Diagnosis and Treatment Protocol for Coronavirus Disease 2019(Trial Version 7)

(Released by the National Health Commission & National Administration of Traditional Chinese Medicine,People's Republic of China on March 3, 2020)

Since December 2019, multiple cases of Coronavirus Disease 2019 (COVID-19) have been identified in Wuhan, Hubei.With the spread of the epidemic, such cases have also been found in other parts of China and other countries.As an acute respiratory infectious disease, COVID-19 has been included in Class B infectious diseases prescribed in the Law of the People's Republic of China on Prevention and Treatment of Infectious Diseases,and managed as an infectious disease of Class A.By taking a series of preventive control and medical treatment measures, the rise of the epidemic situation in China has been contained to a certain extent, and the epidemic situation has eased in most provinces,but the incidence abroad is on the rise.With the increased understanding of the clinical manifestations and pathology of the disease, and the accumulation of experience in diagnosis and treatment, in order to further strengthen the early diagnosis and early treatment of the disease, improve the cure rate,reduce the mortality rate, avoid nosocomial infection as much as possible and pay attention to the spread caused by the imported cases from overseas, we revised the Diagnosis and Treatment Protocol for COVID-19 (Trial Version 6) to Diagnosis and Treatment Protocol for COVID-19 (Trial Version 7).

I.ETIOLOGICAL CHARACTERISTICS

The novel coronaviruses belong to the β genus.They have envelopes, and the particles are round or oval, often polymorphic, with diameter being 60 to 140 nm.Their genetic characteristics are significantly different from SARS-CoV and MERS-CoV.Current research shows that they share more than 85%homology with bat SARS-like coronaviruses (bat-SL-CoVZC45).When isolated and cultured in vitro,the 2019-nCoV can be found in human respiratory epithelial cells in about 96 hours, however it takes about 6 days for the virus to be found if isolated and cultured in Vero E6 and Huh-7 cell lines.

Most of the know-how about the physical and chemical properties of coronavirus comes from the research on SARS-CoV and MERS-CoV.The virus is sensitive to ultraviolet and heat.Exposure to 56 ℃for 30 minutes and lipid solvents such as ether, 75%ethanol, chlorine-containing disinfectant, peracetic acid, and chloroform can effectively inactivate the virus.Chlorhexidine has not been effective in inactivating the virus.

II.EPIDEMIOLOGICAL CHARACTERISTICS

1.Source of Infection

Now, the patients infected by the novel coronavirus are the main source of infection;asymptomatic infected people can also be an infectious source.

2.Route of Transmission

Transmission of the virus happens mainly through respiratory droplets and close contact.There is the possibility of aerosol transmission in a relatively closed environment for a long-time exposure to high concentrations of aerosol.As the novel coronavirus can be isolated in feces and urine, attention should be paid to feces or urine contaminated environmental that leads to aerosol or contact transmission.

3.Susceptible Groups

People are generally susceptible.

III.PATHOLOGICAL CHANGES

Pathological findings from limited autopsies and biopsy studies are summarized below:

1.Lungs

Solid changes of varying degrees are present in the lungs.

Alveolar damage involves fibromyxoid exudation and hyaline membrane formation.The exudates are composed of monocytes and macrophages, with plenty of multinucleated syncytial cells.Type II alveolar epithelial cells are markedly hyperplastic, some of which are desquamated.Viral inclusions are observed in type II alveolar epithelial cells and macrophages.Alveolar interstitium is marked with vascular congestion and edema,infiltration of monocytes and lymphocytes, and vascular hyaline thrombi.The lungs are laden with hemorrhagic and necrotic foci, along with evidence of hemorrhagic infarction.Organization of alveolar exudates and interstitial fibrosis are partly present.

The bronchi are filled with desquamated epithelial cells, mucus and mucus plugs.Hyperventilated alveoli,interrupted alveolar interstitium and cystic formation are occasionally seen.

On electron microscopy, cytoplasmic COVID-19 viruses are observed in the bronchial epithelium and type II alveolar epithelium.COVID-19 virus antigen positivity in some alveolar epithelia and macrophages are revealed through immunohistochemistry staining, which are positive for COVID-19 virus nucleic acid via RT-PCR.

2.Spleen, Hilar Lymph Nodes and Bone Marrow

The spleen is evidently shrunk.Lymphocytopenia and focal hemorrhage and necrosis are present.Macrophagocyte proliferation and phagocytosis are noted in the spleen.Lymph nodes are found with sparse lymphocytes and occasional necrosis.CD4+ T and CD8+ T cells are present in reduced quantity in the spleen and lymph nodes, revealed by immunohistochemistry staining.Pancytopenia is identified in bone marrow.

3.Heart and Blood Vessels

Degenerated or necrosed myocardial cells are present, along with mild infiltration of monocytes,lymphocytes and/or neutrophils in the cardiac interstitium.Endothelial desquamation, endovasculitis and thrombi are seen in some blood vessels.

