COVID-19 is affecting elderly people more and increasing in its severity

Objective The important changes occur in routine blood tests in Corona Virus Disease 2019 (COVID-19). Methods The biochemical, hematological and inammatory biomarkers of a total of 3969 COVID-19 patients’ results (3746 in the non-intensive care unit (non-ICU) group and 223 in the ICU group) were analyzed by dividing into three groups as spring, summer and autumn. Results In the non-ICU group, lymphocyte to monocyte ratio were lower in autumn than the other two seasons and neutrophil to lymphocyte ratio was higher in autumn than the other two seasons. Also, monocyte and platelet were higher in spring than autumn and eosinophil, hematocrit, hemoglobin, lymphocyte and red blood cells decreased from spring to autumn. In the non-ICU group, alanine aminotransferase and gamma-glutamyltransferase gradually increased from spring to autumn while albumin, alkaline phosphatase, calcium, total bilirubin and total protein gradually decreased. Additionally, C-reactive protein was higher in autumn than the other seasons, erythrocyte sedimentation rate was higher than the only summer. the Kruskal Wallis Test was carried out. An independent t-test or Mann-Whitney test was carried to evaluate the continuous variables between any two groups. Using the χ2 test, proportions for categorical variables have been compared. All statistical analyses have been conducted by using SPSS software (version 20.0, SPSS Inc, Chicago, States). Statistical signicance can be shown as the p-values < 0.05.

In the non-ICU group, alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) values gradually increased from spring to autumn while albumin, alkaline phosphatase (ALP), calcium, total bilirubin, total protein, and estimated glomerular ltration rate (eGFR) gradually decreased. Additionally, aspartate aminotransferase (AST) was lower in spring than other seasons and HDL was higher in spring than other seasons while AST/ALT, direct bilirubin and chlorine were lower in autumn than other seasons. Moreover, glucose, creatinine (only in men), urea and uric acid were higher in autumn than in other seasons, and lactate dehydrogenase (LDH) was higher in summer than in other seasons while creatine kinase myocardial band (CK-MB), creatinine (only in women) and lipase were lower in summer than autumn and cholesterol were higher in spring than autumn. Also, sodium was higher in summer than autumn and AIP was higher in summer than spring. In the ICU group, ALT, GGT and creatinine (only in men) increased in summer than autumn, and AST, glucose and urea were higher in autumn than other seasons while calcium and eGFR were lower in autumn than other seasons and, albumin and ALP were higher in spring than other seasons. Additionally, LDH was higher in autumn than spring and the total protein value was lower in autumn than spring (Table 3). While ALT, AST, AST/ALT, ALP, CK-MB, direct bilirubin, GGT, glucose, creatinine, creatine kinase (CK), LDH, magnesium, sodium, total bilirubin and urea were higher, albumin, iron, calcium, total protein and eGFR were lower in the ICU group compared to the non-ICU group (Table 4).              0.74 * p < 0.05, ** p < 0.01, *** p < 0.001, p values denoted comparison of total median values between ICU and non-ICU groups. AIP, atherogenic index of plasma; Alb, albumin; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Ca, calcium; CI, chlorine; CK, creatine kinase; CK-MB, creatine kinase myocardial band; D. Bil, direct bilirubin; eGFR, estimated glomerular ltration rate; GGT, gamma glutamyltransferase; HDL, high density lipoprotein; IQR, interquartile range; K, potassium; LDH, lactate dehydrogenase; LDL, low density lipoprotein; Mg, magnesium; Na, sodium; T. Bil, total bilirubin; T.Col., total cholesterol; TG, triglyceride; TIBC, total iron binding capacity; T. Protein, total protein, UA, uric acid.

