Expert consensus on comprehensive treatment of coronavirus disease in Shanghai 2019
Shanghai Medical Association 3/3
[Editor's note]
On March 1, the Chinese Journal of Infectious Diseases, which was hosted by the Shanghai Medical Association, pre-published the "Expert Consensus on Comprehensive Treatment of Coronavirus in Shanghai 2019" (http://rs.yiigle.com/m/yufabiao/1183266 .htm), which has attracted widespread attention in the industry. Shanghai TV also reported on the news last night. This consensus was reached by 30 experts representing the strongest medical force in the treatment of new-type coronavirus pneumonia in Shanghai. Through the research and summary of more than 300 clinical patients, and fully drawing on the treatment experience of colleagues at home and abroad, the "Shanghai Plan" was finally formed. At the end of the article, the list of 30 subject experts (18 writing experts and 12 consulting experts) from various medical institutions in Shanghai is attached.
Corona virus disease 2019 (COVID-19) was first reported on December 31, 2019 in Wuhan, Hubei Province. COVID-19, as a respiratory infectious disease, has been included in the Class B infectious diseases stipulated in the Law of the People's Republic of China on the Prevention and Control of Infectious Diseases and managed as a Class A infectious disease.
With the deepening of understanding of the disease, COVID-19 has accumulated certain experience in the prevention and control of COVID-19. The Shanghai New Coronary Virus Disease Clinical Treatment Expert Group follows the National New Coronary Virus Pneumonia Diagnosis and Treatment Program and draws on the treatment experience of colleagues at home and abroad in order to improve the success rate of clinical treatment and reduce the patient mortality rate, prevent the progress of the disease, and gradually reduce the disease. The proportion of patients with severe disease improves their clinical prognosis. On the basis of continuously optimizing and refining the treatment plan, an expert consensus has been formed on related clinical diagnosis and treatment.
I. Etiology and epidemiological characteristics
2019 novel coronavirus (2019-nCoV) is a new coronavirus belonging to the genus β. On February 11, 2020, the International Committee on Taxonomy of Viruses (ICTV) named the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with COVID-19 and asymptomatic infection can transmit 2019-nCoV. Respiratory droplet transmission is the main route of transmission and can also be transmitted through contact. There is also the risk of aerosol transmission in confined enclosed spaces. COVID-19 patients can detect 2019-nCoV in stool, urine and blood; some patients can still test positive for fecal pathogenic nucleic acid after the pathogenic nucleic acid test of respiratory specimens is negative. The crowd is generally susceptible. Children, infants, and young children also develop disease, but the condition is relatively mild.
Clinical characteristics and diagnosis.
(A) clinical characteristics
The incubation period is 1 to 14 d, mostly 3 to 7 d, with an average of 6.4 d. Main symptoms are fever, fatigue, and dry cough. May be accompanied by runny nose, sore throat, chest tightness, vomiting and diarrhea. Some patients have mild symptoms, and a few patients have no symptoms or pneumonia.
The elderly and those suffering from basic diseases such as diabetes, hypertension, coronary atherosclerotic heart disease, and extreme obesity tend to develop severe illness after infection. Some patients develop symptoms such as dyspnea within 1 week after the onset of the disease. In severe cases, they can progress to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. The time to progression to severe illness was approximately 8.5 days. It is worth noting that in the course of severe and critically ill patients, there may be moderate to low fever, even without obvious fever. Most patients have a good prognosis, and deaths are more common in the elderly and those with chronic underlying disease.
The early CT examination showed multiple small patches or ground glass shadows, and the internal texture of the CT scans was thickened in the form of grid cables, which was obvious in the outer lung zone. A few days later, the lesions increased and the scope expanded, showing extensive lungs, multiple ground glass shadows, or infiltrating lesions, some of which showed consolidation of the lungs, often with bronchial inflation signs, and pleural effusions were rare. A few patients progressed rapidly, with imaging changes reaching a peak on days 7-10. Typical "white lung" performance is rare. After entering the recovery period, the lesions are reduced, the scope is narrowed, the exudative lesions are absorbed, part of the fiber cable shadow appears, and some patients' lesions can be completely absorbed.
