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1.
Histol Histopathol ; 36(9): 947-965, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1513241

ABSTRACT

Infection by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) leads to multi-organ failure associated with a cytokine storm and septic shock. The virus evades the mitochondrial production of interferons through its N protein and, from that moment on, it hijacks the functions of these organelles. The aim of this study was to show how the virus kidnaps the mitochondrial machinery for its benefit and survival, leading to alterations of serum parameters and to nitrosative stress (NSS). In a prospective cohort of 15 postmortem patients who died from COVID-19, six markers of mitochondrial function (COX II, COX IV, MnSOD, nitrotyrosine, Bcl-2 and caspase-9) were analyzed by the immune colloidal gold technique in samples from the lung, heart, and liver. Biometric laboratory results from these patients showed alterations in hemoglobin, platelets, creatinine, urea nitrogen, glucose, C-reactive protein, albumin, D-dimer, ferritin, fibrinogen, Ca²âº, K⁺, lactate and troponin. These changes were associated with alterations in the mitochondrial structure and function. The multi-organ dysfunction present in COVID-19 patients may be caused, in part, by damage to the mitochondria that results in an inflammatory state that contributes to NSS, which activates the sepsis cascade and results in increased mortality in COVID-19 patients.


Subject(s)
COVID-19/pathology , Mitochondria/pathology , Nitrosative Stress/physiology , Aged , Female , Humans , Male , Middle Aged , SARS-CoV-2
2.
Clin Hemorheol Microcirc ; 78(2): 199-207, 2021.
Article in English | MEDLINE | ID: covidwho-1352794

ABSTRACT

INTRODUCTION: Coronavirus disease-19 (COVID-19) is a new type of epidemic pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The population is generally susceptible to COVID-19, which mainly causes lung injury. Some cases may develop severe acute respiratory distress syndrome (ARDS). Currently, ARDS treatment is mainly mechanical ventilation, but mechanical ventilation often causes ventilator-induced lung injury (VILI) accompanied by hypercapnia in 14% of patients. Extracorporeal carbon dioxide removal (ECCO2R) can remove carbon dioxide from the blood of patients with ARDS, correct the respiratory acidosis, reduce the tidal volume and airway pressure, and reduce the incidence of VILI. CASE REPORT: Two patients with critical COVID-19 combined with multiple organ failure undertook mechanical ventilation and suffered from hypercapnia. ECCO2R, combined with continuous renal replacement therapy (CRRT), was conducted concomitantly. In both cases (No. 1 and 2), the tidal volume and positive end-expiratory pressure (PEEP) were down-regulated before the treatment and at 1.5 hours, one day, three days, five days, eight days, and ten days after the treatment, together with a noticeable decrease in PCO2 and clear increase in PO2, while FiO2 decreased to approximately 40%. In case No 2, compared with the condition before treatment, the PCO2 decreased significantly with down-regulation in the tidal volume and PEEP and improvement in the pulmonary edema and ARDS after the treatment. CONCLUSION: ECCO2R combined with continuous blood purification therapy in patients with COVID-19 who are criti-cally ill and have ARDS and hypercapnia might gain both time and opportunity in the treatment, down-regulate the ventilator parameters, reduce the incidence of VILI and achieve favorable therapeutic outcomes.


Subject(s)
COVID-19/complications , Carbon Dioxide/isolation & purification , Extracorporeal Circulation/methods , Hemofiltration/methods , Hypercapnia/therapy , Respiratory Distress Syndrome/therapy , SARS-CoV-2/isolation & purification , Aged , COVID-19/transmission , COVID-19/virology , Humans , Hypercapnia/physiopathology , Hypercapnia/virology , Male , Positive-Pressure Respiration , Respiration, Artificial , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/virology
3.
Vasc Health Risk Manag ; 17: 273-298, 2021.
Article in English | MEDLINE | ID: covidwho-1262578

