Effect of SARS-CoV-2 mRNA vaccination on ocular herpes simplex and varicella-zoster virus reactivation: should preventive antiviral treatment be given in known herpes patients,Journal of Ophthalmic Inflammation and Infection

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Effect of SARS-CoV-2 mRNA vaccination on ocular herpes simplex and varicella-zoster virus reactivation: should preventive antiviral treatment be given in known herpes patients
Journal of Ophthalmic Inflammation and Infection Pub Date : 2021-09-17 , DOI: 10.1186/s12348-021-00262-2
Carl P Herbort ₁ , Ioannis Papasavvas ₁

Affiliation

To the editor.

Herpesviruses, including herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) are commensal viruses of humans since millenaries.

Close to 80% of adults in temperate countries are exposed to HSV-1 and this proportion reaches more than 97% in case of VZV [1].

After primoinfection these viruses remain in a latent form in sensory neuronal ganglia. The colonisation of the ganglia, including the trigeminal ganglion, occurs by progression of the virus mainly within peptidergic neurons [2]. Latency is an active and complex immune mechanism where CD8-positive T cells play an important role [3]. Although mRNA vaccines stimulate CD8+ T cells it could be hypothesised that it might dysregulate latency mechanisms in the sensory nerve ganglions [4]. In case of sarcoidosis when T cells are monopolised in the granulomas there is rescue humoral compensation to control herpes viruses by polyclonal anti-herpes antibody activation [5]. In case of transient or prolonged dysfunction of the immune system by diverse causes, reactivation of the virus can occur. It then reinfects peripheral sites by travelling down neurons causing herpes labialis, dendritic keratitis, herpetic uveitis or shingles in case of VZV virus. A recent study reported 14/414 (3.4%) cases of herpes simplex and varicella-zoster eruptions among cutaneous findings after mRNA-based vaccinations, a relatively large percentage [6]. However, no details were given on these patients. We recently reported on three cases of herpes zoster ophthalmicus (HZO) after mRNA anti-SARS-CoV-2 vaccinations (Moderna and Pfizer BioNTech respectively), 2 weeks after first dose vaccination in two patients and 2 weeks after a Pfizer Bio NTech booster vaccination in another patient who had undergone Covid-19 infection [7]. Non ocular varicella-zoster reactivations after mRNA vaccinations have recently been reported [8].

We recently examined a 53-year-old man, treated in the past for herpes kerato-uveitis OD that had been inactive for 18 months without treatment. Five days after the second dose of Moderna vaccine, he presented with a severe flare-up of a granulomatous hypertensive uveitis in his right eye with numerous granulomatous KPs and an increased pressure of 41 mmHg (Fig. 1). Under valacyclovir (500 mg QID), 0.1% dexamethasone drops QID and dorzolamide hydrochloride – timolol maleate eye drops BID, pressure normalised within 6 days, laser flare photometry (LFP) flare, decreased from 19.4 ph/ms to 13.2 ph/ms 3 weeks later and granulomatous KPs had almost disappeared. Because of fluctuating IOP and LFP values thereafter, Valacyclovir (500 mg BID), Acetazolamide (125 mg/day), dorzolamide hydrochloride BID and dexamethasone 0.1% eye drops once daily had to be maintained until the last recorded follow-up two and a half months later with LFP values of 12.2 ph/ms and an IOP value of 16 mmHg.

It is difficult to know whether this episode was purely inflammatory. Even if this was the case dual corticosteroid and antiviral therapy has to be given in such circumstances.

Since this case, we advise patients having had several herpes uveitis episodes to remain under valacyclovir therapy during vaccination despite quiet uveitis to avoid potential reactivation, which was undertaken for two patients so far.

HSV-1 and VZV infections can cause substantial ocular morbidity. Since the availability of efficient antiviral agents, management of eye disease caused by herpes viruses are successfully treated in most cases and complications have been reduced [9]. However, each new episode can harm eye structures. Moreover, some herpes reactivations such as acute retinal necrosis are much more deleterious and their management much more difficult. Therefore, in patients having presented herpesvirus infections in the past, the question can be raised whether preventive antiviral therapy should be recommended, possibly at least in high-risk patients, in case of mRNA vaccination after discussing it with the patient.

For data, please refer to corresponding author.

