Parvovirus (B19V) is a compact, non-enveloped, spherical virus with a single-stranded DNA genome. In immunocompetent individuals, parvovirus B19V infection is typically asymptomatic or mildly symptomatic. However, in patients with compromised immune systems, it can lead to severe anemia in patients with compromised immune systems; renal transplant recipients taking immunosuppressive therapies often experience B19-induced anemia and red cell aplasia. The coinfections of hepatitis B virus, hepatitis C virus, cytomegalovirus (CMV), HIV, and BK virus with B19V have been reportedly investigated. This review explores the interactions of B19V with other viral pathogens and provide insight into its intricate interplay in various clinical scenarios. In hepatitis B virus, B19 has been implicated in liver inflammation and disease, and, in hepatitis C virus, B19 correlates with chronic hepatitis, which may affect the progression of the disease. Immunocompromised individuals, particularly, patients with HIV and renal transplant recipients, often experience B19-induced anemia, which can be complicated by coinfection with CMV and BK. Pregnant women having coinfections of parvovirus B19 with CMV are at risk for fetal developmental complications. Its coexistence with Epstein-Barr virus can result in bone marrow failure. Notably, fatal cases of B19 and influenza A/H1N1 and more recent cases of coinfection with SARS-CoV-2, have been reported, highlighting the complex interactions between B19V and other viral pathogens.

Two feral cats (from the same colony) were presented to the veterinary clinic for weakness, weight loss, and anorexia. The cats were part of a study on feline hepatotropic viruses (collection A, 43 animals). On metaviromic investigation, parvoviral reads were identified in the sera of the two cats. The feline parvovirus genome was 5.3 kb long with an organization similar to other members of the Erythroparvovirus genus. In the ORF1 (nonstructural proteins) and ORF2 (VP1/VP2 precursor) the feline virus displayed 43.1% and 49.1% nucleotide identity to human parvovirus B19, and 48.9% and 56.6% to chipmunk parvovirus. Sequence identity to canine/feline protoparvovirus (Protoparvovirus carnivoran 1) was as low as 36.5% % and 29.2% in the ORF1 and ORF2, respectively. Using a quantitative PCR assay, the virus was also identified in an additional ten cats (prevalence 27.6%, 12/43) from collection A and in 15/1150 (1.3%) of archival sera (collection B), revealing a higher infection rate in cats with altered hepatic markers, suggestive of hepatic distress. The findings of our study extend the list of known parvoviruses in the feline host.

Parvovirus B19, pathogen of children's fifths disease, is among the causes of viral/idiopathic pericarditis. This paper presents 3 adult cases of complicated effusive-constrictive parvovirus B19 pericarditis presenting with overt diastolic heart failure during an outbreak in September to October 2023. Comprehensive transthoracic echocardiography and cardiac magnetic resonance played a key role in noninvasive assessment of constrictive physiology and pericardial inflammation, guiding successful treatment with low-dose prednisolone, having failed standard colchicine and nonsteroidal anti-inflammatory drugs.

We report the case of a 34-year-old male recipient of an ABO-incompatible living donor kidney transplant who was repeatedly hospitalised for anaemia. Acute kidney injury in a patient with severe and recurrent anaemia related to parvovirus B19 infection was diagnosed through viral and histopathological analysis. In view of the patient's impaired immune response due to the immunosuppressive regimen, clinical stabilisation was reached by repeated intravenous immunoglobulin administration as a maintenance therapy in a prolonged course, although viral clearance did not occur. Review of the literature highlighted a variety of pathological renal lesions associated with parvovirus B19 infection, although epidemiological data on parvovirus B19 infection in kidney transplant recipients, standardised diagnostic and therapeutic protocols, and the prospect for specific antiviral therapy are still scarce. Increased awareness of clinical relevance of parvovirus B19 infection in patients who have had a kidney transplant should direct future efforts towards better consideration and comprehension of viral-induced pathogenesis, aimed at effective diagnosis and appropriate therapy.

Parvovirus B19 (B19V) infection can affect individuals of all ages, both immunocompetent and immunocompromised. This infection is typically acute and self-limiting, most commonly resulting in rash diseases and acute febrile illness. However, its involvement in atypical manifestations such as chronic kidney disease and acute liver failure have also been reported. Diagnosis of B19V is rarely conducted in these populations, and available studies on its prevalence are limited, outdated, and do not accurately depict the current situation. This study describes and discusses retrospective investigations into the role of B19V in cases of rash diseases, acute febrile illness, anemia, occurring in the context of chronic kidney disease and HIV coinfection, and acute liver failure when no identifiable etiological agent was found, focusing on various populations in Brazil. This overview underscores the importance of recognizing the potential for severe B19V infection in all individuals, regardless of perceived immune status, as well as of considering the possibility of B19V concurrent infection, in both high-risk groups and healthy individuals to reduce the risk of serious complications and improve patient outcomes, by considering the inclusion of B19V in the routine of diagnosis and implementing management strategies. This study was limited by the absence of national surveillance data of B19V in Brazil and by the analyses that occurred retrospectively.

This case report identifies parvovirus B19 as a potential trigger for fibromyalgia, underscoring the contribution of viral infections to the pathogenesis of chronic pain syndromes. Awareness of this association may prompt clinicians to consider infectious agents in the differential diagnosis of new-onset fibromyalgia, facilitating timely recognition and personalized management strategies.

A Parvovirus B19 (B19V) outbreak has been reported in Europe in 2023-2024. The aims of this study were 1) to describe the incidence of primary cases from 2012 to 2024 in one French hospital 2) to analyze the genome of 2023 strains 3) to identify virological profiles according to the clinical presentations of B19V infection.

