Cardiovascular consequences of viral infections: from COVID to other viral diseases.

Infection of the heart muscle with cardiotropic viruses is one of the major aetiologies of myocarditis and acute and chronic inflammatory cardiomyopathy (DCMi). However, viral myocarditis and subsequent dilated cardiomyopathy is still a challenging disease to diagnose and to treat and is therefore a significant public health issue globally. Advances in clinical examination and thorough molecular genetic analysis of intramyocardial viruses and their activation status have incrementally improved our understanding of molecular pathogenesis and pathophysiology of viral infections of the heart muscle. To date, several cardiotropic viruses have been implicated as causes of myocarditis and DCMi. These include, among others, classical cardiotropic enteroviruses (Coxsackieviruses B), the most commonly detected parvovirus B19, and human herpes virus 6. A newcomer is the respiratory virus that has triggered the worst pandemic in a century, SARS-CoV-2, whose involvement and impact in viral cardiovascular disease is under scrutiny. Despite extensive research into the pathomechanisms of viral infections of the cardiovascular system, our knowledge regarding their treatment and management is still incomplete. Accordingly, in this review, we aim to explore and summarize the current knowledge and available evidence on viral infections of the heart. We focus on diagnostics, clinical relevance and cardiovascular consequences, pathophysiology, and current and novel treatment strategies.

Parvovirus B19 detection analysis in thyroid tissue paired samples: an observational study from a tertiary surgical oncology department.

PURPOSE: In the present study, we sought to investigate the presence of Parvovirus B19 in both abnormal and normal adjacent thyroid tissue specimens after total thyroidectomy as well as the extent that this phenomenon occurs in a population group referred to a tertiary surgical oncology department. METHODS: We detected Parvovirus B19 by Real-Time PCR in both abnormal and normal adjacent thyroid tissue specimens from 41 patients who underwent total thyroidectomy for thyroid disease (cancerous or benign). Hashimoto's thyroiditis, thyroid gland weight, maximum size of the predominant thyroid nodule as well as sex and age of the patients were also evaluated in respect to the Parvovirus B19 presence. RESULTS: Parvovirus B19 virus genome was detected in 21/41 (51.2%) patients in at least one of the paired thyroid tissue samples. No statistically significant difference was noted regarding the sex, age, postoperative diagnosis, thyroid weight and maximum nodule diameter and presence of multifocal disease. The correlation between the incidence of Hashimoto thyroiditis and absence of Parvovirus B19 genome was statistically significant. CONCLUSION: Our findings showed high prevalence of Parvovirus B19 DNA in thyroid tissue disease in the population examined. Its actual role of the virus and its potential implication in the development or progression of thyroid diseases remain to be elucidated. Larger cohort studies are needed in order to validate a quasi-mutually exclusive role of Hashimoto's thyroiditis and Parvovirus B19 presence in thyroid disease in terms of geographical distribution.

Human parvovirus B19 interacts with globoside under acidic conditions as an essential step in endocytic trafficking.

The glycosphingolipid (GSL) globoside (Gb4) is essential for parvovirus B19 (B19V) infection. Historically considered the cellular receptor of B19V, the role of Gb4 and its interaction with B19V are controversial. In this study, we applied artificial viral particles, genetically modified cells, and specific competitors to address the interplay between the virus and the GSL. Our findings demonstrate that Gb4 is not involved in the binding or internalization process of the virus into permissive erythroid cells, a function that corresponds to the VP1u cognate receptor. However, Gb4 is essential at a post-internalization step before the delivery of the single-stranded viral DNA into the nucleus. In susceptible erythroid Gb4 knockout cells, incoming viruses were arrested in the endosomal compartment, showing no cytoplasmic spreading of capsids as observed in Gb4-expressing cells. Hemagglutination and binding assays revealed that pH acts as a switch to modulate the affinity between the virus and the GSL. Capsids interact with Gb4 exclusively under acidic conditions and dissociate at neutral pH. Inducing a specific Gb4-mediated attachment to permissive erythroid cells by acidification of the extracellular environment led to a non-infectious uptake of the virus, indicating that low pH-mediated binding to the GSL initiates active membrane processes resulting in vesicle formation. In summary, this study provides mechanistic insight into the interaction of B19V with Gb4. The strict pH-dependent binding to the ubiquitously expressed GSL prevents the redirection of the virus to nonpermissive tissues while promoting the interaction in acidic intracellular compartments as an essential step in infectious endocytic trafficking.

