Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 138
Filter
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.
Phytother Res ; 35(8): 4258-4283, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1355894

ABSTRACT

Emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, COVID-19, has become the global panic since December 2019, which urges the global healthcare professionals to identify novel therapeutics to counteract this pandemic. So far, there is no approved treatment available to control this public health issue; however, a few antiviral agents and repurposed drugs support the patients under medical supervision by compromising their adverse effects, especially in emergency conditions. Only a few vaccines have been approved to date. In this context, several plant natural products-based research studies are evidenced to play a crucial role in immunomodulation that can prevent the chances of infection as well as combat the cytokine release storm (CRS) generated during COVID-19 infection. In this present review, we have focused on flavonoids, especially epicatechin, epigallocatechin gallate, hesperidin, naringenin, quercetin, rutin, luteolin, baicalin, diosmin, ge nistein, biochanin A, and silymarin, which can counteract the virus-mediated elevated levels of inflammatory cytokines leading to multiple organ failure. In addition, a comprehensive discussion on available in silico, in vitro, and in vivo findings with critical analysis has also been evaluated, which might pave the way for further development of phytotherapeutics to identify the potential lead candidatetoward effective and safe management of the SARS-CoV-2 disease.


Subject(s)
COVID-19 , Cytokine Release Syndrome , Flavonoids/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Cytokines , Humans , Pandemics
3.
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
4.
Pediatr Blood Cancer ; 68(9): e29102, 2021 09.
Article in English | MEDLINE | ID: covidwho-1272230

ABSTRACT

The cytokine storm of secondary haemophagocytic lymphohistiocytosis (sHLH)/macrophage activation syndrome (MAS) can cause life-threatening multiorgan failure. Interleukin-1 (IL-1) receptor blockade with anakinra can be effective in the management of sHLH/MAS. Subcutaneous (SC) dosing regimens are widely described; however, intravenous (IV) dosing is advantageous where time-critical intervention is vital and where SC oedema and/or hypoperfusion limits absorption. We review three critically ill children (aged 9, 11 and 17) with sHLH and rapidly progressive multiorgan dysfunction, successfully treated with continuous IV anakinra infusion. This case series significantly enhances the incipient knowledge regarding the safety and efficacy of IV anakinra for life-threatening sHLH.


Subject(s)
Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lymphohistiocytosis, Hemophagocytic , Macrophage Activation Syndrome , Administration, Intravenous , Child , Critical Illness , Cytokine Release Syndrome , Humans , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Lymphohistiocytosis, Hemophagocytic/drug therapy , Macrophage Activation Syndrome/drug therapy , Multiple Organ Failure/drug therapy , Multiple Organ Failure/etiology
5.
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
6.
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
7.
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.

8.
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
9.
Arch Argent Pediatr ; 119(3): e252-e255, 2021 06.
Article in English, Spanish | MEDLINE | ID: covidwho-1242314

ABSTRACT

Coronavirus infections (CoV) are common in pediatric patients. In general, they produce a mild clinical presentation consisting of an upper respiratory tract infection that does not usually infect the lungs, with the exception of preterm infants and children with chronic diseases. These infections exceptionally affect other organs (heart, brain, gastrointestinal tract), thus increasing their severity. In relation to the temporal coincidence with the beginning of the current situation of pandemic by the new beta coronavirus SARS-CoV-2 responsible for its associated disease (COVID-19), this study presents a clinical case of a 5-year-old patient showing multiple-organ failure and neurological sequelae due to bulbar injury and vascular thrombosis caused by an alpha coronavirus (CoV-NL63) due to its severity and exceptionality.


Las infecciones por coronavirus son habituales en los pacientes pediátricos. Por lo general, producen un cuadro clínico leve de infección del tracto respiratorio superior que no suele afectar a los pulmones, salvo en prematuros y niños con enfermedades crónicas de base. Excepcionalmente, afectan a otros órganos (corazón, cerebro, tracto gastrointestinal) e incrementan su gravedad. En relación con la coincidencia temporal con el inicio de la actual pandemia por el nuevo beta coronavirus (SARSCoV- 2), responsable de su enfermedad asociada (COVID-19), se presenta el caso clínico de un paciente de 5 años con fracaso multiorgánico y secuelas neurológicas por afectación bulbar y trombosis vascular ocasionados por un alfa coronavirus (CoVNL63) debido a su gravedad y excepcionalidad.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus NL63, Human/isolation & purification , Multiple Organ Failure/virology , Respiratory Tract Infections/diagnosis , COVID-19/diagnosis , Child, Preschool , Coronavirus Infections/complications , Diagnosis, Differential , Humans , Multiple Organ Failure/diagnosis , Respiratory Tract Infections/complications
10.
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.

