory), we also discuss if statins and hydroxyurea, both agents possessing anti-inflammatory, antithrombotic and antiviral potentials, might be inexpensive agents to be repurposed in the treatment of SARS-CoV-2.


Subject(s)
COVID-19/drug therapy , Cytokine Release Syndrome/virology , Interferons/deficiency , Interferons/therapeutic use , Janus Kinase 1/antagonists & inhibitors , Janus Kinase 2/antagonists & inhibitors , Protein Kinase Inhibitors/therapeutic use , SARS-CoV-2/pathogenicity , Animals , COVID-19/immunology , COVID-19/pathology , Clinical Trials as Topic , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Humans , SARS-CoV-2/immunology
11.
Clin Microbiol Rev ; 34(3)2021 06 16.
Article in English | MEDLINE | ID: covidwho-1166352

ABSTRACT

Several viruses target the human respiratory tract, causing different clinical manifestations spanning from mild upper airway involvement to life-threatening acute respiratory distress syndrome (ARDS). As dramatically evident in the ongoing SARS-CoV-2 pandemic, the clinical picture is not always easily predictable due to the combined effect of direct viral and indirect patient-specific immune-mediated damage. In this review, we discuss the main RNA (orthomyxoviruses, paramyxoviruses, and coronaviruses) and DNA (adenoviruses, herpesviruses, and bocaviruses) viruses with respiratory tropism and their mechanisms of direct and indirect cell damage. We analyze the thin line existing between a protective immune response, capable of limiting viral replication, and an unbalanced, dysregulated immune activation often leading to the most severe complication. Our comprehension of the molecular mechanisms involved is increasing and this should pave the way for the development and clinical use of new tailored immune-based antiviral strategies.


Subject(s)
DNA Viruses , Lung Injury , RNA Viruses , Respiratory Tract Infections , Virus Diseases , Adult , Aged , Antiviral Agents/therapeutic use , COVID-19 , Child , Child, Preschool , Female , Humans , Immunologic Factors/therapeutic use , Infant , Infant, Newborn , Interferons/therapeutic use , Lung/immunology , Lung/virology , Lung Injury/diagnosis , Lung Injury/drug therapy , Lung Injury/immunology , Lung Injury/virology , Male , Middle Aged , Pandemics , SARS-CoV-2
12.
Cells ; 10(3)2021 03 23.
Article in English | MEDLINE | ID: covidwho-1159480

ABSTRACT

As highlighted by the COVID-19 global pandemic, elderly individuals comprise the majority of cases of severe viral infection outcomes and death. A combined inability to control viral replication and exacerbated inflammatory immune activation in elderly patients causes irreparable immune-mediated tissue pathology in response to infection. Key to these responses are type I, II, and III interferons (IFNs), which are involved in inducing an antiviral response, as well as controlling and suppressing inflammation and immunopathology. IFNs support monocyte/macrophage-stimulated immune responses that clear infection and promote their immunosuppressive functions that prevent excess inflammation and immune-mediated pathology. The timing and magnitude of IFN responses to infection are critical towards their immunoregulatory functions and ability to prevent immunopathology. Aging is associated with multiple defects in the ability of macrophages and dendritic cells to produce IFNs in response to viral infection, leading to a dysregulation of inflammatory immune responses. Understanding the implications of aging on IFN-regulated inflammation will give critical insights on how to treat and prevent severe infection in vulnerable individuals. In this review, we describe the causes of impaired IFN production in aging, and the evidence to suggest that these impairments impact the regulation of the innate and adaptive immune response to infection, thereby causing disease pathology.


Subject(s)
Adaptive Immunity , Aging/immunology , COVID-19/immunology , Immunity, Innate , Interferons/physiology , SARS-CoV-2/immunology , Virus Replication/immunology , Aged , COVID-19/drug therapy , COVID-19/virology , Humans , Inflammation/drug therapy , Inflammation/immunology , Interferon Type I/immunology , Interferon Type I/therapeutic use , Interferon-gamma/immunology , Interferon-gamma/therapeutic use , Interferons/immunology , Interferons/therapeutic use
13.
Inflamm Res ; 70(4): 389-405, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1092089