Flame Figures in Linear Immunoglobulin A Bullous Dermatosis Secondary to Parvovirus B19 Infection.

ABSTRACT: Flame figures represent a characteristic but nondiagnostic histological finding in eosinophilic dermatoses. Some bullous autoimmune diseases with a predominant eosinophilic infiltrate, such as bullous pemphigoid, pemphigoid gestationis, and pemphigus vegetans, may show them. However, it is rare to find them in predominant neutrophilic bullous dermatoses such as linear immunoglobulin A. We present a 60-year-old man with a history of chronic urticaria, which presented a bullous disease after an acute parvovirus B19 infection. The histological findings showed an exceptional linear immunoglobulin A bullous dermatosis with an eosinophilic infiltrate in the dermis forming "flame figures." The clinical and histopathological findings for this entity may be identical to those of other dermatoses. For this reason, combining these findings with direct immunofluorescence analysis is essential for correct diagnosis of this bullous disease.

Detection of parvovirus mRNAs as markers for viral activity in endomyocardial biopsy-based diagnosis of patients with unexplained heart failure.

Erythroparvovirus (B19V) genomes have been detected in various organs of infected individuals including endothelial cells of the heart muscle. However, the role of B19V as a causative pathogen of myocardial damage is still unknown. The majority of reports focus on the presence of viral DNA ignoring proof of viral RNAs as important markers for viral activity. During this study, we established (RT-) qPCR to characterize expression of B19V RNAs (NS1 and VP1/2) in endomyocardial biopsies (EMBs) of 576 patients with unexplained heart failure. 403/576 (70%) EMBs were positive for B19V DNA. B19V mRNAs NS1 and/or VP1/2, indicating viral activity, could be detected in 38.5% of B19V DNA positive samples using the newly established B19V RT-PCRs. 22.1% of samples were characterized by only NS1 mRNA detection while 6.0% revealed only VP1/2 mRNA expression. Detection of both intermediates was successful in 10.4% of samples. Applying the molecular testing, our study revealed that a high proportion (38.5%) of B19V DNA positive EMBs was characterized by viral transcriptional activity. Further prospective studies will evaluate relevance of viral transcription intermediates as a diagnostic marker to differentiate between latent B19V infection and clinically relevant transcriptionally active B19V-infection of the heart muscle.

Acute viral encephalitis associated with human parvovirus B19 infection: unexpectedly diagnosed by metagenomic next-generation sequencing.

We report here a case of a 17-year-old boy with viral encephalitis associated with human parvovirus B19 who presented consciousness disturbance, left hemiparesis, and focal neurologic signs. The diagnosis was based on the specific sequence reads corresponding to human parvovirus B19 (PVB19) in a CSF sample as analyzed by metagenomic next-generation sequencing (mNGS). Thus, PVB19 should be considered in the differential diagnosis of encephalitis and encephalopathy of unknown etiology. The introduction of mNGS into the diagnostic protocol of neuropathies, especially for those undiagnosed, could interrogate all genetic information in a biologic sample and facilitate the identification of the etiological agent.

When a viral eruption hides another one: intrafamilial outbreak of parvovirus B19 and measles virus co-infections: case report.

