Rule-out of Bacterial Coinfection
PCT on admission
Test PCT as an aid for early risk assessment and prioritization of high risk patients
- <0.5 µg/L* → low risk for bacterial coinfection and adverse outcome
- ≥0.5 µg/L → high risk patients, bacterial coinfection likely
PCT during hospital stay
Monitor PCT to detect secondary infections and progression of the severity of bacterial infection
* Majority of patients with mild disease had PCT values <0.25 µg/L or even <0.1 µg/L. Ref-1-6
Likelihood of bacterial infection and recommendation to start antibiotics in patients with LRTI at PCT >0.25 µg/L. Ref-7
The biomarker Procalcitonin (PCT) is widely used to assess the risk of bacterial infection and progression to severe bacterial sepsis and septic shock in conjunction with other laboratory findings and clinical assessment. Further, the change of PCT over time is used to determine the mortality risk in patients with bacterial sepsis.
In patients with suspected or confirmed lower respiratory tract infections (LRTI), including communityacquired pneumonia (CAP), acute bronchitis and acute exacerbations of COPD (AECOPD), PCT is an aid in decision making on antibiotic therapy for inpatients or patients presenting in the emergency department (ED).
Procalcitonin has now been shown, in evolving descriptive studies, to be an additional valuable tool in the current COVID-19 pandemic to early identify patients at low risk for bacterial coinfection and adverse outcome. Ref-1-6, 17
New analysis of 1099 COVID-19 patient data sets from a range of medical centers in China Ref-2 show that PCT was low (<0.5 µg/L) in > 96% of cases with low disease severity and absence of adverse outcome (combined endpoint of ICU admission, invasive ventilation, death). Most of COVID-19 patients even had PCT values below 0.25 µg/L or even below 0.1 µg/L.Ref-2-3 This correlates to findings from previous viral epidemics (influenza H1N1, SARS, MERS) that PCT is usually low (<0.1 − <0.5 µg/L) in hospitalized patients with pure viral infection. Ref-8-13
In cases with bacterial coinfection and higher severity of disease PCT has been found >0.5 µg/L. Ref-1-6
Thus, according to a recent meta-analysis of published COVID-19 patient data, PCT >0.5 µg/L corresponds to an almost 5 times higher risk of severe infection (OR, 4.76; 95% CI, 2.74-8.29) compared to patients with lower PCT Ref-14. Acute Respiratory Distress Syndrome (ARDS) and septic shock were most frequent complications of COVID-19; secondary infections during the hospital stay were an additional risk factor. Ref-1-6 Death was in an almost all patients associated with sepsis/septic shock and respiratory failure/ARDS.Ref-2-3,6,8
IFCC Information Guide on COVID-19
The IFCC identifies PCT on the Recommended Test List for potential clinical and biological significance in recognizing bacterial (super) infection
“The essential role of clinical laboratories in this pandemic extends beyond etiological diagnosis of COVID- 19. Biochemical monitoring of COVID-19 patients through in vitro diagnostic testing is critical for assessing disease severity and progression as well as monitoring therapeutic intervention. Several common in vitro diagnostic tests have been implicated in unfavourable COVID-19 progression, potentially providing important prognostic information. A recommended test list based on current literature is included below along with the major laboratory abnormalities associated with adult COVID-19 patients and their potential clinical indication” Ref-15
Cochairs of the ATS/IDSA CAP guidelines provide guideline interpretation for the management of patients with COVID-19
Treatment of Community-Acquired Pneumonia During the Coronavirus Disease 2019 (COVID-19) Pandemic.
"Still, we endorse the use of a low procalcitonin value early in the course of confirmed COVID-19 illness to guide the withholding or early stopping of antibiotics, especially among patients with less severe disease." Ref-18
CDC Interim Clinical Guidance
for Management of Patients with Confirmed Coronavirus Disease (COVID-19)
The CDC identifies PCT among a list of inflammatory markers correlating to the severity of illness.
“Procalcitonin is typically normal on admission, but may increase among those admitted to the ICU. Patients with critical illness had high plasma levels of inflammatory markers, suggesting potential immune dysregulation.” Ref-16
Take home message:
- PCT testing on admission seems to be a valuable additional piece of information to aid in early risk assessment and rule-out of bacterial coinfection in COVID-19 patients. Ref-1-6
- Monitoring of PCT was identified to be useful for detection of secondary infections and progression to more severe disease state like sepsis / septic shock.Ref-2-3, 14-16
Further links
Find out which B·R·A·H·M·S PCT assay might be available in your laboratory.
