Association between thrombocytopenia and the severity of Covid-19 infection among hospitalized Egyptian patients.

Background: COVID-19, which is caused by the corona virus 2 that causes severe acute respiratory syndrome, causes a respiratory and systemic illness that in 10-15% of patients escalates to a severe form of pneumonia. Thrombocytopenia is frequent in patients with COVID-19. We aimed to evaluate the association between thrombocytopenia and the severity of COVID-19 infection in hospitalized patients.
Methods: A cross-sectional study was done on 800 Egyptian patients with confirmed covid-19 infection. They were divided into Group I (Mild): 200 symptomatic patients meeting the case definition for COVID-19 without radiological evidence of pneumonia or hypoxia. Group II (Moderate): 200 patients with clinical signs of non-severe pneumonia and radiological evidence of pneumonia. Group III (Severe): 200 patients with clinical signs of pneumonia plus: respiratory or lung dysfunction. Group IV: 200 critically ill patient in ICU: Acute respiratory distress syndrome (ARDS).
Results: there was a highly statistically significant difference between the studied groups regarding thrombocytopenia (p < 0.001). Thrombocytopenia was statistically higher in severe and critically ill patients. In addition, a statistically significant difference found in outcome among the studied groups (p < 0.05) {critically ill (40%), severe (17.5%)}. The most common cause of death was respiratory failure, which occurred in 28 severe patients (80%) and 65 critically ill patients (81.25%), followed by hemorrhage due to thrombocytopenia, which occurred in 7 severe patients (20%) and 15 critically ill patients, respectively (18.75%).
Conclusion: The Platelet count is a straightforward, inexpensive, as well as easily available laboratory parameter that is frequently linked to severe covid-19 infection and a significant death risk.

Introduction

Corona virus disease (COVID-19), which iscaused by severe acute respiratory syndrome corona virus 2 (SARSCoV-2), can lead to respiratory and lead also to systemic diseases that progress to sever pneumonia in 10–15% of patients [1]. Severe COVID-19 can lead to serious illness, with acute respiratory distress syndrome (ARDS) can result with severe covid-19 and multiorgan failure (MOF) as the primary complications, eventually followed by disseminated intravascular coagulopathy [2]. Clinical manifestations in COIVD-19 patients have been widely reported since the outbreak. [3] COVID-19 infected patients can present with pulmonary symptoms, abdominal symptoms, acute heart injury, liver injury and kidney injury, coagulation abnormalities, and major changes in whole blood cells characterized by lymphopenia and thrombocytopenia [4].

Thrombocytopenia is a common manifestation of infection with COVID-19 which is also an indicator of a poor prognosis of severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS), and COVID-19 [5]. Furthermore, low platelet counts are linked to an increase in the illness severity scores like Multiple Organ Dysfunction Score (MODS), Simplified Acute Physiology Score (SAPS II), and the Acute Physiology and Chronic Health Assessment (APACHEII) [6]. In chronic liver diseases like viral hepatitis B or C, COVID-19 infection can manifest as a serious infection (globally health burden particularly in Egypt) [[7], [8], [9], [10], [11], [12]]. Little is known regarding the impact of COVID-19 infection among people suferring from cirrhosis in the liver [[13], [14], [15], [16]].

Therefore, this study aimed to assess the relationship between thrombocytopenia and severity of COVID-19 infection in hospitalized patients.

Methods

Eight hundred patients with different demographic data were enrolled in a prospective study during the time span between April 2020 to March 2021. All included patients in this study who were suspected clinically and based on covid-19 imaging abnormalities, which were verified by + VE PCR (nasopharyngeal and oropharyngeal samples), divided according to the Ministry of Health Program (MOHP) in Egypt into 4 groups; Group I (Mild), included 200 symptomatic patients who met the COVID-19 case description without any radiological evidence of pneumonia or hypoxia. Group II (Moderate), included 200 patients with clinical signs of non-severe pneumonia and radiological evidence of pneumonia. Group III (Severe), included 200 patients with clinical signs of pneumonia plus one of the following: respiratory rate >30 breaths/min; severe respiratory distress; or SpO 2 < 93% on room air and radiological evidence of pneumonia; patients with more than 50% lesions progress within 24–48 h in lung imaging. Group IV, included 200 severly critically ill patients in intensive care unit: acute respiratory distress syndrome (ARDS) which met any of the following criteria as the occurance of respiratory failure requiring mechanical ventilation; the presence of shock; sepsis, other organ failures that require monitoring and treatment in the intensive care unit.

