Virus Infection Research Articles

DOENÇA DE KAWASAKI EM ADOLESCENTES: UMA REVISÃO DE LITERATURA

Kawasaki disease (KD) is defined as an acute systemic vasculitis that affects small and medium-sized arteries of unknown etiology, believed to be related to an atypical immunological response triggered by viral or bacterial infections. It remains one of the main causes of acquired heart disease in developed countries. It mainly affects children under 5 years of age and has a low prevalence in adolescents. The study seeks to carry out an analysis of the literature on the disease in adolescents and its repercussions. As a methodology, a search was carried out on free online platforms over the last 15 years in Portuguese and English. As a result, it was observed that Kawasaki disease in adolescents remains of uncertain etiology, predominates in males, presents in most cases incompletely, being wrongly diagnosed as infectious diseases, thus delaying its diagnosis and treatment, consequently, increases the main complication, which is coronary aneurysm. As it does not present a pathognomonic diagnostic test, health professionals should be encouraged to study and recognize Kawasaki disease early in order to avoid complications and morbidity and mortality.

Movement Disorders after Dengue Virus Infection: A Scoping Review.

Movement disorders after dengue virus (DENV) infection have been increasingly recognized. We aimed to synthesize the clinical and paraclinical characteristics, treatment responses, and outcomes of these neurologic complications. We systematically reviewed PubMed, Embase, Scopus, and LILACS databases up to September 2023 following a published protocol. We identified 73 cases of DENV-induced movement disorders. Cerebellar ataxia was the most common, followed by parkinsonism, opsoclonus-myoclonus-ataxia syndrome, and dystonia. Movement disorders typically developed within 14 days of DENV infection and were associated with a range of neurological symptoms, including cognitive impairment and psychiatric disturbances. Neuroimaging studies frequently showed abnormalities in the basal ganglia and brainstem. Treatment varied depending on the specific movement disorder and included corticosteroids, intravenous immunoglobulin, and symptomatic medications. Whereas a handful of cases met the criteria for acute encephalitis, many lacked sufficient data to establish a definitive diagnosis. Para-infectious and postinfectious immune-mediated movement disorders were also reported. A rare case of chronic progressive panencephalitis due to DENV infection highlights the potential for long-term neurological consequences. Other DENV-related complications, such as stroke, pituitary apoplexy, subacute thyroiditis, and metabolic disturbances, can also cause movement disorders. We emphasize the importance of recognizing the diverse neurological manifestations of DENV infection and the need for further research to improve our understanding of the underlying mechanisms and optimize treatment strategies. We propose a more rigorous approach to determining the causality between infection and movement disorder, demanding stronger evidence beyond mere association and advocating for targeted research to fill the existing knowledge gaps. © 2025 International Parkinson and Movement Disorder Society.

Direct-Acting Antivirals Induce Lymphoproliferative Disease Response in HCV-Infected Patients With Indolent B-Cell Non-Hodgkin's Lymphoma: A Prospective Observational Study.

B-cell non-Hodgkin lymphoma (NHL) in one of the most serious extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. No prospective studies have been conducted in the United States (US) on the impact of direct-acting antivirals (DAAs) in HCV-infected patients with indolent B-cell NHL not requiring chemotherapy. In this prospective study, we evaluated the general characteristics of US patients with HCV-associated indolent B-cell NHL and the oncologic impact of only DAA treatment without systemic cancer therapy in those patients. We enrolled patients seen at our center during 2014-2021; we analyzed only chemotherapy-naïve patients treated with DAAs. Patients who required immediate conventional treatment for lymphoma were excluded from the study. The primary endpoints were sustained virologic response at 12weeks (SVR12) and lymphoproliferative disease response, classified as complete response, partial response, stable disease, or progressive disease. The secondary endpoints were overall response rate (ORR) of NHL, duration of response (DOR), overall survival (OS), and progression-free survival (PFS). Nine patients met the study criteria and were analyzed. Most patients were male (n=6), White (n=6), younger than 65years (n=6), and non-cirrhotic (n=8); had HCV genotype 1 (n=5); and had been infected for more than 30years (n=7). All patients achieved SVR12. Six patients (67%) had complete response, and 3 (33%) had progressive disease. The ORR was 67%. The median DOR was 51months (range 16-81months). The 5-year DOR, OS, and PFS rates were 100%, 83%, and 67%, respectively. HCV-associated NHL is a late extrahepatic complication of HCV. Infected patients with indolent NHL have an excellent virologic responses to DAAs and most of them experienced a favorable oncologic response after HCV eradication without chemotherapy.