ABSTRACT

COVID-19 sepsis is characterized by acute respiratory distress syndrome (ARDS) as a consequence of pulmonary tropism of the virus and endothelial heterogeneity of the host. ARDS is a phenotype among patients with multiorgan dysfunction syndrome (MODS) due to disseminated vascular microthrombotic disease (VMTD). In response to the viral septicemia, the host activates the complement system which produces terminal complement complex C5b-9 to neutralize pathogen. C5b-9 causes pore formation on the membrane of host endothelial cells (ECs) if CD59 is underexpressed. Also, viral S protein attraction to endothelial ACE2 receptor damages ECs. Both affect ECs and provoke endotheliopathy. Disseminated endotheliopathy activates two molecular pathways: inflammatory and microthrombotic. The former releases inflammatory cytokines from ECs, which lead to inflammation. The latter initiates endothelial exocytosis of unusually large von Willebrand factor (ULVWF) multimers and FVIII from Weibel-Palade bodies. If ADAMTS13 is insufficient, ULVWF multimers activate intravascular hemostasis of ULVWF path. In activated ULVWF path, ULVWF multimers anchored to damaged endothelial cells recruit circulating platelets and trigger microthrombogenesis. This process produces "microthrombi strings" composed of platelet-ULVWF complexes, leading to endotheliopathy-associated VMTD (EA-VMTD). In COVID-19, microthrombosis initially affects the lungs per tropism causing ARDS, but EA-VMTD may orchestrate more complex clinical phenotypes, including thrombotic thrombocytopenic purpura (TTP)-like syndrome, hepatic coagulopathy, MODS and combined micro-macrothrombotic syndrome. In this pandemic, ARDS and pulmonary thromboembolism (PTE) have often coexisted. The analysis based on two hemostatic theories supports ARDS caused by activated ULVWF path is EA-VMTD and PTE caused by activated ULVWF and TF paths is macrothrombosis. The thrombotic disorder of COVID-19 sepsis is consistent with the notion that ARDS is virus-induced disseminated EA-VMTD and PTE is in-hospital vascular injury-related macrothrombosis which is not directly  related to viral pathogenesis. The pathogenesis-based therapeutic approach is discussed for the treatment of EA-VMTD with antimicrothrombotic regimen and the potential need of anticoagulation therapy for coinciding macrothrombosis in comprehensive COVID-19 care.


Subject(s)
COVID-19/epidemiology , Endothelial Cells/metabolism , Fibrinolytic Agents/therapeutic use , Hemostasis/physiology , SARS-CoV-2 , Sepsis/complications , Thrombosis/etiology , COVID-19/complications , Humans , Pandemics , Phenotype , Sepsis/metabolism , Thrombosis/drug therapy , Thrombosis/metabolism
4.
Inflamm Res ; 70(8): 877-889, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1258183

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, known as coronavirus disease 2019 (COVID-19) causes cytokine release syndrome (CRS), leading to acute respiratory distress syndrome (ARDS), acute kidney and cardiac injury, liver dysfunction, and multiorgan failure. Although several studies have discussed the role of 5-lipoxygenase (5-LOX) in viral infections, such as influenzae and SARS, it remains unexplored in the pathophysiology of COVID-19. 5-LOX acts on free arachidonic acid (AA) to form proinflammatory leukotrienes (LTs). Of note, numerous cells involved with COVID-19 (e.g., inflammatory and smooth muscle cells, platelets, and vascular endothelium) widely express leukotriene receptors. Moreover, 5-LOX metabolites induce the release of cytokines (e.g., tumour necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and interleukin-1ß [IL-1ß]) and express tissue factor on cell membranes and activate plasmin. Since macrophages, monocytes, neutrophils, and eosinophils can express lipoxygenases, activation of 5-LOX and the subsequent release of LTs may contribute to the severity of COVID-19. This review sheds light on the potential implications of 5-LOX in SARS-CoV-2-mediated infection and the anticipated therapeutic role of 5-LOX inhibitors.


