Reactivation Of Latent Virus Research Articles

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.

Laboratory Findings and Biomarkers in Long COVID: What Do We Know So Far? Insights into Epidemiology, Pathogenesis, Therapeutic Perspectives and Challenges.

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far it has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; a chronic, low-grade inflammatory response; immune dysregulation and a defective immune response; the reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal and metabolic dysregulation; mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response, although this effort may be hampered by challenges pertaining to the non-specific nature of the majority of clinical manifestations in the LC spectrum, small sample sizes of relevant studies and other methodological issues. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation, including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, the reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; and cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers, their link to etiopathogenetic mechanisms or the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on pathogenetic mechanisms and the main LC symptomatology in the frame of the epidemiological and clinical aspects of the syndrome and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.

Chronic Stress and Latent Virus Reactivation: Effects on Immune Aging, Chronic Disease Morbidity, and Mortality.

Social stress has been shown to affect immune functioning. Past research has found that chronic social stress and latent viral infections accelerate immune aging, leading to chronic disease morbidity and mortality. Chronic stress may also reactivate latent viral infections, like cytomegalovirus (CMV), accelerating the aging of the immune system. Utilizing panel survey data from 8,995 U.S. adults aged 56 or older from the Health and Retirement Study, this study investigates whether chronic stress interacts with CMV positivity to drive aging of the immune system, multimorbidity, and mortality. Results of moderated mediation analysis indicate that the effect of CMV positivity on morbidity and mortality as mediated by immune aging indicators is amplified by chronic stress. These findings suggest that immune aging is a biological pathway underlying the stress process and help explain past findings in the literature on stress and health.

CLEAR Strategy Inhibited HSV Proliferation Using Viral Vectors Delivered CRISPR-Cas9.

Herpes simplex virus type 1 (HSV-1) is a leading cause of encephalitis and infectious blindness. The commonly used clinical therapeutic drugs are nucleoside analogues such as acyclovir. However, current drugs for HSV cannot eliminate the latent virus or viral reactivation. Therefore, the development of new treatment strategies against latent HSV has become an urgent need. To comprehensively suppress the proliferation of HSV, we designed the CLEAR strategy (coordinated lifecycle elimination against viral replication). VP16, ICP27, ICP4, and gD-which are crucial genes that perform significant functions in different stages of the HSV infection lifecycle-were selected as targeting sites based on CRISPR-Cas9 editing system. In vitro and in vivo investigations revealed that genome editing by VP16, ICP27, ICP4 or gD single gene targeting could effectively inhibit HSV replication. Moreover, the combined administration method (termed "Cocktail") showed superior effects compared to single gene editing, which resulted in the greatest decrease in viral proliferation. Lentivirus-delivered CRISPR-Cas9/gRNA editing could effectively block HSV replication. The CLEAR strategy may provide new insights into the potential treatment of refractory HSV-1-associated diseases, particularly when conventional approaches have encountered resistance.

Homoeopathic Treatment of Childhood Herpes Zoster—A Case Series

Abstract Background Herpes zoster (HZ) is a relatively rare infectious disease in the paediatric population as compared to adults, occurring due to the reactivation of latent varicella-zoster virus that persists in the posterior root ganglion. HZ can develop any time after the primary infection and is characterised by grouped vesicular rashes limited to single dermatome. Diagnosis is based on a distinct clinical appearance of HZ. Its clinical course is variable, and it requires prompt medical treatment to prevent the complications. In conventional method, antiviral and other treatment modalities are available; however, these are fraught with potentially severe side effects and is expensive that demands an alternative method of treatment. Methods A case series of three children with HZ treated with individualised homeopathy is presented here. The cases are reported according to HOM-CASE guidelines and followed up with photographic documentation. The Modified Naranjo Criteria for Homeopathy (MONARCH) inventory was used as a tool for assessing the causal relationship between homeopathic intervention and clinical outcome. Results All cases of HZ were successfully cured with individualised homoeopathy within 10 days without any complication. Individual curative response of the homoeopathic medicine in each case was assessed through MONARCH which demonstrated a positive causal attribution of homeopathy. Conclusion Successful results of this case series suggest a positive response of individualised homeopathic medicines in the treatment of childhood HZ. The remissions of the HZ lesion presented in this case series may be attributed to homeopathic medicines in each case. Hence, this case series could serve as a basis for further research into the role of individualised homeopathic medicine in the treatment of childhood herpes zoster.

