Acute Viral Infections Research Articles

Burden and Risk Factors for Coinfections in Patients with a Viral Respiratory Tract Infection

Which patients should be monitored for coinfections or should receive empirical antibiotic treatment, in patients with an acute viral respiratory infection, is largely unknown. We evaluated the prevalence, characteristics, outcomes of coinfected patients, and risk factors associated with a coinfection among patients with an acute viral infection. A retrospective, single-center study recruited consecutive patients from October 2022 to March 2023 presenting to the emergency department with signs of a respiratory tract infection. Patients were screened for respiratory viruses and bacterial/fungal secondary infections according to local standard procedures. Outcomes included severe disease, in-hospital complications, all-cause in-hospital and ICU-related mortality, time to death, time to discharge, and time to coinfection. The analysis included 652 patients. A viral infection and a secondary bacterial/fungal infection were detected in 39.1% and 40% of cases. Compared with the rest of the cohort, coinfected patients had more frequently severe disease (88.3%, p < 0.001; 51% in patients with SARS-CoV-2) and higher in-hospital mortality (16.5%, p = 0.010). Nephropathy (OR 3.649, p = 0.007), absence of COVID-19 vaccination (OR 0.160, p < 0.001), SARS-CoV-2 infection (OR 2.390, p = 0.017), and lower blood pressure at admission (OR 0.980, p = 0.007) were independent risk factors for coinfection. Multidrug-resistant pathogens were detected in 30.8% of all coinfections. Patients with a viral infection are at high risk of bacterial coinfections, which carry a significant morbidity and mortality burden.

Hardware treatment of diseases of the upper respiratory tract in acute respiratory viral infections

Acute respiratory viral infections are among the most common diseases affecting the health of the population and often leading to complications from the upper respiratory tract. Medical treatment of acute respiratory viral infection is often complemented by hardware therapies that help reduce the risk of complications and accelerate recovery. This paper describes modern hardware methods for the treatment of acute respiratory viral infections, including low-frequency ultrasound cavitation, photochromotherapy, ultraviolet irradiation and UHF therapy. The clinical efficacy was evaluated in comparison with drug-based approaches. The possibilities of using these methods both in medical institutions and at home using the MULTILOR device were also investigated. Data analysis has shown that the use of hardware treatment methods significantly reduces the severity of symptoms of acute respiratory viral infections, shortens the duration of the disease and reduces the risk of complications. It is important to note that devices such as MULTILOR allow for treatment at home, increasing the availability of therapy. Hardware treatment of acute respiratory viral infections (ARVI) of the upper respiratory tract is a promising direction in modern medical practice, due to its proven effectiveness, safety and variety of technologies used. The inclusion in therapeutic regimens of such methods as low-frequency ultrasonic cavitation, ultraviolet irradiation (UVF), as well as UHF therapy, allows not only to significantly accelerate the regression of clinical symptoms, but also prevents the development of complications often associated with acute respiratory viral infections. The combined effect of these methods contributes to a significant reduction in symptoms, improvement of the condition of the mucous membranes and prevention of disease recurrence.

Influence of saponin tauroside Sx1 on lifespan and expression of vitamin D receptors in the liver tissue of mice with influenza infection