Subject(s)
Arachidonate 5-Lipoxygenase/metabolism , COVID-19/drug therapy , COVID-19/enzymology , COVID-19/physiopathology , Interleukins/metabolism , Lipoxygenase Inhibitors/pharmacology , SARS-CoV-2 , Animals , Arachidonic Acid/metabolism , Cytokine Release Syndrome , Cytokines/metabolism , Enzyme Inhibitors/pharmacology , Humans , Inflammation , Leukotrienes/metabolism , Treatment Outcome , Virus Diseases/drug therapy
5.
Crit Care Res Pract ; 2021: 5585291, 2021.
Article in English | MEDLINE | ID: covidwho-1255646

ABSTRACT

BACKGROUND: COVID-19 may result in multiorgan failure and death. Early detection of patients at risk may allow triage and more intense monitoring. The aim of this study was to develop a simple, objective admission score, based on laboratory tests, that identifies patients who are likely going to deteriorate. METHODS: This is a retrospective cohort study of all COVID-19 patients admitted to a tertiary academic medical center in New York City during the COVID-19 crisis in spring 2020. The primary combined endpoint included intubation, stage 3 acute kidney injury (AKI), or death. Laboratory tests available on admission in at least 70% of patients (and age) were included for univariate analysis. Tests that were statistically or clinically significant were then included in a multivariate binary logistic regression model using stepwise exclusion. 70% of all patients were used to train the model, and 30% were used as an internal validation cohort. The aim of this study was to develop and validate a model for COVID-19 severity based on biomarkers. RESULTS: Out of 2545 patients, 833 (32.7%) experienced the primary endpoint. 53 laboratory tests were analyzed, and of these, 47 tests (and age) were significantly different between patients with and without the endpoint. The final multivariate model included age, albumin, creatinine, C-reactive protein, and lactate dehydrogenase. The area under the ROC curve was 0.850 (CI [95%]: 0.813, 0.889), with a sensitivity of 0.800 and specificity of 0.761. The probability of experiencing the primary endpoint can be calculated as p=e (-2.4475+0.02492age - 0.6503albumin+0.81926creat+0.00388CRP+0.00143LDH)/1+e (-2.4475+ 0.02492age - 0.6503albumin+0.81926creat+0.00388CRP+0.00143LDH). CONCLUSIONS: Our study demonstrated that poor outcome in COVID-19 patients can be predicted with good sensitivity and specificity using a few laboratory tests. This is useful for identifying patients at risk during admission.

6.
Microb Pathog ; 158: 105008, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1253396

ABSTRACT

Coronavirus disease 2019 (COVID-19) transmits from person to person mainly through respiratory droplets and coughing. Infection severity ranges from asymptomatic and mild infection to those with moderate and severe symptoms which may lead to multiple organ failure and mortality. Infection severity largely depends on individual's immune response, age and co-morbidities. Present study categorized COVID-19 infected patients based on their infection severity and linked COVID-19 severity with age, gender and ABO blood group types. Clinical details of 383 COVID-19 patients were collected from Rajiv Gandhi Super Specialty hospital (RGSSH), India; divided into three groups; mild, moderate and severe patients, based on their symptoms. Present analysis revealed that age plays major role in infection severity, as the symptoms are more severe in patients above 45 years. Infection rate was higher in males compared to females. Most patients with A(+ve) and B(+ve) blood group were severely affected compared to those of blood group type O(+ve) and AB(+ve). O(+ve) blood group was least represented in severe patients. Present findings could be helpful in generating awareness amongst the population regarding susceptibility towards the COVID-19 infection. This supportive information would help clinicians and health workers to propose new strategies and tactical solution against COVID-19 infection.


Subject(s)
ABO Blood-Group System , COVID-19 , Comorbidity , Female , Humans , India/epidemiology , Male , Middle Aged , SARS-CoV-2
7.
SAGE Open Med Case Rep ; 9: 2050313X211015899, 2021.
Article in English | MEDLINE | ID: covidwho-1238639

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which started in Wuhan, Hubei Province, China, and progressed to a pandemic affecting over 210 countries and territories including the United States. The severity of symptoms range from mild to critical disease involving multi-organ failure; however, many pregnant COVID-19 patients have mild symptoms. The understanding of COVID-19 is evolving and there is limited data about its effects in pregnancy. This case series features two pregnant patients with COVID-19 with a range of symptoms, including fever, non-productive cough, headache, and worsening dyspnea. Both patients had chest x-ray findings notable for lung opacities, and lymphopenia was a consistent abnormal laboratory finding. Both of the patients had hypoxia which was treated with hydroxychloroquine and lopinavir-ritonavir with significant improvement in clinical symptoms and prolongation of pregnancy.

