crp as a prognostic indicator in hospitalized patient with covid 19

1. PRESENTED BY
MAJ CHOWDHURY TANJINA MUNTAKIM
TRAINEE OFFICER
AFIP

2. C-Reactive protein as a prognostic indicator in
hospitalized patients with COVID-19
Emory University Hospital, Atlanta, Georgia, United States of America
Milad Sharifpour, Srikant Rangaraju, Michael Liu , Darwish Alabyad ,
Fadi B. Nahab , Christina M. Creel-Bulos , Craig S. Jabaley
Journal plos one, Published November 20, 2020

3. CORONAVIRUS DISEASE-2019
COVID-19

4. Coronavirus
• Large family of viruses, causing illness both
humans and animals like bats, camels, and
civets.
• Previous Coronaviruses have included
SARS- CoV and MERS-CoV.
• Severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) is a new strain
of coronavirus that has not been previously
identified in humans.
Coronavirus

5. Common human
coronaviruses
HCoV-229E
HCoV-NL63
HCoV-HKU1
HCoV-OC43
Novel Coronaviruses
2003 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)
2012 Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
2019 Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)

6. • Enveloped RNA virus
• Spike (S) protein
• Membrane (M) protein
• Nucleocapsid (N) protein
• Small envelope (E) protein
SARS- CoV-2
Coronaviruses derive their name
from crown-like appearance.

7. Source: www.worldometer’s.info/coronavirus
Global Situation
As of 07 March 2021 global COVID-19 situation
Total deaths 2,603,036
Total confirmed cases 117,327,203
More than 300 million vaccine given
worldwide

8. Source: www.corona.gov.bd
Bangladesh Scenario

9. Transmission

10. • Positive test for SARS-CoV-2
• Absence of clinical signs and symptoms
• Normal CXR and CT scan
Asymptomatic
infection
• Fever, fatigue, myalgia
• Dry cough, sneezing
• Vomiting, nausea, diarrhea
Mild infection
• Persistent fever
• Pneumonia
Moderate infection
• Respiratory and GIT infection
• Development of dyspnoea and hypoxia
Severe infection
• ARDS or Respiratory failure
• Multi organ failure
Critical infection
Clinical Feature

11. I

12. Pathophysiology

13. Pathophysiology
Pathophysiology

14. Serology
RT PCR
Threshold of
detection
Antigen
Laboratory diagnosis

15. Laboratory diagnosis

16.  Nasopharyngeal swab
 Oropharyngeal swab
 Bronchoalveolar lavage
 Bronchial brushing
 Sputum
 Blood
Specimen Collection

17.  Most commonly used and reliable technique
 Based on NAAT.
 Target genes : S, RdRP, N, E, ORF
 Sensitivity of clinical samples
 Average sensitivity 95.2% (ranging from
68% to 100%)
 Average specificity 98.9%.
Reverse Transcription RT-PCR
Sample Sensitivity
Nasal swab 63%
Pharyngeal swab 32%
Sputum 72–75%
Bronchoalveolar lavage 93–95%

18. GeneXpert technique
Rapid, real-time RT-PCR test for qualitative
detection of nucleic acid from the SARS-CoV-2 .
The Xpert Xpress SARS-CoV-2 test contains
primers and probes and internal controls used
in RT-PCR.
Target genes : N2 and E.
It requires only 01 hour to get the result.
Sensitivity : 97.8%
Specificity : 95.6%
Cartridge based NAAT

19. Rapid Antigen Test
 Immunochromatography
technique
 Nasal swab or
oropharyngeal swab are
used
 ICT discs are used
 POCT
 Only 15 mins required
 Sensitivity: According to
the WHO sensitivity
ranges between 34% and
80%.
 Specificity: 97.85% to
100%
RAT NEGATIVE
RAT POSITIVE

20.  Immunochromatography
method:
 Blood samples are taken
 IgG and IgM are detected
 ICT discs are used
 POCT
 Only 15 mins required
 Sensitivity :60% to 95.5%
 Specificity : 97.38% to 100%
Serological test
ICT Negative
ICT POSITIVE
Antibody detection is based on
ICT and CLIA

21. Serological test
• CHEMILUMINISCENCE
IMMUNOASSAY
• Quantitative determination of IgM and
IgG antibody to SARS-CoV-2
• Sensitivity:88.8% to 97.2%
• Specificity:94.4% to 99.1%
• IgM antibodies are generally detectable
several days after initial infection
• IgG antibodies generally become
detectable 10–14 days after infection and
peaking around 28 days

22.  Haematological:
 PBF: Neutrophilic leukocytosis ,
Lymphopenia,Thrombocytopenia
 Coagulation profile: FDP, D-Dimer
 Biochemical test:
 Serum Bilirubin, ALT, AST, Albumin
 Serum ferritin
 Serum Creatinine
 Immunological marker:
 CRP
 IL-6
 Radiology: X-ray chest , CT scan
Supportive test