Treatment with Brivudine in Immunocompromised Pediatric Patients with Herpes Zoster

Introduction: Herpes zoster (HZ) is caused by endogenous reactivation of latent varicella-zoster virus (VZV) that persists in sensory ganglia after primary infection. The incidence and severity of HZ increase during immunosuppression. Especially, immunocompromised patients are at high risk of developing a cutaneous rash and suffering from delayed healing of lesions. Bromovinyl deoxyuridine (brivudine), one of the most potent oral inhibitors of VZV replication, is widely used in the therapy of HZ in adult patients, particularly in Europe. In this study, we investigated the efficacy of brivudine in immunocompromised children to provide an outpatient treatment option. Methods: In this retrospective study, we included 64 immunocompromised pediatric patients with a median age of 14 years. Forty-seven patients received immunosuppressive therapy as part of hematopoietic stem cell transplantation and 17 patients as part of chemotherapy. Primary diagnosis was made clinically by examining the nature and the localization of the skin lesions. Laboratory confirmation was conducted based on the detection of VZV DNA in vesicle fluid and blood samples. Brivudine was administered orally at a single dose of 2 mg/kg per day. We monitored the patients’ response for the full time of treatment and observed the time of full crusting of lesions, loss of crusts, and any adverse effects that occurred. Results: Patients received medication for 7–21 days (median: 14 days). All children responded promptly to antiviral treatment and recovered completely from their HZ infections without complications. Crusting of lesions was reached after 3–14 days (median: 6 days). Full healing of skin lesions was ascertained within 7–21 days (median: 12 days). Overall, brivudine therapy was well tolerated. No clinical side effects during or after the treatment were observed. High compliance was achieved due to the once-daily dosing regimen. All patients were treated in an outpatient manner. Conclusion: Oral brivudine was a very effective and well-tolerated therapy in immunocompromised children with HZ infection. The oral administration offers the potential for outpatient treatment of HZ in these patients.

Viral reactivations and co-infections in COVID-19 patients: a systematic review

BackgroundViral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and co-infections are currently in limit. Thus, the primary purpose of this review is to perform an overarching investigation on the cases of latent virus reactivation and co-infection in COVID-19 patients to build collective evidence contributing to improving patient health. The aim of the study was to conduct a literature review to compare the patient characteristics and outcomes of reactivations and co-infections of different viruses.MethodsOur population of interest included confirmed COVID-19 patients who were diagnosed with a viral infection either concurrently or following their COVID-19 diagnosis. We extracted the relevant literature through a systematic search using the key terms in the online databases including the EMBASE, MEDLINE, Latin American Caribbean Health Sciences Literature (LILACS), from inception onwards up to June 2022. The authors independently extracted data from eligible studies and assessed the risk of bias using the Consensus-based Clinical Case Reporting (CARE) guidelines and the Newcastle–Ottawa Scale (NOS). Main patient characteristics, frequency of each manifestation, and diagnostic criteria used in studies were summarized in tables.ResultsIn total, 53 articles were included in this review. We identified 40 reactivation studies, 8 coinfection studies, and 5 studies where concomitant infection in COVID-19 patients was not distinguished as either reactivation or coinfection. Data were extracted for 12 viruses including IAV, IBV, EBV, CMV, VZV, HHV-1, HHV-2, HHV-6, HHV-7, HHV-8, HBV, and Parvovirus B19. EBV, HHV-1, and CMV were most frequently observed within the reactivation cohort, whereas IAV and EBV within the coinfection cohort. In both reactivation and coinfection groups, patients reported cardiovascular disease, diabetes, and immunosuppression as comorbidities, acute kidney injury as complication, and lymphopenia and elevated D-dimer and CRP levels from blood tests. Common pharmaceutical interventions in two groups included steroids and antivirals.ConclusionOverall, these findings expand our knowledge on the characteristics of COVID-19 patients with viral reactivations and co-infections. Our experience with current review indicates a need for further investigations on virus reactivation and coinfection among COVID-19 patients.

