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1.
Signal Transduct Target Ther ; 7(1): 57, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1702971

ABSTRACT

The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.


Subject(s)
Acute Kidney Injury/complications , COVID-19/complications , Cytokine Release Syndrome/complications , Disseminated Intravascular Coagulation/complications , Lymphopenia/complications , Myocarditis/complications , Pulmonary Embolism/complications , Acute Kidney Injury/drug therapy , Acute Kidney Injury/immunology , Acute Kidney Injury/virology , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Clinical Trials as Topic , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/virology , Endothelial Cells/drug effects , Endothelial Cells/immunology , Endothelial Cells/virology , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/virology , Myocarditis/drug therapy , Myocarditis/immunology , Myocarditis/virology , Pulmonary Embolism/drug therapy , Pulmonary Embolism/immunology , Pulmonary Embolism/virology , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity
2.
Naunyn Schmiedebergs Arch Pharmacol ; 394(3): 561-567, 2021 03.
Article in English | MEDLINE | ID: covidwho-1235720

ABSTRACT

Coronavirus disease 2019 (COVID-19) has been characterized by lymphopenia as well as a proinflammatory cytokine storm, which are responsible for the poor prognosis and multiorgan defects. The transcription factor nuclear factor-κB (NF-κB) modulates the functions of the immune cells and alters the gene expression profile of different cytokines in response to various pathogenic stimuli, while many proinflammatory factors have been known to induce NF-κB signalling cascade. Besides, NF-κB has been known to potentiate the production of reactive oxygen species (ROS) leading to apoptosis in various tissues in many diseases and viral infections. Though the reports on the involvement of the NF-κB signalling pathway in COVID-19 are limited, the therapeutic benefits of NF-κB inhibitors including dexamethasone, a synthetic form of glucocorticoid, have increasingly been realized. Considering the fact, the abnormal activation of the NF-κB resulting from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection might be associated with the pathogenic profile of immune cells, cytokine storm and multiorgan defects. Thus, the pharmacological inactivation of the NF-κB signalling pathway can strongly represent a potential therapeutic target to treat the symptomatology of COVID-19. This article signifies pharmacological blockade of the phosphorylation of inhibitor of nuclear factor kappa B kinase subunit beta (IKKß), a key downstream effector of NF-κB signalling, for a therapeutic consideration to attenuate COVID-19.


Subject(s)
COVID-19/drug therapy , Drug Delivery Systems/trends , I-kappa B Kinase/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Signal Transduction/physiology , Animals , COVID-19/epidemiology , COVID-19/metabolism , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/metabolism , Heterocyclic Compounds, 3-Ring/administration & dosage , Humans , I-kappa B Kinase/metabolism , Lymphopenia/drug therapy , Lymphopenia/epidemiology , Lymphopenia/metabolism , NF-kappa B/metabolism , Nitriles/administration & dosage , Pyridines/administration & dosage , Signal Transduction/drug effects , Sulfones/administration & dosage
3.
J Leukoc Biol ; 109(1): 49-53, 2021 01.
Article in English | MEDLINE | ID: covidwho-1188016

ABSTRACT

Bruton's tyrosine kinase (BTK) signaling is involved in innate immune responses and regulates the production of proinflammatory cytokines that can contribute to COVID-19 immunopathology. Clinical trials with BTK inhibitors in COVID-19 treatment have been proposed, and previous studies have attempted to investigate the therapeutic effects of ibrutinib and underlying mechanisms in treating viral pneumonia. These attempts, however, did not consider potential off target effect of BTK inhibitors on T cell differentiation, function, and survival, which may be beneficial in treatment for COVID-19. Here, we summarize the current knowledge of BTK/IL-2-inducible T-cell kinase (ITK) signaling in immunopathology and lymphopenia and discuss the potential of BTK/ITK dual inhibitors such as ibrutinib in modulating immunopathology and lymphopenia, for COVID-19 therapy.


