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1.
J Infect Dis ; 225(5): 856-861, 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1666006

ABSTRACT

We tested the combination of a broadly neutralizing HIV antibody with the latency reversal agent vorinostat (VOR). Eight participants received 2 month-long cycles of VRC07-523LS with VOR. Low-level viremia, resting CD4+ T-cell-associated HIV RNA (rca-RNA) was measured, and intact proviral DNA assay (IPDA) and quantitative viral outgrowth assay (QVOA) were performed at baseline and posttreatment. In 3 participants, IPDA and QVOA declines were accompanied by significant declines of rca-RNA. However, no IPDA or QVOA declines clearly exceeded assay variance or natural decay. Increased resistance to VRC07-523LS was not observed. This combination therapy did not reduce viremia or the HIV reservoir. Clinical Trials Registration. NCT03803605.


Subject(s)
HIV Infections , HIV-1 , Broadly Neutralizing Antibodies , CD4-Positive T-Lymphocytes , HIV-1/genetics , Humans , Viremia/drug therapy , Virus Latency , Vorinostat/therapeutic use
2.
mBio ; 12(6): e0290721, 2021 12 21.
Article in English | MEDLINE | ID: covidwho-1518121

ABSTRACT

Oncogenic gammaherpesviruses express viral products during latent and lytic infection that block the innate immune response. Previously, we found that Kaposi's sarcoma herpesvirus (KSHV/human herpesvirus-8) viral microRNAs (miRNAs) downregulate cholesterol biogenesis, and we hypothesized that this prevents the production of 25-hydroxycholesterol (25HC), a cholesterol derivative. 25HC blocks KSHV de novo infection of primary endothelial cells at a postentry step and decreases viral gene expression of LANA (latency-associated nuclear antigen) and RTA. Herein we expanded on this observation by determining transcriptomic changes associated with 25HC treatment of primary endothelial cells using RNA sequencing (RNA-Seq). We found that 25HC treatment inhibited KSHV gene expression and induced interferon-stimulated genes (ISGs) and several inflammatory cytokines (interleukin 8 [IL-8], IL-1α). Some 25HC-induced genes were partially responsible for the broadly antiviral effect of 25HC against several viruses. Additionally, we found that 25HC inhibited infection of primary B cells by a related oncogenic virus, Epstein-Barr virus (EBV/human herpesvirus-4) by suppressing key viral genes such as LMP-1 and inducing apoptosis. RNA-Seq analysis revealed that IL-1 and IL-8 pathways were induced by 25HC in both primary endothelial cells and B cells. We also found that the gene encoding cholesterol 25-hydroxylase (CH25H), which converts cholesterol to 25HC, can be induced by type I interferon (IFN) in human B cell-enriched peripheral blood mononuclear cells (PBMCs). We propose a model wherein viral miRNAs target the cholesterol pathway to prevent 25HC production and subsequent induction of antiviral ISGs. Together, these results answer some important questions about a widely acting antiviral (25HC), with implications for multiple viral and bacterial infections. IMPORTANCE A cholesterol derivative, 25-hydroxycholesterol (25HC), has been demonstrated to inhibit infections from widely different bacteria and viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, its mechanism of activity is still not fully understood. In this work, we look at gene expression changes in the host and virus after 25HC treatment to find clues about its antiviral activity. We likewise demonstrate that 25HC is also antiviral against EBV, a common cancer-causing virus. We compared our results with previous data from antiviral screening assays and found the same pathways resulting in antiviral activity. Together, these results bring us closer to understanding how a modified form of cholesterol works against several viruses.


Subject(s)
Cytokines/immunology , Epstein-Barr Virus Infections/immunology , Herpesvirus 4, Human/drug effects , Herpesvirus 8, Human/drug effects , Hydroxycholesterols/pharmacology , Hydroxycholesterols/therapeutic use , Inflammation/immunology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , B-Lymphocytes/virology , Cells, Cultured , Cytokines/genetics , Endothelial Cells/drug effects , Endothelial Cells/immunology , Endothelial Cells/virology , Epstein-Barr Virus Infections/drug therapy , Gene Expression Regulation, Viral , Herpesvirus 4, Human/genetics , Herpesvirus 8, Human/genetics , Humans , Hydroxycholesterols/immunology , Sequence Analysis, RNA , Virus Latency , Virus Replication
3.
Pediatrics ; 148(3)2021 09.
Article in English | MEDLINE | ID: covidwho-1378143

