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Latest updates on the battle against 2019-NCP: JAMA published the latest research results of Peng Zhiyong team from Zhongnan Hospital of WHU
Author:  Date:2020-02-17  Clicks:

On February 7, the Journal of the American Medical Association (JAMA) published online an article entitled "Clinical Characteristics of 138 Hospitalized Patients With 2019 Coronavirus - Infected Pneumonia in Wuhan, China". This research by Peng Zhiyong, director of the ICU in Zhongnan Hospital of Wuhan University, discussed about the "clinical characteristics of patients with pneumonia caused by the novel coronavirus."

This paper by Peng Zhiyong is a multidisciplinary collaboration co-completed by the department of infection and the department of emergency. It has received full supports from the Wang Xinghuan, dean of Zhongnan Hospital of Wuhan University and concurrently dean of Leishenshan Hospital . The paper also sets unprecedented high level of clinical research published in the international top medical journal by the clinical school of Wuhan University.

Describing the clinical characteristics of the novel coronavirus pneumonia in a large sample for the first time

Novel coronavirus pneumonia is an acute infectious pneumonia caused by a novel coronavirus (2019 novel coronavirus, 2019-nCoV) not previously found in humans. The case first appeared at Wuhan, Hubei province, in December 2019, and has spread to other parts of China and beyond. On 30 January 2020, WHO declared the outbreak of novel coronavirus pneumonia a public health emergency of international concern (PHEIC). On February 7, 2020, the National Health Commission decided to name it "Novel Coronavirus Pneumonia" (NCP). As of 9 February 2020, a total of 37,280 NCP cases have been confirmed nationwide, with 24 countries reporting such cases.

Zhongnan Hospital of Wuhan University got down to the reception and treatment of NCP patients as early as the beginning of the outbreak in early January. On January 8, a patient was transferred to the ICU for advanced respiratory support and received ECMO treatment because the routine respiratory support treatment had been unsustainable due to dyspnea and severe hypoxemia. By February 9, a total of 56 patients in critical condition had been admitted to the ICU.

This outbreak is caused by a novel coronavirus (2019-nCoV) infection, and its clinical manifestations and treatment have their own characteristics. Early publications have focused on revealing the mode of transmission and epidemiology of the disease. This paper by Prof. Peng Zhiyong is the largest case study of new coronary pneumonia so far, which is the first to comprehensively summarize the course characteristics of patients, clinical manifestations, treatment effect, differences between severe and non-severe patients and prognosis.

In this article, Prof. Peng Zhiyong focuses on 138 patients admitted to Zhongnan Hospital from January 6 to January 28, with an average age of 56 and 75 (54.3%) male. Compared with patients who did not receive ICU treatment, ICU patients were significantly older (66[57-78] VS 51[37-62]. The median time from first symptom to dyspnea was 5.0 days, median time to admission was 7.0 days, and median time to ARDS (respiratory distress syndrome) was 8.0 days. As of 3 February, 47 patients (34.1 per cent) had been discharged from the hospital, with a median stay of 10 days for those who survived.

Compared with non-ICU patients (n = 102), ICU patients (n = 36) were older (median age: 66 vs. 51), more likely to have comorbidities (26 [72.2%] vs. 38 [37.3%]), dyspnea (23 [63.9%] vs. 20 [19.6%]), and anorexia (24 [66.7%] vs. 31 [30.4%]).

In the study of clinical examination index, they compared the inspection results of five dead patients with those of 28 alive, including white blood cell, neutrophil counts, lymphocyte counts, d-dimer, blood urea nitrogen and blood creatinine. The results showed that lymphocyte counts declined in most of the patients during hospitalization, but were more severe in the patients who died. Neutrophils and white blood cells were higher overall in the patients who died. At the same time, with the progress and deterioration of the disease, the patients who died will witness a rapid increase in blood urea nitrogen and creatinine in the late stage of the disease. Based on these data, Prof. Peng Zhiyong's team speculated the cause of death during the discussion session: neutrophils may be related to cytokine storm caused by virus invasion; coagulation activation may be associated with a sustained inflammatory response; acute kidney injury may be related to the direct effects of virus, hypoxia, and shock. These three pathways may be synergistic factors leading to death.

