June 2020
Dr Eddie Silberbauer – Medical Microbiologist
Dr Marita du Plessis – Chemical Pathologist
Ampath | ampath.co.za
Why Test Inflammatory Markers in COVID-19?
The problem:
- Inflammatory responses are a critical factor in the progression of COVID-19.
- SARS-CoV-2 replication and infected cell destruction trigger cytokine release and recruitment of immune cells.
- This results in a “cytokine storm”, a hyperinflammatory state that can lead to multi-organ failure and death.
Inflammatory Markers Associated with Severe COVID-19
Key markers:
- Procalcitonin (PCT)
- Serum ferritin
- Erythrocyte sedimentation rate (ESR)
- C-reactive protein (CRP)
- Interleukin-6 (IL-6)
These markers are significantly elevated in patients at high risk for severe COVID-19 and may help monitor disease progression and prognosis.
Understanding Interleukin-6 (IL-6)
IL-6 functions:
- Acts on both lymphoid and non-lymphoid cells
- Involved in:
- Host defence against pathogens (e.g. Candida, Listeria)
- Differentiation of B- and T-cells
- Production of immunoglobulins
- T-helper 17 cell differentiation
- Cytotoxic T-cell responses to viruses
- Induces fever, inflammation, and acute-phase proteins (e.g. CRP)
IL-6 levels are low in healthy individuals but rise rapidly during bacterial or viral infection, inflammation, or trauma.
IL-6 in COVID-19:
- A subgroup of patients with severe COVID-19 progress to ARDS (acute respiratory distress syndrome) due to hypercytokinaemia.
- Elevated IL-6 and ferritin are linked to increased mortality.
- IL-6 levels may be used to evaluate disease severity.
- Patients with IL-6 >100 pg/mL often have detectable SARS-CoV-2 RNA in the blood (RNAaemia).
- A decrease in LDH or CK may indicate treatment response and viral clearance.
Procalcitonin (PCT)
What it is:
- A marker of bacterial infection
- PCT production is amplified during bacterial infection by cytokines such as IL-1β, TNF-α, and IL-6
- PCT synthesis is suppressed by interferon-γ, which increases in viral infections
PCT generally remains normal in uncomplicated COVID-19, and elevations suggest bacterial co-infection.
Clinical relevance:
- Meta-analysis: Elevated PCT is linked to a nearly 5-fold increase in risk of severe COVID-19
- Pooled odds ratio: 4.76 (95% CI, 2.74–8.29)
Uses:
- Risk assessment on admission
- Rule out bacterial co-infection
- Detect secondary infections
- Guide initiation and discontinuation of antibiotics
C-reactive Protein (CRP)
- CRP is a non-specific acute-phase marker of inflammation, infection, or tissue damage.
Findings in COVID-19:
- Higher CRP levels correlate with more severe disease
- Median CRP values:
- Severe cases: 43.8 mg/L
- Non-severe cases: 12.1 mg/L
- Odds ratios (Wang et al., 2020):
- Univariate: 1.049 (95% CI, 1.028–1.070; P <.001)
- Multivariate: 1.056 (95% CI, 1.025–1.089; P <.001)
Biochemical Markers and Disease Progression
Markers that increase with COVID-19 severity:
- CRP
- IL-6
- Lactate dehydrogenase (LDH)
- Creatine kinase (CK)
A consistent rise in these markers suggests worsening inflammation, while a decline in LDH or CK may signal clinical improvement and viral clearance.
Summary: When to Use Inflammatory Markers
IL-6:
- Evaluate cytokine storm and disease severity
- Predict respiratory failure and ICU need
PCT:
- Rule out bacterial co-infection
- Monitor for secondary infection
- Guide antibiotic use
CRP:
- Assess overall inflammatory response
- Track disease progression or improvement
LDH and CK:
- Monitor multi-organ involvement and tissue damage
- Evaluate treatment response
References
- Zeng F. et al. (2020). International Journal of Infectious Diseases
- Rich R.R. (2019). Clinical Immunology: Principles and Practice
- Metha P. et al. (2020). Lancet 395: 1033–1034
- Chen X. et al. (2020). Preprint: medRxiv
- Yuan J. et al. (2020). Inflammation Research
- Lippi G. & Plebani M. (2020). Clinica Chimica Acta 505: 190–191
- Wang G. et al. (2020). Open Forum Infectious Diseases, 7(5)
📌 For clinical support, contact your local Ampath pathologist.
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