In this study, 95 adult cases were confirmed COVID-19 positive by nucleic acid test in Shanghai, but they had normal chest CT imaging at the early stage of the disease. The majority of these patients were young and middle-aged, had no underlying condition. They were obviously different from the severe cases, and majority of them were old and had underlying condition [4].
The COVID-19 patients with non-pneumonia or mild symptoms are moving sources of virus, and they were always difficult to be recognized. Without timely diagnosis and isolation of these patients, the virus will infect other close contacts and cause the spread of COVID-19. Because it is not clear whether these patients with mild syndromes will progress to severe type, early identification and management of the infected people with non-pneumonia are one of the important measures to prevent disease exacerbation and spread of COVID-19.
50% of local cases were admitted to the fever emergency department due to fever. Chest CT scans showed no pneumonia. However, all of the patients had clear epidemiological history. Combined with the results of routine blood tests, COVID-19 infection could not be excluded. The patients were immediately isolated in a single compartment and received nucleic acid test for SARS-CoV-2. It is a key to have a detailed and comprehensive epidemiological history for early identification of COVID-19 infected patients. After diagnosis, the close contacts of these patients were immediately screened for COVID-19 infection. In addition, the close contacts of family cluster should be isolated and observed after their family member was initially diagnosed. In this study, we found 2 asymptomatic patients who were infected with COVID-19. Therefore, it was highly recommended that high-risk close contacts should be screened for nucleic acid of SARS-CoV-2 to avoid delay and misdiagnosis.
There were limited number of local cases in this study. They had clear epidemiological history and 8 cases (50%) had incubation period of more than 14 days, quite different from the incubation period in large samples, as recently reported in China and other countries. The research group of Zhong Nanshan recently reported that 1099 cases had median incubation period of 4 days; 13 cases had over 14 days of median incubation period in China [5]. It was also pointed out that the disease incubation period was estimated in 291 cases by the research group of Zhong Nanshan, due to the uncertainty of exact infection date. A biased retrospective estimate may exist during evaluation. In addition, the patients who had recovered by symptom relief treatment or were in mild condition and treated at home may be missed out during early diagnosis and statistical analysis. Therefore, the subjects who had been exposed to these patients should be subject to rigorous epidemiological investigation.
Because there are high proportion of patients with incubation period over 14 days, that may cause potential difficulties in the prevention of COVID-19 spread. In addition, the COVID-19 infected patients with non-pneumonia, mild symptoms also become potential sources of virus spread. If the prevention and management are inappropriately exerted among these patients, widespread of the virus may occur. Due to a clear epidemiological history, the patients in this study were immediately isolated and observed and followed by nucleic acid test for SARS-CoV-2. They were admitted into hospital after the diagnosis was confirmed. The family members and other close contacts were also isolated and observed for a certain period, so that transmission to others may be prevented. In this group, fever and respiratory symptoms were the main symptoms at early phase of the disease. Thus, we should be highly vigilant on the high-risk patients with such symptoms.
Among the imported cases, clear epidemiological history cannot be determined among some patients (36.6%), due to the difficulties in the investigation of infectious chain. However, since they were all inbound by flight, nucleic acid test was carried out in place by the center of disease prevention and control. Meanwhile, other flight passengers were isolated for observation to prevent further spread of COVID-19. Some patients with clinical symptoms during quarantine was diagnosed by virus nucleic acid test. In addition to fever and respiratory symptoms, non-respiratory symptoms are more frequent initial symptoms among these patients, mainly manifested as diarrhea, taste or smell disorders. Therefore, attention should be paid to the high-risk population with such symptoms.
With the increasing cases with the long incubation period [6] and reversed positive test of SARS-CoV-2 after discharged from hospital, it is necessary to continue the follow-up of their health status for 14 days, require them to wear masks, stay in a single compartment and avoid outdoor activities, according to the Guidelines for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Infection by the National Health Commission (the sixth edition) [7]. After these measures were taken, new local cases were not reported in Shanghai so far.