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) is a serious, sometimes life-threatening late complication of coronavirus disease 2019 (COVID-19) with multiorgan involvement and evidence of immune activation. The pathogenesis of MIS-C is not known, nor is the pathogenesis of the severe organ damage that is the hallmark of MIS-C. Human herpesvirus 6 (HHV-6), the virus responsible for roseola, is a ubiquitous herpesvirus that causes close to universal infection by the age of 3 years. HHV-6 remains latent for life and can be activated during inflammatory states, by other viruses, and by host cell apoptosis. HHV-6 has been associated with end-organ diseases, including hepatitis, carditis, and encephalitis. In addition, ∼1% of people have inherited chromosomally integrated human herpesvirus 6 (iciHHV-6), which is HHV-6 that has been integrated into chromosomal telomeric regions and is transmitted through the germ line. iciHHV-6 can be reactivated and has been associated with altered immune responses. We report here a case of MIS-C in which an initial high HHV-6 DNA polymerase chain reaction viral load assay prompted testing for iciHHV-6, which yielded a positive result. Additional research may be warranted to determine if iciHHV-6 is commonly observed in patients with MIS-C and, if so, whether it may play a part in MIS-C pathogenesis.


Subject(s)
COVID-19/virology , Herpesvirus 6, Human , Roseolovirus Infections/virology , Systemic Inflammatory Response Syndrome/virology , COVID-19 Nucleic Acid Testing , Child , DNA, Viral/isolation & purification , Herpesvirus 6, Human/genetics , Herpesvirus 6, Human/isolation & purification , Humans , Male , Polymerase Chain Reaction , Telomere/virology , Viral Load , Virus Latency
4.
Retrovirology ; 18(1): 21, 2021 08 03.
Article in English | MEDLINE | ID: covidwho-1365362

ABSTRACT

HIV-1 persists in infected individuals despite years of antiretroviral therapy (ART), due to the formation of a stable and long-lived latent viral reservoir. Early ART can reduce the latent reservoir and is associated with post-treatment control in people living with HIV (PLWH). However, even in post-treatment controllers, ART cessation after a period of time inevitably results in rebound of plasma viraemia, thus lifelong treatment for viral suppression is indicated. Due to the difficulties of sustained life-long treatment in the millions of PLWH worldwide, a cure is undeniably necessary. This requires an in-depth understanding of reservoir formation and dynamics. Differences exist in treatment guidelines and accessibility to treatment as well as social stigma between low- and-middle income countries (LMICs) and high-income countries. In addition, demographic differences exist in PLWH from different geographical regions such as infecting viral subtype and host genetics, which can contribute to differences in the viral reservoir between different populations. Here, we review topics relevant to HIV-1 cure research in LMICs, with a focus on sub-Saharan Africa, the region of the world bearing the greatest burden of HIV-1. We present a summary of ART in LMICs, highlighting challenges that may be experienced in implementing a HIV-1 cure therapeutic. Furthermore, we discuss current research on the HIV-1 latent reservoir in different populations, highlighting research in LMIC and gaps in the research that may facilitate a global cure. Finally, we discuss current experimental cure strategies in the context of their potential application in LMICs.


Subject(s)
Antiretroviral Therapy, Highly Active/standards , Developing Countries/statistics & numerical data , Disease Reservoirs/virology , HIV Infections/drug therapy , Virus Latency/drug effects , Africa South of the Sahara/epidemiology , Antiretroviral Therapy, Highly Active/methods , Antiretroviral Therapy, Highly Active/statistics & numerical data , Cost of Illness , HIV Infections/epidemiology , HIV Infections/prevention & control , HIV-1/genetics , HIV-1/pathogenicity , Humans
5.
Elife ; 92020 04 02.
Article in English | MEDLINE | ID: covidwho-1352927

ABSTRACT

The COVID-19 pandemic is a harsh reminder of the fact that, whether in a single human host or a wave of infection across continents, viral dynamics is often a story about the numbers. In this article we provide a one-stop, curated graphical source for the key numbers (based mostly on the peer-reviewed literature) about the SARS-CoV-2 virus that is responsible for the pandemic. The discussion is framed around two broad themes: i) the biology of the virus itself; ii) the characteristics of the infection of a single human host.


