Herpesvirus Infections In Patients Research Articles

Changes in the cytotoxic and regulatory functions of NK cells in patients with long-COVID under the influence of the human herpesvirus 6 (pilot study).

Long-COVID are often accompanied by the development of autoimmun disorders. Such dysregulation of the immune system can be caused by reactivation of "sluggish" herpesvirus infection in patients after COVID-19. The one of the possible causes of autoimmunization is a change in the cytotoxic functions of NK cells under the influence of HHV6. The aim of research was to study the expression of receptor-ligand Fas-FasL, regulating marker CD38 and inhibitory receptor TIM-3 on NK cells in patients with long-COVID after mild, moderate, and severe stage of COVID-19 in the anamnesis with or without reactivation of HHV-6 and to identify risk factors for the formation of autoimmune disorders in these patients. This study investigated 124 adults (73 female and 51 male) aged 18 to 65years with long-COVID. The groups of patients with long-COVID were divided depending on mild, moderate, and severe forms of COVID-19 in the anamnesis and with/without reactivation of HHV-6. The control group included 20 healthy participants. Molecular genetic studies (PCR) were performed for all patients to detect the existence of DNA HHV6. Multiparametric flow cytometry was performed on 124 EDTA peripheral blood samples collected from long-COVID patients and 20 healthy controls. There was defined an imbalance between acute antiviral mechanisms, the response contributing to tissue damage and immunopathology, probably autoimmunity in patients with long-COVID after different forms of COVID-19 with reactivation of HHV-6. The presence of HHV-6 in groups with long-COVID was accompanied by higher expression of FasL and CD38, especially in patients, who had a severe form of COVID-19 in the anamnesis. The decrease in TIM-3 in patients with reactivation of HHV-6 compared to patients without HHV-6 puts the preservation of immunological tolerance at risk of Th1-dependent immune responses. The reactivation of HHV-6 is accompanied by higher expression of FasL and CD38, which indicates increased hyperactivation of NK cells, their cytotoxic activity, and subsequent exhaustion. NK cells of these patients lose their immunoregulatory ability, this creates prerequisites for the development of immunopathology, probably autoimmune processes.

Interferon system in typical chronic and atypically occurring chronic active herpes virus infections

Objective: to study the characteristics of the functioning of the IFN system, the presence of autoantibodies to INFα in patients suffering from atypical chronic active herpesvirus infections (ACA-HVI) in comparison with patients with a typical course of chronic herpesvirus infections (CHVI).Materials and methods: under our supervision were 485 patients of both sexes aged 23 to 70 years, suffering from chronic herpes virus infections, of which 335 patients suffered from AHA-HVI and 150 people suffered from CHVI. The comparison group was 250 conditionally healthy individuals (CG). The complex of the study included methods for detecting herpesviruses: serodiagnostics, PCR-RT. The IFN system (spontaneous and induced production, serum concentration) was tested by ELISA. The study was approved by the ethics board and informed consent was obtained from all patients.Results: the incidence of various mono-mixed herpesvirus infections in patients with ACA-HVI (mono – 26,6% and mixed – 73.4%) and CHVI (mono – 23.1% and mixed – 76.9%) was determined, with EBV dominance in patients of both groups. Serum IFNα deficiency was detected in 100% of cases in both groups, and IFNα in 67% in ACA-HVI and 57% in CHVI. At the same time, significant differences were found between the ACA-HVI and HGVI groups in the level of IFNα reduction: 10 and 5 times, respectively, and for IFNγ – 2.0 and 2.6 times, respectively. The induced IFNα production decreased by 89.1% in ACA-HVI and 47.2% in CHVI. A decrease in induced IFNγ production is characteristic of 50% of patients in both groups. At the same time, the level of induced production of IFN α in patients with ACA-HVI was 9 times lower than in the control group and 4.75 times lower than in the group of patients with CHVI. And the level of induced IFNγ production was 2 times lower compared to CHVI and the control group.Conclusions: when assessing the state of the IFN system in patients with various chronic herpes virus infections, significant differences were revealed. Thus, the most pronounced manifestations of interferonopathy, consisting in a significant decrease in serum IFNα and IFNγ and defects in induced IFN production of both types, are observed statistically significantly more often in the group of patients with an atypical course of the disease than in the group of patients with a typical course of CHVI. The most pronounced disorders in the IFN system and the lack of recovery of IFNα and IFNγ levels in the interrelational period cause atypicity of the course and active viral replication in patients with ACA-HVI.

