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Bloodstream HSV-1 and HSV-2 infections can cause devastating outcomes with high morbidity and mortality, especially in neonates or immunocompromised individuals. Proper patient management for herpes simplex virus (HSV) bloodstream infections is time-sensitive and requires a rapid, accurate, and definitive diagnosis. The absence of the U.S. Food and Drug Administration (FDA)-approved molecular assays for HSV detection in blood, coupled with a lack of consensus on the optimal sample type, underscores the unmet need for improved diagnostics. We prospectively compared the cycle threshold values in paired samples including whole blood (WB), plasma, serum, and peripheral blood mononuclear cells (PBMCs) from patients with bloodstream HSV infections. This analysis employed a modified use of the FDA-cleared Simplexa HSV-1 & 2 Direct assay. The clinical performance in serum was assessed by comparing the results of 247 remnant specimens on this sample-to-answer platform to established laboratory-developed tests in a blinded fashion. Serum samples exhibited significantly lower cycle thresholds than whole blood samples [2.6 cycle threshold (Ct) bias, P < 0.001]. The modified Simplexa assay demonstrated 100% positive percent agreement for the detection of HSV-1 and HSV-2 DNA in serum samples and yielded an overall agreement of 95% (95% CI, 0.92 to 0.97), with a κ statistic of 0.75 (95% CI, 0.62 to 0.86) compared to the composite reference method. Discordance rates were 5.20% for HSV-1 and 0.81% for HSV-2. This investigation demonstrates that serum is an optimal specimen type for HSV detection when compared to several blood compartments. Serum offers a promising sample type for rapid and accurate diagnosis of HSV bloodstream infections using the modified Simplexa assay., Importance: Rapid, accurate, and definitive diagnosis of herpes simplex virus (HSV) infections is crucial in clinical settings for patient management. The absence of FDA-authorized molecular assays for HSV-1/2 detection in blood, coupled with a lack of consensus on the optimal sample type, underscores the need for improved diagnostic methods. Furthermore, rapid diagnosis of HSV bloodstream infections enables timely administration of antiviral treatment, influences patient management decisions for those at high risk, and can contribute to shorter hospital stays, thereby reducing healthcare costs., Competing Interests: The authors declare no conflict of interest.

Herpes Simplex Virus Type 1 (HSV-1) is a widespread human pathogen known for causing a spectrum of clinical manifestations, ranging from mild cold sores to severe complications like encephalitis. Understanding the strain-specific variations of HSV-1 is crucial for elucidating its pathogenesis and developing targeted therapeutic interventions. In this multifaceted study, we investigated the strain-specific characteristics of HSV-1 using an in vivo rat model. Firstly, a pilot study was conducted to assess the capacity of three HSV-1 strains (Fisher (F), KOS (K), and MacIntyre (M)) to induce cold sores in rats. Remarkably, the F strain exhibited pronounced pathogenicity, inducing erythema, swelling, and disrupted epidermis with ulceration, distinguishing it from the K and M strains. Subsequently, the treatment capability of intravenous acyclovir injection in HSV-1 F strain-infected rats was evaluated. Acyclovir treatment resulted in a significant reduction in HSV-1 viral copy numbers in serum and dissected neuronal tissues, particularly in the spinal cord, brain, and lower lip. Lastly, whole genome sequencing data revealed that high-impact mutations occurred in the K and M strains within the UL49, US2, and US3 genes. These mutations may play a pivotal role in influencing viral replication, dissemination, pathogenesis, and infectivity. In contrast, the moderate missense variant mutations detected in the US12, US8, UL3, UL30, UL31, and UL36 genes appeared to have no effect on viral pathogenesis and infectivity, based on RT-PCR data for spinal cord, trigeminal nerve, brain, and the lower lip. These strain-specific mutations underscore the dynamic nature of HSV-1 evolution. Collectively, our findings contribute to a deeper understanding of HSV-1 strain diversity and pave the way for the development of targeted therapeutic strategies against this medically significant virus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to report a case of herpes simplex virus-1 (HSV-1) keratitis misdiagnosed as fungal keratitis due to its clinical presentation being similar to that of fungal keratitis, ultimately diagnosed by NGS. Patients and Methods: A 59-year-old male presented with reduced vision in the right eye, combined with a history of trauma with vegetative matter. The corneal ulcer was accompanied with feathery infiltration, satellite lesion, and endothelial plaques. In vivo confocal microscopy (IVCM) showed hyper-reflective linear, thin, and branching interlocking structures. Fungal keratitis was diagnosed. Voriconazole 100 mg orally daily, topical tobramycin and 1% voriconazole were initiated empirically right away. The condition was aggravated and penetrating keratoplasty was performed. Anterior segment optical coherence tomography (AS-OCT) demonstrated the presence of plaques with a clear boundary between plaques and endothelium, resembling the AS-OCT images observed in cases of viral keratitis. Next-generation sequencing (NGS) further detected HSV-1 deoxyribonucleic acid, and no fungal component was found. Antifungal agents were discontinued and antiviral treatments were added. Results: We successfully treated a patient with HSV-1 keratitis who was misdiagnosed due to clinical features and IVCM findings similar to fungal keratitis. The patient's infection was controlled. At 2 years after surgery, the cornea recovered well. Conclusions: HSV-1 keratitis with atypical clinical presentation can be easily misdiagnosed. This case report emphasizes the importance of NGS in diagnosing the pathogens of keratitis.

