Observational Study Medicine ®

Blood urea nitrogen and clinical prognosis in

patients with COVID-19
A retrospective study
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Jiangtao Yin, MDa, Yuchao Wang, MDb, Hongyan Jiang, MDc, Caixia Wu, MDb, Ziyi Sang, MDb, Wen Sun, MDd,
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Junfei Wei, MDe, Wenli Wang, MDa, Dadong Liu, MDa,f, Hanpeng Huang, MDg,*

Abstract
The aim of this study was to estimate the association between blood urea nitrogen (BUN) and clinical prognosis in patients with
COVID-19. A multicenter, retrospective study was conducted in adult patients with COVID-19 in 3 hospitals in Zhenjiang from
January 2023 to May 2023. Patients were divided into survival and death group based on whether they survived at day 28.
The demographic, comorbidities, and laboratory data were independently collected and analyzed, as well as clinical outcomes.
Total 141 patients were enrolled and 23 (16.3%) died within 28 days. Patients who died within 28 days had a higher level of
BUN compared with survivors. Bivariate logistic regression analysis showed that BUN was a risk factor for 28-day mortality
in patients with COVID-19. ROC curve showed that BUN could predict 28-day mortality of COVID-19 patients (AUC = 0.796,
95%CI: 0.654–0.938, P < .001). When the cutoff value of BUN was 7.37 mmol/L, the sensitivity and specificity were 84.62%
and 70.31%. Subgroup analysis demonstrated that hyper-BUN (≥7.37 mmol/L) was associated with increased 28-day mortality
among COVID-19 patients. Patients with COVID-19 who died within 28 days had a higher level of BUN, and hyper-BUN (≥7.37
mmol/L) was associated with increased 28-day mortality.
Abbreviations: ALT = alanine aminotransferase, AST = aspartate aminotransferase, BUN = blood urea nitrogen, CRP =
C-reactive protein, ICU = intensive care unit, PCT = procalcitonin.
Keywords: blood urea nitrogen, COVID-19, mortality

1. Introduction Timely detection of COVID-19 patients at high risk of death

On February 11, 2020, the World Health Organization (WHO)
officially named the disease caused by SARS-CoV-2 as “2019
Coronavirus disease” (COVID-19), and declared COVID-19
pandemic in March of the same year.[1–3] Since then, more vari-
ants of the novel coronavirus have emerged, posing a challenge
to healthcare systems around the world. SARS-CoV-2 infection
may only be asymptomatic, which can be alleviated by symp-
tomatic treatment.[4] However, some patients will develop severe
acute respiratory distress syndrome (ARDS), and require inten-
sive care unit (ICU) hospitalization, mechanical ventilation,
and even extracorporeal membrane oxygenation (ECMO).
Consequently, some patients may die from multiple organ
failure.[5,6]
and supportive care can effectively reduce the incidence of per-
sistent critical illness and in-hospital mortality.[7] Currently, many
laboratory markers, such as D-dimer, C-reactive protein (CRP),
lactate dehydrogenase (LDH), ferritin, procalcitonin (PCT), and
cytokines, especially interleukin-6, have been proposed to pre-
dict and guide the treatment of COVID-19.[8,9] However, these
markers and some disease scoring systems such as CURB-65
and APACHE II may not be practical for early assessment in
terms of risk stratification and prediction to COVID-19 critical
illness.
Therefore, it is necessary to identify novel, reliable and
convenient prognostic biomarkers or predictors of COVID-
19.[10] Blood urea nitrogen (BUN), as a nitrogen-containing
end product of protein metabolism, has been associated with
mortality of various diseases.[11,12] BUN to serum albumin

