Comment to: Disseminated cutaneous herpes simplex, COVID-19 vaccination and rheumatoid arthritis patient: a case report and review.

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Infections with Herpes simplex and Varicella zoster virus.

Human herpes viruses belong to the DNA viruses and are among the most common viral pathogens. Currently, eight human herpes viruses have been characterized. Primary infection is typically followed by virus latency. Viral reactivations are more often symptomatic than primary infections and lead more often to medical consultation. In daily practice, infections with herpes simplex virus (HSV) and varicella zoster virus (VZV) are the most common. If HSV primary infections become clinically manifest, they are often accompanied by systemic symptoms whereas manifest HSV reactivations are usually harmless, self-limiting and present as grouped vesicles on an erythematous base (herpetiform). Primary VZV infection leads to the clinical picture of varicella (chickenpox). VZV reactivation manifests clinically as shingles and can be accompanied by severe acute neuralgiform pain. In immunosuppression, complicated (necrotizing, ulcerative, hemorrhagic, generalized) manifestations may occur. The diagnosis is usually made clinically. Therapeutic options include topical agents and systemic antivirals. Adequate therapeutic management includes the recognition and treatment of complications such as the possible involvement of other organ systems and pain. Infection during pregnancy may result in transmission to the unborn child.

A rare case of aseptic herpes simplex virus-1 meningitis in a patient with recent COVID-19.

The aim of presenting this case was to show the difficulties in making the differential diagnosis of viral meningitis during the COVID pandemic situation.

Herpes simplex virus retinitis following ChAdOx1 nCoV- 19 (Covishield) vaccination for SARS CoV 2: A case report.

PURPOSE: To report a case of herpes simplex virus retinitis following ChadOx1 nCoV-19 (covishield) vaccination. CASE REPORT: A 29 year old immunocompetent male presented with unilateral disc edema with adjacent retinitis two days after receiving the first dose of ChAdOx1 nCoV-19 vaccination. Extensive investigations to rule out infective etiology were negative except for polymerase chain reaction (PCR) of the vitreous specimen which was positive for the herpes simplex virus. A diagnosis of herpes simplex (HSV) retinitis post covid vaccination was made. The patient responded well to oral antivirals and steroids. CONCLUSION: HSV retinitis is a rare complication following the COVID-19 vaccination.

Herpes Simplex Virus 1 Anterior Uveitis following Coronavirus Disease 2019 (COVID-19) Vaccination in an Asian Indian Female.

PURPOSE: To describe a case of herpes simplex virus 1 (HSV 1) infection following coronavirus disease 2019 (COVID-19) vaccination in an Asian Indian female. METHODS: Retrospective case report. RESULT: A 40-year-old female presented with decreased vision, pain, and photophobia of 2 weeks duration. She reported receiving the second dose of COVISHIELDTM (ChAdOx1-S [recombinant]) 1 week prior to the onset of ocular symptoms. Left eye examination revealed granulomatous anterior uveitis. Aqueous sample from the left eye tested positive for HSV1 by polymerase chain reaction(PCR) method. She was managed with oral antiviral therapy, topical steroids, and cycloplegic agent and showed significant improvement of inflammation within 1 week and resolved within 3 weeks. CONCLUSION: This report demonstrates a potential association of HSV 1 anterior uveitis with COVID-19 vaccination. A high index of suspicion of viral etiology is warranted when uveitis presents with reduced corneal sensations and pigmented keratic precipitates, following a recent history of COVID-19 vaccination.

The Term Newborn: Congenital Infections.

Maternal pathogens can be transmitted to the fetus resulting in congenital infection with sequelae ranging from asymptomatic infection to severe debilitating disease and still birth. The TORCH pneumonic (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus) is used widely, but it provides a limited description of the expanding list of pathogens associated with congenital infection. This article focuses on the evaluation and management of infants with common congenital infections such as cytomegalovirus, and infections that warrant early diagnosis and treatment to prevent serious complications, such as toxoplasmosis, human immunodeficiency virus, and syphilis. Zika virus and Chagas disease remain uncommon.

False positive Herpes Simplex IgM serology in COVID-19 patients correlates with SARS-CoV-2 IgM/IgG seropositivity.

Differentiating COVID-19 from other causes of viral pneumonia, like herpes simplex (HSV), can be complicated by shared clinical and laboratory features. Viral pneumonia is mostly diagnosed based on molecular or serological techniques. Serological immunoassay interferences, often attributed to concurrent appearance of heterologous (viral) immunoglobulins, is well-known, but has not been studied in COVID-19 patients. Following false positive HSV immunoglobulin M (IgM) results in our index patient, 25 other COVID-19 patients were tested for HSV-1/2 IgM with the chemiluminescent Liaison assay and Euroimmun enzyme-linked immunosorbent assay. Forty-five percent of COVID-19 patients tested positive for HSV IgM with Liaison. No HSV indices were positive with Euroimmun enzyme-linked immunosorbent assay, suggesting immunoassay interference. Significant correlation between HSV IgM and SARS-CoV-2 IgM/IgG positivity was found. Adding 0.5% polyvinylpyrrolidone, inhibiting non-specific solid-phase adsorption, abolished interference in 22% of false positive cases, suggesting interference caused by solid-phase reactive IgM. Hence, serologic immunoassay results should be interpreted with caution in COVID-19 patients.

Seroprevalence of Toxoplasma gondii, Rubella, Group A Streptococcus, CMV and HSV-1 in COVID-19 Patients with Vitamin D Deficiency.

<b>Background and Objective:</b> In recent years, respiratory tract viral infections have caused many pandemics that impact the whole world. To investigate the seropositivity of <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> in recovered COVID-19 patients and correlate these findings with vitamin D levels. <b>Materials and Methods:</b> A total of 417 COVID-19 patients with diarrhoea were enrolled in this study. Vitamin D and seroprevalence for <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> were evaluated and correlated. <b>Results:</b> It was found that recent infection in COVID-19 patients with HSV-1, rubella, <i>Toxoplasma</i> and CMV, respectively. IgG was detected indicating the development of adaptive immunity with all microbes. <b>Conclusion:</b> Current study detected a correlation between vitamin D levels and HSV-1 and no correlation between this infection and vitamin D deficiency with the other microbes.

COVID-19 pandemic as a risk factor for the reactivation of herpes viruses.

The appearance on the skin of herpes virus lesions, concomitantly with the coronavirus disease 2019 (COVID-19) pandemic, leads us to suspect an underlying infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Diagnostic reverse transcriptase polymerase chain reaction tests and immunoglobulin M (IgM) and IgG seroconversion studies have therefore been carried out. We present three cases of herpes virus infections in immunocompetent patients: one of the infections was herpes simplex 1 in a 40-year-old woman, and the other two were herpes varicella-zoster infections in a 62-year-old man and a 25-year-old woman. The patients were in the care of the southern health district of Seville of the SAS (Andalusian Health Service) during the Spanish state of alarm over the COVID-19 pandemic. The SARS-CoV-2 infection was confirmed in only one of the three cases. In this study, we briefly review the etiopathogenic role of the COVID-19 pandemic situation, whereby immunodeficiencies are generated that favour the appearance of other viral infections, such as herpes virus infections.

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.

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.

Positive detection of SARS-CoV-2 combined HSV1 and HHV6B virus nucleic acid in tear and conjunctival secretions of a non-conjunctivitis COVID-19 patient with obstruction of common lacrimal duct.

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