Severe Herpes Research Articles

The immunogenetic basis of severe herpes simplex infections in neonates and children: a review.

Human herpes simplex virus (HSV) is a double stranded DNA virus with two distinct types, HSV-1 and HSV-2. The global burden of HSV is high with an estimated 2/3 of the adult population seropositive for at least one of these types of HSV. HSV rarely causes life-threatening disease in immunocompetent children and adults. However, in neonates and children with a developmentally immature immune system it can cause disseminated disease and herpes simplex encephalitis (HSE). Recent studies in children and neonates suggest that genetic risk-factors can contribute to severe HSV phenotypes in neonates and children. In particular, genetic defects in theToll Like Receptor 3 (TLR3) signaling pathway that attenuate the type I interferon response to HSV are being increasingly recognized in children with severe phenotypes of HSV. In this review, we discuss the epidemiology and immunological aspects of HSV disease in neonates and children and provide an in-depth review of the studies characterizing the role of inborn errors in the TLR3 pathway and other immune genes in HSV. We highlight the need for future research to identify the immunogenetic basis of severe or recurrent HSV disease in neonates and children. IMPACT: Review the epidemiology and phenotypes of herpes simplex virus (HSV) infection in neonates and children. Discuss the mechanisms of immunity against HSV highlighting the developmental vulnerability of neonates and infants to severe HSV disease. Explore in depth the genes and immune pathways that underlie genetic predisposition to severe HSV disease in neonates and children, and outline strategies for multi-disciplinary clinical evaluation of severe disease.

A Novel Heterozygous NFKB2 Variant in a Multiplex Family with Common Variable Immune Deficiency and Autoantibodies Against Type I IFNs.

We studied a family with three male individuals across two generations affected by common variable immune deficiency (CVID). We identified a novel missense heterozygous variant (c.2602T>A:p.Y868N) of NFKB2 in all patients and not in healthy relatives. Functional studies of the mutant allele in an overexpression system and of the patients' cells confirmed the deleteriousness of the NFKB2 variant and genotype, respectively, on the activation of the non-canonical NF-κB signaling pathway. Impaired processing of p100 into p52 underlies p100 accumulation, which results in gain-of-function (GOF) of IκBδ inhibitory activity and loss-of-function (LOF) of p52 transcriptional activity. The three patients' plasma contained autoantibodies that neutralized IFN-α2 and/or IFN-ω, accounting for the severe or recurrent viral diseases of the patients, including influenza pneumonia in one sibling, and severe COVID-19 and recurrent herpes labialis in another. Our results confirm that NFKB2 alleles that are IκBδ GOF and p52 LOF can underlie CVID and drive the production of autoantibodies neutralizing type I IFNs, thereby predisposing to severe viral diseases.

Severe herpes simplex virus − 1 Kaposi varicelliform eruption and SARS-CoV-2 infection in atopic dermatitis treated with dupilumab

Herpes Simplex Virus-1 (HSV-1) Kaposi varicelliform eruption (KVE) is a rare and severe cutaneous manifestation, clinically characterized by the presence of widespread vesicles and pustules. A case report details a patient with a history of Atopic Dermatitis (AD) and recent SARS-CoV-2 infection who developed a severe KVE subsequent to the viral illness. The patient, a 35-year-old male, presented with severe atopic dermatitis (AD) subsequent to a SARS-CoV-2 infection. In a period of four months, the dermatological eruption underwent a rapid progression to a severe state, characterised by the presence of extensive vesicles and pustules, in addition to the emergence of symptoms. In conjunction with a chest CT scan, plasma and antigen testing, the patient was confirmed to be positive for HSV-1 positive. The patient exhibited elevated levels of IgE and a notable reduction in the absolute number of immune cells. The patient was treated with valaciclovir, piperacillin-tazobactam, IVIG at the same time. Within seven days of treatment, the blisters had dried up and the scabs had fallen off without any pain, pruritus, or fever. This case highlights the potential for severe viral eruptions, such as KVE in individuals with underlying dermatological conditions following viral infections.

