To investigate the influence of cold agglutination caused by severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2) infection on routine blood parameters and the effect of 30 min correction at 37 ℃, and to improve the accuracy of routine blood test results.

From December 26th, 2022 to January 17th, 2023, a total of 2 875 blood routine samples of patients infected with SARS-CoV-2 were collected from the First People’s Hospital of Tianmen, which were classified as the coronavirus disease 2019 (COVID-19) group. Total of 50 influenza patients with SARS-CoV-2 nucleic acid negative were selected as the control group, while 28 072 inpatients with SARS-CoV-2 nucleic acid negative were selected as the non-COVID-19 group from August to November 2022, and the COVID-19 group was further divided into the cold agglutination group (54 cases) and the non-cold agglutination group (2 821 cases). The COVID-19 group was divided into four groups: light, medium, severe and critical groups. According to the mean corpuscularhemoglobin concentration (MCHC) results, the cold agglutination group was divided into the strong cold agglutination group (> 380 g/L) (32 cases) and the weak cold agglutination group (≤ 380 g/L) (22 cases). The cold agglutination specimens were warmed at 37 ℃, and the changes of blood routine parameters in each group before and after the correction were compared.

The cold agglutination rate of the COVID-19 infected group was 1.88% (54/2 875) compared with that of the non-COVID-19 group [0.071% (20/28 072)], the difference was statistically significant (χ² = 356.97, P < 0.001). There were no significant differences in white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT) and platelet (PLT) between COVID-19 infected patients and non-COVID-19 infected patients (Z = -1.680, t = 1.376, t = 1.069, t = 1.127, Z =-0.532; P = 0.093, 0.185, 0.299, 0.274, 0.601); The differences of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and MCHC were statistically significant (t =-3.194, Z = -3.622, -2.435; P = 0.005, < 0.001, 0.015). The incidence of cold agglutination in mild, medium, severe and critical COVID-19 patients was 0.18% (4/2 242), 3.96% (18/455), 17.88% (27/151) and 18.52% (5/27), respectively, with significant difference (Z = 260.40, P < 0.001). Comparison between moderate and mild, severe and light, critical and light, and severe and medium showed statistically significant differences (χ² = 97.97, 18.87, 20.66, 93.85; all P < 0.001). There were no significant difference between severe and medium type, severe and critical type (χ² = 3.068, P = 0.08; χ² = 1.06, P = 0.937). The cold agglutination group samples were all corrected after incubation at 37℃ for 30 min, and there were significant differences between WBC, RBC, HCT, MCV, MCH and MCHC before and after correction (Z =-4.953, t = 10.137, t = 8.614, t =-6.307, t =-4.918, Z =-6.334; all P < 0.001), PLT (Z =-1.317, P = 0.188), HGB (t = 0.212, P = 0.833) had no significant difference. There were also significant differences between WBC and PLT before and after incubation in strong condensing group (MCHC > 380 g/L) (Z =-4.283, -3.489; both P < 0.001), but there was no significant difference in PLT before and after mild condensation group (Z =-1.923, P = 0.054).

Patients with COVID-19 are prone to cold agglutination, and the condensation increased with the severity of the disease. Besides affecting erythrocyte parameters, cold agglutination may also lead to lower level of WBC and PLT. Therefore, timely correction of COVID-19 cold agglutination can improve the accuracy of blood routine test results.