HSV-1:: Herpes simplex virus 1
VZV:: Varicella-zoster virus
CD8+ T cells:: Cluster of differentiation 8 positive T cells
mRNA:: Messenger ribonucleic acid
HZO:: Herpes zoster ophthalmicus

1.
Olsson J, Kok E, Adolfsson R, Lövheim H, Elgh F (2017) Herpes virus seroepidemiology in the adult Swedish population. Immun Ageing 14(1):10. https://doi.org/10.1186/s12979-017-0093-4. eCollection 2017
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2.
Herbort CP, Weissmann SS, Payan DG (1989) Role of peptidergic neurons in ocular herpes simplex infection. FASEB J 3(13):2537–2541. https://doi.org/10.1096/fasebj.3.13.2553522
CAS Article PubMed Google Scholar
3.
St Leger AJ, Hendricks RL (2011) CD8+ T cells patrol HSV-1 infected trigeminal ganglia and prevent viral reactivation. J Neuro-Oncol 17(6):528–534. https://doi.org/10.1007/s13365-011-0062-1
Article Google Scholar
4.
Perng GC, Jones C. Towards an understanding of the herpes simplex virus type 1 latency-reactivation cycle
5.
Papasavvas I, Gehrig B, Herbort CP Jr (2021) The comparative value of serum angiotensine converting enzyme (ACE) and lysozyme and the use of polyclonal antibody activation in the work-up of ocular sarcoidosis. Diagnostics (Basel) 11(4):608. https://doi.org/10.3390/diagnostics11040608
CAS Article Google Scholar
6.
McMahon DE, Amerson E, Rosenbach M, Lipoff JB et al (2021) Cutaneous reactions reported after Moderna and Pfizer Covid-19 vaccination: a registery-based study of 414 cases. J Am Acad Dermatol 85(1):46–55. https://doi.org/10.1016/j.jaad.2021.03.092 Epub 2021 Apr 7
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7.
Papasavvas I, de Courten C, Herbort CP Jr. Varicella-zoster virus reactivation causing herpes zoster ophthalmicus (HZO after SARS-CoV-2 vaccination : 3 cases. J Ophthalmic Inflamm Infect 2021; in print
8.
Rodriguez-Jimenez P, Chicharro P, Cabrera LM, Segui M, Morales-Caballero A, Llamas-Velasco M, Sanchez-Perez J (2021) Varicella-zoster virus reactivation after SARS-Cov-2 BNT162b2 mRNA vaccination: report of 5 cases. JAAD Case Rep 12:58–59. https://doi.org/10.1016/j.jdcr.2021.04.014 Epub 2021 Apr 24
Article PubMed PubMed Central Google Scholar
9.
Herbort CP, Buechi ER, Piguet B, Zografos L, Fitting P (1991) High-dose oral acyclovir in acute herpes ophthalmicus: the end of the corticosteroid era. Curr Eye Res 10(Suppl):171–175. https://doi.org/10.3109/02713689109020375
Article PubMed Google Scholar

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Inflammatory and Retinal Eye Diseases, Centre for Ophthalmic Specialised Care (COS), Rue Charles-Monnard 6, 1003, Lausanne, Switzerland
Carl P. Herbort Jr & Ioannis Papasavvas

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All authors contributed equally in writing and editing the article.

Corresponding author

Correspondence to Carl P. Herbort Jr.

Ethics approval and consent to participate

This brief report has been performed in accordance with the ethical standards as laid down in 1964 by the declaration of Helsinki and its later amendments. Anonymous case reports are approved by the ethics committee of our institution (EC-COS-MTC) as long as written consent is obtained from the patients.

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Consent was signed by the patient.

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Herbort, C.P., Papasavvas, I. Effect of SARS-CoV-2 mRNA vaccination on ocular herpes simplex and varicella-zoster virus reactivation: should preventive antiviral treatment be given in known herpes patients. J Ophthal Inflamm Infect 11, 33 (2021). https://doi.org/10.1186/s12348-021-00262-2

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Received: 23 June 2021
Accepted: 29 August 2021
Published: 17 September 2021
DOI: https://doi.org/10.1186/s12348-021-00262-2

