A novel COVID 19 is a world wide spread viral infection started in December 2019 in Wuhan city, affects mainly respiratory tract and could be ended by multiple organs failure. Efforts have been made to stop the spread, started by early diagnosis and isolation, ended by vaccine production, but the challenges are the continuous mutation of the virus. A wide range of tests used during period of pandemic, the tests should be aiding the detection of infection as early as possible, even an asymptomatic case, stage of the illness, predict critical case, assess severe cases and follow the sequences of illness. The clinical course is thoroughly studied by Aguilar RH, et al whom choose about 70 article in different countries and different languages to be reviewed - the course and severity are varies according to many factors among them genetic variation, and is divided into three stages, started by fever, cough, fatigue, also may include abdominal pain, insomnia…and other constitutional symptoms, few patients are asymptomatic, this is a stage (I) and take about 5-7 days, during this stage, the diagnosis should be confirmed by PCR, and patient may have lymphopenia and high D-dimer. stage (II), lasts for 5-7 days, localized inflammation of the lung becomes evident, patient needs CXR and/or CT scan, 10-15% of patients may progress to stage (III) with high morbidity and mortality rate which is usually due to uncontrolled inflammation, in this stage, the laboratory inflammatory marker is markedly increased [1-3]. The WHO recommend the definite tests for diagnosis are the predicting antigen by PCR (polymerase chain reaction) and positive serological test -identification of specific COVID 19 antibodies-. The sensitivity of both PCR and antibody detection is depending on many factors (symptomatic, asymptomatic, days of incubation period and days of starting symptoms). PCR usually become positive at mid or the end of stage I, while IgM turned positive at stage II [4-7]. Other tests like C-reactive protein, S. ferritin, complete blood count, lactate dehydrogenase enzyme, procalcitonin are performed to assess the severity or for follow up, useful for detecting the severity and risk of the complications [8-9].

Haematological changes were reported, both haemopoeitic system and haemostasis have a significant impact. It has an important role through monitoring of infectious process, suspicion of their severity and course of the illness. Haemocytometry (CBC) is widely available, cheap, rapid, informative and explain the haematopoietic changes. The most common recorded haematological finding is lymphopenia, followed by neutrophilia, eosinopenia, mild thrombocytopenia and, even thrombocytosis. The total leucocyte count may be normal, reduced or increased [5,10,11]

Three Groups are Included in this Study

• First group during second wave between January - March 2021

• Second group during third wave between July - September 2021

• Third group, also during third wave between July - September 2021, represent vaccinated patients-post (vaccine infection)

For all patients, 2 cc of venous blood were collected from 220 adult patients (118 males, 102 females) in EDTA anticoagulant tubes.

Complete blood count is performed by Sysmex (XN-350)-5-diff auto-analyzer, the results of those who proved to be COVID-19 infection either by PCR and or antibodies screen test are statistically analyzed.

Data analysis was including: white blood cell counts with differential count, and platelet count, haemoglobin and red blood indices were not included because its highly affected by the general health preceding the infections. 

The results were compared with the normal ranges according to textbook of Dacie and Lewis /practical haematology, twelfth edition. 

Statistical study done and the relation between the mean of the groups is tested by one way ANOVA. 

A cross-sectional study was including persons attended to the outpatient department at Al-Salam hospital/ Mosul city, either as a part of preoperative screening test, or seeking advice due to accidental contact with COVID-19 infected patients, or those who feeling unwell and recent attack of mild constitutional symptoms either headache, mild fever, abdominal pain. etc. all those patients are screened for COVID 19 in addition to complete blood count. Patients with COVID 19 confirmed by PCR or by serological tests are included in this study. Patients receiving cortisone, cytotoxic drugs, and those who already has autoimmune disease are excluded.

A total 220 adult patients, (122) males, (98 females) from three groups first group during second wave of Iraq, second and third group during third wave and including patients received Pfizer vaccine. In both first and second groups (non- vaccinated patients), the constant finding is eosinopenia (less than 0.02 x10⁹/L). Accompanied either by another single or more parameter abnormalities.

The percentage of the significant parameter changes is illustrated in the Table 1. 