Immunomodulating agent Galavit for the prevention of frequent acute respiratory viral infections after COVID-19: A review

Many convalescents of the new coronavirus infection caused by the SARS-CoV-2 virus, including mild and moderate severity, have frequent acute respiratory viral infections (ARVI) and other diseases of the ENT organs during the first 6 months after recovery. A well-known problem of COVID-19 is immune disorders due to the negative impact of the virus on the immune system, which is associated with various consequences described as a post-COVID syndrome. One of the manifestations of post-COVID syndrome is a decrease in infection resistance due to the immunodeficiency state. In particular, exacerbations of bacterial and viral ENT diseases, frequent ARVI, and exacerbation of herpes virus infection were reported. Moreover, the infections tend to be prolonged, cyclic, and often recurrent, significantly reducing patients' physical activity and quality of life. ARVI symptoms, accompanying the post-COVID syndrome, negatively affect the general condition of patients. Immunocorrection can interrupt the vicious circle of recurrent ARVI and restore impaired immunity after COVID-19. The immunomodulatory drug Galavit has a pathogenetic basis for use in the post-COVID period to restore the immune system. It was shown effective in preventing frequent recurrent ARVI and herpes virus infection in patients in the post-COVID period. The article shows the experience of using Galavit in coronavirus infection convalescents with frequent episodes of acute respiratory infections.

Atypical chronic active herpesvirus infections: Etiological structure, frequency of occurrence, clinical syndromes associated with them

BACKGROUND: Every year, a steady, progressive increase in the number of atypical chronic, active forms of infections caused by herpesviruses is recorded. Diagnosing and selecting adequate therapeutic strategies for treating these infections present significant difficulties for physicians due to the polysyndromicity and many clinical manifestations.
 AIMS: This study determines the prevalence of atypical chronic, active infections caused by herpesviruses among patients infected with herpesvirus infections and studies the etiological structural features and clinical manifestations/criteria and signs of atypically occurring chronic forms of herpes viral infections.
 MATERIALS AND METHODS: Under our supervision at the Clinical and Diagnostic Center Medsi in Belorusskaya (Moscow), 98 patients of both sexes aged 23 to 60 years suffering from atypical chronic, active forms of infections caused by herpesviruses comprised the herpesviruses group. The comparison group consisted of 30 conditionally healthy subjects comparable in sex and age to patients. In addition to traditional methods (history collection, physical examination, general blood test, and others), serodiagnostic methods with ELISA were used to detect herpesvirus infections. ELISA was also used for detecting the genome of viruses in biomaterials. The study was approved by the ethics committee, and all patients received informed consent to participate in the study. Statistical analysis was performed using adequate methods.
 RESULTS: The study of the etiological structure of herpesvirus infections in patients with atypical chronic, active forms of infections caused by herpesviruses, mixed herpesvirus infections were shown to occur in 83.4% of patients, and mono herpesvirus infections in 16.6% of cases. It was shown that the EpsteinBarr virus was the dominant virus among patients with mono and mixed herpesvirus infections. A high rate of EpsteinBarr virus DNA detection was demonstrated in saliva (84.2%), posterior pharyngeal wall scrapings (73.5%), tonsils (42.9%), urine (12.6%), and blood (8.3%) is a marker of the high replicative activity of the virus. The primary clinical syndromes associated with mono and mixed atypical chronic and active forms of infections caused by herpesviruses were identified.
 CONCLUSIONS: This study identified and quantitatively assessed the viral load associated with the severity of the course and clinical manifestations of atypical chronic, active forms of infections caused by herpesviruses. Clarifying the features of clinical manifestations and syndromes in patients suffering from various mono and mixed herpesvirus infections will allow us to outline the goals for the further development of an adequate diagnostic algorithm for these atypical forms of herpesvirus infections and the concept of targeted, personalized etio- and immunopathogenetic therapy.

