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1.
J Infect Dev Ctries ; 15(10): 1384-1387, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1518650

ABSTRACT

Occurrence and recurrence of COVID-19 cases have been observed globally. The complex relationship of host-pathogen and the environment plays a vital role in understanding the widespread recurrence of the SARS-CoV-2 among humans. Though the pathobiology of the disease is not completely understood, it is well established that COVID-19 poses a greater threat to individuals with co-morbidities and a weakened immune system. The article deals with the notion of innate immunity, natural selection, and the survival of the fittest during the COVID-19 outbreak. The article also attempts to introduce the concept of "lifestyle and cultural immunity" that needs to be addressed and incorporated at an early stage of childhood to boost up the human immune system. The communication further discusses the role of vaccination and micro-organisms pre-existing in the environment which are required to enhance the immunity of an individual.


Subject(s)
COVID-19/immunology , COVID-19/mortality , Immunity, Innate , SARS-CoV-2/pathogenicity , Selection, Genetic/genetics , COVID-19/prevention & control , Disease Outbreaks , Disease Susceptibility/immunology , Host-Pathogen Interactions , Humans , SARS-CoV-2/immunology , Selection, Genetic/immunology , Vaccination
2.
Curr Opin Pediatr ; 33(6): 648-656, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1501212

ABSTRACT

PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused extreme concern for patients with inborn errors of immunity (IEIs). In the first 6  months of the pandemic, the case fatality rate among patients with IEIs resembled that of the general population (9%). This review aims at summarizing what we have learned about the course and outcome of coronavirus disease 2019 (COVID-19) in patients with different IEIs and what this can potentially teach us about the immune mechanisms that could confer protection or predisposition to severe disease. RECENT FINDINGS: A total of 649 patients with IEI and COVID-19 have been reported in the last year and a half, spanning all groups of the International Union of Immunological Societies classification of IEIs. For most patients, the underlying IEI does not represent an independent risk factor for severe COVID-19. In fact, some IEI may even be protective against the severe disease due to impaired inflammation resulting in less immune-mediated collateral tissue damage. SUMMARY: We review the characteristics of SARS-CoV-2 infection in a large number of patients with IEI. Overall, we found that combined immunodeficiencies, immune dysregulation disorders, and innate immune defects impairing type I interferon responses are associated with severe disease course.


Subject(s)
COVID-19 , Primary Immunodeficiency Diseases , Disease Progression , Disease Susceptibility , Humans , SARS-CoV-2
3.
Ann Intern Med ; 174(8): 1090-1100, 2021 08.
Article in English | MEDLINE | ID: covidwho-1497804

ABSTRACT

BACKGROUND: The COVID-19 pandemic has induced historic educational disruptions. In April 2021, about 40% of U.S. public school students were not offered full-time in-person education. OBJECTIVE: To assess the risk for SARS-CoV-2 transmission in schools. DESIGN: An agent-based network model was developed to simulate transmission in elementary and high school communities, including home, school, and interhousehold interactions. SETTING: School structure was parametrized to reflect average U.S. classrooms, with elementary schools of 638 students and high schools of 1451 students. Daily local incidence was varied from 1 to 100 cases per 100 000 persons. PARTICIPANTS: Students, faculty, staff, and adult household members. INTERVENTION: Isolation of symptomatic individuals, quarantine of an infected individual's contacts, reduced class sizes, alternative schedules, staff vaccination, and weekly asymptomatic screening. MEASUREMENTS: Transmission was projected among students, staff, and families after a single infection in school and over an 8-week quarter, contingent on local incidence. RESULTS: School transmission varies according to student age and local incidence and is substantially reduced with mitigation measures. Nevertheless, when transmission occurs, it may be difficult to detect without regular testing because of the subclinical nature of most children's infections. Teacher vaccination can reduce transmission to staff, and asymptomatic screening improves understanding of local circumstances and reduces transmission. LIMITATION: Uncertainty exists about the susceptibility and infectiousness of children, and precision is low regarding the effectiveness of specific countermeasures, particularly with new variants. CONCLUSION: With controlled community transmission and moderate mitigation, elementary schools can open safety, but high schools require more intensive mitigation. Asymptomatic screening can facilitate reopening at higher local incidence while minimizing transmission risk. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention through the Council of State and Territorial Epidemiologists, National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, and Facebook.