Table 1: The Percent of Parameters Changes in Each Group

In the first group, 99 adult patients were included, about 37% (37/99) presented with leukocytosis, about 8% (8/99) leucopenia, about 16% (16/99) thrombocytopenia. Differential leucocytes count changes, all 99 patients presented with eosinopenia, about 40% (40/99) patients had two changes (eosinopenia with another parameter changes) were about 36% (36/99) multiple parameter changes or more , about 49% (49/99) neutrophilia, about 45% (45/99) lymphopenia, about 6% (6/99) neutropenia, about 9% (9/99) monocytosis, 8% (8/99) of cases presented with high N/L ratio (neutrophil/lymphocyte) in spite of normal white cell count and differential, and about15% (15/99) have no any abnormality apart from eosinopenia. By follow these patients, from those who has neutropenia 5/6 had IgG positive (previous subclinical or mild infection) presented due to systemic complication. Second group which represent third wave. 105 adult patients were included in this group, 33% (35/105) presented with leukocytosis, about 11% (12/105) leucopenia, 15% (16/105) thrombocytopenia, similar to group one, all 105 patients presented with eosinopenia, 47% (49/105) had two abnormalities (eosinopenia with another parameter changes) while 39% (41/105) had multiple parameter changes, 55% (52/105) neutrophilia, 48% (51/105) lymphopenia, 13% (14/105) neutropenia, 10% (10/105) monocytosis, 7% (7/105) had high N/L ratio, 8% (8/105) cases presented only with eosinopenia. Third group includes 16 patients, represent post vaccine infection, all has normal leucocytes count apart from four, 25% with lower normal limit (<4, >3.8), no one with neutrophilia, 13% (2/16) presented with thrombocytopenia, 38% (6/16) cases presented with single parameter changes, and 25% (4/16) cases presented with two parameter changes, 31% (5/16) neutropenia, 6% (1/16) lymphopenia, 25% (4/16) eosinopenia,13% (2/16) monocytosis.

In general, there are no significant variation of the leucocytes and platelets parameters between the mean of groups 1 and 2. The mean of the parameters studied is symmetrical in both 1^st and 2^nd groups, Table 2.

Table 2: Relation Between the Mean of Each Parameter Of 1st And 2nd Group

Because there are no significant differences between 1^st and 2^nd group, we compared their results together -non-vaccinated group (as one group)- with the 3^rd vaccinated group. There is a significant variation between the mean of total leucocyte count, neutrophil, lymphocyte, eosinophil, but there are no significant differences between the mean of monocyte and platelet count, (Table 3).

Table 3: Relation between the Mean of Each Parameter of Vaccinated and Non-Vaccinated Patients