Seasonal comparison of biochemical biomarkers in the in
In the non-ICU group, CRP was higher in autumn than in other seasons and ferritin (only in men) gradually increased from spring to autumn while ferritin (in women) was lower in spring than other seasons. Additionally, procalcitonin was higher in summer than autumn, and ESR was higher in autumn than summer while aPTT was higher in summer than spring and was higher in spring than autumn. Moreover, LCR (lymphocyte/CRP) and SII were lower in autumn than in other seasons. In the ICU group, ferritin gradually increased from spring to autumn while procalcitonin and SII were higher in summer than autumn and ESR was higher in autumn than spring (Table 5).  Table 6 Comparison oof in ammatory, cardiac and coagulation biomarkers in the intensive care unit (ICU) and non-ICU groups on admission. LCR was lower shows that the patients produced a more powerful in ammatory response in this last period. Previous studies reported that increased CRP, ESR, LDH and decreased albumin, eosinophil, and lymphocyte are the most important laboratory ndings of the disease [9,10,13].
While the results that MCV, neutrophil, plateletcrit, PDW, RDW, WBC, P-LRC, NLR, d-NLR and PLR were higher and eosinophil, hematocrit, hemoglobin, lymphocyte, MCHC, monocyte, RBC and LMR were lower in the ICU group were expected, they indicate that the immune response is defective in this group, that lymphocytic and erythrocyte series in the bone marrow might have been suppressed and there might be platelet and erythrocyte deformities. Lymphopenia is the most important laboratory ndings that show defective immune response and risk of hospitalization in the intensive care unit in COVID-19 [9]. Neutrophil might be related to hyperin ammation and cytokine storm or superimposed bacterial infection [16]. NLR shows the severity of in ammation and it is a powerful predictive and prognostic indicator [11,17]. Also, the PLR value is asserted to be correlated with the severity of cytokine storm [18]. It was asserted that eosinopenia can be used in diagnosis in combination with lymphopenia [19]. Additionally, changes in the RBC parameters are related to distorted erythropoiesis [8]. High RDW is reported to be related to high mortality [20].
Moreover, the result that ALT, AST, AST/ALT, ALP, CK-MB, direct bilirubin, GGT, glucose, creatinine, CK, LDH, magnesium, sodium, total bilirubin, urea and troponin values were high while albumin, iron, calcium, total protein and eGFR were low in the ICU group indicates that this group had more muscle, liver, cardiac, pancreas, lung and kidney pathologies. This multi-organ involvement in COVID-19 was associated with the widespread distribution of angiotensinconverting enzyme (ACE2) receptors in the body [21]. High creatinine, AST, LDH, troponin, CRP, ferritin, procalcitonin, D-dimer, and brinogen values were reported to be the indicator of clinical deterioration and mortality in these patients [22,23]. It is asserted that live function tests such as ALT, AST, GGT, ALP and bilirubin often increase in COVID-19 but they do not require treatment and the underlying reasons for these increased values are hyper in ammation and thrombotic microangiopathy [24]. The ratio of AST/ALT (de ritis ratio) was found to be an important indicator especially in women [25]. It was reported that fasting hyperglycemia increases mortality as well as the development of complications [26]. It was stated that sodium, potassium and calcium are low in severe COVID-19 patients; thus, electrolytes should be monitored [27]. The reason for high sodium in the ICU group in the present study might have been iatrogenic.
Additionally, increased CRP, ferritin, procalcitonin, ESR and decreased LCR values in the ICU group show that this group had a more powerful in ammatory response. CRP is a sensitive indicator of in ammation and tissue damage and it increases in most COVID-19 patients [28,29]. Previous studies reported that high CRP and LDH and lymphopenia may show the necessity to transfer the patient to intensive care [10]. It is asserted that low LCR is an indicator of high mortality and the need for mechanical ventilation [30]. A high level of procalcitonin might be due to secondary bacterial infection [12]. Increased d-Dimer and brinogen are the indicators of intravascular blood clot coagulation and high PT and INR values. Therefore, these patients should be monitored in terms of the development of disseminated intravascular coagulopathy (DIC) and acute respiratory distress (ARDS) [12,21,31].
Another new information provided by this study is that the ratio of the changes in routine blood biomarkers was revealed clearly. Accordingly, the increases in these tests were mostly lower than twice while decreases were lower than half (bigger than 0.5 times). Thus, even small changes in the laboratory tests of these patients must be considered.
The limitations of this study are that it was designed retrospectively and single-center and that comorbidities and medications received were not included in the study.
In conclusion, this study showed that the changes in routine laboratory tests in COVID-19 vary in the period from the emergence of the disease until now. There were increases in some tests, decreases in some and similarities in some during this period. Thus, the timely changes in the routine laboratory tests in COVID-19 should be checked with new studies. Also, the timely change of routine laboratory tests was mostly more negative in this study and this indicates that the disease progresses more severely compared to the period when it rst emerged.