Subject(s)
COVID-19/prevention & control , COVID-19/transmission , Risk Assessment , Schools , Age Factors , COVID-19 Vaccines/administration & dosage , Disease Susceptibility , Humans , Mass Screening , Pandemics , Physical Distancing , Quarantine , SARS-CoV-2 , United States/epidemiology
4.
mBio ; 11(2)2020 03 03.
Article in English | MEDLINE | ID: covidwho-1452919

ABSTRACT

Obesity is associated with increased disease severity, elevated viral titers in exhaled breath, and significantly prolonged viral shed during influenza A virus infection. Due to the mutable nature of RNA viruses, we questioned whether obesity could also influence influenza virus population diversity. Here, we show that minor variants rapidly emerge in obese mice. The variants exhibit increased viral replication, resulting in enhanced virulence in wild-type mice. The increased diversity of the viral population correlated with decreased type I interferon responses, and treatment of obese mice with recombinant interferon reduced viral diversity, suggesting that the delayed antiviral response exhibited in obesity permits the emergence of a more virulent influenza virus population. This is not unique to obese mice. Obesity-derived normal human bronchial epithelial (NHBE) cells also showed decreased interferon responses and increased viral replication, suggesting that viral diversity also was impacted in this increasing population.IMPORTANCE Currently, 50% of the adult population worldwide is overweight or obese. In these studies, we demonstrate that obesity not only enhances the severity of influenza infection but also impacts viral diversity. The altered microenvironment associated with obesity supports a more diverse viral quasispecies and affords the emergence of potentially pathogenic variants capable of inducing greater disease severity in lean hosts. This is likely due to the impaired interferon response, which is seen in both obese mice and obesity-derived human bronchial epithelial cells, suggesting that obesity, aside from its impact on influenza virus pathogenesis, permits the stochastic accumulation of potentially pathogenic viral variants, raising concerns about its public health impact as the prevalence of obesity continues to rise.


Subject(s)
Disease Susceptibility , Influenza A virus/physiology , Influenza, Human/etiology , Obesity/complications , Animals , Host-Pathogen Interactions , Humans , Influenza, Human/metabolism , Mice , Mutation , Phenotype , RNA, Viral , Respiratory Mucosa/metabolism , Respiratory Mucosa/virology , Severity of Illness Index , Virulence , Virus Replication
5.
J Math Biol ; 83(5): 54, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1491092

ABSTRACT

Motivated by modelling epidemics like COVID-19, this paper proposes a generalized chain binomial process which integrates two types of infectives, those with symptoms and those without. Testing of infectives and vaccination of susceptibles are then incorporated as preventive protective measures. Our interest relates to the distribution of the state of the population at the end of infection and to the reproduction number [Formula: see text] with the associated extinction condition. The method uses the construction of a family of martingales and a branching approximation for large populations, respectively. A more general branching process for epidemics is also constructed and studied. Finally, some results obtained are illustrated by numerical examples.


Subject(s)
COVID-19 , Epidemics , Basic Reproduction Number , Disease Susceptibility , Humans , Models, Biological , SARS-CoV-2
6.
J Korean Med Sci ; 36(41): e291, 2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1485031

