MR

Hematology’s Indispensable Role in

COVID-19 Diagnosis & Prognosis

Hematology team,
IVD division,
International sale and marketing.
2020.02
CONTENTS

01 CBC test 01
of COVID-19

02 Hematology products against COVID-19

03 Appendix
03

2
MR Novel Coronavirus (COVID-19) Outbreaks

With the outbreak of Coronavirus Disease

2019(COVID-19) in Wuhan, China, human beings are
facing the threat of a novel coronavirus(2019-nCoV).
Until 26th Feb, there are total 81,027 COVID-19 cases
worldwide, including most cases in Asia. The explosive
growth has brought new challenges to the medical
system, we must hurry up to fight against COVID-19!

https://www.ecdc.europa.eu/en/geographical-distribution-2019-ncov-cases
MR Novel Coronavirus (COVID-19) Outbreaks
COVID-19 is the infectious disease caused by the most recently discovered coronavirus, named by WHO. This
new virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019.

The laboratory testing of COVID-19

◆ Laboratory testing (Guideline from China CDC1)

Routine blood test White blood cell count is usually normal

or reduced, with decreased lymphocyte count，progressive
lymphocytopenia in severe cases.
C-reactive protein (CRP) increased in most patients.
Nucleic acid testing is the main method of laboratory diagnosis.
2019-nCoV nucleic acid can be detected by RT-PCR or by viral
gene sequencing of throat swabs, sputum, stool or blood
samples.

◆ Guideline from USA CDC2 is in line with China CDC.

1. 关于印发新型冠状病毒感染的肺炎诊疗方案(试行 第六版), interim clinical guidance for diagnosis and treatment of Novel Coronavirus(Version 6).
2. Interim Clinical Guidance for Management of Patients with Confirmed 2019 Novel Coronavirus (2019-nCoV) Infection, CDC, February 12, 2020.
MR Hematological test is most easily accessible for screening COVID-19

• Expensive and not

• Fast and easy easily accessible
• Ambiguous in early stage • Demanding operation

Complete blood count

Golden standard——
CT scanning Clinical key decision molecular diagnosis

Clinical symptoms

• Even though CT and molecular diagnosis result is convincing and decisive, CT devices and reagents
for molecular diagnosis is not easily accessible.
• The entry level Hematological test could be precondition of COVID-19 virus screening.
MR Routine blood test support COVID-19 management

Blood test for COVID-19 CBC results from COVID-19 patients & healthy people5
COVID-19 patients Healthy
A. WBC: normal or increased (24-30% of 73 (median) (median)
Case number 38 patients 120 healthy check-ups
patients )3,4
Lymphocyte(109/L) 0.87 2.13
B. Lymphocyte count and percentage :
Lymphocyte (%) 19.5 33.7
decreased(63% of 41 patients)3
Eosinophil (109/L) 0.0061 0.1417
C. CRP: increased (86% of 73 patients)4 Eosinophil(%) 0.13 2.16

D. Eosinophil count: decreased5 CRP(mg/L) 61.8 <10

• Most patients showed decreased Lymphocyte count, increased CRP and decreased Eosinophil count.
• CBC test is primary method to screen suspected COVID-19.
• Routine blood test is fast and fully automated analyzing method to avoid cross contamination, low cost.

3. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020 Jan 24.
4. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Jan 30.
5. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020 Feb 6.
MR CRP in the diagnosis & prognosis of COVID-19

1. What is CRP? 2. Clinical Features of CRP response in COVID-19?

➢ Full name: C-reactive protein (CRP) CRP concentration in COVID-19 patients(mg/L)

➢ The protein arises in the condition of Case No. Patients Range Normal Reference
(average or mean±SD) Range Article
infection (Confirmed by Avery,1941)
No. 73 51.4 0-5 4
➢ Increase within 4~6h of inflammation and
No. 38 61.8 <10 5
double every 8 hours，Peak at 36~50 h
and 100~1000% higher than normal value. No. 128 35.83±1.88 0-8.2 9

➢ The level and duration of CRP is No. 12 > 30 (8 out 0f 12) <10 10
proportional to the extent of infection Note: Ref 9 is preprint article, which has not been peer-reviewed

Conclusion: Most studies showed that CRP of all patients were increased significantly, especially in
severe patients. The CRP value of COVID-19 patients were over 30, much higher than the upper limit of
normal reference range(<10 mg/L).

4. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Jan 30.
5. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020 Feb 6.
9. Clinical features and laboratory inspection of novel coronavirus pneumonia (COVID-19) in Xiangyang, Hubei. medRxiv 2020.Feb.
Note: This article is a preprint and has not been peer-reviewed.
10. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Science China Life Science.
MR CRP in the diagnosis & prognosis of COVID-19: example

Clinical symptoms, chest CT images and CRP

Example: values shows below during the treatment
Duration Clinical symptoms Chest CT images
Patient A, the close contact of person from (day)
Wuhan, had a low-grade fever for five days
1 Fever only \
before seeking medical care.
2 Fever only Normal
Normal CBC results and no clinical symptoms 5 Fever and body aches Minimal ground-glass
showed on the first day at the hospital, next opacities
day, however, WBC count dipped, CRP 9 Breathing difficulty Worse than that in day 5
slightly increased, and then high-grade fever 13 Breathing difficulty \
happened at 39 ℃. more severe, CPAP used
15 Breathing difficulty Better in lower lung field,
Chest CT showed minimal ground-glass lessened, oxygen more lesions occurred in
opacities in the bilateral lower lung lobes. inhalation other fields of lung
19 Breathing difficulty \
For all these Clinical manifestations, A was kept lessened, oxygen
primarily diagnosed as Novel Coronavirus inhalation
(COVID-19) 22 No symptoms, no oxygen Less lesions with
inhalation obvious fibrosis
25 No symptoms, no oxygen Better than that in day 22
inhalation
MR CRP in the diagnosis & prognosis of COVID-19: example
CBC and CRP results of patient A (on BC-6800Plus, BC-6800, BC-5390CRP, and M-100

Results

Results
Duration (day) Duration (day)

Results
Results

Duration (day) Duration (day)

MR CRP in the diagnosis & prognosis of COVID-19: example

Discussion

Low-grade fever, normal The decreased values of WBC,

WBC and lymphocyte Neu, NLR and CRP and
count found at an early increased lym# indicated a
stage; good recovery after the treatment

Early stage Disease progresses After treatment Cure

Lym decreased, NLR Until day 25, values of WBC,

rapidly upwarded, CRP curve Neu, Lym, NLR and CRP
escalated as the disease became normal, virus check
progresses. In the most was negative, which means,
serious conditions (day 13), the oxygen was not needed and
values of WBC, Neu, NLR and patient could
CRP accessed peaks, while resume normal activities
Lym# reached a nadir
MR CRP in the diagnosis & prognosis of COVID-19

A retrospective study was performed on the clinical characteristics of 128 COVID-19 cases with
laboratory-confirmed from Xiangyang No 1 Hospitalad during January 2020 to 16 February 2020

C-reactive protein (CRP) level of all patients were increased markedly, but it in the severe
group was significantly higher than that in the non-severe group ( P < 0.01 ).
MR A new prognosis indicator - NLR

➢ NLR is Neutrophil to Lymphocyte count Ratio, it’s

calculated from CBC result, easy-to-use parameter.

➢ Study6 in Beijing showed that cut-off value of NLR is

3.13, sensitivity is 0.875 and specificity is 0.717.

➢ Patients should be transferred to ICU with age >50

and NLR>3.13. If NLR<3.13 and age<50, the
patients could isolate at home or community hospital.