Herpes zoster in a 4-year-old child with pulmonary tuberculosis: a case report

Herpes zoster (HZ) is a dermatomal virus infection caused by the reactivation of latent varicella zoster virus (VZV) in sensory ganglia neurons that is previously exposed to primary varicella infection. Herpes zoster is a rare disease experienced in children and is often associated with an immunocompromised condition. A case of a girl four years old with a vesicle on the right chest which spread to the upper armpit and right inguinal was reported. The lessions were obtained on Thoracoaxilla as high as T4 and Inguinal as high as L1 dextra. The patient was treated with acyclovir doses of 30 mg/Kg/day for seven days and showed significant improvements.

Circulating Plasma Exosomal Proteins of Either SHIV-Infected Rhesus Macaque or HIV-Infected Patient Indicates a Link to Neuropathogenesis.

Despite the suppression of human immunodeficiency virus (HIV) replication by combined antiretroviral therapy (cART), 50-60% of HIV-infected patients suffer from HIV-associated neurocognitive disorders (HAND). Studies are uncovering the role of extracellular vesicles (EVs), especially exosomes, in the central nervous system (CNS) due to HIV infection. We investigated links among circulating plasma exosomal (crExo) proteins and neuropathogenesis in simian/human immunodeficiency virus (SHIV)-infected rhesus macaques (RM) and HIV-infected and cART treated patients (Patient-Exo). Isolated EVs from SHIV-infected (SHIV-Exo) and uninfected (CTL-Exo) RM were predominantly exosomes (particle size < 150 nm). Proteomic analysis quantified 5654 proteins, of which 236 proteins (~4%) were significantly, differentially expressed (DE) between SHIV-/CTL-Exo. Interestingly, different CNS cell specific markers were abundantly expressed in crExo. Proteins involved in latent viral reactivation, neuroinflammation, neuropathology-associated interactive as well as signaling molecules were expressed at significantly higher levels in SHIV-Exo than CTL-Exo. However, proteins involved in mitochondrial biogenesis, ATP production, autophagy, endocytosis, exocytosis, and cytoskeleton organization were significantly less expressed in SHIV-Exo than CTL-Exo. Interestingly, proteins involved in oxidative stress, mitochondrial biogenesis, ATP production, and autophagy were significantly downregulated in primary human brain microvascular endothelial cells exposed with HIV+/cART+ Patient-Exo. We showed that Patient-Exo significantly increased blood-brain barrier permeability, possibly due to loss of platelet endothelial cell adhesion molecule-1 protein and actin cytoskeleton structure. Our novel findings suggest that circulating exosomal proteins expressed CNS cell markers-possibly associated with viral reactivation and neuropathogenesis-that may elucidate the etiology of HAND.

Ramsay Hunt Syndrome with Pharyngolaryngeal Involvement Mimicking Acute Stroke: A Case Report.