BACKGROUND: Despite high overall population vaccine coverage, identified clusters of persons refraining from vaccination interfere with pursued measles elimination. Clinical diagnosis of measles is often obvious due to its typical rash. Yet, febrile rashes may occur during many viral infections. Misdiagnosis of a specific primary viral infection may have severe consequences, particularly in immunocompromised subjects or pregnant women. To our knowledge, this case presentation is the first description of a measles and parvovirus B19 coinfection outbreak. Analysis of this outbreak underlines rash diagnosis difficulties and potential serology interpretation pitfalls. This case report is helpful for the clinicians in the context of measles re-emergence and proposes several methods to improve the diagnosis approach. CASE PRESENTATION: We investigated an outbreak of rash in 6 out of 8 Traveler family members presenting to Rennes University Hospital (West of France). Anti-B19V and measles IgM/IgG antibodies were measured and detection of Parvovirus B19 and measles virus genomes were done on blood and/or respiratory samples. Virological investigations finally documented 6 cases of parvovirus B19 infections, including 4 associated with measles. Interestingly, in the four coinfection cases, the rash was typical of B19V primary infection for the two children but typical of measles for the two adults. Clinical diagnosis of rash may be misleading and thorough virological investigations may be required to avoid misdiagnosis. CONCLUSIONS: This investigation first reports an intra-familial outbreak of MeV/B19V coinfections highlighting the high transmissibility of both viruses and the diagnostic challenges of dual rash-associated infections. This report also underlines the potential deleterious consequences of failure to identify measles cases, especially in a community with low vaccination coverage.

Erupción purpúrica petequial, ni en guantes, ni en calcetines / Petechial erythema neither gloves, not socks syndrome

El parvovirus B19 generalmente infecta a niños y adultos jóvenes, presentando cuadros exantemáticos característicos, como el eritema infeccioso. Dentro de las manifestaciones hemorrágicas con erupción purpúrica-petequial, está el síndrome papular-purpúrico en guantes y calcetines. En ocasiones, distribuciones atípicas con erupciones petequiales asimétricas podrían complicar el diagnóstico, llevando a plantear diagnósticos diferenciales y a realizar pruebas de laboratorio. Se describe un caso inusual de parvovirus B19 con erupción petequial atípica, y se hace una revisión de la literatura médica reciente

Parvovirus B19 generally infects children and young adults, presenting characteristic rashes such as erythema infectiosum. Among the hemorrhagic manifestations with purpuric-petechial eruption is the papular purpuric socks and gloves syndrome. Occasionally, atypical distributions with asymmetric petechial rashes could complicate the diagnosis leading to differential diagnoses and laboratory tests. We describe an unusual case of parvovirus B19 with atypical petechial rash, and a recent literature review is reported

New Insights of Human Parvovirus B19 in Modulating Erythroid Progenitor Cell Differentiation.

Human parvovirus B19 (B19), a human pathogen of the erythroparvovirus genus, is responsible for a variety of diseases. B19 cause less symptoms in healthy individuals, also cause acute and chronic anemia in immunodeficiency patients. Transient aplastic crisis and pure red cell aplasia are two kinds of anemic hemogram, respectively, in acute and chronic B19 infection phase, especially occurring in patients with a shortened red cell survival or with immunodeficiency. In addition, B19-infected pregnant women may cause hydrops fetalis or fetal loss. B19 possesses high affinity to bone marrow and fetal liver due to its extremely restricted cytotoxicity to erythroid progenitor cells (EPCs) mediated by viral proteins. The nonstructural protein NS1 is considered to be the major pathogenic factor, which has been shown to inhibit the differentiation and maturation of EPCs through inducing viral DNA damage responses and cell cycle arrest. The time phase property of NS1 activity during DNA replication and conformity to transient change of hemogram are suggestive of its role in regulating differentiation of hematopoietic cells, which is not completely understood. In this review, we summarized the bridge between B19 NS1 and Notch signaling pathway or transcriptional factors GATA, which play an important role in erythroid cell proliferation and differentiation, to provide a new insight of the potential mechanism of B19-induced differential inhibition of EPCs.

[Review of correlation between human parvovirus B19 and autoimmune disease etiology].

Human parvovirus B19 (PVB19) is a small single strand DNA virus distributed throughout the world, with its encoded products being three known proteins. There is conclusive evidence that PVB19 infection is a crucial inducement of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Hashimoto's thyroiditis (HT), myasthenia gravis (MG) and other autoimmune diseases (AIDs). Recent studies have confirmed that anti-B19-VP1u-IgG antibody is able to increase the activity of cytokines such as interleukin 1 (IL-1), tumor necrosis factor α (TNF-α), matrix metalloproteinase-9 (MMP9); PVB19 protein NS 1 and VP1u are capable of inducing the expression of IL-6; PVB19 can induce the production of Th17 cell-related cytokines, resulting in the decrease of IFN-gamma levels and the increase of IL-4 levels in plasma. In this paper, the structure of PVB19, the mechanism of human infection and the relationship between PVB19 and AIDs are summarized.