Herpes simplex virus involvement of the orbit is rare. We report the case of an immunocompetent patient who presented with preseptal edema, erythema, decreased vision, and dacryoadenitis prior to the appearance of vesicular skin lesions and in the absence of corneal dendrites. The patient's clinical picture failed to improve on empiric therapy with intravenous antibiotics. The patient subsequently developed skin vesicles and a nucleic acid amplification swab of the ocular surface was positive for herpes simplex virus-1. The patient demonstrated rapid clinical improvement after initiation of oral antivirals. This is an unusual case of presumed herpes simplex virus dacryoadenitis preceding skin vesicles in an immunocompetent patient., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Serological screening for TORCH(Toxoplasma gondii [TOX], Rubella virus [RV], Cytomegalovirus [CMV], and Herpes simplex virus [HSV]) infections is an effective method for preventing congenital infections caused by TORCH pathogens.In this study, we retrospectively analyzed the characteristics of TORCH infections in 17,807 infertile women of childbearing age in northwest China.We conducted serological detection of TORCH-pathogen-specific IgM and IgG antibodies. The seroprevalence of TORCH infections was statistically analyzed by applying χ2 and Fisher exact-probability tests to evaluate the differences among ages and across quarters of the year. The overall IgM/IgG seroprevalences of TOX, RV, CMV, HSV-1, and HSV-2 were 0.46/3.4%, 0.77/84.93%, 0.68/97.54%, 1.2/82.83%, and 0.62/10.04%, respectively. The positive rates for RV-IgM in women ≥ 40 years old were significantly higher than those for women 25-39 (P < 0.05) years of age. The seroprevalence of HSV1-IgM was higher in the third and fourth quarters of the year (seasons) (P < 0.001), and the seroprevalence of CMV-IgG was statistically significant between differences quarters (P = 0.017), and the seroprevalence of CMV-IgG in the first quarter was lower than that in the third and fourth quarters (Bonferroni correction, P = 0.009 > 0.0083), suggesting no statistically significant difference between the latter two groups. This study showed that in northwestern China the risk of acquiring primary infection by a TORCH pathogen among infertile women of childbearing age were still high, especially Toxoplasma gondii and Herpesvirus type 2 infection. Therefore, effective prevention strategies that include serological screening for TORCH should be implemented., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Syphilis, caused by Treponema pallidum subsp. pallidum (TPA), is becoming a significant public health concern, with rising incidence in Manitoba exceeding the national average. The province has also seen a demographic shift leading to women representing 51.9% of cases in 2021, leading to the re-emergence of congenital syphilis. Given the similarities in lesion appearance between TPA and other pathogens such as herpesviruses, accurate diagnosis is crucial for effective management and prevention. In order to address the potential for missed TPA cases, we conducted a quality assurance study from June 2021 to March 2023, screening over 5,000 mucocutaneous lesion swabs for TPA, initially submitted for herpes simplex virus (HSV) and varicella zoster virus (VZV) testing. Positivity rates were 13% for HSV1, 13% for HSV2, 6.7% for VZV, and 6.6% for TPA. Turnaround times (TAT) for TPA testing, as a send-out to the reference laboratory, averaged 17.8 days. Of the TPA-positive specimens, 36% did not have a corresponding TPA PCR test ordered, and 19% did not have accompanying syphilis serology within 30 days of collection. Creation of a multiplex lesion panel identified high sensitivity and specificity for HSV1, HSV2, VZV, and TPA, with robust reproducibility across multiple runs. Incorporation of TPA into a lesion panel improved the TAT to 4 days. Our findings emphasize the need for improved testing strategies to combat the syphilis epidemic and enhance public health outcomes.IMPORTANCESyphilis resurgence has become a significant global public health concern. In particular, the Canadian Prairies have been struggling with high incidence since 2016, exceeding the national Canadian average. We undertook a quality assurance study that highlighted significant gaps in diagnosis of acute syphilis, which led to the development of a highly sensitive and specific multiplex lesion assay for the dual detection of herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella zoster virus (VZV), and syphilis., Competing Interests: The authors declare no conflict of interest.

The impact of viral keratitis (VK) on individuals and society is notable. Early diagnosis and treatment are crucial in managing viral keratitis effectively. Timely intervention with antiviral medications and supportive care can help mitigate the severity of the infection and improve visual outcomes. We examined the prevalence of varicella-zoster virus (VZV), herpes simplex virus type 1 (HSV-1), adenovirus (AdV) and herpes simplex virus type 2 (HSV-2) in patients suspected for ocular infections. Patients included in the study exhibited various clinical manifestations indicative of ocular pathology, such as infectious keratitis, corneal scar, endogenous endophthalmitis, panuveitis, endothelitis, stromal edema, and other relevant conditions. Four different types of tear fluid, corneal samples epithelium, aqueous humor and vitreous humor were taken. After genome extraction, multiplex real-time PCR was used for diagnosis of viruses. 48 (29.6%) out of the total of 162 (100%) eye specimen were positive. The dominant prevalence was VZV (12.3%) and HSV-1 (11.7%) followed by AdV (4.9%) and HSV-2 (0.6%). There were 4 (8.3%) coinfections within the samples (HSV-1 and VZV). Aqueous humor samples demonstrated superior virus detection ability and our only HSV-2 positive sample was from aqueous humor. The utilization of multiplex real-time PCR assays in differential diagnosis of VK holds promise for expeditious diagnoses while also preventing unwarranted antibiotic prescriptions. Moreover, the aqueous humor appears to be a more sensitive site for detecting viral keratitis., (© 2024. The Author(s).)

Background: Herpes simplex viruses (HSVs) frequently reactivate during immunosuppression and may be a risk factor for adverse outcomes after solid organ transplant (SOT). While suppressive antiviral therapy reduces the risk of symptomatic HSV reactivation, the kinetics of asymptomatic viral shedding with chronic immunosuppression after transplant are not well understood. We report the characteristics of oral HSV shedding among 15 HSV-1 seropositive SOT recipients (n = 8 liver, n = 7 kidney, median age 58.5 years, median 20 months post-transplant) who were not taking daily antiviral suppressive therapy., Methods: Participants self-collected oral swabs three times daily for 6 weeks for HSV quantification and recorded the presence of oral symptoms or lesions in a diary., Results: Sample collection adherence was high (median 122 swabs/person, range: 85.7%-101.6% of expected swabs). Most participants (n = 12, 80%) experienced at least one shedding episode, with a median shedding rate of 8.9% (range: 0%-33.6%). There were 32 total shedding episodes, 24 (75%) of which occurred without symptoms or lesions. For episodes of known duration, the median length was 21.8 hrs (interquartile range: 10.8-46.1 hrs)., Conclusion: Most shedding episodes (78.1%) lasted >12 hrs, suggesting that twice-daily sampling may be sufficient to detect most episodes. These data show that self-collection of oral swabs is feasible for patients who have undergone SOTs and can provide insight into the frequency of oral HSV reactivation, which can be used to design future studies in this population., (© 2024 Wiley Periodicals LLC.)