The incidence of infection in tumor and eye fluid system, and specific humoral immunity to herpes viruses in patients with uveal melanoma

Studies aimed at a direct research of human herpes viruses (HHVs) in the tumor material and eye media have not been carried out so far. Research goal to establish the frequency of detection HHVs DNA in the biomaterial of the eye and blood and to assess the specific humoral immunity to the causative agents of herpes virus infections in patients with uveal melanoma. 38 patients with the uveal tract tumor were examined for the presence of DNA of HHV types 1 and 2 (HSV-1, 2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV), EpsteinBarr virus (EBV) and herpes viruses 6 and 8 types (HHV-6, HHV-8) in tumor tissue, vitreous body, aqueous humour and blood plasma by real-time polymerase chain reaction; blood serum was studied by enzyme-linked immunosorbent assay (ELISA) for IgG and IgM antibodies to HHVs. EBV DNA was present in tumor tissue in 20.6% of cases, in vitreous body in 4.2%, in blood plasma in 2.7%, and was not found in aqueous humor. Ig G antibodies to HSV-1, 2 and CMV were detected in 97.3% of cases, VZV 94.6%, HHV-6 32.4%, antibodies to HHV-8 were not detected. 20 patients (55.6%) had reactivation of chronic HSV-1, 2 infection, and 14 (38.9%) patients had reactivation of CMV infection. Markers of chronic EBV infection were found in all patients, its atypical reactivation was observed in 2 cases (5.4%). Our findings suggest the possible participation of EBV in the oncogenesis of the uveal tract and emphasize the need for further in-depth study of this problem.

Systematic review with meta-analysis of active herpesvirus infections in patients with COVID-19: Old players on the new field

Herpesviruses are ubiquitous and after primary infection they establish lifelong latency. The impairment of maintaining latency with short-term or long-term consequences could be triggered by other infection. Therefore, reactivation of herpesviruses in COVID-19 patients represents an emerging issue. This study provided the first systematic review with meta-analysis of studies that evaluated active human herpesvirus (HHV) infection (defined as the presence of IgM antibodies or HHV-DNA) in COVID-19 patients and included 36 publications collected by searching through PubMed, SCOPUS, and Web of science until November 2022. The prevalence of active EBV, HHV6, HSV, CMV, HSV1, and VZV infection in COVID-19 population was 41% (95% CI =27%-57%), 3% (95% CI=17%-54%), 28% (95% CI=1%-85%), 25% (95% CI=1%-63%), 22% (95% CI=10%-35%), and 18% (95% CI=4%-34%), respectively. There was a 6 times higher chance for active EBV infection in patients with severe COVID-19 than in non-COVID-19 controls (OR=6.45, 95% CI=1.09-38.13, p=0.040), although there was no difference in the prevalence of all evaluated active herpesvirus infections between COVID-19 patients and non-COVID-19 controls. Future research of herpesvirus and SARS-CoV-2 coinfections must be prioritized to define: who, when and how to be tested, as well as how to effectively treat HHVs reactivations in acute and long COVID-19 patients.

Vaccine Prophylaxis of Herpes Zoster In Rheumatic Diseases: Paradigm Revision and New Opportunities

Background. The issues of vaccination against the herpesvirus infection are still important in rheumatological practice.This infection often develops in patients receiving immunosuppressive treatment, especially Janus kinase inhibitors (a class-specific adverse reaction) and genetically engineered biologics.The aim of this review is to highlight the current state of the issue of vaccination against Herpes zoster (HZ).Materials and Methods. 37 publications (4 domestic, 33 foreign) were analyzed, in which the mechanisms of pathogenesisand clinical features of herpesvirus infection in patients with immunodeficiency, both with and without immunoinflammatory rheumatic diseases (IIRD), the frequency and variety of post-vaccination reactions, complications and exacerbations of the course of IIRD were considered.Results. There is currently a trend towards reassessment of the rheumatological community's opinion about HZ vaccination, including live vaccine. Literature data allow us to express optimism regarding the effective prevention of herpes zoster in patients who plan to take drugs, primarily from the group of Janus kinase inhibitors. The advantages of the adjuvant recombinant subunit vaccine (Shingrix®) include the possibility of its use against the background of treatment with antirheumatic drugs without significant restrictions, as well as no need to postpone the initiation of the necessary therapy.Conclusions. Publications on the issues of HZ vaccination are few. It is necessary to conduct carefully controlled studies on the efficacy and safety of antiherpetic vaccines with an emphasis on the post-vaccination course of IIRD in patients with rheumatological profile, including in the Russian Federation.

Beyond arboviruses: A multicenter study to evaluate differential diagnosis of rash diseases and acute febrile illness cases in Rio de Janeiro, Brazil.