The incidence of B19V primary cases was studied through an interrupted time-series analysis. Genomes of 2023 strains were sequenced in the NS1-VP1u region. Blood viral loads, IgG and IgM levels were analyzed in 158 cases according to clinical manifestations with Kruskal-Wallis test and a machine learning approach based on k-nearest neighbors.

During the 2023-2024 B19V outbreak, there was an 8-time increase in the incidence of B19V infections compared with pre-pandemic levels (8.25 (95%CI: 5.79-11.76)). The 2023 strains belonged to genotype 1a and were closely related to pre-2019 strains. Blood viral loads were significantly different between clinical presentations (p<0.0001). Machine learning allowed us to classify 68.8% (95% CI: 60.9-75.9) patients into the correct clinical group.

The 2023-24 epidemic is probably due to the reemergence of the pre-2019 strain. The virological profiles highlighted in this study could assist in accurately interpreting virology results.

Acute liver injury is a common manifestation of parvovirus B19 (PVB19) infection in immunocompromised patients. However, literature in immunocompetent children is scarce. We aimed to study the clinicolaboratory features and outcome of hepatic involvement by PVB19 infection in hospitalized children.

We retrospectively analyzed our prospectively kept database of all children (<18 years old) admitted with acute viral hepatitis (AVH), acute liver failure (ALF) or acute-on-chronic liver failure (ACLF), and PVB19 infection between January 2010 and December 2023. Clinical features, laboratory parameters, and complications were evaluated. Poor outcome was defined as death or liver transplantation.

A total of 35 children (19 boys [54%], median age: 7.25 [interquartile range: 4-10.8] years) with PVB19-related hepatitis were studied (28 [80%] isolated PVB19 infection and 7 [20%] coinfections [3 with Epstein-Barr virus, 2 with hepatitis A, and 1 each with hepatitis-E and cytomegalovirus]). AVH (17, 49%) was the most common presentation, followed by ALF (13, 37%) and acute insult in ACLF (5, 14%). Patients with coinfection had significantly higher bilirubin (14.6 [9.4-21.5] vs 6.8 [4.3-10.9] mg/dl; P=0.004) and transaminases (ALT: 697 [428-1296] vs. 277 [157-478] U/L; P=0.02) but similar mortality (1/7 vs 6/23; P=1.0) than PVB19 alone. Nine cases (25.7%) had extrahepatic complications (hemophagocytic lymphohistiocytosis [HLH]: 3, acute kidney injury: 3, aplastic anemia: 2, and myocarditis: 1). Poor outcome occurred in 38% (5/13) ALF, 11.7% (2/17) AVH (HLH: 1, myocarditis: 1), and none (0/5) of the ACLF cases.

PVB19 should be considered in children presenting with indeterminate acute liver injury, especially in younger children or those with complications such as aplastic anemia, HLH, or myocarditis.

Parvovirus B19 is a common viral pathogen that commonly manifests with mild, flu-like symptoms or an erythematous rash. In rare instances, it may lead to hematological complications, even in immunocompetent individuals. This report presents a case of a 64-year-old male without prior hematological conditions who presented with generalized malaise, intermittent fever, and a pruritic rash. Initial laboratory findings revealed normochromic, normocytic anemia, leukopenia, thrombocytopenia, and acute kidney injury. Extensive diagnostic workup excluded common bacterial and viral etiologies. Serology for parvovirus B19 demonstrated positive IgG and IgM antibodies, indicative of a recent infection. The patient developed severe pancytopenia during hospitalization. Supportive care was provided, and the patient demonstrated complete clinical and hematologic recovery at discharge.. This case underscores the potential for severe hematological complications of parvovirus B19 infection in immunocompetent individuals. Early recognition of these complications is crucial for optimal management and patient outcomes. Clinicians should include parvovirus B19 in the differential diagnosis of unexplained pancytopenia, even in patients without known hematological disorders or other types of immunodeficiency.

In most persons, human parvovirus B19 (B19) causes a mild respiratory illness, but infection can result in adverse health outcomes in persons who are pregnant, immunocompromised, or who have chronic hemolytic blood disorders. During the first quarter of 2024, several European countries reported increases in B19 activity. In the United States, there is no routine surveillance for B19. To assess increases in B19 activity in the United States, trends in testing and results from two independent populations were examined: 1) the presence of immunoglobulin (Ig) M antibodies, a marker of recent infection, in clinical specimens ordered by physicians and 2) B19 nucleic acid amplification testing (NAAT) in pooled donor source plasma from a large commercial laboratory during 2018-2024. The proportion of IgM-positive clinical specimens reached 9.9% in the second quarter (Q2) of 2024 after remaining <1.5% during 2020-2023 and was higher than Q2 peaks in 2018 (3.8%, p<0.001) and 2019 (5.1%, p<0.001). The prevalence of B19-NAAT-positive donor pools (512 donations per pool) reached 20% in June 2024 after remaining <2% during 2020-2023 and was higher than peaks in 2018 (6.7%, p<0.001) and 2019 (7.3%, p<0.001). Considering the B19 activity increase in the United States in 2024, promotion of measures to prevent respiratory viruses and monitor for adverse B19-related outcomes by health care providers and public health authorities might reduce adverse health outcomes in pregnant persons and others at increased risk.

Sickle cell disease (SCD) is among the most frequent hereditary disorders globally and its prevalence in Europe is increasing due to migration movements.