The Rab6 post-Golgi secretory pathway contributes to herpes simplex virus 1 (HSV-1) egress.

Herpes simplex virus 1 (HSV-1) infects a majority of people. It establishes a life-long latent infection and occasionally reactivates, typically causing characteristic oral or genital lesions. Rarely in healthy natural hosts, but more commonly in zoonotic infections and in elderly, newborn, or immunocompromised patients, HSV-1 can cause severe herpes encephalitis. The precise cellular mechanisms used by HSV-1 remain an important area of research. In particular, the egress pathways that newly assembled virus particles use to exit from infected cells are unclear. In this study, we used fluorescence microscopy to visualize individual virus particles exiting from cells and found that HSV-1 particles use the pre-existing cellular secretory pathway.

Efficacy and safety of the type I interferon receptor inhibitor anifrolumab in patients with systemic lupus erythematosus (results of a 6-month study)

Objective: to evaluate the efficacy and safety of the type I interferon (IFN) receptor inhibitor anifrolumab (AFM, Safnelo®) in patients with systemic lupus erythematosus (SLE) in real-life clinical practice over an observation period of 6 months.Material and methods. The prospective 6-month study included 21 patients with SLE fulfilling the 2012 SLICC criteria, predominantly women (n=17,81%), median age – 31 [27; 46] years, disease duration – 9 [6.0; 11.0] years. Standard laboratory values and immunological markers of SLE were examined in all patients. The SLEDAI-2K index was used to determine the activity of SLE, and the severity of the mucocutaneous syndrome was assessed using the Cutaneous Lupus Disease Area and Severity Index (CLASI) index. Organ damage was assessed using the SLICC/ACR Damage Index (DI). After 6 months, the achievement of low activity was assessed according to the Lupus Low Disease Activity State (LLDAS) indexResults and discussion. At the time of inclusion in the study, the mean SLEDAI-2K activity index for the group was 8 [6.0; 10.0] points, the median CLASI index – 8.6±8.2 points, 81% of patients had skin and mucosal lesions, 66% had non-erosive polyarthritis, and high immunological activity was observed in all cases. Various irreversible organ damage was observed in 86 of patients. The average DI was 2.2±1.5 points. At the start of AFM therapy, all patients received glucocorticoids (GCs) at a mean dose of 10.7±5.6 mg/day, 52% of patients received a dose above 10 mg/day, 76% of patients continued to take hydroxychloroquine, and 33% of patients took immunosuppressants. Significant positive dynamics were observed with AFM therapy. The average CLASI index for the group after 3 months of treatment was 1.2±4.1 points, after 6 months – 0.3±1.2 points (p<0.0001). The SLEDAI-2K index fell significantly in the group on average from 8 [6.0; 10.0] to 2 [2.0; 4.0] points from the 3rd month of treatment (p<0.0001) and remained at the same level after 6 months. At month 6 of treatment, 13 (62%) of 21 patients met the LLDAS criteria for low disease activity. After the 3rd month of treatment, a significant decrease in antibodies against dsDNA was observed, which persisted for 6 months after the start of treatment. In the group as a whole, there were no significant changes in complement fractions values during the observation period. There was no increase in irreversible organ damage (DI – mean 2.2±1.5 points). The mean daily dose of GCs was significantly reduced from 10.7±5.6 mg/day to 7.5±4.0 mg/day (p<0.01) by the 3rd month and to 5.2±2.1 (p<0.001) by the 6th month of treatment. No infusion reactions were observed in any case. Adverse events occurred in 9 (42%) out of 21 patients, mainly herpes infections of varying severity, mainly after the 1st to 3rd infusions. In one case, severe herpes zoster was observed, so the drug was discontinued.Conclusion. At a dose of 300 mg intravenously monthly AFM is a highly effective drug with a relatively good safety profile in patients with active SLE in whom autoantibodies are present and who do not respond adequately to standard therapy.

