Experimental Herpes Simplex Virus Encephalitis

Baringer, J. Richard; Klassen, Toni; Grumm, Fred

doi:10.1001/archneur.1976.00500060048010

Cited by 23 publications

(5 citation statements)

References 25 publications

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“…The anti-inflammatory effects of glucocorticoids are always rapid and significant and are commonly used in the suppression of strong and harmful inflammatory process in pathophysiologic conditions. However, slow-down of the clearance of virus (including SARS-CoV-2) is always observed in the infected cases with systemic usage of glucocorticoids [13][14][15]. This might be the reason why the recurrence of COVID-19 happened in the case we reported here.…”

Section: Review and Discussionmentioning

confidence: 68%

A complex COVID-19 case with rheumatoid arthritis treated with tocilizumab

Cai

Sun

et al. 2020

Clin Rheumatol

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Recurrences of COVID-19 were observed in a patient with long-term usage of hydroxychloroquine, leflunomide, and glucocorticoids due to her 30-year history of rheumatoid arthritis (RA). Tocilizumab was applied and intended to target both COVID-19 and RA. However, disease of this patient aggravated after usage of tocilizumab. After the discussion of a multiple disciplinary team (MDT) including rheumatologists, antimicrobial treatments were applied to target the potential opportunistic infections (Pneumocystis jirovecii and Aspergillus fumigatus), which were authenticated several days later via high throughput sequencing. As an important cytokine in immune responses, IL-6 can be a double-edged sword: interference in the IL-6-IL-6 receptor signaling may save patients from cytokine release storm (CRS), but can also weaken the anti-infectious immunity, particularly in rheumatic patients, who may have received a long-term treatment with immunosuppressive/modulatory agents. Thus, we suggest careful considerations before and close monitoring in the administration of tocilizumab in rheumatic patients with COVID-19. Besides tocilizumab, several disease-modifying antirheumatic drugs (DMARDs) can also be applied in the treatment of COVID-19. Therefore, we also reviewed and discussed the application of these DMARDs in COVID-19 condition. Keywords Coronavirus disease 2019. Rheumatoid arthritis. Secondary opportunistic infection. Tocilizumab Coronavirus disease 2019 (COVID-19) has progressed to a worldwide pandemic situation, and millions of people are suffering from this lethal disease. Many cytokines involved in the pathogenesis of rheumatic diseases (particularly rheumatoid arthritis, RA), such as IL-6, were elevated in COVID-19 [1-3]. Persistent and dramatic elevation of serum IL-6 level was associated with higher mortality in COVID-19 patients [4]. It seems that administration of tocilizumab can be a perfect solution to treat COVID-19 and RA at the same time. However, every coin has two sides. Application of tocilizumab may bring unsuspected effects. Here, we first reported the complex treatment process of a COVID-19 patient with RA history and illustrated the importance of recognizing the feasibility of tocilizumab application in the therapeutic process. Case presentation The case we reported here was a 72-year-old female with a history of RA for nearly 30 years. She had taken leflunomide (LEF, 20 mg po qd) for 10 years and hydroxychloroquine (HCQ, 0.2 g po bid) for 1 year. Based on the clinical characteristics and therapeutic processes, this report was divided into two parts.

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Section: Review and Discussionmentioning

confidence: 68%

A complex COVID-19 case with rheumatoid arthritis treated with tocilizumab

Cai

Sun

et al. 2020

Clin Rheumatol

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“…These animal models are thus convenient to study the efficacy of corticosteroids or other immunomodulatory drugs to ameliorate the outcome of HSE, as reported in Table 2. The first study evaluated the effect of subcutaneous injections of methylprednisolone started 1 day prior to inoculation of HSV-1 on the scarified cornea of rabbits and continued until their sacrifice (198). Treatment with steroids did not markedly affect viral replication.…”

Section: Clinical and Animal Studies With Corticosteroidsmentioning

confidence: 99%

Immunomodulatory Strategies in Herpes Simplex Virus Encephalitis

Piret

Boivin

2020

Clin Microbiol Rev

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SUMMARY Herpes simplex virus 1 (HSV-1) can be responsible for life-threatening HSV encephalitis (HSE). The mortality rate of patients with HSE who do not receive antiviral treatment is 70%, with most survivors suffering from permanent neurological sequelae. The use of intravenous acyclovir together with improved diagnostic technologies such as PCR and magnetic resonance imaging has resulted in a reduction in the mortality rate to close to 20%. However, 70% of surviving patients still do not recover complete neurological functions. Thus, there is an urgent need to develop more effective treatments for a better clinical outcome. It is well recognized that cerebral damage resulting from HSE is caused by viral replication together with an overzealous inflammatory response. Both of these processes constitute potential targets for the development of innovative therapies against HSE. In this review, we discuss recent progress in therapy that may be used to ameliorate the outcome of patients with HSE, with a particular emphasis on immunomodulatory agents. Ideally, the administration of adjunctive immunomodulatory drugs should be initiated during the rise of the inflammatory response, and its duration should be limited in time to reduce undesired effects. This critical time frame should be optimized by the identification of reliable biomarkers of inflammation.

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“…Results from animal studies as to the effect of steroids on viral disease have been heterogeneous. While some authors describe an exacerbation or unchanged outcome in steroid-treated animals [ 30 ], others see more favorable results [ 31 , 32 ]. In a mouse model of HSV-1 encephalitis, a reduction of chronic progressive magnetic resonance imaging (MRI) changes was detected in mice treated with methylprednisolone and acyclovir compared to those on acyclovir monotherapy [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Steroids for the treatment of viral encephalitis: a systematic literature review and meta-analysis

et al. 2023

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Background Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its utility. We present a systematic review and meta-analysis on the outcome of steroid use in VE. Methods We conducted a systematic literature review and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two observational studies from unpublished or partially published data were added. For the meta-analysis, we employed the metaphor package of the statistical software R-4.3.1. Results We screened 378 studies and included 50. 155 patients were added from the Houston and Linz cohorts. Individual data were available for 281 persons, 120 (43%) of whom received steroids. The most common pathogens were herpes simplex virus 1, West Nile virus, and measles. Study designs and patient outcomes were heterogeneous. Only three of the trials report an advantage of steroid therapy. Steroid-induced side effects were scarce. Ten cohorts were included into the meta-analysis. For the pooled data, the null hypothesis could not be rejected (p = 0.245) using a random effects model, i.e., a benefit of steroid treatment on survival in VE could not be shown. Conclusions Steroids as potent anti-inflammatory agents may act through a reduction of secondary inflammation-mediated damage. Our data do not support the use of steroids in VE. However, multiple shortcomings apply. Standardized controlled trials are needed to investigate optimal dosing and timing of steroid administration and to explore potential subgroups that could benefit.

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Experimental Herpes Simplex Virus Encephalitis

Cited by 23 publications

References 25 publications

A complex COVID-19 case with rheumatoid arthritis treated with tocilizumab

A complex COVID-19 case with rheumatoid arthritis treated with tocilizumab

Immunomodulatory Strategies in Herpes Simplex Virus Encephalitis

Steroids for the treatment of viral encephalitis: a systematic literature review and meta-analysis

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