Herpes Virus Reactivation, Causes and Consequences, Part II

INTRODUCTION: In this 2nd Part, we will present reports dealing with the reaction of another group of Herpes viruses, human herpes virus 6 & 7 (HHV 6-7). Over the last 18 months the SARS-CoV-2 virus has led to an increase in Herpes virus reactivations. This virus (SARS-CoV-2) has a series of evasion mechanisms that allow it to circumvent our immune system, thereby leaving the host vulnerable and thus facilitating replication of the virus and the increase in viral load. Two of these evasion mechanisms include 1) the alteration of the synthesis and functionality of interferons type I (INF-alpha & beta) and type 2 (INF-gamma). This allows SARS-CoV-2 to replicate in host cells without opposition or without an effective antiviral state. And 2) a cytokine storm or excessive activation of M1 macrophages with an inordinate amount of pro-inflammatory cytokines released into the serum1. It is the down-regulation INF-gamma which is thought to lead to the reactivation of many Herpes viruses.

 

DISCUSSION: Pityriasis rosea (PR) is caused by the reactivation of HHV-6-7 and we have seen a rapid rise in cases during the SARS-CoV-2 pandemic. Dursun and Temiz2 found a 5-fold increase in the rate of Pityriasis rosea patients who applied to a dermatology outpatient clinic during the last year (April 1 & May 1 2019 through April 1 & May 1 2020). Collecting data from 2 different months, 1 year apart was to reduce any seasonal development of the disease. There are many other reports of PR in the literature. Birlutiu et al3, reported that the PR cases associated with SARS-CoV-2 infection are in young patients (12-39 years old), with a mean age of 24.12 years, with equal distribution by gender (50/50). The time periods between the onset of the rash and the presentation of the patient to the doctor varied between 3 days and 2 weeks. Healing of the skin lesions required 2-4 weeks ((using antihistamines, antipyretics and topical corticosteroids). Their report adds to other findings regarding the association of PR with SARS-CoV-2 infection, in context of the pandemic, suggesting the need to test patients with PR skin lesions for SARS-CoV-2 infection.  Another type of Herpes virus related disease is Kawasaki disease which is a systemic vasculitis of childhood that can affect the coronary arteries. The exact etiology of Kawasaki disease is still unknown; however, many believe HHV-6 is a primary cause. In a study conducted during the COVID-19 pandemic, Kawasaki disease was found to increase 30-fold compared to previous years4. The study by Dursun & Temiz found a 10-fold increase in patients with Kawasaki disease who applied to the dermatology outpatient clinic, compared to the previous year. They believe this increase of Kawasaki disease during the pandemic may be due to the Coronavirus triggering (i.e., reactivation) of HHV-6.

 

CONCLUSION: In Part I we showed the reports of a large increase of Bell’s Palsy associated with the SARS-CoV-2 infections which is thought to be due to the reactivation of either HSV1/2 or Varicella zoster virus. In Part II we showed the reactivation of other Herpes viruses, HHV-6-7, during the SARS-CoV-2 pandemic. Data is accumulating that the suppression of the immune response during the Coronavirus infection is resulting in the reactivation of a wide range of Herpes viruses.

 

REFERENCES:

 

  • Maldonado, M.D., J. Rmoero-Aibar, and M.A. Perez-San-Gregorio. (2021) COVID-19 pandemic as a risk factor for the reaction of herpes viruses. Epidemiology and Infection 149, e145,1-5. Https://doi.org/10.1017/S09502688s1001333
  • Dursun, R., and A. Temiz. (2020). The clinics of HHV-6 infection in COVID-19 pandemic: Pityriasis rosea and Kawasaki disease. Dermatol Ther 33(4), e13730. Https://doi.org/10.1111/dth.13730.
  • Birlutiu, V., R.M. Birlutiu, and G.M. Lancu. (2021) Pityriasis rosea Gibert triggered by SARS-CoV-2 infection. Medicine 100, 14, 1-5. http://dx.doi.org/10.1097/MD.0000000000025352.
  • Verdoni, L., A. Mazza, A. Gervasoni, L. Martelli, M. Ruggeri, M. Cuiffreda, E. Bonanomi, and L. D’Antiga. (2020) An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 395, 1771-78. https://doi.org/10.1016/S0140-6736(20)31103-X