HIV and skin infections

HIV infection alters the skin microbiome and predisposes to a wide range of cutaneous infections, from atypical presentations of common skin infections to severe disseminated infections involving the skin that are AIDS-defining illnesses. Bacterial infection of the skin, most commonly caused by Staphylococcus aureus, occurs frequently and can result in bacteremia. Nontuberculous mycobacterial infections that are usually localized to the skin may disseminate, and guidance on the treatment of these infections is limited. Herpes simplex can be severe, and less common presentations such as herpetic sycosis and herpes vegetans have been reported. Severe herpes zoster, including disseminated infection, requires intravenous antiviral treatment. Viral warts can be particularly difficult to treat, and in atypical or treatment-resistant cases a biopsy should be considered. Superficial candidosis occurs very commonly in people living with HIV, and antifungal resistance is an increasing problem in non-albicans Candida species. Systemic infections carry a poor prognosis. In tropical settings the endemic mycoses including histoplasmosis are a problem for people living with HIV, and opportunistic infections can affect those with advanced HIV in all parts of the world. Most cutaneous infections can develop or worsen as a result of immune reconstitution in the weeks to months after starting antiretroviral therapy. Direct microscopic examination of clinical material can facilitate rapid diagnosis and treatment initiation, although culture is important to provide microbiological confirmation and guide treatment.

Herpes Virus Infections in Kidney Transplant Patients (HINT) – a prospective observational cohort study

BackgroundKidney transplant recipients receive maintenance immunosuppressive therapy to avoid allograft rejection resulting in increased risk of infections and infection-related morbidity and mortality. Approximately 98% of adults are infected with varicella zoster virus, which upon reactivation causes herpes zoster. The incidence of herpes zoster is higher in kidney transplant recipients than in immunocompetent individuals, and kidney transplant recipients are at increased risk of severe herpes zoster-associated disease. Vaccination with adjuvanted recombinant glycoprotein E subunit herpes zoster vaccine (RZV) prevents herpes zoster in older adults with excellent efficacy (90%), and vaccination of kidney transplant candidates is recommended in Danish and international guidelines. However, the robustness and duration of immune responses after RZV vaccination, as well as the optimal timing of vaccination in relation to transplantation remain unanswered questions. Thus, the aim of this study is to characterize the immune response to RZV vaccination in kidney transplant candidates and recipients at different timepoints before and after transplantation.MethodsThe Herpes Virus Infections in Kidney Transplant Patients (HINT) study is a prospective observational cohort study. The study will include kidney transplant candidates on the waiting list for transplantation (n = 375) and kidney transplant recipients transplanted since January 1, 2019 (n = 500) from all Danish kidney transplant centers who are offered a RZV vaccine as routine care. Participants are followed with repeated blood sampling until 12 months after inclusion. In the case of transplantation or herpes zoster disease, additional blood samples will be collected until 12 months after transplantation. The immune response will be characterized by immunophenotyping and functional characterization of varicella zoster virus-specific T cells, by detection of anti-glycoprotein E antibodies, and by measuring cytokine profiles.DiscussionThe study will provide new knowledge on the immune response to RZV vaccination in kidney transplant candidates and recipients and the robustness and duration of the response, potentially enhancing preventive strategies against herpes zoster in a population at increased risk.Trial registrationClinicalTrials.gov (NCT05604911).

The CLARION study: first report on safety findings in patients newly initiating treatment with cladribine tablets or fingolimod for multiple sclerosis

