Original Research

IJNHS
Levels of Lymphocytes, Neutrophils,
Leukocytes, and Outcome of Covid-19
Patients
Maniur Arianto Siahaan1, Sri Dearmaita Purba2, Amila3
1Health Analyst Study Program, Sari Mutiara University, Medan, Indonesia
2,3College of Nursing, Sari Mutiara University, Medan, Indonesia

Article info Abstract

Introduction: Coronavirus Disease 2019 can cause
Article history: systemic infections that significantly affect the immune
Received: October 14th, 2022 response and hemostatic conditions. A biomarker is
Revised: November 14th, 2022 needed to predict patients in the severity of the disease or
Accepted: December 9th, 2022 severe complications or when doing triage upon
admission to the hospital, providing early intervention to
reduce mortality. Changes in levels of lymphocytes,
Correspondent author: neutrophils, and leukocytes can predict the risk of
Name: Amila worsening Covid-19 patients. Objective: to determine the
Address: Sari Mutiara Indonesia effect of lymphocytes, neutrophils, and leukocytes on the
University, Jl. Kapten Muslim No.79 outcome of Covid-19 patients. Method: This study uses an
20123 Medan North Sumatra observational analytic design with a retrospective
E-Mail: [email protected] approach. The population of this research is medical
records of Covid-19 confirmed positive by real-time
Polymerase chain reaction (rt-PCR) from the Laboratory of
H. Adam Malik General Hospital Medan for the period
International Journal of Nursing and January-December 2021. Sampling using purposive
Health Services (IJNHS) sampling of as many as 175 medical records. The test used
Volume 5, Issue 6, December 20th, 2022 to determine the relationship of lymphocytes, neutrophils,
DOI: 10.35654/ijnhs.v5i6.652 and leukocytes to the outcome of Covid-19 patients is the
E-ISSN: 2654-6310 Spearman correlation test. Result: The results showed that
there was a weak and positive relationship between
lymphocytes (p = 0.006; r = 0.208) and the outcome of
Covid-19 patients, there was a moderate and positive
relationship between neutrophils (p = 0.000; r = 0.276) and
the outcome of Covid-19 patients. moderate and positive
relationship between leukocytes (p = 0.000; r = 0.350) and
the outcome of Covid 19 patients. Recommendation: It is
recommended to conduct a study in a large group by
comparing the severity of the disease and the length of
stay.

Keywords: Covid-19, lymphocytes, neutrophils,

leukocytes, outcome

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International Journal of Nursing and Health Services (IJNHS), Volume 5, Issue 6, December 20th, 2022
 Open Access article distributed under the terms of the
Creative Commons Attribution 4.0 International License
CC BY -4.0

