Article Type : Research Article
Authors : Mohamed RAA, Gorish BMT, Amin FAM, Satti OKS, Mostafa MSI, Mubarak AMH, Mohgoub MM, Mohamed MHK and Yahia WI
Keywords : COVID-19; Lymphocytes; Prognosis; Died group; Recovered group
The novel coronavirus SARS-CoV-2
also known as COVID-19 is highly contagious infection caused by single strand
positive sense RNA virus belong to genus Beta coronavirus, in subgenus
Sarbecovirus [1]. In December 2019 the disease was first identified in Wuhan,
China. The World Health Organization regard the covid19 as pandemic in March
2020. Based on WHO data, there have been 53,766,728 confirmed cases of
COVID-19, including 1,308,975 deaths by the end of 13 November 2020 [2].
COVID-19 is transmitted mainly through the air via small droplets or aerosols
when people are coming to cluster each other long enough. It can be transmitted
as early as 2 days before infected persons possess symptoms and even from
asymptomatic patients [3]. Although most patients with COVID-19 are asymptomatic
or have mild symptoms, a few portions could develop severe pneumonia and
eventually lead to acute respiratory distress syndrome. Some patients however
may go so far in disease progression to mount multi-organ failure and death
[4]. Clinical remarks and laboratory findings are very important during
pandemic situation to predict disease morbidity and mortality. Viral infection
is well established cause of abnormal haematological parameters and COVID-19 is
not exception of the general rule. Many studies have demonstrated that COVID-19
is associated with lymphopenia as well as cytokine storm syndrome.
Additionally, Autopsy of patients who passed due to COVID-19 revealed shrunken
spleen organ with reduced lymphocyte, macrophage proliferation, and phagocytosis.
These features could reveal that the immune system particularly lymphocytes
could play a key role in determining COVID-19 infection prognosis [5-7]. In
this article we evaluate the clinical implication of haematological parameter
particularly lymphocytes count in determining the severity and outcome of
COVID-19 disease.
Ethics
approval and consent to participate
All the protocol has
approved and carried out according to ethical guidelines of the declaration of
Helsinki for human research. Ethics Review Committees Jabra Hospital for
Emergency and Injuries also provided the authorization. Participant informed
consent was not obtained since the study performed in retrospective manner as
granted by the ethical committees.
Data
collection and analysis
Data was collected during the period from April
to June 2020 using the laboratory database of Jabra Hospital for Emergency and
Injuries; all patients who tested positively for COVID-19 were included and
monitored in this study. However, all patients tested negative for COVID-19 are
excluded from this study. The data
included age, gender, and full blood count. Information regarding patient
outcomes was also analysed. The statistical analysis was performed by using SPSS
version 20. A comparison of lymphocyte counts in each group (dead group,
recovered group) was carried out using chi-squared test
The study cohort
comprises of 65 patients. All of them tested positive for SARS-CoV-2 RNA. 39
(60%) of the patients are male and 26 (40%) are female. Of the 65 patients, 28
died from the infection, while 37 had recovered. The mean age of our cohort was
52.87 ± 16.033 years with a minimum of 23 years and maximum of 82 years old.
Result shows that there was insignificant difference between male and female in the COVID-19 infection outcome since the P. value was (0.438) (Table 1). However, the mean of age for the COVID-19 died group 65.86 ± 6.87 years was significantly higher than that of the COVID-19 recovered group 42.89 ± 13.7 with P. value 0.00 (Table 1). When we categorized the patients into age groups, we found a highly significant difference between the age groups in the death and recovery rates P. value 0.00. The death occurrence was 0 (0%) among patients aged below 40 years old, while the highest prevalence 18 (78.6%) of death was found among patients over 60 years old compared to only 5 (13.6%) patients recovered in the same group (Table 1). Amongst patients aged between 40 to 60 years the recovery rate 6 (21.4%) was higher than the death rate 14 (37.8%). Haematological markers, including haemoglobin concentration (g/dl) white cell count (WBC) (×103 cell/µl) and lymphocyte count (×103 cell/µl) as well as platelet count (×103 cell/µl) were evaluated on both died and recovered patients. The result of haemoglobin concentration and platelet count shows no effect on the COVID-19 infection outcome with P. Value of 0.754 and 0.10 respectively. The results show that In the Covid-19 died group 32.1% (n=9) had normal WBC, 7.2% (n=2) had leucopoenia, and 60.7 % (n=17) leucocytosis. On the other hand, in the Covid-19 recovered group, 48.6% (n=18) had normal WBC and 27.3 % (n=9) had leucocytosis and 24.1 % (n=10) had leucopoenia. There was statistically significant difference between groups in the WBC with P. value of 0.008 and the mean of WBC was significantly higher 13.429 ± 6.17 among died group than recovered group 8.281 ± 3.67. The result show that amongst the COVID-19 died group 85.7% (n=24) had lymphocyte percentage less than 10% and 14.3% (n=4) hade lymphocyte percentage more than 10%. In contrast, amongst COVID-19 recovered group 27.0% (n=10) had lymphocyte percentage less than 10% and 73.0% (n=27) hade lymphocyte percentage more than 10% with P. value of 0.00 (Table 1). On the other hand, 35.7% (n=10) of a died group had Neutrophil percentage less than 85% and 64.3% (n=18) in the same group had neutrophil percentage more than 85% while amongst recovered group, 81.1% (n=30) had Neutrophil percentage less than 85% and 18.9% (n=7) in the same group had Neutrophil percentage more than 85% with P. value 0.00. The degree of lymphopenia, using absolute lymphocyte count ×103 cell/µl (ALC), was also assessed on admission. The mean ALC was shown to be 0.73 ± 0.50 ×103 cell/µl in the Covid-19 died group which is highly significantly lower than that of recovered group 1.58 ± 0.89 ×103 cell/µl with P. value 0.00.