ABSTRACT

BACKGROUND: Evidence for the association between underlying non-alcoholic fatty liver disease (NAFLD), the risk of testing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive, and the clinical consequences of coronavirus disease 2019 (COVID-19) is controversial and scarce. We aimed to investigate the association between the presence of NAFLD and the risk of SARS-CoV-2 infectivity and COVID-19-related outcomes. METHODS: We used the population-based, nationwide cohort in South Korea linked with the general health examination records between January 1, 2018 and July 30, 2020. Data for 212,768 adults older than 20 years who underwent SARS-CoV-2 testing from January 1 to May 30, 2020, were obtained. The presence of NAFLDs was defined using three definitions, namely hepatic steatosis index (HSI), fatty liver index (FLI), and claims-based definition. The outcomes were SARS-CoV-2 test positive, COVID-19 severe illness, and related death. RESULTS: Among 74,244 adults who completed the general health examination, there were 2,251 (3.0%) who were SARS-CoV-2 positive, 438 (0.6%) with severe COVID-19 illness, and 45 (0.06%) COVID-19-related deaths. After exposure-driven propensity score matching, patients with pre-existing HSI-NAFLD, FLI-NAFLD, or claims-based NAFLD had an 11-23% increased risk of SARS-CoV-2 infection (HSI-NAFLD 95% confidence interval [CI], 1-28%; FLI-NAFLD 95% CI, 2-27%; and claims-based NAFLD 95% CI, 2-31%) and a 35-41% increased risk of severe COVID-19 illness (HSI-NAFLD 95% CI, 8-83%; FLI-NAFLD 95% CI, 5-71%; and claims-based NAFLD 95% CI, 1-92%). These associations are more evident as liver fibrosis advanced (based on the BARD scoring system). Similar patterns were observed in several sensitivity analyses including the full-unmatched cohort. CONCLUSION: Patients with pre-existing NAFLDs have a higher likelihood of testing SARS-CoV-2 positive and severe COVID-19 illness; this association was more evident in patients with NAFLD with advanced fibrosis. Our results suggest that extra attention should be given to the management of patients with NAFLD during the COVID-19 pandemic.


Subject(s)
COVID-19/etiology , Non-alcoholic Fatty Liver Disease/complications , SARS-CoV-2 , Adult , Aged , Cohort Studies , Disease Susceptibility , Female , Humans , Male , Middle Aged , Severity of Illness Index
7.
Clin Immunol ; 230: 108824, 2021 09.
Article in English | MEDLINE | ID: covidwho-1482503

ABSTRACT

The current intersection of the COVID-19 and HIV-1 pandemics, has raised concerns about the risk for poor COVID-19 outcomes particularly in regions like sub-Saharan Africa, disproportionally affected by HIV. DPP4/CD26 has been suggested to be a potential therapeutic target and a biomarker for risk in COVID-19 patients with high risk co-morbidities. We therefore evaluated soluble DPP4 (sDPP4) levels and activity in plasma of 131 HIV-infected and 20 HIV-uninfected South African individuals. Flow cytometry was performed to compare cell surface expression of DPP4/CD26 and activation markers on peripheral blood mononuclear cells of extreme clinical phenotypes. Progressors had lower specific DPP4 activity and lower frequency of CD3+ T-cells expressing CD26 than HIV-1 controllers, but more activated CD3+CD26+ T-cells. The frequency of CD26-expressing T-cells negatively correlated with HLA-DR+ and CD38+ T-cells. Divergent DPP4/CD26 expression between HIV-1 controllers and progressors may have implications for risk and treatment of COVID-19 in people living with HIV.


Subject(s)
COVID-19/complications , Dipeptidyl Peptidase 4/metabolism , HIV Infections/complications , HIV-1 , SARS-CoV-2 , Adult , CD4 Lymphocyte Count , Case-Control Studies , Comorbidity , Cross-Sectional Studies , Disease Susceptibility , Female , Humans , Male , Risk Factors , South Africa , Viral Load , Young Adult
8.
Technol Cancer Res Treat ; 20: 15330338211050764, 2021.
Article in English | MEDLINE | ID: covidwho-1477207

ABSTRACT

A pandemic of coronavirus diseases 2019 (COVID-19) outbreak is a major public health emergency that has spread in the fastest speed, and caused the most extensive infection world widely. Transbronchial biopsy (TBB) and computed tomography guided percutaneous needle biopsy (CTPNB) is the most common and significant method for the diagnosis of lung cancer. During the COVID-19 pandemic, the indications of TBB and CTPNB must be managed strictly. Therefore, it is extremely indispensable to perform meticulous and individualized management for lung cancer patients to protect the patients from COVID-19.