8.
Immunopharmacol Immunotoxicol ; 43(3): 247-258, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1238099

ABSTRACT

SARS-CoV-2 is a type of beta-CoV that develops acute pneumonia, which is an inflammatory condition. A cytokine storm has been recognized as one of the leading causes of death in patients with COVID-19. ALI and ARDS along with multiple organ failure have also been presented as the consequences of acute inflammation and cytokine storm. It has been previously confirmed that SARS-CoV, as another member of the beta-CoV family, activates NLRP3 inflammasome and consequently develops acute inflammation in a variety of ways through having complex interactions with the host immune system using structural and nonstructural proteins. Numerous studies conducted on Tranilast have further demonstrated that the given drug can act as an effective anti-chemotactic factor on controlling inflammation, and thus, it can possibly help the improvement of the acute form of COVID-19 by inhibiting some key inflammation-associated transcription factors such as NF-κB and impeding NLRP3 inflammasome. Several studies have comparably revealed the direct effect of this drug on the prevention of inappropriate tissue's remodeling; inhibition of neutrophils, IL-5, and eosinophils; repression of inflammatory cell infiltration into inflammation site; restriction of factors involved in acute airway inflammation like IL-33; and suppression of cytokine IL-13, which increase mucosal secretions. Therefore, Tranilast may be considered as a potential treatment for patients with the acute form of COVID-19 along with other drugs.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Inflammasomes/immunology , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , SARS-CoV-2/immunology , ortho-Aminobenzoates/therapeutic use , COVID-19/immunology , COVID-19/pathology , Humans
9.
Anaesthesiol Intensive Ther ; 53(2): 153-161, 2021.
Article in English | MEDLINE | ID: covidwho-1234881

ABSTRACT

Patients hospitalized in the intensive care unit (ICU) due to the COVID-19 experience a high incidence (up to 43%) of venous thromboembolic events. While laboratory findings in COVID-19-associated coagulopathy (CAC) show increased D-dimer and fibrinogen levels, the abnormalities in standard coagulation tests and platelet count are minimal. Recent studies suggest contribution of fibrinolysis shutdown to this phenomenon. Endothelial injury and alteration of its antithrombotic activity can lead to micro- and macrovascular thrombosis in the lungs, occurrence of which is associated with poor clinical outcome in critically ill patients with COVID-19. Additionally, the hypercoagulability induced by activation of coagulation pathways during the immune response to SARS-CoV-2 infection contributes to impaired organ perfusion. This, alongside with hypoxemia, leads to multiorgan failure. Various diagnostic regimens, some of which include global assays of haemostasis, are currently being published and discussed. Numerous guidelines and recommendations of scientific societies and groups of specialists have been published. However, there is no single optimal algorithm for anticoagulation treatment and monitoring specific to the ICU patients with COVID-19. The authors have attempted to summarize the data related to CAC and thrombotic disease and develop an algorithm consistent with the latest clinical practice guideline recommendations.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , COVID-19/complications , Algorithms , Blood Coagulation/drug effects , COVID-19/drug therapy , Female , Humans , Intensive Care Units , Male , Thrombosis/etiology , Thrombosis/prevention & control , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
10.
Pulmonology ; 28(1): 34-43, 2022.
Article in English | MEDLINE | ID: covidwho-1213484