We present a case of a primigravida in her 30s who had a caesarean delivery of dichorionic diamniotic twins at 33 weeks of gestation. Her postpartum course was complicated by a herpes simplex virus (HSV) infection of her nipple, found after her neonates were diagnosed with HSV encephalitis. She was evaluated at her 3-week postpartum visit and reported that her neonates were concurrently admitted to the neonatal intensive care unit with disseminated neonatal HSV-1. The patient and her partner were in a monogamous relationship with no known history of HSV. Physical examination demonstrated a vertical fissure on the face of her right nipple and a small cluster of vesicles on her left hand. PCR swabs of the lesions were positive for HSV-1 at both locations. The patient was started on oral valacyclovir 1000 mg two times per day, topical acyclovir ointment applied 4-6 times per day and mupirocin ointment applied 3 times per day to her breast with resolution of her breast lesions. She was able to continue expressing her breastmilk with the help of a pump and then resumed breastfeeding once her infection was cleared. Her infants recovered after prolonged parenteral antiviral therapy with age-appropriate development at follow-up., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A. baumannii is an important and common clinical pathogen, especially in the intensive care unit (ICU). This study aimed to characterize one hypervirulent A. baumannii strain in a patient with community-acquired pneumonia and herpes simplex type 1 virus infection., Methods: Minimum inhibitory concentrations (MICs) were determined using the Kirby-Bauer (K-B) and broth microdilution methods. Galleria mellonella infection model experiment was conducted. Whole-genome sequencing (WGS) was performed using the Illumina and Nanopore platforms. The resistance and virulence determinants were identified using the ABRicate program with ResFinder and the VFDB database. The capsular polysaccharide locus (K locus) and lipooligosaccharide outer core locus (OC locus) were identified using Kleborate with Kaptive. Phylogenetic analyses were conducted using the BacWGSTdb server., Results: A. baumannii XH2146 strain belongs to ST10 Pas and ST447 Oxf . The strain was resistant to cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole (TMP-SMX). Bautype and Kaptive analyses showed that XH2146 contains OCL2 and KL49. WGS analysis revealed that the strain harbored bla ADC-76 , bla OXA-68 , ant(3'')-IIa, tet(B), and sul2. Notably, tet(B) and sul2, both were located within a 114,700-bp plasmid (designated pXH2146-1). Virulence assay revealed A. baumannii XH2146 possessed higher virulence than A. baumannii AB5075 at 12 h. Comparative genomic analysis showed that A. baumannii ST447 strains were mainly isolated from the USA and exhibited a relatively close genetic relationship. Importantly, 11 strains were observed to carry bla OXA-58 ; bla OXA-23 was identified in 11 isolates and three ST447 A. baumannii strains harbored bla NDM-1 ., Conclusions: Early detection of community-acquired hypervirulent Acinetobacter baumannii strains is recommended to prevent their extensive spread in hospitals., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Hemophagocytic lymphohistiocytosis is a severe hyperinflammatory syndrome that can be potentially life-threatening without appropriate treatment. Although viral infection is the most common trigger of hemophagocytic lymphohistiocytosis, cases of herpes simplex virus type 1-induced hemophagocytic lymphohistiocytosis are rare in adults. This study aims to provide a comprehensive overview of the clinical characteristics and treatment outcomes associated with HSV-1-induced HLH. We herein report an adult case of hemophagocytic lymphohistiocytosis caused by herpes simplex virus type 1, diagnosed on the basis of peripheral blood metagenomic next-generation sequencing results. The patient exhibited a favorable response to treatment, involving dexamethasone, intravenous immunoglobulin, and acyclovir. Notably, etoposide administration was deemed unnecessary, and there has been no recurrence of the disease within the year following treatment. Early and sensitive recognition, rapid and precise diagnosis, and timely and appropriate treatment facilitated the successful treatment of this case., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Herpes simplex keratitis stands as a prominent factor contributing to infectious blindness among developed nations. On a global scale, over 60% of the population tests positive for herpes simplex virus type-1 (HSV-1). Despite these statistics, there is currently no vaccine available for the virus. Moreover, the conventional nucleoside drugs prescribed to patients are proving ineffective in addressing issues related to drug resistance, recurrence, latency, and the escalating risk of vision loss. Hence, it is imperative to continually explore all potential avenues to restrict the virus. This review article centers on the present treatment methods for HSV-1 keratitis (HSK), highlighting the ongoing clinical trials. It delves into the emerging drugs, their mode-of-action and future therapeutics., Areas Covered: The review focuses on the significance of a variety of small molecules targeting HSV-1 lifecycle at multiple steps. Peer-reviewed articles and abstracts were searched in MEDLINE, PubMed, Embase, and clinical trial websites., Expert Opinion: The exploration of small molecules that target specific pathways within the herpes lifecycle holds the potential for substantial impact on the antiviral pharmaceutical market. Simultaneously, the pursuit of disease-specific biomarkers has the capacity to usher in a transformative era in diagnostics within the field.

Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide. Despite various campaigns towards the eradication of yaws and elimination of syphilis, these two diseases are still present in Ghana. The aetiological agents of both diseases, two Treponema pallidum subspecies, are genetically similar. This study aimed to assess the prevalence of these treponematoses and the occurrence of pathogens causing similar skin lesions in the Ashanti region of Ghana. A point-of-care test was used to determine the seroprevalence of the treponematoses. Both yaws and syphilis were identified in the Ashanti region of Ghana. Multiplex PCR was used to identify treponemes and other pathogens that cause similar skin lesions. The results indicated that the seroprevalences of T. pallidum in individuals with yaws-like and syphilis-like lesions were 17.2% and 10.8%, respectively. Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and T. pallidum respectively. Among syphilis-like lesions, 28.3% were positive for herpes simplex virus -2 (HSV-2) by PCR. To our knowledge, this is the first time HSV-I and HSV-2 have been reported from yaws-like and syphilis-like lesions, respectively, in Ghana. The presence of other organisms apart from T. pallidum in yaws-like and syphilis-like lesions could impede the total healing of these lesions and the full recovery of patients. This may complicate efforts to achieve yaws eradication by 2030 and the elimination of syphilis and warrants updated empirical treatment guidelines for skin ulcer diseases., Competing Interests: JBP reports research support from Gilead Sciences, non-financial support from Abbott Laboratories, and consulting for Zymeron Corporation, all outside the scope of this work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors declare no com-peting interests., (Copyright: © 2024 Boaitey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Herpes simplex virus type 1 (HSV-1) is one of the most common human viral infections and has a double-stranded DNA genome belonging to the Herpesviridae family. Smoking is one of the leading causes of disease and premature death worldwide, responsible for the death of up to six million people annually. The purpose of the current study was to determine the seroprevalence of HSV-1 infection among smokers.‎ Methods. The search strategy was conducted in the period from December 2022 to January 2023. The study included a random sample of 94 (88 males, and 6 females) healthy participants, aged between ≤ 20 to ≥ 60 years, with 50 participants as the control group. The HSV serological testing consisted of detecting antibodies to HSV-1 IgG with the help of ELISA., Results: Most participants were university students, consisting of 45.7% males and 5.3% females, followed by employed smokers, consisting of 0.2% males and 1.1% females. The number of females was much lower than that of males reaching 6.4 and 93.6% respectively, due to customs and traditions. The seroprevalence was 24.47, 22.3 and 2.1% in males and females respectively. The seroprevalence rate was 13.8% in hookah and cigarette smokers, 9% in cigarette smokers and 1.1% in hookah smokers exclusively. The highest rate was observed in the age groups of 21-30 and 31-40 years with 12.80% and 7.40% respectively., Conclusions: The study revealed that the seroprevalence of HSV-1 IgG was 24.47%, and was higher among hookah and cigarette smokers compared to those who exclusively smoked cigarettes or hookah.

Human parechovirus, a member of the Picornaviridae family (PeVs), can lead to severe infections, including severe meningitis, meningoencephalitis, and sepsis-like syndrome. We report a case of human parechovirus-related encephalitis in a 52-year-old woman diagnosed with glioblastoma multiforme. She underwent surgical resection in June 2022. Unfortunately, her disease recurred, and she underwent a second resection in August 2022, followed by radiation therapy and Temozolomide therapy. She presented to the hospital with acute confusion followed by seizures, necessitating intubation for airway support. A cerebrospinal fluid (CSF) sample was obtained and processed using the Biofire FilmArray, which reported the detection of HSV-1. Despite being on Acyclovir, the patient did not show signs of improvement. Consequently, a second CSF sample was obtained and sent for next-generation sequencing (NGS), which returned a positive result for Parechovirus. In this presented case, the patient exhibited symptoms of an unknown infectious cause. The utilization of NGS and metagenomic analysis helped identify Parechovirus as the primary pathogen present, in addition to previously identified HSV. This comprehensive approach facilitated a thorough assessment of the underlying infection and guided targeted treatment. In conclusion, the application of NGS techniques and metagenomic analysis proved instrumental in identifying the root cause of the infection., (© 2024. The Author(s).)

