This cross-sectional, single-centre study was performed in University of Ordu Training and Research Hospital, which was determined to treat COVID-19 patients by Turkish Republic Ministry of Health, between November 15 August 2020 and 01 September 2020. The mild severity COVID-19 patients; was defined as patients who were followed outpatient, non-hospitalized, and who had constituional symptoms including fever, muscle and / or joint pain, cough, sore throat, without respiratory distress (respiratory rate <24/minutes, peripheral capillary oxigen saturation (SpO2) > 93% at room) according to the World Health Organization and the Republic of Turkey Ministry of Health COVID-19 Treatment Guidelines . 120 patients with mild severity COVID-19 disease who were older than 18 years old and treated with only hydroxychloroquine and/or favipiravir were respectively enrolled in the study. Patients with systolic heart failure (LVEF ≤ 50%), coronary artery disease, chronic inflammatory disease, hypertension, severe chronic renal and liver failure, right or left ventricular failure, atrial fibrillation, complete or incomplete branch block, moderate-severe valve pathology, pacemaker, anemia, chronic renal failure, thyroid dysfunction, pulmonary embolism, cancer, chronic lung disease, body mass index (BMI) > 30 kg/m2 were excluded. In addition, patients who were given steroids and/or heparin treatments along with hydroxychloroquine and/or favipiravir due to COVID-19 and those who had any other active infection disease and used antibiotics and poor echocardiographic images were excluded. After the exclusion criterias were applied, the study continued with 96 mild severity COVID-19 patients. Age and sex matched 96 healthy individuals forming the control group were selected consecutively from the outpatient clinic. Demographic data, baseline characteristics, medical history, drugs and medications used for COVID-19, smoking habits and laboratory values were obtained using the hospital’s medical database. Laboratory parameters including; complete blood count (CBC), C - reactive protein (CRP), D-dimer, ferritin, cardiac troponin I (cTnI) and other biochemical parameters were measured at the first admission to the hospital before COVID-19 treatment started. The entire study population were evaluated via two-dimensional echocardiography and speckle tracking echocardiographic imaging. The COVID-19 patients’ echocardiographic examinations were performed average 4.5 (3-6 months) months after COVID-19 diagnosis. The research procedures were revised and approved by the local hospital’s ethics committee and Ministry of Health Scientific Research Platform (No: 2020-11-07T18_44_00) according to the ethical considerations stipulated in the Helsinki Declaration.
Diagnosis of COVID-19
According to the World Health Organization and the Republic of Turkey Ministry of Health according to the COVID-19 Treatment Guidelines, patients who were matching the definition of probable SARS-CoV-2 infection case underwent testing with molecular methods to scan for viruses. Throat and nasopharynx swab samples were collected from all patients in our study to extract SARS-CoV-2 RNA. Real-time reverse transcription polymerase chain reaction assay (RT-PCR) molecular method was applied for RNA analysis of SARS-CoV-2 virus. Cases with SARS-CoV-2 RNA in RT-PCR method were accepted as COVID-19.
Two-dimensional echocardiography (2DE)
Conventional 2D echocardiographic examination was performed using a commercially available echocardiography device (EPIQ 7C; Philips Medical Systems, Andover, Massachusetts) in line with the recommendations of the American Echocardiography Association[8] . All these echocardiographic examinations were performed by experienced two operators. Echocardiographic examinations were performed in left lateral decubitus position after resting for at least 15 min. Blood pressures of the study population were measured prior to echocardiographic examination; right arm average systolic blood pressure was measured 118.5 mmHg / diastolic blood pressure was measured 78.5 mmHg, left arm average systolic blood pressure was measured 120.5 mmHg / diastolic blood pressure was measured 80.5 mmHg. All measurements were taken in three consecutive cycles, and average values were calculated. Patients with optimal views of left ventricul for STE analysis were included in the study. 12 patients were excluded due to poor echocardiographic images. The patients were monitored by electrocardiogram throughout the procedure. Left ventricle (LV) and left atrium (LA) diameters and LV wall thicknesses were measured from parasternal long axis views by M-mode echocardiography. Left ventricular ejection fraction (LVEF) was calculated from the apical 4-chamber and 2-chamber images using the Modified Simpson method[9]. Pulsed vawe Doppler velocity recordings were obtained in apical four-chamber images via placing the sample volume at the tips of the mitral valve.
E/A ratio was calculated following assessment of mitral early peak velocity (E) and mitral late peak velocity (A). Stroke volume (EDV—ESV, ml) and cardiac output (stroke volume x heart rate, l/m) were driven after calculation of LV end-diastolic volume (LV EDV, ml) and end-systolic volume (LV ESV, ml). Tricuspid regurgitation peak velocity was used for measurement of systolic pulmonary artery pressure (sPAP). Devereux formula was used to calculate the LV mass [10]. Finally, all measurements were re-analysed considering the body mass index (BMI).
Speckle Tracking Echocardiography
The myocardial deformation quantitative analysis function of 2D-STE was used to evaluate myocardial function. The end of systole was defined as the time at which the aortic valve is closed and the end of diastole was defined as the peak R wave in the electrocardiogram. Endocardial borders were monitored within the frame of 2D images at the end of systole. A wide myocardial width was adjusted to determine the epicardial border. Automatic function was used to determine the midpoints between the endocardial and epicardial borders and the middle myocardial border. In order to ensure correct tracking and to involve all LV wall thickness for 2D speckle viewing width, manual adjustment was performed when necessary. Apical four-, three-, and two- chamber views were used for evaluation of LV-GLS.
All images used for speckle‐tracking echocardiographic analysis were obtained using the QLAB-CMQ software program Philips Epiq 7C at a frame rate of 50 to 70 fps. Peak systolic strain measurements of each segment were automatically taken by a software (analysis) program. Following assessment of longitudinal strain values of a total of 18 segments, the mean value was determined as the global strain[11] (Figure 1). The circumferential strain used to evaluate myocardial shortening/ lengthening along the LV curvature was measured from the LV mid-ventricular short-axis view. The global circumferential strain was calculated from the average peak systolic strain value of six segments. Negative values were used to determine global longitudinal and circumferential strains, and less negative values indicated lower strains. (Figure 2).
Statistical analyses
In all statistical analysis SPSS 22.0 Statistical Package Program for Windows (SPSS Inc., Chicago, IL, USA)was used. In order to test normality of distribution Kolmogorov–Smirnov test was used. Quantitative variables were specified as the mean ± standard deviation. Categorical variableswere shown as number and percentage values. Differences between groups were evaluated by using Student's t-test andMann Whitney U test. Categorical variables were compared with Chi-square test. Spearman correlation analysis was performed to examine the relationship between LV GCS, LV GLS and NLR, CRP. A p value of <0.05 was accepted as statistically significant.