Subject(s)
Agammaglobulinaemia Tyrosine Kinase , COVID-19/drug therapy , Lymphopenia , SARS-CoV-2 , Signal Transduction , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Agammaglobulinaemia Tyrosine Kinase/immunology , Agammaglobulinaemia Tyrosine Kinase/metabolism , COVID-19/enzymology , COVID-19/immunology , Cytokines/immunology , Humans , Immunity, Innate/drug effects , Lymphopenia/drug therapy , Lymphopenia/enzymology , Lymphopenia/immunology , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/immunology , Protein-Tyrosine Kinases/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Signal Transduction/drug effects , Signal Transduction/immunology
4.
Virulence ; 12(1): 918-936, 2021 12.
Article in English | MEDLINE | ID: covidwho-1147910

ABSTRACT

The coronavirus disease 19 (COVID-19) caused by the novel coronavirus known as SARS-CoV-2 has caused a global public health crisis. As of 7 January 2021, 87,640,402 confirmed cases and 1,891,692 mortalities have been reported worldwide. Studies focusing on the epidemiological and clinical characteristics of COVID-19 patients have suggested a dysregulated immune response characterized by lymphopenia and cytokine storm in these patients. The exaggerated immune response induced by the cytokine storm causes septic shock, acute respiratory distress syndrome (ARDS), and/or multiple organs failure, which increases the fatality rate of patients with SARS-CoV-2 infection. Herein, we review the recent research progress on epidemiology, clinical features, and system pathology in COVID-19. Moreover, we summarized the recent therapeutic strategies, which are either approved, under clinical trial, and/or under investigation by the local or global health authorities. We assume that treatments should focus on the use of antiviral drugs in combination with immunomodulators as well as treatment of the underlying comorbidities.


Subject(s)
COVID-19/immunology , COVID-19/pathology , SARS-CoV-2/pathogenicity , Adaptive Immunity , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/virology , Humans , Immunity, Innate , Immunologic Factors/therapeutic use , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/pathology , Lymphopenia/virology , SARS-CoV-2/immunology , Viral Load
5.
J Ethnopharmacol ; 277: 113888, 2021 Sep 15.
Article in English | MEDLINE | ID: covidwho-1056890

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The coronavirus disease 2019 (COVID-19) has formed a global pandemic since late 2019. Benefitting from the application experience of Chinese Medicine (CM) for influenza and SARS, CM has been used to save patients at the early stage of COVID-19 outbreak in China. AIM OF THE STUDY: In order to evaluate the efficacy and safety of CM, and compare with Western Medicine (WM) for COVID-19, we conducted a retrospective case series study based on the patients in Wuhan Jinyintan Hospital, Wuhan, China. METHODS: The inclusion and exclusion criteria of data extraction were set for this retrospective study. All patients who were admitted by the Wuhan Jinyintan Hospital between January 17th and February 25th 2020 were considered. In addition, patients enrolled met the severe defined by the guidelines released by the National Health Commission of the People's Republic of China. In these cases included in the study, CM or WM treatment was selected according to the wishes of the patients at the beginning of hospitalization. The patients in CM group were treated with Huashi Baidu granule (137 g po, bid) combined with the injections of Xiyanping (100 mg iv, bid), Xuebijing (100 ml iv, bid) and Shenmai (60 ml iv, qd) according to the syndrome of epidemic toxin blocking the lung in the theory of Traditional Chinese Medicine. The WM group received antiviral therapy (including abidor capsule 0.2 g po, tid; Lopinavir-Ritonavir tablets, 500 mg po, bid), antibiotics (such as cefoperazone 2 g iv, bid; moxifloxacin hydrochloride tablets, 0.4 g po, qd) or corticosteroid therapy (such as methylprednisolone succinate sodium 40 mg iv, qd; prednisone, 30 mg po, qd). In addition, patients in both groups received routine supportive treatment, including oxygen inhalation, symptomatic therapy, and/or human intravenous immunoglobulin, and/or serum albumin, and treatment for underlying diseases. The clinical outcomes were evaluated based on changes related with clinical manifestations, computer tomography (CT) scan images, and laboratory examinations before and after the treatment. RESULTS: 55 severe COVID-19 patients, with 23 in CM group and 32 in WM group, were included for analyzed. There was no case of death, being transferred to ICU, or receiving invasive mechanical ventilation in two groups during hospitalization. The median time of SARS-CoV-2 RNA clearance in CM and WM group were 12 days and 15.5 days respectively, the ratio of nucleic acid negative conversion of CM group at different follow-up time points was significantly higher than that of WM group (HR: 2.281, P = 0.018). Further, the chest CT imaging showed more widely lung lesion opacity absorbed in the CM group. The high sensitivity C-reactive protein and serum ferritin decreased significantly in the CM group (P<0.05). There was no significant difference in adverse events in terms of liver function and renal function between the two groups. CONCLUSION: Based on this retrospective analysis from Wuhan Jinyintan Hospital, CM has better effects in SARS-CoV-2 RNA clearance, promoting lung lesion opacity absorbed and reducing inflammation in severe COVID-19 patients, which is effective and safe therapy for treating severe COVID-19 and reducing mortality.