IntroductionA wide variety of viruses can cause rash diseases (RDs) or acute febrile illness (AFIs) in children, adolescents and adults; however, approximately 19% of RD cases and 40% of AFI cases remain without a defined etiology. Parvovirus B19 (B19V) and herpesvirus infection can also cause RD and/or AFI, and in some risk groups, these infections can become persistent (or latent) and may require hospital treatment. Since these infections do not have mandatory reporting, they can be hidden by other diseases, such as those caused by arboviruses (e.g., dengue virus). In this context, the aim of this study was to pursue the differential laboratory diagnoses of B19V and herpesvirus infections in patients with RD and AFI, without a defined etiology, seen in hospitals and/or reference centers for infectious diseases in Rio de Janeiro.MethodsA total of 114 participants were enrolled in the study, including 54 children and 60 adults. B19V infection was assessed by real-time PCR (qPCR) and ELISA (anti-B19V IgM and IgG). EBV was assessed through qPCR, and betaherpesviruses (HCMV, HHV-6 and HHV-7) were assessed through multiplex qPCR. Sociodemographic and clinical data were obtained from the medical record data of these participants.ResultsThe median age of children with RD was 2 years (interquartile range (IQR): 5), and 55.6% were male. Among adults with AFI, the median age was 38 years (IQR: 21), and 56.7% were female. Regarding RD patients, viral prevalence (and load) were 5.5%(104IU/mL), 3.4%(104IU/mL), 5.5%(104IU/mL) and 11.1%(105IU/mL) for B19V, EBV, HCMV and HHV-6 infection, respectively, and in AFI patients they were 6.6%(105IU/mL), 1.6%(103IU/mL), 3.3%(104IU/mL) for B19V, HCMV and HHV-6, respectively. HHV-7 was not detected in RD or AFI patients.ConclusionThese results suggest the importance of including B19V and herpesviruses in the differential laboratory diagnoses for patients with RD and AFI, not only for epidemiological purposes but also for the proper management of the patient.

Gastric herpes simplex virus type 1 infection is associated with functional gastrointestinal disorders in the presence and absence of comorbid fibromyalgia: a pilot case–control study

PurposeAnimal studies have linked gastric herpesvirus infections to symptoms associated with functional gastrointestinal disorders (FGIDs). Herpesviruses have also been hypothesized to contribute to fibromyalgia (FM), a chronic pain syndrome frequently comorbid with FGIDs. The purpose of this study was to compare the prevalence of gastric herpesvirus infection in patients with FGIDs, with and without comorbid FM, to that of controls.MethodsFor this pilot case–control study, we enrolled 30 patients who met both the Rome IV diagnostic criteria for one or more FGIDs and the American College of Rheumatology 2010 criteria for FM, 15 patients with one or more FGIDs without comorbid FM, and 15 control patients. Following endoscopic examination, gastric biopsies were analyzed for herpesvirus DNA and protein, Helicobacter pylori infection, and histological evidence of gastritis. Importantly, the viral nonstructural protein ICP8 was used as a marker to differentiate cell-associated actively replicating virus from latent infection and/or free virus passing through the GI tract.ResultsGastric herpes simplex virus type 1 (HSV-1) infection, as indicated by ICP8 presence, was significantly associated with FGIDs in the presence (OR 70.00, 95% CI 7.42–660.50; P < .001) and absence (OR 38.50, 95% CI 3.75–395.40; P < .001) of comorbid FM. Neither histological gastritis nor H. pylori infection were found to be associated with FGIDs or FM.ConclusionsHSV-1 infection was identified in gastric mucosal biopsies from patients with diverse FGIDs, with and without comorbid FM. Larger, multi-center studies investigating the prevalence of this association are warranted.