Ramsay Hunt syndrome is a clinical manifestation of the reactivation of latent varicella zoster virus in the geniculate ganglion after acute infection. It is commonly associated with an acute peripheral facial nerve paralysis, auricular vesicular eruption and acute sensorineural hearing loss. However, in some rare cases the involvement of other cranial nerves, especially the glossopharyngeal and vagal is described. We present a 56-year-old male patient who was diagnosed with acute pharyngitis. Two days later, the patient developed dysarthria, hoarseness, and left side facial weakness. Considering a patient's history of cardiovascular events, the acute stroke was suspected. Magnetic resonance imaging ruled out an acute cerebrovascular accident. The patient's otalgia aggravated and he reported hearing loss. Clinical examination revealed facial paralysis affecting the left side of the face, erythematous rash on the left auricle, multiple vesicles present on patient's left tympanic membrane, ulcerous lesion on the left side of the soft palate and ipsilateral velopharyngeal palsy. Indirect laryngoscopy revealed ulcerous lesions in the left side of the epiglottis and left vocal cord paralysis. The patient was diagnosed with Ramsay Hunt syndrome with cranial polyneuropathy. Oral acyclovir and oral prednisolone were administered. Seven months after discharge, facial paralysis improved to lower grade and flexible laryngoscopy showed that the left vocal cord had resumed normal movement. Ramsay Hunt syndrome can be accompanied by involvement of other cranial nerves. Previous history of hypertensive crises and myocardial infarction may influence a diagnosis of Ramsay Hunt syndrome, especially when it has atypical presentation. However, this diagnosis should be considered in patients with unilateral multiple cranial nerve palsies.

Therapeutic targeting of HCMV-encoded chemokine receptor US28: Progress and challenges.

The pervasive human cytomegalovirus (HCMV) causes significant morbidity in immunocompromised individuals. Treatment using the current standard-of-care (SOC) is limited by severe toxic adverse effects and anti-viral resistance development. Furthermore, they only affect HCMV in its lytic phase, meaning viral disease is not preventable as latent infection cannot be treated and the viral reservoirs persist. The viral chemokine receptor (vCKR) US28 encoded by HCMV has received much attention in recent years. This broad-spectrum receptor has proven to be a desirable target for development of novel therapeutics through exploitation of its ability to internalize and its role in maintaining latency. Importantly, it is expressed on the surface of infected cells during both lytic and latent infection. US28-targeting small molecules, single-domain antibodies, and fusion toxin proteins have been developed for different treatment strategies, e.g. forcing reactivation of latent virus or using internalization of US28 as a toxin shuttle to kill infected cells. These strategies show promise for providing ways to eliminate latent viral reservoirs and prevent HCMV disease in vulnerable patients. Here, we discuss the progress and challenges of targeting US28 to treat HCMV infection and its associated diseases.

Human herpesvirus-6 in hematopoietic stem cell transplant recipients: a prospective cohort study in Egypt

BackgroundImmunocompromised patients face reactivation of latent viruses that increase the risk of morbidity.AimThe study aimed to detect human herpes virus 6 (HHV-6) reactivation among allogeneic (allo) and autologous (auto) hematopoietic stem cell transplant (HSCT) recipients and to correlate potentially attributed clinical manifestations to HHV-6 DNA plasma level.MethodsA prospective study included all (forty) patients undergoing allo and auto-HSCT from Jan 2020 till June 2022. Plasma samples were collected for HHV-6 serology, and for HHV-6 quantitative PCR at post-transplantation weeks 2, 4, 6. Demographic and clinical data were recorded.ResultsOut of 40 peripheral blood stem cell transplant (PBSCT) recipients, 34 (85%) were HHV-6 IgG positive pre-HSCT. Of which, fourteen patients (14/34, 41.2%) showed positive HHV-6 DNaemia. HHV-6 DNAemia (15/40, 37.5%) was significantly higher among allo (8/12, 66.7%) versus auto (7/28, 25%) HSCT recipients (p = 0.030). Patients with HHV-6 DNAemia developed fever, delayed engraftment and bone marrow suppression in 6/15, 40%, thrombocytopenia (5/15, 33.3%), rash and pneumonitis (2/15, 13.3%), acute GVHD (aGVHD) (1/15, 6.7%). HHV-6 DNAemia ranged from 101 to 102,000 copies/mL. Univariate analysis identified conditioning with busulfan–cyclophosphamide as a significant risk (p = 0.043), while receiving BEAM protocol was a protective factor (p = 0.045). In multivariate analysis, receiving BEAM protocol retained significance (p = 0.040).ConclusionFrequent HHV-6 reactivation was detected after HSCT, especially in allo-HSCT recipients with clinical manifestations which could not be otherwise explained. To our best knowledge this is the first study of HHV6 reactivation in HSCT recipients from Egypt. Raising awareness for HHV-6 reactivation manifestations and screening in HSCT recipients could be lifesaving.

