Reactivation Of Latent Virus Research Articles

Kaposi Sarcoma as a Possible Cutaneous Adverse Effect of ChAdOx1 nCov-19 Vaccine: A Case Report

The COVID-19 pandemic prompted the rapid development of vaccines, including the ChAdOx1 nCov-19 (AstraZeneca) vaccine. While effective, adverse effects have been reported, including cutaneous manifestations. Kaposi sarcoma (KS), a vascular tumor linked to Kaposi sarcoma herpesvirus/human herpesvirus 8 (HHV-8), has seen increased detection during the pandemic. This study reports a case of classic cutaneous KS in a 79-year-old male following the first dose of the ChAdOx1 nCov-19 vaccine, without prior SARS-CoV-2 infection. The patient developed multiple reddish-blue papules on his legs and feet, confirmed as KS through histopathology. Treatment included radiotherapy and sequential chemotherapy with Doxorubicin. The potential reactivation of latent HHV-8 by the vaccine is explored through mechanisms involving the SARS-CoV-2 spike protein and adenovirus vector, which may induce immune responses and inflammatory pathways. Although establishing a direct causal link remains challenging, the case highlights the need for vigilance regarding KS reactivation post-vaccination. Further large-scale studies are warranted to elucidate the relationship between COVID-19 vaccines and latent virus reactivation, ensuring comprehensive safety assessments and informed public health decisions.

Lipo-pam™ adjuvanted herpes zoster vaccine induces potent gE-specific cellular and humoral immune responses

Herpes zoster (HZ), also known as shingles, is caused by the reactivation of latent varicella-zoster virus (VZV). Decreased VZV-specific T-cell immune responses significantly contribute to the development of HZ. Shingrix is a recombinant zoster vaccine that is currently used to prevent HZ. However, Shingrix has high reactogenicity and pain at the injection site due to QS21, one of the adjuvant components. In this study, we developed a new herpes zoster vaccine formulation called CVI-VZV-001, containing gE protein and a novel liposome-based adjuvant Lipo-pam™, which consists of two TLR agonists. We evaluated the immunogenicity of CVI-VZV-001 in mouse and rabbit models. CVI-VZV-001 elicited robust gE-specific T-cell immune responses and gE-specific antibody production. Specifically, CVI-VZV-001 induced polyfunctional CD4+ T cell populations that secrete multiple cytokines. Furthermore, CVI-VZV-001 sustained the gE-specific immune responses for up to six months after immunization. To ensure CVI-VZV-001’s safety for further development, we conducted a good laboratory practice (GLP) toxicity test, which confirmed that CVI-VZV-001 is safe for use. At present, CVI-VZV-001 is undergoing phase I clinical trials. This study suggests that CVI-VZV-001 can be a potent candidate for the HZ vaccine with high immunogenicity and safety.

Evidence of aberrant anti-epstein-barr virus antibody response, though no viral reactivation, in people with post-stroke fatigue

BackgroundFatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke.AimsWe performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue.MethodsIn a chronic ischemic stroke cohort (> 5 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F < 40) and low fatigue (FACIT-F > 41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher’s exact test for categorical data.ResultsWe observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar, we observed an altered circulating anti-EBV antibody profile in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (2.244 ± 0.926 vs. 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to anti-EBV antibodies (3.23 × 105 ± 4.44 × 104 high fatigue versus 4.60 × 105 ± 9.28 × 104 low fatigue; P = 0.288).ConclusionsThese data indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke.

Infections and antimicrobial prophylaxis in patients with myelodysplastic syndromes