Frequency of detection of Helicobacter pylori and herpesvirus infection in patients with morphological changes in gastric mucosa

Aim. Based on the histological conclusion, to evaluate the frequency of detection of helicobacteriosis and herpesvirus infection in patients with morphological changes in the gastric mucosa.Materials and methods. Retrospectively, according to the logs of registration of endoscopic studies and registration of directions for histological studies for 2017–2021 of the endoscopic office of the polyclinic No. 2 in Smolensk city of Russia, the results of histological studies of biopsies of the gastric mucosa in 651 patients tested for H. pylori infection and herpesvirus infection were evaluated.Results. It is preferable to consider in the formation of inflammation the influence not of individual H. pylori bacteria, but the value of the entire mucosal microflora of the stomach and duodenum. The role of herpes viruses in the development of inflammatory and destructive pathology of the stomach and duodenum is noted. In patients infected with H. pylori and HVI in the SOH, there are structural changes in which destructive processes may have a deeper character, which will affect the timing of achieving remission.Conclusions. 1). In the description of the histological picture of the gastric mucosa, H. pylori was determined in 85.41 % of cases: with polyposis –97.05 %, oncopathology – 100 %, peptic ulcer – 94.50 %, chronic gastritis – 89.28 % of cases. 2). Herpes types 1, 2, 6, 8, EBV, cytomegalovirus from 220 biopsies were detected in 83.18 % of cases. EBV was most often present in the gastric mucosa from herpesvirus infection – 74.20 % of cases (with peptic ulcer in 78.00 %, with chronic gastritis in 84.71 %). 3). Simultaneously, herpesvirus infection and H. pylori were detected in 120 patients: with peptic ulcer – 68.00 %, with chronic gastritis – 75.29 % of cases.

Immune response and phagocytosis of children with streptococcal tonsillitis and infected with the herpes virus type 6.

The aim of the work is to study the indicators of cellular and humoral immune response and FAN of patients with tonsillitis in children infected with HHV-6 type.&#x0D; Materials and methods of research. In 72 children aged 3–15 years (mean age 8.42±1.44 years), patients with streptococcal tonsillitis of moderate severity, the levels of the main subpopulations of blood lymphocytes were determined using monoclonal antibodies by solid-phase enzyme-linked immunosorbent assay, phagocytic activity of neutrophils (FAN) using the nitrosine tetrazolium reduction test (HCT test) and serum IgA, IgM, IgG levels by radial immunodiffusion. The studies were carried out in the acute period and in the period of convalescence. Mathematical and statistical processing of the data obtained was carried out using Microsoft Excel 2003 and Statistica 6.0 programs. The significance of differences between the mean values was determined using the Student's test (t).&#x0D; Results. Different mechanisms of formation of pathological process at streptococcal tonsillitis at children depending on the concomitant HHV-6 type infection are revealed. In patients with mixed infection in the acute period of tonsillitis determine the signs of deficiency of the cellular immune system with the maximum deviation of CD-lymphocytes (t=3.13 vs. t=2.16 in mono-infection), the tension in the humoral link of the immune response Ig deviation (t=1.63 against t=0.91 in mono-infection) on the background of phagocytosis violation in terms of FAN deviation (t=3.22 against t=2.01 in mono-infection). By the period of convalescence, the restoration of the imbalance of specific and non-specific protection factors does not occur. Increased IgG content in the acute period is one of the features of streptococcal tonsillitis in children on the background of HHV-6t infection.&#x0D; Conclusions. Concomitant VGL-6 type infection in children with streptococcal tonsillitis affects the mechanisms of formation of the inflammatory process and the reactivity of patients, forming the preconditions for adverse outcomes of the disease. The obtained results can be the basis for early detection of herpes virus infection in patients with tonsillitis, will help to optimize the management of patients in different periods of the disease.

Post-Transplantation Cyclophosphamide Is Associated with an Increase in Non-Cytomegalovirus Herpesvirus Infections in Patients with Acute Leukemia and Myelodysplastic Syndrome

