Retrospective registration

Identification and Clinical Treatment of Severe novel coronavirus pneumonia (COVID-19) Patients

Identification and Clinical Treatment of Severe novel coronavirus pneumonia (COVID-19) Patients

Li Mengdie 

Lu Yibin 

1 Siyi Road, Shihe District, Xinyang, He'nan, China

1 Siyi Road, Shihe District, Xinyang, He'nan, China

Xinyang Central Hospital

Xinyang Central Hospital

Yes

Ethics Committee of Xinyang Central Hospital

Ren Shuwei

1 Siyi Road, Shihe District, Xinyang, He'nan, China

Xinyang Central Hospital

1 Siyi Road, Shihe District, Xinyang, He'nan, China

Xinyang Science and Technology Research Project Fund

Novel Coronavirus Pneumonia (COVID-19)

U07.100x001

Observational study

0

Factorial 

I. In December 2019, there were many pneumonia cases of unknown causes in Wuhan City, Hubei Province [1]. On January 07, 2020, the China Center for Disease Control and Prevention (CDC) found a kind of novel coronavirus from these patients, which was named "2019-NCOV" by WHO [2]. Subsequently, except Wuhan, there were different numbers of 2019-nCoV infection cases in cities all over the country. As of February 19, 2020, 74,283 cases had been confirmed nationwide, involving the death toll of 2009. The epidemic situation is extremely serious. Xinyang City, Henan Province, is located in the southernmost part of Henan Province and is the "southern gate" of Henan Province. It has 8 counties and 2 districts under its jurisdiction. It is close to Wuhan. As a result of the spring transportation, 100,000 people have returned home from Wuhan, making it the hardest hit area of the epidemic. As of February 19, a total of 268 confirmed cases of 2019-nCoV infection were found in Xinyang City, with 3 deaths. Most of the cases were treated in isolation in Xinyang Central Hospital and Xinyang Fifth People's Hospital. According to "novel coronavirus Diagnosis and Treatment Plan (Trial Sixth Edition)" [3], clinical types are divided into light, common, heavy and critical types. (1) Light. The clinical symptoms were mild and no pneumonia was found on imaging. (2) Ordinary type. Symptoms such as fever and respiratory tract are present, and pneumonia can be seen on imaging. (3) Heavy duty. Meet any of the following: 1. Respiratory distress, RR≥30 times/min; 2. In the resting state, oxygen saturation ≤ 93%; 3. arterial partial pressure of oxygen (PaO2)/ oxygen concentration (FiO2)≤300mmHg(1mmHg=0.133kPa). (4) Critical type. One of the following conditions is met: 1. Respiratory failure occurs and mechanical ventilation is required; 2. Shock; 3. ICU monitoring and treatment are required for patients with other organ failure. At present, the proportion of dangerous and severe cases in novel coronavirus is relatively high. Recently, relevant researches [4,5,6] have collected baseline data, epidemiology and laboratory test indexes on admission of common, dangerous and severe patients with new crown pneumonia. These data are divided into two groups for statistical analysis, and it is concluded that some indexes have statistical significance. We think that we can collect clinical data of novel coronavirus cases in Xinyang city, and evaluate the disease severity and risk factors of death through multivariate logistic regression analysis. According to these statistical data, it is planned to find out the early clinical characteristics of the patients with severe and dangerous diseases in novel coronavirus, and then identify the patients with severe and dangerous diseases in the early stage, and intervene as soon as possible to reverse the outcome of the patients, improve the prognosis and reduce the mortality rate. Second, preliminary guidelines have been recommended for the treatment of patients in novel coronavirus, but there are still many problems to be solved. We plan to conduct clinical research on the following three issues. 1. Comparative analysis of the application of nasal high-flow oxygen therapy and non-invasive mechanical ventilation in patients with severe and dangerous diseases in novel coronavirus. The "Diagnosis and Treatment Plan for Pneumonia Infected in novel coronavirus (Trial 6th Edition)" issued by the State Health and Planning Commission suggests that high-flow nasal catheter oxygen therapy or non-invasive mechanical ventilation should be given to respiratory support for severe and critical cases [3], but the existing guidelines do not provide specific implementation and monitoring indicators. With the wide application of nasal high-flow oxygen therapy in ARDS patients, more and more scholars apply this therapy to patients with acute hypoxic respiratory failure. Ricard[7] research found that the use of nasal catheter high-flow oxygen therapy can not only significantly reduce the risk of invasive mechanical ventilation, but also improve the success rate of treatment. Frat [8] and other studies compared nasal catheter high-flow oxygen therapy, nasal catheter low-flow oxygen therapy and non-invasive ventilation. The results showed that the number of days of non-mechanical ventilation in the high-flow oxygen therapy group was significantly higher than that in the other two groups, and the mortality rate was significantly lower than that in the other two groups, but there was no significant difference in tracheal intubation rate among the three groups. Chanques[9] and other studies pointed out that the reason why nasal catheter high-flow oxygen therapy is more comfortable is that the heating and humidification of inhaled gas can dilute the viscous secretion of respiratory tract, thus relieving atelectasis and making patients feel comfortable. The systematic evaluation by Wang ke et al. [10] also confirmed that nasal catheter has higher comfort for high-flow oxygen therapy. This study was divided into high flow oxygen therapy group and non-invasive mechanical ventilation group according to the oxygen therapy methods given to severe and critical patients with ARDS in novel coronavirus. The intubation rate, blood gas analysis, oxygenation index, complications, hospitalization time, prognosis and other indicators of the two groups were closely observed and statistically analyzed. According to the research results, we can further judge which of the two oxygen therapies can improve the prognosis of patients and provide more effective respiratory support for patients with newly crowned pneumonia. 