The basic pathophysiological event of SCD is polymerization of deoxygenated sickle hemoglobin, resulting in hemolysis, vasoocclusion, and multiorgan damage. While the pathophysiological cascade offers numerous targets for treatment, currently only two disease-modifying drugs have been approved in Europe and transfusion remains a mainstay of both preventing and treating severe complications of SCD. Allogeneic stem cell transplantation and gene therapy offer a curative option but are restricted to few patients due to costs and limited availability of donors.

Further efforts are needed to grant patients access to approved treatments, to explore drug combinations and to establish new treatment options.

Parvovirus B19 infection can cause chronic pure red cell aplasia in immunosuppressed hosts or acute and transient aplastic crisis in immunocompetent hosts. In dialysis patients, only transient aplastic crisis induced by parvovirus B19 infection has been reported. We herein report the first case of an adult dialysis patient who developed chronic pure red cell aplasia associated with parvovirus B19 infection. Repeated pneumonia and heart failure may contribute to an immunocompromised status, making the patient more vulnerable to parvovirus B19 infection. This case expands on the differential diagnosis of chronic anemia in patients undergoing dialysis.

Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19-induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24- cells among CD19+ B cells (termed 'plasmablasts' for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.

This study aims to evaluate the role of parvovirus B19 (B19V) in the pathogenesis of myocarditis in a paediatric population, including post-mortem samples from two children.

From 2004 to 2023, endomyocardial biopsies (EMBs) from children under 16 years of age were analyzed using histology, immunohistochemistry, and molecular pathology. A total of 306 children with acute and 1060 children with chronic lymphocytic myocarditis were identified.

B19V infection was more frequent in acute myocarditis than in chronic myocarditis (43% vs. 14%), with higher viral loads in acute cases regardless of age. The most prominent cardiac CD3+ T cell infiltration was noted in children < 2 years, correlating with high cardiac B19V loads. In two male infants who died from B19V infection, B19V DNA was localized in the endothelial cells of multiple organs using in situ hybridization. Virus replication was found in the endothelial cells of small cardiac arterioles and venules but not in capillaries. B19V DNA/mRNA was also detected in immune cells, especially in the spleen and lymph nodes, revealing virus replication in B lymphocytes.

B19V can induce severe lymphocytic myocarditis, especially in young children. The simultaneous histopathological and molecular assessment of EMBs is important for early diagnosis of viral myocarditis, preventing severe disease, and ensuring appropriate therapy.

Parvovirus B19 (B19V) is a human pathogen belonging to the Parvoviridae family. It is widely diffused in the population and responsible for a wide range of diseases, diverse in pathogenetic mechanisms, clinical course, and severity. B19V infects and replicates in erythroid progenitor cells (EPCs) in the bone marrow leading to their apoptosis. Moreover, it can also infect, in an abortive manner, a wide set of different cell types, normally non-permissive, and modify their normal physiology. Differences in the characteristics of virus-cell interaction may translate into different pathogenetic mechanisms and clinical outcomes. Joint involvement is a typical manifestation of B19V infection in adults. Moreover, several reports suggest, that B19V could be involved in the pathogenesis of some autoimmune rheumatologic diseases such as rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), or vasculitis. This review provides basic information on the B19 virus, highlights characteristics of viral infection in permissive and non-permissive systems, and focuses on recent findings concerning the pathogenic role of B19V in rheumatologic diseases.

Parvoviruses, characterized by their tropism for blood cells, can manifest as asymptomatic infections. With their ability to persist in blood, assessing the prevalence of Parvovirus B19 (B19V) and Parvovirus 4 (PARV4) among healthy blood donors is essential for evaluating the potential transmission risks through blood transfusions, emphasizing the need for comprehensive screening protocols.

Four hundred blood donors participated in the study, with their blood specimens subjected to Real-Time PCR analysis for B19V and PARV4 nucleic acids after obtaining informed consent. Additionally, Complete Blood Count (CBC) assessments and determination of anti-B19 V-IgM and anti-B19 V-IgG antibody titers were performed using Enzyme-Linked Immunosorbent Assay (ELISA) for all collected samples.

The results reveal that 12 out of 400 individuals (3 %) exhibited positive results for B19V DNA, while 6 out of 400 individuals (1.5 %) tested positive for PARV4 DNA. Additionally, 8 out of 400 individuals (2 %) displayed positive results for anti-B19V IgM, and 306 out of 400 individuals (76.5 %) exhibited positive results for anti-B19 IgG. Notably, one donation from a donor presenting anti-IgM antibodies was subsequently confirmed as B19V DNA-positive through Real-Time PCR. In the analysis of CBC, a significant disparity in platelet levels was observed between B19V-positive donors, PARV4-positive donors, and B19V-negative donors.

The study suggests that individuals at high risk, lacking detectable B19V antibodies, should undergo systematic screening and exclusion. This precaution is intended to minimize potential contamination risks within the studied cohort, despite the undefined pathogenesis and clinical implications of PARV4.

Parvovirus B19(B19) is a DNA virus. The most common B19 disease is erythema infectiosum (fifth-disease). PCR and ELISA are sensitive for detecting of acute disease. However, it is not clear which test better and the relationship between laboratory tests and clinical findings.

To discuss the clinical and laboratory characteristics of pediatric patients infected with B19.

236 children were examined. Children with at least one positive molecular or serological test were included. Positive serum B19-DNA and/or B19-IgM was considered an acute B19 infection.

B19DNA was detected in 80.8 % of acute cases. Serological tests were less positive. Acute B19 infection was observed in 24 patients. Only 17 patients were positive for B19 DNA, 3 for IgM and 4 for both. The sensitivity of B19 DNA is 87.5 %. However, this rate is 29.2 % for B19 IgM.

