Clinical characteristics on admission
A cohort of 78 patients who were hospitalized at Jining Infectious Disease Hospital, Jining City, Shandong Province, China, between January 24 and March 1, 2020 were recruited. All patients were diagnosed with COVID-19 pneumonia by a positive SARS-CoV-2 nucleic acid test. As shown in Table 1, the median age of patients was 43.82 ± 15.91 years, and males accounted for 76.9%. Of 78 patients, 6 (7.7%) cases developed into a severe type. As for comorbidities, there were no significant differences in the percentages of hypertension, diabetes, cardiovascular disease, tumor, cerebrovascular disease, and lung disease between the moderate and severe cohorts (all P > 0.05). We surveyed smoking habits and alcohol consumption in all patients,. No significant differences were found in term of the sex percentage, coexisting disorders, smoking, or alcohol consumption between these two groups (all P > 0.05).
Among the clinical symptoms including fever, shortness of breath, dry cough, fatigue, sputum production, gastrointestinal symptoms, hemoptysis, myalgia, headache, pharyngodynia, and rhinobyon, the top five common symptoms were fever (80.8%), followed by dry cough (46.2%), gastrointestinal symptoms (17.9%), fatigue (14.1%), and shortness of breath (10.3%) in the total patient population. The mean age of the severe group was not different from that of the moderate cohort. We noted that shortness of breath and fatigue appeared more frequently in the severe cohort than in the moderate cohort (50% vs. 6.9%, P = 0.013; 50% vs. 11.1%, P = 0.034).
As compared to patients with moderate disease, the severe patients had a higher level of white blood cells (WBC) [8.35 (5.73-13.15) vs. 5.16 (4.15-6.46) × 109/L, P = 0.008], neutrophil percentages [86.95 (76.9-91.88) % vs. 55.2 (48.08-65.35) %, P < 0.001], neutrophil counts [6.47 (5.1-11.09) vs. 2.84 (2.08-3.88) × 109/L, P = 0.001], and C-reactive protein (CRP) [58.08 (19.26-90.37) vs. 0.54 (0.50-4.06) mg/L, P < 0.001], but lower levels of lymphocyte percentages [9.0 (4.08-13.38)% vs. 31.65 (22.6-39.95)%, P < 0.001], lymphocyte counts [0.74 (0.42-1.31) vs. 1.57 (1.18-1.89) × 109/L, P = 0.002], and platelets [185 (79-230.75) vs. 243.75 (195.0-308.75) × 109/L, P = 0.022] (Table 2). According to the parameters from the peripheral blood routine tests, we then calculated the neutrophil to platelet ratio (NPR), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR), in order to further investigate the factors related with illness severity between the mild and severe groups. Notably, indices including NPR [4.64 (2.40-11.44) vs. 1.24 (0.88-1.67), P < 0.001] and NLR [9.79 (5.87-22.96) vs. 1.72 (1.17-2.77), P < 0.001] were significantly increased in severe patients as compared to those in moderate cases.
Compared to the patients in the moderate group, severe patients were more susceptible to hepatic insufficiency, as indicated by the elevation of aspartate aminotransferase (AST) [33.5 (23.75-68) vs. 21 (18-27) U/L, P = 0.004] and lactate dehydrogenase (LDH) [389.5 (241.5-497.5) vs. 197.5 (160.25-229.75) U/L, P = 0.002], and the decreased albumin concentration [35.5 (32.75-38.25) vs. 42 (39-44) g/L, P = 0.003]. In addition, severe patients also showed more frequently disturbed blood electrolytes and impaired glucose, as demonstrated by the reduction of sodium [136 (134.25-137.5) vs. 141 (139-143) mmol/L, P = 0.001] and calcium [96.5 (93.75-98) vs. 100 (97-102) mmol/L, P = 0.015], and the increased glucose level [6.2 (5.63-11.5) vs. 4.9 (4.4-5.6) mmol/L, P = 0.007] (Table 2).
Factors associated with disease severity
For all the demographic data, clinical characteristics, and laboratory data, our analyses revealed that the severe group had significant higher proportions of patients showing shortness of breath, fatigue, neutrophil percentages > 70%, neutrophil counts > 6.3 × 109/L, lymphocyte percentages < 20%, lymphocyte counts < 1.0 × 109/L, platelet < 100×109/L, CRP > 10 mg/L, NPR > 2.3, NLR > 3.9, AST > 40 U/L, albumin < 40 g/L, LDH > 245 U/L, and glucose > 6.1 mmol/L than that the moderate cohort (Table 1, Table 2). Therefore, our findings suggest that these factors might be associated with the disease severity of patients with COVID-19 pneumonia.
To further investigate the risk factors related with illness severity of COVID-19 pneumonia patients, we performed a case-control study at a ratio of 2:1. We selected 12 sex-, age- and underlying comorbidity-matched patients from the moderate patient group and matched them with 6 severe cases. The ages of the moderate patients were the same or ± 2 years as matched to each severe case, as many of the moderate patients were younger. As shown in Table 3, we found no significant differences in the demography and clinical presentation between severe patients and the matched case-control severe cases. Contrary to the moderate patients, there were significantly elevated concentrations of WBC, neutrophil percentages, neutrophil counts, CRP, and LDH in severe cases; while there were reduced levels of lymphocyte percentages, lymphocyte counts, NPR, NLR, albumin, and sodium in severe patients (Table 4). Table 3 and Table 4 show that the matched case-control severe cases had higher percentages of neutrophil percentages > 70%, neutrophil counts > 6.3 × 109/L, lymphocyte percentages < 20%, NPR > 2.3, NLR > 3.9, albumin < 40 g/L, and LDH > 245 U/L than those in the moderate cohorts.