Infectious complications are an important cause of morbidity and mortality in patients with myelodysplastic syndromes (MDS). Preventing infections could significantly improve both survival and quality of life. Unfortunately, both infections and antimicrobial prophylaxis in patients with MDS are incompletely assessed due to the heterogeneity of disorders included in each publication, changing definitions over time, and lack of standardized prophylaxis practices. Despite these limitations, some basic statements can be made. Infections in MDS are associated with neutropenia. Patients with lower-risk (LR) MDS tend to have fewer infections compared to patients with higher-risk (HR) MDS, which may be related to the different prevalence of neutropenia in the 2 groups. Pneumonia is the most common infection, and bacteria are the most common pathogens. Invasive fungal infections (IFI) are uncommon. Reactivation of latent viruses are rare. With the limited data available, we agree that antibacterial prophylaxis can be considered in patients with HR-MDS during severe neutropenia and early cycles of therapy when infections are most likely to occur. Given the low prevalence of IFI and viral reactivation, antimicrobial prophylaxis for these pathogens is less likely to be advantageous for most patients, although antifungal prophylaxis with activity against mold is commonly used in patients with persistent, profound neutropenia. Ultimately, improved data collection regarding infections and antimicrobial prophylaxis is needed to improve care for patients with MDS.

MENSA, a Media Enriched with Newly Synthesized Antibodies, to Identify SARS-CoV-2 Persistence and Latent Viral Reactivation in Long-COVID.

Post-acute sequelae of SARS-CoV-2 (SARS2) infection (PASC) is a heterogeneous condition, but the main viral drivers are unknown. Here, we use MENSA, Media Enriched with Newly Synthesized Antibodies, secreted exclusively from circulating human plasmablasts, to provide an immune snapshot that defines the underlying viral triggers. We provide proof-of-concept testing that the MENSA technology can capture the new host immune response to accurately diagnose acute primary and breakthrough infections when known SARS2 virus or proteins are present. It is also positive after vaccination when spike proteins elicit an acute immune response. Applying the same principles for long-COVID patients, MENSA is positive for SARS2 in 40% of PASC vs none of the COVID recovered (CR) patients without any sequelae demonstrating ongoing SARS2 viral inflammation only in PASC. Additionally, in PASC patients, MENSAs are also positive for Epstein-Barr Virus (EBV) in 37%, Human Cytomegalovirus (CMV) in 23%, and herpes simplex virus 2 (HSV2) in 15% compared to 17%, 4%, and 4% in CR controls respectively. Combined, a total of 60% of PASC patients have a positive MENSA for SARS2, EBV, CMV, and/or HSV2. MENSA offers a unique antibody snapshot to reveal the underlying viral drivers in long-COVID thus demonstrating the persistence of SARS2 and reactivation of viral herpes in 60% of PASC patients.

CRISPR/Cas9-mediated genome editing of the thymidine kinase gene in a clinical HSV-1 isolate identifies F289S as novel acyclovir-resistant mutation

Herpes simplex virus type 1 (HSV-1) is a neurotropic alphaherpesvirus that establishes a lifelong infection in sensory neurons of infected individuals, accompanied with intermittent reactivation of latent virus causing (a)symptomatic virus shedding. Whereas acyclovir (ACV) is a safe and highly effective antiviral to treat HSV-1 infections, long-term usage can lead to emergence of ACV resistant (ACVR) HSV-1 and subsequently ACV refractory disease. Here, we isolated an HSV-1 strain from a patient with reactivated herpetic eye disease that did not respond to ACV treatment. The isolate carried a novel non-synonymous F289S mutation in the viral UL23 gene encoding the thymidine kinase (TK) protein. Because ACV needs conversion by viral TK and subsequently cellular kinases to inhibit HSV-1 replication, the UL23 gene is commonly mutated in ACVR HSV-1 strains. The potential role of the F289S mutation causing ACVR was investigated using CRISPR/Cas9-mediated HSV-1 genome editing. Reverting the F289S mutation in the original clinical isolate to the wild-type sequence S289F resulted in an ACV-sensitive (ACVS) phenotype, and introduction of the F289S substitution in an ACVS HSV-1 reference strain led to an ACVR phenotype. In summary, we identified a new HSV-1 TK mutation in the eye of a patient with ACV refractory herpetic eye disease, which was identified as the causative ACVR mutation with the aid of CRISPR/Cas9-mediated genome engineering technology. Direct editing of clinical HSV-1 isolates by CRISPR/Cas9 is a powerful strategy to assess whether single residue substitutions are causative to a clinical ACVR phenotype.

Interactions of TTV with BKV, CMV, EBV, and HHV-6A and their impact on post-transplant graft function in kidney transplant recipients.