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中文翻译：

SARS-CoV-2 mRNA 疫苗接种对眼部单纯疱疹和水痘-带状疱疹病毒再激活的影响：已知疱疹患者是否应给予预防性抗病毒治疗

给编辑。

疱疹病毒，包括单纯疱疹病毒 1 (HSV-1) 和水痘-带状疱疹病毒 (VZV)，自千年以来就是人类的共生病毒。

在温带国家，接近 80% 的成年人暴露于 HSV-1，在 VZV 的情况下，这一比例达到 97% 以上 [1]。

初次感染后，这些病毒在感觉神经节中保持潜伏状态。神经节的定植，包括三叉神经节，主要是由于病毒在肽能神经元内的进展而发生的 [2]。潜伏期是一种活跃且复杂的免疫机制，CD8 阳性 T 细胞在其中发挥重要作用 [3]。尽管 mRNA 疫苗会刺激 CD8+ T 细胞，但可以假设它可能会失调感觉神经节中的潜伏机制 [4]。当 T 细胞在肉芽肿中被垄断时，在结节病的情况下，可以通过多克隆抗疱疹抗体激活来挽救性体液补偿来控制疱疹病毒 [5]。如果由于多种原因导致免疫系统暂时或长期功能障碍，病毒可能会重新激活。然后它通过沿着神经元向下移动，导致唇疱疹、树突状角膜炎、疱疹性葡萄膜炎或带状疱疹（在 VZV 病毒的情况下）重新感染外周部位。最近的一项研究报告了 14/414 (3.4%) 例在基于 mRNA 的疫苗接种后的皮肤发现中出现单纯疱疹和水痘-带状疱疹的病例，这一比例相对较大 [6]。但是，没有提供这些患者的详细信息。我们最近报告了三例在 mRNA 抗 SARS-CoV-2 疫苗接种后（分别为 Moderna 和 Pfizer BioNTech）、两名患者首次接种疫苗后 2 周和辉瑞 Bio NTech 加强疫苗接种后 2 周的三例带状疱疹眼科 (HZO) 病例在另一名经历过 Covid-19 感染的患者中 [7]。最近报道了 mRNA 疫苗接种后非眼部水痘-带状疱疹再激活 [8]。疱疹性葡萄膜炎或带状疱疹在 VZV 病毒的情况下。最近的一项研究报告了 14/414 (3.4%) 例在基于 mRNA 的疫苗接种后的皮肤发现中出现单纯疱疹和水痘-带状疱疹的病例，这一比例相对较大 [6]。但是，没有提供这些患者的详细信息。我们最近报告了三例在 mRNA 抗 SARS-CoV-2 疫苗接种后（分别为 Moderna 和 Pfizer BioNTech）、两名患者首次接种疫苗后 2 周和辉瑞 Bio NTech 加强疫苗接种后 2 周的三例带状疱疹眼科 (HZO) 病例在另一名经历过 Covid-19 感染的患者中 [7]。最近报道了 mRNA 疫苗接种后非眼部水痘-带状疱疹再激活 [8]。疱疹性葡萄膜炎或带状疱疹在 VZV 病毒的情况下。最近的一项研究报告了 14/414 (3.4%) 例在基于 mRNA 的疫苗接种后的皮肤发现中出现单纯疱疹和水痘-带状疱疹的病例，这一比例相对较大 [6]。但是，没有提供这些患者的详细信息。我们最近报告了三例在 mRNA 抗 SARS-CoV-2 疫苗接种后（分别为 Moderna 和 Pfizer BioNTech）、两名患者首次接种疫苗后 2 周和辉瑞 Bio NTech 加强疫苗接种后 2 周的三例带状疱疹眼科 (HZO) 病例在另一名经历过 Covid-19 感染的患者中 [7]。最近报道了 mRNA 疫苗接种后非眼部水痘-带状疱疹再激活 [8]。4%) 在基于 mRNA 的疫苗接种后的皮肤发现中出现单纯疱疹和水痘-带状疱疹的病例，这一比例相对较大 [6]。但是，没有提供这些患者的详细信息。我们最近报告了 3 例在 mRNA 抗 SARS-CoV-2 疫苗接种后（分别是 Moderna 和 Pfizer BioNTech）、两名患者首次接种疫苗后 2 周和辉瑞 Bio NTech 加强疫苗接种后 2 周的三例带状疱疹眼科 (HZO) 病例在另一名经历过 Covid-19 感染的患者中 [7]。最近报道了 mRNA 疫苗接种后非眼部水痘-带状疱疹再激活 [8]。4%) 在基于 mRNA 的疫苗接种后的皮肤发现中出现单纯疱疹和水痘-带状疱疹的病例，这一比例相对较大 [6]。但是，没有提供这些患者的详细信息。我们最近报告了三例在 mRNA 抗 SARS-CoV-2 疫苗接种后（分别为 Moderna 和 Pfizer BioNTech）、两名患者首次接种疫苗后 2 周和辉瑞 Bio NTech 加强疫苗接种后 2 周的三例带状疱疹眼科 (HZO) 病例在另一名经历过 Covid-19 感染的患者中 [7]。最近报道了 mRNA 疫苗接种后非眼部水痘-带状疱疹再激活 [8]。我们最近报告了三例在 mRNA 抗 SARS-CoV-2 疫苗接种后（分别为 Moderna 和 Pfizer BioNTech）、两名患者首次接种疫苗后 2 周和辉瑞 Bio NTech 加强疫苗接种后 2 周的三例带状疱疹眼科 (HZO) 病例在另一名经历过 Covid-19 感染的患者中 [7]。最近报道了 mRNA 疫苗接种后非眼部水痘-带状疱疹再激活 [8]。我们最近报告了 3 例在 mRNA 抗 SARS-CoV-2 疫苗接种后（分别是 Moderna 和 Pfizer BioNTech）、两名患者首次接种疫苗后 2 周和辉瑞 Bio NTech 加强疫苗接种后 2 周的三例带状疱疹眼科 (HZO) 病例在另一名经历过 Covid-19 感染的患者中 [7]。最近报道了 mRNA 疫苗接种后非眼部水痘-带状疱疹再激活 [8]。