B19-DNA and IgM together provide a better, highly accurate diagnosis.

Human Erythrovirus (parvovirus) B19 infection can produce symptoms similar to those produced by Dengue, Chikungunya, and Zika viruses, making clinical diagnosis difficult. The importance of erythrovirus B19 in human pathology has been increased and reported in numerous studies published globally.

The B19V infection was investigated by real-time PCR in sera samples from patients with signs and symptoms related to classic arboviral symptoms. This study was conducted to provide information on the genetic diversity of Human Erythrovirus B19 (B19V) circulating in the state of Mato Grosso do Sul, Midwest region of Brazil, from 2017 to 2022. A total of 773 sera samples of patients with negative diagnostic results for Dengue, Chikungunya, and Zika, during the study period were analyzed.

Erythrovirus DNA was found in 10.6% (82/773) of patients, among them 10 were pregnant women. Four samples were completely sequenced, and the other five partially, to genotype by phylogenetic reconstruction. All samples belong to worldwide dispersed genotype 1, subgenotype 1a.

The findings of the study demonstrate the importance of including B19V in differential laboratory diagnosis for epidemiological purposes and appropriate patient management. The diagnosis for B19V should be performed, particularly among pregnant women, immunocompromised patients, and individuals with hemolytic diseases, given that the infection is more severe in these cases.

We report an epidemic of parvovirus B19 infections in Denmark during the first quarter of 2024, with a peak incidence 3.5 times higher than during the most recent epidemic in 2017. In total, 20.1% (130/648) of laboratory-confirmed cases were pregnant. Severe adverse outcomes were observed among 12.3% (16/130) of pregnant people and included foetal anaemia, foetal hydrops and miscarriage. Parvovirus B19 infection is not systematically monitored, but a national laboratory-based surveillance system is currently being established in Denmark.

Parvovirus B19 infection, typically associated with erythema infectiosum in children, presents variably in adults, often leading to misdiagnosis. This case series describes three adult patients diagnosed with parvovirus B19 infection in an internal medicine outpatient clinic in March 2024. Symptoms included fatigue, joint pain, swelling, and skin rash, with misdiagnoses including early rheumatoid arthritis. The diagnosis was confirmed via positive parvovirus antibodies and polymerase chain reaction (PCR). All patients received supportive care, and symptoms resolved within an average of 18 days. This series underscores the need for heightened clinical suspicion and timely serological testing for parvovirus B19 in adults presenting with flu-like symptoms, joint pain, and rash, especially during mini-outbreaks and following contact with infected children.

Diamond-Blackfan anaemia (DBA), first described over 80 years ago, is a congenital disorder of erythropoiesis with a predilection for birth defects and cancer. Despite scientific advances, this chronic, debilitating, and life-limiting disorder continues to cause a substantial physical, psychological, and financial toll on patients and their families. The highly complex medical needs of affected patients require specialised expertise and multidisciplinary care. However, gaps remain in effectively bridging scientific discoveries to clinical practice and disseminating the latest knowledge and best practices to providers. Following the publication of the first international consensus in 2008, advances in our understanding of the genetics, natural history, and clinical management of DBA have strongly supported the need for new consensus recommendations. In 2014 in Freiburg, Germany, a panel of 53 experts including clinicians, diagnosticians, and researchers from 27 countries convened. With support from patient advocates, the panel met repeatedly over subsequent years, engaging in ongoing discussions. These meetings led to the development of new consensus recommendations in 2024, replacing the previous guidelines. To account for the diverse phenotypes including presentation without anaemia, the panel agreed to adopt the term DBA syndrome. We propose new simplified diagnostic criteria, describe the genetics of DBA syndrome and its phenocopies, and introduce major changes in therapeutic standards. These changes include lowering the prednisone maintenance dose to maximum 0·3 mg/kg per day, raising the pre-transfusion haemoglobin to 9-10 g/dL independent of age, recommending early aggressive chelation, broadening indications for haematopoietic stem-cell transplantation, and recommending systematic clinical surveillance including early colorectal cancer screening. In summary, the current practice guidelines standardise the diagnostics, treatment, and long-term surveillance of patients with DBA syndrome of all ages worldwide.

In adults and fetuses, N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac failure and myocardial remodelling. We examined the effect of anemia and intrauterine transfusion (IUT) on NT-proBNP concentrations in fetuses with anemia and established gestational age-dependent reference values of a control group.

We analyzed NT-proBNP levels in anemic fetuses that underwent serial intrauterine transfusions (IUT), focusing on different causes and severity of anemia and comparing the results to a non-anemic control group.

In the control group, the average NT-proBNP concentration was 1339 ± 639 pg/ml, decreasing significantly with increasing gestational age (R = - 74.04, T = - 3.65, p = 0.001). Subjects had significantly higher NT-proBNP concentrations before initiation of IUT therapy (p < 0.001), showing fetuses with parvovirus B19 (PVB19) infection having the highest concentrations. Hydropic fetuses also showed an increased NT-proBNP concentration compared to non-hydropic fetuses (p < 0.001). During the course of therapy, NT-proBNP concentration before subsequent IUT decreased significantly from pathologically high levels, while MoM-Hb and MoM-MCA-PSV remained pathological.

NT-pro BNP levels in non-anemic fetuses are higher than in postnatal life, decreasing with ongoing pregnancy. Anemia is a hyperdynamic state and its severity correlates with circulating NT-proBNP levels. Highest concentrations occur in fetuses with hydrops and with PVB19 infection, respectively. Treatment by IUT leads to a normalisation of NT-proBNP concentrations, so the measurement of its levels may be useful in therapy monitoring.