A Mathematical Model for Determining the Body’s Fluctuating Need for and Synthesis of Active Vitamin D

The process by which 1,25(OH)2D3 is synthesized and degraded and how it is transported out of the cell and body is described. The changing demand for the synthesis of 1-25(OH)2D3 during different conditions experienced by the body is reviewed. A method of determining 1,25(OH)2D3 synthesis and demand, and the percent utilization of 25(OH)D3 to make 1,25(OH)2D3 is presented based on the measurement of the end metabolites of 1,25(OH)2D3 and of its immediate precursor, 25(OH)D3. A mathematical model has been developed to allow the calculation of 1,25(OH)2 D synthesis, and demand, and the percent utilization of 25(OH)D3. Simple algebraic equations have been derived which allow the calculation of these new parameters using the concentrations of the end metabolites of 1,25(OH)2D3 and its immediate precursor, 25(OH)D3 in the serum and urine. Vitamin D plays an important role in combating invading bacteria and viruses and in subduing the body's associated inflammatory response. This new approach to evaluating vitamin D status may help clinicians determine 25(OH)D3 and 1,25(OH)2D3 levels needed to suppress bacterial infections, viral replication during new viral infections and the reactivation of latent viruses, and to downregulate the inflammatory responses caused by bacteria and viruses.

Рецидивирующие респираторные заболевания и активные герпесвирусные инфекции у детей: проблемы и варианты их решения

Background: recurrent respiratory infections (RRI) in children are a relevant medical and social issue. Reactivation of latent herpes simplex virus (HSV) infections is recognized as one of the leading causes of recurrent respiratory infections. Its rate in children is up to 40%. Therapeutic options for recurrent respiratory infections in children are discussed given the activity of HSV infections and immune disorder treatment. Aim: to assess the efficacy of inosine pranobex (Normomed®) for recurrent respiratory infections and active HSV infection in children. Patients and Methods: we examined 96 children aged 1–17 years who requested medical care in an outpatient department with complaints typical of recurrent respiratory infections and laboratory-confirmed active HSV infection. Children received inosine pranobex (50–75 mg/kg/day) in three 10-day courses (10-day breaks). 5±1 weeks after finishing therapy, control clinical and laboratory tests and virology were performed. The nature of ARI episodes during the follow-up period and HSV infection activity over time were evaluated. Results: during treatment, a reduction in the rate and severity of respiratory diseases was reported in 94% of children. Fever severity decreased twice (p=0.035), oropharynx condition improved in 66.7% (p&lt;0.01), and the severity of lymphoproliferative syndrome reduced in 62.5% (tonsil hypertrophy in 52.1%, lymphadenopathy in 50.6%, hepatomegaly in 55.3%, splenomegaly in 66.7%). During treatment with inosine pranobex, a decrease in HSV infection activity was reported in 88.6% of children. The active HSV count also decreased. A significant (p&lt;0.01) reduction in the percentage of patients with active HHV 6A/B (from 78.1% to 12.5%), Epstein– Barr virus (from 45.8% to 7.3%), and HSV type 1 (from 14.6% to 1.0%) was reported. Conclusion: significant improvement in the somatic and virological status of children with recurrent respiratory infections and HSV infection after a course of inosine pranobex, which is characterized by antiviral and immunomodulatory effects, was established. KEYWORDS: monthly respiratory infections, recurrent respiratory infections, Epstein–Barr virus, human herpes virus 6A/B, children, inosine pranobex, Normomed. FOR CITATION: Melekhina E.V., Preobrazhenskaia D.V., Muzyka A.D., Soldatova E.Yu., Gorelov A.V. Recurrent respiratory infections and active herpesvirus infections in children: problems and solutions. Russian Medical Inquiry. 2023;7(11):704–712 (in Russ.). DOI: 10.32364/2587- 6821-2023-7-11-2.

