Intrauterine transfusion in 103 fetuses with severe anemia caused by parvovirus infection. A multicenter retrospective study.

PURPOSE: Evaluating procedure-related complications and perinatal outcomes after intrauterine transfusion (IUT) before or after 20+0 weeks of gestation in fetuses with severe anemia due to intrauterine human parvovirus B19 infection. METHODS: A retrospective study investigating fetuses requiring IUT for fetal Parvo B19 infection in two tertiary referral centers between December 2002 and December 2021. Procedure-related complications, intrauterine fetal death (IUFD), and perinatal outcome were correlated to gestational age (GA) at first IUT, the presence of hydrops and fetal blood sampling results. RESULTS: A total of 186 IUTs were performed in 103 fetuses. The median GA at first IUT was 19+3 (13+0-31+4) weeks of gestation. IUFD occurred in 16/103 fetuses (15.5%). Overall survival was 84.5% (87/103). Hydrops (p = 0.001), lower mean hemoglobin at first IUT (p = 0.001) and low platelets (p = 0.002) were strongly associated with IUFD. There was no difference observed in fetuses transfused before or after 20+0 weeks of gestation. CONCLUSION: IUT is a successful treatment option in fetuses affected by severe anemia due to parvovirus B19 infection in specialized centers. In experienced hands, IUT before 20 weeks is not related to worse perinatal outcome.

Parvovirus B19-Associated Severe Anemia in Adult Liver Transplant Recipients: A Case Series and Review of the Literature.

Background: Parvovirus B19 (B19V) infection is a rare cause of severe anemia in liver transplant recipients. However, few studies have systematically reviewed reported cases and summarized experience in managing this disease. Objective: We described a retrospective case series of eight adult liver transplant recipients with B19V-associated severe anemia and performed a literature review of epidemiology, etiology, clinical courses, diagnosis, treatment options available, and outcomes of B19V-associated anemia in adult liver transplant recipients. Patients and Methods: We systematically reviewed articles describing adult liver transplant recipients with B19V-associated anemia from PubMed and ScienceDirect databases from database inception to May 2022. Results: Eight articles containing 23 cases were identified in addition to eight cases from our center for a total of 31 patients (mean age, 45.7 ± 9.7 years; 74.2% male). Eighty-seven percent developed transfusion-dependent anemia within two months after liver transplantation (LT). Fever and progressive anemia are among the major manifestations. Intravenous immunoglobulin (IVIG)-based therapy was given to all patients and the treatment protocols varied among different centers. Except for two cases who died of comorbidities, 17 patients obtained long-term recovery from anemia after one course of treatment and six (19%) experienced relapses that were reversed by repeated courses of IVIG therapy. Two recipients presented with IVIG-associated side effects and two developed acute cellular rejection (ACR) after reduction of immunosuppression. Conclusions: B19V infection should be suspected early as a cause of severe anemia of unknown etiology in adult liver transplant recipients. The clearance of B19V typically lags behind recovery of anemia, and inadequate clearance of virus after cessation of IVIG appears to be a potential risk of anemia recurrence. Moreover, more attention should be paid to the side effects of high-dose IVIG infusion and ACR because of reduction of immunosuppression.

Parvovirus B19 myocarditis in children: a diagnostic and therapeutic approach.

Parvovirus B19 is one of the most frequent causes of pediatric myocarditis, associating high mortality rates or need for cardiac transplantation. The aim of this study is to describe the clinical course of Parvovirus B19 myocarditis in children with emphasis on the role of endomyocardial biopsy and cardiac magnetic resonance, and the use of an innovative therapeutic strategy. Eleven patients and 12 episodes of polymerase chain reaction (PCR)-confirmed Parvovirus B19 myocarditis were prospectively collected for 14 years. Diagnosis was confirmed either histopathologically or by magnetic resonance. A life-threatening clinical presentation is described, similar to previous series, but with 83.3% overall survival without transplantation. We also present a case of recurrent myocarditis, which is extraordinarily rare. Electrocardiographic patterns presented chiefly peaked p waves, low QRS voltages, and negative T waves on inferior or lateral leads. Endomyocardial biopsy is the gold standard diagnostic test; alternatively magnetic resonance could be a useful diagnostic tool. A good concordance between myocardial and blood PCRs was observed. Seven patients received treatment with corticosteroids and beta interferon and all underwent a significant cardiac function improvement. CONCLUSION: A severe clinical presentation is reported, similar to previous reports but with better outcomes. Endomyocardial biopsy is the gold standard diagnostic test; alternatively magnetic resonance may be used. Both blood and myocardium PCR can be used in children to establish the microbiological etiology. Steroids with IFNß could be a useful therapeutic option, although further multicenter studies are needed to confirm these results. WHAT IS KNOWN: • Parvovirus B19 is one of the most frequent causes of myocarditis in children. It is associated with a fulminant clinical presentation. • Endomyocardial biopsy is the gold standard diagnostic test but it is an invasive procedure. WHAT IS NEW: • Myocarditis may recur in pediatrics, even it is extraordinarily rare. • IFNß with steroids may be a useful therapeutic option to improve the outcomes.