Subject(s)
COVID-19/drug therapy , Medicine, Chinese Traditional/adverse effects , Medicine, Chinese Traditional/methods , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Anti-Bacterial Agents/therapeutic use , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/mortality , China , Female , Hospitalization , Humans , Inflammation/drug therapy , Kaplan-Meier Estimate , Lung/diagnostic imaging , Lung/pathology , Lymphopenia/drug therapy , Male , Middle Aged , RNA, Viral/analysis , RNA, Viral/drug effects , Retrospective Studies , SARS-CoV-2/drug effects , Tomography, X-Ray Computed , Treatment Outcome
6.
FASEB J ; 35(2): e21245, 2021 02.
Article in English | MEDLINE | ID: covidwho-1048438

ABSTRACT

Lymphopenia is commonly observed in SARS and COVID-19 patients although the lymphocyte count is not always below 0.8 × 109 /L in all the patients. It is suggested that lymphopenia serves as a useful predictor for prognosis in the patients. It is also hypothesized that lymphopenia is related to glucocorticoids and apoptosis. However, the ordering between lymphopenia and apoptosis appears different between SARS and COVID-19 patients, ie, lymphopenia is prior to apoptosis in SARS patients whereas apoptosis is prior to lymphopenia in COVID-19 patients. This paper attempts to figure out this contradiction through three players, lymphopenia, glucocorticoids, and apoptosis. Although the literature does not provide a solid explanation, the level of glucocorticoids could determine the ordering between lymphopenia and apoptosis because the administration of high doses of glucocorticoids could lead to lymphopenia whereas low doses of glucocorticoids could benefit patients. In the meantime, this paper raises several questions, which need to be answered in order to better understand the whole course of COVID-19.


Subject(s)
COVID-19 , Glucocorticoids , Lymphopenia , SARS Virus/metabolism , SARS-CoV-2/metabolism , Severe Acute Respiratory Syndrome , Apoptosis/drug effects , COVID-19/complications , COVID-19/drug therapy , COVID-19/metabolism , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Humans , Lymphopenia/drug therapy , Lymphopenia/etiology , Lymphopenia/metabolism , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/metabolism
7.
Ann Hematol ; 100(2): 309-320, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1014126