Peer-assisted telemedicine hepatitis-C treatment for people who use drugs in rural communities: a mixed methods study

BackgroundThe increase in opioid use disorder among young, nonurban people has fueled sharp rises in hepatitis C virus (HCV) infections. Innovative treatment models are needed that circumvent healthcare system barriers for people who use drugs (PWUD), particularly in rural areas. The Oregon HOPE TeleHCV study randomized PWUD living with HCV in rural Oregon to peer-facilitated and streamlined telemedicine HCV treatment (Peer TeleHCV) versus enhanced usual care (EUC) and assessed sustained virologic response at 12 weeks post treatment (SVR12). Peer Support Specialists (peers) conducted HCV screening in the community, facilitated pretreatment evaluation and linkage to telemedicine HCV treatment clinicians, and supported Peer TeleHCV study participants in HCV medication adherence. A qualitative investigation queried telemedicine clinicians and peers about their experiences with the implementation of the model and key drivers of implementation effectiveness.MethodsTwo remote audio/video recorded focus groups were conducted, one with the study’s clinicians and one with the peers. Participants were asked their views of key elements for successful implementation and outcomes of the Peer TeleHCV model. Group interviews lasted one hour. Recordings were professionally transcribed for thematic analysis with a mixed deductive and inductive framework, using Atlas.ti. Patients were surveyed about their interactions and satisfaction with peers.ResultsQuantitative data (n = 78) indicated patients had high levels of satisfaction with and support from the peers. Three themes were identified from the qualitative data (n = 12) including. (1) Key peer-level elements such as providing support during potentially difficult lab draws, creating a peer-facilitated “bubble of trust” between patients and clinicians, enabling technology access, conducting outreach to maintain contact and support treatment retention, and facilitating stabilizing wrap-around services (e.g., housing vouchers) (2) Key clinician-level factors such as capacity for unscheduled peer-facilitated appointments, having dedicated time for case consults with peers, and clinicians trained in working with PWUD and skilled in identifying related clinical concerns (3) Key systems-level elements such as standing lab orders, challenges related to specialty pharmacies and Medicaid managed care organizations, and streamlined communication strategies between peers and clinicians.ConclusionAll participants reported that the Peer TeleHCV model built trust and eased barriers for PWUD initiating and remaining in HCV treatment. This low-barrier model makes space for PWUD to receive HCV treatment, regardless of drug use. Implementing support from peer specialists, telemedicine technology, and streamlined testing and treatment strategies may connect more rural PWUD living with HCV with the cure.

Molecular characterization of lumpy skin disease virus during the first outbreak of lumpy skin disease in Northern Himalayas, India.

Lumpy skin disease (LSD) is a highly contagious and fatal transboundary viral disease of cattle and water buffaloes caused by the Lumpy Skin Disease virus (LSDV) which belongs to the genus Capripoxvirus of the Poxviridae family. The disease causes huge economic impact and has been listed as a notifiable disease by World Organization for Animal Health. We present the molecular epidemiology of an LSD outbreak, the first-ever outbreak of the disease in the Union Territory (UT) of Jammu and Kashmir, India; a region lying in Northern Himalayas. During the outbreak, 1661 samples were collected from clinically affected, in-contact cattle as well as apparently healthy animals and screened for LSDV by qPCR. From these 1661 samples, 643 (38.7%) were found positive. Five LSDV-positive samples were randomly selected and the GPCR gene was amplified, cloned and sequenced. A 12-nucleotide deletion was observed in the GPCR gene when compared to the 2019 Indian LSDV isolate from Odhisa, India. Based on the data obtained by qPCR analysis, the occurrence of LSD was determined with respect to the age, sex and breed of the animals. Furthermore, ticks collected from the affected animals and flies on the farm were identified and were found positive for LSDV.