Mono and combined reactivation of latent viruses occurs frequently under immunosuppressive therapy in kidney transplant patients. Recently, monitoring torque teno virus (TTV) reactivation came more into focus as a potential biomarker for immune status. The surrogate characteristics of TTV reactivation on acute rejection, and the combined reactivation with other latent viruses such as cytomegalovirus (CMV), human BK virus (BKV), Epstein-Barr virus (EBV), and human herpes virus-6A (HHV-6A) on allograft function, are unknown so far. Blood samples from 93 kidney transplant recipients obtained during the first post-transplant year were analyzed for TTV/BKV/CMV/EBV/HHV-6A load. Clinical characteristics, including graft function [glomerular filtration rate (GFR)], were collected in parallel. TTV had the highest prevalence and viral loads at 100% and a mean of 5.72 copies/ml (cp/ml) (log10). We found 28.0%, 26.9%, 7.5%, and 51.6% of simultaneous reactivation of TTV with BKV, CMV, EBV, and HHV-6, respectively. These combined reactivations were not associated with a significantly reduced estimated GFR at month 12. Of interest, patients with lower TTV loads <5.0 cp/ml (log10) demonstrated not only a higher incidence of acute rejection, but also an unexpected significantly earlier occurrence and higher incidence of BKV and HHV-6A reactivation. Correlations between TTV loads, other latent viruses, and immunosuppressive medication were only significant from 6 months after transplant. We were able to observe and support previously introduced TTV load thresholds predicting kidney allograft rejection. However, due to a possible delayed relation between immunosuppressive medication and TTV viral load adaptation, the right time points to start using TTV as a biomarker might need to be further clarified by other and better designed studies.

Neuralgia Pasca Herpes

Herpes zoster, also known as snake pox and shingles , is a skin disease caused by reactivation of latent varicella zoster virus (VVZ) infection also known as human herpesvirus-3 (HHV-3) in the dorsal root sensory ganglion after primary infection. Mrs. A, 64 years old female was consulted with complaints of burning pain in the lower right abdomen to the right waist, that happened approximately 2 month after diagnosed with herpes zoster. Based on anamneses and physical examination the patient was diagnosed by Postherpetic neuralgia. Postherpetic neuralgia is persistent chronic pain and the most common complication in herpes zoster. In the majority of patients, pain from shingles is usually felt within 2 to 4 weeks. However, patients who experience NPH will experience continuous pain at the site of infection for 3 to 9 weeks after infection. The patients was given supportive treatment accompanied by education that can be provided to relieve the symptoms caused by this disease.

Long COVID and post-acute sequelae of SARS-CoV-2 pathogenesis and treatment: A Keystone Symposia report.

In 2023, the Keystone Symposia held the first international scientific conference convening research leaders investigating the pathology of post-acute sequelae of COVID-19 (PASC) or Long COVID, a growing and urgent public health priority. In this report, we present insights from the talks and workshops presented during this meeting and highlight key themes regarding what researchers have discovered regarding the underlying biology of PASC and directions toward future treatment. Several themes have emerged in the biology, with inflammation and other immune alterations being the most common focus, potentially related to viral persistence, latent virus reactivation, and/or tissue damage and dysfunction, especially of the endothelium, nervous system, and mitochondria. In order to develop safe and effective treatments for people with PASC, critical next steps should focus on the replication of major findings regarding potential mechanisms, disentangling pathogenic mechanisms from downstream effects, development of cellular and animal models, mechanism-focused randomized, placebo-controlled trials, and closer collaboration between people with lived experience, scientists, and other stakeholders. Ultimately, by learning from other post-infectious syndromes, the knowledge gained may help not only those with PASC/Long COVID, but also those with other post-infectious syndromes.

BioNTech COVID-19 (BNT162b2) Vaccination and Varicella Zoster Reactivation: A Comprehensive Cross-sectional Study.