In the early stage of the disease, the total number of white blood cells in the peripheral blood was normal or decreased, and the lymphocyte count was reduced. Some patients may have abnormal liver function, and the levels of lactate dehydrogenase, muscle enzyme, and myoglobin may increase; troponin levels may be increased. Most patients had elevated CRP and ESR levels and normal procalcitonin levels. In severe cases, D-dimer levels are elevated, other coagulation indicators are abnormal, lactic acid levels are elevated, peripheral blood lymphocytes and CD4 + T lymphocytes are progressively reduced, and electrolyte disorders and acid-base imbalances are caused by metabolic alkalosis See more. Elevated levels of inflammatory cytokines (such as IL-6, IL-8, etc.) may occur during the disease progression stage.
(II) diagnostic criteria
1. Suspected case: Combined with the following epidemiological history and clinical manifestations. Suspected cases were diagnosed as having any one of epidemiological history and meeting any two of the clinical manifestations, or having no clear epidemiological history but meeting three of the clinical manifestations. ① Epidemiological history: travel history or residence history of Wuhan City and surrounding areas, or other communities with case reports within 14 days before the onset; history of contact with 2019-nCoV infection (positive nucleic acid test) within 14 days before the onset ; Patients with fever or respiratory symptoms from Wuhan and surrounding areas or from communities with case reports within 14 days before the onset of the disease; cluster onset. ② Clinical manifestations: fever and / or respiratory symptoms; with the above-mentioned imaging features of the new coronavirus pneumonia; the total number of white blood cells is normal or decreased in the early stage of onset, and the lymphocyte count is reduced.
2. Confirmed cases: Those with one of the following etiology evidence are diagnosed as confirmed cases. ① Real-time fluorescent reverse transcription PCR detected 2019-nCoV nucleic acid positive. ② Viral gene sequencing revealed high homology with known 2019-nCoV. ③ Except for nasopharyngeal swabs, take sputum as much as possible. Patients undergoing endotracheal intubation can collect lower respiratory tract secretions and send viral nucleic acid test positive.
(III) differential diagnosis
It is mainly distinguished from other known viral pneumonias such as influenza virus, parainfluenza virus, adenovirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, severe acute respiratory syndrome (SARS) coronavirus, etc. Different from Mycoplasma pneumoniae, Chlamydia pneumonia and bacterial pneumonia. In addition, it must be distinguished from non-infectious diseases such as pulmonary interstitial lesions and organizing pneumonia caused by connective tissue diseases such as vasculitis and dermatomyositis.
(IV) clinical classification
1. Mild: The clinical symptoms are slight, and no pneumonia manifestations on imaging examination.
2. Ordinary type: fever, respiratory tract symptoms, etc. Pneumonia manifestations on imaging examination.
Early warning of severe cases of common patients should be strengthened. Based on current clinical studies, elderly (aged> 65 years) with underlying diseases, CD4 + T lymphocyte counts <250 / µL, blood IL-6 levels significantly increased, and lesions were found on lung imaging on 2 to 3 days Significant progress> 50%, lactic dehydrogenase (LDH)> 2 times the upper limit of normal value, blood lactic acid ≥3 mmol / L, metabolic alkalosis, etc. are all early warning indicators of severe disease.
3. Heavy: Any one of the following. ① Shortness of breath, respiratory rate ≥ 30 times / min; ② In resting state, arterial oxygen saturation (SaO2) ≤ 93%; ③ arterial partial pressure of oxygen, PaO2) / fraction of inspired oxygen (FiO2) ≤300 mmHg (1 mmHg = 0.133 kPa). At high altitudes (above 1,000 m), PaO2 / FiO2 should be corrected according to the following formula: PaO2 / FiO2 × [Atmospheric Pressure (mmHg) / 760].
Pulmonary imaging examination showed that the lesions progressed significantly within 24 to 48 hours, and those with more than 50% of the lesions were managed as severe.
4. Dangerous: A person who meets any of the following conditions can be judged as critical. ① Respiratory failure occurs and requires mechanical ventilation; ② Shock occurs; ③ Combined failure of other organs requires ICU monitoring and treatment.
(V) Clinical monitoring
The clinical manifestations, vital signs, fluid volume, gastrointestinal function and mental state of the patients were monitored dynamically daily.