The detection, treatment of parvovirus B19 infection induced anemia in solid organ transplants: A case series and literature review of 194 patients.

BACKGROUND: There are no optimal diagnostic, treatment and post-infection surveillance strategies for parvovirus B19 infection in solid organ transplantation (SOT) recipients. METHODS: We conducted a retrospective review of all PVB19 infected cases confirmed by qPCR among SOT recipients at our institution over a 3-year period and reviewed the literature from 1990 to 2021. RESULTS: Eight kidney and two heart transplant patients with refractory anemia had PVB19 infection. The viral DNA load in peripheral blood ranged from 2.62×102 to 8.31×106 copies/mL. Two patients with the lowest PVB19 DNA load only reduced the use of immunosuppressants and anemia was relieved. Eight received intravenous immunoglobulin (IVIG) (ranging from 0.25 to 0.5g/kg/day). The median time to anemia improvement (hemoglobulin>100g/L) was 16days (8-70days) after treatment. One patient had a PVB19 relapse and viral DNA load>1.00×108 copies/mL at diagnosis. A total of 86 studies involving 194 SOTs were screened from the literature, and the most common symptom was anemia and low reticulocyte count. PVB19 DNA was detected in all cases. Of that, 91.4% of cases received IVIG, 53.8% received IVIG and immunosuppression reduction, 6.5% of cases showed reduced immunosuppression without IVIG, and 2.1% did not receive any special treatment. The recurrence rate was 17.5%. CONCLUSION: PVB19 infection is a cause of anemia after SOT, and treatment mainly relies on IVIG and/or immunosuppression reduction.

Hemophagocytic lymphohistiocytosis associated with parvovirus B19-induced aplastic crisis in a hereditary spherocytosis patient: A case report and literature review.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathologic immune activation. It occurs because of severe inflammation due to uncontrolled proliferation of activated lymphocytes and histiocytes, characterized by the production of excessive levels of cytokines. Virus-associated HLH is a well-known entity, and parvovirus B19 is one of the common causes. Parvovirus B19 can also affect blood cell lineages. Therefore, HLH may be accompanied by several diseases such as cytopenia, aplastic anemia, and myelodysplastic syndrome. Herein, we report the case of a patient with hereditary spherocytosis who was diagnosed with parvovirus B19-induced HLH and aplastic crisis. A 7-year-old girl presented to our hospital with fever, pleural effusion, pancytopenia, hepatosplenomegaly, and hypotension. A bone marrow biopsy was performed under the suspicion of HLH, which revealed hemophagocytes. The diagnostic criteria for HLH were met, and prompt chemoimmunotherapy was initiated considering the clinically unstable situation. Her health improved rapidly after initiating treatment. Further study revealed that she had hereditary spherocytosis, and parvovirus B19 had caused aplastic crisis and HLH. The patient's clinical progress was excellent, and chemoimmunotherapy was reduced and discontinued at an early stage. This case shows that aplastic crisis and HLH can coexist with parvovirus B19 infection in patients with hereditary spherocytosis. Although the prognosis was good in this case of HLH caused by parvovirus B19, early detection and active treatment are essential.

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 infection in pregnancy - A review.

Parvovirus B19 (B19V) is a widespread infection that may affect 1-5% of pregnant women, mainly with normal pregnancy outcome. Vertical transmission occurs in 33-51% of cases of maternal infection. B19V infection is an important cause of fetal morbidity (fetal anaemia and non-immune hydrops) and mortality, predominantly in the second trimester. Diagnosis of B19V infection requires a multi-method approach using mainly serology and PCR techniques. Severe fetal anaemia is managed with intrauterine transfusion with perinatal survival rates following intrauterine transfusion ranging from 67% to 85%. If fetal anaemia is mild, and considering that hydrops can spontaneously resolve, invasive therapy is not recommended and B19V complicated pregnancy may be non-invasively monitored by serial ultrasound examination and MCV-PSV measurements. As an alternative, intrauterine IVIG therapy has been described with successful treatment of fetal hydrops. No specific antiviral therapy or vaccine is presently available for B19V infection but efforts in the search for compounds inhibiting B19V replication are now being pursued. New virus-like-particle based parvovirus B19 vaccine candidates, produced by co-expressing VP2 and either wild-type VP1 or phospholipase-negative VP1 in a regulated ratio from a single plasmid inSaccharomyces cerevisiae have been developed and show sufficient promise to test in humans.

