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SCIENCE CHINA Life Sciences, Volume 63 , Issue 3 : 364-374(2020) https://doi.org/10.1007/s11427-020-1643-8

Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury

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  • ReceivedFeb 5, 2020
  • AcceptedFeb 8, 2020
  • PublishedFeb 9, 2020

Abstract

The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.


Funded by

the National Science and Technology Major Project(2017ZX10103011,2017ZX10204401)

Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2017-I2M-1-009)

Shenzhen Science and Technology Research and Development Project(JCYJ20180504165549581,JCYJ20170413141236903)

China Postdoctoral Science Foundation(2019T120147)


Acknowledgment

The authors would like to thank a scientist who insists on being anonymous. The authors would also like to thank Shunwang Li and Xiaoyun Li who helped data analysis and making figures and tables. This work was supported by the National Science and Technology Major Project (2017ZX10103011 and 2017ZX10204401), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2017-I2M-1-009), Shenzhen Science and Technology Research and Development Project (JCYJ20180504165549581 and JCYJ20170413141236903), China Postdoctoral Science Foundation (2019T120147).


Interest statement

The author(s) declare that they have no conflict of interest.


Supplement

SUPPORTING INFORMATION

Figure S1 Computed tomographic (CT) scans of human cases with 2019-nCoV. CT scans of cases 1 and 3–12 taken at indicated date are shown.

Figure S2 Assessment of the myocardial function in case 4. A and B, The ultrasonic cardiogram results. C, The left ventricular ejection fraction (LVEF) and the left ventricular diameter (LV) at the indicated date.

Figure S3 The correlation between APACHE II scores and viral Ct value in 2019-nCoV-infected patients. The viral titers were detected available in 10 patients with 2019-nCoV infection. APACHE II scores were detected from 12 2019-nCoV-infected patients. Spearman rank correlation analysis (r) and P values are provided in the graph.

Table S1 The Ct values of different sample types from the same case determined by qRT-PCR

The supporting information is available online at http://life.scichina.com and https://link.springer.com. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.


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  • Figure 1

    A timeline of events in human cases with 2019-nCoV. Patients are ordered in chronological order based on the date of admission to our hospital. Various milestones in the disease course are indicated with different graphics. Patients within a family were marked in red and blue, respectively.

  • Figure 2

    (Color online) Computed tomographic (CT) scans and chest radiographs of case 2. (A) CT scans and (B) chest radiographs of case 2 taken at indicated date are shown. d.a.o, days after illness onset.

  • Figure 3

    The Ct value of virus are highly correlated with clinical and laboratory manifestations in 2019-nCoV-infected patients. The Ct value of virus is highly correlated with (A) PaO2/FiO2 ratio, Murray score and (B) CRP, ALB, LYM (%), LYM, NEU in 2019-nCoV-infected patients. The Ct value was detected available in 10 patients with 2019-nCoV infection. PaO2/FiO2 ratio, Murray score, ALB, LYM (%), LYM, NEU, CRP, and LDH were detected from 12 2019-nCoV-infected patients. Spearman rank correlation analysis (r) and P values are provided in each graph.

  • Figure 4

    The Murray score is highly correlated with laboratory manifestations in 2019-nCoV-infected patients. The Murray score is highly correlated with ALB, LYM, LDH, LYM (%), NEU (%), and CRP. Murray score, ALB, LYM, LDH, LYM (%), NEU (%), and CRP were detected from 12 2019-nCoV-infected patients. Spearman rank correlation analysis (r) and P values are provided in each graph.

  • Figure 5

    (Color online) Receiver operating characteristic (ROC) curve of clinical and biochemical indicators of 2019-nCoV-infected patients. (A) ROC curve of the age, Murray score, Ct value of 2019-nCoV, PaO2/FiO2 ratio and (B) ROC curve of the ALB, LYM, CRP, LYM (%), LDH and NEU (%) were calculated between four mild 2019-nCov-infected patients and eight severe 2019-nCov-infected patients. Detailed information is shown in Tables 1 and 2.

  • Figure 6

    (Color online) Plasma angiotensin II levels are increased in 2019-nCoV-infected patients and correlated with viral Ct value and PaO2/FiO2 ratio. (A) Box plot of angiotensin II levels in plasma of healthy controls (n=8) and 2019-nCov-infected patients (n=12). ***, P<0.001 (Mann-Whiney U test). The correlation analysis between plasma angiotensin II levels and (B) viral Ct value, or (C) PaO2/FiO2 ratio of patients with 2019-nCoV infection. The viral titers were detected available in 10 patients with 2019-nCoV infection. The PaO2/FiO2 ratio was detected from 12 2019-nCoV-infected patients. Spearman rank correlation analysis (r) and P values are provided in each graph.