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis in recipients of haploidentical and fully matched transplantations is on the increase. Published studies have reported an increased incidence of cytomegalovirus (CMV) infection with the use of PTCy. Limited data exist on the incidence and outcomes of infection with non-CMV herpesviruses (NCHV) in this setting. The aim of this study was to evaluate the cumulative incidence of NCHV infections and the association of NCHV infections with transplantation-specific outcomes in recipients of haploidentical transplantation with PTCy (HaploCy), matched sibling donor transplantation with PTCy (SibCy), and matched sibling donor transplantation with calcineurin inhibitor-based prophylaxis (SibCNI). We hypothesized that, like CMV infection, HaploCy recipients of also will have a higher risk of NCHV infections. Using the Center for International Blood and Marrow Transplantation Research database, we analyzed 2765 patients (HaploCy, n=757; SibCNI, n=1605; SibCy, n=403) who had undergone their first hematopoietic stem cell transplantation (HCT) between 2012 and 2017 for acute myelogenous leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. The cumulative incidence of NCHV at 6 months post-NCT was 13.9% (99% confidence interval], 10.8% to 17.3%) in the HaploCy group, 10.7% (99% CI, 7.1% to 15%) in the SibCy group, and 5.7% (99% CI, 4.3% to 7.3%) in the Sib CNI group (P < .001). This was due primarily to a higher frequency of human herpesvirus 6 viremia reported in patients receiving PTCy. The incidence of Epstein-Barr viremia was low in all groups, and no cases of post-transplantation lymphoproliferative disorder were seen in either PTCy group. The incidence of NCHV organ disease was low in all 3 cohorts. The development of NCHV infection was associated with increased treatment-related mortality, particularly in the HaploCy group. There was no association with the development of GVHD, relapse, or disease-free survival. Patients in PTCy cohorts who did not develop NCHV infection had lower rates of cGVHD. This study demonstrates that the use of PTCy is associated with an increased risk of NCHV infection. The development of NCHV infection was associated with increased nonrelapse mortality, especially in the HaploCy group. Prospective trials should consider viral surveillance strategies in conjunction with assessment of immune reconstitution for a better understanding of the clinical relevance of viral reactivation in different HCT settings.

Assessment of the prevalence of herpetic infection in coronary atherosclerosis

Background and Aims: Cardiovascular diseases are currently the leading cause of death in industrialized countries. Currently, there is a large list of infections that are either associated with the development of atherosclerosis or increase the risk of developing cardiovascular diseases. Much attention in this list is paid to human herpes viruses.The aim of the study was to study the prevalence of herpesvirus infection in patients with different severity of coronary atherosclerosis.

775e Active Herpes Simplex Virus Type 1 Infection of the Gastric Mucosa is Associated with Functional Gastrointestinal Disorders: A Pilot Case-Control Study

Neurotropic herpes viruses establish lifelong latent infections in ganglionic neurons, including intrinsic enteric neurons and extrinsic neurons that project to the GI tract. Upon reactivation, virus replication within innervated tissues can result in enteric disorders such as herpetic gastritis, esophagitis, and enteric zoster. In animal models, enteric neuronal infection results in gut dysmotility, indicating herpesviruses may play a role in functional gastrointestinal disorders (FGIDs). Neurotropic herpesviruses have also been theorized to contribute to fibromyalgia (FM), a functional somatic syndrome frequently comorbid with IBS and other FGIDs. Because overlapping upper and lower GI symptoms are common in patients with FGIDs, we hypothesized an association of gastric herpesvirus infection with IBS and other FGIDs. We compared the prevalence of active gastric herpesvirus infection in patients with FGIDS, with and without comorbid FM, to that in controls.

THE EFFECTIVENESS OF THERAPY BY CRYOPRESERVED HUMAN PLASMA IN PATIENTS WITH DEFICIENCY OF MANNOSE BINDING LECTIN SUFFERING FROM HERPES VIRUS INFECTION

The aim: To research the effectiveness of cryopreserved blood plasma replacement therapy in patients with primary mannose binding lectin (MBL) deficiency, suffering from chronic active herpes virus infections. Materials and methods: Patients of the study group (SG) n= 36 additionally received cryopreserved blood plasma therapy Octaplas (Octapharma, Switzerland). Patients of the control group (CG) n=36 received only chemotherapy with Valganciclovir 450 mg 2/day per os for 1-3 months. The diagnosis of active herpes virus infection was established by PCR of blood leukocytes. Statistical analysis of the obtained information was processed by the calculation of the chi-square (χ2) Pearson criterion, the odds ratio and the associated 95% confidence interval (95% CI). Results: The adding cryopreserved blood plasma substitute to standard therapy with valganciclovir for the treatment of chronic active herpes virus infection in patients with total serum MBL deficiency below 50 ng/ml, allowed to get more negative PCR results. The effectiveness of combination therapy was 50% higher in carrier of HHV-6 (χ2=8,533 and р=0,004; Yeats correction 6,533 and significance 0,011; OR=11,667 and 95% CI=1,939-70,180) and 43% in carrier of HHV-7 (χ2=8,846 and р=0,003; Yeats correction 7,165 and significance 0,008; OR=6,375 and 95% CI=1,711-23,758), compared with monotherapy. The close association between deficit MBL compensation and the results of antiviral treatment is also reported. The effect of such treatment in patients with chronic EBV infection was less (27%). Conclusions: We assumed, that virostatic effect of valganciclovir is increased by MBL-mediated clearance of blood serum from viral particles.

