SARS-CoV-2 omicron variant clearance delayed in breakthrough cases with elevated fasting blood glucose

Baseline characteristics of patients with COVID-19

Among the 239 patients with COVID-19, 52 were excluded because of the undefined history of the vaccine. Data from 187 patients were analyzed, including 73 patients who had two doses of vaccine injection and 114 patients who received three doses. The duration from the first, second, and third vaccine injections to infection was defined as T1, T2, and T3, respectively. Only 5 patients had a T2 < 6 months, and none of the patients had a T3 < 1 month.

For comorbidity, 3 patients had chronic hepatitis B, 8 had diabetes, 17 had hypertension, 1 had pulmonary tuberculosis, and 1 had chronic kidney disease. None of the patients was administered glucocorticoid or immunosuppressor at admission or during hospitalization.

A total of 43 patients had elevated fasting blood glucose (≥ 6.1 mmol/L) at admission, among whom 7 patients had a diabetes history, and 1 patient was diagnosed with diabetes during hospitalization. Among the 35 patients who were not diagnosed with diabetes, the fasting blood glucose in 17 patients decreased to a normal level in a week without any hypoglycemic treatment, and 18 patients with slightly elevated glucose (≥ 6.1 mmol/L and < 7.5 mmol/L) did not undergo a repeat test. In addition, only 9 patients had a glucose ≥ 7.9 mmol/L at admission, and 4 patients had a normal glucose level in a week and were excluded from diabetes.

Fever was the most common symptom (125/187, 66.8%), and most patients (123/125, 98.4%) had a fever duration of < 7 days. Other symptoms included cough (30/187, 16.0%), pharyngalgia (22/187, 11.8%), muscular soreness (9/187, 4.8%), headache (9/187, 3.2%), and diarrhea (6/187, 3.2%). According to CT scans, 13 individuals were diagnosed with unilateral pneumonia and 6 with bilateral pneumonia, while none developed severe pneumonia or ARDS. The median duration of SARS-CoV-2 RNA-positivity was 9 days, and the difference between patients with two and three doses of vaccine injection was insignificant (Z = 0.356, P = 0.722).

Characteristics of patients with and without SARS-CoV-2 clearance on day 7

As shown in Table 1, 65 (34.8%) patients had an undetectable RNA test on day 7. No significant difference was detected in age, diabetes, T1, T2, and duration of fever between patients with and without SARS-CoV-2 clearance. Patients with viral clearance on day 7 had a lower glucose level than those with a positive RNA test (Z = 3.943, P < 0.01). In addition, neutrophils were higher, while the lymphocyte and platelet counts were lower in patients with a positive RNA test than those with a negative RNA test (Z = 2.160, 2.014, and 2.114, respectively; P < 0.05). Moreover, CD4+ T lymphocytes were higher in patients with viral clearance on day 7 (Z = 2.647, P < 0.01).

Table 1 Characteristics of patients with and without SARS-CoV-2 on day 7Risk factors for SARS-CoV-2 RNA positivity on day 7

As shown in Table 2, the univariable logistic analysis showed that baseline glucose, uric acid, lymphocyte count, platelet count, and CD4+T lymphocyte count are associated with SARS-CoV-2 RNA positivity on day 7. Then, multivariable analysis showed that baseline glucose and CD4+T lymphocytes count were independent risk factors for SARS-CoV-2 RNA positivity on day 7 (odds ratio (OR) = 0.631 and 1.001, 95% confidence interval (CI): 0.456–0.874 and 1.000–1.002, P < 0.01 and P = 0.02, respectively).

Table 2 Risk factors for SARS-CoV2 clearance on day 7

More patients had a glucose level ≥ 6.1 mmol/L at admission in the RNA-positive group (35/122, 28.7%) compared to those in the RNA-negative group (8/65, 12.3%) (χ2 = 6.426, P = 0.01). Then, the multivariable analysis used glucose ≥ 6.1 mmol/L as a categorical value, and the data showed that glucose ≥ 6.1 mmol/L and CD4+ T lymphocytes count were independent risk factors for SARS-CoV-2 RNA-positivity on day 7 (OR = 0.351 and 1.001, 95% CI: 0.150–0.825 and 1.000–1.002, P = 0.02 and P = 0.01, respectively).

Characteristics of patients with and without SARS-CoV-2 clearance on day 14

As shown in Table 3, most patients had an undetectable RNA test on day 14 (163/187, 87.2%). Patients with viral clearance at day 14 had higher uric acid levels and lymphocyte counts than those with a positive RNA test (Z = 2.997 and 2.084, P < 0.01 and = 0.04, respectively). The CD4+ and CD8+ T cell count was high in patients with viral clearance (Z = 2.382 and 2.094, both P < 0.05).

Table 3 Characteristics of patients with and without SARS-CoV-2 on day 14Risk factors for SARS-CoV-2 RNA positivity on day 14

As shown in Table 4, the univariate logistic analysis showed that baseline uric acid, lymphocyte count, platelet count, and CD4+ and CD8+ T lymphocyte count were associated with SARS-CoV-2 RNA-positivity on day 14. Then, multivariate analysis showed that only baseline uric acid is the independent risk factor for SARS-CoV-2 RNA positivity on day 14 (OR = 1.008, 95% CI: 1.002–1.014, P = 0.01).

Table 4 Risk factors for SARS-CoV2 clearance on day 14

Adjusted multivariable analysis was conducted when CD4+ and CD8+ T lymphocyte count was deleted, and data showed that uric acid is the only independent risk factor for SARS-CoV-2 RNA positivity on day 14.

Correlation between glucose, uric acid, CD4 +T, and CD8 +T cell count

As shown in Fig. 1, baseline glucose was negative with uric acid, lymphocyte count, CD4+ T cell count, and CD8+ T cell count (all P < 0.05), while uric acid was positively correlated with CD4+ T cell and CD8+ T cell count (both P < 0.05). In addition, there was a positive correlation between CD4+ T and CD8+ T cell count (r = 0.710, P < 0.01).

Fig. 1figure 1

Correlation between serum glucose, uric acid, CD4+T and CD8+T cells count in Omicron variant infected patients

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