Table 1: Summary of the epidemiological and hematological characteristics of the cohort.
Parameter |
COVID-19 disease out come |
P. value |
|
Died |
Recovered |
||
Gender |
|||
Male |
16 (57.1%) |
23 (62.2%) |
0.438 |
Female |
12 (42.9%) |
14 (37,8) |
|
Age groups / years |
|||
Less than 40 |
0 (0%) |
18 (48.6%) |
0.00 |
6
(21.4%) |
14
(37.8%) |
||
More than 60 |
22 (78.6%) |
5 (13.6%) |
|
Age mean |
65.86 ± 6.87 |
42.89 ± 13.7 |
|
Hemoglobin group g/dl |
|||
Less than 8.0 |
1 (3.6%) |
1 (2.7%) |
0.754 |
8.0 – 11.0 |
9 (32.1%) |
9 (24.3%) |
|
More than 11.0 |
18 (64.3%) |
27 (73.0%) |
|
mean of
hemoglobin |
11.282 ± 1.40 |
12.424 ± 2.33 |
|
WBC group ×103
cell/µl |
|||
Less than 4.0 |
2 (7.2%) |
10 (24.1%) |
0.008 |
4.0 – 11.0 |
9 (32.1%) |
18 (48.6%) |
|
More than 11.0 |
17 (60.7%) |
9 (27.3%) |
|
mean of WBC |
13.429 ± 6.17 |
8.281 ± 3.67 |
|
Plate lets group cell/µl×103 cell/µl
|
|||
Less than 150 |
6 (23.4%) |
4 (10.8%) |
0.10
|
150 - 450 |
14 (50%) |
28 (75.7%) |
|
More than 450 |
8 (28.6%) |
5 (13.5%) |
|
Plate lets
mean |
353.54 ± 252.1 |
294.27 ± 126.6 |
|
LYMPH% group
|
|||
Less than 10% |
24 (85.7%) |
10 (27.0%)
|
0.00 |
More than 10% |
4 (14.3%) |
27 (73.0%)
|
|
LYMPH% mean |
6.257 ± 5.0
|
21.681 ± 13.6
|
|
Neutrophil% group
|
|||
Less than 85% |
10 (35.7%) |
30 (81.1%)
|
0.00 |
More than 85% |
18 (64.3%) |
7 (18.9%)
|
|
Neutrophil%
mean |
87.004 ± 7.6 |
70.395 ± 15.4
|
|
ALC ×103 cell/µl
|
|||
Less than 0.6 |
15 (53.6%) |
0
(0%)
|
0.00 |
0.6 - 1.0 |
9 (32.1%) |
13 (35.1%)
|
|
More than 1.0 |
4 (14.3%) |
24 (64.9 %)
|
|
ALC mean |
0.73 ± 0.50 |
1.58 ± 0.89
|
|
ANC Group×103 cell/µl
|
|||
Less than 3.0 |
0 (0%) |
9 (24.3%)
|
0.00 |
3.0 - 6.0 |
3 (10.7%) |
11(29.7%)
|
|
More than 6.0 |
25 (89.3%) |
17 (45.9%)
|
|
ANC mean |
11.896 ± 6.1 |
6.207 ± 3.65
|
Figure 1: Show the distribution of patients ALC. Y axis = ALC 103 cell/µl. X axis= patients. The left the figure show that with exception of 4 cases, all died group patients shows ALC less than 1.0×103 cell/µl. In the right figure majority of recovered group have ALC more than 1.0×103 cell/µl.
The result also
demonstrated that amongst COVID-19 died group 53.6% (n=15) had ALC less than
0.6×103 cell/µl, 32.1% (n=9) had ALC between 0.6 – 1.0 ×103
cell/µl, and 14.3% (n=4) had ALC more than 1.0 ×103 cell/µl.