B·R·A·H·M·S PCT (Procalcitonin) Assays >
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Overcoming Challenges in COVID-19 patient management with PCT
References
Ref-1: Huang C et al: Lancet 2020; 395: 497–506, https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930183-5
Ref-2: Guan W. et al., NEJM 28 Feb 2020, https://www.nejm.org/doi/pdf/10.1056/NEJMoa2002032
Ref-3: Zhou et al., Lancet , March 9, 2020 , https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930566-3
Ref-4: Chen N. et al., Lancet 2020; 395: 507–13, https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930211-7
Ref-5: Xiao-Wei Xu. et al., BMJ (Online); London 2020, 368 (Feb 19, 2020), https://www.bmj.com/content/bmj/368/bmj.m606.full.pdf
Ref-6: Huang Y et al., medRxiv preprint 2020, doi: https://doi.org/10.1101/2020.02.27.20029009
Ref-7: Schuetz P. et al., Exp. Rev Anti-infect. Ther., 2018, 16:7, 555-564, DOI: 10.1080/14787210.2018.1496331
Ref-8: Ingram P.R. et al., Intensive Care Med 2010;36 (3),Jan 13: 528-32
Ref-9: Cuquemelle E. et al., Intensive Care Med 2011, 37(5):796-800
Ref-10: Rodriguez A.H. et al., J. Infect 2016, 72:143-152
Ref-11: Chua, A. P., and K. H. Lee. 2004, J. Infect. 48:303–306
Ref-12: Ji-Young Rhee et al., Jpn. J. Infect. Dis., 2016, 69:361–366
Ref-13: Karhu J. et al., Cytokine 2019, 113:272-276
Ref-14: Lippi G. & Plebani M., Clin Chim Acta 2020, March 4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094472/pdf/main.pdf
Ref-15: IFCC 2020, 6th April, https://www.ifcc.org/ifcc-news/2020-03-26-ifcc-information-guide-on-covid-19
Ref-16: CDC 2020, https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html#lab-findings
Ref-17: AACC 2020, https://www.aacc.org/publications/cln/cln-stat/2020/april/16/key-biomarkers-in-managing-covid-19
Ref-18: Metlay J. P. & Waterer G. W., Ann Intern Med. doi:10.7326/M20-2189, May 7, 2020 https://www.acpjournals.org/doi/full/10.7326/M20-2189#t1-M202189
Publications
Publications on PCT in COVID-19
Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis
Langford BJ et al.,
Clinical Microbiology and Infection 2021
https://doi.org/10.1016/j.cmi.2020.12.018
Use of procalcitonin for antibiotic stewardship in patients with COVID-19: A quality improvement project in a district general hospital
Peters C. et al.
Clinical Medicine 2020, Vol 21 No 1 January 2021; DOI: 10.7861/clinmed.2020-0614
https://pubmed.ncbi.nlm.nih.gov/33355197/
Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19
Liu F. et al.
Journal of Clinical Virology 127 (2020) 104370
https://doi.org/10.1016/j.jcv.2020.104370
Procalcitonin and secondary bacterial infections in COVID-19: association with disease severity and outcomes
Vazzana N. et al.
Acta Clinica Belgica 2020
https://doi.org/10.1080/17843286.2020.1824749
Bacterial and Fungal Coinfection in Individuals With Coronavirus: A Rapid Review To Support COVID-19 Antimicrobial Prescribing
Rawson T.M. et al.
Clinical Infectious Diseases 2020;71(9):2459–68; DOI: 10.1093/cid/ciaa530
https://pubmed.ncbi.nlm.nih.gov/32358954/
Antibiotic prescribing patterns for coronavirus disease 2019 (COVID-19) in two emergency departments with rapid procalcitonin
Pulia M.S. et al.
Infection Control & Hospital Epidemiology (2020), 1–3; DOI:10.1017/ice.2020.1329
https://pubmed.ncbi.nlm.nih.gov/33208206/
Evaluation of procalcitonin as a contribution to antimicrobial stewardship in SARS-CoV-2 infection: a retrospective cohort study
Williams et al.
J. Hosp Infect 2021, 110:103-107
https://doi.org/10.1016/j.jhin.2021.01.006
Bacterial infections and patterns of antibiotic use in patients with COVID‐19
Mendes Neto A.G. et al.
J Med Virol. 2020;1–7.; DOI: 10.1002/jmv.26441
https://pubmed.ncbi.nlm.nih.gov/32808695/
Co-infections in people with COVID-19: a systematic review and meta-analysis
Lansbury L. et al.
J. Infection 2020
https://doi.org/10.1016/j.jinf.2020.05.046
Association of procalcitonin levels with the progression and prognosis of hospitalized patients with COVID-19
Liu, Ze-Ming et al.
