Analysis of the predictive factors for a critical illness of COVID-19 during treatment － relationship between serum zinc level and critical illness of COVID-19

Abstract

Objectives: Because most severely ill patients with COVID-19 in our hospital showed zinc deficiency, we aimed to examine the relationship between the patient's serum zinc level and severe cases of COVID-19.

Methods: Serum zinc <70 μg/dL was defined as the criterion for hypozincemia, and patients continuously with serum zinc <70 μg/dL were classified in the hypozincemia cohort. To evaluate whether hypozincemia could be a predictive factor for a critical illness of COVID-19, we performed a multivariate analysis by employing logistic regression analysis.

Results: Prolonged hypozincemia was found to be a risk factor for a severe case of COVID-19. In evaluating the relationship between the serum zinc level and severity of patients with COVID-19 by multivariate logistic regression analysis, critical illness can be predicted through the sensitivity and false specificity of a ROC curve with an error rate of 10.3% and AUC of 94.2% by only two factors: serum zinc value (P = 0.020) and LDH value (P = 0.026).

Conclusions: Proper management of the prediction results in this study can contribute to establishing and maintaining a safe medical system, taking the arrival of the second wave, and the spread of COVID-19 in the future into consideration.

Keywords: COVID-19; Critical illness; Japan; Logistic regression analysis; Predictive factors; Serum zinc.

Figure 1

Comparison of serum zinc concentrations in patients with COVID-19 (n = 29) between the mild/moderate and severe (intubation) conditions. Statistical significance: p < 0.01 by Student-t test. The central red lines correspond to the mean values, and the upper and lower red lines correspond to the means + standard deviation (SDs) and means – SDs, respectively. The dotted line denotes the threshold concentration of hypozincemia as 70 μg/dL.

Figure 2

Colinear relationship between the serum ferritin and LDH values in all patients (n = 62) with moderate correlation (r = 0.633, P < 0.001). Collinearity between the data of serum ferritin and LDH was statistically recognized because both parameters would be increased by the infection and inflammation.

Figure 3

Receiver operating characteristic (ROC) curve for all patients with COVID-19 (n = 62) by LDH and ages.

Figure 4

Receiver operating characteristic (ROC) curve for patient subgroups with COVID-19 (n = 29) by LDH and serum Zn.

Figure 5

Time-dependent changing profiles of serum zinc concentrations in four critically ill (severe) patients after pathogenesis of COVID-19. These patients were monitored continuously for one month after pathogenesis, treated with enteral nutrition delivered from the tube inserted through the nose. The dotted line denotes the threshold concentration of hypozincemia as 70 μg/dL.