COVID-19 and Secondary Infections

Using procalcitonin as a prognostic indicator of COVID-19 severity of illness

Procalcitonin (PCT) is a biomarker that, when used in conjunction with other laboratory findings and clinical assessments, can indicate the risk of bacterial infection. In addition, PCT also has a role to play in confronting the coronavirus. It can identify a superimposed bacterial infection and thus support the use of antibiotics only in those COVID-19 patients who need it.

In recent, evolving studies, PCT has identified COVID-19 patients at low risk for bacterial coinfection and adverse outcome.1-7 While the majority of COVID-19 patients can avoid antibiotics altogether, one study of 38 Michigan hospitals found that antibiotics may have been started in COVID-19 patients “just in case.” In these hospitals, 56.6% of patients were prescribed early, empiric antibacterial therapy despite a low prevalence of confirmed bacterial infection (3.5%).8 Inappropriate antibiotic prescribing can be harmful, sometimes deadly, and leads to increased antibiotic exposure and resistance.

PCT insight for COVID-19 disease severity and bacterial coinfection

An analysis of 1,099 COVID-19 patient data sets from medical centers in China 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).2 In fact, most COVID-19 patients had PCT values < 0.25 µg/L or even < 0.1 µg/L.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.9-14

In cases with bacterial coinfection and higher severity of disease, PCT has been found to be higher (> 0.5 µg/L).1-6 Thus, according to a recent meta-analysis of published COVID-19 patient data, PCT > 0.5 µg/L corresponds to an almost five-times higher risk of severe infection (OR, 4.76; 95% CI, 2.74-8.29) compared to patients with lower PCT.15 Acute Respiratory Distress Syndrome (ARDS) and septic shock were the most frequent complications of COVID-19; secondary infections during the hospital stay were an additional risk factor.1-6 Patient mortality was almost always associated with sepsis/septic shock and respiratory failure/ARDS.2,3,6,9

PCT on admission

Test PCT as an aid for early risk assessment of patients at high risk of bacterial coinfection.

  • 0.25 - < 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.1-6 Likelihood of bacterial infection and recommendation to start antibiotics in patients with lower respiratory tract infection at PCT > 0.25 µg/L.15

PCT and COVID-19 Patient Management
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PCT and COVID-19 guidelines

With the right biomarkers in place, hospitals have the opportunity to bolster their antibiotic stewardship programs and reduce unnecessary antibiotic exposure. Procalcitonin equips clinicians with objective insights, making it easier to determine whether to prescribe or discontinue antibiotic therapy. Such a customized treatment approach is only possible if the proper education is in place.

 

International Federation of Clinical Chemistry and Laboratory Medicine (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:17

“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.”17

Co-chairs 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:18

"... 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.”18

Centers for Disease Control and Prevention (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.19

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.”19

Helpful resources

Learn more about implementing optimized procalcitonin testing in your hospital.

References
  1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet Infect Dis. 2020 Feb 15;395(10223):497-506.
  2. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. NEJM. 2020 Apr 30;382(18):1708-20.
  3. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet Infect Dis. 2020 Mar 11.
  4. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Yu T. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet Infect Dis. 2020 Feb 15;395(10223):507-13.
  5. Xu XW, Wu XX, Jiang XG, Xu KJ, Ying LJ, Ma CL, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series. BMJ. 2020 Feb 19;368.
  6. Huang Y, Zhou H, Yang R, Xu Y, Feng X, Gong P. Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China. medRxiv. 2020 Jan 1.
  7. American Association of Clinical Chemistry. Key biomarkers in managing COVID-19 [Internet]. Washington, DC, USA. [Apr 16; cited 2020 Dec 14] Available here.
  8. Vaughn VM, Gandhi T, Petty LA, Patel PK, Prescott HC, Malani AN, et al. Empiric antibacterial therapy and community-onset bacterial coinfection in patients hospitalized with COVID-19: a multi-hospital cohort study. Clin Infect Dis. 2020 Aug 21.
  9. Ingram PR, Inglis T, Moxon D, Speers D. Procalcitonin and C-reactive protein in severe 2009 H1N1 influenza infection. Intensive Care Med. 2010 Mar 1;36(3):528-32.
  10. Cuquemelle E, Soulis F, Villers D, Roche-Campo F, Somohano CA, Fartoukh M, et al. Can procalcitonin help identify associated bacterial infection in patients with severe influenza pneumonia? A multicentre study. Intensive Care Med. 2011 May 1;37(5):796-800.
  11. Rodríguez AH, Avilés-Jurado FX, Díaz E, Schuetz P, Trefler SI, Solé-Violán J, Cordero L, et al. Procalcitonin (PCT) levels for ruling-out bacterial coinfection in ICU patients with influenza: A CHAID decision-tree analysis. J Infect. 2016 Feb 1;72(2):143-51.
  12. Chua AP, Lee KH. Procalcitonin in severe acute respiratory syndrome (SARS). J Infect. 2004 May 1;48(4):303-6.
  13. Rhee JY, Hong G, Ryu KM. Clinical implications of five cases of Middle East respiratory syndrome coronavirus infection in South Korea outbreak. Jpn J Infect Dis. 2016:JJID-2015.
  14. Karhu J, Ala-Kokko TI, Vuorinen T, Ohtonen P, Julkunen I, Syrjälä HT. Interleukin-5, interleukin-6, interferon induced protein-10, procalcitonin and C-reactive protein among mechanically ventilated severe community-acquired viral and bacterial pneumonia patients. Cytokine. 2019 Jan 1;113:272-6.
  15. Lippi G, Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis. Clin Chim Acta. 2020 Jun;505:190.
  16. Schuetz P, Bolliger R, Merker M, Christ-Crain M, Stolz D, Tamm M, et al. Procalcitonin-guided antibiotic therapy algorithms for different types of acute respiratory infections based on previous trials. Expert Rev Anti Infect Ther. 2018 Jul 3;16(7):555-64.
  17. International Federation of Clinical Chemistry and Laboratory Medicine. IFCC information guide on COVID-19 [Internet]. Milano, IT. [Aug 23; cited 2020 Dec 14] Available here.
  18. Metlay JP, Waterer GW. Treatment of community-acquired pneumonia during the coronavirus disease 2019 (COVID-19) pandemic. Ann Intern Med. 2020 Aug 18;173(4):304-305.
  19. Centers for Disease Control and Prevention. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19) [Internet]. Atlanta (GA). [Dec 8; cited 2020 Dec 14] Available here.