  • Table 1   Epidemiological and clinical features of human subjects hospitalized with 2019-nCoV infection

    Characteristics

    Case 1

    Case 2

    Case 3

    Case 4

    Case 5

    Case 6

    Case 7

    Case 8

    Case 9

    Case 10

    Case 11

    Case 12

    Age

    65

    66

    62

    63

    63

    36

    10

    35

    51

    65

    72

    56

    Sex

    Female

    Male

    Male

    Male

    Female

    Male

    Male

    Male

    Male

    Female

    Male

    Female

    Onset to admission (days)

    9

    8

    4

    5

    8

    5

    5

    7

    13

    16

    16

    7

    Initial symptoms

     

     

     

     

     

     

     

     

     

     

     

     

    Fever

    Yes

    Yes

    Yes

    Yes

    Yes

    Yes 

    No 

    Yes

    No 

    Yes

    Yes

    Yes

    Cough

    Yes

    Yes

    Yes

    Yes

    Yes

    Yes

    No

    Yes

    Yes

    Yes

    Yes

    Yes

    Headache

    No

    No

    No

    No

    No

    No

    No

    No

    No

    No

    No

    No

    Myalgia

    Yes

    Yes

    No

    No

    Yes

    No

    No

    No

    Yes

    No

    No

    No

    Chill

    Yes

    Yes

    Yes

    No

    Yes

    No

    No

    No

    Yes

    No

    No

    No

    Nausea or vomiting

    No

    Yes

    No

    No

    No

    Yes

    No

    No

    No

    No

    No

    No

    Diarrhea

    No

    No

    Yes

    No

    No

    Yes

    No

    No

    No

    No

    No

    No

    Underlying diseases

     

     

     

     

     

     

     

     

     

     

     

     

    Chronic heart disease

    Yes

    Yes

    Yes

    No

    No

    No

    No

    No

    No

    No

    Yes

    No

    Chronic lung disease

    No

    No

    No

    Yes

    No

    No

    No

    No

    No

    No

    No

    No

    Chronic renal disease

    No

    No

    Yes

    No

    No

    No

    No

    No

    No

    No

    Yes

    No

    Chronic liver disease

    No

    No

    No

    No

    No 

    No

    No

    No

    No

    No

    No

    No

    Diabetes

    No

    No

    No

    No

    No

    No

    No

    No

    No

    Yes

    No

    Yes

    Hypertension

    Yes

    Yes

    No

    No

    No

    No

    No

    No

    No

    No

    Yes

    No

    Cancer

    No

    No

    No

    No

    No

    No

    No

    No

    No

    No

    No

    No

    Bacterial co-infections

    No

    Yes

    No

    Yes

    No

    No

    No

    No

    No

    No

    No

    No

    Complications

     

     

     

     

     

     

     

     

     

     

     

     

    Pneumonia

    Yes

    Yes

    Yes

    Yes

    Yes

    Yes

    Yes

    Yes

    Yes

    Yes

    Yes

    Yes

    ARDS

    Yes

    Yes

    Yes

    Yes

    Yes

    No

    No

    No

    No

    Yes

    No

    No

    Severe ARDS

    No

    Yes

    No

    Yes

    No

    No

    No

    No

    No

    No

    No

    No

    Respiratory failure

    No

    Yes

    No

    Yes

    No

    No

    No

    No

    No

    Yes

    No

    No

    Hepatic insufficiency

    No

    Yes

    No

    Yes

    No

    No

    No

    No

    No

    No

    No

    No

    Renal insufficiency

    No

    Yes

    No

    Yes

    No

    No

    No

    No

    No

    No

    No

    No

    Cardiac failure

    No

    No

    No

    Yes

    No

    No

    No

    No

    No

    No

    No

    No

    Shock

    No

    No

    No

    Yes

    No

    No

    No

    No

    No

    No

    No

    No

    Treatment

     

     

     

     

     

     

     

     

     

     

     

     

    Antiviral agents

    Oseltamivir Ribavirin Interferon

    Oseltamivir Ribavirin Interferon

    Oseltamivir Ribavirin Interferon

    Oseltamivir Ribavirin Interferon

    Ribavirin Interferon

    Ribavirin Interferon

    Ribavirin Interferon

    Ribavirin Interferon

    Ribavirin Interferon

    Ribavirin Interferon

    Ribavirin Interferon

    Ribavirin Interferon

    Corticosteroid

    No

    Yes

    No

    Yes

    No

    No

    No

    No

    No

    Yes

    No

    No

    Mechanical ventilation

    Yes

    Yes

    Yes

    Yes

    Yes

    No

    No

    No

    No

    Yes

    No

    No

    Invasive mechanical ventilation

    No 

    Yes

    No

    Yes

    No

    No

    No

    No

    No

    Yes

    No

    No

    Immunoglobulin

    No

    Yes

    No 

    Yes

    Yes

    No

    No

    No

    No

    Yes

    No

    No

    Severe ARDS, PaO2/FiO2 <100.