Subject(s)
Betacoronavirus/physiology , Clinical Laboratory Techniques , Coronavirus Infections , Pandemics , Pneumonia, Viral , COVID-19 , COVID-19 Testing , Coronavirus/genetics , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Coronavirus Infections/virology , Genome, Viral , Humans , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , RNA, Viral , SARS-CoV-2 , Virus Latency , Virus Replication
6.
EMBO Mol Med ; 13(8): e13901, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1346766

ABSTRACT

HIV-1 infects lymphoid and myeloid cells, which can harbor a latent proviral reservoir responsible for maintaining lifelong infection. Glycolytic metabolism has been identified as a determinant of susceptibility to HIV-1 infection, but its role in the development and maintenance of HIV-1 latency has not been elucidated. By combining transcriptomic, proteomic, and metabolomic analyses, we here show that transition to latent HIV-1 infection downregulates glycolysis, while viral reactivation by conventional stimuli reverts this effect. Decreased glycolytic output in latently infected cells is associated with downregulation of NAD+ /NADH. Consequently, infected cells rely on the parallel pentose phosphate pathway and its main product, NADPH, fueling antioxidant pathways maintaining HIV-1 latency. Of note, blocking NADPH downstream effectors, thioredoxin and glutathione, favors HIV-1 reactivation from latency in lymphoid and myeloid cellular models. This provides a "shock and kill effect" decreasing proviral DNA in cells from people living with HIV/AIDS. Overall, our data show that downmodulation of glycolysis is a metabolic signature of HIV-1 latency that can be exploited to target latently infected cells with eradication strategies.


Subject(s)
HIV Infections , HIV-1 , CD4-Positive T-Lymphocytes , Down-Regulation , Glycolysis , Humans , Oxidative Stress , Proteomics , Virus Activation , Virus Latency
8.
Virologie (Montrouge) ; 25(2): 63-92, 2021 04 01.
Article in French | MEDLINE | ID: covidwho-1298417

ABSTRACT

Epigenetics play an important role in viral replication and in viral associated pathogenesis. In fact, viruses interact with epigenetic factors to promote the viral replication by stimulating the entry into the lytic cycle, but also by promoting viral latency. Furthermore, epigenetics control the immune response implemented by the host to counteract viral infections. Thus, epigenetic modifications are identified as potential therapeutic targets to control viral infections. Several studies have already shown the efficiency of inhibitors of histone deacetylases, demethylases, acetyltransferases and methyltransferases, as well as inhibitors of DNA methyltransferases in viral infections repression or in latency reactivation. In this review, we will examine the epigenetic regulation of viral infections by several DNA viruses, e.g. HSV, EBV, HCMV, KSHV, HBV, HPV and HAdV, and RNA viruses, e.g. HCV, HIV, IAV and CoV. Also, we will discuss the potential use of therapeutic approaches targeting epigenetics for the control of viral infections.


Subject(s)
Herpesvirus 8, Human , Virus Diseases , Epigenesis, Genetic , Humans , Virus Diseases/drug therapy , Virus Diseases/genetics , Virus Latency , Virus Replication/genetics
9.
Front Immunol ; 11: 594963, 2020.
Article in English | MEDLINE | ID: covidwho-1094164

ABSTRACT

When viruses infect cells, they almost invariably cause metabolic changes in the infected cell as well as in several host cell types that react to the infection. Such metabolic changes provide potential targets for therapeutic approaches that could reduce the impact of infection. Several examples are discussed in this review, which include effects on energy metabolism, glutaminolysis and fatty acid metabolism. The response of the immune system also involves metabolic changes and manipulating these may change the outcome of infection. This could include changing the status of herpesviruses infections from productive to latency. The consequences of viral infections which include coronavirus disease 2019 (COVID-19), may also differ in patients with metabolic problems, such as diabetes mellitus (DM), obesity, and endocrine diseases. Nutrition status may also affect the pattern of events following viral infection and examples that impact on the pattern of human and experimental animal viral diseases and the mechanisms involved are discussed. Finally, we discuss the so far few published reports that have manipulated metabolic events in-vivo to change the outcome of virus infection. The topic is expected to expand in relevance as an approach used alone or in combination with other therapies to shape the nature of virus induced diseases.