Introduction: Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients and is associated with a worse outcome. The aim of this study is to determine whether antiviral therapy in HSV-positive patients improves outcome., Methods and Analysis: Prospective, multicentre, open-label, randomised, controlled trial in parallel-group design. Adult, mechanically ventilated patients with pneumonia and HSV type 1 detected in bronchoalveolar lavage (≥10 5 copies/mL) are eligible for participation and will be randomly allocated (1:1) to receive acyclovir (10 mg/kg body weight every 8 hours) for 10 days (or until discharge from the intensive care unit if earlier) or no intervention (control group). The primary outcome is mortality measured at day 30 after randomisation (primary endpoint) and will be analysed with Cox mixed-effects model. Secondary endpoints include ventilator-free and vasopressor-free days up to day 30. A total of 710 patients will be included in the trial., Ethics and Dissemination: The trial was approved by the responsible ethics committee and by Germany's Federal Institute for Drugs and Medical Devices. The clinical trial application was submitted under the new Clinical Trials Regulation through CTIS (The Clinical Trials Information System). In this process, only one ethics committee, whose name is unknown to the applicant, and Germany's Federal Institute for Drugs and Medical Devices are involved throughout the entire approval process. Results will be published in a journal indexed in MEDLINE and CTIS. With publication, de-identified, individual participant data will be made available to researchers., Trial Registration Number: NCT06134492., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Most individuals are latently infected with herpes simplex virus type 1 (HSV-1), and it is well-established that HSV-1 establishes latency in sensory neurons of peripheral ganglia. However, it was recently proposed that latent HSV-1 is also present in immune cells recovered from the ganglia of experimentally infected mice. Here, we reanalyzed the single-cell RNA sequencing (scRNA-Seq) data that formed the basis for that conclusion. Unexpectedly, off-target priming in 3' scRNA-Seq experiments enabled the detection of non-polyadenylated HSV-1 latency-associated transcript ( LAT ) intronic RNAs. However, LAT reads were near-exclusively detected in mixed populations of cells undergoing cell death. Specific loss of HSV-1 LAT and neuronal transcripts during quality control filtering indicated widespread destruction of neurons, supporting the presence of contaminating cell-free RNA in other cells following tissue processing. In conclusion, the reported detection of latent HSV-1 in non-neuronal cells is best explained using compromised scRNA-Seq datasets.IMPORTANCEMost people are infected with herpes simplex virus type 1 (HSV-1) during their life. Once infected, the virus generally remains in a latent (silent) state, hiding within the neurons of peripheral ganglia. Periodic reactivation (reawakening) of the virus may cause fresh diseases such as cold sores. A recent study using single-cell RNA sequencing (scRNA-Seq) proposed that HSV-1 can also establish latency in the immune cells of mice, challenging existing dogma. We reanalyzed the data from that study and identified several flaws in the methodologies and analyses performed that invalidate the published conclusions. Specifically, we showed that the methodologies used resulted in widespread destruction of neurons which resulted in the presence of contaminants that confound the data analysis. We thus conclude that there remains little to no evidence for HSV-1 latency in immune cells., Competing Interests: The authors declare no conflict of interest.

The knife-cut sign is a distinctive manifestation of herpes simplex virus (HSV) type 1 or HSV type 2 infection that has been described in at least 10 immunocompromised patients. It appears as an extremely painful linear erosion or fissure in an intertriginous area such as the body folds beneath the breast, or within the abdomen, or in the inguinal region. Also, concurrent HSV infection at other mucocutaneous sites, or viscera, or both have been observed. The patients had medical conditions (at least 9 patients) and/or immunosuppressive drug therapy (6 patients). The diagnosis of HSV infection was confirmed by viral culture (8 patients), biopsy (4 patients), direct fluorescence antibody testing (3 patients), immunohistochemistry staining (2 patients), polymerase chain reaction (2 patients), or Western blot serologic assay (1 patient). Knife-cut sign-associated HSV infection is potentially fatal; three patients died. However, clinical improvement or complete healing occurred in the patients who received oral valacyclovir (1 patient), or intravenous acyclovir (2 patients), or intravenous acyclovir followed by foscarnet (1 patient). In summary, HSV infection associated with a positive the knife-cut sign is a potentially fatal variant of HSV infection that occurs in the intertriginous areas of immunocompromised patients and usually requires intravenous antiviral therapy.

Herpetic geometric glossitis is a unique morphologic variant of HSV (herpes simplex virus) type 1 infection on the dorsum of the tongue that presents as an extremely painful linear central lingual fissure with a branched pattern. in the center of the tongue; there is a branched pattern of fissures that extend bilaterally from the central linear fissure. Herpetic geometric glossitis has been reported in 11 patients; 8 of these individuals were immunocompromised. Medical conditions and immunosuppressive medication treatment (7 patients) or only medical disorders (3 patients) or neither (1 patient) were present. HSV type 1 infection was diagnosed by viral culture in (7 patients), Tzanck preparation (2 patients) or clinically (2 patients). Mucocutaneous HSV infection at non-lingual locations--including the lips, labial mucosa, face and chest--were observed in 5 patients. All patients' symptoms and lesions responded to treatment with oral antiviral therapy: acyclovir (9 patients), famciclovir (1 patient) or valacyclovir (1 patient). The lingual pain and dorsal tongue fissures completely resolved completely within two to 14 days. In summary, herpetic geometric glossitis is a unique HSV type 1 infection, usually in immunocompromised patients, that occurs on the dorsal tongue and responds completely after treatment with orally administered antiviral therapy.

Introduction: The epidemiology of encephalitis varies by region and time. Available Finnish data are outdated and there are no data from eastern parts of the country nor concerning the occurrence of autoimmune encephalitides., Materials and Methods: Patients with encephalitis were identified from mandatory administrative registries in North Karelia Central Hospital. The diagnoses were verified and data extracted by reviewing the patient records. Study period was 2010-2021. Only patients &gt;16 years of age were included., Results: Fifty-one patients with a clinical encephalitis were identified (55% men) with a median age of 65 years (interquartile range 45, 73; total age range 16-88 years) indicating a crude incidence of 3.1/100,000 person-years for the entire study period. A specific aetiology could be identified in 31 cases (61%) with tick-borne encephalitis (TBE) being the most common one (20% of all 51 cases), followed by herpes simplex virus type 1 (HSV-1, 16%) and varicella zoster virus (VZV, 14%). Autoimmune aetiology was confirmed in 10%. TBE was most often found in the youngest age group (16-52 years of age) and the herpes viruses in the oldest group (71 years or older). A specific cause was most often identified in the oldest patients (78%). TBE patients were younger than patients with VZV (p = 0.0009) or HSV-1 (p = 0.0057), but there was no difference when they were compared to patients with autoimmune (p = 0.27) or unknown (p = 0.074) aetiology. At presentation, there were differences in the occurrence of some clinical signs and symptoms between aetiologies but nothing specific. Eight patients (16%) were immunosuppressed. Inpatient seizures occurred in 10 patients (20%). In these cases, the aetiology was HSV-1 in 50% and TBE or VZV in none. A full recovery was observed in 51% of all patients while 3 patients (6%) had died of the encephalitis while in hospital or shortly after discharge., Conclusions: Adult-onset encephalitis was more common and the patients older in easternmost Finland than previously reported in other parts of the country. TBE, HSV-1, and VZV are the most commonly identified specific aetiologies whereas a fifth of the cases are probably caused by autoimmunity. Prognosis depended on aetiology but was very good in the majority of cases., (© 2024 S. Karger AG, Basel.)