  • Table 2   Clinical characteristics and laboratory results of subjects hospitalized with 2019-nCoV infection

    Normal range

    Case 1

    Case 2

    Case 3

    Case 4

    Case 5

    Case 6

    Case 7

    Case 8

    Case 9

    Case 10

    Case 11

    Case 12

    PaO2/FiO2

    400–500

    131

    96

    159

    65

    256

    438

    469

    561

    420

    126

    249

    386

    WBC (×109 L–1)

    3.5–9.5

    4.31

    5.24

    3.85

    6.79

    6.71

    13.55

    6.72

    4.62

    4.94

    5.89

    4.99

    3.98

    LYM (%)

    20–50

    20.4

    23.1

    21.6

    3.8

    11.5

    17.5

    56.4

    34.4

    29.4

    7.1

    19.8

    20.9

    LYM (×109 L–1)

    1.10–3.20

    0.88

    1.21

    0.83

    0.26

    0.77

    2.37

    3.79

    1.59

    1.45

    0.42

    NA

    0.83

    NEU (%)

    40–75

    72.6

    67.4

    58.7

    93

    80.9

    77.4

    33.7

    56.8

    64.3

    90.9

    74.8

    75.3

    NEU (×109 L–1)

    1.8–6.3

    3.13

    3.53

    2.26

    6.31

    5.43

    10.49

    2.26

    2.62

    3.18

    5.35

    3.73

    3

    PLT (×109 L–1)

    100–300

    161

    118

    121

    119

    215

    250

    196

    236

    184

    118

    99

    152

    AST (U L–1)

    0–45

    26.7

    33.6

    26

    107

    26.2

    29.3

    34.7

    28.9

    37.7

    52

    42.1

    36.1

    ALT (U L–1)

    0–45

    26.6

    26.5

    26

    62

    45.3

    30

    32.8

    22.4

    39.5

    15.7

    29

    23.6

    TB (µmol L–1)

    3.0–22

    10.8

    9.5

    9.1

    6.2

    11.6

    12

    8.5

    7.8

    7.8

    8.4

    9.6

    5.9

    ALB (g L–1)

    40.0–55.0

    36.8

    39.5

    41.6

    35.1

    38.3

    48.9

    46.4

    43.4

    46.2

    34.6

    42.6

    38.4

    CRE (µmol L–1)

    58–110

    46.5

    81.9

    104

    220

    44.1

    79.7

    53

    95.4

    82.5

    54.1

    122

    43.6

    BUN (mmol L–1)

    3.2–7.1

    2.87

    5.37

    5.51

    9.81

    4.8

    6.65

    7.65

    4.21

    3.71

    4.48

    6.89

    3.12

    CK (U L–1)

    50–310

    46

    118

    97

    876

    NA

    111

    70

    NA

    NA

    NA

    NA

    NA

    MYO (ng mL–1)

    0–110

    25.2

    38.66

    50.1

    390.97

    32.7

    35

    18.7

    20.5

    27

    40.1

    111.9

    23.7

    Ctnl (µg mL–1)

    0–0.1

    0.012

    0.012

    0.012

    11.37

    0.012

    0.012

    0.012

    0.012

    0.012

    0.014

    0.012

    0.012

    BNP (pmol L–1)

    0–23.1

    4.32

    5.7

    3.78

    161.99

    NA

    NA

    NA

    NA

    NA

    NA

    NA

    NA

    CK-MB (ng mL–1)

    0–2.37

    0.24

    0.48

    <0.22

    20.53

    <0.22

    0.25

    0.26

    <0.22

    <0.22

    0.23

    0.97

    <0.22

    LDH (U L–1)

    114.0–240.0

    662

    593

    169

    720

    696

    491

    475

    558

    476

    1266

    510

    648

    CRP (mg L–1)

    <10

    52.6

    38.6

    52.95

    89.94

    53.6

    5.8

    <5

    35.6

    13

    33.2

    85

    28.4

    PCT (ng mL–1)

    0–0.5

    0.048

    0.04

    0.095

    9.18

    0.031

    <0.020

    <0.020

    0.029

    <0.020

    0.077

    0.218

    0.033

    CD4 (count μL–1)

    34–52

    47.3

    45.8

    41.2

    18.7

    30.9

    NA

    NA

    NA

    50.2

    34.9

    50.7

    43

    CD8 (count μL–1)

    21–39

    16.7

    16.5

    11.6

    10.9

    23

    NA

    NA

    NA

    24.9

    14.3

    17

    17.4

    CD4/CD8

    0.9–3.6

    2.83

    2.78

    3.56

    1.72

    1.34

    NA

    NA

    NA

    2.02

    2.45

    2.98

    2.47

    NA, not available.

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