ABSTRACT

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a world-wide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, treatment of severe COVID-19 is far from clear. Therefore, it is urgent to develop an effective option for the treatment of patients with COVID-19. Most patients with severe COVID-19 exhibit markedly increased serum levels of pro-inflammatory cytokines, including interferon (IFN)-α, IFN-γ, and interleukin (IL)-1ß. Immunotherapeutic strategies have an important role in the suppression of cytokine storm and respiratory failure in patients with COVID-19. METHODS: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar preprint database using all available MeSH terms for Coronavirus, SARS-CoV-2, anti-rheumatoid agents, COVID-19, cytokine storm, immunotherapeutic drugs, IFN, interleukin, JAK/STAT inhibitors, MCP, MIP, TNF. RESULTS: Here, we first review common complications of COVID-19 patients, particularly neurological symptoms. We next explain host immune responses against COVID-19 particles. Finally, we summarize the existing experimental and clinical immunotherapeutic strategies, particularly anti-rheumatoid agents and also plasma (with a high level of gamma globulin) therapy for severe COVID-19 patients. We discuss both their therapeutic effects and side effects that should be taken into consideration for their clinical application. CONCLUSION: It is suggested that immunosuppressants, such as anti-rheumatoid drugs, could be considered as a potential approach for the treatment of cytokine storm in severe cases of COVID-19. One possible limitation of immunosuppressant therapy is their inhibitory effects on host anti-viral immune response. So, the appropriate timing of administration should be carefully considered.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Cytokine Release Syndrome/drug therapy , Immunologic Factors/therapeutic use , Animals , Antirheumatic Agents/therapeutic use , COVID-19/immunology , Cytokines/metabolism , Enzyme Inhibitors/therapeutic use , Humans , Immunization, Passive , Immunosuppressive Agents/therapeutic use , Immunotherapy , Inflammation/drug therapy , Interferons/therapeutic use , Interleukin-1/antagonists & inhibitors , Interleukin-6/antagonists & inhibitors , Janus Kinase 1/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Respiratory Insufficiency/therapy , STAT1 Transcription Factor/antagonists & inhibitors , Signal Transduction
14.
Exp Hematol ; 96: 1-12, 2021 04.
Article in English | MEDLINE | ID: covidwho-1077891

ABSTRACT

Interferons are an ancient and well-conserved group of inflammatory cytokines most famous for their role in viral immunity. A decade ago, we discovered that interferons also play an important role in the biology of hematopoietic stem cells (HSCs), which are responsible for lifelong blood production. Though we have learned a great deal about the role of interferons on HSC quiescence, differentiation, and self-renewal, there remains some controversy regarding how interferons impact these stem cells, with differing conclusions depending on experimental models and clinical context. Here, we review the contradictory roles of Type 1 and 2 interferons in hematopoiesis. Specifically, we highlight the roles of interferons in embryonic and adult hematopoiesis, along with short-term and long-term adaptive and maladaptive responses to inflammation. We discuss experimental challenges in the study of these powerful yet short-lived cytokines and strategies to address those challenges. We further review the contribution by interferons to disease states including bone marrow failure and aplastic anemia as well as their therapeutic use to treat myeloproliferative neoplasms and viral infections, including SARS-CoV2. Understanding the opposing effects of interferons on hematopoiesis will elucidate immune responses and bone marrow failure syndromes, and future therapeutic approaches for patients undergoing HSC transplantation or fighting infectious diseases and cancer.


Subject(s)
Hematopoiesis/drug effects , Hematopoietic Stem Cells/drug effects , Immunologic Factors/therapeutic use , Interferons/therapeutic use , Animals , Antineoplastic Agents/immunology , Antineoplastic Agents/therapeutic use , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/immunology , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/immunology , Humans , Immunologic Factors/immunology , Interferons/immunology
15.
Ann Neurol ; 89(4): 780-789, 2021 04.
Article in English | MEDLINE | ID: covidwho-1070695

ABSTRACT

OBJECTIVE: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). METHODS: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. RESULTS: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. INTERPRETATION: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists. ANN NEUROL 2021;89:780-789.