Background: The recent mpox outbreak has highlighted the need to rapidly diagnose the causative agents of viral vesicular disease to inform treatment and control measures. Common causes of vesicular disease include Monkeypox virus (MPXV), clades I and II, Herpes simplex viruses Type 1 and Type 2 (HSV-1, HSV-2), human herpes virus 6 (HHV-6), Varicella-zoster virus (VZV) and Enteroviruses (EVs). Here, we assessed a syndromic viral vesicular panel for rapid and simultaneous detection of these 7 targets in a single cartridge., Objective: The aim of this study was to evaluate the QIAStat-Dx ® viral vesicular (VV) panel and compare with laboratory developed tests (LDTs). Limit of detection, inter-run variability, cross-reactivity and specificity were assessed. Positive and negative percent agreement, and correlation between assays was determined using 124 clinical samples from multiple anatomical sites., Results: The overall concordance between the QIAstat and LDTs was 96%. Positive percent agreement was 82% for HHV-6, 89% for HSV-1 and 100% for MPXV, HSV-2, EV and VZV. Negative percent agreement was 100% for all targets assessed. There was no cross-reactivity with Vaccinia, Orf, Molluscum contagiosum viruses, and a pooled respiratory panel., Conclusion: The QIAstat VV multi-target syndromic panel combine ease of use, rapid turnaround, good sensitivity and specificity for enhanced diagnosis, clinical care and public health responses., Competing Interests: Declaration of Competing Interest The authors do not have any conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Since December 2019 the world has been facing the outbreak of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Identification of infected patients and discrimination from other respiratory infections have so far been accomplished by using highly specific real-time PCRs. Here we present a rapid multiplex approach (RespiCoV), combining highly multiplexed PCRs and MinION sequencing suitable for the simultaneous screening for 41 viral and five bacterial agents related to respiratory tract infections, including the human coronaviruses NL63, HKU1, OC43, 229E, Middle East respiratory syndrome coronavirus, SARS-CoV, and SARS-CoV-2. RespiCoV was applied to 150 patient samples with suspected SARS-CoV-2 infection and compared with specific real-time PCR. Additionally, several respiratory tract pathogens were identified in samples tested positive or negative for SARS-CoV-2. Finally, RespiCoV was experimentally compared to the commercial RespiFinder 2SMART multiplex screening assay (PathoFinder, The Netherlands)., Competing Interests: The authors have declared that no competing interests exist.

Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hematological malignancies not undergoing allogeneic or autologous hematopoietic stem cell transplantation or other cellular therapy including diagnostic, prophylactic, and therapeutic aspects. Particularly, strategies of risk adapted pharmacological prophylaxis and vaccination are outlined for different patient groups. This guideline updates the guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) from 2015 "Antiviral prophylaxis in patients with solid tumours and haematological malignancies" focusing on herpes simplex virus and varicella zoster virus., (© 2022. The Author(s).)

The present study describes a 19-year-old woman with systemic herpes simplex virus (HSV)-1 infection and hemophagocytic lymphohistiocytosis (HLH) postpartum, and a fatal course of neonatal herpesvirus infection. Functional investigation of cells from the mother demonstrated significantly impaired induction of antiviral interferons and cytokines in the context of normal activation of the transcription factors NF-κB and IRF3. Whole-exome sequencing did not reveal any functionally validated genetic variants. We suggest that the functionally impaired antiviral responses, potentially caused by a variant in CASP8 or other variants in noncoding regions of the genome, contributed to the unusually severe disease course observed in two generations., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Abstract: Three α-herpesviruses are known to be associated with central nervous system (CNS) infection; however, there are limited data on the incidence and clinical characteristics of α-herpesviruses CNS infections. This study aimed to assess the clinical manifestations, laboratory findings, and outcomes in patients with human herpes simplex virus 1 (HSV-1), human herpes simplex virus 2 (HSV-2), and varicella-zoster virus (VZV) CNS infections.We identified cases of HSV-1, HSV-2, and VZV CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with HSV-1, HSV-2, and VZV polymerase chain reaction positivity in cerebrospinal fluid (CSF) who visited Pusan National University Hospital between 2010 and 2018.During the 9-year study period, a total of 727 CSF samples were examined, with 72.2% (525/727) patients identified as having a CNS infection. Of 471 patients with aseptic meningitis and encephalitis, the causative virus was identified in 145 patients, and no virus was detected in 337 patients. A total of 15.2% (80/525) were diagnosed with one of the 3 herpesviruses as causative agents, 59 patients had meningitis, and 21 patients had encephalitis. Eleven patients with HSV-1, 27 patients with HSV-2, and 42 patients with VZV CNS infections were included. The distribution of cases by age showed different patterns depending on the type of herpesvirus infection. Compared with the HSV-1 group, the median age in the HSV-2 group was younger (HSV-1: 58 years; HSV-2: 38 years; P = .004), and patients with VZV infections showed a bimodal age distribution. Encephalitis was more common in the HSV-1 group, and HSV-1 infection was associated with a poor prognosis at discharge. CSF white blood cell counts were significantly lower in patients infected with HSV-1 (117 × 106 cells/L) than in patients infected with VZV (301 × 106 cells/L) (P = .008).These 3 herpesviruses are important causes of CNS infections regardless of immunologic status. HSV-1 infection was commonly associated with encephalitis and poor prognosis; HSV-2 and VZV CNS infections were associated with a low risk of mortality and neurological sequelae., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose : To compare the Schlemm's canal area (SCA) and to define iris features in patients with unilateral herpetic anterior uveitis (HAU) by using anterior segment spectral-domain optical coherence tomography (AS SD-OCT). Methods : Unilateral HAU cases that had been in complete remission for ≥ 3 months were included. Two investigators analyzed the iris features of HAU. SCA in both healthy (N), and affected eyes (HAU) were compared. Results : The mean age of the participants (n = 22) was 36.3 ± 15 (17-70) years. The mean nasal and temporal (n-t) SCA was measured as 10,844 ± 4806 µm 2 and 8,772 ± 3138 µm 2 in HAU in comparison with 10,200 ± 4,824 µm 2 and 10,045 ± 3,889 µm 2 in N, respectively ( p = .47 and p = .12, respectively). The most common iris features were the sectoral iridoplegia (100%) on biomicroscopy and the disorganization of the iris layers (DIL) (77%) on AS SD-OCT images. Conclusion : SCA found similar on both sides. DIL is the most common iris feature of affected eyes.