4.Liver and Gall Bladder

Appearing enlarged and dark-red, the liver is found degenerated with focal necrosis infiltrated with neutrophils.The liver sinusoids are found hyperemic.The portal areas are infiltrated with lymphocytes and monocytes and dotted with microthrombi.The gall bladder is prominently filled.

5.Kidneys

The kidneys are noted with protein exudation in the Bowman's capsule around glomeruli,degeneration and desquamation of the epithelial cells of renal tubules, and hyaline casts.Microthrombi and fibrotic foci are found in the kidney interstitium.

6.Other Organs

Cerebral hyperemia and edema are present,with degeneration of some neurons.Necrosis foci are noted in the adrenal glands.Degeneration,necrosis and desquamation of epithelium mucosae at varying degrees are present in the esophageal,stomach and intestine.

IV.CLINICAL CHARACTERISTICS

1.Clinical Manifestations

Based on the current epidemiological investigation, the incubation period is one to 14 days, mostly three to seven days.

Main manifestations include fever, fatigue and dry cough.Nasal congestion, runny nose, sore throat, myalgia and diarrhea are found in a few cases.Severe cases mostly developed dyspnea and/or hypoxemia after one week.In severe cases,patients progress rapidly to acute respiratory distress syndrome, septic shock, metabolic acidosis that is difficult to correct, coagulopathy, multiple organ failure and others.It is worth noting that for severe and critically ill patients, their fever could be moderate to low, or even barely noticeable.

Some children and neonatal cases may have atypical symptoms, manifested as gastrointestinal symptoms such as vomiting and diarrhea, or only manifested as low spirits and shortness of breath.

The patients with mild symptoms did not develop pneumonia but only low fever and mild fatigue.

From current situations, most patients have good prognosis and a small number of patients are critically ill.The prognosis for the elderly and patients with chronic underlying diseases is poor.The clinical course of pregnant women with COVID-19 is similar to that of patients of the same age.Symptoms in children are relatively mild.

2.Laboratory Tests

2.1 General findings

In the early stages of the disease, peripheral WBC count is normal or decreased and the lymphocyte count decreases.Some patients see an increase in liver enzymes, lactate dehydrogenase(LDH), muscle enzymes and myoglobin.Elevated troponin is seen in some critically ill patients while most patients have elevated C-reactive protein and erythrocyte sedimentation rate and normal procalcitonin.In severe cases, D-dimer increases and peripheral blood lymphocytes progressively decrease.Severe and critically ill patients often have elevated inflammatory factors.

2.2 Pathogenic and serological findings

1) Pathogenic findings: Novel coronavirus nucleic acid can be detected in nasopharyngeal swabs,sputum, lower respiratory tract secretions, blood, feces and other specimens using RT-PCR and/or NGS methods.It is more accurate if specimens from lower respiratory tract (sputum or air tract extraction) are tested.The specimens should be submitted for testing as soon as possible after collection.

2) Serological findings: COVID-19 virus specific IgM becomes detectable around 3-5 days after onset;IgG reaches a titration of at least 4-fold increase during convalescence compared with the acute phase.

3.Chest Imaging

In the early stage, imaging shows multiple small patchy shadows and interstitial changes,apparent in the outer lateral zone of lungs.As the disease progresses, imaging then shows multiple ground glass opacities and infiltration in both lungs.In severe cases, pulmonary consolidation may occur while pleural effusion is rare.

V.CASE DEFINITIONS

1.Suspect Cases

Considering both the following epidemiological history and clinical manifestations:

1.1 Epidemiological history

1.1.1 History of travel to or residence in Wuhan and its surrounding areas, or in other communities where cases have been reported within 14 days prior to the onset of the disease;

1.1.2 In contact with novel coronavirus infected people (with positive results for the nucleic acid test)within 14 days prior to the onset of the disease;

1.1.3 In contact with patients who have fever or respiratory symptoms from Wuhan and its surrounding area, or from communities where confirmed cases have been reported within 14 days before the onset of the disease; or

1.1.4 Clustered cases (2 or more cases with fever and/or respiratory symptoms in a small area such families, offices, schools etc within 2 weeks).

1.2 Clinical manifestations

1.2.1 Fever and/or respiratory symptoms;

1.2.2 The aforementioned imaging characteristics of COVID-19;

1.2.3 Normal or decreased WBC count, normal or decreased lymphocyte count in the early stage of onset.

A suspect case has any of the epidemiological history plus any two clinical manifestations or all three clinical manifestations if there is no clear epidemiological history.

2.Confirmed Cases

Suspect cases with one of the following etiological or serological evidences:

2.1 Real-time fluorescent RT-PCR indicates positive for new coronavirus nucleic acid;

2.2 Viral gene sequence is highly homologous to known new coronaviruses.

2.3 COVID-19 virus specific Ig M and IgG are detectable in serum; COVID-19 virus specific IgG is detectable or reaches a titration of at least 4-fold increase during convalescence compared with the acute phase.

VI.CLINICAL CLASSIFICATION

1.Mild Cases

The clinical symptoms were mild, and there was no sign of pneumonia on imaging.