Limited transmission of avian influenza viruses, avulaviruses, coronaviruses and Chlamydia sp. at the interface between wild birds and a free-range duck farm

Recent outbreaks of highly pathogenic avian influenza in Europe have raised questions regarding the epidemiological role of commensal wild birds on free-range poultry farms. This study aimed to assess the prevalence of avian influenza viruses (AIV), avulaviruses, coronaviruses and Chlamydia sp. in commensal wild birds on a free-range duck farm in southwestern France and to evaluate possible transmission events at the wild‒domestic interface. From 2019 through 2021, a longitudinal study was conducted on wild birds, domestic ducks and their shared environment on farms. Commensal wild birds were captured and sampled for blood and swabs, and fresh feces from cattle egrets visiting the farm were collected. In parallel, domestic ducks were sampled, and environmental samples were collected. The presence of the four pathogens was tested by q(RT-)PCR, and the immunity of wild birds to AIV and Newcastle disease virus (NDV) was tested by ELISA. Wild birds were found to shed AIV and Chlamydia only, with a low prevalence (< 3%). The seroprevalence rates were less than 10% for AIV and less than 4.5% for NDV. No significant temporal trend was identified. Ducks and their environment frequently test simultaneously positive for the same pathogens (19 to 44% of flocks), mostly during fall‒winter. In addition to unrelated temporal patterns, the identification of pathogens in wild birds seemed unrelated to that in domestic ducks. These results suggest a low transmissibility of the avian pathogens tested in our study at the wild‒domestic interface and highlight the limited contribution of commensal wild birds in comparison with free-range poultry to the global microbiological pressure on the environment.

Metabolic deficiencies underlie reduced plasmacytoid dendritic cell IFN-I production following viral infection

Type I Interferons (IFN-I) are central to host protection against viral infections, with plasmacytoid dendritic cells (pDC) being the most significant source, yet pDCs lose their IFN-I production capacity following an initial burst of IFN-I, resulting in susceptibility to secondary infections. The underlying mechanisms of these dynamics are not well understood. Here we find that viral infection reduces the capacity of pDCs to engage both oxidative and glycolytic metabolism. Mechanistically, we identify lactate dehydrogenase B (LDHB) as a positive regulator of pDC IFN-I production in mice and humans; meanwhile, LDHB deficiency is associated with suppressed IFN-I production, pDC metabolic capacity, and viral control following infection. In addition, preservation of LDHB expression is sufficient to partially retain the function of otherwise exhausted pDCs, both in vitro and in vivo. Furthermore, restoring LDHB in vivo in pDCs from infected mice increases IFNAR-dependent, infection-associated pathology. Our work thus identifies a mechanism for balancing immunity and pathology during viral infections, while also providing insight into the highly preserved infection-driven pDC inhibition.

Spatial proteomics identifies a CRTC-dependent viral signaling pathway that stimulates production of interleukin-11.

Appropriate cellular recognition of viruses is essential for the generation of an effective innate and adaptive immune response. Viral sensors and their downstream signaling components thus provide a crucial first line of host defense. Many of them exhibit subcellular relocalization upon activation, resulting in the expression of interferon and antiviral genes. To comprehensively identify signaling factors, we analyzed protein relocalization on a global scale during viral infection. cAMP-responsive element-binding protein (CREB)-regulated transcription coactivators 2 and 3 (CRTC2/3) exhibited early cytoplasmic-to-nuclear translocation upon infection with multiple viruses in diverse cell types. This movement was dependent on mitochondrial antiviral signaling protein (MAVS), cyclo-oxygenase proteins, and protein kinase A. A key effect of CRTC2/3 translocation is transcription of the fibro-inflammatory cytokine interleukin (IL)-11. This may be important clinically in viral infections associated with fibrosis, including SARS-CoV-2. Nuclear translocation of CRTC2/3 is, therefore, identified as an important pathway in the context of viral infection.