Herpes simplex virus 1 (HSV-1) is responsible for herpes simplex virus encephalitis (HSE), associated with a 70% mortality rate in the absence of treatment. Despite intravenous treatment with acyclovir, mortality remains significant, highlighting the need for new anti-herpetic agents. Herein, we describe a novel neurovirulent recombinant HSV-1 (rHSV-1), expressing the fluorescent tdTomato and Gaussia luciferase (Gluc) enzyme, generated by the Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) (CRISPR-Cas9) system. The Gluc activity measured in the cell culture supernatant was correlated (P = 0.0001) with infectious particles, allowing in vitro monitoring of viral replication kinetics. A significant correlation was also found between brain viral titers and Gluc activity in plasma (R 2  = 0.8510, P < 0.0001) collected from BALB/c mice infected intranasally with rHSV-1. Furthermore, evaluation of valacyclovir (VACV) treatment of HSE could also be performed by analyzing Gluc activity in mouse plasma samples. Finally, it was also possible to study rHSV-1 dissemination and additionally to estimate brain viral titers by in vivo imaging system (IVIS). The new rHSV-1 with reporter proteins is not only as a powerful tool for in vitro and in vivo antiviral screening, but can also be used for studying different aspects of HSE pathogenesis., (© 2021. The Author(s).)

Darier disease (DD) is a rare autosomal dominant keratinizing disorder often characterized by brown scaly pruritic papules over the face, neck, and trunk. Herein is reported a patient who developed secondary cutaneous herpes simplex virus (HSV) following exacerbation of his DD as a result of radiation therapy. In November 2020, a 78-year-old man presented to clinic for a pruritic rash on his back consistent with DD. He had developed the rash after the conclusion of chemoradiation therapy for recently diagnosed urothelial carcinoma of the bladder with squamous differentiation. However, he returned two weeks later complaining of a marked worsening of the rash associated with a pain and burning sensations. Histopathology was non-conclusive, but the lesions were found to be positive for HSV-1 by PCR. The patient recovered without complication over a period of two weeks following a course of valacyclovir. There is precedent in the literature for ionizing radiation inducing flares of DD lesions in overlying skin. In addition, DD has been shown to put a patient at increased risk for secondary infections such as HSV. This case report demonstrates that HSV could pose a significant risk to those with DD receiving radiation therapy and thus could warrant prophylactic treatment.

Herpes simplex virus (HSV) infections of the lung are rare, but HSV is occasionally detected in bronchoalveolar lavage (BAL) specimens. We assessed whether routinely performing HSV PCR tests in BAL specimens is warranted. HSV was detected in 7% (52/722) of BALs. In 47% of HSV-positive patients a typical respiratory virus or pathologic microorganism was identified. Oral HSV reactivation was identified in 27%; however, anti-HSV therapy was initiated in just three patients following the positive HSV test. Patients undergoing BAL for transplant surveillance received anti-HSV prophylaxis more often than those with acute respiratory failure, but both groups did not differ significantly in terms of patient outcome or co-infections. No patient was diagnosed with HSV pneumonia. These findings suggest that positive HSV PCR results in BAL specimens most commonly represents contamination from oral HSV reactivation, and that HSV PCR should be ordered selectively, rather than routinely, as part of a test panel., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study evaluated the impact of the TLR7 Gln11Leu (rs179008) and TLR9 -1237 T/C (rs5743836) single nucleotide polymorphisms (SNPs) on susceptibility to placental infections and pregnancy complications in 455 Brazilian women. Demographic, socioeconomic, gynecological, and clinical characteristics of the women were collected. Placental tissues were sampled from pregnant women and human and viral DNA was extracted. Human alphaherpesvirus 1 (Herpes simplex virus type 1, HSV-1), Human alphaherpesvirus 2 (Herpes simplex virus type 2, HSV-2) and Human betaherpesvirus 5 (Human cytomegalovirus, HCMV) were detected by nested PCR. TLR9 and TLR7 SNPs were genotyped by PCR amplification of bi-directional specific alleles (Bi-PASA) and restriction fragment length polymorphism (RFLP), respectively. Infections at the time of birth were detected in 45.71 % of women. The presence of the TT genotype (recessive model) of the TLR7 SNP was associated with increased susceptibility to HSV-1 infection (O.R. = 2.23, p = 0.05). The presence of the C allele of the TLR9 SNP, in heterozygosis or homozygosis (dominant model), decreased the infection risk by HCMV (O.R. = 0.31, p-mod<0.05). The TT genotype (recessive model) of the TLR7 SNP was significantly associated (p < 0.05) with increased occurrence of pre-treated hypertension. The codominant model of the TLR9 SNP was significantly associated (p < 0.05) with reduced risk of hospitalization during pregnancy. In combination, the AA/CT (TLR7-TLR9) genotypes significantly decreased the risk of placental infection by HSV-1 and/or HSV-2 (O.R. = 0.47, p = 0.02), the susceptibility to all infectious agents considered in combination (O.R. = 0.4, p = 0.00), and the need of hospitalization (O.R. = 0.48, p = 0.02). In conclusion, TLR7 and TLR9 SNPs are potential modulating factors for the risk of placental infections and pregnancy complications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

SARS-CoV-2 infection can lead to severe acute respiratory distress syndrome with the need of invasive ventilation. Pulmonary herpes simplex-1 (HSV-1) reactivation in invasively ventilated patients is a known phenomenon. To date very little is known about the frequency and the predisposing factors of HSV-1 reactivation in COVID-19. Therefore, we evaluated our cohort of invasively ventilated COVID-19 patients with severe pneumonia for HSV-1 in respiratory specimens and combined these results with functional immunomonitoring of the peripheral blood. Tracheal secretions and bronchial lavages were screened by PCR for HSV-1 positivity. Comprehensive immunophenotyping and quantitative gene expression analysis of Interferon-stimulated genes (IFI44L, MX1, RSAD2, ISIG15 and IFIT1) and IL-1 beta were performed in whole blood. Time course of infection beginning at symptom onset was grouped into three phases ("early" phase 1: day 1-10, "middle" phase 2: day 11-30 and "late" phase 3: day 31-40). Pulmonary HSV-1 reactivation was exclusively observed in the later phases 2 and 3 in 15 of 18 analyzed patients. By FACS analysis a significant increase in activated CD8 T cells (CD38+HLADR+) in phase 2 was found when compared with phase 1 (p<0.05). Expression of Interferon-stimulated genes (IFI44L, RSAD2 ISIG15, MX1, IFIT1) was significantly lower after HSV-1 detection than before. Taken together, reactivation of HSV-1 in the later phase of SARS-CoV-2- infection occurs in parallel with a drop of antiviral innate responsiveness as shown by decreased expression of Interferon-stimulated genes and a concurrent increase of highly activated CD38+HLADR+ CD8 T cells., Competing Interests: The authors have declared that no competing interests exist.