RAMSAY HUNT SYNDROME: A CASE REPORT

Ramsay Hunt Syndrome (RHS) is a rare disease caused by reactivation of latent Varicella Zoster Virus in the geniculate ganglion which lead to inflammation, edema, and compression of facial nerve. RHS may affect both immunocompetent and immunocompromised patient. Clinical manifestation of RHS include herpes zoster oticus that manifest as vesicular rash on auricular area or oral mucosa in combination with peripheral nerve palsy. We reported a 67-years-old female patient with herpetic vesicle on left side of face and ear accompanied with ipsilateral peripheral facial paralysis since 2 days before admission. Patient was treated with acyclovir for 5 days. Follow up examination showed satisfying clinical improvement with disappearance of vesicles and otalgia, as well as facial weakness improvement from House Brackmann grade III to grade II. Early recognition and treatment of Ramsay Hunt Syndrome is crucial as delay of treatment may lead to sequelae, including postherpetic neuralgia and permanent facial paralysis.

EE265 Health, Productivity and Budget Impact of Vaccinating 50-64 Year Old Employees in Austria Against Herpes Zoster With Recombinant Zoster Vaccine

Herpes zoster (HZ) is caused by reactivation of latent varicella zoster virus. Age-related immunity decline is the main risk factor for the disease. HZ can lead to debilitating chronic pain (postherpetic neuralgia, PHN) and other complications, impacting work productivity. We assessed the public health and budget impact of vaccination with recombinant zoster vaccine (RZV) to Austrian healthcare payers and to employers, respectively.

Detection Analysis and Study of Genomic Region Variability of JCPyV, BKPyV, MCPyV, HPyV6, HPyV7 and QPyV in the Urine and Plasma of HIV-1-Infected Patients.

Since it was clearly established that HIV/AIDS predisposes to the infection, persistence or reactivation of latent viruses, the prevalence of human polyomaviruses (HPyVs) among HIV-1-infected patients and a possible correlation between HPyVs and HIV sero-status were investigated. PCR was performed to detect and quantify JCPyV, BKPyV, MCPyV, HPyV6, HPyV7 and QPyV DNA in the urine and plasma samples of 103 HIV-1-infected patients. Subsequently, NCCR, VP1 and MCPyV LT sequences were examined. In addition, for MCPyV, the expression of transcripts for the LT gene was investigated. JCPyV, BKPyV and MCPyV's presence was reported, whereas HPyV6, HPyV7 and QPyV were not detected in any sample. Co-infection patterns of JCPyV, BKPyV and MCPyV were found. Archetype-like NCCRs were observed with some point mutations in plasma samples positive for JCPyV and BKPyV. The VP1 region was found to be highly conserved among these subjects. LT did not show mutations causing stop codons, and LT transcripts were expressed in MCPyV positive samples. A significant correlation between HPyVs' detection and a low level of CD4+ was reported. In conclusion, HPyV6, HPyV7 and QPyV seem to not have a clinical relevance in HIV-1 patients, whereas further studies are warranted to define the clinical importance of JCPyV, BKPyV and MCPyV DNA detection in these subjects.