The advancement of point-of-care diagnostics is crucial to improving patient outcomes, especially in areas with low access to hospitals or specialized laboratories. In particular, rapid, sensitive, and multiplexed detection of disease biomarkers has great potential to achieve accurate diagnosis and inform high quality care for patients. Our Coulter counting and immunocapture based detection system has previously shown its broad applicability in the detection of cells, proteins, and nucleic acids. This paper expands the capability of the platform by demonstrating multiplexed detection of whole-virus particles using electrically distinguishable hydrogel beads by demonstrating the capability of our platform to achieve simultaneous detection at clinically relevant concentrations of hepatitis A virus (>2 × 103 IU mL-1) and human parvovirus B19 virus like particles (>106 IU mL-1) from plasma samples. The expanded versatility of the differential electrical counting platform allows for more robust and diverse testing capabilities.

Sepsis is a leading cause of pediatric mortality. Little attention has been paid to the association between viral DNA and mortality in children and adolescents with sepsis.

To assess the association of the presence of viral DNA with sepsis-related mortality in a large multicenter study.

This cohort study compares pediatric patients with and without plasma cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), human herpesvirus 6 (HHV-6), parvovirus B19 (B19V), BK polyomavirus (BKPyV), human adenovirus (HAdV), and torque teno virus (TTV) DNAemia detected by quantitative real-time polymerase chain reaction or plasma IgG antibodies to CMV, EBV, HSV-1, or HHV-6. A total of 401 patients younger than 18 years with severe sepsis were enrolled from 9 pediatric intensive care units (PICUs) in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Data were collected from 2015 to 2018. Samples were assayed from 2019 to 2022. Data were analyzed from 2022 to 2023.

Death while in the PICU.

Among the 401 patients included in the analysis, the median age was 6 (IQR, 1-12) years, and 222 (55.4%) were male. One hundred fifty-four patients (38.4%) were previously healthy, 108 (26.9%) were immunocompromised, and 225 (56.1%) had documented infection(s) at enrollment. Forty-four patients (11.0%) died in the PICU. Viral DNAemia with at least 1 virus (excluding TTV) was detected in 191 patients (47.6%) overall, 63 of 108 patients (58.3%) who were immunocompromised, and 128 of 293 (43.7%) who were not immunocompromised at sepsis onset. After adjustment for age, Pediatric Risk of Mortality score, previously healthy status, and immunocompromised status at sepsis onset, CMV (adjusted odds ratio [AOR], 3.01 [95% CI, 1.36-6.45]; P = .007), HAdV (AOR, 3.50 [95% CI, 1.46-8.09]; P = .006), BKPyV (AOR. 3.02 [95% CI, 1.17-7.34]; P = .02), and HHV-6 (AOR, 2.62 [95% CI, 1.31-5.20]; P = .007) DNAemia were each associated with increased mortality. Two or more viruses were detected in 78 patients (19.5%), with mortality among 12 of 32 (37.5%) who were immunocompromised and 9 of 46 (19.6%) who were not immunocompromised at sepsis onset. Herpesvirus seropositivity was common (HSV-1, 82 of 246 [33.3%]; CMV, 107 of 254 [42.1%]; EBV, 152 of 251 [60.6%]; HHV-6, 253 if 257 [98.4%]). After additional adjustment for receipt of blood products in the PICU, EBV seropositivity was associated with increased mortality (AOR, 6.10 [95% CI, 1.00-118.61]; P = .049).

The findings of this cohort study suggest that DNAemia for CMV, HAdV, BKPyV, and HHV-6 and EBV seropositivity were independently associated with increased sepsis mortality. Further investigation of the underlying biology of these viral DNA infections in children with sepsis is warranted to determine whether they only reflect mortality risk or contribute to mortality.

This study aimed to estimate the serological status and dynamic changes in the prevalence of Parvovirus B19 (PVB19) antibodies within the general population residing in the northern part of the Republic of Serbia (Province of Vojvodina) during a 16-year period. Serum samples were analyzed for Human PVB19-specific IgM and IgG antibodies using enzyme-linked immunosorbent assay (ELISA). Throughout the study period, the overall seroprevalence was 49.51%. Approximately 10% of patients exhibited a serologic profile positive for PVB19 IgM antibodies. Notably, seroprevalence varied significantly, ranging from 9.12% in the pediatric cohort (ages 1-4 years) to 65.50% in the adult demographic (40-59 years old). Seroprevalence was higher (51.88%) among women compared to men (42.50%). Immunologically naive pregnant women in the age groups 26-36 and 36-45 years had 45% (OR = 0.55, 95% CI: 0.31-1.00) and 52% (OR = 0.48; 95% CI: 0.24-0.94) lower odds of having negative IgM and IgG compared to those in age group 16-25 years old. Improved knowledge of the epidemiology of PVB19 may assist clinicians in the differential diagnosis of PVB19 clinical manifestations. The PVB19 detection is particularly important for monitoring individuals in risk groups such as women of reproductive age, medical staff, patients with hematological disorders, and those with immunodeficiency.

Erythema infectiosum occurs worldwide. School-aged children are most often affected. Since the diagnosis is mainly clinical, physicians should be well-versed in the clinical manifestations of erythema infectiosum to avoid misdiagnosis, unnecessary investigations, and mismanagement of the disease.

The purpose of this article is to familiarize physicians with the wide spectrum of clinical manifestations and complications of erythema infectiosum associated with parvovirus B19 infection.

A search was conducted in July 2022 in PubMed Clinical Queries using the key terms "Erythema infectiosum" OR "Fifth disease" OR "Slapped cheek disease" OR "Parvovirus B19". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article.