JY, YW, and HJ contributed equally to this work.
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are
available from the corresponding author on reasonable request.
a
Department of Critical Care Medicine, Digestive Disease Institute of Jiangsu
University, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic
of China, b Medical School of Jiangsu University, Zhenjiang, People’s Republic
of China, c Department of Cardiology, Danyang People’s Hospital, Zhenjiang,
People’s Republic of China, d Department of Critical Care Medicine, Jurong
Hospital Affiliated to Jiangsu University, Zhenjiang, People’s Republic of China,
e
Department of Critical Care Medicine, Traditional Chinese Medicine Hospital
of Zhenjiang, Zhenjiang, People’s Republic of China, f Department of Critical
Care Medicine, Jinling Hospital, Medical School of Nanjing Medical University,
Nanjing, People’s Republic of China, g Department of Pulmonary and Critical Care
Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic
of China.
* Correspondence: Hanpeng Huang, Department of Pulmonary and Critical Care
Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, People’s
Republic of China (e-mail: hhpxhld2019@163.com).
Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open-access article distributed under the terms of the Creative
Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is
permissible to download, share, remix, transform, and buildup the work provided
it is properly cited. The work cannot be used commercially without permission
from the journal.
How to cite this article: Yin J, Wang Y, Jiang H, Wu C, Sang Z, Sun W, Wei J,
Wang W, Liu D, Huang H. Blood urea nitrogen and clinical prognosis in patients
with COVID-19: A retrospective study. Medicine 2024;103:8(e37299).
Received: 28 December 2023 / Received in final form: 24 January 2024 /
Accepted: 26 January 2024
http://dx.doi.org/10.1097/MD.0000000000037299

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 Yin et al. • Medicine (2024) 103:8Medicine
ratio was associated with mortality of COVID-19 patients.[13]
Therefore, this study aimed to evaluate BUN level in patients
with COVID-19 and assess the association between BUN and
clinical prognosis.
2. Materials and methods
2.1. Study design
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A multicenter, retrospective study was designed at the Affiliated
Hospital of Jiangsu University, Jurong Hospital Affiliated to
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Jiangsu University and Traditional Chinese Medicine Hospital
of Zhenjiang from January 2023 to May 2023. This study was
conducted according to the Strengthening the Reporting of
Observational Studies in Epidemiology (STROBE) reporting
guideline. This was a retrospective and non-interventional study,
and ethics review and signed informed consent of the patients
were waived.
2.2. Patients
Adult patients with a diagnosis of COVID-19 were recruited in
this study. The diagnostic criteria of COVID-19 were accord-
ing to the criteria issued by the National Health Bureau of the
People Republic of China. Patients who met the following cri-
teria were excluded: no BUN test results within 24 hours after
admission; younger than 18 years old; chronic kidney disease;
received kidney replacement.
2.3. Data collection
The demographic data included age, gender, body mass index
(BMI) and smoking history. The comorbidities contained hyper-
tension, diabetes, cardiopathy, chronic obstructive pulmonary
disease (COPD) and malignant tumor. The laboratory data
within 24 hours after hospital admission were recorded, which
included blood counts, liver and kidney function, as well as lev-
els of electrolytes.
The clinical outcomes included the length of hospital stay and
the 28-day mortality. All clinical data were independently col-
lected and analyzed by the trained medical staffs.
2.4. Statistical analysis
Data were analyzed by SPSS 20.0 software. Continuous vari-
ables were presented as median (interquartile range, IQR)
and analyzed by Nonparametric Tests (Mann-Whitney U).
Figure 1. Flow diagram of the participants.
2
Categorical variables were presented as frequencies (percent-
ages), and analyzed by Chi-square tests or Fisher exact test.
Bivariate logistic regression was used to explore the influ-
ence factors of 28-day mortality in patients with COVID-
19. Receiver operating characteristic (ROC) curve was used
to evaluate the predictive value of BUN for 28-day mortal-
ity. Subgroup analysis was performed according to the opti-
mal cutoff value of the ROC curve to analyze the difference
in the incidence of 28-day mortality. Cox regression was used
to explore the relationship between BUN and 28-day mortal-
ity. Variables were selected for inclusion in the models based
on statistical significance in the univariate analyses. Kaplan–
Meier was used to draw survival curve. In addition, a nomo-
gram was formulated based on multivariate logistic regression
analysis. P < .05 was considered significant.
3. Results
3.1. Patient inclusion
In total, 326 adult patients with COVID-19 were screened
in this study. After a rigorous screening process, excluding
22 patients with no BUN detection records within 24 hours
after admission, 119 patients younger than 18 years old,
and 44 patients with chronic renal failure. Finally, 141 adult
patients with COVID-19 were included in this study (Fig. 1).
All of these included patients had one or more symptoms of
COVID-19 and were vaccinated against COVID-19. Their
median age was 74.0 (66.0, 81.0) years, and female patients
accounted for 35.5%. Among these patients, 23 (16.3%)
died within 28 days. Univariate analysis showed that
patients who died within 28 days had a higher incidence of
diabetes, higher level of D dimer, alanine aminotransferase
(ALT), aspartate aminotransferase (AST), BUN and creati-
nine, and lower level of hematocrit and calcium compared
with survivors (Table 1).
3.2. BUN was a risk factor for 28-day mortality
Variables with statistical significance (including diabetes,
hematocrit, calciumion, D dimer, ALT, AST, BUN and cre-
atinine) were included in the bivariate logistic regression.
Univariate analysis showed that diabetes, hematocrit, ALT,
AST, calcium, and BUN were the risk factors of 28-day mor-
tality in patients (Table 2). Furthermore, multivariate analy-
sis revealed that BUN was the risk factor for 28-day mortality
(Table 2).
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Table 1
Basic data of the included patients with COVID-19.
Total Survivor Death
Variables (n = 141) (n = 118) (n = 23) P value