Herpes zoster (HZ) results from reactivation of latent varicella-zoster virus. Recent observations have suggested that HZ is associated with vaccination against COVID-19. To investigate the association between the vaccine and HZ severity, a single-centre, cross-sectional study of all patients diagnosed with HZ and 2 control diagnoses (cellulitis and bone fractures), between 2017 and 2021, was performed. Hospital visits and hospitalization rates were compared. All medical records of patients diagnosed with HZ in the first year after the COVID-19 vaccination campaign began were reviewed, in order to generate a retrospective cohort comparing vaccinated and unvaccinated patients with HZ. All participants had received the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine. During the study period, 2,413 patients were diagnosed with HZ, and when normalized to control diagnoses the number of cases remained stable. The retrospective cohort included 365 patients. A multivariate analysis controlling for sex, age, autoimmune diseases, malignancies, and immunosuppressive therapy showed higher admission rates in vaccinated compared with unvaccinated individuals (odds ratio (OR) 2.75, 95% CI 1.27-5.96, p = 0.01). However, matching techniques and stratification by age, used to better control for confounders, invalidated these findings. No differences were observed in other variables indicative of disease severity (hospital stay length and complications). In conclusion, COVID-19 vaccination was not found to be associated with an increased risk of HZ-related admission and complications.

Progressive shingles in a toddler due to reactivation of Varicella Zoster vaccine virus four days after infection with SARS-CoV-2; a case report

BackgroundHerpes zoster (HZ) is the clinical syndrome associated with reactivation of latent varicella-zoster virus (VZV). Several factors have been implicated to promote VZV reactivation; these include immunosuppression, older age, mechanical trauma, physiologic stress, lymphopenia, and more recently, infection with severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2). Recent reports suggest an increase in the number of HZ cases in the general population during the global COVID-19 pandemic. However, it is unknown what proportion of HZ during the pandemic is due to reactivation of wild-type or vaccine-strain VZV.CaseHere we report the first known case of HZ concomitant with SARS-CoV2 infection in a 20-month-old female who was treated with a single dose of dexamethasone, due to reactivation of the vaccine-type strain of VZV after presenting with a worsening vesicular rash.ConclusionIn this case, we were able to show vaccine-strain VZV reactivation in the context of a mild acute symptomatic COVID-19 infection in a toddler. Being able to recognize HZ quickly and effectively in a pediatric patient can help stave off the significant morbidity and mortality associated with disease process.

The immunogenicity and the safety of the adjuvanted glycoprotein E (gE)-based recombinant vaccine against herpes zoster (RZV) in cancer patients during immunotherapy

ABSTRACT Herpes zoster (HZ) is caused by the reactivation of latent varicella zoster virus (VZV). Severe immunocompromising conditions, such as solid tumors, have been largely associated with an increased risk for HZ due to waning VZV-specific cellular immunity. With the approval of the adjuvanted glycoprotein E (gE)-based recombinant vaccine (RZV; Shingrix™, GSK) also in immunocompromised subjects, HZ is considered a vaccine-preventable disease changing perspectives in immunocompromised subjects. To date, no clinical trial has evaluated the immunogenicity in the patients with cancer undergoing immunotherapy. In this study, we describe the humoral and cell-mediated immune responses in 38 cancer patients treated with immune checkpoint inhibitors (ICIs) and receiving RZV. We used samples collected at baseline (T0), 3 weeks (T2), and 6 months (T3) after the complete RV vaccination schedule. Our data showed that a significant proportion (40,5%) of RZV recipients mounted a stronger humoral and cell-mediated immune response at 3 weeks (T2) after complete RZV vaccination schedule. Interestingly, both humoral and cell-mediated immune responses were mostly stable over 6 months (T3). Interestingly, the overall IFNγ-producing lymphocytes was mainly associated with CD4 T cell response (p = .0012). In conclusion, data from our pilot study suggest a strong and long-lasting immunogenicity of RZV in ICI-treated patients. Prospective analyses at 1 year after vaccination will be performed in order to evaluate the long-term persistence of humoral and cell-mediated response against RZV.