2. Analysis on the Effectiveness and Safety of Integrated Traditional Chinese and Western Medicine in Treating Common Patients in novel coronavirus The guideline of "novel coronavirus Diagnosis and Treatment Plan (6th Edition)" recommends the treatment method of combination of traditional Chinese and western medicine. This study is to discuss the application effect analysis of combination of traditional Chinese and western medicine in novel coronavirus ordinary patients. Treatment mechanism of traditional Chinese medicine [11]: Coronavirus has spike protein (S protein) on its surface, which consists of S1 and S2 subunits. S1 subunit includes N-terminal domain and C-terminal RBD domain which interact directly with host receptor. It promotes virus infection by binding host receptor, and S2 subunit mediates fusion between virus and host cell membrane. 2019-nCoV belongs to Nestoridae, Coronaviridae, Beta Coronavirus, and is a linear single-stranded RNA virus. It can infect cells by binding S protein RBD domain with angiotensin converting enzyme 2(ACE2) receptor on the surface of human cells, causing a series of pathological changes, one of which is to activate the classical renin-angiotensin system (RAS) regulatory pathway and down-regulate ACE2 expression. At present, most of the traditional Chinese medicine prescriptions recommended in the guidelines include astragalus root, ginseng, areca nut, honeysuckle, forsythia, etc., all of which show regulatory effects on RAS [12,13]. the monomer astragaloside iv in astragalus root can activate ACE2-Ang-(1-7)-Mas pathway in RAS system to raise its level, thus playing a protective role on kidney and respiratory system [14,15]. Ginsenoside Rg3 can protect the kidney by up-regulating the expression of ACE2 in the kidney, thus increasing the degradation of AngII, reducing the inflammation and oxidative stress mediated by AngII in the kidney, and thus reducing the pathological changes of the kidney [16]. This clinical study analyzes the effectiveness and safety of integrated traditional Chinese and western medicine in treating patients with novel coronavirus, and plans to find more effective treatment schemes, providing new ideas for the clinical treatment of 2019-nCoV infected patients, thus saving more patients. 3. Analysis of influencing factors of ECMO treatment for patients with severe and dangerous diseases in novel coronavirus ECMO, also called extracorporeal life support, is a respiratory and circulatory support technology that can replace lung and heart functions. In recent years, extracorporeal membrane oxygenation (ECMO) has been widely used in clinic [17]. Relevant studies have confirmed that active and effective treatment and intervention is the key to promote the prognosis of patients with severe respiratory failure, alleviate anoxia symptoms and prolong survival time [18]. At present, common clinical treatment schemes, such as positive end-respiratory pressure ventilation, high-frequency oscillatory ventilation, prone position ventilation and other ventilation modes, can only improve the ventilation function of patients, are difficult to fully promote their oxygenation recovery, and have poor long-term efficacy [19,20]. ECMO, as a new technology, can apply cardiopulmonary bypass to assist the heart and lung, rapidly improve the anoxic state of the body and promote the prognosis of the disease [21,22]. Most of the cases in novel coronavirus are mild, most of which can be cured and some of which can progress to severe danger. Severe patients suffer from dyspnea and hypoxemia about one week after onset. Severe patients can rapidly progress to ARDS and cause multiple organ failure, eventually leading to the death of patients. For the treatment of severe novel coronavirus, the latest edition of the guidelines of the National Health and Safety Commission holds that if non-invasive mechanical ventilation lasts for 2 hours, the condition of the patient does not improve, or the patient cannot tolerate non-invasive ventilation, airway secretions increase, severe cough, or hemodynamic instability, the patient should transition to invasive mechanical ventilation in a timely manner. Invasive mechanical ventilation adopts low tidal volume "lung protective ventilation strategy" to reduce ventilator-associated lung injury. When necessary, prone position ventilation, lung recruitment or extracorporeal membrane oxygenation (ECMO) should be adopted. At present, there are also many institutions carrying out studies on ECMO treatment of novel coronavirus. There are few researches on the clinical characteristics of patients with acute respiratory distress syndrome caused by novel coronavirus and the effectiveness and safety of ECMO treatment. This project will study the clinical characteristics of critical novel coronavirus patients admitted to Xinyang Central Hospital and Xinyang Fifth People's Hospital, and make statistical analysis on the effectiveness and safety of ECMO treatment. To provide reference opinions for ECMO treatment of patients with dangerous and severe novel coronavirus, which is helpful for the formulation and implementation of policies and programs in the next step.