23. • Tab Paracetamol (500mg)
• Antihistamine
• Thromboprophylaxis: For Mild COVID 19 cases with risk factor
Mild case
• Oxygen inhalation
• Thromboprophylaxis
• Antiviral - Remdesivir
Moderate
case
• I/V steroid
• Broad spectrum I/V antibiotic
• For cytokine storm -Tocilizumab
Severe
case
• ICU admission
• Ensure adequate oxygenation and Mechanical ventilation if needed
• Rx according to complications
Critical
case
Treatment

26. C-Reactive Protein

27. These are the class of proteins whose plasma concentration increase or
decrease in response to inflammation or infection
APP
Positive
APP
Plasma concentration
increases in response to
the stimuli
Negative
APP
Plasma concentration
decrease in response to
the stimuli
Acute phase protein

28. Positive APPs Negative APPs
C reactive proteins ( CRP) Albumin
Serum Amyloid A (SAA) Transferrin
Heptoglobin (Hp) Transthyretin
Ceruloplasmin Retinol-binding protein
α2- Macroglobulin
α1- Acid glycoprotein
(AGP)
Fibrinogen
Complement (C3, C4)
Acute phase protein

29. CRP is a direct and quantitative measure of the acute-phase
reactions.
C-Reactive Protein

30.  Synthesize primarily in hepatocytes
 CRP Gene- Chromosome 1, long arm
 IL-6 and IL-1 regulate CRP at transcriptional
level.
 Normal range: Less than 10mg/L
 CRP value rises within 4 to 6 hours of exposure
to noxious stimuli and falls within 18 to 20 hours
of resolution of the stimuli.
 It has highest affinity for,
• Phosphocholine on bacteria and eukaryotic
cell membranes
C-Reactive Protein

31.  First described in 1930 by Tillet & Francis
 In serum from patients of pneumonia
(Inflammation)
 High seroreactivity with C-polysaccharide
capsule of Streptococcus pneumoniae
 C FRACTION ( C-reactive protein) reacted
heavily with the serum of an acutely ill
patient CRP
C-Reactive Protein

32. CRP
Induces
complement
activation
Increases
LDL uptake
and
oxidation
Inhibits
nitric oxide
production
Induces
production
of tissue
factor
Up regulates
the
expression
of adhesion
molecules
Inhibits
fibrinolysis
by
increasing
expression
of PAI-1
Facilitates
infiltration of
monocyte
into vessel
wall
Functions

33. IL-1ß,IL-6
TNF
pCRP
mCRP
Activated platelet
Activated leukocytes
Microparticles
Activated endothelial cell
Ischemic, necrotic, apoptotic cells
ß Amyloid
Liver
pCRP
• bis PC
• Anti-CRP compound
Platelet activation
Complement fixation
Endothelial activation
Leukocyte activation
Activation of CRP

34. Factor Effect
Gender Women have higher levels than men
Body mass effect Weight loss- decrease
Ethnicity Black have higher levels than whites
Exercise After exercise CRP levels decrease
Alcohol consumption Decrease
Factor affecting CRP levels

35. Clinical importance of CRP
Assessment of disease activity and inflammatory
condition:
– Rheumatoid Arthritis
– Ankylosing Spondylitis
– Cardiovascular events (Myocardial Infarction)
Diagnosis of infection :
– Bacterial endocarditis
– Septicemia and meningitis
– Post operative complications
Determination of treatment
efficacy

36. COVID-19 and CRP
CRP
Lung lesion
Diameter
China: Descriptive study (BY –NC_ND (htt://creative commons.org/licenses/by-nc-nd/4.0/)

37. Methods for detection of CRP
Latex Agglutination
Test
Nephalometry

38. Latex agglutination test for CRP
CRP
CRP
CRP

39. Interpretation

40. Nephalometry

41. Journal Proper
Journal Proper

42. C-Reactive protein as a prognostic
indicator in hospitalized patients with
COVID-19

43.  A systemic inflammatory response is observed in Coronavirus Disease
2019(COVID-19).This pandemic has taxed global critical care capacity as
manifestations may include acute respiratory failure along with significant
end-organ damage.
 Derangements in laboratory markers of inflammatory response, including C-
reactive protein (CRP) have been identified as predictors of clinical severity
and complications
 Recently, several studies have reported that C-reactive protein is a
convenient biomarker in predicting severity of COVID-19.
Introduction

44. To explore the utility of CRP values as a sensitive indicator in assessing
disease progression, risk stratification and prognostication of COVID-19.
Aim

45. Method : Retrospective cohort study
Place : Emory Healthcare Acute-care Hospital Atlanta, USA
Time : March 6, 2020 to May 5, 2020
Sample size : 268 COVID-19 Positive Adult Patients
Tools : Medical case history and all relevant medical records
Research Particulars

46. Materials & Methods
 All patients were 18 years or older, with SARS-CoV-2 infection confirmed
by molecular testing, with a minimum of two CRP values within 7 days of
admission.
 Electronic medical records were reviewed
 Basic demographic data including age, sex, race, body mass index (BMI),
and comorbid diseases were collected.
 Length of hospital and ICU stay, time of intubation, duration of mechanical
ventilation, and final disposition were also recorded.

