Baseline clinical characteristics of patients with COVID-19
The age of patients with COVID-19 was 46.17 ± 14.39, and 60.4% patients were male. The mean of the time from onset to hospitalization (TOH) was 5 days. Among the 106 COVID-19 patients, 83 (78.3%) patients had a clear exposure history, and 33 (31.1%) patients had one or more comorbidities. The most frequent comorbidity was bacterial infection (11.3%), followed by diabetes (9.4%) and hypertension (7.5%). As expected, fever (91.5%), dry cough (43.4%), and chest tightness (32.1%) were the top three frequent symptoms. Chills (20.8%), fatigue (19.8%), and sore throat (18.9%) were also common, but rhinorrhea or rhinobyon (5.7%), diarrhea (6.6%), and myalgia (7.5%) were relatively rare in COVID-19 patients (Table 1).
Independent indictors for severe COVID-19
As shown in Table 1, univariate logistic regression indicated that the TOH of severe patients was significantly longer than of mild patients [7 (4 - 10) vs. 4 (2 - 7) days; p = 0.011]. The frequency of comorbidities in severe patients was higher than mild patients (45.5% vs. 24.7%; p = 0.035). The frequency of sputum production, chest tightness, or polypnea was higher in severe patients than mild patients (all p < 0.05). The level of C-reactive protein, as well as levels of direct bilirubin, γ-glutamyl transpeptidase, lactate dehydrogenase, and D-dimer were significantly higher in severe patients than mild patients (all p < 0.05). However, the levels of lymphocyte count and albumin were significantly lower in severe cases compared to mild cases. Multivariate logistic regression showed that chest tightness, lymphocyte count, and γ-glutamyl transpeptidase were the independent indictors to predict severe COVID-19.
Lymphocyte subsets in severe COVID-19 patients
Giving the lymphocyte count was an important indicator to predict severe COVID-19, we further investigated the alteration of lymphocyte subsets in patients with severe COVID-19. As shown in Figure 1A, the T cell count in severe patients was significantly lower than that in mild patients [487.00 (291.50, 819.50) vs. 766.00 (525.50, 1036.50) /μL; p = 0.004]. The CD4+ T cell and B cell counts in severe patients were also significantly lower than that in mild patients [272.00 (177.00, 497.50) vs. 455.00 (283.50, 612.50) and 92.00 (57.50, 160.00) vs. 136.00 (82.50, 213.00) /μL; p = 0.003 and 0.046, respectively]. There is no significant difference for CD8+ T cell or NK cell count between severe and mild patients. The difference of CD4+ to CD8+ ratio between severe and mild patients was not significant. No significant difference for proportion of lymphocyte subset was observed between severe and mild patients (Figure 1B).
Lymphocyte subsets alterations with CT manifestation
In order to assess the manifestation of lesions in lung CT, present study simply scored the number, quadrant, and area of lesions. For the number of lesions, patients were classified to 3 subgroups named patients with no lesion, ≤3 lesions, and >3 lesions. For the quadrant of lesions, patients were classified to 3 subgroups, that is, patients with no quadrant, ≤3 quadrants, and >3 quadrants. For the area of the maximum lesion, patients were classified no infiltration when there is no lesion in CT. patients with minor and major infiltration were classified when the area of the maximum lesion were ≤100 cm2 and >100 cm2 respectively. As shown in Figure 2A-C, the lymphocyte counts were gradually decreased with the increased number, quadrant, or area of lesions (p = 0.002, 0.002, and <0.001 respectively). No significant trend of absolute count of any lymphocyte subset was observed with the increase of lesion number (Figure 3A). Only the T cell count was gradually decreased with the increase of infiltrated quadrants [919.50 (699.00, 1274.75), 715.00 (452.00, 1020.50), and 607.00 (398.00, 912.00) /μL, p = 0.043] (Figure 3B). The T cell, CD4+ T cell, and CD8+ T cell counts were gradually decreased with the increase of infiltrated area [919.50 (699.00, 1274.75), 724.00 (487.00, 1021.00), and 494.00 (263.00, 796.00) /μL, p = 0.002 for T cell; 547.00 (428.75, 835.00), 411.00 (266.00, 587.00), and 325.00 (173.00, 501.00) /μL, p = 0.003 for CD4+ T cell; 292.00 (217.00, 351.75), 228.00 (128.00, 359.00), and 158.00 (83.50, 283.00) /μL, p = 0.028 for CD8+ T cell; respectively] (Figure 3C). However, the trend of CD4+ to CD8+ ratio was not significant no matter with the increase of the number, quadrant, or the area of lesions. For proportion, there is also no significant trend of any lymphocyte subset with aggravated CT manifestation (Figure 3D-F).
Lymphocyte subsets alterations with TOH
The lymphocyte counts were gradually decreased with the increased TOH (p < 0.001, Figure 2D). Lymphocyte subsets analysis showed that the T cell count, as well as CD4+ T cell, and CD8+ T cell counts were gradually decreased with the increased TOH [736.50 (541.50, 1022.00), 764.00 (495.00, 1016.50), 512.00 (227.00, 950.00), 425.00 (136.00, 694.00), p = 0.003 for T cell count; 481.00 (303.25, 596.00), 404.00 (243.25, 546.00), 259.00 (131.00, 707.00), 272.00 (96.00, 502.00), p = 0.002 for CD4+ T cell count; 250.00 (140.75, 345.75), 238.00 (158.75, 378.00), 200.00 (63.00, 370.00), 75.00 (45.00, 180.00), p = 0.013 for CD8+ T cell count]. The NK cell count was also gradually decreased with the increased TOH [120.50 (88.00, 218.75), 111.50 (86.25, 175.25), 93.00 (48.00, 180.00), 69.00 (61.00, 110.00), p = 0.012] (Figure 4A). There is no significant trend of CD4+ to CD8+ ratio with the delayed hospitalization. The proportion of T cell was gradually decreased with the increased TOH [74.25 (67.33, 79.35), 75.85 (62.93, 80.88), 67.20 (56.60, 79.30), 61.70 (54.00, 68.50), p = 0.031], but the proportion of B cell was gradually increased with the increased TOH [11.70 (8.85, 17.05), 11.25 (7.48, 17.35), 17.80 (13.60, 23.50), 17.40 (13.40, 26.30), p = 0.003] (Figure 4B).