我们最近检查了一名 53 岁的男性，他过去曾接受过疱疹性角膜葡萄膜炎 OD 治疗，并且在没有治疗的情况下已经 18 个月没有活动。接种第二剂 Moderna 疫苗 5 天后，他的右眼出现严重的肉芽肿性高血压葡萄膜炎，伴有大量肉芽肿性 KP，压力增加 41 mmHg（图 1）。在伐昔洛韦（500 毫克 QID）下，0.1% 地塞米松滴剂 QID 和盐酸多佐胺 - 马来酸噻吗洛尔滴眼液 BID，6 天内压力正常化，激光耀斑光度 (LFP) 耀斑，从 19.4 ph/ms 降至 13.2 ph/ms 3 周后来肉芽肿性 KP 几乎消失了。由于此后 IOP 和 LFP 值波动，伐昔洛韦（500 毫克 BID）、乙酰唑胺（125 毫克/天）、盐酸多佐胺 BID 和地塞米松 0。

很难知道这一事件是否纯粹是煽动性的。即使是这种情况，在这种情况下也必须给予双重皮质类固醇和抗病毒治疗。

由于这种情况，我们建议已经发生过几次疱疹性葡萄膜炎的患者在接种疫苗期间尽管葡萄膜炎是安静的，但仍继续接受伐昔洛韦治疗，以避免潜在的再激活，目前已对两名患者进行了这种治疗。

HSV-1 和 VZV 感染可导致严重的眼部发病率。由于有效的抗病毒药物的出现，由疱疹病毒引起的眼部疾病的治疗在大多数情况下都得到了成功的治疗，并发症也有所减少[9]。然而，每一个新的发作都会伤害眼睛结构。此外，一些疱疹再激活，如急性视网膜坏死，危害更大，治疗难度更大。因此，对于过去曾出现疱疹病毒感染的患者，在与患者讨论后进行 mRNA 疫苗接种的情况下，可以提出是否应该推荐预防性抗病毒治疗的问题，可能至少在高危患者中是这样。

数据请参考通讯作者。

HSV-1：: 单纯疱疹病毒1
VZV：: 水痘带状疱疹病毒
CD8+ T 细胞：: 分化簇 8 个阳性 T 细胞
mRNA：: 信使核糖核酸
赫兹：: 眼科带状疱疹

1.
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Herbort, CP, Papasavvas, I. SARS-CoV-2 mRNA 疫苗接种对眼部单纯疱疹和水痘-带状疱疹病毒再激活的影响：已知疱疹患者是否应给予预防性抗病毒治疗。J Ophthal Inflamm Infect 11, 33 (2021)。https://doi.org/10.1186/s12348-021-00262-2

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