The value of common blood parameters for the differential diagnosis of respiratory tract infections in children

Mycoplasma pneumoniae and influenza A virus are common pathogens that cause respiratory tract infection in children. Both pathogens present with similar clinical symptoms, and their epidemic periods often overlap. Consequently, it is challenging for clinicians to make a rapid preliminary diagnosis. However, common blood tests is simple and efficient, Therefore, the purpose of this study is to preliminarily distinguish Mycoplasma pneumoniae and influenza A virus infection in children by analyzing the results of common blood tests, thereby guiding clinical diagnosis and treatment.The results showed that, compared with children in the influenza A virus-positive group, children in the Mycoplasma pneumoniae-positive group had higher white blood cell (WBC), red blood cell (RBC), haemoglobin (HGB), platelet (PLT) counts, lymphocyte (LYM) and eosinophil (EOS) counts and ratios, as well as higher concentrations of C-reactive protein (CRP) and serum amyloid A (SAA), while neutrophil (NEU) and monocyte (MONO) counts and ratios, Neutrophil to Lymphocyte ratio( NLR) were lower, in addition, LYM, EOS counts and ratios, and NLR were all more effective in differentiating between the two pathogen infections, A combined analysis of these indicators further improved the differentiation efficacy. Therefore, LYM and EOS counts and ratios, along with NLR, can serve as effective blood parameters for differentiating Mycoplasma pneumoniae infections from influenza A virus infections in children.

Small circular RNAs as vaccines for cancer immunotherapy.

Messenger RNA vaccines have shown strong prophylactic efficacy against viral infections. Here we show that antigen-encoding small circular RNAs (circRNAs) loaded in lipid nanoparticles elicit potent and durable T cell responses for robust tumour immunotherapy after subcutaneous injection in mice, particularly when combined with immune checkpoint inhibition. The small circRNA vaccines are highly stable and show low levels of activation of protein kinase R as well as low cytotoxicity, enabling long-lasting antigen translation (longer than 1 week in cells). Relative to large protein-encoding unmodified or modified mRNAs and circRNAs, small circRNA vaccines elicited up to 10-fold antigen-specific T cells in mice and accounted for 30-75% of the total peripheral CD8+ T cells over 6 months. Small circRNA vaccines encoding tumour-associated antigens, neoantigens and oncoviral or viral antigens elicited substantial CD8+ and CD4+ T cell responses in young adult mice and in immunosenescent aged mice. Combined with immune checkpoint inhibition, monovalent and multivalent circRNA vaccines reduced tumour-induced immunosuppression and inhibited poorly immunogenic mouse tumours, including melanoma resistant to immune checkpoint blockade.

Vitamin D as an Adjuvant Immune Enhancer to SARS-Cov-2 Vaccine.

The SARS-CoV-2 vaccine is an important keystone in fighting against the virus. The vaccination alone could not prevent all SARS-CoV-2 viral infections or even its spread, especially after the emergence of newly mutant strains. The immune response to the SARS-CoV-2 vaccines varies greatly from one person to another. Age, along with adequate micronutrients, especially vitamin D, are major factors influencing immunity. We aimed to analyze SARS-CoV-2 vaccine neutralization potency and the total IgG antibodies along with 25-hydroxy-cholecalciferol concentrations in a cohort of healthy Egyptian vaccinated adults. 196 individuals were included; 145 females and 51 males, with an age range between 22 and 59 years old, from the first time of vaccination and over 16weeks long. Three blood samples were taken from each individual at three time points; before the 1st dose of vaccination, before the 2nd dose of vaccination, and after 8 weeks of complete vaccination. The samples were analyzed using a chemiluminescent immunoassay to measure vitamin D level and titer of neutralizing and IgG antibodies. A lower level of neutralizing antibodies was detected in deficient and insufficient vitamin D-vaccinated individuals. However, a sufficient titer was detected in individuals with normal vitamin D. Vitamin D deficiency is associated with a suppressed immune response against SARS-CoV-2 despite vaccination. Thus, we made inquiries about using vitamin D as an adjuvant to SARS-CoV-2 vaccination, and its relation with the production of anti-SARS-CoV-2 antibodies.

Prevalence and incidence of comorbidities in patients with atopic dermatitis, psoriasis, alopecia areata, and vitiligo using a Japanese claims database.

