Teachable Moment
Pitfalls to Procalcitonin—Elevation in a Postvaccine Fever
Virginia H. Sun, Esdras O. Rodriguez, Clement D. Lee
JAMA Intern Med Published Online: April 13, 2026
doi: 10.1001/jamainternmed.2026.0673
A man in his mid-50s with end-stage kidney disease (ESKD) receiving peritoneal dialysis (PD) presented to the emergency department with fever, myalgias, and headaches 1 day after receiving COVID-19 and influenza vaccinations. He denied respiratory symptoms but had missed 1 PD session due to feeling unwell. His temperature was 101.5 °F, with otherwise normal vital signs. A complete blood cell count was unremarkable. However, a markedly elevated procalcitonin level of 9.1 ng/mL (reference range, 0-0.25 ng/mL) prompted admission due to concern for bacterial infection.
Subsequent evaluation, including an extended respiratory viral panel, peritoneal fluid analysis, chest radiography, computed tomography of the abdomen and pelvis, and blood cultures, were unrevealing. The patient’s fever resolved spontaneously without antibiotic treatment, and he was discharged home. His symptoms were ultimately attributed to a postvaccination inflammatory response. He reported doing well at a follow-up visit.
This patient presented with symptoms consistent with a postvaccination inflammatory response. However, a markedly elevated procalcitonin level led to concerns for a severe bacterial infection, prompting extensive diagnostic testing and hospitalization that might have been unnecessary.
Procalcitonin is a precursor of the hormone calcitonin, primarily produced in thyroid C and neuroendocrine cells. Its production is upregulated by inflammatory cytokines such as interleukin-6, tumor necrosis factor-α, and interleukin-1β, often in response to bacterial infections.1-3 On the other hand, interferon-γ, primarily secreted during viral infections, decreases production of procalcitonin.1 These pathways underlie procalcitonin’s theoretical utility as a biomarker to distinguish bacterial from viral infections.1
The magnitude of procalcitonin elevation often correlates with the severity of bacterial infection, if present. In adults, levels less than 0.25 ng/mL suggest that bacterial infection is unlikely, whereas higher values increase its likelihood.1 However, procalcitonin can be elevated in other conditions, including proinflammatory states (Box). Uninfected patients receiving PD have been found to have elevated baseline procalcitonin levels (0.32-1.18 ng/mL), with levels decreasing after successful dialysis, likely due to clearance of inflammatory mediators.2There is no consensus on higher procalcitonin cutoffs in ESKD, although some studies use 0.5 ng/mL or greater to suggest bacterial infection.2,4
Box.
Nonbacterial Causes of Elevated Procalcitonin1-5
- Recent surgery
- Trauma
- Burns
- Heart failure
- Acute liver failure
- Chronic kidney disease and end-stage kidney disease
- Viral, fungal, and parasitic infections
- Medications (eg, muromonab or alemtuzumab)
- Paraneoplastic release (eg, medullary thyroid or small cell lung cancer)
- Newborns within first 48 hours
- Vaccinations
- Cross-reactivity with high calcitonin
- Hyperinflammatory conditions
Severe viral infections can paradoxically raise procalcitonin levels.3 While the precise mechanism remains uncertain, it may involve pathways that counteract the inhibitory effects of interferon-γ .3 The impact of vaccination on procalcitonin in adults has not been studied, although pediatric studies have demonstrated mild postvaccination elevations (0.1-3.6 ng/mL; mean [SD], 0.8 [0.9] ng/mL).5
Despite its potential utility in specific situations, procalcitonin is frequently overused and applied in the wrong clinical contexts. US Food and Drug Administration approval of procalcitonin testing is limited to antibiotic management in severe sepsis and lower respiratory tract infections (LRTIs). Randomized clinical trials have demonstrated that procalcitonin-guided algorithms can reduce antibiotic duration and help exclude bacterial LRTIs, but these algorithms are poorly adhered to in everyday practice.1,4 As a result, the diagnostic performance of procalcitonin in routine clinical care is variable, with sensitivities and specificities as low as 38% and 72%, respectively.3,4 In fact, procalcitonin use may paradoxically contribute to overtreatment. In one meta-analysis of patients with suspected LRTIs, patients with procalcitonin testing received longer antibiotic courses and had longer hospital stays without experiencing improvements in mortality.4 Organizations such as the American Thoracic Society and Infectious Diseases Society of America therefore do not recommend routine use of procalcitonin to guide antimicrobial initiation in LRTIs.4 However, procalcitonin may still have a role in guiding antibiotic de-escalation in critically ill patients with sepsis.1
In the present patient, there were several factors to consider when interpreting his elevated procalcitonin. The patient’s ESKD and missed dialysis session likely contributed to a higher baseline level, and pediatric data have shown that procalcitonin can rise after vaccination.5 This case highlights the limited clinical value of measuring procalcitonin outside established, evidence-based indications, such as antibiotic de-escalation in patients with LRTIs or sepsis. Importantly, an isolated procalcitonin level should not supersede clinical judgment. In this context, obtaining procalcitonin for this patient may have prompted unnecessary testing and hospitalization, which is accompanied by costs to both the patient and the health care system.