Patients with atypical symptoms may become a potential source of infection for the spread of the virus

The article also analyzed the clinical features of patients in critical condition. The early symptoms of the disease are mostly fever, dry cough, muscle pain, fatigue, dyspnea, and hypoxemia. Less common symptoms are headache, dizziness, abdominal pain, diarrhea, nausea and vomiting. A quarter of the patients experienced abdominal symptoms such as diarrhea and vomiting one to two days before the onset of fever and dyspnea. The disease can spread quickly among people in the early stage. In addition to the high infectivity of the virus itself, the presence of atypical symptoms allows patients infected with the new coronavirus to spread the virus silently.

In  Prof. Peng Zhiyong's study, only 12 of 138 patients in the hospital had a clear exposure to Huanan seafood markets. Fifty-seven patients (41.3%) were considered to have nosocomial infections, including 17 hospitalized patients with other illnesses and 40 medical workers. Of the 40 medical workers, 77.5% came from general departments (31), 17.5% from emergency departments (7), and 5% (2)from ICU. In Peng's sample, one patient was admitted to hepatopancreatobiliary surgery department due to abdominal symptoms and was later diagnosed with novel coronavirus pneumonia. He infected more than 10 medical staff associated with him, including a doctor who passed the virus on to his family. Familial aggregation is also seen in this case sample. The strong human-to-human transmission of the disease was also confirmed.

The presence of atypical symptoms, especially abdominal symptoms, is a significant finding, suggesting that the fecal-oral route may be one of the transmission routes of the disease. Studies have confirmed detection of the virus in the feces of patients who infected novel coronavirus pneumonia with abdominal symptoms. On the other hand, it also suggests that the protection against novel coronavirus pneumonia should not be limited to patients with symptoms or typical symptoms. The medical staff and the people should strengthen isolation and protection at any time to reduce the cross-infection in people.

It is worth mentioning that director Peng Zhiyong judged that the novel coronavirus pneumonia was a severe infectious disease at the early stage of the epidemic and took strict isolation and protection measures in the department. Therefore, only 2 of the 40 infected medical workers were ICU staff.

The treatment is highly effective, and the prognosis of critically ill patients is better than that of other medical units at the same level

In terms of prognosis, 36 of 138 patients were critically ill patients transferred to the ICU, with a critical illness rate of 26%. Six of the 36 eventually died, with an ICU fatality rate of 16.7% and an overall mortality rate of 4.3%. Of the surviving patients admitted to the ICU, 9 were discharged home, 10 were transferred out of the ICU after their conditions were stable, and 11 remained in the ICU. Compared with the data online as of January 27, both the overall mortality rate and the ICU mortality rate in Zhongnan Hospital were relatively low. Once published, the article has aroused the great interest of each medical unit, and people have consulted Prof. Peng Zhiyong for the hospital's experience in the NCP diagnosis and treatment of Prof. Peng Zhiyong introduced that respiratory support is crucial in the treatment of the novel coronavirus pneumonia. Respiratory distress and hypoxemia are evident in critically ill patients, usually accompanied by respiratory frequency greater than 30 breaths per minute, oxygen saturation less than 93% (when oxygen concentration is 21% in a silent state), oxygenation index less than 300, and a high degree of dependence on respiratory support. In most patients, nasal catheter or mask oxygen inhalation is difficult to improve, requiring high-flow oxygen inhalation and non-invasive mechanical ventilation. In some patients, invasive mechanical ventilation or even ECMO support is required. Inappropriate respiratory support strategies may worsen the disease and increase the mortality of patients.

According to the article published by Prof. Peng, in terms of respiratory support, of the 36 patients in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received non-invasive ventilation, 17 (47.2%) received invasive ventilation, and 4 received ECMO treatment. Two patients have been successfully removed from machine, 1 has been turned out of ICU, the other is in recovery.

The study found that most of the patients received antiviral therapy early (oseltamivir, 124 [89.9%]), but the results showed no significant effect of antiviral drugs, and the pneumonia protocol for novel coronavirus pneumonia infection issued by the National Health Commission also showed that there were no effective antiviral drugs at present. Some patients received antibacterial treatment (moxifloxacin, 89 [64.4%]; Ceftriaxone, 34 [24.6%]; Azithromycin, 25 [18.1%]), mainly targeting secondary bacterial infections; 62 patients were treated with glucocorticoids, with a higher proportion of severe patients (26/36,72.2%) than non-severe patients (36/102,35.3%).

Links to papers: https://jamanetwork.com/journals/jama/fullarticle/2761044

doi:10.1001/jama.2020.1585

Rewritten by: Wu Buer

Edited by: Cao Siyi, She Yuxi and Hu Sijia

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