Objectives: As part of the CLARION study: (1) characterize the incidence of severe infections, herpes zoster, and malignancies in patients newly initiating cladribine or fingolimod for relapsing multiple sclerosis (MS); (2) estimate the incidence of severe lymphopenia among cladribine users; and (3) describe prior/subsequent disease-modifying therapy (DMT) in both cohorts. Methods: Patients were identified from seven participating MS registries/data sources. The incidence rate (IR) of each outcome per 1000 patient-years and its 95% confidence interval (95%CI) were estimated for cohorts using Poisson regression. Results: By cut-off date (01-April-2020), 742 cladribine and 867 fingolimod users were included. Mean follow-up was ∼1 year. The IR for severe infections from all contributing sources (except Denmark) was: cladribine, 7.37 (2.76,19.6); fingolimod, 6.55 (2.46,17.4). The corresponding IR for herpes zoster was 5.51 (1.78,17.1) and 3.27 (0.82,13.1), respectively, while values for opportunistic infections were 0 (0,6.76) and 1.63 (0.23,11.6), respectively. There were no events of progressive multifocal leukoencephalopathy in either cohort. The IR of severe lymphopenia was 63.9 (40.7,100.1) in 349 cladribine users from contributing sources. The IR of malignancies (cut-off date 01-April-2022) was 3.55 (1.59,7.90) for the cladribine cohort (N = 1035) and 3.55 (1.48,8.52) for the fingolimod cohort (N = 843) from three MS registries/data sources. In the combined data sources, 36.8% of cladribine and 27.4% of fingolimod users were DMT-naïve; after initiation of study treatment, 2.5% and 20.2% switched to another DMT, respectively. Conclusion: No new safety signal was observed in patients treated with cladribine tablets, although results are limited by a relatively short duration of follow-up.

Dupilumab strengthens herpes simplex virus type 1–specific immune responses in atopic dermatitis

Impaired virus clearance in a subgroup of atopic dermatitis (AD) patients can lead to severe herpes simplex virus (HSV) infections called eczema herpeticum (EH). We recently identified a type 2 skewed viral immune response in EH patients. Clinical data suggest a reduced incidence of EH in AD patients treated with dupilumab, although immunologic investigations of this phenomenon are still lacking. We examined the impact of dupilumab on the HSV type 1 (HSV-1) specific immune response in AD, focusing on patients with (ADEH+) and without (ADEH-) a history of EH. Sera and peripheral blood mononuclear cells were collected from ADEH+ and ADEH- patients, a subgroup of whom was receiving dupilumab treatment, and healthy controls. Serum samples were tested for IgE against HSV-1 glycoprotein D (n= 85). Peripheral blood mononuclear cells were stimulated with HSV peptides, and activated CD4+ and CD8+ cells were characterized by flow cytometry after magnetic enrichment via CD154 or CD137 (n= 60). Cytokine production of HSV-1-reactive T-cell lines (n= 33) and MHC-I tetramer+ (HSV-1-UL25) CD8+ T cells was investigated by bead assay and intracellular cytokine staining (n= 21). We confirmed that HSV-1-specific IgE is elevated in ADEH+ patients. During dupilumab treatment, the IgE levels were significantly decreased, reaching levels of healthy controls. HSV-1-specific TC1 frequencies were elevated in ADEH- patients treated with dupilumab compared to dupilumab-negative patients. There were no changes in the frequencies of HSV-1-specific TH cells while receiving dupilumab therapy. AD patients receiving dupilumab exhibited elevated IFN-γ and reduced IL-4 production in HSV-1-UL25-epitope-specific T cells compared to dupilumab-negative patients. Dupilumab may improve the HSV-1-specific immune response in AD as a result of an increased type I immune response and a reduction of HSV-1-specific IgE.

Autoantibodies targeting type I interferons: Prevalence, mechanisms of induction, and association with viral disease susceptibility.

The type I IFN (IFN-I) system is essential to limit severe viral disease in humans. Thus, IFN-I deficiencies are associated with serious life-threatening infections. Remarkably, some rare individuals with chronic autoimmune diseases develop neutralizing autoantibodies (autoAbs) against IFN-Is thereby compromising their own innate antiviral defenses. Furthermore, the prevalence of anti-IFN-I autoAbs in apparently healthy individuals increases with age, such that ∼4% of those over 70 years old are affected. Here, I review the literature on factors that may predispose individuals to develop anti-IFN-I autoAbs, such as reduced self-tolerance caused by defects in the genes AIRE, NFKB2, and FOXP3 (among others), or by generally impaired thymus function, including thymic involution in the elderly. In addition, I discuss the hypothesis that predisposed individuals develop anti-IFN-I autoAbs following "autoimmunization" with IFN-Is generated during some acute viral infections, systemic inflammatory events, or chronic IFN-I exposure. Finally, I highlight the enhanced susceptibility that individuals with anti-IFN-I autoAbs appear to have towards viral diseases such as severe COVID-19, influenza, or herpes (e.g., varicella-zoster virus, herpes simplex virus, cytomegalovirus), as well as adverse reactions to live-attenuated vaccines. Understanding the mechanisms underlying development and consequences of anti-IFN-I autoAbs will be key to implementing effective prophylactic and therapeutic measures.

