Fraternal Twins: The Enigmatic Role of the Immune System in Alphaherpesvirus Pathogenesis and Latency and Its Impacts on Vaccine Efficacy.

Although the establishment, maintenance and reactivation from alphaherpesvirus latency is far from fully understood, some things are now manifestly clear: Alphaherpesvirus latency occurs in neurons of the peripheral nervous system and control of the process is multifactorial and complex. This includes components of the immune system, contributions from non-neuronal cells surrounding neurons in ganglia, specialized nucleic acids and modifications to the viral DNA to name some of the most important. Efficacious vaccines have been developed to control both acute varicella and zoster, the outcome of reactivation, but despite considerable effort vaccines for acute herpes simplex virus (HSV) infection or reactivated lesions have thus far failed to materialize despite considerable effort. Given the relevance of the immune system to establish and maintain HSV latency, a vaccine designed to tailor the HSV response to maximize the activity of components most critical for controlling reactivated infection might limit the severity of recurrences and hence reduce viral transmission. In this review, we discuss the current understanding of immunological factors that contribute to HSV and VZV latency, identify differences between varicella-zoster virus (VZV) and HSV that could explain why vaccines have been valuable at controlling VZV disease but not HSV, and finish by outlining possible strategies for developing effective HSV vaccines.

Herpes simplex and herpes zoster viruses in COVID-19 patients.

BACKGROUND: Reactivation of herpes family viruses in immunocompromised patients may result in detrimental outcomes for the hosts; therefore, herpes simplex virus-1 and varicella zoster virus infections in the context of COVID-19 may have clinical and prognostic implications. Several reports associated this human herpes virus with COVID-19 infection and have claimed that it can be an indicator for latent COVID-19 infection. However, since most of these were case reports, it is impossible to assess the prevalence of these associations. METHODS: The University of Florida patient registry i2b2 with ICD-10 diagnosis codes was used for retrieval of patients with diagnosis of COVID-19 and each of the other viruses over the period of October 2015-June 2020. RESULTS: The prevalence of the herpes simplex-1 occurrence in the COVID-19 group was 2.81% compared to 0.77% in the hospital population odds ratio of 5.27. When adjusted for gender, race, and age, the odds were 5.18, 4.48, and 4.61, respectively. After adjustment for respiratory disease, endocrine disease, obesity, diabetes, circulatory disease, and smoking, the odds were 1.94, 3.18, 1.37, 3.54, 3.7, and 5.1, respectively. The prevalence of the varicella zoster virus in COVID-19 patients was 1.8% compared to 0.43% in the hospital population, odds ratio of 5.26 before adjustment, and 5.2, 5.47, and 4.76 after adjusting for gender, age, and race, respectively. When adjusted for respiratory disease, endocrine disease, obesity, diabetes, and circulatory and neurological diseases, the odds were 1.3, 2.2, 1.48, 2.33, 2.85, and 2.6, respectively. CONCLUSION: Herpes simplex-1 and varicella zoster viruses are strongly associated with COVID-19 infection.

Prenatal infection and schizophrenia: A decade of further progress.

Epidemiologic studies have provided evidence that prenatal exposure to maternal infection is associated with an increased risk of developing schizophrenia in the offspring. Research over the past decade has added further to our understanding of the role of prenatal infection in schizophrenia risk. These investigations include several well-powered designs, and like some earlier studies, measured maternal antibodies to specific infectious agents in stored serum samples and large registers to identify clinically diagnosed infections during pregnancy. Convergent findings from antibody studies suggest that prenatal maternal infection with Toxoplasma gondii is associated with increased schizophrenia risk in the offspring, while associations with HSV-2 infection are likely attributable to confounding. Maternal influenza infection remains a viable candidate for schizophrenia, based on an early serological study, though there has been only one attempt to replicate this finding, with a differing methodology. A prior association between maternal serologically confirmed cytomegalovirus infections require further study. Clinically diagnosed maternal infection, particularly bacterial infection, also appears to be associated with increased risk of offspring schizophrenia, and heterogeneity in these findings is likely due to methodological differences between studies. Further clarification may be provided by future studies that address the timing, type, and clinical features of infections. Important insight may be gained by examining the long-term offspring outcomes in emerging epidemics such as Zika virus and COVID-19, and by investigating the interaction between exposure to prenatal infection and other risk or protective factors.

Hepatic Manifestations of Nonhepatotropic Infectious Agents Including Severe Acute Respiratory Syndrome Coronavirus-2, Adenovirus, Herpes Simplex Virus, and Coxiella burnetii.

Nonhepatotropic viruses such as adenovirus, herpes simplex virus, flaviviruses, filoviruses, and human herpes virus, and bacteria such as Coxiella burnetii, can cause liver injury mimicking acute hepatitis. Most of these organisms cause a self-limited infection. However, in immunocompromised patients, they can cause severe hepatitis or in some cases fulminant hepatic failure requiring an urgent liver transplant. Hepatic dysfunction is also commonly seen in patients with severe acute respiratory syndrome coronavirus-2 infection. Patients with preexisting liver diseases are likely at risk for severe coronavirus disease 2019 (COVID-19) and may be associated with poor outcomes.

Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic.

Neonatal herpes simplex virus (HSV) infection is rare, with an estimated incidence of 3.58 per 100 000 live births in the UK and should be suspected in any newborn with fever and bacterial culture-negative sepsis. We describe a case of a previously well full-term male neonate who presented with persistent fever and elevated ferritin level that was carried out during the era of the COVID-19 pandemic as part of SARS-CoV-2 panel investigations. Despite the initial negative HSV serology, HSV-1 PCR from a scalp lesion returned positive. He made a full recovery after acyclovir therapy. This case highlights the importance of maintaining a high clinical index of suspicion of HSV infection in any febrile neonate even with absence of maternal history and negative serology, particularly if associated with hyperferritinaemia. We also address the challenge of interpreting inflammatory biomarkers' results for SARS-CoV-2 infection in neonates.

Short report - Herpes simplex lesion in the lip semimucosa in a COVID-19 patient.

OBJECTIVE: The present case report aims to make a discussion concerning oral manifestations in a patient with a confirmed diagnosis of COVID-19. Female patient, 20 years old, nursing technician, showed severe sore throat and headache without presence of fever. She tested positive for COVID-19 RT-PCR test in 2 episodes. She also showed lesions in the median lower lip semimucosa and severe pruritus, with a clinical course of 14 days, in which we performed a clinical diagnosis of herpes simplex infection. We need to be precise in terms of clinical appearance and possible relation with the disease, as the clinicians have access to the patients.

Impact of COVID-19 and other viruses on reproductive health.

Male infertility is linked to some viral infections including human papillomavirus (HPV), herpes simplex viruses (HSV) and human immunodeficiency viruses (HIVs). Almost nothing is known about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effect on fertility. The possible risk factors of coronavirus disease 2019 (COVID-19) infection on fertility comes from the abundance of angiotensin-Converting Enzyme-2 (ACE2), receptor entry of the virus, on testes, a reduction in important sex hormone ratios and COVID-19-associated fever. Recent studies have shown a gender difference for COVID-19 rates and comorbidity. In this review, we will discuss the potential effect of COVID-19 on male fertility and talk about what needs to be done by the scientific community to tackle our limited understanding of the disease. On the other side, we will focus on what is known so far about the risk of COVID-19 on pregnancy, neonatal health and the vertical transfer of the virus between mothers and their neonates. Finally, because reproduction is a human right and infertility is considered a health disease, we will discuss how assisted reproductive clinics can cope with the pandemic and what guidelines they should follow to minimise the risk of viral transmission.