Acute retinal necrosis (ARN) is a form of infectious uveitis caused by alpha herpesviruses, including herpes simplex virus type 1 (HSV-1). We previously found that the long non-coding RNA (lncRNA) U90926 is upregulated in murine retinal photoreceptor cells following HSV-1 infection, leading to host cell death. However, to date, an orthologous transcript has not been identified in humans. We investigated U90926 orthologous transcript in humans and examined its utility as a prognostic marker for visual acuity in patients with ARN. We identified two human orthologous transcripts (1955 and 592 bases) of lncRNA U90926. The amount of the longer human U90926 transcript was approximately 30- and 40-fold higher in the vitreous fluid of patients with ARN than in those with sarcoidosis and intraocular lymphoma, respectively. Furthermore, the expression of the longer human U90926 transcript in the vitreous fluid was highly correlated with the final best-corrected logarithm of the minimum angle of resolution visual acuity in patients with ARN (r = 0.7671, p = 0.0079). This suggests higher expression of the longer human U90926 transcript in the vitreous fluid results in worse visual prognosis; therefore, expression of the longer human U90926 transcript is a potential negative prognostic marker for visual acuity in patients with ARN.

Purpose: To report clinical features of acute retinal necrosis (ARN) using optical coherence tomography angiography., Methods: A 59-year-old female patient presented with blurred vision in the left eye for 1 day. The patient presented posterior uveitis with multiple peripheral areas of retinal pallor with presumed acute retinal necrosis. Herpes simplex virus Type 1 infection was confirmed after serologic tests, and the polymerase chain reaction analysis of the aqueous humor tested positive., Results: The left eye examination revealed anterior chamber reaction, mild vitritis, optic disk swelling, and yellowish white retinal lesions with discrete borders along the superotemporal arcade and temporal periphery. Baseline optical coherence tomography angiography revealed decreased vascular density of superficial and deep plexuses of superotemporal macular region. One month after oral valacyclovir 2,000 mg twice daily, visual acuity and retinal lesions improved, and optical coherence tomography angiography images showed improvement of vascular density., Conclusion: Occlusive arterial vasculopathy is one of the main clinical characteristics of acute retinal necrosis. We herein describe for the first time the features of retinal vasculature in acute retinal necrosis revealed by optical coherence tomography angiography, showing decreased vascular density of superficial and deep plexuses.

After allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially from an unrelated donor, infectious complications are frequent and severe, sometimes with fatal outcomes. Despite using highly sensitive molecular techniques for close monitoring in the early post-transplant period for early diagnosis, not every viral infection or reactivation can be detected adequately early, even with highly sensitive methods. Particularly after toxic and deeply immunosuppressive treatment, multiple infections or reactivations, uncommon infections, or infections in unusual locations can occur. Here, we present a case of multiple viral infections or reactivations and cerebral toxoplasmosis in a 17-year-old youth with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) treated with allo-HSCT who suffered multiple viral infections followed by cerebral toxoplasmosis., (Copyright © 2021. Published by Elsevier Inc.)

Neonatal herpes simplex virus (HSV) infection is rare, with an estimated incidence of 3.58 per 100 000 live births in the UK and should be suspected in any newborn with fever and bacterial culture-negative sepsis. We describe a case of a previously well full-term male neonate who presented with persistent fever and elevated ferritin level that was carried out during the era of the COVID-19 pandemic as part of SARS-CoV-2 panel investigations. Despite the initial negative HSV serology, HSV-1 PCR from a scalp lesion returned positive. He made a full recovery after acyclovir therapy. This case highlights the importance of maintaining a high clinical index of suspicion of HSV infection in any febrile neonate even with absence of maternal history and negative serology, particularly if associated with hyperferritinaemia. We also address the challenge of interpreting inflammatory biomarkers' results for SARS-CoV-2 infection in neonates., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The role of viruses as a cause of breast cancer (BC) has been significantly investigated in recent years. Human papillomavirus (HPV) has been detected in invasive breast carcinomas, while most studies have only focused on the detection of viral DNA, we aimed to examine the prevalence and genotypes of HPV among Iranian BC patients. We also examined the presence of herpes simplex-1 (HSV-1), herpes simplex-2 (HSV-2), varicella zoster virus (VZV), and cytomegalovirus (CMV) in these samples., Methods: We collected and analyzed 70 Formalin-Fixed Paraffin-Embedded (FFPE) blocks including 59 BC samples, and 11 benign breast lesions as control from Iranian patients using nested PCR. Real-time PCR utilized as a confirming test to nested PCR findings. Genotyping of HPV positive samples was performed, the samples were also subjected to a multiplex PCR to detect HSV-1, HSV-2, VZV, and CMV in BC., Results: Papillomavirus DNA was present in 7 of 59 BC samples (11.8%); while none was detected in control samples. The most prevalent type was HPV18, followed by HPV 6. All HPV positive patients had high tumor grades (II/ III) with a histologic diagnosis of ductal carcinoma. The patient age range was 33 to 73 years with a median of 51 years. Most of HPV positive patients had low levels of education. HPV16 was not detected. Also, 5 of 59 BC specimens (8.47%), were positive for HSV-1. But none of the samples were positive for HSV-2, VZV, and CMV., Conclusions: Our results suggest a carcinogenesis role for High-risk HPV (HPV18) in breast tumors. Our findings of HSV-1 and low-risk HPV (HPV6) in BCs may propose a cancer-causing role for them. Further large-scale studies are warranted to assess the significance of our findings.

Background: An association between chronic infectious diseases and development of dementia has been suspected for decades, based on the finding of pathogens in postmortem brain tissue and on serological evidence. However, questions remain regarding confounders, reverse causality, and how accurate, reproducible and generalizable those findings are., Objective: Investigate whether exposure to Herpes simplex (manifested as herpes labialis), Chlamydophila pneumoniae (C. pneumoniae), Helicobacter pylori (H. pylori), and cytomegalovirus (CMV) modifies the risk of dementia in a populational cohort., Methods: Questionnaires regarding incidence of herpes infections were administered to Original Framingham Study participants (n = 2,632). Serologies for C. pneumoniae, H. pylori, and CMV were obtained in Original (n = 2,351) and Offspring cohort (n = 3,687) participants. Participants are under continuous dementia surveillance. Brain MRI and neuropsychological batteries were administered to Offspring participants from 1999-2005. The association between each infection and incident dementia was tested with Cox models. Linear models were used to investigate associations between MRI or neuropsychological parameters and serologies., Results: There was no association between infection serologies and dementia incidence, total brain volume, and white matter hyperintensities. Herpes labialis was associated with reduced 10-year dementia risk (HR 0.66, CI 0.46-0.97), but not for the duration of follow-up. H. pylori antibodies were associated with worse global cognition (β -0.14, CI -0.22, -0.05)., Conclusion: We found no association between measures of chronic infection and incident dementia, except for a reduction in 10-year dementia risk for patients with herpes labialis. This unexpected result requires confirmation and further characterization, concerning antiviral treatment effects and capture of episodes.