Demographic data
Age (yr) 74.0 (66.0, 81.0) 74.0 (66.0, 80.0) 76.0 (65.5, 84.0) .514
Female (%) 50 (35.5) 38 (32.2) 12 (52.2) .067
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BMI (kg/m2) 23.4 (21.5, 26.0) 23.4 (21.4, 25.9) 25.0 (22.6, 26.8) .140
Smoking (%) 30 (21.3) 25 (21.2) 5 (21.7) 1.000
Comorbidities (%)
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Hypertension 84 (59.6) 67 (56.8) 17 (73.9) .126

Diabetes 43 (30.5) 29 (24.6) 14 (60.8) .001
Cardiopathy 25 (17.7) 21 (17.8) 4 (17.4) 1.000
COPD 13 (9.2) 10 (8.5) 3 (13.0) .765
Malignant tumor 29 (20.6) 26 (22.0) 3 (13.0) .488
Laboratory values during the first day after admission
Hematocrit (%) 34.4 (30.3, 39.6) 34.6 (30.8, 39.8) 32.9 (21.8, 35.0) .028
WBC (109/L) 6.3 (4.5, 8.4) 6.2 (4.5, 8.2) 6.9 (4.0, 14.6) .360
Neutrophil (109/L) 5.0 (3.2, 9.4) 5.0 (3.2, 9.2) 5.8 (3.1, 13.7) .722
Lymphocyte (109/L) 0.9 (0.6, 1.3) 0.9 (0.7, 1.3) 0.7 (0.4, 0.9) .054
Platelet (109/L) 168.0 (113.0, 229.0) 172.0 (117.0, 229.0) 139.0 (98.0, 255.5) .394
T lymphocytes (109/L) 0.5 (0.3, 0.8) 0.5 (0.4, 0.8) 0.5 (0.2, 0.5) .126
CRP (mg/L) 43.5 (16.6, 95.9) 41.4 (14.4, 93.5) 68.1 (36.0, 122.5) .124
PCT (ng/mL) 0.11 (0.03, 0.41) 0.11 (0.02, 0.39) 0.68 (0.10, 3.24) .050
D dimer (mg/L) 1.0 (0.5, 2.2) 0.9 (0.4, 1.9) 2.5 (1.0, 7.4) .005
Fibrinogen (g/L) 4.7 (3.7, 5.7) 4.7 (3.7, 5.7) 4.7 (3.8, 5.9) .974
ALT (U/L) 22.9 (15.7, 38.9) 21.9 (14.9, 35.6) 34.0 (23.4, 58.1) .018
AST (U/L) 26.0 (18.2, 38.0) 24.7 (17.9, 35.1) 45.0 (26.2, 60.7) .001
Blood glucose (mmol/L) 7.3 (5.6, 9.5) 7.1 (5.5,9.3) 8.1 (6.8,12.3) .087
Potassium (mmol/L) 3.8 (3.4, 4.2) 3.8 (3.4,4.2) 3.9 (3.5,4.7) .517
Sodium (mmol/L) 138.6 (136.2, 141.0) 138.7 (136.2140.7) 138.6 (133.8145.6) .586
Calcium (mmol/L) 2.1 (2.0, 2.3) 2.2 (2.0,2.3) 2.0 (1.8,2.2) .024
BUN (mmol/L) 6.1 (4.3, 10.0) 6.0 (4.2,8.3) 15.3 (7.6,43.7) <.001
Creatinine (µmol/L) 71.9 (55.6, 103.7) 68.5 (54.8,89.0) 123.1 (76.8395.1) .004
ALT = alanine transaminase, AST = aspartate aminotransferase, BMI = body mass index, BUN = blood urea nitrogen, COPD = chronic obstructive pulmonary disease, CRP = C-reactive protein, PCT =
procalcitonin, WBC = white blood cell.