2.Moderate Cases

Showing fever and respiratory symptoms with radiological findings of pneumonia.

3.Severe Cases

Adult cases meeting any of the following criteria:

3) Arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2)300mmHg(l mmHg=0.133kPa);

In high-altitude areas (at an altitude of over 1,000 meters above the sea level), PaO2/ FiO2 shall be corrected by the following formula:

PaO2/FiO2 x[Atmospheric pressure (mmHg)/760]

Cases with chest imaging that showed obvious lesion progression within 24-48 hours ＞50% shall be managed as severe cases.

Child cases meeting any of the following criteria:

3) Labored breathing (moaning, nasal fluttering,and infrasternal, supraclavicular and intercostal retraction), cyanosis, and intermittent apnea;

4) Lethargy and convulsion;

5) Difficulty feeding and signs of dehydration.

4.Critical Cases

Cases meeting any of the following criteria:

4.1 Respiratory failure and requiring mechanical ventilation;

4.2 Shock;

4.3 With other organ failure that requires ICU care.

VII.CLINICAL EARLY WARNING INDICATORS OF SEVERE AND CRITICAL CASES

1.Adults.

1.1 The peripheral blood lymphocytes decrease progressively;

1.2 Peripheral blood inflammatory factors,such as IL-6 and C-reactive proteins, increase progressively;

1.3 Lactate increases progressively;

1.4 Lung lesions develop rapidly in a short period of time.

2 Children.

2.1 Respiratory rate increased;

2.2 Poor mental reaction and drowsiness;

2.3 Lactate increases progressively;

2.4 Imaging shows infiltration on both sides or multiple lobes, pleural effusion or rapid progress of lesions in a short period of time;

2.5 Infants under the age of 3 months who have either underlying diseases (congenital heart disease, bronchopulmonary dysplasia, respiratory tract deformity, abnormal hemoglobin, and severe malnutrition, etc.) or immune deficiency or hypofunction (long-term use of immunosuppressants).

VIII.DIFFERENTIAL DIAGNOSIS

1.The mild manifestations of COVID-19 need to be distinguished from upper respiratory tract infections caused by other viruses.

2.COVID-19 is mainly distinguished from other known viral pneumonia and mycoplasma pneumoniae infections such as influenza virus,adenovirus and respiratory syncytial virus.Especially for suspect cases, methods such as rapid antigen detection and multiplex PCR nucleic acid detection should be adopted as much as possible for detection of common respiratory pathogens.

3.It should also be distinguished from non-infectious diseases such as vasculitis,dermatomyositis and organizing pneumonia.

IX.CASE FINDING AND REPORTING

Health professionals in medical institutions of all types and at all levels, upon discovering suspect cases that meet the definition, should immediately put them in single room for isolation and treatment.If the cases are still considered as suspected after consultation made by hospital experts or attending physicians, it should be reported directly online within 2 hours; samples should be collected for new coronavirus nucleic acid testing and suspect cases should be safely transferred to the designated hospitals immediately.People who have been in close contact with patients who have been confirmed of new coronavirus infection are advised to perform new coronavirus pathogenic testing in a timely manner, even though common respiratory pathogens are tested positive.

If two nucleic acid tests, taken at least 24-hour apart, of a COVID-19 suspect case are negative,and the COVID-19 virus specific IgM and IgG are negative after 7 days from onset, the suspect diagnosis can be ruled out.

X.TREATMENT

1.Treatment Venue Determined by the Severity of the Disease

1.1 Suspected and confirmed cases should be isolated and treated at designated hospitals with effective isolation, protection and prevention conditions in place.A suspect case should be treated in isolation in a single room.Confirmed cases can be treated in the same room.

1.2 Critical cases should be admitted to ICU as soon as possible.

2.General Treatment

2.1 Letting patients rest in bed and strengthening support therapy; ensuring sufficient caloric intake for patients; monitoring their water and electrolyte balance to maintain internal environment stability;closely monitoring vital signs and oxygen saturation.

2.2 According to patients' conditions, monitoring blood routine result, urine routine result, c-reactive protein (CRP), biochemical indicators (liver enzyme,myocardial enzyme, renal function etc.), coagulation function, arterial blood gas analysis, chest imaging and cytokines detection if necessary.

2.3 Timely providing effective oxygen therapy,including nasal catheter and mask oxygenation and nasal high-flow oxygen therapy.If possible,inhalation of mixed hydrogen and oxygen (H2/O2:66.6%/33.3%) can be applied.