[Results of a study of parvovirus B19 (Parvoviridae, Parvovirinae, Erythroparvovirus, Primate erythroparvovirus 1) prevalence and circulation activity in socially significant categories of the population].

Currently, along with the increasing need of medical organizations for blood preparations, algorithms for laboratory testing of blood donors are not available for all infections with hemo-contact mechanism of transmission. A representative example is infection caused by parvovirus В19. PURPOSE OF THE STUDY: The article presents the results of the original study, the purpose of which was to study the prevalence of antibodies to parvovirus B19 and the activity of the circulation of this virus in socially important categories of the population. MATERIAL AND METHODS: The materials of the study were blood samples from blood donors of Saint Petersburg, as well as parvovirus В19 sequences isolated from DNA-positive plasma samples. RESULTS AND DISCUSSION: According to the results of the laboratory examination, a high proportion of carriers of virus-specific IgG antibodies was found in studied group of donors, which confirms the previous infection of parvovirus B19 in them and illustrates the high prevalence of infection in this socially significant group. Based on the results of the blood preparations testing, the presence of parvovirus DNA В19 in a significant number of samples was determined by polymerase chain reaction method. This indicates an current parvovirus infection in the examined donors and points to a high epidemiological risk of the blood products obtained from them. Sequencing and phylogenetic analysis of a fragment of the VP1 gene demonstrated that the studied isolates belonged to А1 genotype and its subtype 1А2, which correlates with the genotypes of parvovirus В19 circulating in the European Union and Asia. In addition, two previously unknown В19 parvovirus isolates were isolated, the nucleotide sequences of which were deposited into the international GenBank database. CONCLUSION: Based on the results of the study, it is justified to include testing of blood samples for markers of В19 parvovirus infection in existing algorithms of laboratory examination of donors, which will ensure prevention of hemo-contact infection of blood recipients with parvovirus В19.

A Meta-Analysis on the Seroprevalence of Parvovirus B19 among Patients with Sickle Cell Disease.

BACKGROUND: Parvovirus B19 (B19 V) infection had been reported to be more frequent with serious clinical outcomes in patients with sickle cell disease (SCD) than in the general population. There is a wide variation in data among the existing literature regarding the seroprevalence of B19 V in patients with SCD. These data require further summary and analyses for better accuracy. This systematic review and meta-analysis was done to estimate the seroprevalence of B19 V in patients with SCD. METHODS: This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases of MEDLINE/PubMed, Virtual Health Library (VHL), ScienceDirect, Google Scholar, and OpenGrey were used for the systematic search. The random-effects model was used to estimate the pooled prevalence with the corresponding 95% confidence interval (CI) using OpenMeta Analyst software. Publication bias was estimated based on Begg's test, Egger's test, and examination of the funnel plot. Subgroup analyses and metaregression were used to explore the moderators of heterogeneity between studies. RESULTS: A total of 18 studies including 2890 patients were analyzed. The overall IgG seroprevalence of B19 V infection among patients with SCD was found to be 48.8% (95% CI 39.5%-58.0%). Evidence of publication bias was not detected. Evidence of acute viral infection detected by positive IgM antibodies among the screened SCD patients was found in 8.30% (95% CI 5.20%-11.4%) of them. There was a statistically significant association between seroprevalence of B19 V and geographical areas. CONCLUSION: There was a high prevalence of B19 V in patients with SCD. Healthcare providers need to be aware of the magnitude of B19 V infection in patients with SCD to ensure effective management. This review could provide a comprehensive view of B19 V prevalence in this susceptible population.

The risk of maternal parvovirus B19 infection during pregnancy on fetal loss and fetal hydrops: A systematic review and meta-analysis.

