It has been reported that about 70%-85% of COVID-19 patients have a mild form of disease, a self-limiting disease, while approximately 15%-30% of patients have a severe form of disease [17–19]. Most of mild patients can heal themselves, while severe patients need medical intervention. If some clinical or imaging indicators can differentiate them, it will help clinicians choose more beneficial treatment regimens. In this study, 20.4% of patients were severe after admission to the hospital, receiving ICU care, while 79.6% of patients were non-severe, receiving general therapy (i.e. supportive therapy, oxygen therapy, antiviral and antibiotic therapy). Our results indicated that some laboratory and imaging indicators of COVID-19 patients in severe group can be distinguished from those in non-severe group. And we semi-quantitatively evaluated the extent of involvement of the lesion and found that it was related to many indicators of laboratory testing.
In our study, most hospitalized patients with COVID-19 pneumonia were elderly. There was no obvious predilection for sex and underlying disease in full cohort, consistent with previous reports (17). The epidemiological history showed that patients with a close contact accounted for only 7.4%, while patients with familial aggregation accounted for 24.1%. It suggested that the confirmed patients should be strictly isolated from their families, and the isolation measures similar to the shelter hospital may curb the spread of the epidemic. Patients with underlying diseases accounted for half of the cases, higher than reported literatures (5, 18), which may be related to the fact that most of the patients in our cohort were elderly. Fever, cough, sputum production, dyspnea and short of breath were the most common symptoms in patients with COVID19 pneumonia, indicating that the receptor of target cells of might be primarily located in the lower airway, consistent with reported literature (5, 17, 18, 20). However, the intestinal symptoms such as diarrhea seemed more prominent in our cohort than previously reported, which may be related to the difference in the route of infection and the course of disease.
Our results showed that there was no obvious difference in age, gender and underlying diseases between the two groups, but previous studies showed that patients with severe disease were generally older, and had a greater number of underlying diseases than those with non-severe disease [17, 18]. These results may be related to the insufficient sample size. Compared with non-severe group, some laboratory indicators such as the leukocyte count, neutrophil count, NLR and the percentage of neutrophils were higher in severe patients, which may indicate that severe patients may be associated with other microbial infections, such as bacterial infection. In addition, neutrophilia may be related to cytokine storm induced by virus invasion. The percentage of lymphocytes was lower in severe patients, which may be due to the increased proportion of neutrophils. The lymphocyte count of the two groups decreased, but there was no significant difference between two groups. In general, the lymphocyte count of viral infection increased, but SARS-CoV-2 infection, similar to severe acute respiratory syndrome (SARS) (21, 22) and the Middle East respiratory syndrome (MERS) (23, 24), also caused the lymphopenia of peripheral blood. In the published literature, most patients had the normal ALT and AST and increased LDH in the whole cohort, consistent with previous reports (17, 18). However, the levels of ALT, AST and LDH of severe patients were higher than those of mild patients, which were inconsistent with our studies. Some researchers believed that virally induced cytotoxic T cells and the induction of a dysregulated innate immune response were a more probable explanation for the association between deranged liver markers and COVID-19 disease severity (25).
Chest CT has a high sensitivity for diagnosis of COVID-19 pneumonia (25). It can be used in the early screening of highly suspected cases, especially for the patients whose PCR are negative for the first time. Our study showed ground-glass opacities (100%), consolidation (92.6%), reticulation (66.7%), traction bronchiectasis (57.4%), mixed pattern (57.4%) and architectural distortion (53.7%) are the most common imaging findings. These features may correspond to the alveolar exudation combined with fibroblasts proliferated in the alveolar cavity and interstitium. It suggests that the inflammatory process of injury and repair occur simultaneously in the lesions. However, unlike other published studies (13, 14, 27), our study showed that the frequency of consolidation and reticulation is higher. This may be related to the long course of infection leading to organic pneumonia. That is, with the increase of time course, the frequency of reticulation and consolidation increase in our study. This study showed that architectural distortion was more likely to be seen in severe patients, and traction bronchiectasis has a high frequency in severe patients. These findings may indicate pulmonary fibrosis. A follow-up study of patients recovering from SARS showed that traction bronchiectasis was recoverable at 114 days after symptom onset and did not certainly represent irreversible fibrosis (28). It is not known whether these signs in severe patients with COVID-19 represent irreversible fibrosis and further follow-up research is needed. Tree-in-bud sign may be due to infectious bronchiolitis in our study. The frequency of tree-in-bud sign is very low, different from H1N1 influenza A pneumonia (29), which may serve to distinguish SARS-CoV-2 from other types of viral pneumonia. Our research showed that consolidation-dominant pattern and air bronchogram are more common in severe patients, suggesting alveolar exudation is still predominant. There was a high virus load in the body at this time, then alveolar macrophages engulf the virus in large quantities, and lung tissue damage is dominant. Pleural effusion suggested poor prognosis in many studies about COVID-19 (10, 14), consistent with our study. Previous studies also showed that the presence of pleural effusion in patients infected with MERS was a poor prognostic indicator (30). For lesion distribution, patients with COVID-19 tended to have peripheral distribution (64.8%), bilateral involvement (98.1%), diffuse distribution in craniocaudal plane (51.9%), and be diffuse in numbers (94.4%), which were consistent with results of previous studies except for lower lung zone distribution (10). The severe patients were usually more diffuse in axial distribution, that is, inferior one-thirds of the lung zone was also affected, indicating that inflammation spreads from the periphery to the central lung. CT score was higher in severe patients, suggesting that the affected lungs are more extensive in severe patients, consistent with many studies (10, 14). Our study revealed CT score was associated with a number of laboratory indicators, it’s probably because they're all related to the severity of the disease. The significance of this result is that if the laboratory indicators change during the follow-up after treatment, it seems that the laboratory indicators can be used instead of frequent CT examination to assess the severity of the disease. The laboratory indicators are more convenient to obtain, and the radiation dose of CT can be reduced correspondingly.
There are some limitations in our study. First, due to the small sample size of severe patients, it may cause selection bias. Second, the time-interval between laboratory testing and the CT examination was variable, which may limit the ability to determine the relationship between laboratory tests and CT score. However, the median time-interval between laboratory testing and the CT scan was 4 day, during this time interval, it may not cause major changes in indicators. Third, because the diagnosis standard of severe pneumonia is not uniform, it can cause reference test bias. Finally, CT scoring is a semi-quantitative scoring system, which still has some subjectivity. Artificial intelligence is expected to play a more important role in future research.