ABSTRACT

INTRODUCTION AND OBJECTIVES: Severe asthma management during the coronavirus disease 2019 (COVID-19) pandemic is a challenge and will continue to be, at least in the next few months, as herd immunity is still a mirage. A lot has to be learned about how COVID-19 affects underlying diseases, and severe asthma is no exception. METHODS: Narrative review of papers available until February 2021 in PubMed and Google Scholar, relating severe asthma and COVID-19. Four main research topics were reviewed: SARS-CoV-2 infection: immunology and respiratory pathology; interrelationship of severe asthma endotypes and COVID-19 disease mechanisms; severe asthma epidemiology and COVID-19; and biologics for severe asthma in the context of COVID-19. RESULTS: COVID-19 disease mechanisms start with upper respiratory cell infection, and afterwards several immunological facets are activated, contributing to disease severity, namely cell-mediated immunity and antibody production. Although infrequent in the COVID-19 course some patients develop a cytokine storm that causes organ damage and may lead to acute respiratory distress syndrome or multiorgan failure. Regarding severe asthma endotypes, type2-high might have a protective role both in infection risk and disease course. There is conflicting data regarding the epidemiological relationship between COVID-19 among severe asthma patients, with some studies reporting increased risk of infection and disease course, whereas others the other way round. Biologics for severe asthma do not seem to increase the risk of infection and severe COVID-19, although further evidence is needed. CONCLUSIONS: Globally, in the era of COVID-19, major respiratory societies recommend continuing the biologic treatment, preferably in a self-home administration program.


Subject(s)
Asthma , Biological Products , COVID-19 , SARS-CoV-2/immunology , Asthma/complications , Asthma/epidemiology , Asthma/immunology , COVID-19/epidemiology , COVID-19/immunology , Humans , Immunologic Factors , Pandemics , Risk Factors , Severity of Illness Index
11.
PLoS One ; 16(4): e0245414, 2021.
Article in English | MEDLINE | ID: covidwho-1207627

ABSTRACT

BACKGROUND: Chile has become one of the countries most affected by COVID-19, a pandemic that has generated a large number of cases worldwide. If not detected and treated in time, COVID-19 can cause multi-organ failure and even death. Therefore, it is necessary to understand the behavior of the spread of COVID-19 as well as the projection of infections and deaths. This information is very relevant so that public health organizations can distribute financial resources efficiently and take appropriate containment measures. In this research, we compare different time series methodologies to predict the number of confirmed cases of and deaths from COVID-19 in Chile. METHODS: The methodology used in this research consisted of modeling cases of both confirmed diagnoses and deaths from COVID-19 in Chile using Autoregressive Integrated Moving Average (ARIMA henceforth) models, Exponential Smoothing techniques, and Poisson models for time-dependent count data. Additionally, we evaluated the accuracy of the predictions using a training set and a test set. RESULTS: The dataset used in this research indicated that the most appropriate model is the ARIMA time series model for predicting the number of confirmed COVID-19 cases, whereas for predicting the number of deaths from COVID-19 in Chile, the most suitable approach is the damped trend method. CONCLUSION: The ARIMA models are an alternative to modeling the behavior of the spread of COVID-19; however, depending on the characteristics of the dataset, other methodologies can better predict the behavior of these records, for example, the Holt-Winter method implemented with time-dependent count data.


Subject(s)
COVID-19/epidemiology , Algorithms , COVID-19/diagnosis , COVID-19/mortality , Chile/epidemiology , Forecasting , Humans , Models, Statistical , Public Health , SARS-CoV-2/isolation & purification
12.
Int J Mol Sci ; 22(9)2021 Apr 26.
Article in English | MEDLINE | ID: covidwho-1201474

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of Coronavirus Disease-2019 (COVID-19) in humans. ACE-2 is a type I transmembrane metallocarboxypeptidase expressed in vascular endothelial cells, alveolar type 2 lung epithelial cells, renal tubular epithelium, Leydig cells in testes and gastrointestinal tract. ACE2 mediates the interaction between host cells and SARS-CoV-2 spike (S) protein. However, ACE2 is not only a SARS-CoV-2 receptor, but it has also an important homeostatic function regulating renin-angiotensin system (RAS), which is pivotal for both the cardiovascular and immune systems. Therefore, ACE2 is the key link between SARS-CoV-2 infection, cardiovascular diseases (CVDs) and immune response. Susceptibility to SARS-CoV-2 seems to be tightly associated with ACE2 availability, which in turn is determined by genetics, age, gender and comorbidities. Severe COVID-19 is due to an uncontrolled and excessive immune response, which leads to acute respiratory distress syndrome (ARDS) and multi-organ failure. In spite of a lower ACE2 expression on cells surface, patients with CVDs have a higher COVID-19 mortality rate, which is likely driven by the imbalance between ADAM metallopeptidase domain 17 (ADAM17) protein (which is required for cleavage of ACE-2 ectodomain resulting in increased ACE2 shedding), and TMPRSS2 (which is required for spike glycoprotein priming). To date, ACE inhibitors and Angiotensin II Receptor Blockers (ARBs) treatment interruption in patients with chronic comorbidities appears unjustified. The rollout of COVID-19 vaccines provides opportunities to study the effects of different COVID-19 vaccines on ACE2 in patients on treatment with ACEi/ARB.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , Cardiovascular Diseases/pathology , SARS-CoV-2/physiology , ADAM17 Protein/metabolism , COVID-19/complications , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , Cardiovascular Diseases/complications , Humans , Receptors, Virus/metabolism , SARS-CoV-2/isolation & purification , Serine Endopeptidases/metabolism
13.
J Med Virol ; 93(1): 8-19, 2021 01.
Article in English | MEDLINE | ID: covidwho-1196413