Subject(s)
COVID-19/metabolism , Herpesviridae Infections/metabolism , Herpesviridae/physiology , Obesity/metabolism , SARS-CoV-2/physiology , Animals , COVID-19/complications , Energy Metabolism , Herpesviridae Infections/complications , Humans , Immunity , Lipid Metabolism , Nutritional Physiological Phenomena , Obesity/complications , Pandemics , Virus Latency
10.
Front Immunol ; 11: 594572, 2020.
Article in English | MEDLINE | ID: covidwho-1083323

ABSTRACT

Mycobacterium tuberculosis (Mtb), the causative organism of pulmonary tuberculosis (PTB) now infects more than half of the world population. The efficient transmission strategy of the pathogen includes first remaining dormant inside the infected host, next undergoing reactivation to cause post-primary tuberculosis of the lungs (PPTBL) and then transmit via aerosol to the community. In this review, we are exploring recent findings on the role of bone marrow (BM) stem cell niche in Mtb dormancy and reactivation that may underlie the mechanisms of PPTBL development. We suggest that pathogen's interaction with the stem cell niche may be relevant in potential inflammation induced PPTBL reactivation, which need significant research attention for the future development of novel preventive and therapeutic strategies for PPTBL, especially in a post COVID-19 pandemic world. Finally, we put forward potential animal models to study the stem cell basis of Mtb dormancy and reactivation.


Subject(s)
Bone Marrow Cells/microbiology , Mycobacterium tuberculosis/physiology , Tuberculosis, Pulmonary , Virus Activation/physiology , Virus Latency/physiology , COVID-19 , Humans , Mesenchymal Stem Cells/microbiology , SARS-CoV-2 , Stem Cell Niche/physiology , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/transmission
11.
Drug Discov Ther ; 14(6): 262-272, 2021 Jan 23.
Article in English | MEDLINE | ID: covidwho-1067907

ABSTRACT

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in 2019 in Wuhan, China. Clinically, respiratory tract symptoms as well as other organs disorders are observed in patients positively diagnosed coronavirus disease 2019 (COVID-19). In addition, neurological symptoms, mainly anosmia, ageusia and headache were observed in many patients. Once in the central nervous system (CNS), the SARS-CoV-2 can reside either in a quiescent latent state, or eventually in actively state leading to severe acute encephalitis, characterized by neuroinflammation and prolonged neuroimmune activation. SRAS-CoV-2 requires angiotensin-converting enzyme 2 (ACE2) as a cell entry receptor. The expression of this receptor in endothelial cells of blood-brain barrier (BBB) shows that SRAS-CoV-2 may have higher neuroinvasive potential compared to known coronaviruses. This review summarizes available information regarding the impact of SRAS-CoV-2 in the brain and tended to identify its potential pathways of neuroinvasion. We offer also an understanding of the long-term impact of latently form of SARS-CoV-2 on the development of neurodegenerative disorders. As a conclusion, the persistent infection of SRAS-CoV-2 in the brain could be involved on human neurodegenerative diseases that evolve a gradual process, perhapes, over several decades.


Subject(s)
COVID-19/virology , Central Nervous System Viral Diseases/virology , Neurodegenerative Diseases/virology , Neurons/virology , SARS-CoV-2/pathogenicity , Viral Tropism , Animals , COVID-19/complications , Central Nervous System Viral Diseases/metabolism , Central Nervous System Viral Diseases/pathology , Host-Pathogen Interactions , Humans , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Neurons/metabolism , Neurons/pathology , Virus Latency
12.
Int J Infect Dis ; 102: 70-72, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1060401

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has reached pandemic levels. Cardiovascular complications in COVID-19 have been reported frequently, however evidence for a causal relationship has not been established. This report describes the detection of SARS-CoV-2 viral genomes in a patient with symptoms of heart failure, in whom endomyocardial biopsy was investigated following a latency period of 4 weeks after the onset of pulmonary symptoms. The viral infection was accompanied by myocardial inflammation indicating an infection of the heart muscle.