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International Journal of Nursing and Health Services (IJNHS), Volume 5, Issue 6, December 20th, 2022
INTRODUCTION
Coronavirus disease 2019 (Covid-19) protein (CRP), erythrocyte sedimentation
was declared a global pandemic from March rate (ESR), and ferritin (4). Elevated
2020 until May 2021. It has infected nearly biomarkers are associated with bleeding and
163 million people worldwide and caused inflammatory disorders suggesting an
the death of 3.3 million people by the end of increased risk of ICU admission, need for
August 2021. This pandemic has infected 217 ventilators, and death (5). A study confirmed
million people and caused the death of 4.5 that most of the Covid-19 patients at the time
million people. WHO (2022) confirmed that had lymphocytopenia (83.2%),
on October 3, 2022, there were 615.310.890 thrombocytopenia (36.2%), and leukopenia
confirmed cases of Covid-19 and in 33.7% (6). This study aims to determine
approximately 6.524.568 deaths (1). the effect of laboratory biomarker
Based on data from the Ministry of parameters of lymphocytes, neutrophils, and
Health of the Republic of Indonesia on leukocytes on the outcome of Covid-19
October 4, 2022, it was found that Indonesia patients.
had 6,437,570 confirmed cases (+ 1,851), The urgency of the research is that the
6.262.820 cases recovered (97.3%), 158,156 impact of Covid-19 varies from
cases died (2.5%) and 16.594 cases of Active asymptomatic or mild symptoms to acute
(0.3%) (2). The high gravity of this disease respiratory distress syndrome, multi-organ
requires early detection, prevention, and failure, and death. Recognizing/evaluating
rapid treatment to reduce the incidence. The the early signs of the emergency of Covid-19
WHO standard regarding early detection is patients through the results of biomarker
the examination of saliva, nasal mucus, or examinations is very important to predict
blood specimens for the presence of the patients falling into the degree of disease or
nucleic acid of the SARS-CoV-2 virus (3). severe complications and identifying
Examination of hematological outcomes. Identification of Covid-19 effects
parameters is essential, especially in is needed to prepare for further management
asymptomatic patients suspected of positive to maintain quality of life. Specific
PCR results. In addition to other supporting parameters are required to be able to predict
tests, namely chest X-rays and clinical the clinical outcome of Covid-19 patients, in
manifestations that occur in patients. Some addition to providing appropriate treatment
evidence suggests that Covid-19 patients and resource efficiency, as well as reducing
with severe symptoms may experience a mortality in Covid-19 sufferers.
compromised immune response, which may
lead to the development of OBJECTIVE
hyperinflammation of the virus. Therefore, The study aimed to determine the
biomarkers (biological markers) in the blood effect of lymphocytes, neutrophils, and
circulation can represent inflammatory and leukocytes on the outcome of Covid-19
immune status that are useful as potential patients at Haji Adam Malik General
predictors in the prognosis of Covid-19 Hospital Medan.
patients.
Early and effective predictors based on METHODS
hemostasis laboratory results are needed Design
because they can assess risk levels, compare This study is an observational
therapeutic methods, assess survival, and analytical study with a retrospective design.
predict patient prognosis. Changes in The samples obtained from the medical
laboratory results can occur in Covid-19 records of Covid-19 confirmed positive by
patients, including thrombocytopenia, real-time Polymerase chain reaction (rat-
lymphopenia, increased D-dimer, and PCR) from the Laboratory of Haji Adam
increased inflammatory markers, such as Malik General Hospital Medan. The
lactate dehydrogenase (LDH), C-reactive sampling technique used purposive

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sampling met the inclusion and exclusion laboratory examinations showed more than
criteria with a total of 175 medical records half of the respondents have normal
respondents. The research instrument used lymphocytes (52%). Some of them also have
was the observation sheet for the results of normal neutrophils (51.4%). While most of
blood laboratory examinations. The normal them also were normal leukocytes (73.1%).
laboratory value is based on Haji Adam Most of the outcomes of Covid 19 patients in
Malik General Hospital examination 2021 were recovered (88%).
guidelines. Table 2 shows a weak and positive
relationship between lymphocytes (p =
Data collection process 0.006; r = 0.208). The outcome of Covid 19
This study uses secondary data patients, there is moderate. Whereas there
sourced from medical records with inclusion was a positive relationship between
criteria of patients aged over 18 years with a neutrophils (p = 0.000; r = 0.276) and the
confirmed diagnosis of Covid-19 with real- outcome of Covid-19 patients. there is a
time Polymerase chain reaction (rat-PCR) moderate and positive relationship between
obtained from the Laboratory of Haji Adam leukocytes (p = 0.000; r = 0.350) and the
Malik General Hospital Medan, complete outcome of Covid-19 patients.
medical records, patients treated at Haji
Adam Malik General Hospital Medan for the Table 1. Frequency distribution based on age,
period January 2021 to December 2021. gender, comorbidities, results of
laboratory examinations, and Covid-19
Data analysis patient outcomes in 2021 (n = 175)
Data obtained from the medical
records of Covid-19 confirmed positive by Variables Frequency Percentage
(%)
real-time Polymerase chain reaction (rat-
Age
PCR) from the Laboratory of Haji Adam
Late Teen 11 6.3
Malik General Hospital Medan for January- Early Adult 17 9.7
December 2021. It was tabulated and Late Adult 23 13.1
analyzed using descriptive statistics such as Early Elderly 57 32.6
frequencies, percentage distribution, and Late Elderly 36 20.6
weighted item means for the quantitative Seniors 31 17.7
portion. Gender
The test used to determine the Male 83 46.5
relationship of lymphocytes, neutrophils, Female 92 52.6
and leukocytes to the outcome of Covid-19 Comorbidities
There aren't any 108 61.7
patients is the Spearman correlation test.
There is 67 39.3
- Heart disease 1 0.7
Ethical consideration - Hypertension 28 16
Before the data gathering, ethics - Diabetes Mellitus 23 13.1
clearance was obtained from the research - Chronic Kidney 3 1.7
Ethics of the Muhammadiyah University of Failure
North Sumatra with letter number - Diabetes Mellitus 3 1.7
393/KEPK/FKUMSU/2022. + hypertension
- Other diseases 9 5.1
Laboratory Results
Lymphocytes
RESULTS Normal 60 46.5
Low 59 45.7
table 1 shows that most Covid 19
High 10 7.9
patients are early elderly (32.6%), and 92 are
female (52.6%). More than half of them have Neutrophils
no comorbidities (61.7%). The results of Normal 61 47.3