2.4 Antiviral therapy: Hospitals can try Alphainterferon (5 million U or equivalent dose each time for adults, adding 2ml of sterilized water, atomization inhalation twice daily), lopinavir/ritonavir (200 mg/50mg per pill for adults, two pills each time, twice daily, no longer than 10 days), Ribavirin (suggested to be used jointly with interferon or lopinavir/ritonavir, 500 mg each time for adults, twice or three times of intravenous injection daily, no longer than 10 days), chloroquine phosphate (500 mg bid for 7 days for adults aged 18-65 with body weight over 50 kg; 500 mg bid for Days 1&2 and 500 mg qd for Days 3-7 for adults with body weight below 50 kg), Arbidol (200 mg tid for adults,no longer than 10 days).Be aware of the adverse reactions, contraindications (for example, chloroquine cannot be used for patients with heart diseases) and interactions of the above- mentioned drugs.Further evaluate the efficacy of those drugs currently being used.Using three or more antiviral drugs at the same time is not recommend; if an intolerable toxic side effect occurs, the respective drug should be discontinued.For the treatment of pregnant women,issues such as the number of gestational weeks,choice of drugs having the least impact on the fetus,as well as whether pregnancy being terminated before treatment should be considered with patients being informed of these considerations.

2.5 Antibiotic drug treatment: Blind or inappropriate use of antibiotic drugs should be avoided, especially in combination with broadspectrum antibiotics.

3.Treatment of Severe and Critical Cases

3.1 Treatment principle: On the basis of symptomatic treatment, complications should be proactively prevented, underlying diseases should be treated, secondary infections also be prevented, and organ function support should be provided timely.

3.2 Respiratory support:

3.2.1 Oxygen therapy: Patients with severe symptoms should receive nasal cannulas or masks for oxygen inhalation and timely assessment of respiratory distress and/or hypoxemia should be performed.

3.2.2 High-flow nasal-catheter oxygenation or noninvasive mechanical ventilation: When respiratory distress and/or hypoxemia of the patient cannot be alleviated after receiving standard oxygen therapy,high-flow nasal cannula oxygen therapy or noninvasive ventilation can be considered.If conditions do not improve or even get worse within a short time (1-2 hours), tracheal intubation and invasive mechanical ventilation should be used in a timely manner.

3.2.3 Invasive mechanical ventilation: Lung protective ventilation strategy, namely low tidal volume (6-8ml/kg of ideal body weight) and low level of airway platform pressure (＜30cmH2O)should be used to perform mechanical ventilation to reduce ventilator-related lung injury.While the airway platform pressure maintained30cmH2O,high PEEP can be used to keep the airway warm and moist; avoid long sedation and wake the patient early for lung rehabilitation.There are many cases of human-machine asynchronization, therefore sedation and muscle relaxants should be used in a timely manner.Use closed sputum suction according to the airway secretion, if necessary, administer appropriate treatment based on bronchoscopy findings.

3.2.4 Rescue therapy: Pulmonary re-tensioning is recommended for patients with severe ARDS.With sufficient human resources, prone position ventilation should be performed for more than 12 hours per day.If the outcome of prone position ventilation is poor,extracorporeal membrane oxygenation (ECMO)should be considered as soon as possible.Indications include: ①When Fi02＞90%, the oxygenation index is less than 80mmHg for more than 3-4 hours; ②For patients with only respiratory failure when the airway platform pressure35cmH2O, VV-ECMO mode is preferred; if circulatory support is needed, VA- ECMO mode should be used.When underlying diseases are under control and the cardiopulmonary function shows signs of recovery, withdrawal of ECMO can be tried.

3.3 Circulatory support: On the basis of adequate fluid resuscitation, efforts should be made to improve microcirculation, use vasoactive drugs,closely monitor changes in blood pressure, heart rate and urine volume as well as lactate and base excess in arterial blood gas analysis.If necessary,use non-invasive or invasive hemodynamic monitor such as Doppler ultrasound, echocardiography,invasive blood pressure or continuous cardiac output(PiCCO) monitoring.In the process of treatment,pay attention to the liquid balance strategy to avoid excessive or insufficient fluid intake.

If the heart rate suddenly increases more than 20% of the basic value or the decrease of blood pressure is more than 20% of the basic value with manifestations of poor skin perfusion and decreased urine volume, make sure to closely observe whether the patient has septic shock, gastrointestinal hemorrhage or heart failure.

3.4 Renal failure and renal replacement therapy: Active efforts should be made to look for causes for renal function damage in critical cases such as low perfusion and drugs.For the treatment of patients with renal failure, focus should be on the balance of body fluid, acid and base and electrolyte balance, as well as on nutrition support including nitrogen balance and the supplementation of energies and trace elements.For critical cases,continuous renal replacement therapy (CRRT) can be used.The indications include: ① hyperkalemia;② acidosis; ③ pulmonary edema or water overload;④ fluid management in multiple organ dysfunction.

3.5 Convalescent plasma treatment: It is suitable for patients with rapid disease progression,severe and critically ill patients.Usage and dosage should refer to Protocol of Clinical Treatment with Convalescent Plasma for COVID-19 Patients (2nd trial version).

3.6 Blood purification treatment: Blood purification system including plasma exchange,absorption, perfusion and blood/plasma filtration can remove inflammatory factors and block "cytokine storm", so as to reduce the damage of inflammatory reactions to the body.It can be used for the treatment of severe and critical cases in the early and middle stages of cytokine storm.