Ethical consideration including a written informed consent was given by every participant prior to the initiation of study in routine clinical practice at three specialized treatment centers especially concerned with COVID-19 management (Menoufia University Hospitals, National Liver Institute Hospital and Shebin El-Kom Teaching Hospital). The present study was conducted in compliance with the guidelines for Good Clinical Practice. The study methodology was reviewed and confirmed to be compliant with the ethical principles of 1975 Declaration of Helsinki's, as evidenced by prior approval by the institution's human research committee (Institutional Review Board of Faculty of Medicine, Menoufia University, Egypt). The research was established in the Academic Research Registry Department, number 9/2020TROP22. The work has been documented in line with the Strengthening the Reporting of Cohort Studies in Surgery (STROCSS) 2021 criteria [17].

Patients with history of thrombocytopenia or any other cases affecting platelets count such as immune thrombocytopenic purpura, chronic liver disease, sepsis, disseminated intravascular coagulation (DIC), acute liver failure, hypersplenism, heparin or other drug induced were excluded from the current study.

For all selected patients for this study, comprehensive history taking: a particular manifestation of respiratory symptoms (dyspnea, fever and cough) were recorded. A complete general examination (arterial blood pressure respiratory rate and body temperature), local chest examination was assessed. The laboratory research includes (full blood count) including: TLC, lymphocytes, platelet count & hemoglobin (HB) level. C-reactive protein (CRP), D-dimer, serum ferritine, Lactate Dehydrogenase (LDH); and arterial blood gases were done. Coagulation profile, Radiological examination including: pelvi-abdominal ultrasonography and computed tomography. Chest, serology including: RT-PCR for covid-19 was performed for the selected patients.

Statistical analysis

Statistical Package for the Social Sciences (SPSS) version 23 was used to gather, tabulate, and statistically analyses data on an IBM compatible personal computer (Armonk, NY: IBM Corp, 2013). Percentage (percent), Median, Range, and IQR were descriptive statistics, whereas analytic statistics included the chi-square test, to compare different groups for categorical variables. Mann-Whitney test (U) to compare two studied groups for abnormally distributed quantitative variables. One-way ANOVA (F test), to compare more than two groups for normally distributed quantitative variables.Kruskal Wallis testto compare more than two studied groups for abnormally distributed quantitative variables, and Spearman's correlation (r)for correlation between two quantitative variables. Correlation coefficient test (Person test) results may be positive (+) correlation (reverse) or negative (−) correlation (inverse). A statistically significant P value of 0.05 was used.P-value<0.05 was considered statistically significant, P-value<0.01 was considered statistically moderately significant and P-value<0.001 was considered statistically highly significant.

Results

This study had a total of 800 Egyptians patients. The ages of the patients ranged from 21 to 81 years with mean of 53.15 ± 11.82 years old. Most of them were males (n = 478, 59.75%) and (n = 322, 40.25%) were females. There were statistically significant differences among the studied groups in terms of smoking, diabetes, asthma, fever, cough, dyspnea, abdominal pain and diarrhoea, and sore throat, with smoking being statistically significantly higher among severe patients'group, whereas, DM, hypertension, and dyspnea being statistically significantly higher among critically ill patients'group. While, abdominal pain, diarrhoea, and sore throat were more statistically significant higher in mild patients'group. In addition, moderate patients'group had a statistically significant greater of asthma and fever than the other groups (p < 0.05). However, no significant differences reported in age, gender, hypertension (HTN), or CKD among the studied groups (p > 0.05), (Table 1). Regarding, conscious level, crepitation, air entry, and wheezes were statistically significant variations among the studied groups (p < 0.05), where both crepitation and decrease air entry were higher in critically ill patients group and DLC was the most common with critically ill patients group (51.5%). Moderate group had a significant increase in the temperatures than the other studied groups. DBP, RR, and pulse were statistically significant higher in critically ill patients compared to other groups. So2 was also statistically higher in mild and moderate groups than other studied groups. As regards SBP there is no statistically significant difference between the studied groups (p > 0.05), (Table 2). As regard lab investigation, there was a significant difference among studied groups as regard TLC, creatinine, CRP, ferritin, LDH, Hb and D-Dimer where Critically ill patients had statistically significant increased levels of TLC, creatinine, CRP, ferritin, LDH, and D-Dimer than other groups. Hb and platelet count were also statistically significant higher in mild group than other groups (p < 0.05), lymphocytes showed no significant difference among the investigated groups (p > 0.05). In addition, as regard CT chest findings there was a highly statistically significant difference among the studied groups (p < 0.001) while CT findings increase in critically ill groups (Table 3).