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International Journal of Nursing and Health Services (IJNHS), Volume 5, Issue 6, December 20th, 2022
 Low 12 9.3 hypertension, and three people (0.69%) had
High 56 43.4 diabetes.
This study's respondents were early
Leukocytes elderly (46-55 years). A previous study also
Normal 128 73.1
confirmed that some of the COVID-19
Low 10 5.7
High 37 21.1
patients at Mekar Sari Hospital were 46–59-
Outcome year (37.3%). Along with increasing age, the
Healed 117 90.7 ability of the body's immune system to fight
Die 12 9.3 infection will decrease, including the speed
of the immune response. Therefore, the risk
Table 2. The Relationship between Biomarker of illness will increase. The reaction of
Examination Results and Outcome in lymphocytes in the immune system is also
Covid-19 Patients in 2021 (n = 175) reduced, where the immune system of the
elderly group reacts more slowly than the
Variables p r adult group. According to Liu et al.,
Lymphocytes 0.006 0. 208 lymphocyte count decreased in most
patients, and the absolute value of
Neutrophils 0.000 0. 276
lymphocytes was correlated with the
severity of Covid-19 (9). This can be caused
Leukocytes 0.000 0.350
because Covid-19 mainly attacks
lymphocytes.
DISCUSSION Lymphopenia is associated with
The relationship between lymphocytes and increased mortality, the incidence of acute
the outcome of Covid-19 patients respiratory distress syndrome (ARDS), the
The results of this study showed that need for treatment in the intensive care unit
laboratory examination results for Covid-19 (ICU), and the incidence of severe Covid-19
patients were normal lymphocytes (46.5%), symptoms (4). This study's results indicate a
low lymphocytes (45.7%), and high positive and weak relationship between
lymphocytes (7.8%). Several studies in lymphocytes and the outcome of Covid-19
various countries found biomarkers often patients. Several previous studies have
found in laboratory results of Covid-19 shown significant differences in lymphocyte
patients, a decrease in lymphocytes in 83.2% counts between Covid-19 patients with
of patients, a decrease in platelet levels in severe and non-severe cases, ICU and non-
36.2%, and a decrease in leukocyte levels in ICU patients, and survivors and Non-
33.7% of patients. Most patients have survivor patients.
elevated levels of C-reactive protein, and
increased levels of D-dimer were found. The relationship between neutrophils and
According to Liu et al., lymphocyte the outcome of Covid-19 patients
count decreased in most patients, and the The results of this study showed
absolute value of lymphocytes was normal neutrophils (47.3%). Some of them
correlated with the severity of Covid-19. This were high neutrophils (43.4%). In contrast to
can be caused because Covid-19 mainly the study of Tandjungbulu et al. (2021),
attacks lymphocytes (4). SARSCoV-2 is also neutrophils decreased by four samples
more likely to infect people with chronic (3.7%), and some of them showed normal
comorbidities such as heart disease, cerebral neutrophils (40.2%). However, more than
hemorrhage, and diabetes. 1%) had DM. The half of them was a high level of neutrophils
previous study (7) also found that 35 people (56.1%) (10). Study literature reported an
had comorbidities at Fuyang Second increased number of neutrophils and a
People's Hospital. Seven of them (16.28%) decrease of lymphocytes among High NLR
had DM, whereas 13 people (30.23%) had in severe patients (11).