Introduction. Respiratory infections, including influenza, are often accompanied by hepatitis in humans which pathogenesis is not fully understood. According to the available datan D deficiency is presumably a risk factor in the occurrence of acute respiratory viral infections due to its modulation of immune response. Recent studies indicate that several plant compounds can interact with vitamin D receptors (VDRs) and modulate the activity of VDRs. The biologically active components saponins have found widespread use in clinical practice due to their wide range of biological and pharmacological effects which mechanisms are still largely unclear.Aim. To study the effect of oral administration of saponin tauroside Sx1, obtained from Crimean ivy, on life expectancy and activation of vitamin D receptors in the liver of mice during experimental viral infection of varying severity.Materials and methods. The 11 subgroups were formed from male BALB/c mice, were used in the experiment depending on the infectious dose of influenza virus, 5 LD50 virus or 10 LD50 virus, respectively, including control. Saponin tauroside Sx1 was used as a corrector. Immunohistochemical studies were carried out automatically in a BOND-MAX immunohistainer (Leica, Germany). Primary rabbit polyclonal antibodies to the vitamin D receptor were used.Results and discussion. Due to the administration of tauroside Sx1 at a dose of 200 μg/mouse/day increases the average life expectancy of animals receiving saponin by 4.6 days. Reducing the infectious dose of IV from 10 LD50 to 5 LD50 also changed the onset of death of animals by 2 days in both groups. With different infectious doses of the virus, on the 10th day of the experiment in the subgroups, the expression of vitamin D receptors changes without correction. In subgroup 2V, the number of total positive cells was lower than the control group. Moreover, in the 2Vir subgroup, VDR expression was significantly higher than the control group.Conclusion. The saponin tauroside Sx1 at a dose of 200 µg/mouse/day has a fairly pronounced antiviral effect during experimental infection of mice with the influenza A/H1N1 virus, which is manifested by an increase in the average life expectancy of animals (for 4.6 days) and a decrease in the mortality rate during severe influenza infection, compared with the control group, where 100 % mortality was observed by the 14th day of the experiment. The introduction of saponin on the 4th day of the experiment in all subgroups reduces the total number of immune cells that intensively express VDR.

Management of genomic surveillance for respiratory viral infections circulating in the territory of the city of Moscow

Introduction. Outbreaks of respiratory viral infections have an economic impact on the healthcare system and pose a threat to public well-being. Monitoring for the incidence of acute respiratory viral infections in a metropolitan area, especially during the COVID-19 pandemic, was in dire need of an adequate tool to identify mutations and variants that evade vaccine immunity and initiate an increase in incidence. Genomic surveillance was required for a timely response. Purpose of the study. Management of the Moscow Genomic Center for genomic surveillance for acute respiratory viral infections and COVID-19, with an assessment of the results during seasonal outbreaks in the capital. Materials and methods. With the support of the Moscow City Health Department, management and logistics measures were developed and implemented, the NGS testing program in patient samples on a planned basis and during the period of increased incidence of acute respiratory viral infections and COVID-19, technical procedures for high-throughput sequencing were developed, the security of data exchange and biosafety of medical personnel were ensured. Results. The Moscow Genome Center was established within the structure of the Moscow City Health Department. For the period from October 2023 to April 2024, targeted NGS data (a panel of thirty two pathogens, 6528 samples were tested): SARS-COV-2 dominated the entire period, the incidence of influenza A (H3N2) increased sharply from the beginning of December and decreased sharply by the end of January. Sars-CoV-2 genetic lineage rotation: XBB lineage dominated (most represented: XBB.1.16, XBB.1.16.11) from October to the end of January, then JN lineage prevailed (most represented: JN.1, also found: JN.1.13, JN.1.18, JN.1.19, JN.1.4). Influenza A strain rotation: H3N2 (A/Massachusetts/01/2020) and H3N2 (A/Massachusetts/38/2019) dominated from December to February. Research limitations. A targeted panel of 32 respiratory viruses most common in the Moscow population was used for NGS. Incomplete coverage of the entire viriome is a conditional limitation. Conclusion. Representative, high-quality and continuous genetic surveillance has been managed in the capital. The Moscow Genome Center has successfully implemented the NGS Testing Program and support for the Russian Genomic Resource of Microorganisms VGARus.

The effectiveness of a synthetic analogue purine nucleoside bases in the treatment of acute respiratory viral infections

Introduction. The aggravation of the comorbid background of patients with ARVI is the main reason for the addition of secondary pathogenic and conditionally pathogenic bacterial flora and, as a result, the development of local and general complications.Аim. To conduct a clinical assessment of the efficacy and safety of the drug Triazavirin based on riamilovir in the treatment of acute respiratory viral infections.Materials and methods. The study conducted on the basis of the medical center of the Federal State Budgetary Educational Institution of the Russian Ministry of Health involved 56 patients with acute recurrent viral infection. Regarding the prescribed therapy, the patients were divided into 2 groups: group 1 (n = 27) from day 2, triazavirin was taken as an antiviral drug (riamilo- vir) 250 mg (1 capsule) 3 times a day for 5 days; group 2 (n = 29) – as an antiviral drug, Kagocel took 2 tablets 3 times a day for 2 days, then 1 tablet 3 times a day for 5 days. The effect of the therapy was assessed by the severity of intoxication syndrome, rhinorrhea, difficulty in nasal breathing, decreased olfactory function, pain syndrome localized in the nasopharynx and throat, cough severity and laboratory results.Results. In patients with 7 days of therapy, the indicator of psychological health increased by 34.7 points in the first group, by 28.8 points in the second group. Vital activity increased by 33.7 points in patients of group 1 and by 23.8 points in the second group. Physical activity tended to increase by 19.5 points and 6.0 points in the first and second groups, respectively.Conclusions. The analysis of changes in the severity of clinical symptoms affecting the quality of life of patients confirmed the effectiveness and safety of the drug Triazavirin.