International Journal of Medical Sciences 2020; 17(16): 2468-2476.; doi: 10.7150/ijms.48396
https://pubmed.ncbi.nlm.nih.gov/33029089/
Procalcitonin and COVID-19: A Reliable Clinical Tool
Bass J. et al.
Research Square 2020
https://doi.org/10.21203/rs.3.rs-43706/v1
Association between procalcitonin levels and duration of mechanical ventilation in COVID-19 patients
Krause M. et al.
PLoS ONE 2020, 15(9): e0239174.
https://doi.org/10.1371/journal.pone.0239174
Empiric antibacterial therapy and community-onset bacterial co-infection in patients hospitalized with COVID-19: A multi-hospital cohort study
Vaughn V.M. et al.
Clinical Infectious Diseases 2020, ciaa1239,
https://doi.org/10.1093/cid/ciaa1239
Rates of bacterial co-infections and antimicrobial use in COVID-19 patients: a retrospective cohort study in light of antibiotic stewardship
Rothe K. et al.
European Journal of Clinical Microbiology & Infectious Diseases 2020
https://doi.org/10.1007/s10096-020-04063-8
Biomarkers for antimicrobial stewardship: a reappraisal in COVID-19 times?
Van Berkel M. et al.
Critical Care (2020) 24:600
https://doi.org/10.1186/s13054-020-03291-w
Risk Factors of Fatal Outcome in Hospitalized Subjects With Coronavirus Disease 2019 From a Nationwide Analysis in China
Chen R. et al.
CHEST 2020; 158(1):97-105
https://pubmed.ncbi.nlm.nih.gov/32304772/
Characteristics, predictors and outcomes among 99 patients hospitalised with COVID-19 in a tertiary care centre in Switzerland: an observational analysis
Gregoriano C. et al.
Swiss Med Wkly. 2020;150:w20316; doi:10.4414/smw.2020.20316
https://pubmed.ncbi.nlm.nih.gov/32668007/
Procalcitonin levels in COVID-19 patients
Hu R, et al.
Int J Antimicrob Agents 2020; Jun 10: 106051.OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32534186
Clinical characteristics of 182 pediatric COVID-19 patients with different severities and allergic status
Du H, et al.
Allergy 2020; Jun 10: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32524611
Risk factors for disease progression in patients with mild to moderate coronavirus disease 2019-a multi-centre observational study
Cen Y, et al.
Clin Microbiol Infect 2020; Jun 9: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32526275
Characteristics of the initial patients hospitalized for COVID-19: a single-center report
Medetalibeyoglu A, et al.
Turk J Med Sci 2020; Jun 3:
https://www.ncbi.nlm.nih.gov/pubmed/32490641
Epidemiology, Clinical Features, and Disease Severity in Patients With Coronavirus Disease 2019 (COVID-19) in a Children's Hospital in New York City, New York
Zachariah P, et al.
JAMA Pediatr 2020;Jun 3: e202430.
https://www.ncbi.nlm.nih.gov/pubmed/32492092
[COVID-19 associated pneumonia despite repeatedly negative PCR-analysis from oropharyngeal swabs]
Hornuss D, et al.
Dtsch Med Wochenschr 2020; 145 (12), Jun: 844-849.OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32403153
Hospitalization and Mortality among Black Patients and White Patients with Covid-19
Price-Haywood EG, et al.
N Engl J Med 2020; May 27:
https://www.ncbi.nlm.nih.gov/pubmed/32459916
Clinical Characteristics, Associated Factors, and Predicting COVID-19 Mortality Risk: A Retrospective Study in Wuhan, China
Yu C, et al.
Am J Prev Med 2020; May 27: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32564974
Laboratory abnormalities in children with mild and severe coronavirus disease 2019 (COVID-19): A pooled analysis and review
Henry BM, et al.
Clin Biochem 2020; May 27:
https://www.ncbi.nlm.nih.gov/pubmed/32473151
Prognostic value of C-reactive protein in patients with COVID-19
Luo X, et al.
Clin Infect Dis 2020; May 23:
https://www.ncbi.nlm.nih.gov/pubmed/32445579
Biochemical indicators of coronavirus disease 2019 exacerbation and the clinical implications
An PJ, et al.
Pharmacol Res 2020; May 22: 104946.
https://www.ncbi.nlm.nih.gov/pubmed/32450346
Early Predictors of Clinical Deterioration in a Cohort of 239 Patients Hospitalized for Covid-19 Infection in Lombardy, Italy
Cecconi M, et al.