Subject(s)
COVID-19/epidemiology , Lung Neoplasms/diagnosis , Biopsy , Bronchi/pathology , Bronchoscopy/methods , COVID-19/complications , COVID-19/diagnosis , Diagnosis, Differential , Disease Susceptibility , Humans , Image-Guided Biopsy/methods , Lung/pathology , Lung Neoplasms/complications , Medical Oncology/methods , Postoperative Period , Prognosis , SARS-CoV-2 , Telemedicine , Tomography, X-Ray Computed
9.
Comput Math Methods Med ; 2021: 5384481, 2021.
Article in English | MEDLINE | ID: covidwho-1476872

ABSTRACT

In this study we propose a Coronavirus Disease 2019 (COVID-19) mathematical model that stratifies infectious subpopulations into: infectious asymptomatic individuals, symptomatic infectious individuals who manifest mild symptoms and symptomatic individuals with severe symptoms. In light of the recent revelation that reinfection by COVID-19 is possible, the proposed model attempt to investigate how reinfection with COVID-19 will alter the future dynamics of the recent unfolding pandemic. Fitting the mathematical model on the Kenya COVID-19 dataset, model parameter values were obtained and used to conduct numerical simulations. Numerical results suggest that reinfection of recovered individuals who have lost their protective immunity will create a large pool of asymptomatic infectious individuals which will ultimately increase symptomatic individuals with mild symptoms and symptomatic individuals with severe symptoms (critically ill) needing urgent medical attention. The model suggests that reinfection with COVID-19 will lead to an increase in cumulative reported deaths. Comparison of the impact of non pharmaceutical interventions on curbing COVID19 proliferation suggests that wearing face masks profoundly reduce COVID-19 prevalence than maintaining social/physical distance. Further, numerical findings reveal that increasing detection rate of asymptomatic cases via contact tracing, testing and isolating them can drastically reduce COVID-19 surge, in particular individuals who are critically ill and require admission into intensive care.


Subject(s)
COVID-19/transmission , Models, Biological , Pandemics , SARS-CoV-2 , Asymptomatic Infections/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , Computational Biology , Computer Simulation , Contact Tracing , Databases, Factual , Disease Susceptibility , Humans , Kenya/epidemiology , Masks , Pandemics/prevention & control , Pandemics/statistics & numerical data , Physical Distancing , Reinfection/epidemiology , Reinfection/transmission , SARS-CoV-2/immunology
10.
Sci Rep ; 11(1): 20739, 2021 10 20.
Article in English | MEDLINE | ID: covidwho-1475485

ABSTRACT

Since the first coronavirus disease 2019 (COVID-19) outbreak appeared in Wuhan, mainland China on December 31, 2019, the geographical spread of the epidemic was swift. Malaysia is one of the countries that were hit substantially by the outbreak, particularly in the second wave. This study aims to simulate the infectious trend and trajectory of COVID-19 to understand the severity of the disease and determine the approximate number of days required for the trend to decline. The number of confirmed positive infectious cases [as reported by Ministry of Health, Malaysia (MOH)] were used from January 25, 2020 to March 31, 2020. This study simulated the infectious count for the same duration to assess the predictive capability of the Susceptible-Infectious-Recovered (SIR) model. The same model was used to project the simulation trajectory of confirmed positive infectious cases for 80 days from the beginning of the outbreak and extended the trajectory for another 30 days to obtain an overall picture of the severity of the disease in Malaysia. The transmission rate, ß also been utilized to predict the cumulative number of infectious individuals. Using the SIR model, the simulated infectious cases count obtained was not far from the actual count. The simulated trend was able to mimic the actual count and capture the actual spikes approximately. The infectious trajectory simulation for 80 days and the extended trajectory for 110 days depicts that the inclining trend has peaked and ended and will decline towards late April 2020. Furthermore, the predicted cumulative number of infectious individuals tallies with the preparations undertaken by the MOH. The simulation indicates the severity of COVID-19 disease in Malaysia, suggesting a peak of infectiousness in mid-March 2020 and a probable decline in late April 2020. Overall, the study findings indicate that outbreak control measures such as the Movement Control Order (MCO), social distancing and increased hygienic awareness is needed to control the transmission of the outbreak in Malaysia.


