3.1. Analysis of Zn, Cu, and CRP levels in the total study population
Out of the 122 patients recruited in the study, 81 (66.39%) were ICU admitted. The mean age for ICU and non-ICU admitted patients was 50.63 and 40.38 years, respectively. Table 2 depicts the higher persistence of comorbidities in ICU-admitted patients.
Table 2: Patient characteristics in COVID-19 non-ICU and ICU groups
|
Non-ICU
|
ICU
|
Mean Age
|
40.38±14.90
|
50.63±16.99
|
Gender-wise distribution of patients
|
Male
|
26
|
52
|
Female
|
15
|
29
|
|
Patients with comorbidities (%)
|
T2DM
|
16.66
|
35
|
Hypertension
|
23.80
|
41.25
|
CAD
|
2.38
|
8.75
|
CKD
|
11.90
|
8.75
|
Obesity
|
2.38
|
3.75
|
|
|
|
Patients with complications (%)
|
ARDS
|
11.90
|
46.25
|
Mortality
|
2.38
|
30
|
Upon analysis of Zn, Cu, and CRP levels in these groups, we found significantly reduced Zn levels with a median value of 53 սg/dL in ICU patients, whereas levels were within the normal limits, i.e., median 85.20 ug/dL in the non-ICU group (p=0.001, Figure 1). However, no significant difference was observed in the levels of Cu in ICU (median 90.75 ug/dL) and non-ICU patients (median 88.70 ug/dL) which correspond to the normal range of this parameter. Also, ICU admission was found to be accompanied with thirty-one times elevated CRP levels with a median value of 81.30 mg/L as compared to 2.62 mg/L in non-ICU patients (p<0.0001, Figure 1).
Zn and CRP levels were found to be negatively correlated with spearman coefficient (r) -0.476 (Figure 2A, p<0.0001), while no significant correlation was found between Cu and CRP (r=-0.025, p=0.791) as well as between Zn and Cu (r=-0.173, p=0.058) in the total study population (Figure 2B, 2C).
3.2. Age and gender-related variations in Zn, Cu, and CRP levels in COVID-19 patients
A decrease in Zn levels was more pronounced in females where 39% had levels below LLN (lower limit of normal) in comparison to 27% in males. The percentage of females with deranged levels of Cu (below LLN) and CRP (above ULN) was found to be 23% and 73% in comparison to 31% and 79% in males respectively (Figure 3A). Below 50 years of age, 25% of the COVID-19 patients had Zn levels below LLN and 62% had CRP above ULN, whereas, in patients aged above 50 years, deranged levels of Zn and CRP were found in 39% and 73% of patients respectively. There was no substantial effect on the levels of Cu among these two groups (Figure 3B)
3.3. ROC Analysis
Receiver operating characteristics (ROC) analysis was done for individual parameters. The area under the curve (AUC) was found to be 0.770, 0.503, and 0.922 for Zn, Cu, and CRP with the Youden index 0.539, 0.112, and 0.767 respectively (Table 3). Since, among these parameters, Zn and CRP had the maximum significant AUC and Youden index, their ratio was analyzed. ROC analysis of the CRP/Zn ratio displayed an improved AUC of 0.930 with a Youden index of 0.772 with a significant p-value (p<0.0001, Table 3). The cut-off value of the CRP/Zn ratio (CRP and Zn expressed as mg/L and սg/dL respectively) for determining the severity of COVID-19 patients was found to be 0.184. Moreover, the ratio displayed increased sensitivity (90%) in comparison to the individual parameters, i.e. 63.75% and 79.75% for Zn and CRP, respectively (Table 3, Figure 4) indicating the greater potential for the identification of ‘true positives’ and for determining ICU requirement by COVID-19 patients at early stages.
Table 3: Table showing the summary of ROC analysis for various parameters
Parameters
|
AUC
|
95% CI
|
Youden Index
|
Specificity
|
Sensitivity
|
Zinc
|
0.770
|
0.684-0.855
|
0.539
|
90.24
|
63.75
|
Copper
|
0.503
|
0.396-0.610
|
0.112
|
00.00
|
88.75
|
CRP
|
0.922
|
0.866-0.979
|
0.767
|
96.97
|
79.75
|
CRP/Zinc
|
0.930
|
0.882-0.977
|
0.772
|
87.18
|
90.00
|
3.4. Levels of parameters with respect to the survival and mortality status
Out of the 122 patients recruited in the study, 25 died during hospitalization with 24 causalities reported from the ICU ward. The parameters were compared among the patients who survived and recovered with those who died later during their hospital stay due to COVID-19 complications (Figure 5). No significant difference was found between the median values of Zn in these two groups, i.e. (71.45 and 51.80 ug/dL, respectively). However, levels of CRP were significantly higher in the patients who died (97.47 mg/L), in comparison to the ones who survived (27.47 mg/L). Also, no significant difference was found in the ratio of CRP/Zn between the two groups.