Rapid efficacy of anifrolumab across multiple subtypes of recalcitrant cutaneous lupus erythematosus parallels changes in discrete subsets of blood transcriptomic and cellular biomarkers.

Observations with rituximab suggest B-cell independent mechanisms of cutaneous lupus erythematosus (CLE) in systemic lupus erythematosus (SLE), especially discoid lupus erythematosus (DLE). Type-I interferon receptor blockade with anifrolumab shows efficacy in SLE, but efficacy for cutaneous disease of specific morphologies has not been studied. Interferon has pleotropic immune effects and it is unknown which of these are critical to therapeutic response. We evaluated clinical efficacy and quality-of-life impact of type-I interferon-blockade in: (i) rituximab-refractory CLE; (ii) DLE and other morphologies and (iii) transcriptomic and flow cytometric biomarkers. We conducted a prospective single-centre study of anifrolumab in refractory mucocutaneous SLE. CLE Disease Area and Severity Index (CLASI) activity score, health-related quality of life, 96-probe TaqMan® gene expression analysis capturing key SLE blood transcriptome signatures, and eight-colour flow cytometry were undertaken at baseline, 1, 3 and 6 months. Seven patients [DLE (n = 5), chilblain lupus erythematosus (n = 1), subacute CLE (n = 1)] were evaluated. The median number of prior therapies was six (range 3-15), including rituximab in six of seven patients. Median CLASI-A showed rapid and sustained improvement from 17 at baseline to 6 (P = 0.016) at 1 month and 0 (P < 0.001) by 3 months. The median percentage reduction in CLASI-A at 3 months was 60%. Significant improvements were observed in Dermatology Life Quality Index scores (P < 0.001), EuroQol 5D visual analogue scale (P = 0.002) and LupusQoL fatigue, image and planning domains (P ≤ 0.05). One patient discontinued treatment owing to severe herpes zoster. Clinical responses paralleled discrete suppression of interferon-stimulated genes (ISGs) from SLE blood transcriptome module M1.2 with more varied downregulation in other interferon modules. Myeloid and inflammation-annotated genes remained upregulated throughout treatment. Intermediate monocytes (CD14++CD16+) reduced to normal levels during therapy (P = 0.014), while other flow subsets showed no substantive changes. These data indicate rapid efficacy of anifrolumab in DLE and rituximab-resistant CLE. Response is associated with suppression of a subset of ISGs and decline in intermediate monocytes. Suppression of all ISGs or the wider SLE blood transcriptome is not required for response.

Electroencephalography for prognostication of outcome in adults with severe herpes simplex encephalitis