Presence of cytomegalovirus and human herpesvirus 6 in-patients with lymphomas

Background: Cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) remain latent after primary infection and can be reactivated after immunosuppression. Very little is known about the prevalence of these herpes viruses in lymphomas patients following cytotoxic chemotherapy in the absence of allogeneic transplantation. Therefore, this study investigated the frequency of HHV-6, its impact on clinical manifestations and its possible association with the risk of development of CMV infection in Hodgkin's and non-Hodgkin's Lymphoma (HL &NHL). Methods and materials: This study included 62 patients with lymphomas (25 HL and 37 NHL) diagnosed and treated in the hematology department of Farhat Hached Hospital in Sousse (Tunisia) during the period from June 2015 to July 2018. One hundred and twenty-four healthy individuals were used as age and sex-matched control group. Herpesviruses DNA (HHV6 and/or CMV) were detected by multiplex polymerase chain reaction (PCR). Nested PCR was used to discern HHV-6 variants A and B for each HHV6 positive sample. Results: Herpesviruses DNA (HHV6 and/or CMV) was present in 12 of the 62 patients with lymphomas (19.35%), a frequency that was significantly higher than that in the control group (4/124, 3.2%) (p < 0.01).There was no significant difference between HL or NHL groups regarding the presence of HHV6 and or CMV (p = 0.74). The CMV DNA was identified in eight patients (1HL, 7NHL) while in 4 both CMV and HHV-6(3HL, 1NHL).CMV infection was associated with a significantly higher rate of HHV6 infection (p < 0.01). Variant B was found in 2 HL patients and variant B in 2 NHL while all the control group individuals showed positive for HHV-6 variant B. Ten out of twelve infected patients were symptomatic with fever and pneumonia (60%), lymphopenia (<500/μL) (30%), diarrhea (20%), hepatitis (10%). The presence of both herpes viruses DNA was not significantly associated with more frequent symptomatic infection (100% vs. 75%, p = 0.5). Conclusion: The detection of CMV and/or HHV6 were more commonly observed in patients with lymphomas and HHV-6 infection was often revealed with CMV infection. In the future, enhanced prospective surveillance may help shed more light on the clinical significance of these herpes virus infections in patients with lymphomas.

Seroprevalence to herpesviruses in patients with primary brain gliomas

Purpose of the study . The purpose of the study was to assess the level of seroprevalence and the frequency of detection of serological markers of acute herpesvirus infection in patients with PGBT in comparison with those in patients with chronic non-tumor diseases. Materials and methods . Before conducting antitumor therapy, the blood serum of 42 patients with PGBT (the main group) was studied. The comparison group consisted of 137 patients with chronic non-tumor diseases. Antibodies of classes M and G to herpes simplex virus types 1, 2 (HSV-1,2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes virus type 6 (HHV-6) were determined by ELISA using JSC Vector-Best reagent kits. Results . Among patients with PGBT, seropositive for HSV-1,2 were 95.2%, CMV — 92.9%, EBV — 100%, HHV-6-40.5% of patients. No statistically significant differences in seroprevalence and the presence of markers of acute infection (IgM) were found either in comparison with non-tumor diseases or depending on the malignancy grade. Antibodies to HSV-1,2, CMV and EBV in patients with gliomas were significantly more often found in the medium range, and in the comparison group — in the high values of coefficient of positivity (CP) for IgG. In all the studied groups, antibodies to HHV-6 were determined statistically significantly less frequently than to other herpes viruses. Conclusion . The absence of statistically significant differences in seropositivity between groups of patients and their presence between pathogens is most likely a reflection of general trends in the population, and the question of the involvement of various representatives of the Herpesviridae family in neuro-oncogenesis of primary glial brain tumors still remains open.

