2.1. Setting and ethical approval
The study involved the following hospitals: Prince Sultan Medical Military City [Riyadh], King Abdullah Medical City [Makkah], King Fahad Medical City [Riyadh], Prince Mohammad Bin Abdulaziz Hospital [Riyadh], King Fahad Hospital of University [Khobar], and King Faisal Specialist Hospital and Research Center [Riyadh]. All centers are tertiary care hospitals with full-time availability of diagnostic modalities for diagnostic COVID-19 and VTE. Ethical approvals were obtained from the research ethics committee in each hospital.
2.2. Study population
Eligible patients were identified through the electronic pharmacy system. All admitted adult patients [>18 years old] with laboratory-confirmed COVID-19 with or without VTE were included. Confirmed cases included positive real-time reverse transcriptase polymerase chain reaction [rRT-PCR] test of nose/throat swab or sputum sample according to the WHO definition [11]. VTE was defined based on the ICD9-CM code. Exclusion criteria were patients discharged before 24 hours of admission and children or patients≤18 years old.
2.3. Study design and data collection
This retrospective observational cohort study was conducted from March to July 2020. Patients’ data were retrospectively reviewed from the day of admission until hospital discharge or death. Clinical data were collected using a standardized data collection form. The following information was obtained: demographic data including [age, gender, body mass index], medication history, underlying comorbidities [acute coronary syndrome, heart failure, diabetic mellitus [DM], hypertension, dyslipidemia, chronic kidney dieses, hematological disease, cancer, thyroid dysfunction, lung or liver disease], vital signs, laboratory data, rRT-PCR for SARS-CoV-2, and coagulopathy results [fibrinogen, and D-dimer levels].
2.4. Outcomes
- The primary outcome was the incidence of VTE among hospitalized COVID-19-positive patients.
- The secondary outcome was identifying the risk factors associated with increased incidence of VTE among hospitalized COVID-19-positive patients.
2.5. Explanatory Variables
We hypothesized that predisposing factors, comorbid physical conditions, certain medications, and high D-dimer may affect the presence of VTE. Therefore, explanatory variables included the following: 1] predisposing factors: i. age [19-39, 40-49, 50-59, ≥60]; ii. sex; and iii. body mass index [underweight/normal [below 24.9]; overweight [25-29.9]; obese [≥30]]; 2] comorbid physical conditions: the presence of diabetes mellitus, hypertension, dyslipidemia, heart failure, ischemic heart disease, chronic kidney disease, dialysis, thyroid dysfunction, hematological disorders, lung disease, liver disease, and cancer; 3] medications: antiplatelet, anticoagulant, anti-diabetics, angiotensin-converting enzyme inhibitor [ACEIs] and angiotensin receptor blockers [ARBs], spironolactone, statin, diuretics, beta-blockers, calcium channel blockers, inhaled corticosteroid, and levothyroxine; and 4] high D-dimer>0.50 mg/l [yes, no] and high fibrinogen>200 mg/dl [yes/no]. We included all the explanatory variables in the explanatory variables. Nevertheless, we included only variables associated with VTE from the bivariate analysis in the multivariable analysis.
2.6 Statistical Analysis
Categorical variables were compared using a Chi-square test or Fisher’s exact tests. Multivariable logistic regression methods were used to explore the risk factors associated with VTE. In the final model, the following variables were included: age, sex, diabetes, hypertension, dyslipidemia, heart failure, ischemic heart disease, chronic kidney disease, thyroid dysfunction, hematological disorders, and cancer as well as the use of ACEIs/ARBs, statins, beta-blockers, and levothyroxine. P-values of less than or equal to 0.05 were defined as statistically significant. The statistical analysis was conducted using STATA 16.