Conclusion: NLR is meaningful parameters for prognosis and risk stratification management, which would
be helpful to alleviate insufficient medical resources.
6. Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage. medRxiv 2020.Feb.10
Note: This article is a preprint and has not been peer-reviewed.
MR A new prognosis indicator - NLR
Studies showed that patients in ICU had high NLR results.
Neutrophil (109/L) Lymphocyte (109/L) Reference
Case No. NLR
median (interquartile range) median article
41 5.0(3.3-8.9) 0.8 6.25 3
73 5.0(3.3-8.1) 0.9 5.55 4
61 2.8(2.3-4.4) 0.7-1.1 3.6 6
138 4.6(2.6-7.9) 0.8 5.75 7

Family cluster case study8 : patient1 and patient3(with mask) is exposure in hospital.
Elder patients, with high NLR, showed severe symptoms.
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 7 mother father mother
1 2 7
Age 65 66 37 36 10 63
Neutrophil 4.0 3.2 3.1 8.1 3.2 2.7 daughter son
3 4
Lymphocyte 0.6 0.7 2.2 2.7 2.8 1.2
NLR 6.66 4.57 1.41 3 1.14 2.25
5 child

3. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020 Jan 24.
4. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Jan 30.
6. Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage. medRxiv 2020.Feb.10
7. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. Jama 2020
8. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission_ a study of a family cluster. The Lancet. 2020 Jan 24
MR A new prognosis indicator - NLR

• Progressive lymphocytopenia is commonly found in severe cases.

• 5 out of 138 patients were in severe illness with Neu# ↑ and a Lym# ↓ , ultimately, death7.
• Neu# ↑ and Lym# ↓ is a progressive increased NLR result.

NLR of survious and non survious

50
45
40
Nonsurvious
35
30 Survivous
25
20
15
10
5
0
0 5 10 15 20
days after disease onset

7. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. Jama 2020
MR A new prognosis indicator – NLR: example
Back to the example of patient A
Severe
diagnose recover
recover

Count (x109/L)

Count (x109/L)
• Innitially, the Neu#, Lym#, NLR were normal.
• As getting worse, patient has progressive diagnose
Severe
neutrophilia, lymphocytopenia, and increasing
CRP until 13 days after disease onset.
• With intensive healthcare, the patient was cured,
and Lym#, NLR and CRP became normal Days after disease onset Days after disease onset
generally. Severe Severe

Concentration(mg/L)
Ratio
recover diagnose

recover
Conclusion: Lym, NLR and CRP are
diagnose
meaningful parameters for treatment
monitoring.
The abnormal range would be a little different Days after disease onset
Days after disease onset
in different hospitals.
CBC+DIFF test with CRP on Mindray BC-5390CRP, BC-6800Plus, BC-6900, CRP-M100
MR Distinction of disease stage: NLR & RDW-SD

Novel Coronavirus (COVID-19)

Moderate Severe
144 specimen 38 specimen

According to the right graphs,the

number of WBC and neutrophil
grows, while Lym# goes down with
the condition progress, in addition,
NLR and RDW-SD increase.
MR Distinction of disease stage: NLR & RDW-SD

• The left graph is the ROC curve of differentiating moderate and severe patients using blood routine
parameters.
• The positive samples were from severe patients, and the negative samples were from moderate
patients.
• The results show that NLR is the best single parameter for distinguishing moderate and severe types,
and its AUC is 0.89.

• In view of the obvious differences of RDW-SD

between moderate and severe groups, a linear
fitting graph of NLR and RDW-SD was created
according to the formula in the figure above,
fitting parameter NLR & RDW-SD were created
as well, its AUC was 0.94.
• When the Cut-off value was 1.06, the sensitivity
of distinguishing moderate type from severe type
is 90%, and the specificity is 84.7%.
• In conclusion, when Cut-off value is
greater than 1.06, it will
more probably be severe type.
MR Routine blood test support COVID-19 management

CBC
◆ Routine CBC test is primary screening method for COVID-19 disease.
CRP
◆ CBC test + CRP + NLR support COVID-19 prognosis. NLR
➢ CRP, an inflammation response protein, plays an active role in COVID-19
screening and prognosis.
➢ NLR is meaningful parameters for prognosis and risk stratification
management, which is intended to alleviate insufficient medical
resources.
➢ NLR & CRP is great of prognostic value, which can be used for
treatment monitoring.

