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Original Article
Page 1 of 10

Red cell distribution width (RDW): a prognostic indicator of severe

COVID-19

Changzheng Wang1#, Hongmei Zhang2#, Xiaocui Cao2#, Rongrong Deng3, Yi Ye4, Zhongxiao Fu1,
Liyao Gou4, Feng Shao5, Jin Li4, Weiyang Fu6, Xiaomei Zhang4, Xiao Ding1, Jianping Xiao4, Chuanjian
Wu4, Tao Li1, Huan Qi4, Chengbin Li1, Zhongxin Lu2

1 Department of Laboratory Medicine, The Second Clinical Medical College, Yangtze University, Jingzhou, China; 2Department of Laboratory
Medicine, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 3Pediatric
Medical Center, The Second Clinical Medical College, Yangtze University, Jingzhou, China; 4Clinical Department (IVD), Shenzhen Mindray Bio-
Medical Electronics Co., Ltd, Shenzhen, China; 5Department of Intensive Care Unit (ICU), The Second Clinical Medical College, Yangtze University,
Jingzhou, China; 6Department of Respiratory Medicine, Jingzhou Infectious Disease Hospital, Jingzhou, China
Contributions: (I) Conception and design: Y Ye, L Go, J Li, X Zhang, F Shao; (II) Administrative support: H Zhang, R Deng; (III) Provision of study
materials or patients: C Wu, T Li; ( IV) Collection and assembly of data: Z Fu, W Fu, X Ding; (V) Data analysis and interpretation: C Wang, H Zhang,
X Cao; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript : All authors.
#
These authors contributed equally to this work.
Correspondence to: Professor Huan Qi. Clinical Department (IVD), Shenzhen Mindray Bio-Medical Electronics Co., Ltd, Shenzhen, China. Email:
qihuan@mindray.com ; Professor Chengbin Li. Department of Laboratory Medicine, Jingzhou Central Hospital, The Second Clinical Medical College,
Yangtze University, Jingzhou, China. Email: jzlcb002@163.com ; Professor Zhongxin Lu. Department of Laboratory Medicine, the Central Hospital of
Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Email: lzx71 @yahoo.com.

Background: The global mortality rate for coronavirus disease 2019 (COVID-19) is 3.68%, but the
mortality rate for critically ill patients is as high as 50%. Therefore, the exploration of prognostic
predictors for patients with COVID-19 is vital for prompt clinical intervention. Our study aims to explore
the predictive value of hematological parameters in the prognosis of patients with severe COVID-19.
Methods: Ninety-eight patients who were diagnosed with COVID-19 at Jingzhou Central Hospital and
Central Hospital of Wuhan, Hubei Province, were included in this study.
Results: The median age of the patients was 59 [28–80] years; the median age of patients with a good prognosis was 56 [28–79] years, and the median age of patients

with a poor outcome was 67 [35–80] years. The patients in the poor outcome group were older than the patients in the good outcome group (P<0.05). The comparison

of hematological parameters showed that lymphocyte count (Lym#), red blood cells (RBCs), hemoglobin (HGB) , hematocrit (HCT), mean corpuscular volume (MCV), and

mean corpuscular hemoglobin (MCH) were significantly lower in the poor outcome group than in the good outcome group (P<0.05). Further, the red cell volume

distribution width-CV (RDW-CV) and red cell volume distribution width-SD (RDW-SD) were significantly higher in the poor outcome group than in the good outcome

group (P<0.0001).Receiver operating characteristic (ROC) curves showed RDW-SD, with an area under the ROC curve (AUC) of 0.870 [95% confidence interval (CI) 0.796–

0.943], was the most significant single parameter for predicting the prognosis of severe patients . When the cut-off value was 42.15, the sensitivity and specificity of

RDW-SD for predicting the prognosis of severe patients were 73.1% and 80.2%, respectively. Reticulocyte (RET) channel results showed the RET level was significantly

higher in critical patients than in moderate patients and severe patients (P<0.05), which may be one cause of the elevated RDW in patients with a poor outcome.When

the cut-off value was 42.15, the sensitivity and specificity of RDW-SD for predicting the prognosis of severe patients were 73.1% and 80.2%, respectively. Reticulocyte

(RET) channel results showed the RET level was significantly higher in critical patients than in moderate patients and severe patients (P<0.05), which may be one cause

of the elevated RDW in patients with a poor outcome.When the cut-off value was 42.15, the sensitivity and specificity of RDW-SD for predicting the prognosis of severe

patients were 73.1% and 80.2%, respectively. Reticulocyte (RET) channel results showed the RET level was significantly higher in critical patients than in moderate

patients and severe patients (P<0.05), which may be one cause of the elevated RDW in patients with a poor outcome.