BACKGROUND: Human parvovirus B19 (B19) is widespread infection in humans, yet the impact on adverse pregnancy outcomes is controversial. OBJECTIVE: to evaluate the impact of B19 infection during pregnancy on adverse pregnancy outcome, and investigated the incidence of fetal loss and fetal hydrops after maternal B19 infection during pregnancy. STUDY DESIGN: A systematic literature search was performed using Embase, Medline, PubMed, Web of science, and the Cochrane Library database for relevant publications up to 10th August 2018. Cohort studies and case-control studies were included in analyses. RESULTS: In total, 36 eligible studies were included. Of these, 18 studies reported the risk of maternal B19 infection during pregnancy on fetal loss and 20 studies reported the incidence of fetal loss or fetal hydrops after maternal B19 infection. Collectively, the results indicated that maternal B19 infection increased the risk of fetal loss, spontaneous abortion, and stillbirth with ORs of 2.68 (95% CI: 2.02-3.55), 2.42 (95% CI: 1.76-3.33), and 3.53 (95% CI: 1.91-6.54), respectively, when compared with uninfected pregnant women. In addition, the incidence of fetal loss and fetal hydrops in B19 infected pregnant women was 7.6% (95% CI: 5.5-9.5) and 9.3% (95% CI: 5.6-13.0), respectively. CONCLUSIONS: maternal parvovirus B19 infection during pregnancy increased the risk of fetal loss, spontaneous abortion, and stillbirth. A high incidence of fetal loss and fetal hydrops was observed in pregnant women with parvovirus B19 infection.

Neumonía muy atípica en paciente de dos años / Very atypical pneumonia in a two-year-old patient

La neumonía adquirida en la comunidad es una causa importante de morbilidad y mortalidad en Pediatría. La gran mayoría de las neumonías se resuelven de forma ambulatoria, sin necesidad de realizar un diagnóstico etiológico. La edad es el parámetro que mejor se correlaciona con el agente causal, sin embargo, hasta un 20-30% de los casos se debe a una infección mixta por diferentes gérmenes. Lo más frecuentemente descrito son coinfecciones por virus y bacterias, especialmente virus respiratorio sincitial con Streptococcus pneumoniae y Mycoplasma pneumoniae. La asociación de tres o más patógenos es excepcional. El papel de la coinfección es desconocido en cuanto a pronóstico y evolución, ni se puede precisar si los agentes son concomitantes en el tiempo o agravantes evolutivos. Presentamos el caso de una niña con una neumonía por Mycoplasma pneumoniae que presenta clínica y radiografía compatible con Streptococcus pneumoniae y además serología positiva IgM para virus de Epstein-Barr y parvovirus B19

Childhood community-acquired pneumonia is an important cause of morbidity and mortality in children. Most of them are solved on an outpatient setting, without an etiological diagnosis. Age is the parameter that best correlates with the etiology, however, up to 20-30% of cases is due to a mixed infection by different germs. Most frequently coinfections by viruses and bacteria are described, especially respiratory syncytial virus with Streptococcus pneumoniae and Mycoplasma pneumoniae. However, the association of three or more pathogens is exceptional. The role of this co-pathogenicity is unknown about prognosis and evolution and cannot be specified if agents are concomitant over time or developmental aggravating factors. We present the case of a girl with pneumonia by Mycoplasma pneumoniae who presents symptoms and radiography similar to Streptococcus pneumoniae infection and also positive serology testing IgM for Epstein-Barr virus and parvovirus B19

Quantitative real-time PCR for differential diagnostics of parvovirus B19 infection in acute liver failure patients.

BACKGROUND: Human Parvovirus B19 (B19V) is a common pathogen worldwide. After primary infection, B19V-DNA may permanently persist in non-erythroid tissues, including the liver of patients with acute liver failure (ALF). OBJECTIVE: To validate a real-time PCR (qPCR) for the quantification of B19V-DNA, in order to establish a differential diagnosis for B19V infection in ALF patients. METHODS: The qPCR techniques were based on Sybr Green® and TaqMan® methodologies. To evaluate the quality parameters of both methods, samples from patients with or without B19V infection were tested. The diagnostic utility of qPCR in the detection B19V-DNA in patients with ALF was evaluated by testing archived serum and hepatic tissue explants from 10 patients. RESULTS: The Sybr Green® methodology showed 97% efficiency, the limits of detection and quantification were 62.6 and 53,200 copies/mL, respectively. The TaqMan® methodology showed 95% efficiency, the limits of detection and quantification were 4.48 and 310 copies/mL, respectively. A false positive result was found only with the Sybr Green® methodology. Among ALF patients without defined etiology, three (30%) were positive for B19V DNA in serum and liver. CONCLUSION: The qPCR methods validated here were effective in clarifying uncommon cases of B19V-related ALF and are fit for differential diagnosis of ALF causes.