Table 2
Bivariate logistic regression based on 28-day mortality.
Univariate analysis Multivariate analysis
Variables OR 95%CI P value Variables OR 95%CI P value

Age 1.012 0.961, 1.065 .661 Diabetes 2.804 0.618, 12.728 .181
Hypertension 1.994 0.548, 7.255 .295 Hematocrit 0.921 0.847, 1.001 .054
Diabetes 4.251 1.302, 13.878 .016 ALT 1.006 0.991, 1.021 .451
Cardiopathy 0.758 0.172, 3.586 .755 AST 1.013 0.996, 1.031 .146
Malignant tumor 0.699 0.155, 3.153 .699 Calcium 0.066 0.001, 4.147 .198
Hematocrit 0.905 0.843, 0.971 .005 BUN 1.037, 1.167 .001
D dimer 1.016 0.963, 1.072 .559
ALT 1.009 1.002, 1.016 .016
AST 1.014 1.002, 1.026 .025
Calcium 0.021 0.001, 0.486 .016
BUN 1.105 1.052, 1.160 <.001
Creatinine 1.002 1.000, 1.004 .120
95% CI = 95% confidence interval, ALT = alanine transaminase, AST = aspartate aminotransferase, BUN: blood urea nitrogen, OR = odds ratio.

3.3. BUN could predict the 28-day mortality
ROC curve was used to evaluate BUN to predict the 28-day
mortality of COVID-19 patients. Results showed that BUN
could predict the 28-day mortality of COVID-19 patients
(AUC = 0.796, 95%CI: 0.654–0.938, P < .001; Fig. 2). When
the cutoff value of BUN was 7.37 mmol/L, the sensitivity and
specificity were 84.62% and 70.31%. Moreover, the level
of BUN was used to form the nomogram in predicting the
28-day mortality of COVID-19 patients (Fig. 3). For each
patient, higher total points indicated a higher risk of 28-day
mortality.
3.4. Subgroup analysis based on the cutoff value of serum
BUN
According to the cutoff value, the serum BUN values were
categorized into 2 groups: hypo-BUN (<7.37 mmol/L) and
hyper-BUN (≥7.37 mmol/L). We identified that hyper-BUN was
associated with increased 28-day mortality (Table 3, Fig. 4).
Meanwhile, we also found significant differences in some basic
data (including age, hypertension, diabetes, hematocrit, WBC,
neutrophil, lymphocyte, T lymphocytes, CRP, PCT) of patients
in hypo-BUN and hyper-BUN (Table 3). To further explore the
effect of BUN levels on 28-day mortality, hypo-BUN was selected

