The results of this study indicated that the percentage of patients with occult infection in group A was 2.91% with median age of 33 years (IQR: 31.00–49.00 years), which was significantly lower than that of other three groups. All of them had no symptoms and basic diseases as well as normal blood routine, CRP and SpO2. Only new single or multiple patch or cluster shadows were found in chest CT (Figure A & B). Occult infection is an important feature for 2019-nCoV infection. A previous news media reported that a COVID-19 patient in a Wuhan hospital had no symptoms before surgery, who caused the infections of 14 medical staffs. This indicated that occult infection was an important infection source and added the difficulty for the prevention and control of COVID-19.
In previous published clinical studies on 2019-nCoV, the percentages of patients with fever were 83-98.6%5–7, but Guan et al.9 reported that only 43.1% of patients had fever symptom in early stage. Our study showed that the percentage of patients with complaint of fever in visit was 50.81%, which was similar to the results of the later study. As all the patients in the previous studies were in hospital, they had already progressed into moderate or advanced stage and fever symptom was more common. However, all the patients in our study were in the early stage, therefore our result was similar to the later one. The incidences of cough in relevant reports were 59.4–82%6,7,9, and our study found that the percentage of dry cough was 35.28%. This difference of results may be related with the difference of included subjects. All the subject in our study were patients in the outpatients, who was less severe than patients in hospital and had less fever and respiratory symptoms in the early stage. This indicated that the percentage of pneumonia patients without fever after the 2019-nCoV infection was significantly higher than that of SARS10 and MERS (middle east respiratory syndrome)11. If we use fever to screen early infected patients, it will lead to the missed diagnosis of many patients, which indicated that it was more difficult to prevent and control 2019-nCoV infection.
During this COVID-19 epidemic, many pneumonia patients visited with extra-respiratory symptoms such as fatigue, fatigue, loss of appetite, and muscle soreness, which are patients of group D in our study. The percentage of group D was 28.16% with median age of 58.00 years (IQR: 50.00–65.00 years) who was older than those of other three groups of patients without statistically significant difference. 67.82% (59/87) of them were female. All of them had no fever. The time from disease onset to visit was almost around 10 days. Their blood routines were almost normal. The scope of effusion lesions were relatively wide in chest CT (Figure G & H), which were significantly different from the clinical symptoms of severe acute respiratory syndrome coronavirus (SARS-CoV) infection 10. However, above relevant clinical studies5–7 seldomly described the features of patients with this syndrome.
As the infection of 2019-nCoV is occult without symptom or with first symptoms beyond respiratory tract, this group of patients may visit other non-infection departments, which causes missed diagnosis, thus increases the risk of virus spread. The daily new cases of China mainland gradually decreased recently, but this numbers in other countries such as European Region are continuously increasing12. In order to control the epidemic, we suggested that 1) physicians in epidemic areas should pay attention to patients with atypical and extra-respiratory symptoms and people with close contact history, and perform chest CT scanning to screen COVID-19 especially in areas with limited capability to detect 2019-nCoV nucleic acid; 2) it is not enough for disease prevention and control organization of epidemic area as well as control and prevention staffs in public place to just monitor body temperature to screen COVID-19, but also need to collect information of atypical symptoms such as fatigue, loss of appetite and muscle soreness.
The results of study by Wang et al from Zhong Nan Hospital of Wuhan University
indicated that decreased lymphocytes was one of the features for COVID-19 and consistent decreasing for this number indicated poor prognosis7. Due to the consistent inflammatory response, the apoptosis of lymphocytes increased with the dramatical decreasing for the number of lymphocytes, thus started “immune inhibition” or “immune paralysis” condition 13. During the rescue treatment for patients with severe infection, except for pathogen, we should pay attention to immune imbalance secondary to excessive inflammatory response, which is an important feature of pathophysiological process, and main cause of the aggravation and death of patients with severe infection14. Our study showed that the percentage of patients with decreased lymphocytes was 12.94% (95% CI: 9.41–17.21%) and the median number of lymphocytes was 1.20 × 109/L (IQR: 0.95–1.53) × 109/L, which were significantly different from the report of Wang et al 7. This may be related with subjects with first visit to the outpatient. Most patients in this group were in the early stage and some patients probably had no decreased lymphocytes.
Although the imaging of viral pneumonia was not non-specific 15, chest CT scanning had convenient and rapid advantages, especially during initial stage that it was difficult to detect viral nucleic acid. Although we found that lung imaging of each group had their own features (Figure A-H), our study did not find statistical difference of imaging signs among each group probably due to lack of digital tools to describe the imaging features and not able to describe the location and scope of signs distribution. We though that in area with high incidence of disease, HRCT had imaging features of viral pneumonia, which could make the clinical diagnosis of COVID-19 together with epidemiological materials and clinical symptoms. However, Wáng et al. 16 thought that the clinical significance of CT examination for 2019-nCoV was not defined, avoided as much as possible, and recommended chest X-ray examination to observe the progression and regression of lung lesions for patients with moderate/severe patients. We thought that if this strategy causes mild or early patients not able to be diagnosed timely, it will increase the risk to spread virus for this group of patients as infection source.
Our study had several limitations. Firstly, all the included subjects were outpatient patients. The information of outpatient medical record system is relatively simple, which may miss some important information, and the number of severe patients in the outpatient is small, which may have selection bias. Secondly, as the number of patients in group A is small, and the power of test is small when group A is compared with other groups, which may explain why the difference among the groups was statistically significant but comparisons between each group were negative. Thirdly, as lots of patients were still in hospital, we could not analyze the risk factors of adverse consequence and need to continuously follow up these patients.
In conclusion, the heterogeneity of early clinical symptoms for COVID-19 patients was significant. It was impossible to early screen these patients by only symptoms of fever and cough, which may lead to the missed diagnosis of patients without symptoms or only with extra-respiratory symptoms. In the epidemic area, it is necessary to screen COVID-19 for patients without fever, patients with symptoms such as fatigue, loss of appetite, and muscle soreness as well as people with close contact history.