ABSTRACT

Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2. Primarily an infection of the lower respiratory tract, it is now well known to cause multisystem abnormalities. Hematologic manifestations constitute a significant area of concern. Severe acute respiratory syndrome coronavirus 2 infects monocytes and endothelial cells leading to a complex downstream cascade, cytokine storm, and eventual intravascular thrombosis. Coronavirus disease 2019 causes lymphopenia, neutrophilia, and thrombocytopenia. Prophylactic anticoagulation is vital in patients with coronavirus disease 2019, as its effect on the coagulation system is associated with significant morbidity and mortality. The disease can cause both arterial and venous thromboses, especially pulmonary embolism and pulmonary microthrombi. A high index of suspicion is indispensable in recognizing these complications, and timely institution of therapeutic anticoagulation is vital in treating them. Virus-induced disseminated intravascular coagulation is uncommon but shares some similarities to sepsis-induced disseminated intravascular coagulation. Marked elevations in hematologic biomarkers such as lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein are associated with worse outcomes. Understanding the pathophysiology and recognizing factors associated with poor prognosis are crucial in improving patient outcomes with coronavirus disease 2019.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , SARS-CoV-2/isolation & purification , Biomarkers/blood , COVID-19/prevention & control , COVID-19/virology , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hematologic Diseases/blood , Hematologic Diseases/complications , Hematologic Diseases/drug therapy , Humans , Lymphopenia/blood , Lymphopenia/complications , Lymphopenia/drug therapy , SARS-CoV-2/physiology , Thrombocytopenia/blood , Thrombocytopenia/complications , Thrombocytopenia/drug therapy
8.
Clin Immunol ; 221: 108611, 2020 12.
Article in English | MEDLINE | ID: covidwho-856558

ABSTRACT

Since December 2019, Coronavirus Disease 2019 (COVID-19) has emerged as a global pandemic. We aimed to investigate the clinical characteristics and analyzed the risk factors for prolonged viral RNA shedding. We retrospectively collected data from 112 hospitalized COVID-19 patients in a single center in Wuhan, China. Factors associated with prolonged viral RNA shedding (≥28 days) were investigated. Forty-nine (43.8%) patients had prolonged viral RNA shedding. Patients with prolonged viral shedding were older and had a higher rate of hypertension. Proinflammatory cytokines, including interleukin-2R (IL-2R) and tumor necrosis factor-α (TNF-α), were significantly elevated in patients with prolonged viral shedding. Multivariate analysis revealed that hypertension, older age, lymphopenia and elevated serum IL-2R were independent risk factors for prolonged viral shedding. This comprehensive investigation revealed the distinct characteristics between patients with or without prolonged viral RNA shedding. Hypertension, older age, lymphopenia and high levels of proinflammatory cytokines may be correlated with prolonged viral shedding.


Subject(s)
COVID-19/virology , Cytokine Release Syndrome/virology , Diabetes Mellitus/virology , Hypertension/virology , Lymphopenia/virology , RNA, Viral/blood , SARS-CoV-2/pathogenicity , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/immunology , China , Comorbidity , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Diabetes Mellitus/diagnosis , Diabetes Mellitus/drug therapy , Diabetes Mellitus/immunology , Drug Combinations , Female , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/immunology , Interferons/therapeutic use , Lopinavir/therapeutic use , Lymphopenia/diagnosis , Lymphopenia/drug therapy , Lymphopenia/immunology , Male , Middle Aged , Receptors, Interleukin-2/biosynthesis , Retrospective Studies , Risk Factors , Ritonavir/therapeutic use , Severity of Illness Index , Tumor Necrosis Factor-alpha/biosynthesis , Virus Shedding
9.
JAMA Intern Med ; 181(1): 71-78, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-775497