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Figure 2. ROC curve evaluated BUN prediction of 28-d mortality in COVID-19 patients.
Figure 3. Nomogram for predicting 28-d mortality. BUN = blood urea nitro-
gen, ROC = receiver operating characteristic.
as the reference group for the Cox regression model. The results
demonstrated that hyper-BUN was associated with increased
28-day mortality among COVID-19 patients (Table 4).
4. Discussion
Kidney damage was reported to be a common complication of
COVID-19 infection, especially in patients with severe symp-
toms.[14,15] The mechanism of kidney injury caused by SARS-
CoV-2 infection is still unclear. SARS-CoV-2 might affect kidney
cells directly.[16,17] Bourgonje et al performed complete autopsy
data on 12 patients who died of COVID-19 and reported high
viral RNA titers in the kidneys.[18] In addition, in a study of 701
COVID-19 patients, acute kidney injury was found in 5.1% of
4
patients.[19] Angiotentin converting enzyme 2 (ACE 2) is a func-
tional receptor involved in SARS-CoV-2 infection and cytokine
storms.[20–22] Single-cell transcriptome analysis found that ACE
2 and TMPRSS 2 were highly co-expressed in podocytes and
proximal tubule cells.[16]
The nitrogenous end products of human protein metab-
olism are mainly excreted by the kidney in the form of urea
(90%).[23] Unlike other markers of the kidney such as blood cre-
atinine (Cr), about 40%-50% of BUN is reabsorbed in the renal
tubules, and renal urea reabsorption plays a crucial role in the
urinary concentration capacity of the kidney.[24] Elevated BUN
level, as an indicator of disease severity, plays an important role
in the risk stratification of various diseases such as heart fail-
ure, aortic dissection, acute pancreatitis, and peripheral artery
disease.[25–28] In hospitalized ICU patients, elevated BUN levels
indicate impaired renal function and are associated with poor
prognosis.[29]
For COVID-19, major risk factors reported previously
include age, masculinity, obesity, smoking, and chronic comor-
bidities such as hypertension and diabetes.[30,31] In our study,
we found that dead patients had a higher proportion of dia-
betes, lower hematocrit and calcium ion levels compared with
survived patients. Moreover, dead patients had higher D dimer,
ALT, AST, BUN and Cr levels which were partly consistent with
previous studies.[7,31] Diabetes, hemocytometer, ALT, AST, cal-
cium ion and BUN were the factors affecting the 28-day mortal-
ity of COVID-19 patients.
We also identified BUN as the risk factor for 28-day mortality,
consistent with previous reports.[19,29] Moreover, BUN could pre-
dict 28-day mortality of COVID-19 patients. In previous study
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Table 3
Hyper-BUN was associated with higher 28-d mortality.
Total Hypo-BUN Hyper-BUN
Variables (n = 141) (n = 92) (n = 49) P value

28-d mortality (%) 23 (16.3) 7 (7.6) 16 (32.7) <.001

LOS of hospital (d) 11.0 (7.5, 16.0) 11.5 (8.0, 15.8) 10.0 (6.5, 16.0) .440
Demographic data
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Age (yr) 74.0 (66.0, 81.0) 73.0 (61.8, 79.0) 77.0 (69.0, 84.0) .008
Female (%) 50 (35.5) 30 (32.6) 20 (40.8) .332
BMI (kg/m2) 23.4 (21.5, 26.0) 23.4 (21.3, 25.9) 23.4 (21.8, 26.7) .376
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Smoking (%) 30 (21.3) 22 (23.9) 8 (16.3) .295