Subject(s)
COVID-19/complications , Heart Failure/virology , Myocarditis/virology , SARS-CoV-2/isolation & purification , Biopsy , COVID-19/virology , COVID-19 Nucleic Acid Testing , Female , Heart/virology , Humans , Lung/pathology , Middle Aged , Pandemics , Virus Latency
13.
Gac. méd. Méx ; 156(4): 324-329, Jul.-Aug. 2020. graf
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-1042995

ABSTRACT

Abstract In the efforts to explain COVID-19 pathophysiology, studies are being carried out on the correspondence between the expression of SARS-CoV-2 cell receptors and viral sequences. ACE2, CD147 and TMPRSS2 receptors expression could indicate poorly explored potential infection targets. For the genomic analysis of SARS-CoV-2 receptors, using BioGPS information was decided, which is a portal that centralizes genetic annotation resources, in combination with that of The Human Protein Atlas, the largest portal of human transcriptome and proteome data. We also reviewed the most recent articles on the subject. RNA and viral receptor proteins expression was observed in numerous anatomical sites, which partially coincides with the information reported in the literature. High expression in testicular cells markedly stood out, and it would be therefore important ruling out whether this anatomical site is a SARS-CoV-2 reservoir; otherwise, germ cell damage, as it is observed in infections with other RNA viruses, should be determined.


Resumen En el afán por explicar la fisiopatogenia de COVID-19 se están realizando estudios en torno a la correspondencia entre la expresión de receptores celulares de SARS-CoV-2 y las secuencias virales. La expresión de los receptores ACE2, CD147 y TMPRSS2 podría indicar blancos de infección poco explorados. Para el análisis genómico de los receptores de SARS-CoV-2 se optó por utilizar la información del BioGPS, un portal que centraliza los recursos de anotación genética, en combinación con la de The Human Protein Atlas, el portal más grande de datos del transcriptoma y proteoma humanos. También se revisaron los artículos más recientemente respecto al tema. En numerosos sitios anatómicos se observó la expresión de ARN y proteínas de los receptores del virus, que coinciden parcialmente con la información reportada en la literatura. Resaltó la alta expresión en las células de los testículos, por lo que sería importante descartar si este sitio anatómico es un reservorio de SARS-CoV-2; de no ser así, determinar el daño en las células germinales, tal como sucede en infecciones por otros virus ARN.


Subject(s)
Humans , Pneumonia, Viral/virology , Testis/virology , Coronavirus Infections/virology , Betacoronavirus/isolation & purification , Pneumonia, Viral/physiopathology , Serine Endopeptidases/genetics , Gene Expression Regulation , Virus Latency , Coronavirus Infections/physiopathology , Peptidyl-Dipeptidase A/genetics , Basigin/genetics , Pandemics , Angiotensin-Converting Enzyme 2 , SARS-CoV-2 , COVID-19
14.
J Theor Biol ; 513: 110587, 2021 03 21.
Article in English | MEDLINE | ID: covidwho-1026278

ABSTRACT

In this paper we develop an SEIR-type model of COVID-19, with account for two particular aspects: non-exponential distribution of incubation and recovery periods, as well as age structure of the population. For the mean-field model, which does not distinguish between different age groups, we demonstrate that including a more realistic Gamma distribution of incubation and recovery periods may not have an effect on the total number of deaths and the overall size of an epidemic, but it has a major effect in terms of increasing the peak numbers of infected and critical care cases, as well as on changing the timescales of an epidemic, both in terms of time to reach the peak, and the overall duration of an outbreak. In order to obtain more accurate estimates of disease progression and investigate different strategies for introducing and lifting the lockdown, we have also considered an age-structured version of the model, which has allowed us to include more accurate data on age-specific rates of hospitalisation and COVID-19 related mortality. Applying this model to three comparable neighbouring regions in the UK has delivered some fascinating insights regarding the effect of lockdown in regions with different population structure. We have discovered that for a fixed lockdown duration, the timing of its start is very important in the sense that the second epidemic wave after lifting the lockdown can be significantly smaller or larger depending on the specific population structure. Also, the later the fixed-duration lockdown is introduced, the smaller is the resulting final number of deaths at the end of the outbreak. When the lockdown is introduced simultaneously for all regions, increasing lockdown duration postpones and slightly reduces the epidemic peak, though without noticeable differences in peak magnitude between different lockdown durations.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , SARS-CoV-2/physiology , Virus Latency/physiology , Adolescent , Adult , Age Distribution , Age Factors , Aged , Aged, 80 and over , COVID-19/transmission , Child , Child, Preschool , Disease Susceptibility , England/epidemiology , Humans , Infant , Infant, Newborn , Middle Aged , Models, Biological , Time Factors , Young Adult
15.
Dig Dis Sci ; 66(11): 4026-4034, 2021 11.
Article in English | MEDLINE | ID: covidwho-1002116