Furthermore, amongst COVID-19 recovered group 0% (n=0) had ALC less than 0.6 × 103
cell/µl, 35.1% (n=13) had ALC between 0.6 – 1.0 ×103 cell/µl, and
64.9% (n=64) had ALC more than 1.0 ×103 cell/µl. There was
significant effect of ALC in predication of COVID-19 infection outcome with P.
value of 0.00. The result show that a mortality of Covid-19 died group 89.3% (n
=25) had Absolute neutrophil count (ANC) more than 6.0 ×103 cell/µl
and none of them 0% (n=0) had ANC less than 3.0. In contrast 45.9% (n=17) of
COVID-19 recovered group had ANC more than 6.0 ×103 cell/µl, 29.7%
(n=11) had ANC between 3.0-6.0 ×103
cell/µl and 24.3% (n=9) had ANC less than 3.0. There was also significant
effect of ANC in predication of COVID-19 infection outcome with P. value of
0.00 (Table 1) (Figure 1).
In December 2019,
COVID-19 was first identified in Wuhan, China. Science that time and during the
pandemic start up many researches have been conducted of which some are focused
on the clinical remarks while others described the laboratory finding
characteristics of patients [8]. Our study found that gender have no
significant effect on COVID-19 outcome among Sudanese patient and this was in
disagreement with finding of the (Sex, Gender, and COVID-19 Project data) that
most countries with available data indicate a male to female case fatality
ratio higher than 1.0, ranging up to 3.5 in some cases [9]. Inclusion of only
65 cases in our study may affect the result of demographic character analysis.
So, this point needs more analysis in the future studies with inclusion of
large-scale population. Our result indicate that elderly patients have a great
chance to develop sever type of infection and even death, since none of those
under 40 years dead due to infection compared to 78.6% of death rate occur
among those over 60 years. Additionally, all of those over 60 years and have
ALC less than 0.6 × 103 cell/µl die due to the COVID-19 infection.
This is not surprise because many studies have proved that advanced age is a
characteristic features of immune response dysfunction affecting all
lymphocytic lineages. Reduced lymphopoiesis, impaired antigen-specific
immunity, tissue-specific changes [10-12]. In this study there was no
significant difference between both groups of cases in the haemoglobin
concentration means. With exception of 10 cases both groups show a haemoglobin
concentration more than 11.0 g/dl which exclude the presence of anaemia. Most
previous studies confirm our finding [13-16]. Platelet count has been evaluated
as a biomarker to predict the severity of COVID-19, and our study confirm the
finding of the previous reports in which thrombocytosis and thrombocytopenia is
less occasionally occur among COVID-19 patients regardless the severity of the
infection [17-19]. In this study we analysed the level of WBC in both groups of
patients. We find that, the mean of WBC was higher significantly among COVID-19
died group and majority of them 60% have leukocytosis compared to COVID-19
recovered group. In addition, the neutrophil is predominantly detected among
COVID-19 died group compared to the survival group. These two facts may support
the theory of that COVID-19 as like other respiratory viruses predispose the
patients to secondary bacterial infection particularly bacterial pneumonia which
is characterized by elevated WBC and neutrophil and that’s why many of the
treatment policies include azithromycin antibiotic as major treatment used
during the COVID-19 infection starting from the symptoms onset [20]. In this
study the mean of ALC and lymphocytes percentage among COVID-19 died group were
significantly lower than those of survival group. Recent studies have shown an
increased prevalence of low lymphocyte count in Covid-19 +ve patients, compared
with the general population. However, in
our study we compare a COVID-19 died group with a recovered group of patients
to determine the effect of the lymphocytes in COVID-19 infection outcome, we
found that none of those patients over 60 years and having ALC less than 0.6
×103 cell/µl survive after being infected with COVID-19.
Additionally, the recovery rate is increased with improvement of lymphopenia to
reach about 64.9% among those with ALC more than 1.0×103 cell/µl
with only 14.3% death rate in the same group. These findings highlight the prognostic
value of lymphopenia at time of admission, which can be helpful in tailoring a
prompt response for early interventions in Covid-19 disease patients. Our
finding has consistently been recorded in many recently published studies,
claiming that lymphopenia is a marker of severity and poor outcome in Covid-19
+ve patients [15].
Our study demonstrates
that lymphopenia is most a specific prognostic marker of COVID-19 infection
outcome particularly among elder patients and could help physician to predict
patients with poor prognosis earlier. Based on the results of our study, we
therefore propose that lymphocyte transfusion treatment should be taken into
consideration when treating patient with COVID-19 infection particularly older
patients. Further studies with larger cohort are required to better understand
the value of lymphocytes count in diagnosis and treatment of the COVID-19
infection.
Our study has included
a relatively smaller sample size (only 65 cohort).
WBC:
Total White Blood cells count
ALC:
Absolute Lymphocyte Count
ANC:
Absolute Neutrophil Count
Availability
of data and materials
The datasets analysed
during the current study are available from the corresponding author on reasonable
request.
Consent
for publication
Not applicable
Competing
interests
All authors declare that they have no competing
interest.
The authors acknowledge
the laboratory staff of Jabra Hospital for Emergency and Injuries for their support
and kind assistance. We are also very grateful for every patient participate in
this study, and mercy for died group.
Funding
None
RA, FA, MS, AM, MM, MH
and OM have contributed to data collection. WI, BM was accountable for data
analysis, and article writing. All authors contributed to manuscript revising
and editing. All authors read and approved the final manuscript.