ABSTRACT

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


Subject(s)
Bacterial Infections/complications , COVID-19/complications , Coinfection/virology , HIV Infections/complications , Influenza, Human/complications , SARS-CoV-2 , Humans
14.
Adv Mater ; 33(20): e2100012, 2021 May.
Article in English | MEDLINE | ID: covidwho-1173766

ABSTRACT

The COVID-19 pandemic, induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused great impact on the global economy and people's daily life. In the clinic, most patients with COVID-19 show none or mild symptoms, while approximately 20% of them develop severe pneumonia, multiple organ failure, or septic shock due to infection-induced cytokine release syndrome (the so-called "cytokine storm"). Neutralizing antibodies targeting inflammatory cytokines may potentially curb immunopathology caused by COVID-19; however, the complexity of cytokine interactions and the multiplicity of cytokine targets make attenuating the cytokine storm challenging. Nonspecific in vivo biodistribution and dose-limiting side effects further limit the broad application of those free antibodies. Recent advances in biomaterials and nanotechnology have offered many promising opportunities for infectious and inflammatory diseases. Here, potential mechanisms of COVID-19 cytokine storm are first discussed, and relevant therapeutic strategies and ongoing clinical trials are then reviewed. Furthermore, recent research involving emerging biomaterials for improving antibody-based and broad-spectrum cytokine neutralization is summarized. It is anticipated that this work will provide insights on the development of novel therapeutics toward efficacious management of COVID-19 cytokine storm and other inflammatory diseases.


Subject(s)
Biocompatible Materials/chemistry , COVID-19/pathology , Cytokine Release Syndrome/therapy , Cytokines/chemistry , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/immunology , Biocompatible Materials/metabolism , COVID-19/complications , COVID-19/virology , Cytokine Release Syndrome/etiology , Cytokines/immunology , Cytokines/metabolism , Extracellular Vesicles/chemistry , Humans , Nanoparticles/chemistry , Polymers/chemistry , SARS-CoV-2/isolation & purification
15.
Sci Rep ; 11(1): 6357, 2021 03 18.
Article in English | MEDLINE | ID: covidwho-1142469

ABSTRACT

The recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in most individuals, leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. This study explores the proteomic differences between mild, severe, and critical COVID-19 positive patients to further understand the disease progression, identify proteins associated with disease severity, and identify potential therapeutic targets. Blood protein profiling was performed on 59 COVID-19 mild (n = 26), severe (n = 9) or critical (n = 24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed at https://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/ . Our results demonstrate that dynamic changes in blood proteins associated with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.