ABSTRACT

BACKGROUND AND AIM: To investigate the risk of hepatitis B virus reactivation in patients undergoing long-term tocilizumab therapy for rheumatoid arthritis. METHOD: From January 2011 through August 2019, a total of 97 patients were enrolled in this retrospective study. Clinical data, comedications, and the occurrence of HBV reactivation were recorded. RESULTS: Seven patients were HBsAg+ (7.2%), 64 were HBsAg-/HBcAb+ (65.9%), and 26 were HBsAg-/HBcAb- (26.8%). The median disease follow-up time was 9 years. TCZ was administered for a median of 29 months. Four patients (4.1%) experienced HBV reactivation after tocilizumab therapy. Of the 7 HBsAg+ patients, 4 received antiviral prophylaxis and had no HBV reactivation; the remaining 3 patients did not receive antiviral prophylaxis, and all 3 (100%) experienced HBV reactivation and hepatitis flare-up. Hyperbilirubinemia occurred in 2 of these 3 patients, with mild prothrombin time prolongation in one. After salvage entecavir treatment, all patients had a favorable outcome. Of the 64 HBsAg-/HBcAb+ patients, only one became positive for serum HBV DNA (2.5 × 107 IU/mL) after 18 months of tocilizumab treatment (1.6%; 1/64). This patient was immediately treated with entecavir, which prevented hepatitis flare-up. CONCLUSIONS: Tocilizumab is widely used in treating rheumatoid arthritis and has the potential to reduce the mortality rate among severe COVID-19 patients. However, HBV reactivation needs to be considered. HBsAg+ patients have a high risk of HBV reactivation, which could be prevented by antiviral prophylaxis. Although the risk of reactivation is low in HBsAg-/HBcAb+ patients, strict monitoring is necessary.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Hepatitis B, Chronic/drug therapy , Virus Activation/drug effects , Antibodies, Monoclonal, Humanized/adverse effects , Antirheumatic Agents/adverse effects , Antiviral Agents/therapeutic use , Guanine/analogs & derivatives , Guanine/therapeutic use , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/blood , Hepatitis B virus/physiology , Humans , Retrospective Studies , Risk Factors , Virus Latency/drug effects
18.
Biomedica ; 40(Supl. 2): 173-179, 2020 10 30.
Article in English, Spanish | MEDLINE | ID: covidwho-914758

ABSTRACT

Coronaviruses cause respiratory and gastrointestinal disorders in animals and humans. The current SARS-CoV-2, the COVID-19 infectious agent, belongs to a subgroup called betacoronavirus including the SARS-CoV and MERS-CoV responsible for epidemics in 2002 and 2012, respectively. These viruses can also infect the nervous system due to their affinity for the human angiotensin-converting enzyme 2 (ACE2) expressed in neurons and glial cells. Infections with SARS-CoV, MERS-CoV, and now SARS-CoV-2 also produce neurological signs such as acute cerebrovascular disease, impaired consciousness, and muscle injury, as well as dizziness, hypogeusia, hyposmia, hypoxia, neuralgia, and hypoxic encephalopathy. For this reason, close attention should be paid to the neurological manifestations of COVID-19 patients.