Peculiarities of children’s health status after acute respiratory viral infections: a look at the problem, ways to solve it

Peculiarities of children’s health status after acute respiratory viral infections: a look at the problem, ways to solve it

Herpes zoster in an immunocompetent adolescent – A case of rare occurrence

ABSTRACT Herpes zoster is an acute viral infection caused by the reactivation of the varicella zoster virus. It occurs commonly in immunocompromised adults. Odontalgia may be an early prodromal symptom when herpes zoster involves the oral and maxillofacial region, which lays significant emphasis on the role of a dentist in early diagnosis and treatment of the infection. Herpes zoster infection commonly affects adult and elderly patients and is very rare in children. This article shows cases of herpes zoster infection in a 14-year-old immunocompetent boy who presented with dental pain as a prodromal sign. Herpes zoster may occur in children and thus should be considered in the differential diagnosis of acute multiple ulcers occurring in that population.

Transcriptome Profiles Characteristics of the Peripheral Immune in Patients with Severe Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute viral infection disease with a high mortality, but there are no specific effective drugs or vaccines available for use. To develop effective treatment methods, more basic researches are urgently needed to elucidate the response mechanisms of patients. Here, we conducted the transcriptomic analysis of peripheral immunity in 14 SFTS patients, ranging from moderate infection to severe and fatal disease. The results showed orderly cytokine signaling pathway modulation in moderate patients, cellular immunosuppression in severe patients, and significant dysregulation of the inflammatory response and coagulation dysfunction characteristic of deceased patients. In addition, WGCNA further showed a significant positive correlation between fatal outcomes and B cell and immunoglobulin mediated immune function modules, as well as a significant negative correlation with coagulation function modules. Overall, our research findings systematically observed potential immune mechanisms underlying clinical symptom heterogeneity and noteworthily revealed multiple signaling pathways leading to coagulation dysfunction in fatal outcomes, not just related to decreased platelet count, which can further elucidate the interaction between viruses and hosts and contribute to clinical treatment.

Influenza and non-influenza ARVI in children. A relationship between cytokine profile, parameters of the “lipid peroxidation – antioxidant defense system” as well as clinical and laboratory indicators