Erythema infectiosum is a common exanthematous illness of childhood caused by parvovirus B19. Parvovirus B19 spreads mainly by respiratory tract secretions and, to a lesser extent, the saliva of infected individuals. Children between 4 and 10 years of age are most often affected. The incubation period is usually 4 to 14 days. Prodromal symptoms are usually mild and consist of lowgrade fever, headache, malaise, and myalgia. The rash typically evolves in 3 stages. The initial stage is an erythematous rash on the cheeks, with a characteristic "slapped cheek" appearance. In the second stage, the rash spreads concurrently or quickly to the trunk, extremities, and buttocks as diffuse macular erythema. The rash tends to be more intense on extensor surfaces. The palms and soles are typically spared. Central clearing of the rash results in a characteristic lacy or reticulated appearance. The rash usually resolves spontaneously within three weeks without sequelae. The third stage is characterized by evanescence and recrudescence. In adults, the rash is less pronounced than that in children and is often atypical. Only approximately 20% of affected adults have an erythematous rash on the face. In adults, the rash is more frequently found on the legs, followed by the trunk, and arms. A reticulated or lacy erythema is noted in 80% of cases which helps to distinguish erythema infectiosum from other exanthems. Pruritus is noted in approximately 50% of cases. The diagnosis is mainly clinical. The many manifestations of parvovirus B19 infection can pose a diagnostic challenge even to the best diagnostician. Complications include arthritis, arthralgia, and transient aplastic crisis. In most cases, treatment is symptomatic and supportive. When parvovirus B19 infection occurs in pregnant women, hydrops fetalis becomes a real concern.

Erythema infectiosum, the most common clinical manifestation of parvovirus B19 infection, is characterized by a "slapped cheek" appearance on the face and lacy exanthem on the trunk and extremities. Parvovirus B19 infection is associated with a wide spectrum of clinical manifestations. Physicians should be aware of potential complications and conditions associated with parvovirus B19 infection, especially in individuals who are immunocompromised, chronically anemic, or pregnant.

Human parvovirus B19 (B19V) has a wide clinical spectrum, ranging from an asymptomatic infection to a life threatening one. During pregnancy, it can lead to fetal loss and hydrops fetalis. This retrospective study examined the incidence rates of B19V in Israel, analyzing anonymized electronic medical records of 2.7 million individuals between January 2015 and September 2023. A generalized linear model with a Poisson distribution was fit to the data, adjusting for potential confounders. A marked increase in B19V was observed in 2023, with an adjusted incidence rate ratio (IRR) of 6.6 (95% CI 6.33-6.89) when comparing 2023 to previous years. When specifically comparing 2023 to COVID-19 years (2020-2022), adjusted IRR climbs to 9.21 (8.66-9.80). Moreover, in 2023, previously existing seasonality has largely disappeared. High SES characterized most infected individuals with a marked discrepancy in social sectors; the Arab population was significantly less likely to be found B19V positive, even when adjusting for SES. Most infections occurred in school-aged children (6-11 years old). Pregnant women experienced the most significant rise in B19V, with an adjusted IRR of 11.47 (9.44-13.97) in 2023 compared to previous years; most cases were diagnosed in the first trimester. This study demonstrates that Israel is currently experiencing the largest and longest reported outbreak of B19V to date. Policymakers should consider setting screening policies in place, at least for populations at risk, while specifically studying and potentially targeting low socioeconomic populations and specific social sectors to avoid health inequalities.

We report the sequences of four complete genomes of parvovirus B19, extracted from human amniotic fluid specimens collected from pregnant women with abnormal ultrasound features in France. The genome sequences are 5,596 nucleotides long and include long terminal repeats. Several amino acid substitutions were observed in nonstructural protein (NS1).

To understand the epidemiological and genetic characteristics of B19V, a multiple-province surveillance of patients with febrile rash illnesses (FRIs) were conducted in China during 2009 ~ 2021. The clinical specimens of 3,820 FRI patients were collected and tested for B19V DNA. A total of 99 (2.59%) patients were positive for B19V, and 49 (49.49%) were children under 5 years old. B19V infections occurred throughout the year without obvious seasonal pattern. Ten NS1-VP1u sequences and seven genome sequences were obtained in this study, identified as subgenotype 1a. Combined with the globally representative genome sequences, no temporal and geographic clustering trends of B19V were observed, and there was no significant correlation between B19V sequences and clinical manifestations. The evolutionary rate of the B19V genome was 2.30 × 10-4 substitutions/site/year. The number of negative selection sites was higher than that of positive selection sites. It was the first to comprehensively describe the prevalence patterns and evolutionary characteristics of B19V in FRI patients in China. B19V played the role in FRI patients. Children under 5 years old were the main population of B19V infection. Subgenotype 1a was prevalent in FRI patients in China. B19V showed a high mutation rate, while negative selection acted on the genome.

Virus-like particles (VLPs) comprise one or many structural components of virions, except their genetic material. Thus, VLPs keep their structural properties of cellular recognition while being non-infectious. VLPs of Parvovirus B19 (B19V) can be produced by the heterologous expression of their structural proteins VP1 and VP2 in bacteria. These proteins are purified under denaturing conditions, refolded, and assembled into VLPs. Moreover, chimeric forms of VP2 have been constructed to harbor peptides or functional proteins on the surface of the particles without dropping their competence to form VLPs, serving as presenting nanoparticles. The in-vitro assembly approach offers exciting possibilities for the composition of VLPs, as more than one chimeric form of VP2 can be included in the assembly stage, producing multifunctional VLPs. Here, the heterologous expression and in-vitro assembly of B19V structural proteins and their chimeras are reviewed. Considerations for the engineering of the structural proteins of B19V are also discussed. Finally, the construction of multifunctional VLPs and their future potential as innovative medical tools are examined.