Conclusions: In this study, the hematological parameters of COVID-19 patients were statistically
analyzed. RDW was found to be a prognostic predictor for patients with severe COVID-19, and the
increase in RET may contribute to elevated RDW.

© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2020;8(19):1230 | http://dx.doi.org/10.21037/atm-20-6090
Page 2 of 10 Wang et al. Red cell distribution width is a prognostic factor of severe COVID-19

Keywords: Red cell distribution width (RDW); novel coronavirus (SARS-Cov-2); COVID-19; receiver operating
characteristic (ROC); linear discriminant analysis (LDA); prognostic indicator

Submitted Jul 27, 2020. Accepted for publication Sep 28, 2020.
doi: 10.21037/atm-20-6090
View this article at: http://dx.doi.org/10.21037/atm-20-6090

Introduction severe COVID-19 increases significantly (10). Although many

studies on COVID-19 have reported hematological
Severe acute respiratory syndrome coronavirus 2 (SARS-
parameters, most have only focused on the differences in
CoV-2) is the third deadly coronavirus type and the cause of
hematological parameters between patients with different
coronavirus disease 2019 (COVID-19) (1). With the spread of
severities of COVID-19. Only a few studies have reported the
the COVID-19 epidemic, the number of infected people has
predictive role of hematological parameters in the prognosis
escalated. As of April 27, 2020, 185 countries and regions
of patients with severe COVID-19. Therefore, we
were involved in the COVID-19 pandemic, with over
retrospectively analyzed the hematology parameters of
2,970,000 diagnosed cases and over 200,000 deaths
inpatients with severe COVID-19 at our hospital to explore
(mortality rate, approximately 7.0%) reported worldwide (2).
the value of hematological parameters in predicting the
The main manifestations of patients with COVID-19 are
prognosis of severe patients, and found that RDW is a
fever, dry cough, and fatigue. In severe cases, dyspnea or
prognostic predictor for patients with severe COVID-19. We
hypoxemia usually occurs 1 week after disease onset, and
present the following article in accordance with the MDAR
patients may rapidly become critically ill. According to an
reporting checklist (available at http://dx.doi. org/10.21037/
observational study on patients with COVID-19 in Wuhan ,
atm-20-6090).
among 52 critically ill patients, 32 patients (61.5%) died
within 28 days of onset,and the median time from intensive
care unit (ICU) admission to death was 7 days [interquartile Methods
range (IQR) 3–11], showing a high mortality rate for critical
Patients
patients (3). Therefore, it is essential to monitor the dynamic
condition of patients diagnosed with COVID-19 during This study included 98 patients with COVID-19 at Jingzhou
hospitalization, especially to predict the prognosis of Central Hospital and Central Hospital of Wuhan from January
patients in advance so that clinical intervention can be 20, 2020, to March 30, 2020. The trial was divided into two
implemented as early as possible. phases: prognosis analysis and mechanism analysis. For the
As hematological tests can supply the most common and prognosis analysis, the epidemiological information, clinical
easy-to-get diagnosis and treatment evidence, they are information, and hematological test results retrieved using a
widely used in medical institutions at all levels. Because of hematology analyzer (no test results from the reticulocyte
low detection costs and high automation, hematological (RET) channel) for 43 patients who were diagnosed as severe
tests have become the first choice for disease monitoring at admission from January 20, 2020, to March 10, 2020, were
and the evaluation of general conditions. Some collected. According to whether the patients became
hematological parameters transform into patients with critically ill during hospitalization, they were divided into a
COVID-19. Upon disease aggravation in patients with good outcome group (N=31) and a poor outcome group
COVID-19, the lymphocyte count (Lym#) decreases (N=12). In the mechanism analysis, 55 patients with
significantly; the Lym# in patients who die is significantly COVID-19 from March 12, 2020, to March 30, 2020,were
lower than that in survivors (4-7). Also, some studies have included to study the mechanism in positive results for the
shown the red cell volume distribution width (RDW) of prognosis analysis; their hematological test results retrieved
patients with severe COVID-19 increases significantly, using a hematology analyzer (including test results from the
showing that the role of erythroid cell parameters as risk RET channel) were collected to classify patients according to
indicators may be underestimated (8,9 ).It has also been theGuidelines for the Diagnosis and Treatment of COVID-19 (
reported the platelet (PLT) count of patients with Seventh Edition)

© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2020;8(19):1230 | http://dx.doi.org/10.21037/atm-20-6090
Annals of Translational Medicine, Vol 8, No 19 October 2020 Page 3 of 10

issued by the National Health Commission of the Seventy-one hematological test results were collected
People's Republic of China. The numbers of moderate, for the mechanism analysis. The data from the above
severe, and critical cases were 40, 5, and 10, respectively. hematological test results and RET channel data were
For all patients, viral detection confirmed COVID-19 using collected: RET percent (%), reticulocyte count (RET#), high
the SARS-CoV-2 nucleic acid detection kit (fluorescence fluorescence reticulocyte ratio (HFR%), and middle
polymerase chain reaction (PCR), Shanghai BioGerm fluorescence reticulocyte ratio (MFR%), etc. The blood
Medical Biotechnology Co., Ltd.). samples were divided into the moderate group (46
COVID-19 severity was classified according to the cases), severe group (6 cases), and critical group (19
Guidelines for the Diagnosis and Treatment of COVID-19 cases) according to each patient's condition at the time of
(Seventh Edi t ion) is sued by the Nat iona l Hea l th sample collection.
Commission of the People's Republic of China: Hematological tests were performed using a Mindray
(I) Mild: cases were classified as mild cases when patients BC-6800 automatic hematology analyzer (Mindray,
had mild clinical symptoms and no imaging Shenzhen, China).
manifestations of pneumonia; All procedures performed in this study involving human
(II) Moderate: cases were classified as moderate when participants were in accordance with the Declaration of
patients had a fever, respiratory tract symptoms, Helsinki (as revised in 2013). The Ethics Committee approved
and imaging manifestations of pneumonia; this study of Jingzhou Central Hospital and the Ethics
(III) Severe: cases were classified as severe when adult Committee of the Central Hospital of Wuhan. As this study
patients met any of the following criteria: (i) was a retrospective study, there was no patient's private
respiratory rate (RR) ≥30 times/min, (ii) resting data, including patient name, ID number, telephone, and
oxygen saturation (finger) ≤93%, (iii) partial pressure address, were involved. Only demographic information and
of oxygen (PaO2)/fraction of inspired oxygen (FiO2)≤ laboratory testing data of patients were collected and
300 mmHg, and (iv) >50% lesion progression within analyzed, so there is no informed consent in this study.
24–48 h detected by lung imaging;
(IV) Critical: cases were classified as critical when patients
met one of the following criteria: a. respiratory Statistical analysis

failure and the need for mechanical ventilation, b. Continuous variables are expressed as the mean or median,
shock, c. custodial care in the ICU because of organ and categorical variables are presented as the percentage of
failure other than lung failure. composition ratio. Between-group comparisons were
performed using Student's t-test. The Multigroup
Laboratory data collection comparisons were performed using a one-way analysis of
variance, and later pair-wise comparisons were performed
One hundred seventy-three hematological test results were
using the Tukey-Kramer procedure. Categorical variables
collected from the 98 patients. For the prognosis analysis,
were compared using Pearson's chi-square test. Receiver
102 hematological test results were collected, including
operating characteristic (ROC) curves were used to analyze
complete blood count parameters [white blood cell (WBC),
the classification performance of the parameters. Single
red blood cell (RBC), platelet (PLT) ), etc.], WBC classification
parameters were combined into pairs using linear
parameters [neutrophil count (Neu#), lymphocyte count
discriminant analysis (LDA), pairs with intergroup differences
(Lym#), monocyte count (Mon#), etc.] and cell morphological
were screened, and their classification performance was
parameters [red cell volume distribution width-CV (RDW-CV ),
analyzed using ROC curves. P<0.05 was considered
red cell volume distribution width-SD (RDW-SD), mean
statistically significant. GraphPad Prism version 8.0 was used
corpuscular volume (MCV), etc.]. According to whether the
to perform the above statistical analysis.
patients became critical within 3 days after sample
collection, the test results were divided into the poor
outcome group (26 cases) and the good outcome group (76 Results
cases). If a patient was already critically ill before sample
Presentation characteristics
collection,the test results were not included in the statistics.
The epidemiological information, clinical information,

© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2020;8(19):1230 | http://dx.doi.org/10.21037/atm-20-6090
Page 4 of 10 Wang et al. Red cell distribution width is a prognostic factor of severe COVID-19

Table 1 Presentation characteristics

Good outcome Poor outcome

Characteristics Total (N=43) P value
(N=31) (N=12)

Age, median [range] 59 [28–80] 56 [28–79] 67 [35–80] 0.036

Gender 0.987

Male 25 (58.1) 18 (58.1) 7 (58.3)

Female 18 (41.9) 13 (41.9) 5 (41.7)

Exposure history, n (%)

Close contact with suspected cases within 2 weeks 4 (9.3) 2 (6.5) 2 (16.7) 0.308

Close contact with confirmed cases within 2 weeks 6 (14.0) 4 (12.9) 2 (16.7) > 0.999

Comorbidities, n (%)

Hypertension 15 (34.9) 11 (35.5) 4 (33.3) > 0.999

Cardiovascular disease 2 (4.7) 1 (3.2) 1 (8.3) 0.485

Diabetes 5 (11.6) 4 (12.9) 1 (8.3) > 0.999

Malignancy 1 (2.3) 1 (3.2) 0 > 0.999

Cerebrovascular disease 4 (9.3) 2 (6.5) 2 (16.7) 0.308

COPD 0 0 0

Chronic kidney disease 2 (4.7) 0 2 (16.7) 0.073

Viral hepatitis 0 0 0

Signs and symptoms, n (%)

Fever 36 (83.7) 28 (80.7) 8 (95.0) 0.060

Fatigue 16 (37.2) 12 (38.7) 4 (33.3) > 0.999

Dry cough 21 (48.8) 18 (58.1) 3 (25.0) 0.088

Chill 8 (18.6) 6 (19.4) 2 (16.7) > 0.999

Sputum 10 (23.3) 6 (19.4) 4 (33.3) 0.427

Myalgia 5 (11.6) 3 (9.7) 2 (16.7) 0.608

Headache 1 (2.3) 1 (3.2) 0 > 0.999

P value shows the differences between good outcome groups and poor outcome groups. P<0.05 was considered statistically significant.
COPD, chronic obstructive pulmonary disease.

symptoms, and signs of patients in the good outcome group Comparison of differences in Hematological test results for
(31 patients) and poor outcome group (12 patients) were severe patients with different outcomes
compared and analyzed (Table 1). The median age of the
From the comparison of the hematological test results of
patients was 59 years (range 28–80 years). There was a
significant difference (P=0.036) between the median age of blood samples from the good outcome group and poor
the patients in the good outcome group (56 years, range 28– outcome group (Table 2), the Lym#, RBC, hemoglobin
79 years ) and the patients in the poor outcome group (67 (HGB), hematocrit (HCT), MCV, and mean corpuscular
years, range 35–80 years). However, the epidemiological hemoglobin (MCH) in the poor outcome group were
history, comorbidities, symptoms, and signs were not significantly lower than those in the good outcome group
significantly different between the two groups of patients (P<0.05), and the RDW-CV. Further, RDW-SD in the poor
(P>0.05). outcome group were significantly higher than those

© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2020;8(19):1230 | http://dx.doi.org/10.21037/atm-20-6090
Annals of Translational Medicine, Vol 8, No 19 October 2020 Page 5 of 10

Table 2 Comparison of hematology analysis results of severe patients with different prognosis