Table 1

Demographic data, medical history, risk factors and complains & symptoms among the studied groups.

Variables	Studied groups (N = 800)								K	P-value
	MildN = 200		ModerateN = 200		SevereN = 200		Critically illN = 200
Age/yearsMean ± SDRange	49.55 ± 11.4421.00–77.00		53.46 ± 13.3221.00–80.00		53.5 ± 10.922.00–81.00		56.07 ± 11.6622.00–81.00		1.260	0.839
GenderMaleFemale	N	%	N	%	N	%	N	%	X2 = 0.523	0.914
	11684	58.042.0	11882	59.041.0	12377	61.538.5	12179	60.539.5
SmokingNon-smokerSmoker	12179	60.539.5	10892	54.046.0	91109	45.554.5	11585	57.542.5	X2 = 10.46	0.015*
DM (mg/dL)NoYes	14159	70.529.5	13268	66.034.0	12575	62.537.5	10991	54.545.5	X2 = 12.25	0.007*
HTN (mg/dL)NoYes	12377	61.538.5	11684	58.042.0	11288	56.044.0	98102	49.051.0	X2 = 7.02	0.071
CKDNoYes	18713	93.56.5	18218	91.09.0	18416	92.08.0	1919	95.54.5	X2 = 3.78	0.286
AsthmaticNoYes	17723	88.511.5	16040	80.020.0	17525	87.512.5	18218	91.09.0	X2 = 12.07	0.007*
FeverNoYes	4196	2.098.0	0200	0.0100.0	64136	32.068.0	64136	32.068.0	139.45	<0.001*
CoughNoYes	11090	55.045.0	13169	65.534.5	91109	45.554.5	91109	45.554.5	24.70	<0.001*
DyspneaNoYes	1937	96.53.5	7193	3.596.5	1199	0.599.5	0200	0.0100.0	729.56	<0.001*
Abdominal pain and diarrhoeaNoYes	16436	82.018.0	1946	97.03.0	17624	88.012.0	17822	89.011.0	22.28	<0.001*
Sore throatNoYes	99101	49.550.5	17129	85.514.5	1960	98.00.0	2000	100.00.0	246.62	<0.001*

K: Kruskal Wallis test, X: Chi-square test, * statistically significant, Group I: Mild covid-19, Group II: Moderate covid-19, Group III: Severe covid-19, Group IV: Critically ill covid-19, DM: Diabetes mellitus HTN: HypertensionCKD: Chronic kidney disease.

Table 2

General and chest examination among the studied groups.