Subject(s)
COVID-19/epidemiology , COVID-19/physiopathology , Public Health Informatics/methods , Computer Simulation , Disease Outbreaks , Disease Susceptibility/epidemiology , Epidemics , Humans , Malaysia , Models, Theoretical , Public Health , Quarantine , SARS-CoV-2
11.
Int J Mol Sci ; 22(12)2021 Jun 20.
Article in English | MEDLINE | ID: covidwho-1472414

ABSTRACT

Acute kidney injury (AKI) and chronic kidney disease (CKD) are rising in global prevalence and cause significant morbidity for patients. Current treatments are limited to slowing instead of stabilising or reversing disease progression. In this review, we describe mesenchymal stem cells (MSCs) and their constituents, extracellular vesicles (EVs) as being a novel therapeutic for CKD. MSC-derived EVs (MSC-EVs) are membrane-enclosed particles, including exosomes, which carry genetic information that mimics the phenotype of their cell of origin. MSC-EVs deliver their cargo of mRNA, miRNA, cytokines, and growth factors to target cells as a form of paracrine communication. This genetically reprograms pathophysiological pathways, which are upregulated in renal failure. Since the method of exosome preparation significantly affects the quality and function of MSC-exosomes, this review compares the methodologies for isolating exosomes from MSCs and their role in tissue regeneration. More specifically, it summarises the therapeutic efficacy of MSC-EVs in 60 preclinical animal models of AKI and CKD and the cargo of biomolecules they deliver. MSC-EVs promote tubular proliferation and angiogenesis, and inhibit apoptosis, oxidative stress, inflammation, the epithelial-to-mesenchymal transition, and fibrosis, to alleviate AKI and CKD. By reprogramming these pathophysiological pathways, MSC-EVs can slow or even reverse the progression of AKI to CKD, and therefore offer potential to transform clinical practice.


Subject(s)
Biological Therapy , Extracellular Vesicles/metabolism , Extracellular Vesicles/transplantation , Kidney Diseases/therapy , Mesenchymal Stem Cells/metabolism , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/metabolism , Acute Kidney Injury/therapy , Animals , Apoptosis/drug effects , Biological Therapy/methods , Cell Differentiation , Cell Proliferation/drug effects , Cell Self Renewal , Chemical Fractionation , Disease Management , Disease Susceptibility , Exosomes/metabolism , Humans , Kidney Diseases/etiology , Kidney Diseases/pathology , Mesenchymal Stem Cells/cytology , Protective Agents , Renal Insufficiency/diagnosis , Renal Insufficiency/etiology , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/therapy
12.
Int J Biol Macromol ; 193(Pt A): 948-955, 2021 Dec 15.
Article in English | MEDLINE | ID: covidwho-1471998

ABSTRACT

The severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) keeps on destroying normal social integrity worldwide, bringing about extraordinary medical services, cultural and financial interruption. Individuals with diabetes have been demonstrated to be at higher risk of complications and even death when exposed to SARS-CoV-2. Regardless of pandemic scale infection, there is presently limited comprehension on the potential impact of SARS-CoV-2 on individuals with diabetes. Human serum albumin (HSA) is the most abundant circulating plasma protein in human serum and attracted more interest from researchers because most susceptible to non-enzymatic glycation reactions. Albumin down-regulates the expression of ACE2 that is the target receptor of COVID-19. Hypoalbuminemia, coagulopathy, and vascular disease have been connected in COVID-19 and appear to predict outcomes independent of age and morbidity. This review discusses the most recent evidence that the ACE/ACE2 ratio could influence by human serum albumin both the susceptibility of individuals to SARS-CoV-2 infection and the outcome of the COVID-19 disease.


Subject(s)
Angiotensin-Converting Enzyme 2/blood , COVID-19 , SARS-CoV-2/metabolism , Serum Albumin, Human/metabolism , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/therapy , COVID-19/blood , COVID-19/diagnosis , COVID-19/therapy , Disease Susceptibility , Humans , Vascular Diseases/blood , Vascular Diseases/diagnosis , Vascular Diseases/therapy
13.
Int J Mol Sci ; 22(19)2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1463708