ABSTRACT

Importance: Lymphopenia is common and correlates with poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Objective: To determine whether a therapy that increases peripheral blood leukocyte and lymphocyte cell counts leads to clinical improvement in patients with COVID-19. Design, Setting and Participants: Between February 18 and April 10, 2020, we conducted an open-label, multicenter, randomized clinical trial at 3 participating centers in China. The main eligibility criteria were pneumonia, a blood lymphocyte cell count of 800 per µL (to convert to ×109/L, multiply by 0.001) or lower, and no comorbidities. Severe acute respiratory syndrome coronavirus 2 infection was confirmed with reverse-transcription polymerase chain reaction testing. Exposures: Usual care alone, or usual care plus 3 doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF, 5 µg/kg, subcutaneously at days 0-2). Main Outcomes and Measures: The primary end point was the time from randomization to improvement of at least 1 point on a 7-category disease severity score. Results: Of 200 participants, 112 (56%) were men and the median (interquartile range [IQR]) age was 45 (40-55) years. There was random assignment of 100 patients (50%) to the rhG-CSF group and 100 (50%) to the usual care group. Time to clinical improvement was similar between groups (rhG-CSF group median of 12 days (IQR, 10-16 days) vs usual care group median of 13 days (IQR, 11-17 days); hazard ratio, 1.28; 95% CI, 0.95-1.71; P = .06). For secondary end points, the proportion of patients progressing to acute respiratory distress syndrome, sepsis, or septic shock was lower in the rhG-CSF group (rhG-CSF group, 2% vs usual care group, 15%; difference, -13%; 95%CI, -21.4% to -5.4%). At 21 days, 2 patients (2%) had died in the rhG-CSF group compared with 10 patients (10%) in the usual care group (hazard ratio, 0.19; 95%CI, 0.04-0.88). At day 5, the lymphocyte cell count was higher in the rhG-CSF group (rhG-CSF group median of 1050/µL vs usual care group median of 620/µL; Hodges-Lehmann estimate of the difference in medians, 440; 95% CI, 380-490). Serious adverse events, such as sepsis or septic shock, respiratory failure, and acute respiratory distress syndrome, occurred in 29 patients (14.5%) in the rhG-CSF group and 42 patients (21%) in the usual care group. Conclusion and Relevance: In preliminary findings from a randomized clinical trial, rhG-CSF treatment for patients with COVID-19 with lymphopenia but no comorbidities did not accelerate clinical improvement, but the number of patients developing critical illness or dying may have been reduced. Larger studies that include a broader range of patients with COVID-19 should be conducted. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000030007.


Subject(s)
COVID-19/drug therapy , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematologic Agents/therapeutic use , Hospital Mortality , Lymphopenia/drug therapy , Adrenal Cortex Hormones/therapeutic use , Adult , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , B-Lymphocytes , CD4 Lymphocyte Count , COVID-19/blood , COVID-19/complications , COVID-19/physiopathology , China , Disease Progression , Female , Humans , Killer Cells, Natural , Leukocyte Count , Lymphocyte Count , Lymphopenia/blood , Lymphopenia/complications , Male , Middle Aged , Mortality , Noninvasive Ventilation , Oxygen Inhalation Therapy , Recombinant Proteins , Respiratory Distress Syndrome/physiopathology , Respiratory Insufficiency/physiopathology , SARS-CoV-2 , Sepsis/physiopathology , Shock, Septic/physiopathology , Time Factors
10.
Appl Microbiol Biotechnol ; 104(18): 7777-7785, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-709732

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel ß-coronavirus, is the main pathogenic agent of the rapidly spreading pneumonia called coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects much more people, especially the elder population, around the world than other coronavirus, such as SARS-CoV and MERS-CoV, which is challenging current global public health system. Beyond the pathogenesis of SARS-CoV-2, microbial coinfection plays an important role in the occurrence and development of SARS-CoV-2 infection by raising the difficulties of diagnosis, treatment, prognosis of COVID-19, and even increasing the disease symptom and mortality. We summarize the coinfection of virus, bacteria and fungi with SARS-CoV-2, their effects on COVID-19, the reasons of coinfection, and the diagnosis to emphasize the importance of microbial coinfection in COVID-19. KEY POINTS: • Microbial coinfection is a nonnegligible factor in COVID-19. • Microbial coinfection exacerbates the processes of the occurrence, development and prognosis of COVID-19, and the difficulties of clinical diagnosis and treatment. • Different virus, bacteria, and fungi contributed to the coinfection with SARS-CoV-2.