3.7 Immunotherapy: For patients with extensive lung lesions and severe cases who also show an increased level of IL-6 in laboratory testing,Tocilizumab can be used for treatment.The initial dose is 4-8mg/kg with the recommended dose of 400mg diluted with 0.9% normal saline to 100ml.The infusion time should be more than 1 hour.If the initial medication is not effective, one extra administration can be given after 12 hours (same dose as before).No more than two administrations should be given with the maximum single dose no more than 800mg.Watch out for allergic reactions.Administration is forbidden for people with active infections such as tuberculosis.

3.8 Other therapeutic measures

For patients with progressive deterioration of oxygenation indicators, rapid progress in imaging and excessive activation of the body's inflammatory response, glucocorticoids can be used in a short period of time (three to five days).It is recommended that dose should not exceed the equivalent of methylprednisolone 1-2 mg/kg/day.Note that a larger dose of glucocorticoid will delay the removal of coronavirus due to immunosuppressive effects.Xuebijing 100ml/time can be administered intravenously twice a day.Intestinal microecological regulators can be used to maintain intestinal microecological balance and prevent secondary bacterial infections.

Child severe and critical cases can be given intravenous infusion of γ-globulin.

For pregnant severe and critical cases, pregnancy should be terminated preferably with c- section.

Patients often suffer from anxiety and fear and they should be supported by psychological counseling.

4 Traditional Chinese Medicine Treatment

This disease belongs to the category of plague in traditional Chinese medicine (TCM), caused by the epidemic pathogenic factors.According to the different local climate characteristic and individual state of illness and physical conditions, the following treatment rotocol may vary.The use of over-pharmacopoeia doses should be directed by a physician.

4.1 Clinical observation period

4.1.1 Clinical manifestation

Clinical manifestation 1: Fatigue with gastrointestinal discomfort

Recommended Chinese patent medicine:Huoxiang Zhengqi Capsule (藿香正氣膠囊) (Pill,Liquid, Oral liquid)

4.1.2 Clinical manifestation 2: fatigue with fever

Recommended Chinese patent medicines:Jinhua Qinggan Granule (金花清感顆粒), Lianhua Qingwen Capsule (蓮花清瘟膠囊) (Granule),Shufeng Jiedu Capsule (疏風(fēng)解毒膠囊) (Granule)

4.2 Clinical treatment period (Confirmed Cases)

4.2.1 Qingfei Paidu Decoction (清肺排毒湯)

Scope of application: in accordance with the clinical observations of doctors in various locations,it is suitable for mild, moderate and severe cases,and can be used reasonably with the consideration of the actual conditions of critically ill patients.

The basic formula: Ma Huang (Ephedrae Herba) 9g, Zhi Gan Cao (Glycyrrhizae Radix) 6g,Xing Ren (Armeniacae Semen) 9g, Sheng Shi Gao(Gypsum fibrosum) (decocted first) 15-30g, Gui Zhi (Cinnamomi Ramulus) 9g, Ze Xie (Alismatis Rhizoma) 9g, Zhu Ling (Polyporus) 9g, Bai Zhu(Atractylodis macrocephalae Rhizoma) 9g, Fu Ling (Poria) 15g, Chai Hu (Bupleuri Radix) 16g,Huang Qin (Scutellariae Radix) 6g, Jiang Ban Xia(Pinellinae Rhizoma Praeparatum) 9g, Sheng Jiang(Zingiberis Rhizoma recens) 9g, Zi Wan (Asteris Radix) 9g, Kuan Dong Hua (Farfarae Flos) 9g, She Gan (Belamcandae Rhizoma) 9g, Xi Xin (Asari Radix et Rhizoma) 6g, Shan Yao (Dioscoreae Rhizoma) 12g, Zhi Shi (Aurantii Fructus immaturus)6g, Chen Pi (Citri reticulatae Pericarpium) 6g, Huo Xiang (Pogostemonis Herba) 9g.

Administration: traditional Chinese herbal pieces in decoction.One package per day.Take warm twice(40 minutes after meal in the morning and evening).One course of treatment is for three packages.

If possible, half bowl of rice soup after taking the decoction is advised.For the patients with dry tongue due to fluid depletion, one bowl of rice soup is suggested.(Note: If no fever, the dosage of gypsum should be reduced.In case with fever or high fever,the amount of gypsum can be increased.If the symptoms improve but not toally recovered, continue the second course of treatment.If the patient has a special condition or other underlying diseases,the formula can be modified according to the actual situation in the second course.If the symptoms disappear, the drug should be discontinued.

Reference: The General Office of the National Health Commission of the people's Republic of China, The Office of the National Administration of Traditional Chinese Medicine "Notice on Recommending the Use of Qingfei Paidu Decoction in Pneumonia Treated with Integrated Chinese and Western Medicine for the COVID-19 Infection"(National Administration of Traditional Chinese Medicine Office Medical Letter [2020] No.22)

4.2.2 Mild cases

① Cold-damp constraint in the lung pattern

Clinical manifestation: fever, fatigue,generalized body aches, cough, expectoration, chest tightness and labored breathing, poor appetite,nausea, vomiting and sticky stool, pale enlarged tongue with tooth marks or light red tongue and coating which is white, thick, curd-like, and greasy or white and greasy, and soggy of slippery pulse.