Influenza and acute respiratory viral infections (ARVI) impose a substantial damage to the population health in the Russian Federation due to their seasonal circulation and predominantly affect young children. A very few data on the cytokine profile, the nonspecific LPO — AOD system and their relationships with clinical characteristics in such diseases in preschool children are available. The aim of this study was to assess the cytokine profile, LPO — AOD system parameters and their relationship with the clinical and laboratory characteristics of diseases in preschool children with influenza and other ARVI. 86 preschool children (3–6 years old) were examined: with an established diagnosis of influenza (n = 31), non-influenza ARVI (n = 28), apparently healthy children (control group (n = 27). All pediatric samples were analyzed by enzyme-linked immunosorbent assay assessing blood serum concentrations of C-reactive protein and cytokines IL-1β, IL-4, IL-6, IL-8, TNFα, IFNα, IFNγ. Spectrophotometric, fluorometric and enzyme immunoassay methods to assess the state of the “LPO — AOD” system were used. In the group of children with influenza vs other ARVI, a higher incidence of intoxication syndrome was revealed. Cytokine profile in children from both clinical groups compared with control cohort was featured with higher indicators of both pro-inflammatory and anti-inflammatory origin. Children with non-influenza ARVI, had increased magnitude of LPO final products in the nonspecific LPO — AOD system along with lowered concentration of fat-soluble vitamins, general antioxidant activity, GSH level, and SOD activity. In the group with influenza, the level of primary and final lipid peroxidation products was increased, whereas that of for retinol,α-tocopherol, and total antioxidant activity was decreased paralleled with higher GSSG and SOD levels. Numerous correlations were noted in the group of children with ARVI: IL-1β/ketones, IL-6/ketones, IL-8/ketones, TNFα/ketones, IL-4/ketones, IFNg/shortness of breath, IFNα/cough, double bonds/fever, double bonds/AST, SO/intoxication, retinol/fever, GSSG/cough. The influenza group differed in the following relationships: IL-4/ketones, IL-4/fever, IFNα/ketones, CDs/AST. It can be concluded that in preschool children with ARVI and influenza, changes in the cytokine profile are accompanied by increased pro- and anti-inflammatory cytokine levels, increased intensity of lipid peroxidation reactions along with reduced magnitude of antioxidant factors. In the group with ARVI, there was a relationship between the final toxic products of lipid peroxidation — Schiff bases — and the intoxication index, as well as the presence of protective mechanisms in the form of connections between interferons and disease clinical manifestations. The group with influenza was distinguished by the presence of protective relations, which may have a beneficial effect in the context of developing pathological process. The data obtained will help expand the understanding of the pathogenetic mechanisms related to immune reactivity and nonspecific lipid peroxidation reactions in preschool patients and formulate appropriate measures for correction.

Концепция периоперационного риска: обзор литературы

INTRODUCTION: Perioperative risk refers to the likelihood of adverse events occurring during and after surgery. For the purpose of defining and classifying adverse events and predicting them, a comprehensive search of Pubmed and Lens.org was made according to the author expert opinion. OBSERVATIONS: Traditionally, two main types of postoperative adverse events have been investigated: complications and mortality. However, over the past decade, there has been a growing trend to expand the range of adverse events analyzed, from intraoperative critical events and the quality of recovery from anesthesia to the development of intensive care syndrome, assessing quality of life, disability, and survival over time. An important aspect associated with adverse events and outcomes is the provision of additional resources for a long-term stay for patients with acute respiratory viral infections and inpatient care after discharge, among other things. The review formulates its own concept of perioperative risk, based on a critical analysis of literature, with an emphasis on the need to create an ideal tool, such as a calculator, that must undergo external validation. This tool should include available, modifiable variables, and accurately determine the full range of adverse events and outcomes during the intra- and early postoperative periods, as well as delayed events. The concept shall also focus on identifying and characterizing patients with a high risk of perioperative complications.

АНАЛИЗ ОБЪЕМА ПРОДАЖ КОМБИНИРОВАННЫХ ПРЕПАРАТОВ ДЛЯ СИМПТОМАТИЧЕСКОЙ ТЕРАПИИ ОСТРЫХ РЕСПИРАТОРНЫХ ВИРУСНЫХ ИНФЕКЦИЙ И ПРОРАБОТКА АССОРТИМЕНТА АНТИГРИППИНА НА ПРИМЕРЕ АПТЕКИ ГОРОДА КАЗАНИ

There is strong competition between pharmacy providers. The abundance of advertising allows the public to be relatively informed in the variety of medicines offered by suppliers. All of the above, including high rent for inventory storage space, emphasizes the problem of the need for rational assortment formation. Only a properly created assortment of goods will allow the pharmacy to compete in the eyes of consumers, not to lose regular customers and to acquire new ones. With effective management of the product assortment can increase the income of the pharmacy due to the lack of unsatisfied demand. It is also possible to reduce the number of sales lost due to lack of goods, to accelerate the turnover of goods, to reduce the cost of storing medicines. Currently, there is a variety of combination medicines offered by suppliers to combat several symptoms of acute respiratory viral infections. The article presents the results of ABC-analysis, XYZ-analysis and their combination on the example of the assortment of dosage forms of antigrippin of the pharmacy of the state network of the city of Kazan. The distribution of antigrippin assortment into groups is shown and recommendations on the strategy of the pharmacy manager in relation to each of the groups are offered. The fact that these are seasonally consumed commodities with medium forecasting capabilities makes it difficult to plan the procurement of combination medicines to control several symptoms of acute respiratory viral infections. After combining the results of ABC XYZ analysis, it was found that antigrippin pharmacy-made antigrippin and antigrippin effervescent tablets are commodity items with a low share of turnover and number of sales units. They showed a medium degree of forecast reliability due to unstable demand. Antigrippin express powder, antigrippin - ANVI capsules and Vicks Antigripp Max powder made up the majority of the assortment, a small share of the turnover of antigrippin dosage forms and the number of sales units. These products showed low forecast reliability due to non-constant demand and generated little profit. This could be due to the fact that the consumer did not have sufficient information about these products.