Variable	Studied groups (N = 800)								K	P value
	Group IN = 200		Group IIN = 200		Group IIIN = 200		Group IVN = 200
Conscious levelConsciousDLC	No.	%	No.	%	No.	%	No.	%	X2 = 354.14	<0.001*
	2000	100.00.0	2000	100.00.0	2000	100.00.0	97103	48.551.5
CrepitationNoYes	2000	100.00.0	1982	99.01.0	97103	48.551.5	92108	46.054.0	X2 = 279.27	<0.001*
Air entryNormalDecreased	2000	100.00.0	1982	99.01.0	98102	49.051.0	91109	45.554.5	X2 = 279.58	<0.001*
WheezesNoYes	17723	88.511.5	16040	80.020.0	17525	87.512.5	18218	91.09.0	X2 = 12.08	0.007*
Temperature (C°)Mean ± SDRange	38.81 ± 0.6435.80–40.00		38.94 ± 0.5837.90–40.00		38.60 ± 1.1436.90–40.00		38.62 ± 1.1336.90–40.00		6.285	<0.001*
Post Hoc	p1 = 0.179, p2 = 0.018*, p3 = 0.036*, p4<0.001*, p5<0.001*p6 = 0.779
SBP (mmHg)Mean ± SDRange	126.23 ± 78.63100–1220		140.7 ± 134.2100–1220		130.2 ± 70.6100–1110		125.8 ± 11.58100–160		1.31	0.269
DBP (mmHg)Mean ± SDRange	80.64 ± 10.138.00–110.00		83.55 ± 8.5670.00–110.00		83.65 ± 8.5860.00–100.00		84.45 ± 8.4360.00–110.00		6.94	<0.001*
Post Hoc	p1<0.001, p2<0.001, p3 <0.001*, p4 = 0.911, p5 = 0.315, p6 = 0.372
RR (BPM)Mean ± SDRange	20.16 ± 1.6716.00–24.00		20.02 ± 1.8716.00–25.00		23.76 ± 5.1416.00–42.00		36.45 ± 3.9629.00–45.00		995.61	<0.001*
Post Hoc	p1 = 0.697, p2<0.001*, p3<0.001*, p4<0.001*, p5<0.001*, p6<0.001*
PulseMean ± SDRange	82.25 ± 5.8366.00–91.00		81.96 ± 5.0768.00–90.00		82.18 ± 5.8966.00–91.00		105.39 ± 9.5985.00–120.00		580.20	<0.001*
Post Hoc	p1 = 0.676, p2 = 0.923, p3<0.001*, p4 = 0.747, p5<0.001*, p6<0.001*
SO2Mean ± SDRange	96.88 ± 1.1295.00–99.00		96.88 ± 1.1495.00–99.00		77.83 ± 5.1470.00–98.00		76.99 ± 5.0365.00–88.00		1858.053	<0.001*
Post Hoc	p1 = 0.990, p2<0.001*, p3<0.001*, p4<0.001*, p5<0.001*, p6 = 0.025

SBP: Systolic blood pressure,DBP: Diastolic blood pressureRR: Respiratory rateX [2]: Chi square test.

K: Kruskal Wallis test * statistically significant.

P1: mild compared moderate P2: mild compared severe.

P3: mild compared critically ill P4: moderate compared severe.

P5: moderate compared critically ill P6: severe compared critically ill.

Table 3

Laboratory investigations and CT chest among the studied groups.

Variables	Studied groups (N = 800)								K	P value
	Group IN = 200		Group IIN = 200		Group IIIN = 200		Group IVN = 200
Hb (g/dl)Mean ± SDRange	12.10 ± 1.159.50–15.00		11.89 ± 1.1710.00–14.10		10.84 ± 1.138.00–14.00		9.62 ± 0.816.00–12.00		23.84	<0.001*
Post Hoc	p1 = 0.056, p2<0.001*, p3<0.001*, p4<0.001*, p5<0.001*, p6<0.001*
TLC (10 [9]/per liter)Mean ± SDRange	7.47 ± 1.873.30–12.00		7.60 ± 1.754.00–12.00		7.99 ± 1.854.00–13.00		8.08 ± 1.973.00–15.00		5.09	0.002*
Post Hoc	p1 = 0.941, p2<0.001*, p3<0.001*, p4<0.001*, p5<0.001*, p6 = 0.009
Lymphocytes (10 [9]/liter)Mean ± SDRange	0.74 ± 1.270.10–6.00		0.48 ± 0.590.10–3.80		0.59 ± 0.950.10–6.00		0.58 ± 1.000.10–5.50		2.30	0.076
Platelet (10 [9]/L)Mean ± SDRange	358.26 ± 37.11250.0–440.0		315.8 ± 55.66166.0–428.0		199.0 ± 48.2100.0–315.0		185.9 ± 35.5799.00–295.00		71.20	<0.001*
Post Hoc	p1<0.001, p2<0.001, p3<0.001, p4 = 0.033, p5 = 0.009, p6 = 0.638
Creatinine (μmol/L)Mean ± SDRange	0.96 ± 0.540.20–3.50		0.76 ± 0.280.30–1.60		1.07 ± 0.630.30–4.00		1.09 ± 0.550.40–3.80		18.064	<0.001*
Post Hoc	p1<0.001*, p2 = 0.025, p3 = 0.008, p4<0.001*, p5<0.001*, p6 = 0.693
CRP (mg/L)Mean ± SDRange	17.30 ± 8.366.00–48.00		27.72 ± 17.9110.00–84.00		83.17 ± 27.348.0–194.0		129.8 ± 32.7869.00–198.00		984.657	<0.001*
Post Hoc	p1<0.001*, p2<0.001*, p3<0.001*, p4<0.001*, p5<0.001*, p6<0.001*
Ferritin (μg/L)Mean ± SDRange	190.28 ± 64.8852.00–270.00		242.35 ± 55.8110.0–310.0		344.2 ± 58.5170.0–520.0		433.4 ± 48.34280.0–546.0		714.255	<0.001*
Post Hoc	p1<0.001*, p2<0.001*, p3<0.001*, p4<0.001*, p5<0.001*p6<0.001*
LDH (U/L)Mean ± SDRange	213.75 ± 40.15135.0–290.00		228.04 ± 35.6135.0–290.0		237.1 ± 40.1136.0–310.0		276.3 ± 42.98175.0–395.0		90.564	<0.001*
Post Hoc	p1<0.001*, p2<0.001*, p3<0.001*, p4 = 0.023, p5<0.001*, p6=<0.001*
D DimerMean ± SDRange	0.36 ± 0.120.10–0.60		0.64 ± 0.160.30–1.20		1.85 ± 0.840.50–4.00		1.98 ± 0.930.50–5.00		337.120	<0.001*
Post Hoc	p1<0.001*, p2<0.001*, p3<0.001*, p4<0.001*, p5<0.001*p6 = 0.042
CT chest	No.	%	No.	%	No.	%	No.	%	X2	P value
Corad.1	93	46.5	0	0.0	0	0.0	0	0.0	28.973	<0.001*
Corad.2	107	53.5	0	0.0	0	0.0	0	0.0
Corad.3	0	0.0	176	88.0	8	4.0	0	0.0
Corad.4	0	0.0	24	12.0	42	21.0	0	0.0
Corad.5	0	0.0	0	0.0	150	75.0	200	100.0