All patients were dynamically monitored for terminal blood oxygen saturation. For critically ill and critically ill patients, timely blood gas analysis is performed according to the changes in the condition; blood routine, electrolytes, CRP, procalcitonin, LDH, blood coagulation function indicators, blood lactic acid, etc. are tested at least once every 2 days; liver function, kidney function , ESR, IL-6, IL-8, lymphocyte subsets, at least once every 3 days; chest imaging examination, usually every 2 days. For patients with ARDS, routine ultrasound examination of the heart and lungs at the bedside is recommended to observe extravascular lung water and cardiac parameters. For monitoring of extracorporeal membrane oxygenation (ECMO) patients, refer to the implementation section of ECMO.
Treatment plan
(A) antiviral treatment
You can try hydroxychloroquine sulfate or chloroquine phosphate, or Abidol for oral administration, interferon nebulization and inhalation, interferon κ is preferred, and interferon α recommended by the national scheme can also be applied. It is not recommended to use 3 or more antivirals at the same time. The viral nucleic acid should be stopped in time after it becomes negative. The efficacy of all antiviral drugs remains to be evaluated in further clinical studies.
For patients with severe and critical viral nucleic acid positives, recovery plasma can be used for recovery. For detailed operation and management of adverse reactions, please refer to the "Clinical Treatment Program for Recovery of New Coronary Pneumonia Patients During Recovery Period" (trial version 1). Infusion within 14 days of the onset may be more effective. If the viral nucleic acid is continuously detected in the later stage of the disease, it may also be tried in the recovery period of the plasma treatment.
(II) treatment of light and ordinary patients
Supportive treatment needs to be strengthened to ensure sufficient heat; pay attention to water and electrolyte balance to maintain internal environment stability; closely monitor patients' vital signs and finger oxygen saturation. Give effective oxygen therapy in time. Antibacterials and glucocorticoids are not used in principle. The patient's condition needs to be closely monitored. If the condition develops significantly and there is a risk of becoming severe, it is recommended to take comprehensive measures to prevent the disease from progressing to severe. Low-dose short-range glucocorticoids can be used with caution (see the application section of glucocorticoids for specific protocols). ). Heparin anticoagulation and high-dose vitamin C are recommended. Low-molecular-weight heparin 1 to 2 per day, until the patient's D-dimer level returned to normal. Once fibrinogen degradation product (FDP) ≥10 µg / mL and / or D-dimer ≥5 μg / mL, switch to unfractionated heparin. Vitamin C is administered at a dose of 50 to 100 mg / kg daily, and the continuous use time is aimed at a significant improvement in the oxygenation index. If lung lesions progress, it is recommended to apply a large dose of a broad-spectrum protease inhibitor, ulinastatin, at 600 to 1 million units / day, until the lung imaging examination improves. In the event of a "cytokine storm", intermittent short veno-venuous hemofiltration (ISVVH) is recommended.
(III) Organ function supportive treatment for severe and critically ill patients
1. Protection and maintenance of circulatory function: implement the principle of early and actively controlled fluid replacement. It is recommended to evaluate the effective volume and initiate fluid therapy as soon as possible after admission. Severe patients can choose intravenous or transcolonic fluid resuscitation depending on the conditions. The preferred supplement is lactated Ringer's solution. Regarding vasoactive drugs, noradrenaline and dopamine are recommended to maintain vascular tone and increase cardiac output. For patients with shock, norepinephrine is the first choice. It is recommended to start small doses of vasoactive drugs at the same time as fluid resuscitation to maintain circulation stability and avoid excessive fluid infusion. Cardioprotective drugs are recommended for severe and critically ill patients, and sedative drugs that inhibit the heart are avoided as much as possible. For patients with sinus bradycardia, isoprenaline can be used. For patients with sinus rhythm, a heart rate of <50 beats / min and hemodynamic instability, intravenous pumping of small doses of isoproterenol or dopamine is recommended to maintain the heart rate at about 80 beats / min.
2. Reduce pulmonary interstitial inflammation: 2019-nCoV leads to severe pulmonary interstitial lesions that can cause lung function deterioration. It is recommended to use a large dose of a broad-spectrum protease inhibitor ulinastatin.