Exploring the Clinical Characteristics and Outcomes of Rhinovirus Infection in Hospitalized Children Compared with Other Respiratory Viruses

Background: Acute viral respiratory tract infections constitute a significant challenge in pediatric healthcare globally, with rhinovirus representing one of the primary etiological agents. In this context, we conducted a study with the objective of identifying the clinical characteristics and outcomes of rhinovirus infection in comparison with other respiratory viruses in children hospitalized in one of the largest pediatric hospitals in the capital of Romania. Methods: We conducted a retrospective study among children hospitalized for influenza-like illness symptoms and who were tested by multiplex RT-PCR with a nasopharyngeal swab between May 2020 and December 2021. Results: A total of 496 children were eligible for inclusion in the study, and the positivity rate for at least one virus was 58.5%. The rhinovirus was identified in 138 patients (median age 12.5 months), representing 27.8% of all children tested and 49.3% of all positive samples. Although the clinical features of children with rhinovirus were dominated by cough (63.7%) and dyspnea (51.6%), no symptoms were identified that were strongly associated with rhinovirus infection in comparison to other respiratory viruses. The probability of receiving an antibiotic prescription was 1.92 times lower (p = 0.011) in children who tested positive for rhinovirus compared to children with negative RT-PCR results. The incidence of acute bronchiolitis or acute bronchitis, acute respiratory failure, and acute otitis media was higher among rhinovirus-positive children than among those who tested negative via RT-PCR. However, the incidence of these conditions was similar among children who tested positive for other respiratory viruses. Conclusions: Rhinovirus was the most prevalent virus identified in children hospitalized with influenza-like illness symptoms. The utilization of multiplex RT-PCR molecular tests is instrumental in elucidating etiology with precision and implementation of these advanced diagnostic methods, which can bring significant benefits in practice. A positive result for rhinovirus helps to reduce the unnecessary administration of antibiotics and optimizes patient management, thus decreasing the risk of severe complications such as acute respiratory failure and acute otitis media.

Main challenges and measures taken by public health institutions in response to war in Kyiv Region

Abstract Background The establishment of martial law due to Russia’s military aggression against Ukraine led to specific adjustments in the functioning of the Centers for Diseases Control and Prevention (СDС). The negative impact of hostilities is determined by the increased morbidity rate of communicable and non-communicable diseases, insufficient supply of safe drinking water and food to damaged sites, inadequate living conditions, etc. Objectives The purpose of the work was to create an effective system for responding to biological, chemical and radiation hazards and eliminating the consequences of an emergency situation in the realities of martial law. Methods We used the most common methods, namely descriptive, statistical, microbiological and сhemical laboratory tests. Results The activities of the CDC under martial law include daily monitoring studies of environmental objects. The epidemic situation of acute intestinal infection (AII) and other communicable diseases (CD) is constantly analyzed. The Kyiv Oblast CDC became the basic institution for the implementation of the ‘pilot project’ in the direction of sanitary and epidemic assessment and monitoring of environmetal objects in 188 de-occupied areas. The main public health risks were identified: providing the population with high-quality drinking water; low immunization rate of the population; sites for the location of internally displaced persons; natural foci of especially dangerous diseases, such as tularemia, leptospirosis, infection fevers, etc. In 2022, the overall level of CD in the Kyiv region decreased by 44.0% from 2021. The most common nosologies were acute respiratory viral infections and influenza (98.9%), AII (42.4%), tuberculosis (15.3%), Lyme disease (15.3%), and viral hepatitis (14.2%). Conclusions Based on the research conducted, mechanisms have been developed for responding to hazards of various origins by public health institutions, including risk assessmant and laboratory studies. Key messages • The main focus of the Centers for Diseases Control and Prevention is aimed at effective response to hazards of various origins in order to ensure public health under martial law. • Risk assessment in de-occupied territories has become an important tool for identifying correct approaches to prevent negative consequences for public health.