Impact of Psychological Distress on Immune Phenotype in CLL/SLL Patients Managed By Active Observation

Introduction: Asymptomatic patients with a new diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are usually managed by active observation; however, many patients report elevated levels of distress and worry during the ‘watchful waiting’ phase. Psychological distress may have clinical implications given that natural killer [NK] and T cells are not only sensitive to distress, but also critical in controlling disease progression. Thus, the purpose of this study was to examine associations of psychological functioning and quality of life (QOL) with biomarker expression and functional activity of immune cells from peripheral blood of CLL/SLL patients being managed with surveillance. Methods: We conducted a multisite, prospective study in patients with indolent B-cell neoplasms who were managed with surveillance. Participants completed measures of perceived stress (Perceived Stress Scale), anxiety and depressive symptoms (Hospital Anxiety and Depression Scale) and quality of life (FACT-G) at study entry and then every 6 months for up to 2 years or disease progression (whichever occurred first). Blood samples were collected at study entry and every 6 months for immune phenotyping using multiparametric flow cytometry (up to 13-color). Biomarkers of activation, viability, proliferation, exhaustion, and receptor expression were assessed on subsets of T, NK, and myeloid cells, and mean fluorescence intensity or percentage of cells staining were determined. Results: Between April 2016 and November 2020, 233 patients were enrolled at two academic institutions in Philadelphia, including 111 with a diagnosis of CLL/SLL. Of these, 76 patients also had viable samples for immune phenotyping. Participants were predominantly male (60.5%) with a mean age of 63.7 years (SD=9.1 years). Approximately 5% self-reported their race as Black or African American and 4% were of Hispanic ethnicity. At enrollment, the median time since diagnosis was 10.6 months (median follow-up time = 23.6 months). Multivariable regression analyses revealed that increased depressive symptoms were associated with a significant shift from lower percentages of non-classical monocytes (NCM) to higher percentages of classical monocytes (CM; see Figure 1). Similar significant population shifts from reduced NCM toward increased CM were also observed with increased levels of stress and anxiety. These results suggest that patients reporting increased stress, anxiety, and depressive symptoms have fewer of the “patrolling” NCM and increased “sensing” CM in peripheral blood. We also assessed expression of numerous innate immune receptors, including DNAM-1, which can stimulate responses by NK and T cells toward tumors. We observed lower expression of DNAM-1 on CD4 + helper T cells and CD8 + cytotoxic T cells in patients with increased depressive symptoms (p&amp;lt; 0.05). Similarly, patients reporting lower QOL also expressed lower levels of DNAM-1 on CD4 + and CD8 + T cells, as well as cytotoxic CD56 dim NK cells (p&amp;lt;0.05). As DNAM-1 is important for antitumor responses, our data suggest that patients with higher depressive symptoms have T and NK cells with reduced capacity to respond to CLL/SLL tumor cells. NKp30, another activating receptor on NK and CD8+ T cells promoting cytotoxicity, was also expressed at lower levels on CD56 dim NK cells and T cells in the peripheral blood of patients reporting depressive symptoms. Patients who reported higher levels of depressive symptoms had lower levels of expression of the activation marker CD69 on CD4+ and CD8+ T cells. Finally, longitudinal analyses revealed that higher levels of depressive symptoms predicted lower levels of PD-L1 on CD56 dim NK cells over time ( p = 0.04). Conclusion: In CLL/SLL patients, psychological functioning is associated with differential patterns of monocyte distribution. Greater depressive symptoms and lower quality of life predicted lower expression of innate immune receptors, such as DNAM-1 on CD4 + helper T cells and CD8 + cytotoxic T cells. Future directions will investigate whether these measures are associated with disease progression or the occurrence of second primary cancers, given the importance of DNAM-1 and NKp30 in immune surveillance for cancers and reactivation of latent viruses. These findings may have direct translational relevance and enable the early identification of patients at-risk for poor outcomes.

Immunogenicity in Mice Immunized with Recombinant Adenoviruses Expressing Varicella-Zoster Virus Envelope Glycoprotein E.

Herpes zoster (HZ) is a disease caused by the reactivation of latent varicella-zoster virus (VZV). The subunit vaccine, Shingrix®, and live attenuated vaccine, Zostavax®, could be used as an HZ vaccine that prevents HZ from being developed due to the reactivation of latent VZV in the sensory ganglia due to aging, stress or immunosuppression. In this study, the recombinant adenoviruses rChAd63/gE expressing glycoprotein E (gE) of VZV based on chimpanzee adenovirus serotype 63 (ChAd63) were constructed and investigated for the immunogenicity of different immune pathways in C57BL/6 mice. The results showed similar CD4+ T and CD8+ T cell responses to Shingrix® were induced in mice vaccinated using rChAd63/gE via different immune pathways. This study elucidates that recombinant adenoviruses expressing VZV gE could be appropriate for further development as a new HZ vaccine candidate via different immune pathways.