BackgroundElectroencephalography (EEG) is recommended for the practical approach to the diagnosis and prognosis of encephalitis. We aimed to investigate the prognostic value of standard EEG (stdEEG) in adult patients with severe herpes simplex encephalitis.MethodsWe performed a retrospective analysis of consecutive ICU patients with severe herpes simplex encephalitis in 38 French centers between 2006 and 2016. Patients with at least one stdEEG study performed at ICU admission were included. stdEEG findings were reviewed independently by two investigators. The association between stdEEG findings (i.e., background activity, lateralized periodic discharges, seizures/status epilepticus, and reactivity to painful/auditory stimuli) and poor functional outcome, defined by a score on the modified Rankin Scale (mRS) of 3 to 6 (moderate to severe disability or death) at 90 days, were investigated.ResultsWe included 214 patients with at least one available stdEEG study. The first stdEEG was performed after a median time of one (interquartile range (IQR) 0 to 2) day from ICU admission. At the time of recording, 138 (64.5%) patients were under invasive mechanical ventilation. Lateralized periodic discharges were recorded in 91 (42.5%) patients, seizures in 21 (9.8%) and status epilepticus in 16 (7.5%). In the whole population, reactivity to auditory/noxious stimuli was tested in 140/214 (65.4%) patients and was absent in 71/140 (33.2%) cases. In mechanically ventilated patients, stdEEG reactivity was tested in 91/138 (65.9%) subjects, and was absent in 53/91 (58.2%) cases. Absence of reactivity was the only independent stdEEG finding associated with poor functional outcome in the whole population (OR 2.80, 95% CI 1.19 to 6.58) and in the subgroup of mechanically ventilated patients (OR 4.99, 95% CI 1.6 to 15.59). Adjusted analyses for common clinical predictors of outcome and sedation at time of stdEEG revealed similar findings in the whole population (OR 2.03, 95% CI 1.18 to 3.49) and in mechanically ventilated patients (OR 2.62, 95% CI 1.25 to 5.50).ConclusionsAbsence of EEG reactivity to auditory/noxious stimuli is an independent marker of poor functional outcome in severe herpes simplex encephalitis.

Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir.

Practically the entire global population is infected by herpesviruses that establish lifelong latency and can be reactivated. Alpha-herpesviruses, herpes simplex viruses 1 and 2 (HSV-1/HSV-2) and varicella zoster virus (VZV), establish latency in sensory neurons and then reactivate to infect epithelial cells in the mucosa or skin, resulting in a vesicular rash. Licensed antivirals inhibit virus replication, but do not affect latency. On reactivation, VZV causes herpes zoster, also known as shingles. The 76-year-old first author of this paper published an autobiography of his own severe herpes zoster ophthalmicus (HZO) infection with orbital edema, which is considered an emergency condition. Acyclovir (ACV) treatment was complemented with an immunostimulatory viral therapy, which resolved most symptoms within a few days. The orally administered live-attenuated infectious bursal disease vaccine virus (IBDV) delivers its double-stranded RNA (dsRNA) cargo to host cells and activates the natural antiviral interferon (IFN) gene defense system from within the host cells. IBDV has already been demonstrated to be safe and effective against five different families of viruses, hepatitis A virus (HAV), hepatitis B and C virus (HBV/HCV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and varicella zoster virus (VZV). Here we propose a short phase I/II trial in elderly shingles patients who will be assigned to receive either ACV monotherapy or ACV combined with R903/78, an attenuated immunostimulatory IBDV strain. The primary endpoints will be safety, but the efficacy of the combination therapy against the ACV monotherapy also will be assessed.

MRI changes and expressions of neuron-specific enolase and monocyte chemoattractant protein-1 in cerebrospinal fluid in patients with severe herpes simplex virus encephalitis.

The objective of this research was to analyze the MRI changes and the expression of neuron-specific enolase (NSE) and monocyte chemoattractant protein-1 (MCP-1) in cerebrospinal fluid (CSF) of patients with severe herpes simplex encephalitis. For this purpose, 68 patients with severe herpes simplex virus encephalitis diagnosed and treated in our hospital from April 2020 to April 2021 were selected as the study objects of the study group. In addition, 68 healthy people who underwent normal physical examinations in our hospital were selected as the control group at the same time. They were examined by magnetic resonance imaging (MRI) within one week after the study group was enrolled. CSF samples were collected one week after the onset of the disease in the study group and 2-4 days after the first spinal anesthesia in the control group, Enzyme linked immunosorbent assay (ELIEA) was used to detect the expression of NSE and MCP-1 in cerebrospinal fluid of the two groups, and the linear correlation between NSE and MCP-1 were analyzed. Results showed that compared with the control group, the expression of NSE and MCP-1 in the cerebrospinal fluid of the study group increased significantly (P<0.05). The expression of NSE and MCP-1 in patients with severe herpes simplex encephalitis in a coma was significantly higher than that in patients without severe herpes simplex encephalitis in a coma (P<0.05). NSE and MCP-1 were positively correlated (r=0.597, P=0.001). NSE and MCP-1 were risk factors for severe herpes simplex encephalitis, and the difference was statistically significant (P<0.05). In conclusion, magnetic resonance imaging of patients with severe herpes simplex encephalitis is characterized by multiple lesions in the temporal lobe, insula, and frontal lobe base (especially the marginal system involved) with unilateral or bilateral asymmetric distribution, and abnormal high expression of NSE and MCP-1 in the cerebrospinal fluid of such patients, which has important value in the early diagnosis of this disease.