3. Protection of renal function: Reasonable anticoagulant therapy and appropriate fluid therapy are recommended as soon as possible. See chapter "Cytokine storm" for prevention, protection and maintenance of circulatory function.
4. Protection of intestinal function: Prebiotics can be used to improve the intestinal microecology of patients. Use raw rhubarb (15-20 g plus 150 ml warm boiling water) or Dachengqi decoction for oral administration or enema.
5. Nutritional support: parenteral nutrition is preferred, via nasal feeding or via jejunum. The whole protein nutrient preparation is preferred, and the energy is 25-35 kcal / kg (1 kcal = 4.184 kJ) per day.
6. Prevention and treatment of cytokine storm: It is recommended to use large doses of vitamin C and unfractionated heparin. Large doses of vitamin C are injected intravenously at a dose of 100 to 200 mg / kg per day. The duration of continuous use is to significantly improve the oxygenation index. The use of large Dose of the broad-spectrum protease inhibitor ulinastatin, given 1.6 million units, once every 8 h, under mechanical ventilation, when the oxygenation index> 300 mmHg can be reduced to 1 million units / d. Anticoagulation can be taken The treatment protects endothelial cells and reduces the release of cytokines. When FDP ≥ 10 µg / mL and / or D-dimer ≥ 5 μg / mL, heparin (3-15 IU / kg per hour) is given anticoagulation. Heparin is used for the first time. The patient's coagulation function and platelets must be re-examined 4 h later. ISVVH is used for 6 to 10 h every day.
7. Sedation and artificial hibernation: Patients undergoing mechanical ventilation or receiving ECMO need to be sedated on the basis of analgesia. For patients with severe man-machine confrontation during the establishment of an artificial airway, short-term application of low-dose muscle relaxants is recommended. Hibernation therapy is recommended for severe patients with oxygenation index <200 mmHg. Artificial hibernation therapy can reduce the body's metabolism and oxygen consumption, and at the same time dilate the pulmonary blood vessels to significantly improve oxygenation. It is recommended to use continuous intravenous bolus medication, and the patient's blood pressure should be closely monitored. Use opioids and dexmedetomidine with caution. Because severely ill patients often have elevated IL-6 levels, which can easily lead to bloating, opioids should be avoided; 2019-nCoV can still inhibit sinus node function and cause sinus bradycardia, so it should be used with caution on the heart. Inhibitory sedatives. In order to prevent the occurrence and exacerbation of lung infections, and to avoid prolonged excessive sedation, try to withdraw muscle relaxants as soon as possible. It is recommended to monitor the depth of sedation closely.
8. Oxygen therapy and respiratory support: ① Nasal catheter or mask oxygen therapy, SaO2 ≤93% under resting air condition, or SaO2 <90% after activity, or oxygenation index (PaO2 / FiO2) 200-300 mmHg; With or without respiratory distress; continuous oxygen therapy is recommended. ② High-flow nasal cannula oxygen therapy (HFNC), receiving nasal cannula or mask oxygen therapy for 1-2 hours, oxygenation fails to meet treatment requirements, and respiratory distress does not improve; or hypoxemia during treatment And / or exacerbation of respiratory distress; or an oxygenation index of 150 to 200 mmHg; HFNC is recommended. ③ Noninvasive positive pressure ventilation (NPPV), receiving 1 to 2 h of HFNC oxygenation does not achieve the treatment effect, and there is no improvement in respiratory distress; or hypoxemia and / or exacerbation of respiratory distress during treatment; or When the oxygenation index is 150 ～ 200 mmHg; NPPV can be selected. ④ Invasive mechanical ventilation, HFNC or NPPV treatment 1 to 2 hours of oxygenation can not meet the treatment requirements, no improvement in respiratory distress; or hypoxemia and / or exacerbation of respiratory distress during treatment; or oxygenation index <150 mmHg; invasive ventilation should be considered. Protective ventilation strategies with a small tidal volume (4-8 mL / kg ideal body mass) as the core are preferred.
9. Implementation of ECMO: Those who meet one of the following conditions may consider implementing ECMO. ① PaO2 / FiO2 <50 mmHg for more than 1 h; ② PaO2 / FiO2 <80 mmHg for more than 2 h; ③ Arterial blood pH <7.25 with PaCO2> 60 mmHg for more than 6 h. ECMO mode is preferred for intravenous-venous ECMO.