Parameters Good outcome (mean ± SD, N=76) Poor outcome (mean ± SD, N=26) P value

WBC 9.49±4.47 10.43±7.51 0.443

Neu# 7.89±4.46 9.32±7.14 0.235

Lym# 1.02±0.61 0.64±0.40 0.004

Mon# 0.51±0.26 0.41±0.21 0.083

Eos# 0.05±0.09 0.04±0.09 0.745

Baso# 0.02±0.01 0.02±0.02 0.393

NLR 14.72±18.77 17.68±13.17 0.459

PLR 400.10±381.30 445.50±356.80 0.596

RBC 4.15±0.51 3.64±0.84 0.0005

HGB 127.80±16.63 109.00±29.36 0.0001

HCT 38.41±4.71 33.0±8.23 <0.0001

MCV 92.67±3.54 90.52±6.15 0.031

MCH 30.82±1.53 29.77±2.67 0.016

MCHC 332.40±9.36 328.50±11.86 0.090

RDW_CV 12.44±0.50 13.97±1.31 <0.0001

RDW_SD 40.41±1.77 44.62±3.46 <0.0001

PLT 250.20±104.30 213.80±103.70 0.127

MPV 9.74±1.36 10.16±1.48 0.185

PDW 15.81±1.79 16.33±0.62 0.152

PCT 0.24±0.09 0.21±0.11 0.292

Data are shown as mean ± SD. P value indicates the difference between the good outcome group and the poor outcome group. P<0.05 was
considered statistically significant. WBC, white blood cells; Neu#, neutrophil count; Lym#, lymphocyte count; Mon#, monocyte count; Eos#,
eosinophil count; Baso#, basophil count; NLR, neutrophil-lymphocyte ratio; PLR, platelet-lymphocyte ratio; RBC, red blood cells; HGB,
hemoglobin; HCT, hematocrit; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin
concentration; RDW-CV, red cell volume distribution width-coefficient of variation; RDW-SD, red cell volume distribution width-standard
deviation; PLT, platelet; MPV, mean platelet volume; PDW, platelet volume distribution width; PCT, plateletcrit.

in the good outcome group (P<0.05). For the other routine false-negative rate was used as the reference for the choice of
hematological parameters involved in the statistical analysis, the optimal cut-off value. The results showed that RDW-SD was
including WBC, Neu#, Mon#, Eos#, and PLT, there were no the best single parameter for predicting the prognosis of severe
significant differences between the two groups (P> 0.05). patients, with an area under the ROC curve (AUC) of 0.870 [95%
confidence interval (CI) 0.796–0.943]. When the cut-off value was
42.15, the sensitivity and specificity of RDW-SD for predicting the
Hematological test results predict the prognosis of severe
prognosis of severe patients were 73.1% and 80.2%, respectively
patients
(Table 3).
ROC curves were used to analyze the routine hematological LDA was used to linearly combine any two single
parameters significantly different between the good outcome parameters from all hematological test results to generate
group and the poor outcome group. The ROC curves of some new joint parameters. Among them, Lym# & RDW-CV, Lym#
single parameters are shown in Figure 1A. The minimum sum of & RDW-SD, and HGB & RDW-SD had the highest AUCs for
squares of the false positive rate and the predicting the prognosis of severe COVID-19

© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2020;8(19):1230 | http://dx.doi.org/10.21037/atm-20-6090
Page 6 of 10 Wang et al. Red cell distribution width is a prognostic factor of severe COVID-19

A Single parameter ROC

B Combined parameter ROC

100 100
Lym# Lym#&RDW-CV
80 HGB 80 Lym#&RDW-SD

RDW-CV HGB&RDW-SD
Sensitivity%

Sensitivity%
60 60
RDW-SD
40 40

20 20

0 0
0 20 40 60 80 100 0 20 40 60 80 100
100%-Specificity% 100%-Specificity%

C Scatter gram D Lym#&RDW-SD

55
****
6
Good outcome

Poor outcome 4
50

Lym#&RDW-SD
Fit line
2
RDW-SD

45
0
40
-2

35 –4
0 1 2 3

e
e

om
m

Lym# (109/L)
o

tc
tc

ou
ou

or
d
oo

Po
G

Figure 1 Prediction analysis of hematology parameters and the outcomes of patients with severe COVID-19. (A) ROC curve, the single
parameter for predicting the prognosis of ill patients; (B) ROC curve, joint parameters for predicting the prognosis of ill patients; ( C) the linearly
fitted schematic scatter plot for Lym# & RDW-SD; (D) comparison of Lym# & RDW-SD in ill patients with different prognoses. Lym# & RDW-SD:
joint parameter generated after linear fitting of Lym# and RDW-SD. ****, P<0.0001.