Subject(s)
Bacterial Infections/epidemiology , Coronavirus Infections/epidemiology , Cytokine Release Syndrome/epidemiology , Lymphopenia/epidemiology , Mycoses/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Virus Diseases/epidemiology , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Bacterial Infections/virology , Betacoronavirus/drug effects , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Coinfection , Coronavirus Infections/drug therapy , Coronavirus Infections/microbiology , Coronavirus Infections/virology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/microbiology , Cytokine Release Syndrome/virology , Cytokines/biosynthesis , Disease Progression , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate/drug effects , Lymphocytes/microbiology , Lymphocytes/virology , Lymphopenia/drug therapy , Lymphopenia/microbiology , Lymphopenia/virology , Mycoses/drug therapy , Mycoses/microbiology , Mycoses/virology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/microbiology , Pneumonia, Viral/virology , SARS-CoV-2 , Virus Diseases/drug therapy , Virus Diseases/microbiology , Virus Diseases/virology
11.
Cell Mol Immunol ; 17(9): 1001-1003, 2020 09.
Article in English | MEDLINE | ID: covidwho-690856
12.
Adv Biol Regul ; 77: 100741, 2020 08.
Article in English | MEDLINE | ID: covidwho-623932

ABSTRACT

Pandemic coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and poses an unprecedented challenge to healthcare systems due to the lack of a vaccine and specific treatment options. Accordingly, there is an urgent need to understand precisely the pathogenic mechanisms underlying this multifaceted disease. There is increasing evidence that the immune system reacts insufficiently to SARS-CoV-2 and thus contributes to organ damage and to lethality. In this review, we suggest that the overwhelming production of reactive oxygen species (ROS) resulting in oxidative stress is a major cause of local or systemic tissue damage that leads to severe COVID-19. It increases the formation of neutrophil extracellular traps (NETs) and suppresses the adaptive arm of the immune system, i.e. T cells that are necessary to kill virus-infected cells. This creates a vicious cycle that prevents a specific immune response against SARS-CoV-2. The key role of oxidative stress in the pathogenesis of severe COVID-19 implies that therapeutic counterbalancing of ROS by antioxidants such as vitamin C or NAC and/or by antagonizing ROS production by cells of the mononuclear phagocyte system (MPS) and neutrophil granulocytes and/or by blocking of TNF-α can prevent COVID-19 from becoming severe. Controlled clinical trials and preclinical models of COVID-19 are needed to evaluate this hypothesis.


Subject(s)
Antioxidants/therapeutic use , Coronavirus Infections/epidemiology , Extracellular Traps/immunology , Lymphopenia/epidemiology , Neutrophils/immunology , Pandemics , Pneumonia, Viral/epidemiology , Acetylcysteine/therapeutic use , Ascorbic Acid/therapeutic use , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokines/genetics , Cytokines/immunology , Extracellular Traps/drug effects , Extracellular Traps/metabolism , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate/drug effects , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/virology , NF-kappa B/genetics , NF-kappa B/immunology , Neutrophils/drug effects , Neutrophils/virology , Oxidative Stress/drug effects , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/immunology , Reactive Oxygen Species/metabolism , SARS-CoV-2 , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/virology
13.
Microbes Infect ; 22(4-5): 200-205, 2020.
Article in English | MEDLINE | ID: covidwho-621882