Comorbidities (%)
Hypertension 84 (59.6) 48 (52.2) 36 (73.5) .014
Diabetes 43 (30.5) 19 (20.7) 24 (49.0) .001
Cardiopathy 25 (17.7) 15 (16.3) 10 (20.4) .543
COPD 13 (9.2) 9 (9.8) 4 (8.2) 1.000
Malignant tumor 29 (20.6) 20 (21.7) 9 (18.4) .637
Laboratory values during the first day after admission
Hematocrit (%) 34.4 (30.3, 39.6) 35.7 (32.5, 40.5) 31.6 (26.9, 35.3) <.001
WBC (109/L) 6.3 (4.5, 8.4) 6.2 (4.3, 7.4) 7.2 (4.8, 12.6) .016
Neutrophil (109/L) 5.0 (3.2, 9.4) 4.3 (2.7, 6.4) 7.1 (3.8, 18.1) <.001
Lymphocyte (109/L) 0.9 (0.6, 1.3) 1.0 (0.8, 1.6) 0.7 (0.5, 0.9) <.001
Platelet (109/L) 168.0 (113.0, 229.0) 169.0 (113.8, 217.0) 164.0 (116.0, 263.5) .802
T lymphocytes (109/L) 0.5 (0.3, 0.8) 66.0 (53.5, 75.0) 60.0 (48.0, 71.4) <.001
CRP (mg/L) 43.5 (16.6, 95.9) 33.6 (11.1, 81.3) 67.4 (32.5, 106.1) .004
PCT (ng/mL) 0.11 (0.03, 0.41) 0.1 (0.0, 0.2) 0.3 (0.1, 2.0) <.001
D dimer (mg/L) 1.0 (0.5, 2.2) 0.7 (0.4, 1.5) 1.6 (1.0, 3.3) <.001
Fibrinogen (g/L) 4.7 (3.7, 5.7) 4.5 (3.6, 5.2) 5.2 (4.0, 6.3) .039
ALT (U/L) 22.9 (15.7, 38.9) 23.0 (14.7, 37.1) 22.9 (16.9, 36.6) .871
AST (U/L) 26.0 (18.2, 38.0) 27.6 (18.6, 35.8) 24.5 (18.0, 44.9) .864
Blood glucose (mmol/L) 7.3 (5.6, 9.5) 6.9 (5.3, 8.6) 8.7 (6.0, 12.7) .001
Potassium (mmol/L) 3.8 (3.4, 4.2) 3.7 (3.3, 4.1) 4.0 (3.5, 4.6) .007
Sodium (mmol/L) 138.6 (136.2, 141.0) 138.7 (136.9, 140.7) 138.6 (133.8, 142.3) .679
Calcium (mmol/L) 2.1 (2.0, 2.3) 2.2 (2.0, 2.3) 2.1 (2.0, 2.2) .114
Creatinine (µmol/L) 71.9 (55.6, 103.7) 59.7 (51.2, 73.5) 124.3 (83.5, 197.1) <.001
ALT = alanine transaminase, AST = aspartate aminotransferase, BMI = body mass index, BUN: blood urea nitrogen, COPD = chronic obstructive pulmonary disease, CRP = C-reactive protein, LOS = length
of stay, OR = odds ratio, PCT = procalcitonin, WBC = white blood cell.

and increased absorption of water and sodium, and passive

Figure 4. Survival curve based on serum BUN groups. Hyper-BUN was
associated with higher 28-d mortality. BUN = blood urea nitrogen.
BUN to albumin ratio could predict the mortality of COVID-19
patients.[32]
A study showed that about 37% of COVID-19 patients
developed acute kidney injury (AKI), with possible etiol-
ogy including acute tubular necrosis due to sepsis and renal
hypoperfusion, cytokine release syndrome, direct viral inva-
sion, renal medullary hypoxia secondary to alveolar injury,
and cardio-renal syndrome due to viral myocarditis.[33] Novel
coronavirus can activate the renin-angiotensin-aldosterone sys-
tem (RAAS), resulting in reduced renal tubule blood flow and
glomerular UF, which in turn leads to reduced BUN excretion
BUN reabsorption.[34] It is important to note that dehydra-
tion is common in patients with pneumonia, and reabsorption
of BUN by the kidneys is increased in a dehydrated state.[35]
In addition, elevated BUN level reflects inflammatory status,
catabolism, nitrogen balance, and renal hypoperfusion caused
by low blood volume, sepsis or reduced cardiac output. These
pathophysiological changes are closely related to adverse out-
comes in COVID-19 patients.[36] Blood Cr mainly represents
kidney injury and metabolic disorders, while the cytokines
and chemokines produced by SARS-CoV-2-infected cells not
only lead to extensive infiltration of neutrophils and macro-
phages, but also to local and systemic tissue damage.[37] This
may explain why increased blood Cr levels were not associated
with increased 28-day mortality in COVID-19 patients, but
increased BUN levels were associated with increased 28-day
mortality.
This study has limitations. First, although it was a multicenter
study, the sample size was small and more prospective stud-
ies with larger sample sizes are needed to confirm our results.
Second, the results of this retrospective study could not provide
a direct causal effect of elevated BUN on all-cause mortality
from COVID-19. Therefore, the predictive value of BUN for
COVID-19 prognosis still needs to be further validated through
prospective studies and clinical trials. Third, the level of BUN
may be affected by other factors.
In conclusion, BUN was identified as a risk factor for 28-day
mortality in COVID-19 patients and could predict the 28-day
mortality. High levels of BUN (≥7.37 mmol/L) were associated
with increased 28-day mortality. Consequently, monitoring
BUN is necessary in patients with COVID-19.

