Laboratory Tests For Viral Infections: 8 Essential Diagnostics
Essential lab diagnostics for confirming viral skin infections: swabs, cultures, PCR, and more.
Various tests are carried out in a laboratory to establish or confirm the diagnosis of a viral skin infection. Although a thorough history and examination of the patient are vital, laboratory tests can help the clinician to make a diagnosis.
What is a viral skin swab?
A
viral skin swab
is a sterile implement lightly rubbed against a visible skin lesion or vesicle. The swab is then sent to the laboratory in a viral transport medium for further viral cell culture and virus identification.How it works
The swab collects viral particles from the surface of lesions, vesicles, or mucosal areas. These samples are transported in specialized media to preserve viral viability. In the lab, the sample undergoes processing for culture, PCR, or immunofluorescence to detect specific viruses.
A viral swab from an external skin lesion or mucosal surface can detect:
- Herpes simplex virus (HSV)
- Varicella zoster virus (VZV)
- Human papillomavirus (HPV)
- Orf virus
- Molluscum contagiosum virus
- Poxviruses
In addition, a viral swab from oral skin mucosa can detect:
- HSV
- Epstein-Barr virus (EBV)
- Cytomegalovirus (CMV)
Swabs are particularly useful for acute vesicular or ulcerative lesions, providing rapid preliminary results when combined with direct immunofluorescence.
Viral cell cultures
**Viral cell culture** places samples into suitable cell cultures that the virus being tested can infect. When the cells show particular changes—known as cytopathic effects (CPE)—the culture is positive.
Viral cell culture can identify HSV, VZV, morbillivirus (cause of measles), and other viruses. Common cell lines include human fibroblasts, mink lung cells, or monkey kidney cells (e.g., MRC-5, Vero cells). CPE appears as cell rounding, fusion (syncytia), or lysis, typically within 1-7 days.
While gold standard for virus isolation, cell culture is time-consuming (2-14 days) and less sensitive than molecular methods like PCR. It’s still essential for antiviral susceptibility testing and typing specific strains.
Blood tests
Blood tests for the investigation of viral infections include:
- Serology for antiviral antibodies (IgM for acute, IgG for past exposure)
- PCR for viral DNA/RNA detection
- Antigen detection assays
Serology detects immune response: IgM indicates recent infection, IgG lifelong immunity. PCR directly detects viral genomes in plasma, useful for systemic infections like CMV or EBV.
Polymerase chain reaction (PCR)
**PCR** involves isolating and amplifying lengths of DNA (or RNA via RT-PCR) and then detecting known genetic sequences of microorganisms.
Skin swabs can be used to identify:
- HSV-1 and HSV-2
- VZV
- Enteroviruses
- Parvovirus B19
- HHV-6, HHV-7, HHV-8
Real-time PCR (qPCR) is highly sensitive and specific, providing quantitative results within hours. It’s the preferred method for mucosal swabs, CSF, or tissue samples in dermatological viral infections.
Enzyme-linked immunosorbent assay (ELISA)
**ELISA** can test for specific organisms either by detecting the antigen during a current infection or, more commonly, antiviral antibody. The detection of antibody confirms contact with the virus at some time but not necessarily the reason for a current infection.
Most commonly detected viral antibodies are to:
- HSV
- VZV
- EBV
- CMV
- Parvovirus B19
- Hepatitis viruses
- HIV
ELISA is quantitative, measuring antibody titers to assess acute vs. past infection. For example, in parvovirus B19, IgM confirms acute erythema infectiosum.
Electron microscopy
**Electron microscopy** involves directing a beam of electrons at a sample, producing an image with much higher resolution than a standard light microscope. It is rarely used in practice but can be useful to identify atypical and rare viral infections in immunosuppressed patients presenting with unusual skin lesions.
Negative staining reveals viral morphology: herpesviruses show icosahedral capsids (100-200 nm), poxviruses brick-shaped (200-400 nm). Direct EM on vesicle fluid provides rapid (hours) presumptive diagnosis but lacks specificity.
Resistance testing
**Resistance testing** in viruses aids the clinician in determining which antiviral medications may or may not be effective for infection. Viruses mutate rapidly, presenting a therapeutic challenge as antiviral treatments may fail.
The most noteworthy is HIV antiretroviral (ARV) resistance, which poses great risk if medications stop working. Other viruses like HSV, VZV, CMV, and hepatitis B/C also develop resistance to acyclovir, ganciclovir, etc.
Sequence analysis is performed most commonly at the genomic level, looking directly at the HIV genome to identify mutations conferring resistance to specific ARVs. Less commonly, phenotypic analysis subjects the patient’s virus to antivirals in culture to assess response.
Skin biopsy
A skin biopsy may be useful in the diagnosis of viral infection. A
viral cytopathic effect
may be observed on histopathology or Tzanck smear, or specific features characteristic of the particular infection may be present.Tzanck smear: Scrape lesion base, stain with Giemsa—multinucleated giant cells indicate HSV/VZV. Histopathology shows ballooning degeneration, inclusions (e.g., Cowdry type A in HSV). Immunohistochemistry (IHC) confirms specific viruses.
Who needs laboratory tests for viral infections?
Lab tests are indicated for:
- Atypical or severe presentations
- Immunocompromised patients
- Neonates or pregnant women
- Outbreaks or public health concerns
- Failure of empiric antiviral therapy
Routine cases (e.g., classic herpes labialis) may rely on clinical diagnosis.
Investigations summary table
| Test | Sample | Viruses Detected | Turnaround Time | Advantages | Limitations |
|---|---|---|---|---|---|
| Viral Swab | Skin lesion/vesicle | HSV, VZV, HPV | 1-7 days (culture) | Non-invasive | Requires viable virus |
| Cell Culture | Swab/fluid | HSV, VZV, Enterovirus | 2-14 days | Viable virus isolation | Slow, less sensitive |
| PCR | Swab, blood, tissue | All DNA/RNA viruses | Hours | Highly sensitive/specific | Detects non-viable virus |
| ELISA/Serology | Blood | HSV, VZV, EBV, CMV | 1-2 days | Indicates immunity | Not for acute diagnosis |
| Electron Microscopy | Fluid/lesion | Pox, herpesviruses | Hours | Rapid morphology | Rarely used, non-specific |
| Resistance Testing | Blood/swab | HIV, HSV, CMV | Weeks | Guides therapy | Complex, expensive |
Frequently Asked Questions (FAQs)
Q: When should I order a viral swab?
A: For vesicular or ulcerative skin/mucosal lesions suspicious for HSV or VZV, especially if atypical.
Q: Is PCR better than viral culture?
A: Yes, PCR is faster, more sensitive, and detects non-viable virus, making it first-line.
Q: Can blood tests diagnose active skin infections?
A: Serology shows exposure/immunity; PCR detects viremia in systemic cases.
Q: What if antivirals fail?
A: Perform resistance testing via genotyping to select effective drugs.
Q: Is biopsy needed for viral diagnosis?
A: Useful for chronic lesions or when PCR/swabs are negative; shows CPE/inclusions.
References
- Laboratory tests for viral infections — DermNet NZ. 2023. https://dermnetnz.org/topics/laboratory-tests-for-viral-infections
- Erythema Infectiosum – StatPearls — NCBI Bookshelf, NIH. 2023-10-01. https://www.ncbi.nlm.nih.gov/books/NBK513309/
- Skin rash and lesions – general | STI Guidelines Australia — Australian STI Management Guidelines. 2024. https://sti.guidelines.org.au/syndromes/skin-rash-and-lesions-general/
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