Manufacturing and banking canine adipose-derived mesenchymal stem cells for veterinary clinical application.

BACKGROUND: Mesenchymal stem cells (MSCs) have generated a great amount of interest in recent years as a novel therapeutic application for improving the quality of pet life and helping them free from painful conditions and diseases. It has now become critical to address the challenges related to the safety and efficacy of MSCs expanded in vitro. In this study, we establish a standardized process for manufacture of canine adipose-derived MSCs (AD-MSCs), including tissue sourcing, cell isolation and culture, cryopreservation, thawing and expansion, quality control and testing, and evaluate the safety and efficacy of those cells for clinical applications. RESULTS: After expansion, the viability of AD-MSCs manufactured under our standardized process was above 90 %. Expression of surface markers and differentiation potential was consistent with ISCT standards. Sterility, mycoplasma, and endotoxin tests were consistently negative. AD-MSCs presented normal karyotype, and did not form in vivo tumors. No adverse events were noted in the case treated with intravenously AD-MSCs. CONCLUSIONS: Herein we demonstrated the establishment of a feasible bioprocess for manufacturing and banking canine AD-MSCs for veterinary clinical use.

[Treatment-refractory anaemia in a 35-year-old heart transplant recipient on chronic hemodialysis]. / Therapierefraktäre Anämie bei einem 35-jährigen Dialysepatienten nach Herztransplantation.

This article presents a case of pure red cell aplasia in a 35-year-old heart transplant recipient on chronic hemodialysis. Elevated parvovirus B19 immunoglobulin M blood levels were detected along with a high viral load of 80 billion IU/ml quantified by polymerase chain reaction. Bone marrow examination revealed giant proerythroblasts confirming parvovirus B19 infection. High-dose intravenous immunoglobulin was used for treatment. Anaemia had significantly improved 4 weeks later. Parvovirus B19 infection should be excluded in organ transplant recipients with anaemia due to ineffective erythropoiesis.

Bocavirus Infection in a Young Pregnant Woman: A Case Report and Literature Review.

BACKGROUND Human bocavirus (HBoV) is a parvovirus found primarily in children and was first identified in 2005. It usually causes mild upper- and lower-respiratory tract infections. HBoV infection seems to be rare during adulthood, probably due to high antibody titers resulting from childhood infection and seroconversion. The clinical significance, possible complications, and consequences of an adulthood infection are still unclear. Furthermore, the consequences of HBoV infection during pregnancy are seldom reported in the literature. CASE REPORT We report the case of a 22-year-old pregnant woman in her third trimester who presented with a 1-week history of fever and cough followed by progressive shortness of breath. She was treated initially as a case of severe pneumonia; however, her condition deteriorated rapidly, resulting in hypoxic respiratory failure that required intensive care support. The patient was found to have dilated cardiomyopathy on echocardiography, and her fetal ultrasound showed no fetal heart activity; subsequently, labor induction for stillbirth was performed. An extensive workup for an underlying cause was unrevealing apart from positive respiratory viral PCR assay for human bocavirus, performed twice. A provisional diagnosis of HBoV pneumonia complicated by dilated cardiomyopathy, stillbirth, and multiorgan failure was made. Fortunately, the patient had a good recovery and was discharged home in good clinical condition. CONCLUSIONS In addition to severe pneumonia, HBoV infection may result in other life-threatening complications. Although the infection is rare during adulthood, infection in a pregnant woman should be taken seriously and close monitoring of such patients is advised.

[Persistent anemia after kidney transplantation in a 36-year-old male patient-an unusual cause]. / Persistierende Anämie nach Nierentransplantation bei einem 36-jährigen Patienten ­ eine ungewöhnliche Ursache.