New concept for the prevention of acute respiratory infections

Medical personnel and family members of patients with acute respiratory diseases (ARD) are at increased risk of infection during epidemics or pandemics. In this regard, it is necessary to develop and implement accessible preventive measures. The aim of the study was to evaluate the effectiveness of the use of IFNα-2b for the prevention of acute respiratory viral infections in persons located at the source of infection (medical personnel and members of their families). Patients (n = 31) with acute respiratory infections and 117 people from their environment (family members in constant contact with patients) were examined. The subjects underwent a clinical examination and laboratory tests a clinical blood test and a study of the content of the main populations and subpopulations of lymphocytes in the blood. Persons in contact with ARD patients were divided into three groups: persons who received the drug “Grippferon” for 7 days; persons who received the drug “Grippferon” in a prophylactic dose for 7 days; persons in contact with patients with ARD but who have not received the drug “Grippferon”. When assessing the state of the immune system, it was found that the most common type of immune reaction in patients and their people around was activation of innate immunity (48.39% and 66.67%, respectively). At the same time, immunodeficiency in the group of patients with ARD was detected much more often than in persons in contact with them. In addition, patients were more likely to have monocytosis (1.4 times), T lymphocytopenia (2.1 times) and an increase in the number of regulatory T lymphocytes (7.6 times). More than 50% of those examined in both groups showed an increase in the number of NK cells in the blood. An examination of persons in contact with patients with ARD after 7 days of using the “Grippferon” in different doses revealed that the lowest frequency of acute respiratory viral infections symptoms was found in the group receiving IFN at a therapeutic dose. In the group receiving IFN in a prophylactic dose, the frequency of acute respiratory viral infection (ARVI) symptoms was detected in almost 40% of those examined. More than 80% of people from the group who did not receive the “Grippferon” had symptoms of ARVI after a week of contact with patients with ARD. Thus, the use of IFN in therapeutic doses during the epidemic for persons in contact with patients is proposed as a new concept for the prevention of ARD.

Assesment of factors for late diagnosis of idiopathic pulmonary arterial hypertension in real clinical practice

Idiopathic (primary) pulmonary arterial hypertension – a rare progressive disease that shortens life, usually diagnosed at a late stage. Therefore, it is critical to have a low threshold for suspicion of pulmonary hypertension (PH) and to refer patients to specialized centers for diagnostic evaluation and treatment as early as possible. Echocardiography is the method of choice for pulmonary hypertension assessing. Aim of the study. To determine the reason for the late diagnosis of idiopathic pulmonary arterial hypertension.Material and methods. Using the developed questionnaire, 41 patients, men and women aged 18 years and older, who were reliably diagnosed with idiopathic pulmonary arterial hypertension, were interviewed.Results and discussion. The diagnosis of idiopathic pulmonary arterial hypertension in clinical practice is made on average 7.1±6.0 years from the onset of the first symptoms of the disease. In 95% of cases, the onset of idiopathic pulmonary arterial hypertension begins with shortness of breath on exertion. Most often, the development of the disease was preceded by an acute respiratory viral infection. All patients underwent diagnostic echocardiography at the time of their first visit, but the diagnosis was established in only 56% of patients.Conclusions. Reasons for late diagnosis of idiopathic pulmonary arterial hypertension: the nature of the disease at its onset and errors in diagnosis.

Combination of proviral and antiviral roles of B cell-intrinsic STAT1 expression defines parameters of chronic gammaherpesvirus infection.