patients; the ROC curves are shown in Figure 1B. Taking less than 0.92, the probability of patients developing critical
Lym# & RDW-SD as an example, a scatter plot for blood illness within 3 days was low.
samples from severe patients with different outcomes, using
Lym# as the abscissa and RDW-SD as the ordinate, is shown
RET channel test results for patients with different
in Figure 1C. The fitted line is the best mode of the joint
severities of COVID-19
parameter for the differentiation of the two sets of data.
Between-group comparisons showed that Lym# & RDW-SD To investigate the cause of the significant increase in RDW in
was significantly higher in the poor outcome group than in severe patients with a poor outcome, blood samples from
the good outcome group (P <0.0001) (Figure 1D). The AUC COVID-19 patients from March 12, 2020, to March 30, 2020,
for Lym# & RDW-SD for predicting the prognosis of severe were used for a mechanism analysis. A scatter plot of data
patients was 0.920 (95% CI 0.860–0.979). When the cut-off obtained using a hematology analyzer showed as disease
value was 0.92, the sensitivity and specificity of Lym# & severity increased, the RET% increased, which might be an
RDW-SD for predicting the prognosis of severe patients were explanation for the increased RDW in severe patients with a
88.5% and 85.5%, respectively (Table 3). When the Lym# & poor outcome. The RBC volume/hemoglobin concentration
RDW-SD of severe patients were more significant than or (V/HC) scattergram showed that the magenta scatters of
equal to 0.92, there was a high probability that these critical patients were significantly left-skewed, indicating that
patients would develop critical illness within 3 days; when RETs with a low HC increased significantly, which may
the value was represent a particular pattern of erythroid

© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2020;8(19):1230 | http://dx.doi.org/10.21037/atm-20-6090
Annals of Translational Medicine, Vol 8, No 19 October 2020 Page 7 of 10

Table 3 Prediction analysis of hematology parameters of patients with severe COVID-19

Parameters AUC 95% CI Cut-off Sensitivity (%) Specificity (%)

Lym# 0.695 0.582–0.807 0.64 69.2 76.3

HGB 0.701 0.569–0.833 113.5 53.9 82.9

RDW-CV 0.864 0.775–0.952 12.85 73.9 81.9

RDW-SD 0.870 0.796–0.943 42.15 73.1 80.2

Lym & RDW-CV 0.928 0.852–1.000 0.64 95.7 83.3

Lym & RDW-SD 0.920 0.860–0.979 0.92 88.5 85.5

HGB & RDW-SD 0.893 0.820–0.966 0.81 80.8 77.6

AUC, area under the ROC curve; 95% CI, 95% confidence interval.

A RET scatter RBC scatter RBC V/HC scatter B RDW-SD C RET%

RET%: 1.01 VOL 70 8

* ****

FS FS
* ***

60 6
ns

RDW-SD
Moderate

RET%
4
50 ns

2
FL SS HC 40
0
RET%: 2.59 VOL
FS FS

l
re

re
ca

ca
e

e
at

at
ve

ve
iti

iti
er

er
Se

Se
Cr

Cr
od

od
M

M
Severe

D IRF% E HYPOr#

40 0.08 ***
****
**
FL SS HC
*
30 HYPOr# (1012/L) 0.06
RET%: 4.3 VOL
FS FS
ns
IRF%

20 0.04 ns
Critical
10 0.02

0 0.00
al

l
re

re

FL SS HC
ca
e

te
at

ic
ve

ve
ra

iti
it
er

e
Se

Se
Cr

Cr
od

od
M

Figure 2 Differences of RET channel results in patients with different severity of COVID-19. (A) Scattergram of RET channel data from Mindray
BC-6800 hematology analyzer. Blue scatters are RBCs, magenta, and the red scatter is the RETs, and cyan scatters are PLTs. (B,C,D,E)
Comparison of parameters obtained from the RET channel for patients with different severities of COVID-19. Data are shown as the mean ± SD.
****, P<0.0001; *** , P<0.001; **, P<0.01; *, P<0.05. FS, forward scatter; SS, side scatter; FL, fluorescence; HC, hemoglobin concentration; VOL,
volume; ns, nonsignificant.

hyperplasia in critical COVID-19 patients (Figure 2A). patients were significantly higher than those in moderate
Comparisons of output parameters showed RDW-SD, and severe patients (P<0.05); however, those parameters
RET%, immature reticulocyte fraction (IRF%), and were not significantly different between moderate patients
hypochromic reticulocyte count (HYPOr#) in critical and severe patients (Figure 2B,C,D,E).

© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2020;8(19):1230 | http://dx.doi.org/10.21037/atm-20-6090
Page 8 of 10 Wang et al. Red cell distribution width is a prognostic factor of severe COVID-19

Discussion collection were not included in the statistics. From the

comparison of hematological parameters in the two groups,
Since the COVID-19 outbreak began in December 2019,
Lym#, RBC, HGB, HCT, MCV, and MCH were significantly
there have been many reports on hematological parameters
lower in the poor outcome group than in the good outcome
in patients with COVID-19. However, most reports have
group (P<0.05 ), RDW-CV and RDW-SD were significantly
focused on the differences in hematological parameters in
higher in the poor outcome group than in the good outcome
patients with different severities of COVID-19. There are few
group (P<0.0001). ROC curves showed RDW-SD was the best
studies on the role of hematological parameters in
single parameter for predicting the prognosis of ill patients,
predicting the prognosis of patients. In this study, a
with an AUC of 0.870 (95% CI: 0.796–0.943). LDA was used to
comparison of hematological test results of patients with
combine any two random routine hematological parameters
different outcomes showed RDW might be a predictor of
linearly. Among the joint parameters generated, Lym# &
prognosis in patients with severe COVID-19 and that the
RDW-CV had the most significant predictive efficacy, with an
increase in RET may be one cause for the increase in RDW.
AUC of 0.928 (95% CI: 0.852–1.000). When the cut-off value
This study included 98 patients with COVID-19 at Jingzhou
was 0.64, the sensitivity and specificity of Lym# & RDW-CV
Central Hospital and Central Hospital of Wuhan from January
were 95.7% and 83.3%, respectively.Recent studies (11,12)
20, 2020, to March 30, 2020. The prognostic analysis was
have reported that RDW can be a prognostic factor for
performed with 43 patients diagnosed as severe at
infectious diseases (including sepsis and severe viral
admission from January 20, 2020, to March 10, 2020. The infection), which is consistent with the present study.
data collected included the epidemiological information,
clinical information, and hematological test results (without RDW shows the heterogeneity in RBC volume in peripheral
RET channel data) of the patients. The results showed that blood. The higher the RDW is, the more significant the
the increase in RDW might be a prognostic factor in critical heterogeneity in RBC volume. RET channel testing of the blood
patients. To investigate the causes of elevated RDW, we samples was added for the patients in the mechanism analysis
conducted a mechanism analysis with 55 patients with to investigate the cause of increased heterogeneity in RBC
COVID-19 from March 12, 2020, to March 30, 2020, focusing volume in severe patients with a poor outcome. The RET channel
on RET channel data in the hematological analysis of these of the Mindray BC-6800 hematology analyzer can detect the
patients. number, size, and hemoglobin concentration of RBCs using
Epidemiological and clinical information showed that the high-sensitivity laser scattering technology and can quantify and
median age of the included patients was 59 [28–80] years old; classify RETs using fluorescence detection. The results showed
the median age of the patients with a good outcome was 56 [28– that the number of RETs was significantly higher in critical
79] years old, and the median age of the patients with a poor patients than in moderate patients and severe patients. Because
outcome was 67 [35–80] years old. Patients with a poor outcome the volume of a RET is more significant than a mature RBC, the
were older than those with a good outcome (P<0.05), suggesting increase in RETs may cause an increase in RDW.
that elderly patients are more prone to a poor outcome.
However, there were no significant differences in exposure Interestingly, the RBC V/HC scattergram showed RETs
history, comorbidities, symptoms, or signs between the two with low HC was significantly increased in critical
groups. patients. This trend was shown in the histogram of
Currently, many group study laboratory tests only show parameters as significantly increased HYPOr# in the
the results according to the disease initial severity of critically ill group, which may have occurred because the
patients. However, disease severity constantly changes increased erythropoietin synthesis and active erythroid
throughout hospitalization. Therefore, this study separately hyperplasia because of long-term hypoxia and the
classified each blood sample according to the condition of impaired HGB synthesis because of malnutrition or iron
the corresponding patient at the time of sample collection. deficiency in critical patients resulted in low-HC RETs in
Patients who did not develop critical illness within 3 days the newly generated RETs. However, whether such low-
after sample collection were included in the good outcome HC RETs could a diagnostic marker of critical COVID -19
group, and patients who developed critical illness within 3 still requires further investigation. There is no report on
days after sample collection were included in the poor the RET level in patients with COVID-19. However, some
outcome group; patients with critical illness before sample researchers (13,14) have found immature RBCs in

© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2020;8(19):1230 | http://dx.doi.org/10.21037/atm-20-6090
Annals of Translational Medicine, Vol 8, No 19 October 2020 Page 9 of 10

peripheral blood smears from patients with COVID-19, and reporting checklist. Available athttp://dx.doi.org/10.21037/
an increase in RETs often accompanies immature RBCs in atm-20-6090
peripheral blood. Their findings in directly support the
findings in this study. Data Sharing Statement:Available athttp://dx.doi. org/
Because the number of RET significantly increased in 10.21037/atm-20-6090
critical patients, and the volume of RETs was more
significant than mature RBCs, their MCV should also be Conflicts of Interest:All authors have completed the ICMJE
increased. However, the MVC was lower in patients with a uniform disclosure form (available athttp://dx.doi. org/
poor outcome than in patients with a good outcome in this 10.21037/atm-20-6090). The authors have no conflicts of
study (Table 2). This finding suggests that the increase in interest to declare.
numbers of RETs may not be the only cause of the increase
in RDW in patients with COVID-19 with a poor outcome. It Ethical Statement:The authors are accountable for all
has been reported that before aggravation of infection aspects of the work in ensuring that questions related to the
symptoms, the level of oxidative stress in the body increases accuracy or integrity of any part of the work are
significantly, and the release of oxygen free radicals appropriately investigated and resolved. All procedures
increases (15). Also, insufficient circulating nutrients in performed in this study involving human participants were
patients with a poor outcome may lead to an increase in RBC in accordance with the Declaration of Helsinki ( as revised in
membrane instability, increasing RDW. All these factors 2013). The Ethics Committee approved this study of Jingzhou
might cause an increase in RDW and RETs and a decrease in Central Hospital and the Ethics Committee of the Central
MCV in patients with a poor outcome (16,17). Hospital of Wuhan. As this study was a retrospective study,
Because the mechanism analysis included relatively there was no patient's private data, including patient name,
numerous blood samples from ill patients (6 cases), it was ID number, telephone , and address, were involved. Only
difficult to group them according to prognosis. Therefore, demographic information and laboratory testing data of
for the mechanism analysis, statistical analysis was patients were collected and analyzed, so there is no
performed after grouping the blood samples according to informed consent in this study.
disease severity. The conclusion from the analysis was that
the significant increase in RETs in critical patients was only a Open Access Statement: This is an Open Access article
probable reason for the increase in RDW in patients with a distributed in accordance with the Creative Commons
poor outcome. More patient samples will be collected to Attribution-NonCommercial-NoDerivs 4.0 International License
obtain more RET channel data for verification. (CC BY-NC-ND 4.0), which permits the noncommercial replication
In summary, this study statistically analyzed the and distribution of the article with the strict proviso that no
hematological test results of patients with COVID-19 in two changes or edits are made and the original work is properly
hospitals and found RDW can be used as a predictor for the cited (including links to both the formal publication through the
prognosis of severe patients and that an increase in relevant DOI and the license). See: https://
numbers of RETs may be one cause of the increase in RDW. creativecommons.org/licenses/by-nc-nd/4.0/.

Acknowledgments References

We thank all patients who took part in this study. Thanks to 1. China National Health Commission. Diagnosis and
all health-care workers in our hospital for their efforts in treatment of pneumonia caused by new coronavirus
caring for these patients. Thanks to all people who work so infection (version 7) (Mar 3, 2020). Beijing: China
hard to fight against the novel coronavirus pneumonia National Health Commission, 2020.
(COVID-19) . 2. COVID-19 Dashboard by the Center for Systems Science and
Funding: None. Engineering (CSSE) at Johns Hopkins University (JHU).
Available online https://coronavirus.jhu.edu/map. html.
4/27/2020, 10:42 :00 AM
Footnote
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Reporting Checklist: The authors have completed the MDAR critically ill patients with SARS-CoV-2 pneumonia

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Cite this article as: Wang C, Zhang H, Cao X, Deng R, Ye Y, Fu

Z, Gou L, Shao F, Li J, Fu W, Zhang X, Ding X, Xiao J, Wu C, Li T,
Qi H, Li C , Lu Z. Red cell distribution width (RDW): a
prognostic indicator of severe COVID-19. Ann Transl Med
2020;8(19):1230. doi: 10.21037/atm-20-6090

© Annals of Translational Medicine. All rights reserved. Ann Transl Med 2020;8(19):1230 | http://dx.doi.org/10.21037/atm-20-6090