An allogeneic kidney transplantation (match 1­1­0, cytomegalovirus, CMV, donor, D, +/recipient, R, - high risk) was performed in a 36-year-old patient. The patient was on dialysis due to a tubulointerstitial nephritis confirmed by biopsy 11 years previously. Posttransplantation there was a gradual decrease in the hemoglobin (Hb) level from 11.4 g/dl to 7.3 g/dl during the initial hospitalization period. Initially this was explained by the kidney transplantation and chronic fibrosing antral gastritis with erosions. Despite repeated transfusion of red cell concentrates, a refractory anemia persisted, which is why the patient presented several times at our clinic for further diagnosis and treatment. The presence of giant erythroblasts in the bone marrow and quantitative detection of parvovirus B19 (>900 million IU/ml DNA replications) was consistent with a virus-associated red cell aplasia. Intravenous immunoglobulin administration was established and showed long-term therapeutic success.

Changes in Mass Treatment of the Canine Parvovirus ICU Population in Relation to Public Policy Changes during the COVID-19 Pandemic.

Previous work has indicated that canine parvovirus (CPV) prevalence in the Central Texas region may follow yearly, periodic patterns. The peak in CPV infection rates occurs during the summer months of May and June, marking a distinct "CPV season". We hypothesized that human activity contributes to these seasonal changes in CPV infections. The COVID-19 pandemic resulted in drastic changes in human behavior which happened to synchronize with the CPV season in Central Texas, providing a unique opportunity with which to assess whether these society-level behavioral changes result in appreciable changes in CPV patient populations in the largest CPV treatment facility in Texas. In this work, we examine the population of CPV-infected patients at a large, dedicated CPV treatment clinic in Texas (having treated more than 5000 CPV-positive dogs in the last decade) and demonstrate that societal-behavioral changes due to COVID-19 were associated with a drastic reduction in CPV infections. This reduction occurred precisely when CPV season would typically begin, during the period immediately following state-wide "reopening" of business and facilities, resulting in a change in the typical CPV season when compared with previous years. These results provide evidence that changes in human activity may, in some way, contribute to changes in rates of CPV infection in the Central Texas region.

Update on Canine Parvoviral Enteritis.

Canine parvoviral enteritis is one of the most common causes of morbidity and mortality in dogs worldwide. Tests can detect viral antigen in feces, and characteristic decreases in total leukocyte, neutrophil, and lymphocyte counts can increase the index of suspicion in affected cases and can be used to prognosticate morbidity and mortality. The standard of care for infected animals includes IV crystalloid and sometimes colloid fluids, antiemetics, broad-spectrum antibiotics, and early enteral nutrition. Vaccination induces protective immunity in most dogs. Vaccination, along with limiting exposure in young puppies, is the most effective means of preventing parvoviral enteritis in dogs.

Haemostatic changes associated with fluid resuscitation in canine parvoviral enteritis.

The haemostatic status of dogs with canine parvovirus (CPV) enteritis, within 24 h of admission after initial fluid administration, has been described previously, but the haemostatic status at admission and after standard fluid resuscitation, as well as after initial fluid redistribution, has not been investigated previously. The objective of this study was to characterise the haemostatic status at admission and describe the effect of crystalloid fluid resuscitation on haemostatic variables in dogs with CPV enteritis. Twenty-seven client-owned, hospitalised dogs with confirmed natural CPV infection and 15 healthy age-matched controls were included in a prospective, observational clinical study. The volume of resuscitation fluid, haematocrit (HCT), platelet count, thromboelastography (TEG) variables, antithrombin (AT) activity, fibrinogen- and C-reactive protein (CRP) concentrations were measured in all dogs at admission, after fluid resuscitation and, in 10 dogs, after receiving an additional 3 hours of maintenance-rate crystalloid fluids. For the CPV group at admission, the median TEG reaction time (R) and maximum amplitude (MA) or clot strength, as well as the median HCT, fibrinogen and CRP concentrations, were significantly increased compared to the controls. After fluid resuscitation, median R was significantly shorter, MA significantly increased and HCT and AT activity significantly decreased compared to admission values. The haemostatic variables remained unchanged after 3 h of maintenance-rate crystalloid therapy. The increased clot strength present in dogs with CPV enteritis at admission was exacerbated after fluid resuscitation and persisted for hours after large-volume crystalloid fluid administration.

Parvovirus B19 infection masquerading as relapsed acute lymphoblastic leukaemia following haematopoietic stem cell transplantation.

A 7-year-old boy presented with a constellation of bone pain, a skeletal lesion, and pancytopenia after undergoing allogeneic haematopoietic stem cell transplantation for recurrent acute B-cell lymphoblastic leukaemia. Investigations to rule out leukaemia recurrence were unremarkable. Due to presence of maturation arrest in erythropoiesis with giant pronormoblasts and aberrant intranuclear inclusions on a bone marrow aspirate, parvovirus B19 (PVB-19) staining was completed and confirmed the diagnosis of disseminated PVB-19. Though PVB-19 infection after solid organ transplantation was reported in the literature as early as 1986, acquired PVB-19 viremia presenting with a solitary bone lesion is a novel presentation in paediatrics.

