Zhong Nanshan's team's paper reveals that nearly half of patients with new coronary pneumonia did not have fever on admission

On February 29, the reporter learned from Guangzhou Medical University that on February 28, American time, the academician Zhong Nanshan's team published an article online in the international top medical journal "New England Medical Journal".

The research team collected clinical information on 1099 laboratory-confirmed patients with new-type coronavirus extracted from 552 hospitals in 30 provinces and cities across the country from December 11, 2019 to January 29, 2020. Studies have pointed out that strict and timely epidemiological measures are essential to curb the rapid spread of the epidemic, but effective treatments for the disease still need to be continuously explored.

Fever alone as a diagnostic criterion is easy to miss

What are the main highlights of the study? The co-first authors of the paper, Guan Weijie, Liang Wenhua, Professor He Jianxing, and corresponding author, Professor Zhong Nanshan, said that the study collected patients with new coronary pneumonia nationwide for the first time and analyzed the fatality rate (1.4%). For closeness; only 1.9% of patients have a history of direct exposure to wildlife, 31.3% of residents living outside Wuhan have visited Wuhan in the last 2 weeks, and 72.3% of patients have been in the last 2 weeks Contacted personnel in Wuhan area.

Studies have shown that nearly half of patients with new coronary pneumonia have not developed fever at the time of admission, but 88.7% of patients have developed fever as the disease progresses, so it is easy to miss diagnosis based on fever alone; at the same time, gastrointestinal symptoms (including nausea and vomiting) , Diarrhea) are relatively rare, but also pointed out the evidence of neo-crown virus transmission through the digestive tract (virus isolated in feces, gastrointestinal tract damage mucosa, bleeding), suggesting that all sectors of society need to pay attention to prevent fecal-oral transmission.

The study also pointed out that there are some patients with new coronary pneumonia who have positive nucleic acid test and have clinical symptoms, but without any imaging abnormalities upon admission, and the proportion of such patients in non-severe patients is much higher than that of patients with severe new-corona infection; Patients with severe neo-coronary pneumonia were nine times more likely to be admitted to the ICU for invasive mechanical ventilation and death than non-severe patients.

Latest median incubation period is 4 days

How long is the incubation period for patients with new coronary pneumonia? The research team said that the incubation period is mainly determined by the time when the patient reports the last contact with the source of infection (people in the epidemic area, wildlife), and the time when the first symptoms (including fatigue, cough, fever, etc.) occur. The incubation period of the entire population is different. The researchers used the median and the minimum and maximum values ​​to show the concentrated and scattered distribution of the incubation period.

The study found that patients with new coronary pneumonia in the severe and non-severe groups each had an incubation period of 24 days. However, a careful review of the distribution pattern of the incubation period for the entire population revealed a total of 13 cases (12.7%) with an incubation period greater than 14 days, while only 8 cases (7.3%) had an incubation period greater than 18 days. "Assessing the latency of a population based solely on the minimum and maximum values ​​can easily lead to misunderstandings," the research team believes.

In addition, the long-term incubation period for patients who have been living in Wuhan for a long time or in contact with personnel in Wuhan area is mostly 0 days (the contact time is calculated according to the last day); the researchers calculated the unreasonable data and calculated the latest median incubation period. For 4 days. Therefore, in order to better represent the discrete trend of the population, the researchers determined that the interquartile range of the incubation period was 5 days (2-7 days).

Earlier, Academician Zhong Nanshan said: "Our study shows that the median incubation period for all patients is 4 days, and we are about to report the interquartile range in this article, which is 2 days and 7 days (the gap is 5 days). It more scientifically reflects the general situation of the population. "

Research on potential routes of transmission needed

Studies point to the need for studies on these potential routes of transmission because neocoronaviruses have been detected in the gastrointestinal tract, saliva, and urine.

The research team also found that the clinical features of new coronary pneumonia are similar to SARS. Fever and cough are the main symptoms, and gastrointestinal symptoms are not common, so it suggests that the new coronavirus has a different tendency than SARS, MERS, and seasonal influenza.

The proportion of non-fever patients with new coronary pneumonia is higher than that of SARS and MERS infections, so if the definition of surveillance cases focuses on detecting fever, patients who do not have fever may be missed. Lymphopenia is common and severe reductions have been achieved in some cases, which is consistent with the results of two recent reports.

The fatality rate (1.4%) determined by the study is lower than the recently reported fatality rate, most likely due to differences in sample size and case inclusion criteria. The team's findings are more similar to the statistics of the National Health Commission, which showed that as of February 16, 2020, the death rate of 51,857 patients with new coronary pneumonia was 3.2%. Because mild and untreated patients were not included in the study, real-world mortality rates may be lower.

How to distinguish between new coronary pneumonia and influenza? The research team said that although the new coronavirus and SARS-CoV have species similarities, some clinical features can distinguish neocoronary pneumonia from SARS-CoV, MERS-CoV, and seasonal influenza.

The research team also mentioned that the study also had some obvious limitations, including incomplete contact history and laboratory examination records in some cases, lack of infrastructure in non-specialist hospitals, and insufficient training of medical staff. It also mentioned that "we undoubtedly missed asymptomatic or home-treated mild patients, so our study cohort may represent the more serious side of neocoronary pneumonia."

What are the future research directions? The research team said that it is urgent to clarify the dynamic characteristics of virus transmission, the route of transmission, and the addiction of the virus to human tissues. The construction and verification of intelligent predictive models for the spread of viruses in human populations is also the current work focus.

Our reporter Ye Qing