Atopic dermatitis, psoriasis, alopecia areata, and vitiligo have been associated with comorbid conditions, including infections, malignancies, and cardiovascular diseases. This study evaluated the prevalence and incidence rates of these comorbidities in patients from Japan. This retrospective cohort study used data collected from the JMDC claims database between June 2013 and December 2020. Patients with a diagnosis of atopic dermatitis, psoriasis, alopecia areata, or vitiligo were matched (1:1) by age, sex, and index month with individuals with no claims records for atopic dermatitis, psoriasis, alopecia areata, or vitiligo diagnosis. Data included 691 338, 51 988, 43 692, and 8912 patients in the atopic dermatitis, psoriasis, alopecia areata, and vitiligo cohorts, respectively, and matched controls. The most prevalent comorbidities in the atopic dermatitis cohort versus matched controls included allergic rhinitis (47% vs 37%), conjunctivitis (33% vs 23%), asthma (27% vs 20%), viral infection (22% vs 15%), and acne (11% vs 3%). Incidence rates per 100 000 person-years of comorbidities in the atopic dermatitis cohort versus matched controls were: venous thromboembolism, 51.4 (95% confidence interval [CI], 48.3-54.7) versus 31.7 (95% CI, 29.2-34.2); lymphoma, 13.8 (95% CI,12.2-15.6) versus 5.7 (95% CI, 4.7-6.8); cutaneous T-cell lymphoma, 1.6 (95% CI, 1.1-2.2) versus 0.1 (95% CI, 0.0-0.4); and herpes zoster, 740.9 (95% CI, 728.8-753.1) versus 397.6 (95% CI, 388.9-406.6). Similar trends were observed in the psoriasis versus nonpsoriasis cohorts, with 95% CIs mostly overlapping for alopecia areata and vitiligo cohorts versus controls. Overall, patients from Japan with dermatologic diseases have a higher prevalence and incidence of certain health conditions, particularly venous thromboembolism, lymphoma, and infections in patients with atopic dermatitis and psoriasis, compared with individuals without these dermatologic diseases.

PARPs and ADP-ribosylation-mediated biomolecular condensates: determinants, dynamics, and disease implications.

Biomolecular condensates are cellular compartments that selectively enrich proteins and other macromolecules despite lacking enveloping membranes. These compartments often form through phase separation triggered by multivalent nucleic acids. Emerging data have revealed that poly(ADP-ribose) (PAR), a nucleic acid-based protein modification catalyzed by ADP-ribosyltransferases (commonly known as PARPs), plays a crucial role in this process. This review focuses on the role of PARPs and ADP-ribosylation, and explores the principles and mechanisms by which PAR regulates condensate formation, dissolution, and dynamics. Future studies with advanced tools to examine PAR binding sites, substrate interactions, PAR length and structure, and transitions from condensates to aggregates will be key to unraveling the complexity of ADP-ribosylation in health and disease, including cancer, viral infection, and neurodegeneration.

Infections in Patients with Atopic Dermatitis and the Influence of Treatment.

Atopic dermatitis (AD) is a T helper 2-mediated chronic inflammatory skin disease that affects children and adults. Patients with AD are prone to recurrent infections of the skin and other organs, which can severely worsen the disease course. This review summarises the current evidence on the aetiology, pathogenesis, treatment and prevention of infections in patients with AD. PubMed was searched for English-language research articles, systematic reviews, meta-analyses and guidelines published until February 2023 using the key term "atopic dermatitis" and terms relevant to infections. Patients with AD have an increased risk of bacterial, viral and fungal infections of the skin, mainly due to impaired barrier function, altered immune response and frequent scratching. The most common pathogens are Staphylococcus aureus and herpes simplex virus, which can cause impetigo, folliculitis, abscesses, eczema herpeticum and other complications. They also appear to increase susceptibility to systemic infections, including respiratory and urinary tract infections and sepsis. Certain systemic treatments for AD, such as mycophenolate mofetil and Janus kinase inhibitors, increase the risk of viral infections. Prevention and treatment of recurrent infections in patients with AD require a multifaceted approach that includes topical and systemic antimicrobials, skin care and effective control of AD symptoms (to break the itch-scratch cycle). Preventing and limiting the development of infections are important considerations in choosing an AD treatment.

Discovery of Arbutin as Novel Potential Antiviral Agent Against Tomato Yellow Leaf Curl Virus.