Perspectives of cytomegalovirus infection in ulcerative colitis

Herpes virus infection leads to severe and fatal disease in individuals with suppressed immunity. In patients with inflammatory bowel disease (IBD), particularly those with ulcerative colitis (UC), those undergoing immunosuppressive therapy, or those unresponsive to medical therapy, cytomegalovirus (CMV) has been found to be associated with significant clinical morbidity. In addition, other herpes viruses, particularly human herpes virus 6 (HHV‑6) and Epstein-Barr virus (EBV), have been identified recently in the colonic mucosa of individuals with IBD, although the relationship between herpes virus infection other than CMV and exacerbation of IBD remains unknown. In this review, we discuss herpes virus infection in patients with UC, focusing on the prevalence and diagnosis of CMV infection as well as the prevalence of single or mixed infection with herpes virus (HHV‑6 and EBV) in addition to CMV. Moreover, significance of genotyping of CMV in UC is discussed.

Clinical Results and Utility of Herpesviruses Multiplex Polymerase Chain Reaction: Assessment of Aqueous Humor Samples From Patients With Corneal Endotheliitis and High Intraocular Pressure.

The main purpose of this study was to evaluate herpesvirus infection in patients with corneal endotheliitis and high intraocular pressure (IOP) using multiplex polymerase chain reaction (PCR) in aqueous humor samples. This was a retrospective, observational study of immunocompetent patients living in South Korea. Eligible subjects had typical corneal endotheliitis with an IOP≥21 mm Hg or required antiglaucoma medication. Multiplex PCR was performed using aqueous humor samples obtained at first visit to detect the DNA of 6 herpesviruses. Forty-two eyes from 42 patients with >6 months' follow-up were analyzed. Of these, 16 were herpesvirus-positive: 3 herpes simplex virus 1, 3 varicella-zoster virus, 9 cytomegalovirus, and 1 Epstein-Barr virus. Eyes with coin-shaped or fine keratic precipitates (kps), high IOP, and a low baseline endothelial cell count were more likely to show a positive result on multiplex PCR. Univariate analysis showed that male sex (P=0.014), a previous history of uveitic glaucoma (P=0.048), and the presence of fine kps (P=0.031) were significantly associated with a positive PCR result. On multivariate analysis, male sex (P=0.010) and a previous history of uveitic glaucoma (P=0.031) showed a significant positive association. Cytomegalovirus was the most commonly detected herpesvirus in patients with corneal endotheliitis and high IOP. A positive PCR result was seen more frequently in male individuals and patients with fine kps or a history of uveitic glaucoma.

Herpesvirus Infections in Patients Treated with the Mood Stabilizer Valproic Acid: A Nested Case-Control Study in the Spanish Primary Care Database, BIFAP

Purpose: The objective of this study is to evaluate the risk of infections for herpesviruses in patients exposed to Valproic acid and derivatives (VPA) in the Spanish research database BIFAP. Methods: We performed a case-control study nested in a primary cohort selected from the Spanish primary care population-based research database BIFAP over the period 2001 to 2015. The events of interest were those diseases caused by any of the herpesviruses known to infect humans, specifically. For each case, up to 10 controls per case matched by age, gender and calendar date were randomly selected using risk set sampling. A conditional logistic regression was used to compute adjusted odds ratios (OR) and their 95% confidence intervals (95%CI) for infection for herpesviruses associated to the use of VPA after adjusting for potential confounders. Results: Current use of VPA was associated with a trend towards a reduced risk of infection by herpesviruses as compared to non-users (OR 0.84; CI95% 0.7-1.0), being these differences marginally significant (p=0.053). Among current users, a trend to a decreased risk with treatment durations longer than 90 days was also observed. Conclusions: The results of this study show a trend to a reduced risk of infection for herpesviruses in patients exposed to VPA, especially in those with treatment durations longer than 90 days. These results are consistent with in vitro studies showing that, in cultured cells, VPA inhibits the production of infectious progeny of different enveloped viruses causing relevant human and veterinary diseases, including herpesviruses. Funding Statement: Work at Centro de Biologia Molecular Severo Ochoa was supported by grants from the Spanish Ministerio de Economia y Competitividad (AGL2014-52395-C2-1-R and AGL2017-84097-C2-1- R), and by an institutional grant from the Fundacion Ramon Areces and Banco Santander Central Hispano. Work at INIA (MAM-A) was supported by grant AGL2014-56518-JIN. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The scientific committee of BIFAP granted a positive opinion to the study protocol (#08/2015). The investigators had access to only fully anonymized data, and under this condition, no specific ethics review was required according to Spanish law.