Project implementation plan: Item 1: Early Identification of Dangerous and Severe Patients in novel coronavirus We plan to collect clinical data of novel coronavirus patients admitted to Xinyang Central Hospital and Fifth People's Hospital for retrospective study. All patients were divided into two groups: 1. ordinary group 2. dangerous and severe group. the epidemiological data, laboratory examination data and imaging data of the two groups were statistically analyzed to find out the data with statistical significance (p < 0.05) between the two groups. Multivariate logistic regression analysis was used to evaluate the disease severity and risk factors of death. With the improvement of diagnosis and detection technology in future lab, we plan to carry out 2019-nCoV quantitative detection on patients in combination with clinical laboratory, and make comparative analysis on the relationship between viral load and severity of patients in the two groups of patients. Item 2: Comparative analysis of nasal high-flow oxygen therapy and non-invasive mechanical ventilation in the application of dangerous and severe patients in novel coronavirus. We plan to collect the clinical data of novel coronavirus patients admitted to Xinyang Central Hospital and Fifth People's Hospital. We will conduct a randomized double-blind control study. The patients with severe and critical ARDS in novel coronavirus will be treated with oxygen therapy, and they will be divided into high-flow oxygen therapy group and non-invasive mechanical ventilation group. We will closely observe for 6 hours to see if the patients suffer from clinical deterioration and change to invasive mechanical ventilation support at any time according to their condition. The intubation rate, blood gas analysis, oxygenation index, complications, hospital stay and prognosis of the two groups were analyzed clinically. Item 3: Effectiveness and Safety Analysis of Integrated Traditional Chinese and Western Medicine in Treating Common Patients in novel coronavirus The patients with 2019-nCoV pneumonia were included in Xinyang Central Hospital and Xinyang Fifth People's Hospital. Randomized double-blind controlled study was used to randomly divide the patients into western medicine treatment group and integrated traditional Chinese and western medicine treatment group. The western medicine treatment group was treated with western medicine as required by the guidelines of "novel coronavirus Diagnosis and Treatment Plan (Trial 6th Edition)", and the integrated traditional Chinese and western medicine treatment group was treated with traditional Chinese medicine diagnosis and treatment according to syndrome differentiation and treatment of traditional Chinese medicine on the basis of western medicine treatment, and reasonably selected the traditional Chinese medicine prescription recommended by the guidelines and western medicine treatment. The clinical symptoms (body temperature, aversion to cold, muscle soreness, cough, expectoration, headache, pharyngalgia, fatigue) and physical signs, laboratory examination and pulmonary imaging characteristics of the two groups of patients were observed daily. MAIN OUTCOME: Statistical analysis was carried out on the time when the main clinical symptoms of the two groups of patients were relieved, the time when imaging showed the pathological changes from onset to absorption and turnover, the changes of laboratory indexes, and the rate of conversion to severe diseases. Secondary indicators: analysis of adverse drug reactions. Item 4: Analysis of Influencing Factors of ECMO Treatment for Critical and Severe Patients in novel coronavirus The patients with 2019-nCoV pneumonia were included in Xinyang Central Hospital and Xinyang Fifth People's Hospital. Patients treated with ECMO were divided into ECMO survival group and ECMO death group according to prognosis from the time of application of ECMO to one week of discharge. The clinical data of ECMO survival group and ECMO death group were analyzed statistically before, during and after treatment. Observation indexes: (1) General data of patients: gender, age, medical history; (2) General conditions before treatment: diagnosis, etiology, complications, hormone application within one month, invasive mechanical ventilation time before ECMO, time from onset to application of ECMO, time from admission to application of ECMO, oxygenation index before application of ECMO; (3) Clinical data: body temperature, respiratory frequency, heart rate, mean arterial pressure, tidal volume, PEEP, arterial blood gas analysis (pH value, PaO:, PaCO:, blood lactic acid level, etc.), oxygenation index, APACHEII score, Murray score, SOFA score, blood routine, biochemical index, coagulation index, etc. before and 2h, 24h, 48h, 72 h after treatment and 24 h before ECMO withdrawal; (4)ECMO auxiliary complications: including mechanical complications, body complications, etc.; (5) Endpoint observation index: Life cannot be taken care of due to death or severe disability within 1 week after ECMO treatment. Effect evaluation: To compare the differences of clinical data recorded before, during and after treatment between ECMO survival group and ECMO death group, and to compare the differences of clinical indexes between ECMO survival group and ECMO death group during ECMO treatment. The influencing factors of prognosis in the two groups were analyzed. 