Hb: Haemoglobin, TLC: Total Leukocyte Count, AST: Aspartate aminotransferase, ALT: Alanine transaminase, CRP: C - reactive protein test, LDH: lactate dehydrogenase.

K: Kruskal Wallis test X2: chi-square test *statistically significant.

P1: mild compared moderate, P2: mild compared severe P3: mild compared Critically ill.

P4: moderate compared severe, P5: moderate compared Critically ill, P6: severe compared Critically ill.

There was a statistically significant positive correlation between platelet count with So2 where thrombocytopenia statistically significant related with hypoxia. While, we found a statistically significant negative correlation between platelet count with CRP, D-dimer, Serum ferritin, and LDH (p < 0.05) (Table 4).

Table 4

Correlation between platelet count with studied parameters with laboratory investigations among the studied patients.

Variables	PLT
	Mild		Moderate		Severe		Critically ill
	r	p value	r	p value	r	p value	r	p value
CRP	−0.004	0.953	−0.221	0.002*	−0.036	0.616	−0.029	0.688
Ferritin	−0.029	0.681	−0.016	0.825	−0.168	0.018*	−0.006	0.933
LDH	−0.108	0.127	−0.072	0.309	−0.130	0.066	−0.200	0.005*
D-dimer	−0.150	0.206	−0.298	0.001*	−0.019	0.785	−0.103	0.825
So2	0.124	0.081	0.088	0.213	0.200	0.004*	0.210	0.039*

DM: Diabetes mellitus HTN: HypertensionCKD: Chronic kidney diseaseRR: Respiratory rateHb: hemoglobin, TLC: Total Leukocyte Count, CRP: c-reactive protein test, Cr: Computed tomography, LDH: lactate dehydrogenase.

r: correlation coefficient *Significant.

As regards mortality rate, there was a statistically significant difference between the studied groups (p < 0.05). where the mortality rate in severily ill patients' group was (80) is (40%) Severe 35 (17.5%), Where the commonest cause of death was respiratory failure, which took place in 28 severe patients (80%) and 65 critical ill patients (81.25%), followed by thrombocytopenia associated hemorrhage (Table 5).

Table 5

Outcome among the studied groups.