Recommended formula: Sheng Ma Huang(Ephedrae Herba) 6g, Sheng Shi Gao (Gypsum fibrosum) 15g, Xing Ren (Armeniacae Semen) 9g,Qiang Huo (Notopterygii Rhizoma seu Radix) 15g,Ting Li Zi (Lepidii/Descurainiae Semen) 15g, Guan Zhong (Cyrtomii Rhizoma) 9g, Di Long (Pheretima)15g, Xu Chang Qing (Cynanchi paniculati Radix)15g, Huo Xiang (Pogostemonis Herba) 15g, Pei Lan (Eupatorii Herba) 9g, Cang Zhu (Atractylodis Rhizoma) 15g, Yun Ling (Poria) 45g, Sheng Bai Zhu(Atractylodis macrocephalae Rhizoma) 30g, Jiao San Xian (Jiao Shan Zha (Crataegi Fructus), Jiao Shen Qu (Massa medicate fermentata), and Jiao Mai Ya (Hordei Fructus germinatus)) 9g each, Hou Po(Magnoliae officinalis Cortex) 15g, Jiao Bing Lang(Arecae Semen) 9g, Wei Cao Guo (Tsaoko Fructus)9g, Sheng Jiang (Zingiberis Rhizoma recens) 15g.

Administration: one package daily, 600ml after decocting, divide into three times, equally in the morning, afternoon and evening, take before meal.② Damp-heat accumulation in the lung pattern Clinical manifestation: low-grade fever or absence of fever, slight aversion to cold, fatigue,heavy sensation in the head and body, muscle soreness, dry cough with little sputum, sore throat,thirst without desire to drink, or accompanied with chest tightness and epigastric fullness, absence of sweating or disturbed hidrosis, or vomiting with anorexia, loose stool or sticky stool.The tongue is light red and coating is white, thick and greasy or thin and yellow.The pulse is slippery and rapid or soggy.

Recommended formula: Bing Lang (Arecae Semen) 10g, Cao Guo (Tsaoko Fructus) 10g,Hou Po (Magnoliae officinalis Cortex) 10g, Zhi Mu (Anemarrhenae Rhizoma) 10g, Huang Qin(Scutellariae Radix) 10g, Chai Hu (Bupleuri Radix)10g, Chi Shao (Paeoniae Radix rubra) 10g, Lian Qiao (Forsythiae Fructus) 15g, Qing Hao (Artemisiae annuae Herba) (added later) 10g, Cang Zhu(Atractylodis Rhizoma) 10g, Da Qjng Ye (Isatidis Folium) 10g, Sheng Gan Cao (Glycyrrhizae Radix) 5g.

Administration: one pack daily, 400ml after decocting, divide into twice, and half in the morning and half in the evening.

4.2.3 Moderate cases

① Damp-toxin constraint in the lung pattern

Clinical manifestation: fever, cough with little sputum or yellow sputum, chest tightness and shortness of breath, abdominal distension, and constipation with difficult defecation.The tongue body is dark-red, and tongue shape is enlarged.The cotaing is yellow greasy or yellow dry.The pulse is slippery and rapid or wiry and slippery.

Recommended formula: Xuanfei Baidu Fomula(宣肺敗毒方) Sheng Ma Huang (Ephedrae Herba) 6g,Ku Xing Ren: (Armeniacae Semen) 15g, Sheng Shi Gao (Gypsum fibrosum) 30g, Sheng Yi Yi Ren (Coicis Semen) 30g, Mao Cang Zhu (Atractylodis Rhizoma)10g, Guang Huo Xiang (Pogostemonis Herba) 15g,Qing Hao Cao (Artemisiae annuae Herba) 12g, Hu Zhang (Polygoni cuspidati Rhizoma) 20g, Ma Bian Cao (Verbenae Herba) 30g, Gan Lu Gen (Phragmitis Rhizoma) 30g, Ting Li Zi (Lepidii/Descurainiae Semen)15g, Hua Ju Hong (Citri grandis Exocarpium rubrum)15g, Sheng Gan Cao (Glycyrrhizae Radix) 10g.

Administration: one package daily, 400ml after decocting, and equally divide into twice, in the morning and evening.

② Cold-damp obstructing the lung pattern

Clinical manifestation: low-grade fever,unsurfaced fever or no fever, dry cough with little sputum, lassitude and fatigue, chest tightness,stomach discomfort, or nausea, and loose stool.The tongue is pale or light red and coating is white or white greasy.The pulse is soggy.

Recommended formula: Cang Zhu (Atractylodis Rhizoma) 15g, Chen Pi (Citri reticulatae Pericarpium)10g, Hou Po (Magnoliae officinalis Cortex) 10g, Huo Xiang (Pogostemonis Herba) 10g, Cao Guo (Tsaoko Fructus) 6g, ShengMa Huang (Ephedrae Herba) 6g,Qiang Huo (Notopterygii Rhizoma seu Radix) 10g,Sheng Jiang (Zingiberis Rhizoma recens) 10g, Bing Lang (Arecae Semen) 10g.