Human adipose tissue as a major reservoir of cytomegalovirus-reactive T cells.

Cytomegalovirus (CMV) is a common herpesvirus with a high prevalence worldwide. After the acute infection phase, CMV can remain latent in several tissues. CD8 T cells in the lungs and salivary glands mainly control its reactivation control. White adipose tissue (WAT) contains a significant population of memory T cells reactive to viral antigens, but CMV specificity has mainly been studied in mouse WAT. Therefore, we obtained blood, omental WAT (oWAT), subcutaneous WAT (sWAT), and liver samples from 11 obese donors to characterize the human WAT adaptive immune landscape from a phenotypic and immune receptor specificity perspective. We performed high-throughput sequencing of the T cell receptor (TCR) locus to analyze tissue and blood TCR repertoires of the 11 donors. The presence of TCRs specific to CMV epitopes was tested through ELISpot assays. Moreover, phenotypic characterization of T cells was carried out through flow cytometry. High-throughput sequencing analyses revealed that tissue TCR repertoires in oWAT, sWAT, and liver samples were less diverse and dominated by hyperexpanded clones when compared to blood samples. Additionally, we predicted the presence of TCRs specific to viral epitopes, particularly from CMV, which was confirmed by ELISpot assays. Remarkably, we found that oWAT has a higher proportion of CMV-reactive T cells than blood or sWAT. Finally, flow cytometry analyses indicated that most WAT-infiltrated lymphocytes were tissue-resident effector memory CD8 T cells. Overall, these findings postulate human oWAT as a major reservoir of CMV-specific T cells, presumably for latent viral reactivation control. This study enhances our understanding of the adaptive immune response in human WAT and highlights its potential role in antiviral defense.

Immunological Aspects of Reactivation of Latent Infections in Space Flight and Antarctica

The complex of space flight (SF) factors can have a negative impact on the human organism, including the innate and adaptive immunity. One of the negative effects of impaired functional activity of the immune system is a decrease of latent infections immunological control. During short- and long-term SF, reactivation of latent viruses was shown, while the virus was detected in body fluids for some time after returning to Earth. Despite the fact that in most cases reactivation was asymptomatic, there are fears that during long expeditions into deep space, reactivation of latent pathogens can lead to the development of diseases that are dangerous to the crewmembers health. There is a lot of data about the viral pathogens reactivation in SF, but the reactivation of bacterial agents in cosmonauts has received almost no attention. Due to the complexity of conducting research in space, an important role is played by ground-based analog experiments that simulate the space station conditions. One of the most significant analogues of SF is the long-term Antarctic expedition, which makes it possible to obtain unique information about the effect of isolation, increased mental and physiological stress on the latent pathogens reactivation. Currently, latency is increasingly considered as a symbiotic existence of a pathogen and host, during which the human body acquires additional resistance to certain infectious agents. Thus, an important task of the upcoming research is a comprehensive analysis of the personal immunological status in the SF, establishing its relationship with the latent infections reactivation and developing systems for monitoring, preventing and treating the negative consequences of reactivation.

Association between COVID-19 infection and herpes zoster: A case series

Herpes zoster (HZ) is a manifestation of the reactivation of latent varicella zoster virus (VZV) infection in the dorsal root ganglion. The occurrence of HZ has been reported in association with COVID-19. Herein, we describe 10 cases who developed classic HZ within 2–3 weeks of acquiring COVID-19 infection. The triggers in these patients could be severe stress (related to quarantine issues, fear of hospitalisation and death) immune dysregulation and systemic steroid therapy in treating COVID-19. The clinical patterns and therapeutic responses observed were similar to HZ in immunocompetent persons. Increased expression of NKG2A on NK and CD8+ T cells has been proposed as a pathophysiologic mechanism in triggering HZ at the molecular level in COVID-19 patients. Primary physicians should be aware of this association to counsel and treat such patients appropriately, as initiating early treatment could minimise the risk of complications like postherpetic neuralgia.