 

By David Kilpatrick, PhD and Abbas Vafai, PhD

 

MKTG 1062  – Rev A 091021

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Herpes Virus Reactivation, Causes and Consequences, Part I

INTRODUCTION: One of the consequences of the SAR-CoV-2 infections over the last year has been a large increase in reactivation of herpes viruses. There are numerous reports of COVID-19 patients with suspected reactivation of several different herpes viruses, including human herpes virus 1 and 2 (HSV 1/2), varicella zoster virus (VZV), human herpes virus-6 and 7 (HHV 6/7), as well as Cytomegalovirus (CMV). It is known that cell-mediated immunity plays an important role in herpes virus latency. COVID-19 infection decreases cell-mediated immunity by decreasing lymphocytes, such as CD3+, CD4+, and CD8+ T cells. These cells produce gamma interferon (IFN-γ) which is known to suppress reactivation of herpes viruses. So, if the IFN-γ levels are lowered, viral reactivation occurs. This report will discuss the reactivation of herpes viruses which leads to Bell’s palsy.

DISCUSSION: There are numerous reports (thousands) of COVID-19 patients who subsequently have been diagnosed with Bell’s palsy, such as the report by Neo et al1.  Bell’s palsy is a common cause of lower motor neuron neuropathy and is known to occur upon the reactivation of either HSV1/2, or from VZV. Serological studies have shown that the prevalence of antibodies to HSV among patients with Bell’s palsy is higher than that among healthy control subjects, which suggests that HSV may be involved in the pathogenesis of Bell’s palsy (Adour et al2). In addition to HSV, VZV is known to play a role in Bell’s palsy. A portion of Bell’s palsy patients have what is called, Ramsay Hunt syndrome, but these patients have more severe paralysis at the onset and are less likely to recover completely (Sweeney & Gilden3). Patients with Ramsay Hunt syndrome are characterized by peripheral facial paralysis without ear or mouth rash, and the presence of either fourfold rise in antibody to VZV or the detection of VZV DNA in skin, blood mononuclear cells, or middle ear fluid. It is clear that the suppression of IFN-γ during a COVID-19 infection plays a role in reactivating herpes viruses. The ability of IFN-γ to control chronic herpes virus infection and reactivation from latency is known for many herpes viruses (Presti et al4).

CONCLUSION: Over the last 18 months, there have been thousands of cases of Bell’s palsy associated with either being infected with SAR-CoV-2. It would be prudent to test for Herpes viruses (HSV 1/2, VZV) if COVID-19 patients show Bell’s palsy symptoms.

 

REFERENCES:

  1. Neo, W. L., Jeremy Chung Fai Ng and N. Gopalakrishna Iyer. (2020). The great pretender-Bell’s palsy secondary to SARS-CoV-2? Clinical Case Report, 9:1175-77. https://doi.10.1002/ccr3.3716
  2. Adour, K.K., Bell, D. N., and Hilsinger, R.L.J (1975). Herpes simplex virus in idiopathic facial paralysis (Bell palsy). JAMA 233:527-30. https://doi.10.1001/jama.1975.03260060037015
  3. Sweeney, C.J., and D. H. Gilden. (2001). Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry 71:149-154. https://doi.10.1136/jnnp.71.2.149
  4. Presti, R. M., J.L. Pollock, A.J. Dal Canto, A.K. O’Guin, and H.W. Virgin. (1998). Interferon-gamma regulates acute and latent murine cytomegalovirus infection and chronic disease of the great vessels. J. Exp. Med. 188:577-88. https://doi.10.1084/jem.188.3.577

 

By David Kilpatrick, PhD and Abbas Vafai, PhD

MKTG 1061  – Rev A 072621

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