ABSTRACT

The spread of COVID-19 is accelerating. At present, there is no specific antiviral drugs for COVID-19 outbreak. This is a multicenter retrospective cohort study of patients with laboratory-confirmed COVID-19 infection pneumonia from 3 hospitals in Hubei and Guangdong province, 141 adults (aged ≥18 years) without ventilation were included. Combined group patients were given Arbidol and IFN-α2b, monotherapy group patients inhaled IFN-α2b for 10-14 days. Of 141 COVID-19 patients, baseline clinical and laboratory characteristics were similar between combined group and monotherapy group, that 30% of the patients leucocytes counts were below the normal range and 36.4% of the patients experienced lymphocytopenia. The duration of viral RNA of respiratory tract in the monotherapy group was not longer than that in the combined therapy group. There was no significant differences between two groups. The absorption of pneumonia in the combined group was faster than that in the monotherapy group. We inferred that Arbidol/IFN - 2 b therapy can be used as an effective method to improve the COVID-19 pneumonia of mild patients, although it helpless with accelerating the virus clearance. These results should be verified in a larger prospective randomized environment.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Indoles/therapeutic use , Interferon alpha-2/therapeutic use , Pneumonia, Viral/drug therapy , Adult , Aged , Aged, 80 and over , COVID-19 , China , Drug Therapy, Combination/methods , Female , Humans , Length of Stay , Lymphopenia/drug therapy , Male , Middle Aged , Pandemics , RNA, Viral/blood , Retrospective Studies , SARS-CoV-2 , Young Adult
14.
Microbes Infect ; 22(9): 500-503, 2020 10.
Article in English | MEDLINE | ID: covidwho-608942

ABSTRACT

COVID-19 patients (n = 34) suffering from ARDS were treated with tocilizumab (TCZ). Outcome was classified in two groups: "Death" and "Recovery". Predictive factors of mortality were studied. Mean age was 75.3, mean oxygen (O2) requirements 10.4 l/min. At baseline, all patients had multiple biological abnormalities (lymphopenia, increased CRP, ferritin, fibrinogen, D-dimer and liver enzymes). 24 patients (70.5%) recovered after TCZ therapy and 10 died (29.5%). Deceased subjects differed from patients in whom treatment was effective with regard to more pronounced lymphopenia (0.6 vs 1.0 G/l; p = 0.037), lower platelet number (156 vs 314 G/l; p = 0.0001), lower fibrinogen serum level (0.6 vs 1.0 G/l; p = 0.03), higher aspartate-amino-transferase (108 vs 57 UI/l; p = 0.05) and greater O2 requirements (11 vs 8 l/min; p = 0.003).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Lymphopenia/drug therapy , Pneumonia, Viral/drug therapy , Respiratory Distress Syndrome/drug therapy , Thrombocytopenia/drug therapy , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Anticoagulants/therapeutic use , Aspartate Aminotransferases/blood , Betacoronavirus/drug effects , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/virology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/metabolism , Humans , Hydroxychloroquine/therapeutic use , Lymphopenia/diagnosis , Lymphopenia/mortality , Lymphopenia/virology , Male , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Prognosis , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/virology , Retrospective Studies , SARS-CoV-2 , Survival Analysis , Thrombocytopenia/diagnosis , Thrombocytopenia/mortality , Thrombocytopenia/virology , Tomography, X-Ray Computed , Treatment Outcome
15.
Eur J Cancer ; 135: 62-65, 2020 08.
Article in English | MEDLINE | ID: covidwho-605486

ABSTRACT

While confirmed cases of the deadly coronavirus disease 2019 (COVID-19) have exceeded 4.7 million globally, scientists are pushing forward with efforts to develop vaccines and treatments in an attempt to slow the pandemic and lessen the disease's damage. Although no proven effective therapies for treating patients with COVID-19 or for managing their complications currently exist, the rapidly expanding knowledge regarding severe acute respiratory syndrome coronavirus 2 and its interplay with hosts provides a significant number of potential drug targets and the potential to repurpose drugs already tested in other diseases. Herein, we report the biological rationale of immune-activating drugs and a brief summary of literature data on the potential therapeutic value of immune checkpoint inhibitors that have been recently tested beyond cancer treatment for their potential to restore cellular immunocompetence.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Immunologic Factors/therapeutic use , Neoplasms/drug therapy , Pneumonia, Viral/drug therapy , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Apoptosis/drug effects , Apoptosis/immunology , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/immunology , Coronavirus Infections/virology , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/immunology , Humans , Immunologic Factors/pharmacology , Lymphopenia/blood , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/virology , Neoplasms/blood , Neoplasms/immunology , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Randomized Controlled Trials as Topic , SARS-CoV-2 , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Treatment Outcome
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