ABSTRACT

Social behavioral changes, including social isolation or loneliness, increase the risk for stress-related disorders, such as major depressive disorder, posttraumatic stress disorder (PTSD), and suicide, which share a strong neuroinflammatory etiopathogenetic component. The peroxisome-proliferator activated receptor (PPAR)-α, a newly discovered target involved in emotional behavior regulation, is a ligand-activated nuclear receptor and a transcription factor that, following stimulation by endogenous or synthetic ligands, may induce neuroprotective effects by modulating neuroinflammation, and improve anxiety and depression-like behaviors by enhancing neurosteroid biosynthesis. How stress affects epigenetic mechanisms with downstream effects on inflammation and emotional behavior remains poorly understood. We studied the effects of 4-week social isolation, using a mouse model of PTSD/suicide-like behavior, on hippocampal PPAR-α epigenetic modification. Decreased PPAR-α expression in the hippocampus of socially isolated mice was associated with increased levels of methylated cytosines of PPAR-α gene CpG-rich fragments and deficient neurosteroid biosynthesis. This effect was associated with increased histone deacetylases (HDAC)1, methyl-cytosine binding protein (MeCP)2 and decreased ten-eleven translocator (TET)2 expression, which favor hypermethylation. These alterations were associated with increased TLR-4 and pro-inflammatory markers (e.g., TNF-α,), mediated by NF-κB signaling in the hippocampus of aggressive mice. This study contributes the first evidence of stress-induced brain PPAR-α epigenetic regulation. Social isolation stress may constitute a risk factor for inflammatory-based psychiatric disorders associated with neurosteroid deficits, and targeting epigenetic marks linked to PPAR-α downregulation may offer a valid therapeutic approach.


Subject(s)
Aggression , Hippocampus/metabolism , Inflammation/etiology , PPAR alpha/genetics , Social Isolation , Stress, Psychological , Aggression/psychology , Animals , Behavior, Animal , Chromatin Assembly and Disassembly , CpG Islands , Disease Models, Animal , Disease Susceptibility , Epigenesis, Genetic , Gene Expression , Inflammation/metabolism , Inflammation Mediators/metabolism , Male , Methylation , Mice , PPAR alpha/metabolism , Promoter Regions, Genetic , Signal Transduction
14.
Sci Rep ; 11(1): 19752, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1454813

ABSTRACT

Although metabolic syndrome (MetS) is linked to an elevated risk of cardiovascular disease (CVD), the cardiac-specific risk mechanism is unknown. Obesity, hypertension, and diabetes (all MetS components) are the most common form of CVD and represent risk factors for worse COVID-19 outcomes compared to their non MetS peers. Here, we use obese Yorkshire pigs as a highly relevant animal model of human MetS, where pigs develop the hallmarks of human MetS and reproducibly mimics the myocardial pathophysiology in patients. Myocardium-specific mass spectroscopy-derived metabolomics, proteomics, and transcriptomics enabled the identity and quality of proteins and metabolites to be investigated in the myocardium to greater depth. Myocardium-specific deregulation of pro-inflammatory markers, propensity for arterial thrombosis, and platelet aggregation was revealed by computational analysis of differentially enriched pathways between MetS and control animals. While key components of the complement pathway and the immune response to viruses are under expressed, key N6-methyladenosin RNA methylation enzymes are largely overexpressed in MetS. Blood tests do not capture the entirety of metabolic changes that the myocardium undergoes, making this analysis of greater value than blood component analysis alone. Our findings create data associations to further characterize the MetS myocardium and disease vulnerability, emphasize the need for a multimodal therapeutic approach, and suggests a mechanism for observed worse outcomes in MetS patients with COVID-19 comorbidity.


Subject(s)
COVID-19/pathology , Disease Susceptibility , Metabolic Syndrome/pathology , Animals , Blood Coagulation Factors/genetics , Blood Coagulation Factors/metabolism , COVID-19/complications , COVID-19/virology , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Diet, High-Fat/veterinary , Disease Models, Animal , Humans , Immunity, Innate/genetics , Metabolic Syndrome/complications , Metabolic Syndrome/metabolism , Methyltransferases/genetics , Methyltransferases/metabolism , Myocardium/metabolism , Oxidative Stress/genetics , Platelet Aggregation , Receptors, Purinergic P2Y1/genetics , Receptors, Purinergic P2Y1/metabolism , Renin-Angiotensin System , Risk Factors , SARS-CoV-2/isolation & purification , Swine , Urokinase-Type Plasminogen Activator/genetics , Urokinase-Type Plasminogen Activator/metabolism
15.
Eur Rev Med Pharmacol Sci ; 25(18): 5876-5884, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1451047