A case report of severe systemic herpes simplex virus-1 (HSV-1) infection with multi-organ involvement after a course of oral corticosteroid treatment

BackgroundHerpes simplex virus (HSV) rarely causes organ-invasive infection. Diagnosis and treatment for such infections are often delayed, and mortality is high. We present the first reported case of disseminated HSV-1 infection in an adult causing liver failure, myocarditis, and encephalitis in a patient who recovered after receiving parenteral acyclovir treatment.Case presentationA 46-year-old female presented with fever, chills, and malaise after 2 weeks of oral corticosteroid treatment for uveitis. She was diagnosed with disseminated HSV-1 infection with multi-organ involvement causing hepatitis, encephalitis, and myocarditis. Diagnosis was made timely using serum polymerase chain reaction (PCR) for HSV DNA and the patient was given intravenous acyclovir treatment promptly, which led to her survival without significant morbidity.ConclusionsClinicians should have a low threshold for suspecting HSV infection and ordering HSV PCR to decrease morbidity and mortality when there is a high clinical suspicion of systemic HSV infection with multi-organ involvement. Serum PCR for HSV DNA is an excellent modality for an initial diagnostic approach. Further research is warranted to elucidate causality between a course of corticosteroid therapy and systemic HSV-1 infection without major immunosuppressive comorbidities or treatments.

A Clinically Validated, Broadly Active, Oral Viral Superinfection Therapy Could Mitigate Symptoms in Early-stage COVID-19 Patients.

More than 200 viruses infect humans, but treatments are available for less than ten of them. To narrow the gap between 'bugs and drugs,' a paradigm shift is required. The "one drug, one bug" approach can be expanded to a "one drug, multiple bugs" strategy such that the host's defense system is targeted rather than the virus. Viral superinfection therapy (SIT) activates interferon genes' natural, antiviral defense system of host cells following exposure to viral infection, e.g., superinfection with an attenuated infectious bursal disease virus (IBDV) with the release of its double-stranded RNA (dsRNA) cargo inside host cells. An attenuated IBDV therapeutic vaccine has successfully treated hepatitis A virus infection (HAV) in marmoset monkeys as well as acute hepatitis B and hepatitis C virus infections (HBV/HCV) in 42 patients. SIT has also been shown to be safe and effective in four patients with chronic HBV or HCV infection with hepatic decompensation. The proof-of-principle of SIT has also been demonstrated in a 43-year-old male patient with COVID-19. Three doses of orally administered IBDV (3x106 IU) alleviated most of his COVID-19 symptoms; even his sense of smell returned within a week. Two additional COVID-19 patients responded similarly to oral treatment with IBDV. Furthermore, a severe herpes zoster ophthalmicus outbreak with orbital edema responded to a combination of acyclovir and 7 doses of IBDV (7x106 IU) within a few days. IBDV is simple to manufacture and affordable, even in resource-limited settings. Acid-resistant IBDV can be orally administered in an outpatient setting, providing simple dosing and high medication adherence. Under an Emergency Use Authorization, the broad-spectrum IBDV drug candidate could be tested immediately in clinical trials and rapidly distributed to millions of early-stage patients with COVID-19. The German Paul Ehrlich Institute is currently supporting a phase I safety study for persons acutely infected with SARS‑CoV-2. An expert team of the US National Institutes of Health-sponsored ACTIV public-private partnership came to the conclusion that the IBDV drug candidate shows merit as a potential treatment for COVID19, and an FDA-approved clinical trial is in the pipelines in Los Angeles.

