Skip to main content

Main menu

  • Home
  • Content
    • Current Issue
    • Ahead of Print
    • Past Issues
    • Supplements
    • Article Type
  • Specialty
    • Articles by Specialty
  • CME/MOC
    • Articles
    • Calendar
  • Info For
    • Manuscript Submission
    • Authors & Reviewers
    • Subscriptions
    • About CCJM
    • Contact Us
    • Media Kit
  • Conversations with Leaders
  • Conference Coverage
    • Kidney Week 2024
    • CHEST 2024
    • ACR Convergence 2023
    • Kidney Week 2023
    • ObesityWeek 2023
    • IDWeek 2023
    • CHEST 2023
    • MDS 2023
    • IAS 2023
    • ACP 2023
    • AAN 2023
    • ACC / WCC 2023
    • AAAAI Meeting 2023
    • ACR Convergence 2022
    • Kidney Week 2022
    • AIDS 2022
  • Other Publications
    • www.clevelandclinic.org

User menu

  • Register
  • Log in

Search

  • Advanced search
Cleveland Clinic Journal of Medicine
  • Other Publications
    • www.clevelandclinic.org
  • Register
  • Log in
Cleveland Clinic Journal of Medicine

Advanced Search

  • Home
  • Content
    • Current Issue
    • Ahead of Print
    • Past Issues
    • Supplements
    • Article Type
  • Specialty
    • Articles by Specialty
  • CME/MOC
    • Articles
    • Calendar
  • Info For
    • Manuscript Submission
    • Authors & Reviewers
    • Subscriptions
    • About CCJM
    • Contact Us
    • Media Kit
  • Conversations with Leaders
  • Conference Coverage
    • Kidney Week 2024
    • CHEST 2024
    • ACR Convergence 2023
    • Kidney Week 2023
    • ObesityWeek 2023
    • IDWeek 2023
    • CHEST 2023
    • MDS 2023
    • IAS 2023
    • ACP 2023
    • AAN 2023
    • ACC / WCC 2023
    • AAAAI Meeting 2023
    • ACR Convergence 2022
    • Kidney Week 2022
    • AIDS 2022
From the Editor

The initial viral infection may be only part of the story

Brian F. Mandell, MD, PhD
Cleveland Clinic Journal of Medicine September 2021, 88 (9) 476-477; DOI: https://doi.org/10.3949/ccjm.88b.09021
Brian F. Mandell
Roles: Editor in Chief
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Find this author on Cleveland Clinic
  • Article
  • Info & Metrics
  • PDF
Loading

Embedded Image

The concept of “long COVID” is now entrenched in our vocabulary and in the minds of our patients, but the pathogenesis of this protracted syndrome is thus far incompletely understood. Are there pockets of slowly dividing virus or incompletely cleared viral remnants driving a low-level inflammatory response? Is there a central nervous system reservoir of infected neurons contributing to an intense sense of fatigue, brain fog, and sometimes mood changes? Is there persistent infection of vascular cells impacting vascular regulation of blood flow to selected organs?

While we cannot answer these questions now, we clearly see that the coronavirus elicits pathologic syndromes far afield from the respiratory tissues that the virus primarily targets for infection.

A virus eliciting effects seemingly distinct from its primary infection is not a new concept at all, of course. Epstein-Barr virus is recognized as causing not only a lasting malaise in some patients, but also a reactivation syndrome and lymphoproliferative disorders. Hepatitis C and B virus infections are linked to the development of delayed hepatocellular carcinoma in the setting of hepatic fibrosis, as well as several systemic vasculitic disorders occurring during active infection. Parvovirus is associated with aplastic anemia and human papillomavirus is strongly linked to various carcinomas.

But the most common viral infection associated with delayed clinical events is the double-stranded DNA varicella-zoster alpha-herpesvirus (VZV), the causative agent for “chicken pox” and shingles. Seminal work from the laboratories of the late Dr. Don Gilden and others has demonstrated that the viral DNA exists in neurons, in a non-integrated form. Reactivation is best recognized by the appearance of pruritic, painful vesicles in an asymmetric dermatomal distribution. While often no definite trigger for reactivation with viral replication is recognized, it is felt that loss of cellular immunity is at least permissive, and this is increasingly recognized in a minority of patients treated with JAK inhibitors for rheumatoid arthritis and other inflammatory disorders. How a decrease in cellular immunity affects intracellular viral replication is not entirely clear, but more readily understood is that patients who are immunosuppressed often have a more difficult time containing and controlling the reactivation when it occurs. It is often said that stress may also bring about reactivation, and several fascinating studies have demonstrated that after space travel, astronauts experience a self-limited asymptomatic reactivation of VZV as detected by the presence of salivary viral DNA.1

Postherpetic neuralgia is the best-known complication of dermatomal reactivation, and although some risk factors are known, we cannot predict who will develop it, nor do we know how to prevent it. The virus has been detected in cerebral blood vessels, and a VZV vasculopathy, often with giant cells and adventitial inflammation, has been associated with stroke syndromes and, controversially, with giant cell arteritis. VZV stroke syndromes may occur weeks or months after an episode of dermatomal zoster. VZV DNA or, more commonly, anti-varicella IgG antibody can be found in the cerebrospinal fluid of affected patients.