Subject(s)
Biomarkers/blood , COVID-19/blood , Central Nervous System Diseases/virology , Proteome , Aged , COVID-19/complications , Case-Control Studies , Cohort Studies , Female , Gene Expression Profiling , Gliosis/virology , Humans , Male , Middle Aged , Nerve Tissue Proteins/blood
16.
Nutrients ; 13(3)2021 Mar 17.
Article in English | MEDLINE | ID: covidwho-1138747

ABSTRACT

At the end of 2019, a new coronavirus (COVID-19) appeared on the world scene, which mainly affects the respiratory system, causing pneumonia and multi-organ failure, and, although it starts with common symptoms such as shortness of breath and fever, in about 2-3% of cases it leads to death. Unfortunately, to date, no specific treatments have been found for the cure of this virus and, therefore, it is advisable to implement all possible strategies in order to prevent infection. In this context, it is important to better define the role of all behaviors, in particular nutrition, in order to establish whether these can both prevent infection and improve the outcome of the disease in patients with COVID-19. In the literature, it is widely shown that states of malnutrition, overweight, and obesity negatively affect the immune system, leading to viral infections, and several studies have shown that nutritional interventions can act as immunostimulators, helping to prevent viral infections. Even if several measures, such as the assumption of a specific diet regimen, the use of dietary supplements, and other similar interventions, are promising for the prevention, management, and recovery of COVID-19 patients, it is important to highlight that strong data from randomized clinical trials are needed to support any such assumption. Considering this particular scenario, we present a literature review addressing several important aspects related to diet and SARS-CoV-2 infection, in order to highlight the importance of diet and supplementation in prevention and management of, as well as recovery from COVID-19.


Subject(s)
COVID-19/prevention & control , Dietary Supplements , Nutritional Status , Diet , Humans
17.
J Clin Pathol ; 75(6): 383-389, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1136101

ABSTRACT

BACKGROUND: Secondary haemophagocytic lymphohistiocytosis (sHLH) is characterised by a hyper activation of immune system that leads to multiorgan failure. It is suggested that excessive immune response in patients with COVID-19 could mimic this syndrome. Some COVID-19 autopsy studies have revealed the presence of haemophagocytosis images in bone marrow, raising the possibility, along with HScore parameters, of sHLH. AIM: Our objective is to ascertain the existence of sHLH in some patients with severe COVID-19. METHODS: We report the autopsy histological findings of 16 patients with COVID-19, focusing on the presence of haemophagocytosis in bone marrow, obtained from rib squeeze and integrating these findings with HScore parameters. CD68 immunohistochemical stains were used to highlight histiocytes and haemophagocytic cells. Clinical evolution and laboratory parameters of patients were collected from electronic clinical records. RESULTS: Eleven patients (68.7%) displayed moderate histiocytic hyperplasia with haemophagocytosis (HHH) in bone marrow, three patients (18.7%) displayed severe HHH and the remainder were mild. All HScore parameters were collected in 10 patients (62.5%). Among the patients in which all parameters were evaluable, eight patients (80%) had an HScore >169. sHLH was not clinically suspected in any case. CONCLUSIONS: Our results support the recommendation of some authors to use the HScore in patients with severe COVID-19 in order to identify those who could benefit from immunosuppressive therapies. The presence of haemophagocytosis in bone marrow tissue, despite not being a specific finding, has proved to be a very useful tool in our study to identify these patients.


Subject(s)
COVID-19 , Lymphohistiocytosis, Hemophagocytic , Autopsy , Bone Marrow/pathology , COVID-19/complications , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/pathology , Multiple Organ Failure/pathology
18.
Front Med (Lausanne) ; 8: 604263, 2021.
Article in English | MEDLINE | ID: covidwho-1106028

ABSTRACT

Corticosteroid is commonly used to reduce damage from inflammatory reactions in coronavirus disease 2019 (COVID-19). We aim to determine the outcomes of corticosteroid use in critically ill COVID-19 patients. Ninety six critically ill patients, hospitalized in 14 hospitals outside Wuhan from January 16 to March 30, 2020 were enrolled in this study. Among 96 critical patients, 68 were treated with corticosteroid (CS group), while 28 were not treated with corticosteroids (non-CS group). Multivariable logistic regression were performed to determine the possible correlation between corticosteroid use and the treatment outcomes. Forty-six (68%) patients in the CS group died compared to six (21%) of the non-CS group. Corticosteroid use was also associated with the development of ARDS, exacerbation of pulmonary fibrosis, longer hospital stay and virus clearance time. On admission, no difference in laboratory findings between the CS and the non-CS group was observed. After corticosteroid treatment, patients treated with corticosteroids were associated with higher counts of white blood cells, neutrophils, neutrophil-to-lymphocyte ratio, alanine aminotransferase level and Sequential Organ Failure Assessment score. In conclusion, corticosteroid use in critically ill COVID-19 patients was associated with a much higher case fatality rate. Frequent incidence of liver injury and multi-organ failure in corticosteroid treated patients may have contributed to the adverse outcomes. The multi-organ failure is likely caused by more persistent SARS-CoV-2 infection and higher viral load, due to the inhibition of immune surveillance by corticosteroid.