Variables	Studied groups (N = 800)								X [2]	P value
	Group IN = 200		Group IIN = 200		Group IIIN = 200		Group IVN = 200
	N	%	N	%	N	%	N	%
OutcomesSurvivorNon- survivor	2000.00	100.000.00	2000.00	100.00.00	16535	82.5017.50	12080	60.0040.00	6.13	0.024*
Couse of deathRespiratory failureHemorrhage and hemorrhagic shock	00	0.000.00	00	0.000.00	287	80.020.0	6515	81.2518.75	----
ThrombocytopeniaYesNo	00	0.000.00	00	0.000.00	40160	20.080.0	50150	25.075.0	94.06	<0.001*
Death due to Hge/Thrombocytopenia	0	0.00	0	0.00	7/40	17.5	15/50	30.0	----

X2: chi-square test *statistically significant.

Discussion

SARS-CoV-2, a highly transmissible, novel respiratory pathogen infecting humans, caused the latest COVID-19 pandemic, which began in December 2019 [18]. Fever, dry cough, loss of taste or scent, weakness, shortness of breath, and acute respiratory manifestations are all common COVID-19 symptoms [19,20]. A total of 800 Egyptians patients were included in our study, the ages of the patients varied from 21 to 81 years with mean of 53.15 ± 11.82 years. Most of them were males (n = 478, 59.75%) and (n = 322, 40.25%) were females. Statistically, there were no significant differences among the studied groups as regard age and/or gender. These results agreed with the study by Yameny, performed on 504 patients their aged ranged from 20 years to 75 years with mean age 44.5 ± 30.5, male gender was more frequent than female gender with no statistically significant differences [21]. Also, the study by Zhu et al., performed on 167 COVID-19 patients, and their age ranged from 29 to 93, female was frequent in 67.07% [22]. No statistically significant differences in age and gender between the studied groups. These results agreed with Yang et al., who performed a study on 1476 patients, comprising of 1238 (83.9%) survivors and 238 (16.1%) non-survivors, were included. Their median (IQR) age was 57 (47–67) years and 776 (52.6%) patients were males [23].

According to our findings, fever was more frequent in moderate patients' group, while abdominal pain, diarrhoea, and sore throat were more common in mild patients. Dyspnea was more common in critically ill patients. Cough was more common in severe patients' group or critically ill. This result agreed with the study by Yameny, who found that, fever was higher among moderate patients'group while dyspnea and cough were statistically higher among critically ill patients'group [21]. Additionally, World Health Organization, [24] In severe cases, infection can cause pneumonia, severe acute respiratory syndrome and sometimes death, that were increased in critically ill patients.

Also, Kim et al., summarized symptoms of 172 patients who were in community isolation facilities in South Korea for mild illness; the most common symptom was cough in 40.2%, and fever was mentioned in only 11.6% [25]. By contrast, Blair et al., noted fever to be the most common initial symptom (reported by 55.8%) and cough a predominant symptom initially, increasing in the first and second weeks before decreasing to 37.4% and 15.1% in the third and fourth weeks of illness, respectively; these differences may reflect differences in the approach to referring for testing [26]. The present study showed that Hb was statistically significantly lower among critically ill patients group than in other groups.

The present study showed that, CRP, ferritin, D Dimer, LDH, TLC and creatinine levels were statistically significantly higher among critically ill patients' group than mild, moderate and severe patients' groups. While AST and ALT were statistically significantly increased among the severe group than in other groups (p < 0.05).

The study agrees with Yameny, found a significant value with critically ill infection as ferritin level which increased in 71.4% LDH has a high level in 67.7% and D-dimer has positive results in 36.4% [21]. Also, the study by Wool and Miller, reported that, temporally increasing D-dimer levels indicate the progressive severity of COVID-19 infection and can be used as a predictor that more aggressive critical care will be needed [27]. Also, the study by Yang et al., found that, CRP, ferritin, TLC and creatinine levels were statistically significantly increased among critically ill group than other groups [23]. Another study by Helms et al., revealed that, D-dimers are significantly increased in COVID-19 infection [28].

Also, Wool and Miller, reported that temporally increasing D-dimer levels indicate the progressive severity of COVID-19 infection and can be used as a predictor that more + aggressive critical care will be needed [27]. While, Liu et al., [15] reported that more severe cases infected with COVID19 expressed significantly higher CRP levels than non-severe patients suggesting that this biomarker can be monitored to evaluate disease progression [29]. The study by Bayani et al., evaluated the association between CRP and COVID-19 infection, and the findings indicated that a patient with a CRP level >64.75 mg/L was more likely to develop the severe form of the disease [30].