1. Patients with serious heart and lung, liver and kidney functions and central nervous system diseases;
2. Pregnant or lactating patients.

Statisticians used SPSS software to generate random sequences by using the method of random block group stratification and randomization

Blind Blindness is required for drug intervention tests such as placebo. Methods: 1. Mark the outer package of test drug and simulant as A or B, or No.1 and No.2, etc., so that they cannot distinguish between what is therapeutic drug and what is simulant, but can be distinguished into different drugs; 2. If all the test drugs of each subject are packed into one medicine bag, serial numbers (1, 2, 3, ...) shall be numbered outside the medicine bag; Then, different drugs are put into corresponding medicine bags according to the sequence numbers of the treatment group and the control group determined on the random allocation table; 3. If it is not repackaged, the treatment group and the control group determined on the random allocation table need to be marked as A or B, or 1 or 2. The doctor will issue a doctor's order based on this and use the corresponding A, B, or 1 or 2 plan as code, and the pharmacy or nurse will be assigned with A or B, or 1 or 2 drugs; 4. Some tests adopt the envelope package emergency plan or/and the treatment plan accepted by the subject, so as to break the blindness and adopt the correct treatment method when the test needs to be suspended in case of serious adverse reactions.

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On February 1, 2021, the Internet platform was adopted for publicity.

Clinical data are collected and tabulated by the hospital electronic medical record system. Epidemiological data were asked about patients and their families and recorded in tables.