3.1 Demographics and clinical characteristics
3.1.1 Strain and age distribution characteristics in the two waves of pandemic
These data show that 99.5% of the outbreaks in Xi'an from 2021 to 2022 were Delta strain and 5% were Omicron strain (Fig 3, A). Among the 99.5% delta strains, 87.3% were patients over 18 years old, while 12.2% were patients under 18 years old (Fig 3, B). However, the outbreaks in Wuhan from 2019 to 2020 were wild-type strain (WT strain), of which 99.7% were patients over the age of 18, while only 0.3% were patients under the age of 18 (Fig3, C).
3.1.2 Clinical analysis of 5 patients with Omicron strain
There were only 5 cases of Omicron strain in the epidemic in Xi'an. They have flown or been to the airport in the previous 14 days (Table 2). 20% (1/5) of patients were aged 60 years or greater, 60% (3/5) were female, and none had comorbidity. Five cases completed full vaccination. Among them, 20% (1/5) were asymptomatic cases, 40% (2/5) were mild cases, 40% (2/5) were moderate cases. The most common symptoms within three days on admission was cough and sore throat (respectively, 40%), followed by fever, sputum, and shortness of breath (respectively, 20%). 60%（3/5） of the patients had chest CT changes, such as consolidation, reticulations or ground glass opacity. The first nucleic acid test of all patients was positive almost at the same time, and they all produced antibodies. The hospital stay was 15-34 days.
3.1.3 Clinical typing characteristics in the two waves of pandemic.
Most of the outbreaks in Xi'an from 2021 to 2022 were mild and moderate (40.9% and 56.6%, respectively), of while severe and critical are very rare (1.6% and 0.9%, respectively) (Fig. 4 A). As of the time of data statistics, 0.3% of the critically ill patients were recovered, while 0.6% relied on life-support machine (Fig. 4B). Most of the outbreaks in Wuhan from 2019 to 2020 were severe and moderate (24.2% and 72.0%, respectively), of while mild and critical are less (0.70% and 3.10%, respectively) (Fig. 4C). In critically ill patients, 1.3% of the patients were recovered, while 1.80% were died (Fig. 4D). Compared with the epidemic in Wuhan two years ago, the epidemic in Xi'an is dominated by mild and moderate types, while there are few severe and critical cases (Fig. 4E).
The relationship between age and clinical classification was further analyzed. Among the COVID-19 over 18 years old, the cases were mainly WT strain and delta strain cases of moderate, while mild and severe was less (Fig 3, DE). Moreover, the age of the WT strain cases was 50-60 years, while the age of the Delta strain cases was mainly 30-49 years old in the novel coronavirus pneumonia patients (Table 1). Among the COVID-19 under 18 years old, the cases were mainly delta strain cases of mild and moderate, while wild type was very rare (Fig 3, FG) and no severe or critical cases, regardless of infection with the wild-type strain or Delta VOC.
3.1.4 Gender and comorbidity characteristics in the two waves of pandemic.
Patients infected with the Delta VOC and those infected with the wild-type strain shared similar distribution of gender. Among patients older than 18 years, there was no gender difference between the two cohorts, regardless of the severity of the disease. Compared with patients in delta strain group, the basic diseases, such as hypertension, diabetes mellitus, chronic respiratory diseases, coronary heart disease, chronic liver disease, tuberculosis, malignant tumor and so on, were significantly different in patients with moderate type in the wild-type cohort (P＜0.001), but there was no significant difference in other types (Table 1). Among them, the proportion of diabetic patients in the former group was significantly lower than that in the latter group (2.4% vs 19.1%; p < 0.001).
3.1.5 Clinical symptoms and radiological findings
Main clinical symptoms of mild, moderate, and severe cases at the onset of illness are shown in Table 3. The most common symptoms were fever, cough, chest tightness/dyspnea, muscle aches and fatigue. Compared with patients with Delta strain, the proportion of muscle aches and fatigue in patients with WT strain increased significantly in all three types (P＜0.05). Of course, fever, cough and Chest tightness/dyspnea are very high in the two cohort.
Radiologic findings were derived from the electronic medical charts. Chest CT was the primary source of radiologic assessment and was performed within three days of admission, and abnormalities in chest CT images were detected in all patients. Of the 3129 patients, 1666(73.5%) WT strain patients and 521(60.4%) delta patients had multiple ground glass in both lungs, while the patchy shadows and consolidation are less. Further analysis revealed that the proportion of consolidation in the Delta VOC cohort was significantly more than that in the wild-type cohort (11.5% vs 1.7%; p < 0.001) (Table 3).
3.1.6 Laboratory findings
Patients with severe and critical illness are our focus. Therefore, the blood tests of the patients during their hospitalization were collected at admission, 25%, 50%, 75% and discharge (Fig. 2). The results showed that there were differences in lymphocytes, CRP, and ALT at many time points in the two cohorts (Table 4-5; Fig. 5BCE). Compared with cases infected with the wild-type strain, the CRP and ALT of patients with infection delta VOC were significantly higher (Fig. 5CE; p＜0.05), while their lymphocytes were similar (Fig. 5B; p＞0.05), and the CRP and lymphocytes of these two cohorts gradually returned to normal after treatment (Fig. 5BC; p＜0.05), among the severe cases. However, no differences in leukocytes, D-Dimer and BUN were found between the two cohorts in the severe patients (Fig. 5ADF; p＞0.05)). In the next analysis, patients infected with the delta VOC showed significant difference in leukocytes, lymphocytes, CRP, D-Dimer, and BUN among the critical cases when compared with them of patients infected with the wild-type strain. Compared with recovered patients infected with the wild-type strain and delta VOC, the leukocytes, D-Dimer and BUN of dead patients with the wild-type strain and machine supported patients with infection delta VOC were significantly higher (Fig. 6ADF; p＜0.001), while their lymphocytes have been at a relatively low level (Fig. 6B; p＜0.001), and they have not recovered returned to normal after treatment. Further analysis revealed that leukocytes, CRP, D-Dimer and BUN of dead patients with the wild-type strain were very high (Fig. 6ACD; p＜0.001), while ALT was no significant difference, in these four groups (Table 4-5; Fig. 6E; p＞0.05).
3.2 The risk factors for disease progression and outcomes
The univariate Cox regression analysis revealed that the strain, comorbidity (including chronic respiratory disease, hypertension) and symptoms (including cough) were associated with the deterioration to critical illness (p < 0.05). Multivariate Cox regression analysis indicated that delta VOC infection (HR 2.54[95%CI 1.279-5.026]) and chronic respiratory disease (HR 1.97[95%CI 1.15-3.38]) were the independent risk factors associated with the deterioration to critical illness (p < 0.05; Table 6). The Cox regression survival plots for the time from symptom onset to critical status categorized by chronic respiratory disease and virus lineage (Delta VOC vs wild-type strain) in the two cohorts were shown in Fig. 7A and B.