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[8] Malik P, Patel U, Mehta D, et al. Biomarkers and outcomes of COVID-

Table 4
19 hospitalisations: systematic review and meta-analysis. BMJ Evid
Cox regression based on serum BUN groups. Based Med. 2021;26:107–8.
Models HR 95% CI P value [9] Hu H, Pan H, Li R, et al. Increased circulating cytokines have a role
in COVID-19 severity and death with a more pronounced effect
Model 1 10.533 2.328, 47.654 .002 in males: a systematic review and meta-analysis. Front Pharmacol.
Model 2 10.794 2.348, 49.624 .002 2022;13:802228.
Model 3 9.406 1.921, 46.056 .006 [10] Huang D, Yang H, Yu H, et al. Blood urea nitrogen to serum albumin
Model 4 10.290 2.031, 52.133 .005 ratio (BAR) predicts critical illness in patients with coronavirus disease
2019 (COVID-19). Int J Gen Med. 2021;14:4711–21.
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Model 5 24.784 2.463, 249.378 .006

Model 6 21.855 2.404, 198.695 .006 [11] Ugajin M, Yamaki K, Iwamura N, et al. Blood urea nitrogen to serum albu-
min ratio independently predicts mortality and severity of community-
Model 7 21.872 2.341, 204.359 .007
acquired pneumonia. Int J Gen Med. 2012;5:583–9.
wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 03/13/2024

Model 8 16.492 1.606, 169.369 .018

Note: Among the 2 groups, Hypo-BUN (BUN < 7.37mmol/L) was adopted as the reference group.
Hyper-BUN ≥ 7.37mmol/L.
Model 1: unadjusted model.
Model 2: Adjusted for age.
Model 3: Adjusted for variables included in model 2 + hypertension and diabetes.
Model 4: Adjusted for variables included in model 3 + hematocrit.
Model 5: Adjusted for variables included in model 4 + WBC, neutrophil, lymphocyte, T lymphocytes,
CRP and PCT.
Model 6: Adjusted for variables included in model 5 + D dimer and fibrinogen.
Model 7: Adjusted for variables included in model 6 + blood glucose and potassium.
Model 8: Adjusted for variables included in model 7 + creatinine.
CRP = C-reactive protein, BUN = blood urea nitrogen, PCT = procalcitonin, WBC = white blood cell.
Acknowledgments
This work was supported by the Medical Education
Collaborative Innovation Fund of Jiangsu University [grant
numbers JDY2023004]; the COVID-19 Special Research
Fund, Affiliated Hospital of Jiangsu University [grant number
Jdfyxgzx001]; 169 Talent Project of Zhenjiang [grant number
YLJ202105]; and the National Natural Science Foundation of
China [grant number 82202389].
Author contributions
Conceptualization: Jiangtao Yin, Dadong Liu, Hanpeng Huang.
Data curation: Dadong Liu.
Methodology: Yuchao Wang, Dadong Liu.
Project administration: Jiangtao Yin, Yuchao Wang.
Resources: Jiangtao Yin, Yuchao Wang, Caixia Wu, Ziyi Sang,
Wen Sun, Junfei Wei, Wenli Wang.
Software: Hongyan Jiang, Dadong Liu.
Supervision: Hanpeng Huang.
Visualization: Dadong Liu.
Writing – original draft: Yuchao Wang, Dadong Liu.
Writing – review & editing: Jiangtao Yin.
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