19.
Virus Res ; 299: 198347, 2021 07 02.
Article in English | MEDLINE | ID: covidwho-1096265

ABSTRACT

BACKGROUND: There is a marked discrepancy between SARS-CoV-2 seroprevalence and COVID-19 cases and deaths in Africa. MAIN: SARS-CoV-2 stimulates humoral and cellular immunity systems, as well as mitogen-activated protein kinase (MAPK) and nuclear NF-kB signalling pathways, which regulate inflammatory gene expression and immune cell differentiation. The result is pro-inflammatory cytokines release, hyperinflammatory condition, and cytokine storm, which provoke severe lung alterations that can lead to multi-organ failure in COVID-19. Multiple genetic and immunologic factors may contribute to the severity of COVID-19 in African individuals when compared to the rest of the global population. In this article, the role of malaria, NF-kB and MAPK pathways, caspase-12 expression, high level of LAIR-1-containing antibodies, and differential glycophorins (GYPA/B) expression in COVID-19 are discussed. CONCLUSION: Understanding pathophysiological mechanisms can help identify target points for drugs and vaccines development against COVID-19. To our knowledge, this is the first study that explores this link and proposes a biological and molecular answer to the epidemiologic discrepancy in COVID-19 in Africa.


Subject(s)
COVID-19/genetics , COVID-19/immunology , Malaria/genetics , Malaria/immunology , Africa/epidemiology , COVID-19/epidemiology , COVID-19/ethnology , Caspase 12/genetics , Caspase 12/immunology , Glycophorins/genetics , Glycophorins/immunology , Humans , Malaria/epidemiology , Malaria/ethnology , NF-kappa B/immunology , Receptors, Immunologic/genetics , Receptors, Immunologic/immunology , SARS-CoV-2/immunology , Signal Transduction/immunology
20.
Life Sci ; 272: 119251, 2021 May 01.
Article in English | MEDLINE | ID: covidwho-1096150

ABSTRACT

A novel infectious disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in December 2019 and declared as a global pandemic by the World Health. Approximately 15% of patients with COVID-19 progress to severe pneumonia and eventually develop acute respiratory distress syndrome (ARDS), septic shock and/or multiple organ failure with high morbidity and mortality. Evidence points towards a determinant pathogenic role of members of the renin-angiotensin system (RAS) in mediating the susceptibility, infection, inflammatory response and parenchymal injury in lungs and other organs of COVID-19 patients. The receptor for advanced glycation end-products (RAGE), a member of the immunoglobulin superfamily, has important roles in pulmonary pathological states, including fibrosis, pneumonia and ARDS. RAGE overexpression/hyperactivation is essential to the deleterious effects of RAS in several pathological processes, including hypertension, chronic kidney and cardiovascular diseases, and diabetes, all of which are major comorbidities of SARS-CoV-2 infection. We propose RAGE as an additional molecular target in COVID-19 patients for ameliorating the multi-organ pathology induced by the virus and improving survival, also in the perspective of future infections by other coronaviruses.


Subject(s)
COVID-19/complications , Drug Discovery , Multiple Organ Failure/etiology , Multiple Organ Failure/prevention & control , Receptor for Advanced Glycation End Products/antagonists & inhibitors , SARS-CoV-2/physiology , Animals , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/pathology , Humans , Molecular Targeted Therapy , Multiple Organ Failure/metabolism , Multiple Organ Failure/pathology , Receptor for Advanced Glycation End Products/metabolism , Renin-Angiotensin System/drug effects , SARS-CoV-2/drug effects , Signal Transduction/drug effects
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