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 Neutrophils are the main component leukocytes during the incubation period
of leukocytes that actively migrate to the (generally 37 days). Leukocytes and
immune system or organ. An increase in the lymphocytes were not significantly reduced
number of neutrophils indicates the intensity (normal or slightly lower. In the next phase,
of the inflammatory response, while a around 7-14 lymphocytes decreased
decrease in the number of lymphocytes significantly, including T lymphocytes and B
indicates a damaged immune system. Lymphocytes (15). The decrease or change
Dysregulation in immune cell that occurred went straight with the severity
responses results in immunological of the patient (17).
abnormalities that are essential to the degree However, the results showed a
of inflammation caused by viruses. This moderate and positive relationship between
increase in the neutrophil count agrees with leukocytes (p = 0.000; r = 0.350) and the
the study (12), showing that a high outcome of Covid 19 patients. In line with
neutrophil count independently predicts the the study, there was a significant
occurrence of critical illness. The results relationship between leukocyte count and
showed a positive and moderate clinical severity of Covid-19 patients at two
relationship between neutrophils (p = 0.001; Covid-19 referral hospitals in Ambon City in
r = 0.292) and the outcome of Covid-19 2020 (p = 0.029) (18).
patients. In contrast, the study's results
found that the number of leukocytes, CONCLUSIONS AND SUGGESTIONS
neutrophils, and lymphocytes had no The results showed that most Covid-19
relationship to mortality or shock. However, patients were early elderly, normal category
leukocytes can predict shock in septic lymphocytes, normal neutrophils, and
patients (13). leukocytes. The majority of Covid-19
patients have recovered. There is a weak and
Relationship between Leukocytes and positive relationship between lymphocytes
Outcomes of Covid-19 patients and the outcome of Covid-19 patients. There
This study showed that the most is a moderate and positive relationship
normal leukocytes were 128 people (73.1%). between neutrophils and the outcome of
In line with the research of Huang et al., most Covid 19 patients. There is a moderate and
patients with Covid-19 had normal positive relationship between leukocytes
leukocyte levels, and only 25% of patients and the outcome of Covid-19 patients.
with Covid-19 experienced a decrease in Further research is needed with large
leukocyte levels (14). Research by groups by assessing the severity of the
Tandjungbulu et al. (2020) found that disease and length of stay.
leukocytes were normal (53.3%), decreased
(9.3%), and increased (37.4%) (10). REFERENCES
Wang et al. in 2020 in China found that 1. World Health Organization (WHO).
there were changes and differences in the Coronavirus (COVID-19) Dashboard
leukocyte component in mild to severe [Internet]. 2022. Available from:
Covid-19 patients in the form of monocyte https://covid19.who.int/
activation, a decrease in the number of
neutrophils and Natural Killer (NK) cells, T 2. Kementerian Kesehatan Republik
cell dysregulation, to variations in Indonesia. COVID-19 [Internet].
production. Antibodies from B cells (15). Media Informasi Resmi Terkini
Another study concluded a decrease in the Penyakit Infeksi Emerging. 2022.
overall leukocyte count in mild cases of Available from:
Covid-19 compared to severe cases, with an https://infeksiemerging.kemkes.go.id
increase in the overall leukocyte count (16). /dashboard/covid-19
The study conducted by Li et al. (2020) 3. Kementerian Kesehatan Republik
showed a picture of lymphocytes and Indonesia. Pedoman Pencegahan dan