J Clin Med 2020;9 (5),May 20:
https://www.ncbi.nlm.nih.gov/pubmed/32443899
The clinical characteristic of eight patients of COVID-19 with positive RT-PCR test after discharge
Cao H, et al.
J Med Virol 2020; May 15:
https://www.ncbi.nlm.nih.gov/pubmed/32410245
Risk Factors of Severe Disease and Efficacy of Treatment in Patients Infected with COVID-19: A Systematic Review, Meta-Analysis and Meta-Regression Analysis
Zhang JJY, et al.
Clin Infect Dis 2020; May 14:
https://www.ncbi.nlm.nih.gov/pubmed/32407459
Novel coronavirus disease 2019 (COVID-19): relationship between chest CT scores and laboratory parameters
Zhang B, et al.
Eur J Nucl Med Mol Imaging 2020; May 12:
https://www.ncbi.nlm.nih.gov/pubmed/32399620
Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China
Chen R, et al.
J Allergy Clin Immunol 2020; May 11:
https://www.ncbi.nlm.nih.gov/pubmed/32407836
Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical Center in New York City
Chao JY, et al.
J Pediatr 2020; May 11:
https://www.ncbi.nlm.nih.gov/pubmed/32407719
Characterisation of COVID-19 Pandemic in Paediatric Age Group: A Systematic Review and Meta-Analysis
Mustafa NM and L AS
J Clin Virol 2020;128 May 8: 104395.
https://www.ncbi.nlm.nih.gov/pubmed/32417675
Clinical phenotypes of SARS-CoV-2: Implications for clinicians and researchers
Rello J, et al.
Eur Respir J 2020;Apr 27: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32341111
Clinical Pathway for Early Diagnosis of COVID-19: Updates from Experience to Evidence-Based Practice
Xu G, et al.
Clin Rev Allergy Immunol 2020; Apr 24: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32328954
Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis
Zheng Z, et al.
J Infect 2020; Apr 23: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32335169
Risk Factors of Fatal Outcome in Hospitalized Subjects With Coronavirus Disease 2019 From a Nationwide Analysis in China
Chen R, et al.
Chest 2020;Apr 15: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32304772
Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study
Chen T, et al.
J Gerontol A Biol Sci Med Sci 2020;Apr 11: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32279081
Clinical Features of COVID-19-Related Liver Damage
Fan Z, et al.
Clin Gastroenterol Hepatol 2020;Apr 10: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32283325
SARS-Cov-2 in Spanish Intensive Care: Early Experience with 15-day Survival In Vitoria
Barrasa H,et al.
Anaesth Crit Care Pain Med 2020;Apr 9: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32278670
Hematological findings and complications of COVID-19
Terpos E, et al.
Am J Hematol 2020;Apr 13: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32282949
Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China
Zhang G, et al.
J Clin Virol 2020;1 27 Apr 9: 104364.OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32311650
Clinical characteristics and outcomes of patients with severe Covid-19 with diabetes
Yan Y, Yang Y, et al.
BMJ Open Diabetes Res Care 2020; 8 (1),Apr: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32345579
Clinicopathological characteristics of 8697 patients with COVID-19 in China: a meta-analysis
Zhu J, et al.
Fam Med Community Health 2020;8 (2),Apr: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32371463
Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China
Wu P, et al.
JAMA Ophthalmol 2020;Mar 31: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32232433
Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
Zhou F, et al.
Lancet 2020;395 (10229),Mar 28: 1054-1062.OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32171076
Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China
Shi S, et al.
JAMA Cardiol 2020;Mar 25: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32211816
Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study
Qiu H, et al.
Lancet Infect Dis 2020;Mar 25: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32220650
Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study
Sun D, et al.
World J Pediatr 2020;Mar 19: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32193831
Clinical and CT features in pediatric patients with COVID-19 infection: Different points from adults
Xia W, et al.
Pediatr Pulmonol 2020;Mar 5: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32134205
Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis
Lippi G and Plebani M
Clin Chim Acta 2020;Mar 4:
https://www.ncbi.nlm.nih.gov/pubmed/32145275
Clinical Characteristics of Coronavirus Disease 2019 in China
Guan WJ, et al.
N Engl J Med 2020;Feb 28: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32109013
Chest CT Findings in Patients with Corona Virus Disease 2019 and its Relationship with Clinical Features
Wu J, et al.
Invest Radiol 2020;Feb 21: OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32091414
Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series
Xu XW, et al.
BMJ 2020;368 Feb 19: m606.OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32075786
Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study
Chen N, et al.
Lancet 2020;395 (10223),Feb 15: 507-513.OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/32007143
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Huang C, et al.
Lancet 2020;395 (10223),Feb 15: 497-506.OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/31986264