Gammaherpesviruses are species-specific, ubiquitous pathogens that establish lifelong infection in their hosts and are associated with cancers, including B cell lymphomas. Type I and II interferons (IFNs) are critical for the control of acute and chronic gammaherpesvirus infection. However, the cell type-specific role of IFN signaling during natural infection is poorly defined and is masked by the altered viral pathogenesis observed in hosts with global IFN deficiencies. STAT1 is a constitutively expressed transcription factor that is critical for the effector function of type I and II IFNs. In this study, we defined the impact of B cell-specific STAT1 expression on gammaherpesvirus infection using murine gammaherpesvirus 68 (MHV68). While the acute stage of MHV68 infection was not affected, we found opposite, anatomic site-dependent effects of B cell-intrinsic STAT1 expression during chronic infection. Consistent with the antiviral role of STAT1, B cell-specific STAT1 expression attenuated the latent viral reservoir in peritoneal B cells of chronically infected mice. In contrast, STAT1 expression in splenic B cells supported the establishment of the latent MHV68 reservoir in germinal center B cells, revealing an unexpected proviral role of B cell-intrinsic STAT1 expression during chronic gammaherpesvirus infection. These STAT1-dependent MHV68 chronic infection phenotypes were fully recapitulated in the peritoneal cavity but not the spleen of mice with B cell-specific deficiency of type I IFN receptor. In summary, our study uncovers the intriguing combination of proviral and antiviral roles of B cell-intrinsic STAT1 expression during chronic gammaherpesvirus infection.IMPORTANCEInterferons (IFNs) execute broadly antiviral roles during acute and chronic viral infections. The constitutively expressed transcription factor STAT1 is a critical downstream effector of IFN signaling. Our studies demonstrate that B cell-intrinsic STAT1 expression has opposing and anatomic site-dependent roles during chronic gammaherpesvirus infection. Specifically, B cell-intrinsic STAT1 expression restricted gammaherpesvirus latent reservoir in the peritoneal cavity, consistent with the classical antiviral role of STAT1. In contrast, decreased STAT1 expression in splenic B cells led to the attenuated establishment of gammaherpesvirus latency and decreased latent infection of germinal center B cells, highlighting a novel proviral role of B cell-intrinsic STAT1 expression during chronic infection with a B cell-tropic gammaherpesvirus. Interestingly, B cell-specific type I IFN receptor deficiency primarily recapitulated the antiviral role of B cell-intrinsic STAT1 expression, suggesting the compensatory function of B cell-intrinsic type II IFN signaling or an IFN-independent proviral role of B cell-intrinsic STAT1 expression during chronic gammaherpesvirus infection.

A measles virus collective infectious unit that caused lethal human brain disease includes many locally restricted and few widespread copy-back defective genomes.

During virus replication in cultured cells, copy-back defective viral genomes (cbDVGs) can arise. CbDVGs are powerful inducers of innate immune responses in vitro, but their occurrence and impact on natural infections of human hosts remain poorly defined. We asked whether cbDVGs were generated in the brain of a patient who succumbed to subacute sclerosing panencephalitis (SSPE) about 20 years after acute measles virus (MeV) infection. Previous analyses of 13 brain specimens of this patient indicated that a collective infectious unit (CIU) drove lethal MeV spread. In this study, we identified 276 replication-competent cbDVG species, each present in over 100 copies in the brain. Six species were detected in multiple forebrain locations, implying that they travelled long-distance with the CIU. The cbDVG to full-length genomes ratio was often close to 1 (0.6-1.74). Most cbDVGs were 324-2,000 bases in length, corresponding to 2%-12% of the full-length genome; all are predicted to have complementary terminal sequences. If improperly encapsidated, these sequences have the potential to form double-stranded structures that can induce innate immune responses. To assess this, we examined the transcriptome of all brain specimens. Several interferon and inflammatory response genes were upregulated, but upregulation levels did not correlate with cbDVG levels in the specimens. Thus, the CIU that drove MeV pathogenesis in this brain includes, in addition to two complementary full-length genome populations, many locally restricted and few widespread cbDVG species. The widespread cbDVG species may have been positively selected but how they impacted pathogenesis remains to be determined.IMPORTANCECopy-back defective viral genomes (cbDVGs) can drive virus-host interactions. They can suppress virus replication directly, by competing with full-length genomes, or indirectly by stimulating antiviral immunity. In vitro, cbDVG can slow down infections and promote persistence, but there is limited documentation of their presence in human hosts or of their impact on disease. We had the unique opportunity to analyze the brain of a patient who succumbed to subacute sclerosing panencephalitis, a rare but lethal consequence of measles. We detected more than 270 distinct cbDVG species; most were restricted to one specimen, but several reached all lobes of the forebrain, suggesting positive selection. Our analyses provide the missing knowledge of the diversity of cbDVG in a natural infection of a human host. They also reveal that a collective infectious unit that caused lethal human brain disease includes few widespread cbDVG, in addition to two ubiquitous complementary full-length genome populations.