ABSTRACT

The risk stratification of young adults between subjects who will develop a mild form COVID-19 and subjects who will undergo a severe disease remains inaccurate. In this review, we propose that the Barker hypothesis might explain the increased susceptibility to severe forms of COVID-19 in subjects who underwent intrauterine growth restriction (IUGR). In this paper evidence indicating an association between a low birth weight and an adult phenotype which might favor a severe outcome of SARS-CoV-2 infection are presented: lower lung functional capacity; increased respiratory morbidity; changes in fibrinogen and Factor VII serum levels and dysregulation of the hemostasis and thrombosis system; acquisition of a pro-thrombotic phenotype; low nephron number, with decreased ability to sustain renal function and increased renal morbidity; heart remodeling, with a less efficient cardiac function; endothelial dysfunction, a risk factor for the insurgence of the multiple organ failure; remodeling of arteries, with changes in the elastic properties of the arterial wall, predisposing to the insurgence and progression of atherosclerosis; dysfunction of the innate immune system, a risk factor for immune diseases in adulthood. These data suggest that young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of "at risk subjects", more susceptible toward severe forms of COVID-19. Given that LBW may be considered a surrogate of IUGR, this phenotypic marker should be included among the indispensable clinical data collected in every patient presenting with SARS-COV-2 infection, irrespectively of his/her age.


Subject(s)
COVID-19/epidemiology , Disease Susceptibility/epidemiology , Fetal Development , Disease Susceptibility/virology , Fetal Growth Retardation , Humans , Infant, Low Birth Weight , Severity of Illness Index , Young Adult
17.
Int J Biol Sci ; 17(14): 3954-3967, 2021.
Article in English | MEDLINE | ID: covidwho-1449161

ABSTRACT

Furin is a proprotein convertase that activates different kinds of regulatory proteins, including SARS-CoV-2 spike protein which contains an additional furin-specific cleavage site. It is essential in predicting cancer patients' susceptibility to SARS-CoV-2 and the disease outcomes due to varying furin expressions in tumor tissues. In this study, we analyzed furin's expression, methylation, mutation rate, functional enrichment, survival rate and COVID-19 outcomes in normal and cancer tissues using online databases, and our IHC. As a result, furin presented with biased expression profiles in normal tissues, showing 12.25-fold higher than ACE2 in the lungs. The furin expression in tumors were significantly increased in ESCA and TGCT, and decreased in DLBC and THYM, indicating furin may play critical mechanistic functions in COVID-19 viral entry into cells in these cancer patients. Line with furin over/downexpression, furin promoter hypo-/hyper-methylation may be the regulatory cause of disease and lead to pathogenesis of ESCA and THYM. Furthermore, presence of FURIN-201 isoform with functional domains (P_proprotein, Peptidase_S8 and S8_pro-domain) is highest in all cancer types in comparison to other isoforms, demonstrating its use in tumorigenesis and SARS-Cov-2 entry into tumor tissues. Furin mutation frequency was highest in UCES, and its mutation might elevate ACE2 expression in LUAD and UCEC, reduce ACE2 expression in COAD, elevate HSPA5 expression in PAAD, and elevate TMPRSS2 expression in BRCA. These results showed that furin mutations mostly increased expression of ACE2, HSPA5, and TMPRSS2 in certain cancers, indicating furin mutations might facilitate COVID-19 cell entry in cancer patients. In addition, high expression of furin was significantly inversely correlated with long overall survival (OS) in LGG and correlated with long OS in COAD and KIRC, indicating that it could be used as a favorable prognostic marker for cancer patients' survival. GO and KEGG demonstrated that furin was mostly enriched in genes for metabolic and biosynthetic processes, retinal dehydrogenase activity, tRNA methyltransferase activity, and genes involving COVID-19, further supporting its role in COVID-19 and cancer metabolism. Moreover, Cordycepin (CD) inhibited furin expression in a dosage dependent manner. Altogether, furin's high expression might not only implies increased susceptibility to SARS-CoV-2 and higher severity of COVID-19 symptoms in cancer patients, but also it highlights the need for cancer treatment and therapy during the COVID-19 pandemic. CD might have a potential to develop an anti-SARS-CoV-2 drug through inhibiting furin expression.