Administration: one package daily, 400ml after decocting, and equally divide into twice, in the morning and evening.

4.2.4 Severe cases

① Epidemic toxin blocking the lung pattern

Clinical manifestation: fever with red face, cough with little yellow and sticky sputum, or blood-stained sputum, chest tightness and short of breath, lassitude,dryness, bitterness and stickiness in the mouth,nausea and loss of appetite, difficult defecation, and scanty dark urine.The tongue is red with yellow greasy coating.The pulse is slippery and rapid.

Recommended formula: Huashi Baidu Formula(化濕敗毒方)

The basic formula: Sheng Ma Huang (Ephedrae Herba) 6g, Xing Ren (Armeniacae Semen) 9g,Sheng Shi Gao (Gypsum fibrosum) 15g, Gan Cao(Glycyrrhizae Radix) 3g, Huo Xiang (Pogostemonis Herba) (added later) 10g, Hou Po (Magnoliae officinalis Cortex) 10g, Cang Zhu (Atractylodis Rhizoma) 15g, Cao Guo (Tsaoko Fructus) 10g,Fa Ban Xia (Pinellinae Rhizoma Praeparatum) 9g,Fu Ling (Poria) 15g, Sheng Da Huang (Rhei Radix et Rhizoma) (added later) 5g, Sheng Huang Qi(Astragali Radix) 10g, Ting Li Zi (Lepidii/Descurainiae Semen) 10g, Chi Shao (Paeoniae Radix rubra) 10g.

Administration: 1-2 packages daily, decoction,100-200ml each time, 2-4 times per day, oral administration or nasal feeding.

② Blazing of both qi and ying pattern

Clinical manifestation: high fever with polydipsia,tachypnoea and shortness of breath, delirium and unconsciousness, blurred vision or accompanied with macules and papules, or hematemesis, epistaxis or convulsion of the four limbs.The tongue is crimson with little or no coating.The pulse is deep, thready and rapid, or floating, large and rapid pulse.

Recommended formula: Sheng Shi Gao(Gypsum fibrosum) (decocted first) 30-60g, Zhi Mu (Anemarrhenae Rhizoma) 30g, Sheng Di(Rehmanniae Radix) 30-60g, Shui Niu Jiao (Bubali Cornu) (decocted first) 30g, Chi Shao (Paeoniae Radix rubra) 30g, Xuan Shen (Scrophulariae Radix) 30g, Lian Qiao (Forsythiae Fructus) 15g,Dan Pi (Moutan Cortex) 15g, Huang Lian (Coptidis Rhizoma) 6g, Zhu Ye (Phyllostachys nigrae Folium)12g, Ting Li Zi (Lepidii/Descurainiae Semen) 15g,Sheng Gan Cao (Glycyrrhizae Radix) 6g.

Administration: one pack daily, decoction,Shi Gao and Shui Niu Jiao should be decocted first, 100-200 ml each time, 2-4 times per day, oral administration or nasal feeding.

Recommended Chinese patent medicines:Xiyanping Injection (喜炎平注射液), Xuebijing Injection (血必凈注射液), Reduning Injection (熱毒寧注射液), Tanreqing Injection (痰熱清注射液),and Xingnaojing Injection (醒腦靜注射液).Drugs with similar effects can be selected according to individual conditions, or can be used in combination according to clinical symptoms.Traditional Chinese medicine injections can be used together with TCM decoction.

4.2.5 Critical cases

① Internal blockage and external desertion pattern

Clinical manifestation: Dyspnea, panting on exertion or mechanical ventilation required,accompanied with unconsciousness and dysphoria,sweating, cold extremities.The tongue is dark and purple with thick greasy or dry coating.The pulse is floating and large without root.

Recommended formula: Take Su He Xiang Pill(蘇和香丸) or Angong Niuhuang Pill (安宮牛黃丸)with the following decoction composed of Ren Shen(Ginseng Radix) 15g, Hei Shun Pian (Aconiti Radix lateralis praeparata) (decocted first) 10g, Shan Zhu Yu(Corni Fructus) 15g.

If there is mechanical ventilation with abdominal distension, constipation or difficult defecation, 5-10g of Sheng Da Huang (Rhei Radix et Rhizoma) can be considered.If patient-ventilator asynchrony occurs,5-10g of Sheng Da Huang and 5-10g of Mang Xiao(Natrii Sulfas) can be used together with sedation and muscle relaxant.

Recommended Chinese patent medicines:Xuebijing Injection (血必凈注射液), Reduning Injection (熱毒寧注射液), Tanreqing Injection (痰熱清注射液), Xingnaojing Injection (醒腦靜注射液),Shenfu Injection (參附注射液), Shengmai Injection(生脈注射液), and Shenmai Injection (參麥注射液).Drugs with similar effects can be selected according to individual conditions, or can be used in combination according to clinical symptoms.Traditional Chinese medicine injection can be used together with TCM decoction.