In this study is a trial to utilize the results of complete blood count as a screen test for predicting COVID-19, because it is easy test rapid, cheap in comparison to other tests, and available in every clinical unit. Early detection means early isolation (decrease contagious), and also starting conservative measurement earlier. On reviewing the impact of COVID-19 on haematology, there is a variation between the researches which concentrate on haematological parameters, most probable, the results are depending on the stage of the illness. In this study the commonest finding in both non vaccinated groups (1^st and 2^nd) are eosinopenia, followed by high N/L ratio (whether associated with neutrophilia, lymphopenia or only high ratio and - neutrophils, lymphocytes with normal range -), most patients have either neutrophilia, lymphopenia or both, and rarely only high N/L. there is a significant variation between vaccinated and non-vaccinated groups. Also, there is a wide variation in the number of patients between vaccinated and non-vaccinated. In this study the total leucocyte count is normal in more than half of the cases in the 1^st and 2^nd 55%, 54% respectively, and the mean counts are within normal in all three groups. But it is near upper normal in the 1^st and 2^nd groups with high significant variation between vaccinated and non-vaccinated. Leukocytosis is more common in both 1^st and 2^nd group than leucopenia with similar results, by follow up patients with leukocytosis, they have more aggressive constitutional symptoms, this finding is corresponding with other studies, higher total leucocyte count needs close observation and considered a critical finding and most likely indicate severe inflammation [12-14]. Leucopenia is less frequent in first and second group 8%, 11% respectively than in 3d group 25%. Variation in leucocyte count is corresponding with other studies, the leucocyte count may be normal, increased or decreased [10-11]. Small percent (15%, 8%) of 1st and 2^nd group has only eosinopenia, while more than one third of 3d group has only one abnormality. half (51%) of the patients of the second group have additional two parameters’ abnormalities and this was significantly differed from those of 1^st group 23%, and only 7% of third group. By follow up we found that those with more than two abnormalities in addition to eosinopenia suffer from more morbidity course. So, the second group considered more severe than first group and mild in vaccinated group. Neutrophil play a critical role in regulation of inflammatory response in COVID-19, and the hyper inflammatory response is directly correlated with neutrophils and N/L ratio. Recent studies founds that there is close correlation between proinflammatory factors and granulocytic- myeloid – derived suppressor cells which is most probably it is the leading factor of lymphopenia [15-16]. Although nearly half of the patients in the 1^st and 2^nd groups have neutrophilia the mean is mildly elevated, but it’s not a finding in group 3. By follow patients who presented with neutrophilia, 10% of 1^st group and 8% of 2^nd go to hypoxia, three cases who needs obstetric surgery have run difficult operation, these cases represent cases with neutrophilic counts more than 15x10⁹/L, the underlying pathophysiology of neutrophilia is multifactorial and severe neutrophilia is associated with cytokines storm [17-18]. While neutropenia is more significant in 3d (vaccinated) – about one third- followed by 2^nd group (11%), and rare in 1^st group (8%). Cases with neutropenia in 1^st and 2^nd groups have longer clinical coarse, milder respiratory symptom with normal oxygen saturation, and prolonged myalgia and non- respiratory systemic complication, these finding also reported by other researchers [19-20]. Since 2019, the researcher tries to study the correlation between lymphopenia and severity of the illness [21-23]. Lymphopenia is common in 1^st and 2^nd groups with no significant difference (45%, 48%), with similar mean count, while rare in 3d group 6%, and a significant difference in the mean count between vaccinated and non-vaccinated. On follow up, lymphocyte count it become significant when rapidly changed within day to day follow up, those with constant lymphocytes above 0.8 have milder coarse. Few cases of 1^st, 2^nd group have normal neutrophil and lymphocytes count but still have high N/L ratio more than 3.5. Monocytosis is rare in all three groups, no significant differences between their mean count, the higher percent is in the 3d group (13%). Eosinopenia represent the most common finding in this study especially in non-vaccinated cases (100%), and its widely different in 3d group, only 25% of cases presented with eosinopenia and there is a significant variation between the mean of vaccinated and non-vaccinated groups. From these findings, eosinopenia can be considered as an COVID-19 predictor factor in non-vaccinated cases, most probably have no role in predicting the critical cases although those with presented with eosinophil 0.02 have very short coarse not more than 72 hours with mild fever and/or mild generalized weakness. Other studies concentrate on the role of eosinopenia in COVID-19 diagnosis especially when associated with another marker abnormality. In post vaccine cases, although eosinopenia is uncommon, but still could be considered a diagnostic predictor factor. Thrombocytopenia is infrequent in the three groups (16, 15, 13) % respectively with no significant difference in the mean, most probably have significant role in predicting critical cases but not early infection predictor.

Haemocytometry is an important test to predict COVID-19 (screen test) during pandemic. And to predict patients with high morbidity. Eosinopenia considered as COVID-19 predicting factor in non-vaccinated patients and mostly it is associated with high N/L (with or without neutrophilia, and/ or lymphopenia). Eosinopenia is still a predicting factor in limited number of post-vaccine infections. Normal haematological parameter not exclude COVID-19 infection in vaccinated cases. The variation between the parameters of non-vaccinated and vaccinated cases reveal that the vaccine is highly effective in alleviates the effect of viral infection. Eosinopenia have a clinical significance in detecting patients with high morbidity when it is associated with multiple parameter changes. Neutrophilia is a marker of high morbidity.

Aim of the Study

• To assess the role of haemocytometry as a COVID-19 infection predictor in outpatient department. 

• To study the impact of COVID-19 on platelet, leucocyte counts in addition to the differential count, and the variation between vaccinated and non-vaccinated cases

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