Parvovirus B19 infection typically exhibits a biphasic clinical course with varied symptoms. While facial or extremity edemas are common in adult cases, localized eyelid swelling, referred to as Hoagland's sign, had not been recognized as a potential clinical feature. Here, we present the case of a 72-year-old woman with parvovirus B19 infection and Hoagland's sign, characterized by drooping of the swollen upper eyelid and narrowing of the ocular aperture. The patient showed symptoms of fever, myalgia, and neutrophilia with atypical lymphocytes. The diagnosis was confirmed through elevated parvovirus B19 IgM antibody levels. This is the first reported case of parvovirus B19 infection presenting with Hoagland's sign. Parvovirus B19 infection can present with the condition called "infectious mononucleosis-like syndrome" (IML), which mimics classical manifestations of infectious mononucleosis (IM), including Hoagland's sign. Our case suggested that Hoagland's sign may be one of the characteristic symptoms of the second phase in the biphasic course of parvovirus B19 infection. It is important to consider the possibility of parvovirus B19 infection, especially in elderly patients presenting with Hoagland's sign.

Transfusion medicine is traditionally a strong/fundamental part of clinical practice, saving hundreds of millions of lives. However, blood-borne or transmitted infections are a well-known and feared possibility, a risk we relentlessly mitigate. Pathogens are continuously and rather quickly changing, so during the last decade, many, sometimes exotic, new pathogens and diseases were recorded and analyzed, and some of them were proved to be transmitted with transfusions. Blood or blood component transfusions are carried out after cautious preparative screening and inactivation maneuvers, but in some instances, newly recognized agents might escape from standard screening and inactivation procedures. Here, we try to focus on some of these proven or potentially pathogenic transfusion-transmitted agents, especially in immunocompromised patients or bone marrow transplantation settings. These pathogens are sometimes new challenges for preparative procedures, and there is a need for more recent, occasionally advanced, screening and inactivation methods to recognize and eliminate the threat a new or well-known pathogen can pose. Pathogen transmission is probably even more critical in hemophiliacs or bone marrow transplant recipients, who receive plasma-derived factor preparations or blood component transfusions regularly and in large quantities, sometimes in severely immunosuppressed conditions. Moreover, it may not be emphasized enough that transfusions and plasma-derived product administrations are essential to medical care. Therefore, blood-borne transmission needs continued alertness and efforts to attain optimal benefits with minimized hazards.

Myocarditis is an inflammatory disease of the myocardium caused by infectious or non-infectious agents. It can lead to serious short-term and long-term sequalae, such as sudden cardiac death or dilated cardiomyopathy. Due to its heterogenous clinical presentation and disease course, challenging diagnosis and limited evidence for prognostic stratification, myocarditis poses a great challenge to clinicians. As it stands, the pathogenesis and etiology of myocarditis is only partially understood. Moreover, the impact of certain clinical features on risk assessment, patient outcomes and treatment options is not entirely clear. Such data, however, are essential in order to personalize patient care and implement novel therapeutic strategies. In this review, we discuss the possible etiologies of myocarditis, outline the key processes governing its pathogenesis and summarize best available evidence regarding patient outcomes and state-of-the-art therapeutic approaches.

A unique immunological condition, pregnancy ensures fetus from maternal rejection, allows adequate fetal development, and protects against microorganisms. Infections during pregnancy may lead to devastating consequences for pregnant women and fetuses, resulting in the mother's death, miscarriage, premature childbirth, or neonate with congenital infection and severe diseases and defects. Epigenetic (heritable changes in gene expression) mechanisms like DNA methylation, chromatin modification, and gene expression modulation during gestation are linked with the number of defects in the fetus and adolescents. The feto-maternal crosstalk for fetal survival during the entire gestational stages are tightly regulated by various cellular pathways, including epigenetic mechanisms that respond to both internal as well outer environmental factors, which can influence the fetal development across the gestational stages. Due to the intense physiological, endocrinological, and immunological changes, pregnant women are more susceptible to bacterial, viral, parasitic, and fungal infections than the general population. Microbial infections with viruses (LCMV, SARS-CoV, MERS-CoV, and SARS-CoV-2) and bacteria (Clostridium perfringens, Coxiella burnetii, Listeria monocytogenes, Salmonella enteritidis) further increase the risk to maternal and fetal life and developmental outcome. If the infections remain untreated, the possibility of maternal and fetal death exists. This article focused on the severity and susceptibility to infections caused by Salmonella, Listeria, LCMV, and SARS-CoV-2 during pregnancy and their impact on maternal health and the fetus. How epigenetic regulation during pregnancy plays a vital role in deciding the fetus's developmental outcome under various conditions, including infection and other stress. A better understanding of the host-pathogen interaction, the characterization of the maternal immune system, and the epigenetic regulations during pregnancy may help protect the mother and fetus from infection-mediated outcomes.