CBC test CRP test NLR prognosis support COVID-19 management

18
 Mindray hematology products
against COVID-19
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Huoshenshan hospital,
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laboratory could handle over days in Wuhan to tackle
1000 samples/day. COVID-19 outbreak.
+33,900 square meters
With 1000 beds
30 intensive care units(ICU)
Huoshenshan Hospital
+1400 doctors and nurses.
MR Mindray hematology products against COVID-19

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✓ Closed tube to avoid Aerosol
pollution of COVID-19;
✓ NLR parameter available

BC-5310CRP
MR Mindray hematology products against COVID-19

SC-120 ✓ Scalable Automation, BC-6800Plus/BC-

CRP-M100 BC-6800Plus
6800+CRP-M100 + SC-120.
✓ Fast, up to 800T/H for CBC+DIFF, 100T/H for
CRP, 120T/H for slides
✓ NLR result in each CBC+DIFF test.
✓ Closed tube to avoid Aerosol transmitted
1 tube CAL 8000 211
infection.
High capacity
Solution CRP-M100 BC-6800Plus ✓ BC-6800Plus/BC-6800+CRP-M100.
For ✓ Fast, up to 200T/H for CBC+DIFF, 100T/H for
CBC+DIFF+CRP CRP, 120T/H for slides
With NLR ✓ NLR result in each CBC+DIFF test.
✓ Closed tube to avoid Aerosol transmitted
CAL 3000 infection. 21
MR Mindray hematology products against COVID-19

BC-5000 series BC-6000 series

✓ Closed tube to avoid Aerosol
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✓ NLR result in each CBC+DIFF test

22
MR Appendix 1 References

1. 关于印发新型冠状病毒感染的肺炎诊疗方案(试行 第六版), interim clinical guidance for diagnosis and treatment of Novel Coronavirus(Version 6).
2.Interim Clinical Guidance for Management of Patients with Confirmed 2019 Novel Coronavirus (2019-nCoV) Infection, CDC, February 12, 2020.
3. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020 Jan 24.
4. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Jan 30.
5. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020 Feb 6.
6. Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage. medRxiv 2020.Feb.10
Note: This article is a preprint and has not been peer-reviewed.
7. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. Jama 2020
8. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission_ a study of a family cluster. The Lancet. 2020 Jan 24
9. Clinical features and laboratory inspection of novel coronavirus pneumonia (COVID-19) in Xiangyang, Hubei. medRxiv 2020.Feb.
Note: This article is a preprint and has not been peer-reviewed.
10. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Science China Life Science.

MR Appendix 2 What else can the NLR be used for?

• A widely used marker for the assessment of the severity of bacterial infections11.
• The prognosis of patients with pneumonia12,13.
• Predictive index for Acute-on-chronic hepatitis B liver failure14.
• The increase of NLR indicated poor clinical prognosis, if NLR is in great high level, which was a
warning sign for higher mortality risk.
11. Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as
Biomarkers in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome and Nature of Bacteremia[J]. Mediators of Inflammation, 2018.
12. Neutrophil-to-Lymphocyte Ratio in Adult Community-Acquired Pneumonia Patients Correlates with Unfavorable Clinical Outcomes. Clinical laboratory 2019.
13. Neutrophil-to-Lymphocyte Ratio Improves the Accuracy and Sensitivity of Pneumonia Severity Index in Predicting 30-Day Mortality of CAP Patients.
Clinical laboratory 2019
14. Neutrophil-lymphocyte ratio: a novel predictor for short-term prognosis in acute-on-chronic hepatitis B liver failure. Journal of viral hepatitis 2014.
Thank You！