(IV) Special problems and treatment in treatment
1. Application of glucocorticoids: Use glucocorticoids with caution. Imaging showed significant progress in pneumonia. Patients with SaO2 ≤ 93% or shortness of breath (respiratory frequency ≥ 30 breaths / min) or oxygenation index ≤ 300 mmHg in the state of no oxygen inhalation. Glucocorticoids can be added at risk of intubation. Patients are advised to withdraw promptly from glucocorticoid use when intubation or ECMO support can maintain effective blood oxygen concentrations. For non-severe patients using methylprednisolone, the recommended dose is controlled at 20 to 40 mg / d, severe patients are controlled at 40 to 80 mg / d, and the course of treatment is generally 3 to 6 days. Can be increased or decreased according to the body weight.
2. Use of immunoregulatory drugs: Subcutaneous injection of thymosin 2 to 3 times per week has certain effects on improving patients' immune function, preventing the disease from becoming worse, and shortening the time of detoxification. Due to the lack of specific antibodies, high-dose intravenous immunoglobulin therapy is currently not supported. However, some patients have low levels of lymphocytes and are at risk of co-infection with other viruses. Human immunoglobulin can be infused intravenously at 10 g / d for 3 to 5 days.
3. Accurate diagnosis and treatment of combined bacterial and fungal infections: clinical microbiological monitoring of all severe and critically ill patients. The sputum and urine of the patients are kept daily for culture, and the patients with high fever should be cultured in time. All patients with suspected sepsis who have indwelling vascular catheters should be sent for peripheral venous blood culture and catheter blood culture at the same time. All patients with suspected sepsis may consider collecting peripheral blood for molecular diagnostic tests for etiologies, including PCR-based molecular biology testing and next-generation sequencing.
Elevated procalcitonin levels have implications for the diagnosis of sepsis / septic shock. When patients with new type of coronavirus pneumonia become more severe, there is an increase in CRP levels, which is not specific for the diagnosis of sepsis caused by bacterial and fungal infection.
Critically ill patients with open airways are often prone to bacterial and fungal infections at a later stage. If sepsis occurs, empirical anti-infective treatment should be given as soon as possible. For patients with septic shock, empirical antibacterial drugs can be used in combination before obtaining an etiology diagnosis, while covering the most common Enterobacteriaceae, Staphylococcus and Enterococcus infections. Patients with infection after hospitalization can choose β-lactamase inhibitor complex. If the treatment effect is not good, or the patient has severe septic shock, it can be replaced with carbapenem drugs. If considering enterococcal and staphylococcal infections, glycopeptide drugs (vancomycin) can be added for empirical treatment, daptomycin can be used for bloodstream infections, and linezolid can be used for lung infections. Attention should be paid to catheter-related infections in critically ill patients, and treatment should be empirically covered with methicillin-resistant staphylococci. Glycopeptide drugs (vancomycin) can be used for empirical treatment. Candida infection is also more common in critically ill patients. Candida should be covered empirically when necessary. Echinocin drugs can be added. With the length of hospitalization of critically ill patients, drug-resistant infections have gradually increased. At this time, the use of antibacterial drugs must be adjusted according to drug sensitivity tests.
4. Nosocomial infection prevention and control: ① In accordance with the Basic System for Infection Prevention and Control of Medical Institutions (Trial) of the National Health and Health Commission in 2019, actively implement evidence-based infection prevention and control clustering intervention strategies to effectively prevent ventilator-related pneumonia and Multidrug-resistant bacteria and fungal infections such as catheter-related bloodstream infections, catheter-related urinary tract infections, carbapenem-resistant gram-negative bacilli. ② Strictly follow the National Health and Health Commission's "Technical Guidelines for the Prevention and Control of New Coronavirus Infection in Medical Institutions (First Edition)", "Guidelines for the Use of Common Medical Protective Products in the Prevention and Control of Pneumonia of New Coronavirus Infection (Trial)" and "New Coronary Pneumonia" During the epidemic, the technical guidelines for protection of medical personnel (trial), strengthened process management, correctly selected and used personal protective equipment such as masks, gowns, protective clothing, eye masks, protective masks, gloves, and strict implementation of various disinfection and isolation measures. Minimize the risk of nosocomial infections and prevent 2019-nCoV infections in hospitals by medical staff.