Los coronavirus son una familia de virus que se caracterizan por producir afectaciones respiratorias y gastrointestinales en animales y en seres humanos. El actual SARS-CoV-2, agente infeccioso de la COVID-19, pertenece a un subgrupo denominado betacoronavirus del que hacen parte el SARS-CoV y MERS-CoV, virus responsables de epidemias en el 2002 y el 2012, respectivamente. Estos virus también pueden infectar el sistema nervioso debido a su afinidad con la enzima convertidora de angiotensina humana 2 (ACE2), la cual se expresa en neuronas y células gliales. Se ha demostrado que las infecciones con SARS-CoV y MERS-CoV, y ahora también con el SARS-CoV-2, ocasionan condiciones neurológicas como la enfermedad cerebrovascular aguda, la conciencia alterada y las lesiones musculares, así como mareos, hipogeusia, hiposmia, hipoxia, neuralgia y encefalopatía hipóxica. Por ello debe prestarse mucha atención a las manifestaciones neurológicas de los pacientes de COVID-19.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/complications , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Nervous System Diseases/etiology , Pneumonia, Viral/complications , SARS Virus/pathogenicity , Severe Acute Respiratory Syndrome/complications , COVID-19 , Cerebrospinal Fluid/virology , Cerebrovascular Disorders/etiology , Consciousness Disorders/etiology , Coronavirus Infections/epidemiology , Disease Outbreaks , Forecasting , Humans , Musculoskeletal Diseases/etiology , Pandemics , Pneumonia, Viral/epidemiology , Respiratory Distress Syndrome/etiology , SARS-CoV-2 , Sensation Disorders/etiology , Severe Acute Respiratory Syndrome/epidemiology , Virus Latency
19.
Forensic Sci Med Pathol ; 17(1): 136-138, 2021 03.
Article in English | MEDLINE | ID: covidwho-778073

ABSTRACT

We believe that forensic medicine should play a significant role in the COVID-19 pandemic. Forensic pathologists should ask and answer various questions through autopsy cases during the COVID-19 period, thus providing a significant contribution to science. Some of the potential roles of forensic medicine in this issue include: determining the exact cause of death among the deceased who were SARS-CoV-2 positive, contribution to the accuracy of mortality statistics, understanding pathological mechanisms of COVID-19, tracking the presence of the virus over time, survival of the virus after death as well as dealing with medicolegal issues. A detailed multidisciplinary analysis of autopsy samples would undoubtedly help understand this new illness and its clinical management. Therefore, autopsies during the COVID-19 pandemic should not be an exception, but certainly a rule.


Subject(s)
Autopsy , COVID-19/pathology , Forensic Medicine , Pandemics , Professional Role , COVID-19/prevention & control , COVID-19/transmission , Cause of Death , Data Collection , Humans , Infection Control , Infectious Disease Transmission, Patient-to-Professional/prevention & control , SARS-CoV-2 , Virus Latency
20.
Gac Med Mex ; 156(4): 328-333, 2020.
Article in English | MEDLINE | ID: covidwho-732611

ABSTRACT

In the efforts to explain COVID-19 pathophysiology, studies are being carried out on the correspondence between the expression of SARS-CoV-2 cell receptors and viral sequences. ACE2, CD147 and TMPRSS2 receptors expression could indicate poorly explored potential infection targets. For the genomic analysis of SARS-CoV-2 receptors, using BioGPS information was decided, which is a portal that centralizes genetic annotation resources, in combination with that of The Human Protein Atlas, the largest portal of human transcriptome and proteome data. We also reviewed the most recent articles on the subject. RNA and viral receptor proteins expression was observed in numerous anatomical sites, which partially coincides with the information reported in the literature. High expression in testicular cells markedly stood out, and it would be therefore important ruling out whether this anatomical site is a SARS-CoV-2 reservoir; otherwise, germ cell damage, as it is observed in infections with other RNA viruses, should be determined.


En el afán por explicar la fisiopatogenia de COVID-19 se están realizando estudios en torno a la correspondencia entre la expresión de receptores celulares de SARS-CoV-2 y las secuencias virales. La expresión de los receptores ACE2, CD147 y TMPRSS2 podría indicar blancos de infección poco explorados. Para el análisis genómico de los receptores de SARS-CoV-2 se optó por utilizar la información del BioGPS, un portal que centraliza los recursos de anotación genética, en combinación con la de The Human Protein Atlas, el portal más grande de datos del transcriptoma y proteoma humanos. También se revisaron los artículos más recientemente respecto al tema. En numerosos sitios anatómicos se observó la expresión de ARN y proteínas de los receptores del virus, que coinciden parcialmente con la información reportada en la literatura. Resaltó la alta expresión en las células de los testículos, por lo que sería importante descartar si este sitio anatómico es un reservorio de SARS-CoV-2; de no ser así, determinar el daño en las células germinales, tal como sucede en infecciones por otros virus ARN.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Pneumonia, Viral/virology , Testis/virology , Angiotensin-Converting Enzyme 2 , Basigin/genetics , COVID-19 , Coronavirus Infections/physiopathology , Gene Expression Regulation , Humans , Male , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Serine Endopeptidases/genetics , Virus Latency
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