Acyclovir is the drug of choice for the treatment of herpes simplex virus (HSV) infections. Acyclovir-resistant HSV strains may emerge, especially during long-term drug use, and subsequently cause difficult-to-treat exacerbations. Previously, we set up a novel treatment approach, based on enzymatically synthesized pools of siRNAs, or siRNA swarms. These swarms can cover kilobases-long target sequences, reducing the likelihood of resistance to treatment. Swarms targeting the UL29 essential gene of HSV-1 have demonstrated high efficacy against HSV-1 in vitro and in vivo. Here, we assessed the antiviral potential of a UL29 siRNA swarm against circulating strains of HSV-1, in comparison with acyclovir. All circulating strains were sensitive to both antivirals, with the half-maximal inhibitory concentrations (IC 50 ) in the range of 350-1911 nM for acyclovir and 0.5-3 nM for the UL29 siRNA swarm. Additionally, we showed that an acyclovir-resistant HSV-1, devoid of thymidine kinase, is highly sensitive to UL29 siRNA treatment (IC 50 1.0 nM; I max 97%). Moreover, the detected minor variations in the RNAi target of the HSV strains had no effect on the potency or efficacy of UL29 siRNA swarm treatment. Our findings support the development of siRNA swarms for the treatment of HSV-1 infections, in order to circumvent any potential acyclovir resistance.

Background: The current outbreak of COVID-19 has spread rapidly all over the world. Respiratory droplets and contaction with infected patients are the two major transmission routes. However, the value of tear virus nucleic acid is still not clear. We dynamic detected the SARS-CoV-2 in eye sample of one COVID-19 patient with obstruction of common lacrimal ducts., Methods: Besides the routine examination, nasopharyngeal and eye swab were continuously measured by polymerase chain reaction assay and next-generation sequencing (NGS). Gene detection was performed for drug use guidance, and flow cytometry was performed to analyse the lymphocyte subsets., Results: Nasopharyngeal swabs were positive for 22 days, but eye swabs were still continuously positive for 2 weeks after nasopharyngeal swabs turned negative. The low level of lymphocyte and the high level IL-6 lasted for almost 4 weeks, then became near normal. Next-generation sequencing (NGS) confirmed the existing of SARS-CoV-2, HSV1 and HHV6B virus nucleic acid. The gene detection for drug use guidance showed the genetic locus ABCB1 (3435T>C) rs1045642 belonged to type CC and it mean the efficiency of lopinavir-ritonavir would be significantly decreased. The flow cytometry of lymphocyte subsets showed PD-1 +  CD95 + cells was accounting for 94.8% in CD3 +  CD8 + T subset and for 94.8% in CD3 +  TCRγδ + T subset., Conclusions: As obstruction of common lacrimal duct, positively detection in one eye for 2 weeks more after nasopharyngeal swab became negative. More eye swabs should be collected from COVID-19 patients, especially from those immunocompromised, those with eye symptoms and those had a history of ocular diseases., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Serious burn trauma is associated with changes of the immune system, and immunosuppression induced by burn trauma can lead to reactivation of latent infections. Herpetic viruses are known for their lifelong persistence after primary infection and ability to reactivate. Their reactivation in the setting of burn trauma or primary infection can cause serious complications for a weakened burn patient. Presented is a case of a toddler who sustained second-degree scald burns over 20% of his body surface area. The injury was complicated by a multi-resistant bacterial infection in addition to reactivation of a latent HHV-6 infection concurrently with a primary HSV-1 infection. Described further are basic diagnostics, local and systemic treatment strategies, and other complications due to disseminated herpetic infections. To date, HHV-6 reactivation has not been described in conjunction with burn injury.

Background: Herpes simplex virus type 1 (HSV-1) is frequently detected in the BAL fluid of patients on mechanical ventilation., Research Question: The aim of the study was to investigate whether antiviral therapy is associated with improved overall survival within 30 days., Study Design and Methods: This was a retrospective cohort study in four ICUs between January 2011 and December 2017. All adult patients on mechanical ventilation with a respiratory tract infection with positive polymerase chain reaction testing for HSV-1 in the BAL were included. Patients already receiving antiviral agents on the day BAL was performed were excluded. We performed uni- and multivariable Cox and logistic regression modeling., Results: Overall, 306 patients were included in the analysis. Among them, 177 patients (57.8%) received antiviral therapy (90.9% acyclovir, 6.2% ganciclovir, 2.9% both). The overall 30-day mortality rate was 42.4% (n = 75) in the antiviral treatment group and 50.4% (n = 65) in the control group. The adjusted hazard ratio (HR) for the primary outcome was 0.62 (95% CI, 0.44-0.87; P = .005), indicating better overall survival within 30 days for the antiviral-treated group than for the untreated group. This benefit was also present in the subgroup of patients without immunosuppression (n = 246; adjusted HR, 0.53; 95% CI, 0.36-0.78; P = .001). Overall, the median lengths of hospital stay (31 vs 24 days, P = .002) and ICU stay (24 vs 17 days, P < .001), and the duration of mechanical ventilation (18 vs 11 days, P < .001), were longer for patients with therapy. No evidence for the treatment-related deterioration of renal function was observed., Interpretation: These data suggest that detection of HSV-1 in the BAL of patients on mechanical ventilation may be of clinical significance and that specific antiviral treatment may improve clinical outcomes. However, this needs to be proven in multicenter randomized controlled trials before implementation into the clinical routine., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Primary herpetic gingivostomatitis (PHGS) in children, though usually self-limited, might mimic bacterial and enteroviral pharyngitis clinically. We conducted a study to define the clinical features of PHGS in children., Methods: Between January 2012 and December 2016, 282 inpatients aged less than 19 years with cell culture-confirmed herpes simplex virus (HSV) infection in a medical center were identified from the virologic laboratory logbook. Clinical data were retrospectively collected., Results: Among the 282 inpatients, 185 cases were considered as PHGS and were included for analysis. Fever was present in 99.5%. The mean duration of fever was 5.11 days (±2.24) with the longest being 17 days. Common oral manifestations included oral ulcers (84.3%), which equally resided in the anterior and posterior part of the oral cavity (65.4% vs. 63.2%), gum swelling and/or bleeding (67.6%), and exudate coated tonsils (16.8%). Leukocytosis (WBC count > 15,000/uL 3 ) was noted in 52 patients (28.1%) and a serum C-reactive protein level > 40 mg/L in 55 patients (29.7%). Fixty-five patients (35%) were diagnosed with PHGS on admission and were significantly more likely to have ulcers over the anterior oral cavity (76.1% vs. 26.7%) and gum swelling/bleeding (76.2% vs. 7.5%, p-value all < 0.001) on admission and were significantly less likely to receive antibiotic treatment (16.9 vs. 36.7%, p-value < 0.01) than others. Forty-six patients (25%) undiagnosed as PHGS on discharge were significantly more likely to have exudate coated on the tonsils, to receive antibiotic treatment and significantly less likely to have gum swelling/bleeding and oral ulcers (all p-values < 0.01)., Conclusions: Meticulously identifying specific oral manifestations of gum swelling/bleeding and ulcers over the anterior oral cavity in children can help making the diagnosis of PHGS earlier and subsequently reduce unnecessary prescription of antibiotics.