Tomato yellow leaf curl virus (TYLCV), a major plant virus, infects multiple plant species, severely threatening global food security. Arbutin, a natural product used in cosmetics to reduce pigmentation, also exhibits antibacterial and anti-inflammatory properties. However, its potential in plant protection remains undocumented. This study reveals arbutin's ability to inhibit TYLCV infection. In Nicotiana benthamiana, 100 μg/mL arbutin inhibited viral gene accumulation by up to 76.8%, surpassing ningnanmycin (65.8%) and ribavirin (39.5%). Besides, microscale thermophoresis indicated that arbutin bound strongly to the TYLCV coat protein (CP). Molecular docking indicated that arbutin interacted with ARG58, VAL65, and CYS69. RT-qPCR and Western blot experiments confirmed the crucial roles of these amino acids, especially VAL65, in viral infection. Transcriptome analysis revealed that mutating VAL65 affected plant-pathogen interaction pathways and MAPK signaling in host defense mechanisms. This study unveils arbutin's novel antiviral function, providing crucial insights for developing new biopesticides against plant viruses.

Distinct mutations emerge in the genome of serotype O foot-and-mouth disease virus during persistence in cattle.

Our research article describes the genetic changes that occur during the acute and persistent foot-and-mouth disease (FMDV) infection. This is of particular interest to understand viral dynamics within an infected population from which new viral strains could emerge. Especially FMDV, with its high antigenic diversity and very limited cross-reactivity between strains and serotypes, has already demonstrated in the past that new variants can quickly emerge and evade vaccine responses. In our study, we have observed that this dynamic evolution continues during the persistent phase. Persistently infected animals, which are clinically indistinguishable from healthy animals, also pose a reservoir for recombination. A better understanding of viral dynamics is essential for improved vaccines to prevent the emergence of antigenic variants.

Evaluation of humoral immune response and milk antibody transfer in calves and lactating cows vaccinated with inactivated H5 avian influenza vaccine

The detection of Highly Pathogenic Avian Influenza (HPAI) A(H5N1) in dairy cattle in the United States has raised concerns about human exposure. This study evaluated the efficacy of various doses of an inactivated H5 AI vaccine in cattle and assessed antibody transfer in milk against a recent bovine isolate of HPAI A(H5N1, clade 2.3.4.4b). Calves were inoculated with different vaccine doses, while lactating cows received the vaccine four weeks later. The humoral immune response was measured using the Hemagglutination Inhibition (HI) test and ELISA. Results showed a dose-dependent immune response, with higher doses producing stronger and more sustained antibody levels. Group 1 maintained a stable HI titer of 6 log2, while Groups 2, 3, and 4 peaked at 8, 9, and 9 log2, respectively, by the fourth week post-vaccination. Milk antibody transfer was observed, with strong positive responses in milk samples by the second week post-vaccination. The ID Screen ELISA demonstrated higher sensitivity for detecting antibodies in milk compared to serum. The immune response to the AI vaccine differed from responses to other vaccines used in cattle such as Foot and Mouth Disease Virus (FMDV) and Lumpy Skin Disease Virus (LSDV), indicating the need for optimizing vaccine dosage and formulation, including adjuvant and antigen content. Future research should extend the monitoring period, increase sample sizes, and explore different vaccine formulations to develop effective vaccination strategies for cattle. These findings highlight the potential for using inactivated H5 AI vaccines in cattle to enhance immune protection and facilitate antibody transfer through milk.

Impact of enhanced public health and infection control measures on pediatric hospital-acquired respiratory viral infections during the SARS-CoV-2 pandemic.