A myelopathy or segmental peripheral episode of motor weakness can follow an episode of typical zoster. Segmental weakness generally occurs in the area of the zoster outbreak, but not always. Myelopathy may affect legs and sphincter tone and has also been rarely described after infection with cytomegalovirus, another herpesvirus.

Since pain and neurologic complications before, during, or after VZV infection can occur in the absence of the classic skin findings (zoster sine herpete),2 it is important to recognize the wide spectrum of regional VZV syndromes that can occur. How many times have I not recognized impending zoster in the setting of radiculopathy or an unusual regional pain syndrome? I know that I have on multiple occasions diagnosed pre-zoster rash-pain syndromes—oddly, it seems, more in family and friends than in patients in my office. (Patients these days probably cannot get an appointment in time before the vesicles appear.)

It is with this background in mind that I invite you to read the Clinical Picture in this issue by Dr. Mizumoto (page 480).3

  • Copyright © 2021 The Cleveland Clinic Foundation. All Rights Reserved.

References

  1. ↵
    1. Mehta SK,
    2. Laudenslager ML,
    3. Stowe RP,
    4. Crucian BE,
    5. Sams CF,
    6. Pierson DL
    . Multiple latent viruses reactivate in astronauts during Space Shuttle missions. Brain Behav Immun 2014; 41:210–217. doi:10.1016/j.bbi.2014.05.014
    OpenUrlCrossRefPubMed
  2. ↵
    1. Gilden DH,
    2. Wright RR,
    3. Schneck SA,
    4. Gwaltney JM Jr.,
    5. Mahalingam R
    . Zoster sine herpete, a clinical variant. Ann Neurol 1994; 35(5):530–533. doi:10.1002/ana.410350505
    OpenUrlCrossRefPubMed
  3. ↵
    1. Mizumoto J
    . Abdominal pseudohernia due to herpes zoster. Cleve Clin J Med 2021; 88:480–481. doi:10.3949/ccjm.88a.20178
    OpenUrlFREE Full Text
PreviousNext
Back to top

In this issue

Cleveland Clinic Journal of Medicine: 88 (9)
Cleveland Clinic Journal of Medicine
Vol. 88, Issue 9
1 Sep 2021
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Complete Issue (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Cleveland Clinic Journal of Medicine.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
The initial viral infection may be only part of the story
(Your Name) has sent you a message from Cleveland Clinic Journal of Medicine
(Your Name) thought you would like to see the Cleveland Clinic Journal of Medicine web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
The initial viral infection may be only part of the story
Brian F. Mandell
Cleveland Clinic Journal of Medicine Sep 2021, 88 (9) 476-477; DOI: 10.3949/ccjm.88b.09021

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
The initial viral infection may be only part of the story
Brian F. Mandell
Cleveland Clinic Journal of Medicine Sep 2021, 88 (9) 476-477; DOI: 10.3949/ccjm.88b.09021
Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Linkedin Share Button

Jump to section

  • Article
    • References
  • Info & Metrics
  • PDF

Related Articles

  • Abdominal pseudohernia due to herpes zoster
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • The gift of lasting immunity
  • Psychedelics in the medical toolbox?
  • All sulfa drugs are not created equal
Show more From the Editor

Similar Articles

Subjects

  • Cardiology
  • Covid-19
  • Infectious Diseases
  • Pulmonology
  • Rheumatology
  • Vascular Medicine

Navigate

  • Current Issue
  • Past Issues
  • Supplements
  • Article Type
  • Specialty
  • CME/MOC Articles
  • CME/MOC Calendar
  • Media Kit

Authors & Reviewers

  • Manuscript Submission
  • Authors & Reviewers
  • Subscriptions
  • About CCJM
  • Contact Us
  • Cleveland Clinic Center for Continuing Education
  • Consult QD

Share your suggestions!

Copyright © 2025 The Cleveland Clinic Foundation. All rights reserved. The information provided is for educational purposes only. Use of this website is subject to the website terms of use and privacy policy. 

Powered by HighWire