Note: Recommended usage of TCM injections for severe and critical cases

The use of TCM injections follows the principle of starting from a small dosage and modifying based on pattern identification in the instructions.The recommended usage is as follows:

Viral infection or combined with mild bacterial infection: 0.9% sodium chloride injection 250ml with Xiyanping Injection (喜炎平注射液) 100mg (bid), or 0.9% sodium chloride injection 250ml with Reduning Injection (熱毒寧注射液) 20ml, or 0.9% sodium chloride Injection 250ml with Tanreqing Injection (清腦靜注射液) 40ml (bid).

High fever with disturbance of consciousness:0.9% sodium chloride injection 250ml with Xingnaojing Injection (醒腦靜注射液) 20ml (bid).

Systemic inflammatory response syndrome(SIRS) or / and multiple organ failure (MOF): 0.9%sodium chloride injection 250ml with Xuebijing Injection (血必凈注射液) 100ml (bid).

Immunosuppression: glucose injection 250ml with Shenmai Injection (參麥注射液) 100ml or Shengmai Injection (生脈注射液) 20-60ml (bid).

4.2.6 Convalescence

① Lung-spleen qi deficiency pattern

Clinical manifestation: shortness of breath,lassitude and fatigue, poor appetite with nausea and vomiting, abdominal fullness, a sense of incomplete evacuation, and sticky loose stool.The tongue is pale and enlarged with white greasy coating.

Recommended formula: Fa Ban Xia (Pinellinae Rhizoma Praeparatum) 9g, Chen Pi (Citri reticulatae Pericarpium) 10g, Dang Shen (Codonopsis Radix)15g, Zhi Huang Qi (Astragali Radix) 30g, Chao Bai Zhu (Atractylodis macrocephalae Rhizoma) 10g, Fu Ling (Poria) 15g, Huo Xiang (Pogostemonis Herba)10g, Sha Ren (AmomiFructus) (added later) 6g, Gan Cao (Glycyrrhizae Radix) 6g.

Administration: one package daily, 400ml after decocting, and equally divide into twice in the morning and evening.

② Deficiency of both qi and yin pattern

Clinical manifestation: fatigue, shortness of breath, dry mouth, thirst, heart palpitation, profuse sweating, poor appetite, low-grade fever or no fever, dry cough with little sputum.The tongue is dry tongue with scanty fluid.The pulse is thready or weak and forceless.

Recommended formula: Nan Sha Shen(Adenophorae Radix) 10g, Bei Sha Shen (Glehniae Radix) 10g, Mai Dong (Ophiopogonis Radix) 15g, Xi Yang Shen (Panacis quinquefolii Radix) 6g, Wu Wei Zi (Schisandrae Fructus) 6g, Sheng Shi Gao (Gypsum fibrosum) 15g, Dan Zhu Ye (Lophatheri Herba) 10g,Sang Ye (Mori Folium) 10g, Lu Gen (Phragmitis Rhizoma) 15g, Dan Shen (Salviae miltiorrhizae Radix) 15g, Sheng Gan Cao (Glycyrrhizae Radix) 6g.

Administration: one package daily, 400ml after decocting, and equally divide into twice in the morning and evening.

XI.DISCHARGE CRITERIA AND AFTER-DISCHARGE COSIDERATIONS

1.Discharge Criteria

1.1 Body temperature is back to normal for more than three days;

1.2 Respiratory symptoms improve obviously;

1.3 Pulmonary imaging shows obvious absorption of inflammation,

1.4 Nucleic acid tests negative twice consecutively on respiratory tract samples such as sputum and nasopharyngeal swabs (sampling interval being at least 24 hours).

Those who meet the above criteria can be discharged.

2.After-discharge Considerations

2.1 The designated hospitals should contact the primary healthcare facilities where the patients live and share patients' medical record, to send the information of the discharged patients to the community committee and primary healthcare facility where the patients reside.

2.2 After discharge, it is recommended for patients to monitor their own health status in isolation for 14 days, wear a mask, live in wellventilated single room if possible, reduce close contact with family members, separate dinning,practice hand hygiene and avoid going out.

2.3 It is recommended for the patients to return to the hospitals for follow-up and re-visit in two and four weeks after discharge.

XII.PATIENTS TRANSPORTATION PRINCIPLES

Patients should be transported in accordance with the Work Protocol for Transfer of the COVID-19 Patients (Trial Version) issued by the National Health Commission.

XIII.NOSOCOMIAL INFECTION PREVENTION AND CONTROL

Measures to prevent and control nosocomial infection should be implemented in accordance with the requirements of the Technical Guidelines for the Prevention and Control of Infection by the Novel Coronavirus in Medical Institutions (First Edition) and the Guidelines on the Usage of Common Medical Protective Equipment against Novel Coronavirus Infection (Trial Version) formulated by the National Health Commission.

The General Office of National Health Commission and the Office of the National Administration of Traditional Chinese Medicien.

The content of TCM is from the Webside of the National Administration of Traditional Chinese Medicine2020-03-20 14:26:54

Printed and distributed on March 3, 2020