A broad-based probe-free qPCR assay for detection and discrimination of three human herpes viruses

Primary infection or reactivation of latent human cytomegalovirus (HCMV) or herpes simplex viruses (HSV) 1 or 2 during pregnancy can transmit the virus in utero or during natural childbirth to the fetus. The majority of these infections are asymptomatic at birth but may present later with potentially lethal disseminated infection or meningitis (HSV), or long-term neurodevelopmental sequelae including sensorineural hearing loss or neurodevelopmental impairments (HCMV). Unfortunately, early signs and symptoms of disseminated viral infections may be misdiagnosed as bacterial sepsis. Therefore, immediate testing for viral etiologies may not be ordered or even considered by skilled clinicians. In asymptomatic HCMV infections, early detection is necessary to monitor for and treat future neurologic sequelae. In acutely ill-appearing infants, specific detection of viruses against other disease-causing agents is vital to inform correct patient management, including early administration of the correct antimicrobial(s). An ideal test should be rapid, inexpensive, require low sample volumes, and demonstrate efficacy in multiple tissue matrices to aid in timely clinical decision-making for neonatal infections. This work discusses the development of a rapid probe-free qPCR assay for HSV and HCMV that enables early and specific detection of these viruses in neonates. The assay’s probe free chemistry would allow easier extension to a broad-based multiplexed pathogenic panel as compared to assays utilizing sequence-specific probes or nested PCR.

Cognitive dysfunction in post-COVID-19 condition: Mechanisms, management, and rehabilitation.

The long-term effects of COVID-19 on cognitive function have become an area of increasing concern. This paper provides an overview of characteristics, risk factors, possible mechanisms, and management strategies for cognitive dysfunction in post-COVID-19 condition (PCC). Prolonged cognitive dysfunction is one of the most common impairments in PCC, affecting between 17% and 28% of the individuals more than 12 weeks after the infection and persisting in some cases for several years. Cognitive dysfunctions can be manifested as a wide range of symptoms including memory impairment, attention deficit, executive dysfunction, and reduced processing speed. Risk factors for developing PCC, with or without cognitive impairments, include advanced age, preexisting medical conditions, and the severity of acute illness. The underlying mechanisms remain unclear, but proposed contributors include neuroinflammation, hypoxia, vascular damage, and latent virus reactivation not excluding the possibility of direct viral invasion of the central nervous system, illustrating complex viral pathology. As the individual variation of the cognitive impairments is large, a neuropsychological examination and a person-centered multidimensional approach are required. According to the World Health Organization, limited evidence on COVID-19-related cognitive impairments necessitates implementing rehabilitation interventions from established practices of similar conditions. Psychoeducation and compensatory skills training are recommended. Assistive products and environmental modifications adapted to individual needs might be helpful. In specific attention- and working memory dysfunctions, cognitive training-carefully monitored for intensity-might be effective for people who do not suffer from post-exertional malaise. Further research is crucial for evidence-based interventions specific to COVID-19-related cognitive impairments.

Binding of herpesvirus entry mediator (HVEM) and HSV-1 gD affect reactivation but not latency levels.

Previously we reported that the HSV-1 latency associated transcript (LAT) specifically upregulates the cellular herpesvirus entry mediator (HVEM) but no other known HSV-1 receptors. HSV-1 glycoprotein D (gD) binds to HVEM but the effect of this interaction on latency-reactivation is not known. We found that the levels of latent viral genomes were not affected by the absence of gD binding to HVEM. However, reactivation of latent virus in trigeminal ganglia explant cultures was blocked in the absence of gD binding to HVEM. Neither differential HSV-1 replication and spread in the eye nor levels of latency influenced reactivation. Despite similar levels of latency, reactivation in the absence of gD binding to HVEM correlated with reduced T cell exhaustion. Our results indicate that HVEM-gD signaling plays a significant role in HSV-1 reactivation but not in ocular virus replication or levels of latency. The results presented here identify gD binding to HVEM as an important target that influences reactivation and survival of ganglion resident T cells but not levels of latency. This concept may also apply to other herpesviruses that engages HVEM.