11.
J Clin Invest ; 131(10)2021 05 17.
Article in English | MEDLINE | ID: covidwho-1238631

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) is a rare but deadly new disease in children that rapidly progresses to hyperinflammation and shock, and can lead to multiple organ failure if unrecognized. It has been found to be temporally associated with the COVID-19 pandemic and is often associated with SARS-CoV-2 exposure in children. In this issue of the JCI, Porritt, Paschold, et al. identify restricted T cell receptor (TCR) ß-chain variable domain (Vß) usage in patients with severe MIS-C, indicating a potential role for SARS-CoV-2 as a superantigen. These findings suggest that a blood test that determines the presence of specific TCRß variable gene (TRBV) segments may identify patients at risk for severe MIS-C.


Subject(s)
COVID-19 , Child , Humans , Pandemics , SARS-CoV-2 , Superantigens/genetics , Systemic Inflammatory Response Syndrome , T-Lymphocytes
12.
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
13.
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
14.
Antioxidants (Basel) ; 10(5)2021 May 09.
Article in English | MEDLINE | ID: covidwho-1223916

ABSTRACT

Recent reports have demonstrated the association between type 1 diabetes mellitus (T1DM) and increased morbidity and mortality rates during coronavirus disease (COVID-19) infection, setting a priority of these patients for vaccination. Impaired innate and adaptive immunity observed in T1DM seem to play a major role. Severe, life-threatening COVID-19 disease is characterized by the excessive release of pro-inflammatory cytokines, known as a "cytokine storm". Patients with T1DM present elevated levels of cytokines including interleukin-1a (IL), IL-1ß, IL-2, IL-6 and tumor necrosis factor alpha (TNF-α), suggesting the pre-existence of chronic inflammation, which, in turn, has been considered the major risk factor of adverse COVID-19 outcomes in many cohorts. Even more importantly, oxidative stress is a key player in COVID-19 pathogenesis and determines disease severity. It is well-known that extreme glucose excursions, the prominent feature of T1DM, are a potent mediator of oxidative stress through several pathways including the activation of protein kinase C (PKC) and the increased production of advanced glycation end products (AGEs). Additionally, chronic endothelial dysfunction and the hypercoagulant state observed in T1DM, in combination with the direct damage of endothelial cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may result in endothelial and microcirculation impairment, which contribute to the pathogenesis of acute respiratory syndrome and multi-organ failure. The binding of SARS-CoV-2 to angiotensin converting enzyme 2 (ACE2) receptors in pancreatic b-cells permits the direct destruction of b-cells, which contributes to the development of new-onset diabetes and the induction of diabetic ketoacidosis (DKA) in patients with T1DM. Large clinical studies are required to clarify the exact pathways through which T1DM results in worse COVID-19 outcomes.

15.
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
16.
Eur J Immunol ; 51(8): 2074-2085, 2021 08.
Article in English | MEDLINE | ID: covidwho-1212744

ABSTRACT

The aberrant release of inflammatory mediators often referred to as a cytokine storm or cytokine release syndrome (CRS), is a common and sometimes fatal complication in acute infectious diseases including Ebola, dengue, COVID-19, and influenza. Fatal CRS occurrences have also plagued the development of highly promising cancer therapies based on T-cell engagers and chimeric antigen receptor (CAR) T cells. CRS is intimately linked with dysregulated and excessive cytokine release, including IFN-γ, TNF-α, IL 1, IL-6, and IL-10, resulting in a systemic inflammatory response leading to multiple organ failure. Here, we show that mice intravenously administered the agonistic hamster anti-mouse CD3ε monoclonal antibody 145-2C11 develop clinical and laboratory manifestations seen in patients afflicted with CRS, including body weight loss, hepatosplenomegaly, thrombocytopenia, increased vascular permeability, lung inflammation, and hypercytokinemia. Blood cytokine levels and gene expression analysis from lung, liver, and spleen demonstrated a hierarchy of inflammatory cytokine production and infiltrating immune cells with differentiating organ-dependent kinetics. IL-2, IFN-γ, TNF-α, and IL-6 up-regulation preceded clinical signs of CRS. The co-treatment of mice with a neutralizing anti-cytokine antibody cocktail transiently improved early clinical and laboratory features of CRS. We discuss the predictive use of this model in the context of new anti-cytokine strategies to treat human CRS.


Subject(s)
Antibodies, Monoclonal/pharmacology , Antibodies/immunology , CD3 Complex/antagonists & inhibitors , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/metabolism , Cytokines/antagonists & inhibitors , Cytokines/metabolism , Animals , Antibodies/adverse effects , Antibodies, Monoclonal/therapeutic use , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/drug therapy , Cytokines/blood , Disease Models, Animal , Drug Therapy, Combination , Inflammation Mediators/blood , Inflammation Mediators/metabolism , Lymphocyte Activation/immunology , Mice , Phenotype , Severity of Illness Index , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Treatment Outcome
17.
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
18.
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
19.
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
20.
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
SELECTION OF CITATIONS
SEARCH DETAIL