Autosomal recessive hyper‐IgE syndrome due to DOCK8 deficiency: An adjunctive role for omalizumab

AbstractAutosomal recessive hyper‐IgE syndrome (AR‐HIES) is a rare primary immunodeficiency disorder characterized by high serum IgE levels, recurrent viral skin infections, severe allergies, and early‐onset malignancies, associated with mutations in the gene encoding the dedicator of cytokinesis 8 protein (DOCK8). We report a rare case of AR‐HIES with DOCK8 deficiency in a young Japanese male with a past medical history of chronic atopic dermatitis, severe food allergies, and severe herpes simplex virus infection. Treatment was successfully based on infection management, skincare, and dietary elimination. In addition, anti‐IgE therapy with omalizumab was the target treatment for this syndrome.

Lower disease activity but higher risk of severe COVID-19 and herpes zoster in patients with systemic lupus erythematosus with pre-existing autoantibodies neutralising IFN-α

ObjectivesType-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-β and/or IFN-ω subtypes are strong determinants of...

Can skin affection be a clue to COVID-19? results from a dermatology outpatient clinic in Egypt

Background Coronavirus disease 2019 (COVID-19)-infected individuals can be asymptomatic or have mild symptoms. Cutaneous affection with COVID-19 is a unique presentation. Objective To describe the clinical presentations of skin affection in COVID-19-confirmed patients attending a dermatology outpatient clinic. Patients and methods A retrospective analysis was performed on the medical records of a single dermatology outpatient clinic described cutaneous presentations associated with COVID-19 infection in patients attending in the period from October 2020 to December 2020. Results A total of 44 COVID-19-positive patients presented with skin affection. The most common presentation was urticaria (24, 54.5%), followed by herpes simplex (seven, 15.9%), herpes zoster (four, 9.1%), papulosquamous (three, 6.9%), papulovesicular (two, 4.6%), acral lesions (two, 4.6%), leukocytoclastic vasculitis (one, 2.3%), and Kawasaki-like disease (one, 2.3%). Nine (20.5%) patients had asymptomatic COVID-19 infection, 24 (54.5%) patients had mild COVID-19, nine (20.5%) patients had moderate COVID-19, and two (4.5%) patients had severe COVID-19. Among patients with COVID-19 symptoms (35, 79.5%), seven (20%) patients presented with the cutaneous presentation before the onset of COVID-19 symptoms, whereas in the rest of the patients, cutaneous affection was simultaneous with COVID-19 symptoms (28, 80%). Conclusion Cutaneous affection can be the striking presentation for COVID-19 requiring dermatological consultation. Awareness and early recognition of skin affection associated with COVID-19 are required. Dermatologists should follow all of the precautions and use adequate personal protective equipment during their outpatient practices. Skin presentations, notably urticaria, can precede the systemic and respiratory symptoms of COVID-19. Severe mucocutaneous herpes simplex can occur with COVID-19 and require prompt medical treatment.

Fuchs Syndrome with Isolated Oral Mucosa Lesions due to Severe Herpes Simplex Cheilitis in a Patient with Idiopathic Thrombocytopenic Purpura

Stevens-Johnson syndrome (SJS) is a severe dermatological disease classically characterized by erythematous target lesions and mucosal involvement. Fuchs syndrome is an incomplete presentation of SJS which has oral, conjunctival and genital manifestations but no skin lesions. To the best of our knowledge, our case of Fuchs syndrome in an 80-year-old man is the first such case related to herpes simplex virus (HSV)-1 infection to be described. Our patient quickly recovered following IVIG therapy, although specific treatment is still a topic of discussion. Research is required on this poorly understood dermatological disease to determine optimum therapy.LEARNING POINTSWe report a case of Fuchs syndrome in an elderly man after HSV-1 cheilitis.Therapy always includes discontinuation of the causative drug.Specific therapy for Stevens-Johnson syndrome and Fuchs syndrome is still a topic of discussion, although we noted marked improvement following the administration of IVIG therapy.