Assessment of Hematologic and Coagulation Parameters As Predictive Value in COVID-19 with Unfavourable Evolution
Authors: Popov Viola Maria , Iliescu Lelia , Balea Marius Ioan , Georgescu Daniela Georgeta , Andreescu Mihaela , Bumbea Horia , Omer Meilin , Balea Marius Lucian Aurel , Parvu Catalina , Grigorie Andra Bogdana , Popescu Mihaela , Patrinoiu Oana , Rus Ana , Gologanu Daniela , Nedelcu Valentin , Ofiteru Geanina , Despan Claudia , Niculae Badoiu Mihaela , Badea Adriana , Constantin Oana , Mihai Lidia Felicia , Calen Andreea , Ion Silvia , Popescu Gabriel Adrian , Hristea Adriana , Mastalier Bogdan , Diaconescu Bogdan 
Published: February 2021

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly infectious disease. The pathogenic mechanism of COVID-19 pneumonia involved excessive immune reaction in the host - a "cytokine storm", that determined extensive tissue damage associated with coagulation abnormalities. Severity of this disease is associated with comorbidities such as hypertension, obesity, pulmonary disease or age. Thrombotic complications are reported during COVID-19 evolution even with prophylaxis.
OBJECTIVE: In this study, we evaluate hematological and coagulation parameters in order to obtain predictors for an unfavourable evolution of the patient. DESIGN AND SETTING: We performed a prospective study that included all patients admitted in our hospital in Hematology, Pneumology, and Intensive Care Unit (ICU) Department at Colentina Clinical Hospital during April - July 2020. The study group included 144 patients that were split into ICU and non-ICU patients. All patients were SARS-CoV-2-positive by molecular test. The distribution according to gender was as follows: 67 male with median age: 61 (min 22, max 88) and 77 female with median age: 57 (min 17, max 92).
RESULTS: Age is an important risk factor for the severity; 50 patients admitted in ICU with median age 67 (min 34, max 92) and 94 non-ICU patients with median age 52.5 (min 17, max 92), p=0.00003. Associated comorbidities were important and were present in both groups. In ICU patients, we obtained lower level of lymphocytes compared with non ICU group median: 1 x 103/L (min 0.04 x 103/L max 3.28 x 103/L) vs 1.57 x 103/L (min 0.39 x 103/L max 23.35 x 103/L), p=0.0001. There are no significant differences between groups for the rest of hematological parameters. The neutrophil/lymphocytes ratio (NLR) is with statistical difference between ICU and non-ICU groups: 2.34 (min 1.06, max 31.90) vs 7.94 (min 2.18, max 90.04), p&lt;0.000001. This indicator seems to be predictor for severe evolution; a high correlation with IL-6 level (r=0.73, p&lt; 0.001) was obtained. NLR in association with IL-6, CRP and ferritin level are important factors in severe evolution of COVID-19 (severe pneumonia-more than 50% of lung evaluated by CT-scan and presence of any complications during COVID-19 evolution), coefficient of determination-R2 =0.69, R2 - adjusted 0.67, p&lt;0.0001). The ICU patients with unfavourable evolution had a higher level of D-Dimers at the admission in hospital compared with ICU patients who were discharged from the hospital (3.42 mg/ml FEU vs 1.09 mg/ml FEU, p=0.01). Patients with thrombosis (stroke, myocardial infarction, deep venous thrombosis, thromboembolism) during COVID-19 evolution have higher level of D Dimers compared with patients without thrombotic complications (7.35 mg/ml FEU vs 0.82 mg/ml FEU), p=0.0001. There are no difference for another coagulation tests (APTT, Quick time) or Protein C, Protein S and Antithrombin III level.
CONCLUSIONS: We conclude that NLR in association with feritin, CRP and IL-6 assessment are important to be evaluated in COVID-19 patient in order to expect a severe evolution of the disease. D- Dimer should be an important parameter to be evaluated for all COVID-19 patients in order to identify COVID-19 patients with high risk of thrombotic complications.

Disclosures
No relevant conflicts of interest to declare.