Identification and management of congenital parvovirus B19 infection.

Parvovirus B19 (B19V) infection is well known for its mild, self-limiting clinical presentations in children, such as erythema infectiosum. Approximately 40% of women of childbearing age are susceptible to B19V infection. While maternal B19V infection usually has a good prognosis, B19V can cause severe fetal anaemia and pregnancy loss due to its ability to suppress erythroid progenitor cells. Non-invasive ultrasound monitoring for fetal anaemia is usually performed if maternal seroconversion occurs in the first 20 weeks of gestation, with amniocentesis for fetal infection reserved for those who first present with fetal anaemia or hydrops of unknown cause. Intrauterine transfusion is the standard treatment for severe fetal anaemia and is associated with a significant improvement in survival. However, survivors of hydrops fetalis may have a higher rate of long-term neurodevelopmental complications compared with non-hydropic survivors. This review aims to synthesise published data on the diagnosis, surveillance and outcomes of congenital parvovirus infection to assist clinicians in diagnosing and managing this important condition.

Clinical evaluation of hyperimmune plasma for treatment of dogs with naturally occurring parvoviral enteritis.

OBJECTIVE: To evaluate the clinical efficacy of a single infusion of hyperimmune plasma (HIP) in dogs with canine parvovirus (CPV). DESIGN: Prospective, randomized, placebo-controlled clinical trial. SETTING: University teaching hospital. ANIMALS: Client-owned dogs with naturally occurring CPV. INTERVENTIONS: Dogs presenting for CPV treatment (n = 31) underwent cardiovascular resuscitation and were randomized to receive a single dose of either HIP (10 mL/kg IV) or placebo (0.9% sodium chloride [10 mL/kg IV]) during the first 6 hours of hospitalization. All dogs were treated with a standardized treatment protocol (IV fluid therapy [120 mL/kg/d isotonic crystalloids], cefoxitin [30 mg/kg IV q 8 h], maropitant [1 mg/kg IV q 24 h], and buprenorphine [0.01-0.02 mg/kg IV q 8 h]) until hospital discharge. MEASUREMENTS AND MAIN RESULTS: Dogs treated with HIP (n = 16) demonstrated a lower shock index at 24 hours (median = 0.77, range: 0.5-1.5) than those treated with placebo (n = 15, median = 1.34, range: 0.5-1.7; P = 0.02). Plasma lactate concentration was lower at 24 hours in HIP-treated dogs (median = 1.3 mmol/L, range: 0.9-3.4 mmol/L) than in placebo-treated dogs (median = 2.1 mmol/L, range: 1.1-3.4 mmol/L; P = 0.01). There was no difference in duration of hospitalization when comparing HIP-treated dogs (median = 3.2 days, range: 0.83-10 days) to placebo-treated dogs (median = 2.83 days, range: 1-8.38 days; P = 0.35). Survival was 16 of 16 (100%) for the HIP group and 14 of 15 (93.3%) for the placebo group (P = 0.32). CONCLUSIONS: HIP at 10 mL/kg IV administered to dogs with CPV within the first 6 hours of hospitalization improves markers of shock during the initial 24 hours of hospitalization. No effects were observed on duration of hospitalization or mortality; however, this study was underpowered to evaluate these effects. HIP was well tolerated in this population of critically ill dogs.

Double hit: Evans syndrome after malignant thymoma treatment and parvovirus B19 infection.

Malignancies are often associated with autoimmune diseases, which are addressed by treating the underlying cancer. However, there are rare malignancies that can cause autoimmune diseases even after appropriate treatment. Our patient is a 39-year-old Hispanic man with a malignant thymoma recently treated with chemotherapy and radiation who presented with syncope and dyspnoea. He was found to be both anaemic and thrombocytopenic. His labs were consistent with autoimmune haemolytic anaemia (AIHA), except his reticulocyte count was unexpectedly low. Bone marrow biopsy supported a diagnosis of Evans syndrome, a rare autoimmune condition characterised by (AIHA) combined with immune thrombocytopenia. He was also found to have an acute parvovirus B19 infection. He was treated with steroids and RBC transfusion. His blood counts gradually returned to baseline, with improvement in symptoms. This patient's thymoma treatment and active parvovirus B19 infection likely both played a role in the development of Evans syndrome.