Recurrence of Pure Red Cell Aplasia in a Kidney Transplant Recipient Due to Reactivation of Parvovirus B19 Infection Despite Two Cycles of Intravenous Immunoglobulin Therapy.

Parvovirus B19 is a single-stranded DNA virus that typically has an affinity for erythroid progenitor cells in bone marrow and leads to pure red cell aplasia. This is a common pathogen in humans, and the expression of the infection depends on the host's hematologic and immunologic status. Here, we report a female patient who developed severe and persistent anemia after kidney transplant while being on immunosuppressive therapy. The parvovirus B19 immunoglobulin M test was positive, and the virus was detected by polymerase chain reaction as parvovirus B19 (23.5 million copies/mL) in the blood sample. Bone marrow examination revealed giant pronormoblasts. She responded well to intravenous immunoglobulin without adverse event. Hemoglobin levels gradually increased, and normal levels were achieved at 3 months posttreatment. Although her renal function did not deteriorate, severe anemia (with hemoglobin level 5 g/dL) recurred 3 times during 12 months posttransplant.

Measures for concordance and discordance with applications in disease control and prevention.

Bivariate binary response data appear in many applications. Interest goes most often to a parameterization of the joint probabilities in terms of the marginal success probabilities in combination with a measure for association, most often being the odds ratio. Using, for example, the bivariate Dale model, these parameters can be modelled as function of covariates. But the odds ratio and other measures for association are not always measuring the (joint) characteristic of interest. Agreement, concordance, and synchrony are in general facets of the joint distribution distinct from association, and the odds ratio as in the bivariate Dale model can be replaced by such an alternative measure. Here, we focus on the so-called conditional synchrony measure. But, as indicated by several authors, such a switch of parameter might lead to a parameterization that does not always lead to a permissible joint bivariate distribution. In this contribution, we propose a new parameterization in which the marginal success probabilities are replaced by other conditional probabilities as well. The new parameters, one homogeneity parameter and two synchrony/discordance parameters, guarantee that the joint distribution is always permissible. Moreover, having a very natural interpretation, they are of interest on their own. The applicability and interpretation of the new parameterization is shown for three interesting settings: quantifying HIV serodiscordance among couples in Mozambique, concordance in the infection status of two related viruses, and the diagnostic performance of an index test in the field of major depression disorders.

Modeling the parvovirus B19 blood safety risk in Australia.

BACKGROUND: Three probable cases of transfusion-transmitted (TT) parvovirus B19 (B19V) occurred in Australia between 2014 and 2017. This study aimed to determine the B19V DNA prevalence among blood donors, to model the risk to recipients of fresh components, and to assess risk management options. STUDY DESIGN AND METHODS: Plasma samples from 4232 donors were tested for B19V DNA by polymerase chain reaction. Reactive samples were confirmed and viral load determined. A transmission-risk model was used to estimate recipient risk, and the risk from community exposure was estimated using seroprevalence data. RESULTS: Two samples (0.0473%, 95% confidence interval [CI] 0.0130-0.172) confirmed positive for B19V DNA had a potentially infectious viral load of 105 IU/mL or higher. The estimated risk of a TT-B19V-associated significant complication was low overall at approximately 1 in 300,000 (95% CI, 1 in 82,000 to 1 in 1 million) fresh components transfused, with 3.1 (95% CI, 0.85-11.3) complications modeled per year. Among vulnerable recipient groups, the risk was higher than 1 in 15,000 patients, but the risk from community exposure far exceeded the transfusion risk for all patient and age groups. CONCLUSION: In the context of the small contribution of transfusion to the burden of B19V disease, the significant costs that would be incurred by any strategy to reduce the risk, and given the significant uncertainties and likely overestimation of the risk, we conclude TT-B19V is a tolerable risk to blood safety, despite being high for some vulnerable recipient groups.