Subject(s)
COVID-19/physiopathology , Hospitalization/statistics & numerical data , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , COVID-19/mortality , Dimethyl Fumarate/therapeutic use , Female , Fingolimod Hydrochloride/therapeutic use , Humans , Immunologic Factors/therapeutic use , Intensive Care Units/statistics & numerical data , Interferons/therapeutic use , Male , Middle Aged , Mortality , Multiple Sclerosis/complications , Natalizumab/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Young Adult
16.
Int Immunopharmacol ; 90: 107171, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1065213

ABSTRACT

The recently public health crises in the world is emerged by spreading the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also named COVID-19. The virus is originated in bats and transported to humans via undefined intermediate animals. This virus can produce from weak to severe respiratory diseases including acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), pneumonia and even death in patients. The COVID-19 disease is distributed by inhalation via contaminated droplets or contact with infected environment. The incubation time is from 2 to 14 day and the symptoms are typically fever, sore throat, cough, malaise, fatigue, breathlessness among others. It needs to be considered that many infected people are asymptomatic. Developing various immunological and virological methods to diagnose this disease is supported by several laboratories. Treatment is principally supportive; however, there are several agents that are using in treating of COVID-19 patients. Interferons (IFNs) have shown to be crucial in fighting with COVID-19 disease and can be a suitable candidate in treatment of these patients. Combination therapy can be more effective than monotherapy to cure this disease. Prevention necessitates to be performed by isolation of suspected people and home quarantine as well as taking care to infected people with mild or strict disease at hospitals. As the outbreak of SARS-CoV-2 has accelerated, developing effective therapy is an urgent requirement to battle the virus and prevent further pandemic. In this manuscript we reviewed available information about SARS-CoV-2 and probable therapies for COVID-19 patients.


Subject(s)
COVID-19/therapy , Immunotherapy/methods , Interferons/therapeutic use , Pneumonia/therapy , SARS-CoV-2/physiology , Humans , Pandemics
18.
Ann Palliat Med ; 10(1): 707-720, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1030457

ABSTRACT

The whole world is battling through coronavirus disease 2019 (COVID-19) which is a fatal pandemic. In the early 2020, the World Health Organization (WHO) declared it as a global health emergency without definitive treatments and preventive approaches. In the absence of definitive therapeutic agents, this thorough review summarizes and outlines the potency and safety of all molecules and therapeutics which may have potential antiviral effects. A number of molecules and therapeutics licensed or being tested for some other conditions were found effective in different in vitro studies as well as in many small sample-sized clinical trials and independent case studies. However, in those clinical trials, there were some limitations which need to be overcome to find the most promising antiviral against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In conclusion, many of above-mentioned antivirals seems to have some therapeutic effects but none of them have been shown to have a strong evidence for their proper recommendation and approval in the treatment of COVID-19. Constantly evolving new evidences, exclusive adult data, language barrier, and type of study (observational, retrospective, small-sized clinical trials, or independent case series) resulted to the several limitations of this review. The need for multicentered, large sample-sized, randomized, placebo-controlled trials on COVID-19 patients to reach a proper conclusion on the most promising antiviral agent is warranted.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/pharmacology , Alanine/therapeutic use , Amides/pharmacology , Amides/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Azetidines/pharmacology , Azetidines/therapeutic use , Chloroquine/pharmacology , Chloroquine/therapeutic use , Drug Combinations , Humans , Hydroxychloroquine/pharmacology , Hydroxychloroquine/therapeutic use , Immunization, Passive , Indoles/pharmacology , Indoles/therapeutic use , Interferons/pharmacology , Interferons/therapeutic use , Ivermectin/pharmacology , Ivermectin/therapeutic use , Lopinavir/pharmacology , Lopinavir/therapeutic use , Nitro Compounds , Oseltamivir/pharmacology , Oseltamivir/therapeutic use , Purines/pharmacology , Purines/therapeutic use , Pyrazines/pharmacology , Pyrazines/therapeutic use , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Ribavirin/pharmacology , Ribavirin/therapeutic use , Ritonavir/pharmacology , Ritonavir/therapeutic use , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Thiazoles/pharmacology , Thiazoles/therapeutic use
20.
Eur Rev Med Pharmacol Sci ; 24(23): 12593-12608, 2020 12.
Article in English | MEDLINE | ID: covidwho-995021

ABSTRACT

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 Vaccines/therapeutic use , COVID-19/drug therapy , COVID-19/therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Anti-Bacterial Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neutralizing/therapeutic use , Antiparasitic Agents/therapeutic use , COVID-19/prevention & control , Cannabinoids/therapeutic use , Chloroquine/therapeutic use , Complement Inactivating Agents/therapeutic use , Dexamethasone/therapeutic use , Drug Combinations , Enzyme Inhibitors/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Indoles/therapeutic use , Interferons/therapeutic use , Ivermectin/therapeutic use , Lopinavir/therapeutic use , Nitro Compounds , Pyrazines/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2 , Teicoplanin/therapeutic use , Tetracyclines/therapeutic use , Thiazoles/therapeutic use
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