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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Translated information
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
Clinical characteristics and outcomes of cancer patients with COVID-19
Yang F, Shi S, Zhu J, Shi J, Dai K and Chen X
J Med Virol 2020; May 5:
https://www.ncbi.nlm.nih.gov/pubmed/32369209
Clinical phenotypes of SARS-CoV-2: Implications for clinicians and researchers
Rello J, Storti E, Belliato M and Serrano R
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, Yang Y, Du Y, Peng F, Hu P, Wang R, Yin M, Li T, Tu L, Sun J, Jiang T and Chang C
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, Peng F, Xu B, Zhao J, Liu H, Peng J, Li Q, Jiang C, Zhou Y, Liu S, Ye C, Zhang P, Xing Y, Guo H and Tang W
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, Liang W, Jiang M, Guan W, Zhan C, Wang T, Tang C, Sang L, Liu J, Ni Z, Hu Y, Liu L, Shan H, Lei C, Peng Y, Wei L, Liu Y, Hu Y, Peng P, Wang J, Liu J, Chen Z, Li G, Zheng Z, Qiu S, Luo J, Ye C, Zhu S, Liu X, Cheng L, Ye F, Zheng J, Zhang N, Li Y, He J, Li S, Zhong N and Medical Treatment Expert Group for C
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, Dai Z, Mo P, Li X, Ma Z, Song S, Chen X, Luo M, Liang K, Gao S, Zhang Y, Deng L and Xiong Y
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, Chen L, Li J, Cheng X, Jingmao Y, Tian C, Zhang Y, Huang S, Liu Z and Cheng J
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, Rello J, Tejada S, Martin A, Balziskueta G, Vinuesa C, Fernandez-Miret B, Villagra A, Vallejo A, Sebastian AS, Cabanes S, Iribarren S, Fonseca F, Maynar J and Alava CSI
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, Ntanasis-Stathopoulos I, Elalamy I, Kastritis E, Sergentanis TN, Politou M, Psaltopoulou T, Gerotziafas G and Dimopoulos MA
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, Hu C, Luo L, Fang F, Chen Y, Li J, Peng Z and Pan H
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, Wang F, Ren H, Zhang S, Shi X, Yu X and Dong K
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, Zhong Z, Ji P, Li H, Li B, Pang J, Zhang J and Zhao C
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, Duan F, Luo C, Liu Q, Qu X, Liang L and Wu K
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, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H and Cao B
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, Qin M, Shen B, Cai Y, Liu T, Yang F, Gong W, Liu X, Liang J, Zhao Q, Huang H, Yang B and Huang C
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, Wu J, Hong L, Luo Y, Song Q and Chen D
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, Li H, Lu XX, Xiao H, Ren J, Zhang FR and Liu ZS
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, Shao J, Guo Y, Peng X, Li Z and Hu D
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, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS and China Medical Treatment Expert Group for C
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, Wu X, Zeng W, Guo D, Fang Z, Chen L, Huang H and Li C
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, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, Li SB, Wang HY, Zhang S, Gao HN, Sheng JF, Cai HL, Qiu YQ and Li LJ
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, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X and Zhang L
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, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J and Cao B
Lancet 2020;395 (10223),Feb 15: 497-506.OPEN ACCESS
https://www.ncbi.nlm.nih.gov/pubmed/31986264