In the present study, there was a statistically significant difference between the tested groups regarding thrombocytopenia. Thrombocytopenia was shown to be statistically significant higher in severe and critically ill patients. These findings agree with Yang et al., findings that thrombocytopenia is prevalent in patients with severe COVID-19 and is linked to a higher risk of in-hospital mortality [23]. Also, Lippi et al., found that, the rate of thrombocytopenia, a platelet count below the lower limit of the locally defined reference range was associated with an over 5-fold enhanced risk of severe COVID-19 [31]. The decreasing platelet count in patients in the intensive care unit usually indicates the dysfunction of organs or systems and leads to a disorder of homeostasis. Also, low platelet in the ICU tended to increase the risk of death [32]. It has also been reported that 2019-nCoV infection might affect the blood coagulation mechanism resulting in a disorder of blood coagulation [33].

In the present study, there was statistically significant positive correlation between platelet counts with So2. While, there was statistically significant negative correlation between platelet with CRP, D-dimer, Serum ferritin, and LDH (p < 0.05), These results are in agreement with Draz et al, who found that platelets were statistically significant associated with TLC among critically ill patients (P < 0.05) [32]. Also, the study by Yang et al., that there is a statistically significant negative relationship between platelets with LDH among the studied critically ill patients (P < 0.05) [23]. Moreover, Libby et al., indicated that the relationship between leukocyte count and increased platelet reactivity was observed in total leukocyte count, total neutrophil count, and total lymphocyte count [27]. Both neutrophil count and lymphocyte count showed a strong positive correlation with total leukocyte count (p < 0.05).The study by Draz et al., found no significant correlations between platelet count and hemoglobin level and So2 [34].

In the present study, As regards mortality rate, there was a statistically significant difference between the studied groups (p < 0.05). Where the mortality rate in critically ill patients' group was (80) is (40%) Severe 35 (17.5%), where the most common cause of death was respiratory failure, which occurred in 28 severe patients (80%) and 65 critical ill patients (81.25%), followed by thrombocytopenia associated hemorrhage. These findings matched those of Zhu et al., [22]; Yang et al., [23]; and Lippi et al., [31]. Also, Helms et al., found that, outcome of the COVID-19 was statistically significant difference among the studied patients and the rate of mortality was statistically significantly higher among severe and critically ill patients [28].

It was established that mortality increases when platelet count decreases. Abnormal platelet count is quite common in patients in the intensive care unit [35]. In this concern, Lippi et al., found that the rate of thrombocytopenia below the lower limit of the locally defined reference range was associated with an over fivefold enhanced risk of severe COVID-19 [28].

Conclusion

Platelet count is a simple, inexpensive, and readily available laboratory parameter that is frequently linked to severe covid-19 infection and a significant death risk. From this work, we recommended that: special consideration should be given to platelet count as a simple indicator for severe COVID-19 infection. Also, close follow-up of critically ill patients with thrombocytopenia is required to avoid a bad outcome to occur. Wheeze, the Platelet count should be closely observed before and during anticoagulant therapy. Finally, further studies on a wide scale of patients should be done to confirm our results.

Ethical approval

The study methodology was reviewed and found to be compliant with the 1975 Declaration of Helsinki's ethical principles, as evidenced by prior approval by the institution's human research committee (Institutional Review Board of Faculty of Medicine, Menoufia University, Egypt).

Sources of funding

This study did not receive any specific fund.

Author contribution

•All authors contributed to the conceptualization, design, data curation, resource identification, formal analysis, and data interpretation. Validation and technique, as well as revision of new software used in the work. All authors shared writing of this work. All authors reviewed the Manuscript.

Registration of research studies

Name of the registry: the Academic Research Registry Department

Unique Identifying number or registration ID: 9/2020TROP22

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Guarantor

•All data are available upon request from the last author: Dr Ahmed Abozaid Ahmed Teima.

Consent

A written informed consent was given by every participant prior to the initiation of study in routine clinical practice at three specialized treatment centers especially concerned with COVID-19 management (Menoufia University Hospitals, National Liver Institute Hospital and Shebin El-Kom Teaching Hospital).

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Not commissioned, externally peer-reviewed.

Conflicts of interest

No conflict of interest.