Subject(s)
Antineoplastic Agents/therapeutic use , COVID-19/virology , Deoxyadenosines/therapeutic use , Furin/metabolism , Neoplasms/metabolism , Antineoplastic Agents/pharmacology , COVID-19/complications , Cell Line, Tumor , Deoxyadenosines/pharmacology , Disease Susceptibility , Furin/antagonists & inhibitors , Furin/genetics , Humans , Neoplasms/complications , Protein Isoforms/metabolism , Serine Endopeptidases/metabolism
18.
Int J Mol Sci ; 22(19)2021 Sep 30.
Article in English | MEDLINE | ID: covidwho-1444232

ABSTRACT

Natural or experimental infection of domestic cats and virus transmission from humans to captive predatory cats suggest that felids are highly susceptible to SARS-CoV-2 infection. However, it is unclear which cells and compartments of the respiratory tract are infected. To address this question, primary cell cultures derived from the nose, trachea, and lungs of cat and lion were inoculated with SARS-CoV-2. Strong viral replication was observed for nasal mucosa explants and tracheal air-liquid interface cultures, whereas replication in lung slices was less efficient. Infection was mainly restricted to epithelial cells and did not cause major pathological changes. Detection of high ACE2 levels in the nose and trachea but not lung further suggests that susceptibility of feline tissues to SARS-CoV-2 correlates with ACE2 expression. Collectively, this study demonstrates that SARS-CoV-2 can efficiently replicate in the feline upper respiratory tract ex vivo and thus highlights the risk of SARS-CoV-2 spillover from humans to felids.


Subject(s)
COVID-19/veterinary , Cats/virology , Lions/virology , Angiotensin-Converting Enzyme 2/analysis , Animals , COVID-19/transmission , COVID-19/virology , Cat Diseases/transmission , Cat Diseases/virology , Cells, Cultured , Disease Susceptibility , Humans , Lung/cytology , Lung/virology , Nose/cytology , Nose/virology , SARS-CoV-2/isolation & purification , Trachea/cytology , Trachea/virology
20.
Curr Opin Allergy Clin Immunol ; 21(6): 535-544, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1440659

ABSTRACT

PURPOSE OF REVIEW: In the general population, the risk of severe COVID-19 is associated with old age, male sex, hypertension, obesity and chronic diseases. Chronic lung diseases are listed as additional risk factors for hospitalization and ICU admission. The purpose of this review is to define whether chronic lung diseases, such as bronchiectasis and interstitial diseases, represent a risk for a severe SARS-CoV-2 infection in patients affected by common variable immunodeficiency (CVID), the most common symptomatic primary antibody defect. RECENT FINDINGS: CVID patients with SARS-CoV-2 infection have been reported since the beginning of the pandemic with a wide range of clinical presentations ranging from asymptomatic to mild/moderate and severe COVID-19. The meta-analysis of 88 CVID cases described in large cohorts and case reports demonstrated that CVID patients with chronic lung involvement have an increased risk for severe COVID-19 in comparison to CVID without lung diseases (50 vs. 28%, relative risk 1.75, 95% confidence interval 1.04--2.92, P = 0.043). Differently from the general population, age and metabolic comorbidities did not represent a risk factor for severe course in this patient's population. SUMMARY: Underlying chronic lung diseases but not age represent a risk factor for severe COVID-19 in CVID. Prompt therapeutic intervention should be adopted in SARS-CoV-2 positive CVID patients with chronic lung diseases independently of their age.


Subject(s)
Bronchiectasis/epidemiology , COVID-19/diagnosis , Common Variable Immunodeficiency/complications , Lung Diseases, Interstitial/epidemiology , Severity of Illness Index , Age Factors , Bronchiectasis/immunology , COVID-19/immunology , COVID-19/virology , Chronic Disease/epidemiology , Common Variable Immunodeficiency/immunology , Disease Susceptibility , Humans , Lung Diseases, Interstitial/immunology , Risk Factors , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
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