516
International Journal of Nursing and Health Services (IJNHS), Volume 5, Issue 6, December 20th, 2022
 Pengendalian Serta Definisi 9557 (Print) ISSN : 2087-1333 (Online).
Coronavirus Disease (COVID-19). Media Anal Kesehat. 2021;12(2):153–
Germas [Internet]. 2020;11–45. 62.
Available from: 11. Mus R, Abbas M, Sunaidi Y, Studi P,
https://infeksiemerging.kemkes.go.id Teknologi D, Medis L, et al. Studi
/download/REV- Literatur : Tinjauan Pemeriksaan
04_Pedoman_P2_COVID- Laboratorium pada Pasien COVID ‐
19__27_Maret2020_TTD1.pdf [Diakses 19. 2020;5(4).
11 Juni 2021]. 12. Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P,
4. Terpos, Evangelosannis Ntanasis- et al. Coronavirus infections and
Stathopoulos, Ismail Elalamy, immune responses. J Med Virol.
Efstathios Kastritis, Theodoros N. 2020;92(4):424–32.
Sergentanis, Marianna Politou, 13. Danwang C, Endomba FT, Nkeck JR,
Theodora Psaltopoulou, Grigoris Wouna DLA, Robert A, Noubiap JJ. A
Gerotziafas MAD. American J meta-analysis of potential biomarkers
Hematol - 2020 - Terpos - associated with severity of coronavirus
Hematological findings and disease 2019 (COVID-19). Biomark
complications of COVID‐19.pdf. Am J Res. 2020;8(1).
Hematol. 2020. p. 14. 14. Huang I, Pranata R, Lim MA,
5. Tian W, Jiang W, Yao J, Nicholson CJ, Oehadian A, Alisjahbana B. C-reactive
Li R, Sigurslid HH, et al. Predictors of protein, procalcitonin, D-dimer, and
mortality in hospitalized COVID‐19 ferritin in severe coronavirus disease-
patients: A systematic review and 2019: a meta-analysis. Ther Adv Respir
meta‐analysis - Tian - 2020 - Journal of Dis. 2020;14:1–14.
Medical Virology - Wiley Online 15. Li S, Jiang L, Li X, Lin F, Wang Y, Li B,
Library. Med Virol J [Internet]. et al. Clinical and pathological
2020;92:1875–83. Available from: investigation of patients with severe
https://onlinelibrary.wiley.com/doi/ COVID-19. JCI Insight. 2020;5(12):1–
full/10.1002/jmv.26050 13.
6. Guan W, Ni Z, Hu Y, Liang W, Ou C, 16. Khartabil TA, Russcher H, van der Ven
He J, et al. Clinical Characteristics of A, de Rijke YB. A summary of the
Coronavirus Disease 2019 in China. N diagnostic and prognostic value of
Engl J Med. 2020;382(18):1708–20. hemocytometry markers in COVID-19
7. Gao Y, Li T, Han M, Li X, Wu D, Xu Y, patients. Crit Rev Clin Lab Sci
et al. Diagnostic utility of clinical [Internet]. 2020;57(6):415–31. Available
laboratory data determinations for from:
patients with severe COVID-19. J Med https://doi.org/10.1080/10408363.20
Virol. 2020;92(7):791–6. 20.1774736
8. Khaerunnisa R, Rumana NA, Yulia N, 17. Wang J, Jiang M, Chen X, Montaner LJ.
Fannya P. Gambaran Karakteristik J Leukocyte Bio - 2020 - Wang -
Pasien Covid-19 di Rumah Sakit Cytokine storm and leukocyte changes
Mekar Sari Bekasi Tahun 2020-2021. in mild versus severe SARS‐CoV‐2
2022;10(1):64–72. infection Review of (1).pdf. J Leukoc
9. Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li Biol. 2020;108:17–41.
C, et al. Neutrophil-to-lymphocyte 18. Rahman FA, Latuconsina VZ,
ratio predicts critical illness patients Kusadhiani I, Hutagalung I, Jolanda D,
with 2019 coronavirus disease in the Angkejaya OW. Hubungan Jumlah
early stage. J Transl Med. 2020;18(1). Leukosit Dengan Severitas Klinis
10. Tandjungbulu YF, Mahlil, Kalma, Pasien Covid-19 Pada Dua Rumah
Hurustiaty, Widarti, Adi N. Jurnal Sakit Rujukan Covid-19 Di Kota
Media Analis Kesehatan ISSN : 2621- Ambon Tahun 2020. Molucca Medica.

517
International Journal of Nursing and Health Services (IJNHS), Volume 5, Issue 6, December 20th, 2022
2021;14:109–16.

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