Trends of common laboratory biomarkers after SARS-CoV-2 infection

Most studies that explore the long-term effects of COVID-19 are based on subjectively reported symptoms, while laboratory-measured biomarkers are mainly examined in studies of relatively small cohorts. This study investigates the long-term effects of SARS-CoV-2 infection on common laboratory biomarkers. We utilized a retrospective cohort of SARS-CoV-2 infected individuals and rigorously matched controls based on demographic and clinical characteristics, examining 63 common laboratory biomarkers. Additional lab-specific cohorts were matched with an additional criterion of baseline biomarker values. Differences in biomarkers over a 12-month follow-up were analyzed using standardized mean difference-in-differences. The general cohort included 361,061 matched pairs, with 26M laboratory results. The effects on most biomarkers lasted 1-4 months and were consistent with anticipated changes after acute viral infections. Some biomarkers presented prolonged effects, consistent across the general and lab-specific cohorts. One group of such findings included a 7-8 month decrease in WBC counts, mainly driven by decreased counts of neutrophils, monocytes, and basophils. Potassium levels were decreased for 3-5 months. Vaccinated individuals' data suggested potentially smaller effects on WBCs, but cohort sizes limited this analysis. This study explores SARS-CoV-2 infection effects on common laboratory biomarkers, characterizing the direction and duration of these effects on the largest infected cohort to date. The effects of most biomarkers resolve in the first months following infection. The most notable longer-lasting effects involved the immune system. Further research is required to characterize the magnitude of these effects among specific individuals.

Out-of-Hospital Infant Mortality Associated with Herpesviruses

Introduction. Infant mortality is a universally recognized indicator for social well-being of the population. There is a need for an in-depth analysis of the causes and factors leading to the death of infants at home, including determining the etiology of infectious diseases potentially causing death.The purpose of the study — to determine the implication of herpesviruses in infant out-of-hospital death.Materials and methods. Samples from autopsy material of 23 infants (blood, small intestine, heart, lungs, liver, brain), who died at home from various causes, were analyzed by PCR for the presence of viral DNA and RNA from herpesviruses, orthomyxoviruses, paramyxoviruses, picornaviruses, adenoviruses, coronaviruses, parvoviruses, as well as intestinal viruses.Results and discussion. Positive PCR results were found in 11 cases (43.5 %), of which herpesviruses DNA was detected in 10 cases. In these samples, cytomegalovirus predominated, in association with Epstein — Barr virus and human herpesvirus type 6. This association was detected in blood and internal organs samples from four infants diagnosed with generalized viral infection, and from two infants with acute respiratory viral infection. This suggests the presence of a causal relationship between the lethal outcome and the detection of these viruses. Not all infants showed clinical signs characteristic of generalized herpes infection. In one infant with hypertrophic cardiomyopathy, coronavirus, enterovirus and rotavirus DNA was found in samples of internal organs.Conclusion. Results showed the dominant role of the herpesviruses in out-of-hospital infant death cases.

Dual Roles of Host Zinc Finger Proteins in Viral RNA Regulation: Decay or Stabilization.

Host defense mechanisms against viral infections have been extensively studied over the past few decades and continue to be a crucial area of research in understanding human diseases caused by acute and chronic viral infections. Among various host mechanisms, recent findings have revealed that several host RNA-binding proteins play pivotal roles in regulating viral RNA to suppress viral replication and eliminate infection. We have focused on identifying host proteins that function as regulators of viral RNA, specifically targeting viral components without adversely affecting host cells. Interestingly, these proteins exhibit dual roles in either restricting viral infections or promoting viral persistence by interacting with cofactors to either degrade viral genomes or stabilize them. In this review, we discuss RNA-binding zinc finger proteins as viral RNA regulators, classified into two major types: ZCCCH-type and ZCCHC-type. By highlighting the functional diversity of these zinc finger proteins, this review provides insights into their potential as therapeutic targets for the development of novel antiviral therapies.