Replication-initiating HUH endonucleases (Reps) are sequence-specific nucleases that cleave and rejoin single-stranded DNA (ssDNA) during rolling-circle replication. These functions are mediated by covalent linkage of the Rep to its substrate post cleavage. Here, we describe the structures of the endonuclease domain from the Muscovy duck circovirus Rep in complex with its cognate ssDNA 10-mer with and without manganese in the active site. Structural and functional analyses demonstrate that divalent cations play both catalytic and structural roles in Reps by polarizing and positioning their substrate. Further structural comparisons highlight the importance of an intramolecular substrate Watson-Crick (WC) base pairing between the -4 and +1 positions. Subsequent kinetic and functional analyses demonstrate a functional dependency on WC base pairing between these positions regardless of the pair's identity (i.e., A·T, T·A, G·C, or C·G), highlighting a structural specificity for substrate interaction. Finally, considering how well WC swaps were tolerated in vitro, we sought to determine to what extent the canonical -4T·+1A pairing is conserved in circular Rep-encoding single-stranded DNA viruses and found evidence of noncanonical pairings in a minority of these genomes. Altogether, our data suggest that substrate intramolecular WC base pairing is a universal requirement for separation and reunion of ssDNA in Reps. IMPORTANCE Circular Rep-encoding single-stranded DNA (CRESS-DNA) viruses are a ubiquitous group of viruses that infect organisms across all domains of life. These viruses negatively impact both agriculture and human health. All members of this viral family employ a multifunctional nuclease (Rep) to initiate replication. Reps are structurally similar throughout this family, making them targets of interest for viral inhibition strategies. Here, we investigate the functional dependencies of the Rep protein from Muscovy duck circovirus for ssDNA interaction. We demonstrate that this Rep requires an intramolecular Watson-Crick base pairing for origin of replication (Ori) recognition and interaction. We show that noncognate base pair swaps are well tolerated, highlighting a local structural specificity over sequence specificity. Bioinformatic analysis found that the vast majority of CRESS-DNA Oris form base pairs in conserved positions, suggesting this pairing is a universal requirement for replication initiation in the CRESS-DNA virus family.

Aplastic anemia is an uncommon condition defined by peripheral pancytopenia in the context of hypocellular bone marrow. In the majority of cases, it is idiopathic in origin. However, exposure to certain drugs and toxins, autoimmune processes, and viral infections have been linked to this entity. This is the case of a 56-year-old female with an acute presentation of fever, odynophagia, and dysphagia. Physical examination revealed multiple hemorrhagic ulcers affecting her oropharyngeal mucosa with regions of necrosis. Mucosal biopsy was compatible with the presence of local necrosis and keratinization. Hematological analysis showed severe peripheral pancytopenia, and the bone marrow biopsy revealed a hypocellular marrow, findings consistent with aplastic anemia. An ample PCR viral panel revealed the presence of herpes simplex virus type 1 (HSV-1). The patient was placed on systemic antiviral therapy, followed by a rapid improvement of the mucositis as well as the peripheral and central pancytopenia. Our case indicated the possible association of HSV-1 infection and the development of aplastic anemia, an important and not yet recognized association considering the rapid improvement of the clinical picture once the underlying etiology was addressed.

Parvovirus B19 (B19V) infection following pediatric hematopoietic cell transplantation (HCT) is a rare complication and available data is scarce. Therefore, we present the experience with B19V Infection in allogeneic pediatric HCT recipients at our transplant center together with a systematic review of the literature.

Pediatric HCT patients with Parvovirus B19 infection treated at the University Children's Hospital Münster between 1999 and 2021 were retrospectively identified and clinical data were analyzed. Additionally, a systematic MEDLINE search to identify relevant articles was performed.

We identified three out of 445 patients (0.6%) with B19V infection post-transplantation. B19V infection occurred in combination with other complications like Graft-versus-Host disease, additional infections, or autoimmune-mediated hemolysis potentially triggered by B19V. In one patient these complications lead to a fatal outcome. The review of the literature showed considerable morbidity of B19V infection with the potential for life-threatening complications. Most patients were treated by red blood cell transfusion and intravenous immunoglobulins (IVIG) with a high succession rate.

Symptomatic B19V infection following HCT remains a rare but potentially challenging complication. A causal antiviral therapy does not exist as well as general recommendations on dosage and duration of IVIG therapy. Despite this, most patients are treated successfully with these measures. Additionally, transmission via blood or stem cell products is also rare and no general recommendations on B19V screenings exist.

Viral infections have been frequently associated with physiological and pathological changes in the endocrine system for many years. The numerous early and late endocrine complications reported during the current pandemic of coronavirus disease 2019 (COVID-19) reinforce the relevance of improving our understanding of the impact of viral infections on the endocrine system. Several viruses have been shown to infect endocrine cells and induce endocrine system disturbances through the direct damage of these cells or through indirect mechanisms, especially the activation of the host antiviral immune response, which may lead to the development of local or systemic inflammation or organ-specific autoimmunity. In addition, endocrine disorders may also affect susceptibility to viral infections since endocrine hormones have immunoregulatory functions. This review provides a brief overview of the impact of viral infections on the human endocrine system in order to provide new avenues for the control of endocrine diseases.

Parvovirus B19 (B19V) infects human erythroid progenitor cells (EPCs) and causes several hematological disorders and fetal hydrops. Amino acid (aa) 5-68 of minor capsid protein VP1 (VP1u5-68aa) is the minimal receptor binding domain for B19V to enter EPCs. Here, we carried out a genome-wide CRISPR-Cas9 guide RNA screen and identified tyrosine protein kinase receptor UFO (AXL) as a proteinaceous receptor for B19V infection of EPCs. AXL gene silencing in ex vivo expanded EPCs remarkably decreased B19V internalization and replication. Additions of the recombinant AXL extracellular domain or a polyclonal antibody against it upon infection efficiently inhibited B19V infection of ex vivo expanded EPCs. Moreover, B19V VP1u interacted with the recombinant AXL extracellular domain in vitro at a relatively high affinity (KD = 103 nM). Collectively, we provide evidence that AXL is a co-receptor for B19V infection of EPCs.