5. Treatment of infants and young children: only mild oral symptomatic treatment is required for mild children. In addition to symptomatic oral administration for children with common type, syndrome differentiation of traditional Chinese medicine can be considered. If combined with bacterial infection, antibacterial drugs can be added. Severely ill children are mainly symptomatic and supportive treatment. Ribavirin injection was given antiviral therapy empirically at 15 mg / kg (2 times / day). The course of treatment did not exceed 5 days.
(V) Treatment plan of integrated traditional Chinese and western medicine
The combination of traditional Chinese and western medicine for the treatment of new coronavirus pneumonia can improve the synergistic effect. For adult patients, the condition can be improved through TCM syndrome differentiation. For light patients, those with a syndrome of wind-heat type are given the traditional Chinese medicine Yinqiaosan plus and minus treatment; those with gastrointestinal symptoms and those with damp-wetting and yang-type syndrome are given the addition and subtraction of Zhipu Xialing Decoction and Sanren Decoction. For ordinary patients, those with syndromes of hot and evil stagnation of lungs can be treated with Chinese medicine Ma Xing Shi Gan Decoction; those with syndromes of dampness and stagnation of lungs can be treated with traditional Chinese medicine Da Yuan Yin, Gan Lu Fang Dan, etc., which can be controlled to some extent Progression of the disease, reducing the occurrence of common to severe; for anorexia, nausea, bloating, fatigue, anxiety and insomnia, the addition and subtraction of Chinese medicine Xiao Chai Hu Tang can significantly improve symptoms. For severe patients, if the fever persists, or even the high fever, bloating, and dry stools are closed, and those who are heat-tolerant and the lungs are closed, give the Chinese medicine Dachengqi Decoction enema to relieve fever or reduce fever, or use Chinese medicine. The treatment of Baihu Decoction, Shengjiang San and Xuanbai Chengqi Decoction were added and subtracted to cut off the condition and reduce the occurrence of heavy to critical illness. Children with light patients, when the disease belongs to the defender, can be added or subtracted from Yinqiaosan or Xiangsusan. Ordinary children, those with damp heat and closed lungs, are given Ma Xing Shi Gan Decoction and Sanren Decoction; those with moderate scorching dampness and heat such as bloating and vomiting with abdominal distension can be added or subtracted without changing Jinzhengqi San. For severe patients with epidemic and closed lung (currently rare in the country), refer to the adult Xuanbai Chengqi Decoction and Manna Disinfection Danjiao; if the poison is hot, the gas can't pass, and the medicine is not good, the Rhubarb Decoction is given to enema for a short time.
(F) discharge standards
Patients who meet the following conditions at the same time can be considered for discharge: ① The body temperature returns to normal> 3 d; ② Respiratory symptoms have improved significantly; ③ Imaging examination of the lungs shows a marked improvement in acute exudative lesions; ④ Negative nucleic acid test (sampling time) At least 1 d); ⑤ After the nucleic acid test of the respiratory specimen is negative, the fecal pathogenic nucleic acid test is also negative; ⑥ The total disease course is more than 2 weeks.
(VII) Health management of discharged patients
1. For discharged patients, close follow-up is still required. Follow-up is recommended from 2 weeks and 4 weeks after discharge to the designated follow-up clinic.
2. When the patient is discharged from the hospital, the place of residence and address in the city should be specified.
3. Patients should rest at home for 2 weeks after leaving the hospital, avoid activities in public places, and must wear masks when going out.
4. According to the patient's address (including hotel or hotel), the relevant district health and health committee will organize the corresponding medical institution to do a good job of health management. Professionals will visit the patient's temperature twice a day for 2 weeks, ask their health status, and carry out related health education.
5. If fever and / or respiratory symptoms recur, the corresponding medical institution shall report to the District Health and Health Commission and the District Centers for Disease Control and Prevention in a timely manner, and assist in sending them to the designated medical institution in the area for treatment.
6. After receiving the report, the District Health and Health Committee and the District Centers for Disease Control and Prevention report to the superior department in a timely manner.
Conflict of interest: All authors declare no conflict of interest
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