Vitamin D levels and clinical outcomes of SARS-CoV-2 Omicron subvariant BA.2 in children: A longitudinal cohort study

Abstract

Objective: To investigate the picture between vitamin D levels and clinical outcomes of SARS-CoV-2 Omicron subvariant BA.2 in children.

Methods: A retrospective, longitudinal cohort study was performed. All included hospitalized cases were divided into the sufficient (sVD) and insufficient vitamin D (iVD) groups according to whether their serum 25-hydroxyvitamin D [25(OH)D] concentration was ≥30 ng/mL. Dynamic changes in clinical parameters were observed for seven time periods within 28 days after admission.

Results: Serum 25(OH)D concentrations were significantly negatively correlated with age in the included cases (r = -0.6; P < 0.001). Compared with the iVD group (n = 80), the sVD group (n = 36) had higher interleukin-6 (18.4 vs. 12.9; P = 0.003) within the first day; higher procalcitonin within the first (0.15 vs. 0.1; P = 0.03), 2-3 (0.14 vs. 0.07; P = 0.03), 4-5 (0.21 vs. 0.07; P = 0.02) days; more lymphocytes within the first (1.6 vs. 1.2; P = 0.02), 2-3 (3.7 vs. 2; P = 0.001), 4-5 (3.9 vs. 2.1; P = 0.01) and 6-7 (4.9 vs. 2.7; P = 0.02) days; notably, higher cycle threshold for N gene (30.6 vs 19.8; P = 0.03) or ORF1ab gene (31.4 vs 20.1; P = 0.03) within 2 to 3 days. Pneumonia lesions were found in eleven and six cases in the iVD and sVD groups, respectively, without significant difference on computed tomography at admission. Six out of eleven and five out of six had a repeat computed tomography after 1-2 weeks. Lesion improvement was more significant in the sVD group (P = 0.04).

Conclusions: Children with vitamin D insufficiency might have poorer clinical outcomes in Omicron subvariant BA.2 infection, especially in older pediatric patients. Further studies are needed to assess effectiveness of supplements in reducing the same.

Keywords: BA.2; Omicron; SARS-CoV-2; children; subvariant; vitamin D.

Figure 1

Flow chart of the pediatric cases selection and analysis process.

Figure 2

Spearman correlation analysis of serum 25(OH)D concentrations with other clinical parameters, r represents the correlation coefficient. The red dots in B, C, E, F represent outliers. APTT, activated partial thromboplastin time; CT, cycle threshold; IL-6, interleukin-6; PT, prothrombin time; WBC, white blood cell. (A) age; (B) SARS-CoV-2 IgM; (C) lymphocytes; (D) platelets; (E) IL-6; (F) procalcitonin. Equation: (A) Y = −0.276*X + 15.1; (B) Y = −0.03*X + 1.51 (Outlier included); Y = −0.012*X + 0.88 (Outlier excluded); (C) Y = 0.035*X + 0.81 (Outlier included); Y = 0.031*X + 0.86 (Outlier excluded); (D) Y = 0.76*X + 212; (E) Y = 0.38*X + 7.85 (Outliers included); Y = 0.25*X + 9.8 (Outliers excluded); (F) Y = 0.006*X + 0.11 (Outliers included); Y = 0.003*X + 0.13 (Outliers excluded).

Figure 3

Dynamic changes in laboratory results for seven time periods from T₁ to T₇ within 28 hospitalization days after admission. T₁ to T₇ represent the following: T₁ ≤ 1 day; 1 < T₂ ≤ 3; 3 < T₃ ≤ 5; 5 < T₄ ≤ 7; 7 < T₅ ≤ 14; 14 < T₆ ≤ 21; 21 < T₇ ≤ 28 days. The red line represents the iVD group, n = 8–80 per condition. The blue line represents the sVD group, n = 4–36 per condition. Points on the line chart represent mean or median. (A) N gene cycle threshold; (B) ORF1ab gene cycle threshold; (C) white blood cells; (D) lymphocytes; (E) interleukin-6; (F) procalcitonin; (G) platelets; (H) D-dimer; (I) fibrinogen.

Figure 4

The COVID-19 pneumonia lesions included ground-glass opacity (GGO), consolidation (CO), and nodular opacities were identified and measured by AI and radiologists. The differences in the ratio of total lesion volume to total lung volume in computed tomography at admission (not significant) and 1–2 weeks later (P = 0.04) were compared between the iVD (A) and sVD (B) groups.