Visitor restrictions and mask-wearing may reduce hospital-acquired infections (HAI) as part of infection control bundles. The impact of a strict visitor policy and compulsory surgical mask wearing implemented during the SARS-CoV-2 pandemic, but prior to any local community circulating SARS-CoV-2, on the rates of hospital-acquired respiratory viral infections (HA-RVI) was assessed. Retrospective audit of a local HAI database for HA-RVI from 1st April 2019 to 29th March 2021 in a tertiary children's hospital. HA-RVI were standardized against occupied bed days (OBD) and admitted community acquired infections (CAI). Rates of HA-RVI were compared during 52 weeks of SARS-CoV-2-associated enhanced control periods (visitor restrictions with and without universal surgical masking), against 52 weeks standard practice. Total respiratoryvirus infections, respiratory syncytial virus (RSV), and rhinovirus infections were analysed. Comparing standard practice with enhanced measures, 42 v 15 HA-RVI and 1517 v 691 CAI were noted. Enhanced infection controls resulted in significant reductions in total HA-RVI when adjusted for OBD (p=0.0038) and CAI (p=0.0122). Non-significant decreases were seen in hospital-acquired respiratory syncytial virus (HA-RSV) adjusted for both CAI and OBD. Visitor restrictions combined with universal surgical masks significantly decreased adjusted total HA-RVI compared with visitor restrictions alone (adjusted for OBD p=0.0123; adjusted for CAI p=0.0429). HA-RSV decreased non-significantly when mask wearing was combined with visitor restrictions compared with visitor restrictions alone. HA-rhinovirus infections did not decrease with the addition of masks to visitor restrictions. Enhanced infection control measures introduced with SARS-CoV-2 pandemic decreased some HA-RVI. Universal surgical mask wearing decreased HAI rates more than visitor restrictions alone, except for rhinovirus where the HAI rate remained unchanged.

Asymptomatic neonatal herpes simplex virus infection in mice leads to persistent CNS infection and long-term cognitive impairment.

Neonatal herpes simplex virus (nHSV) is a devastating infection impacting approximately 14,000 newborns globally each year. nHSV infection is associated with high neurologic morbidity and mortality, making early intervention critical. Clinical outcomes of symptomatic nHSV infections are well-studied, but little is known about the frequency of, or outcomes following, subclinical or asymptomatic nHSV. Given the ubiquitous nature of HSV infection and frequency of asymptomatic shedding in adults, subclinical infections are underreported and could contribute to long-term neurological damage. To assess potential neurological morbidity associated with subclinical nHSV infection, we developed a low-dose (100 PFU) intranasal HSV infection model in neonatal wild-type C57BL/6 mice. At this dose, HSV DNA was detected in the brain by quantitative PCR (qPCR) but was not associated with acute clinical signs of infection. However, months after neonatal inoculation with this low dose of HSV, we observed impaired mouse performance on a range of cognitive and memory tests. Memory impairment was induced by infection with either HSV-1 or HSV-2 wild-type viruses, indicating that the cognitive impairment associated with neonatal infection was not strain-specific. Maternal immunization reduced neonate central nervous system (CNS) viral burden and prevented offspring from developing neurological sequelae following nHSV infection. Altogether, these results support the idea that subclinical neonatal infections may lead to cognitive decline in adulthood and that maternal vaccination is an effective strategy for reducing neurological sequelae in infected offspring. These findings may have profound implications for understanding and modeling the etiology of human neurodegenerative disorders such as Alzheimer's Disease.

Perforin-2 is overexpressed in Kikuchi-Fujimoto disease.

Kikuchi-Fujimoto disease (KFD) is a self-limited lymphadenopathy characterized by subcortical necrosis and paracortical proliferation of lymphocytes, histiocytes and plasmacytoid dendritic cells with abundant apoptosis. The etiology of KFD remains unknown. Perforin-2 is a highly conserved transmembrane molecule capable of forming pores following intercellular interaction with bacteria and erythrocytes. Perforin-2 is also essential for the activation of type I interferon-induced JAK/STAT signaling and elimination of virus infection. Herein, we hypothesized that perforin-2 or macrophage-expressed gene 1 (MPEG1) protein function is dysregulated in KFD, resulting in an exaggerated immune response, possibly following exposure to an unknown infectious agent. Twelve cases of KFD were the study group. We isolated total RNA from fixed, paraffin-embedded whole tissue sections. We also assessed primary human B-cells and 4 cases of reactive follicular hyperplasia as controls. Perforin-2 mRNA levels were assessed by quantitative real-time PCR (qRT-PCR). We found that perforin-2 mRNA expression was significantly upregulated in 11 of 12 (92%) KFD cases as compared with control samples. These results suggest that expression of perforin-2 is dramatically upregulated in KFD cases. Increased levels of perforin-2 likely explain the abundant apoptosis in KFD. These data also support the hypothesis that upregulation of perforin-2 may be part of the host immune reaction to an unknown infectious agent that is the trigger for KFD.