47.  Within the first 7 days of hospitalization, the peak and slope of CRP
change were determined.
 The median CRP was recorded across the entire hospitalization stay for
each patient.
 All statistical analyses were performed using SPSS statistical package.
Materials & Methods

48. Result

49. Variables Total cohort
(n=268)
Survived (n=201) Died (n=67) P-value
Demographics
Age, Mean (SD) 63 (15) 60(15) 71(13) <0.001
Obesity (BMI>=30 kg/m2),n(%) 141 (52.6%) 117 (58.2%) 24 (35.8%) 0.002
Coronary Artery Disease, n (%) 36 (13.4%) 22 (10.9%) 14 (20.9%) 0.04
Hospitalization details
SOFA (ICU admission) 6 (4-9) 6 (3-9) 7 (4-11) 0.03
Hosp duration, Median (IQR) 16 ( 10-26) 19 (11-28) 12 (7-16) <0.001
Intubation, n (n%) 200 (74.6%) 141 (70.1%) 59 (89.8%) 0.004
Median CRP (hosp wide) 129.6 (82.4-191.4) 114.1 (72-160.4) 206.3 (157.1-287.8) <0.001
Max CRP (d1-7) 247.5 (172.4-340.6) 234 (148-312) 308.9 (245.6-386.9) <0.001
Slope CRP (d1-7) 4.68 (-13.1-19.8) -0.84 (-18.37-13.4) 22.56 (5.12-41.7) <0.001
Patient characteristics and outcomes

50. Optimal threshold of maximum and slope of CRP in the first 7
days of hospitalization as predictors of mortality
CRP Max d1 to d7 Sensitivity Specificity
150 95.5 % 25.9 %
200 88.1 % 39.3 %
250 67.2 % 56.7 %
300 53.7 % 72.6 %
350 41.8 % 82.6 %
CRP slope d1-7 Sensitivity Specificity
0 80.6 % 51.7 %
5 76.1 % 59.2 %
10 70.1 % 69.2 %
15 61.2 % 76.1 %
20 52.2 % 84.6 %
25 46.3 % 87.6 %
30 37.3 % 91.5 %

51. Trends of changes in CRP levels in hospitalized COVID-19
patients

52. Trends in CRP changes in patients who
died(RED) and survived(BLUE)

53. Comparison of median hospitalization–wide CRP levels
between patients who died and survived
CRP value was significantly higher
amongst the patients who died (206
mg/l) compared to those who survived
(114mg/l)

54.  C protein-reactive protein is a non-specific, acute phase inflammatory
protein which is increased in response to tissue injury, inflammation and
infection.
 It is widely available, inexpensive and can reflect the disease severity.
 As an acute- phase reactant ,CRP binds to phosphocholine in pathogens
and membranes of host cells.
Discussion

55.  Base line CRP values are affected by factors such as age, sex, lipid
profile, smoking status.
 Elevated CRP values have been reported in viral respiratory illnesses
such as SARS-CoV,MERS-CoV,H1N1 and have been documented to be
correlated with disease severity and progression.
 CRP levels have been reported to be elevated in hospitalized patient
with COVID-19.
Discussion

56.  It is a single centered retrospective study
 All patients did not have daily CRP values
 Patients who received steroids and Tocilizumab prior to initial CRP
measurement were not recorded in this study.
Limitations

57.  CRP is widely available, inexpensive and easy to obtain biomarker.
 It provides an important clinical evaluation index.
 It provides early thresholds during hospitalization which may facilitate
risk stratification and prognostication.
Conclusion

58. 2019 2020 2021
Feb 11
ICTV named novel
coronavirus as
SARS- CoV-2
Mar 11
WHO declared
COVID 19 as
global pandemic
Apr 2
Confirmed case
reached 1 million
worldwide
Mar 8
First case reported
in Bangladesh
Mar 18
First death in
Bangladesh
July 22
Global coronavirus
cases surpass 15
million
Sept 28
Global deaths
reached 1 million.
Dec 8
First vaccination
started in UK
July 7
AFIP started
Gene Xpert
for COVID 19
Mar 22
AFIP started
RT PCR for
COVID -19
Jan 15
World surpasses
2 million deaths
Jan 27
Bangladesh started
vaccination
Dec 8
First patient
developed
symptoms of
COVID -19 in
Wuhan, China
Nov 12
AFIP started
Rapid Ag test (RAT)
for COVID -19
COVID-19 Timeline
Jan 25
Global coronavirus
cases surpass 100
million

59. 2022 (38%)
425 (8%)
2873 (54%)
Corona Ward
Corona ICU
Others
Total CRP Positive Cases :5320
CRP Positive Cases:
Immunology & Virology Dept, AFIP
( 01st July,2020 to 31st January, 2021)
Positive
5320
Negative
16313
AFIP : 21,633