Viral Infections and Reactivations in Chronic Myeloid Leukemia Patients on Tyrosine Kinase Inhibitors (TKIs)

Introduction Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm characterized by the unregulated growth of myeloid cells, resulting in a proliferation of mature granulocytes. The reciprocal translocation, which results from the fusion of the breakpoint cluster region (BCR) gene on 22q11.2 and the Abelson murine leukemia (ABL1) gene on 9q34.1 is the hallmark of the disease and results in a BCR/ABL1 fusion product with abnormal tyrosine kinase activity, which plays a role in the unregulated cell proliferation. CML accounts for 15-20% of adults leukemias. Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of CML, as it is highly successful and has transformed the prognosis of patients with CML. However, TKIs may be associated with an increased risk of infections. This review highlights the risk of viral infections in patients with CML. Methodology We have performed a literature search for English language articles using PubMed, Scopus, and Google Scholar, for the period 2001-2022. And population consisted of patients over 18 years old with a diagnosis of CML and no history of BMT. Articles include case reports, case series, informative reviews, and clinical trials. The keywords were " CML, Chronic Myelogenous Leukemia, Viral, Infection." Search results were initially reviewed by title and abstract, and articles were selected for more in-depth analysis if deemed relevant. Pertinent articles were examined in-depth for this report. Results In an analysis of 41 patients, with 25 males and 16 females, M:F ratio of 1.56:1, and the median age of 50. Age ranged from 22 to 79 years. Most patients with reported viral infections or reactivations were in the chronic phase of CML, with 22 patients (76%) in the chronic phase, 6 patients (21%) in the accelerated phase, and one patient (3%) in the blast phase. Most cases with reported outcomes responded to treatment to CML; only one had refractory disease, and 8 cases (32%) had Major molecular response. Imatinib was the most commonly used TKI in 30 patients (77%). The most commonly reported viral reactivations were Herpes zoster in 17 cases (41%), followed by Hepatitis B reactivation in 15 cases (37%). Conclusion Patients with a diagnosis of CML have a high risk for viral infections, mainly reactivation of latent viruses like varicella zoster and hepatitis B; this is likely because of the disease itself; adaptive immune responses are dysfunctional in CML patients at diagnosis before starting TKI treatment and before the progression to overt immune deficiency secondary to blastic transformation, as evident by the large number of patients having viral reactivation in the chronic phase; reasons included dysfunctional CD8+ cytotoxic T-cells (CTLs). On the other hand, treatment by TKI can increase this risk of viral reactivation; therapy with imatinib was associated with significant reductions in IgM memory B cells. This review shows the importance of having a hepatitis B serology checked before starting TKI therapy, close monitoring and clinical suspicions for viral infections or reactivations in patients with CML on TKIs; further clinical trials are needed to assess the need for viral prophylaxis for CML patients after starting TKIs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster

Herpes zoster is a localized skin infection caused by reactivation of latent varicella-zoster virus. Tissue-resident T cells likely control skin infections. Zoster provides a unique opportunity to determine if focal reinfection of human skin boosts local or disseminated antigen-specific tissue-resident T cells. Here, we show virus-specific T cells are retained over one year in serial samples of rash site and contralateral unaffected skin of individuals recovered from zoster. Consistent with zoster resolution, viral DNA is largely undetectable on skin from day 90 and virus-specific B and T cells decline in blood. In skin, there is selective infiltration and long-term persistence of varicella-zoster virus-specific T cells in the rash site relative to the contralateral site. The skin T cell infiltrates express the canonical tissue-resident T cell markers CD69 and CD103. These findings show that zoster promotes spatially-restricted long-term retention of antigen-specific tissue-resident T cells in previously infected skin.

Reactivation of Herpes Zoster and HHV-6 Following COVID-19 mRNA Vaccine

A case of Herpes Zoster and HHV-6 reactivation following the COVID-19 mRNA vaccine was presented. The case is unique with a severe Herpes-Zoster reaction, with eyelid edema and hair loss. In addition, there was prominent lymph node swelling as well as high HHV-6 titers at 2.11 and Varicella-Zoster V Ab IgG, more than 4,000. Initial infection of HHV-6 in grown-up is rare, but a mononucleosis-like syndrome of different severity with prolonged lymphadenopathy has been reported. Reactive lymphadenitis positive for HHV-6 have been reported with lymphadenopathy and fever. Reactivation of latent virus usually occurs in an immunocompromised host and Primary infection is not frequent in grown-ups. It is a rare cause of lymphadenitis in an immunocompetent adult.