In local cases, 4 cases had underlying health condition and 3 of them had mild pneumonia during follow-up; 3 cases were older than 60 years old and 2 of them had pneumonia. In the overseas imported cases, 10 had underlying diseases and 9 of them had mild pneumonia during follow-up; one case was over 60 years old and had pneumonia during follow-up. It was widely reported that age and underlying health condition are major high risk factors in the severity of COVID-19 infected cases [8]. Based on our study, age was the highest risk factor in developing severe COVID-19 pneumonia, that was consistent with the previously reported results [9]. Our data also showed that young adult patients without underlying health condition always had mild respiratory symptoms without pneumonia during follow-up. People with underlying condition or the elderly are prone to gradually developing mild pneumonia. During clinical observation, we observed that the peak period was between 7th and 10th day after COVID-19 infection. Symptoms and imaging findings of these patients were often aggravated during the peak period, but 20 cases with pneumonia were under stable condition during hospitalization. They were recovered by supportive care and finally discharged from hospital. These characteristics showed that regardless of the local or overseas imported cases, the pathogenicity of COVID-19 was gradually decreased after multiple generations. More attention and care should be given to those patients with underlying condition and older patients. Because 20 of 95 cases developed pneumonia at the peak of disease, the number was limited and more sample size was required to better understand prognosis of the non-pneumonia patients.
It was noted that most of the local cases occurred before Mid-March and were initially manifested with fever and/or respiratory symptoms (87.5%); but majority of the overseas imported cases occurred after Mid-March, and had symptoms of diarrhea, smell or taste disorder, headache, in addition to fever and respiratory symptoms at early phase. The results showed that virus from different areas had different pathogenic characteristics, though similar laboratory results were obtained among these cases. In addition, the similar duration of hospital stay, the exacerbation and recovery rate were quite comparable between the local and overseas imported patients, suggesting their similar disease severity. They are all treated with supportive care.
This disease was constantly renamed after the disease was recognized further. Initially, the disease was temporarily named by Chinese health commission as "pneumonia caused by new coronavirus infection " and renamed as "Novel coronavirus pneumonia " (NCP) on February 8, 2020 [10]. Due to the involvement of multiple system and organ after novel coronavirus infection, the diseases was formally named by WHO as Coronavirus Disease 2019 (COVID-19) on February 11, 2020 [11]. So far the most common type of COVID-19 is pneumonia. However, it is necessary to scientifically classify COVID-19 into different subtypes after COVID-19 was more well understood. The detailed classification of COVID-19 would provide patients with targeted treatment. For example, patients with bronchitis alone should be diagnosed as novel coronavirus bronchitis, and treated with cough relief pills and expectorant. The patients with only upper respiratory tract infection symptoms should be diagnosed as novel coronavirus cold, and advised for lower physical activities and rest. Those COVID-19 infected patients without symptoms and pneumonia by CT scan should be called as novel coronavirus asymptomatic carriers, and treatment is not recommended among these patients. Because multiple systems were probably involved after novel coronavirus infection, more study is required to define the characteristics, immunological mechanisms of the disease in the future.
In conclusion, there is high proportion of non-pneumonia young adult patients among COVID-19 adult patients. These young patients had mild clinical symptom and/or slight laboratory abnormalities. The most common symptoms were fever, headache, respiratory symptoms, diarrhea, lost/lower smell or taste. Some of them had prolonged incubation period and characteristics of familial cluster. During the follow-up, the patients with underlying condition or elderly were prone to developing mild pneumonia. It suggested that the pathogenicity of the virus maybe gradually reduced after multiple passages, but the virus is still highly infective and contagious to close contacts. All cases in this study were under stable health condition and quickly recovered after supportive treatment. Thus, the strict home isolation and symptomatic therapy for a certain time point was appropriate approach in non-pneumonia patients. But the patients with underlying condition and at older age should be closely monitored for at least 1 week after COVID-19 test positive. The patient should be hospitalized for supportive care if the health condition of patients was deteriorated. It is also important to clearly identify the different characteristics of local and overseas imported cases. Local residents should voluntarily report their health condition and potential COVID-19 exposure history to the local center of prevention and control. Those suspected cases and individuals coming from high-risk area via airline or other public transportation should be centrally isolated and under close observation. Following global epidemic tends to ease, it become more important to focusing on the hard-to-find patients without pneumonia and paying attention to their clinical characteristics. The targeted prevention of COVID-19 would greatly improve the quality of life, reduce social and economic burden. We in this study reported the clinical characteristics of non-pneumonia COVID-19 adults in Shanghai, that would provide useful information for researchers and clinicians in this field.