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Since December 2019, many cases of novel coronavirus pneumonia have been found in Wuhan City, Hubei Province, and with the spread of the epidemic, such cases have also been found in other regions of China and overseas. As an acute respiratory infectious disease, the disease has been listed as a Class B infectious disease as provided by the "Law of the People's Republic of China on Prevention and Control of Infectious Diseases", and is managed as a Class A infectious disease. With a deepened understanding of the disease and accumulation of experience in diagnosis and treatment, we revised "The Diagnosis and Treatment Plan for COVID-19 (Provisional 5th edition)" to make the "The Diagnosis and Treatment Plan for COVID-19 (Provisional 6th edition)".
I. Pathogen Characteristics
The Novel Coronavirus belonging to the genus of betacoronavirus. The enveloped viral particles may appear spherical or oblong, with a diameter of 60-140nm. The genetic characteristics are distinctively different from SARS-CoV or MERS-CoV. Current research found more than 85% homology between the sequences of 2019-nCoV and bat SARS-like coronavirus (bat-SL-CoVZC4). When cultured in vitro, 2019-nCoV appears after 96 hours in the inoculated human respiratory epithelial cells and after 6 days in VeroE6 or Huh-7 cell lines.
Most of the knowledge on physicochemical properties of coronavirus comes from the research on SARS-CoV and MERS-CoV. 2019-nCoV is sensitive to UV radiation and heat, and can be inactivated by heating (30 minutes at 56-degree celsius), diethyl ether, 75% ethanol, chlorine-containing disinfectants, peracetic acid, and organic solvents including chloroform. Chlorhexidine does not effectively inactivate the virus.
II. Epidemiological Characteristics
(1) Source of infection. At present, the source of infection is mainly patients infected by the novel coronavirus. Those who are asymptomatic but infected may also become a source of infection.
(2) Route of transmission. The main route of transmission is respiratory droplets and close contact. There is the possibility of aerosol transmission when exposed to high concentration aerosol for a long time in a relatively closed environment.
(3) Susceptible populations.
The population is generally susceptible.
III. Clinical Characteristics
(1) Clinical presentation. Based on the current epidemiological investigation, the incubation period is 1-14 days, and most often between 3-7 days.
The primary presentations are fever, dry cough, and fatigue. A minority of patients have symptoms such as nasal congestion, nasal discharge, sore throat, muscle pain, and diarrhea. Severe patients often suffer from dyspnea and/or hypoxemia one week after onset, and severe patients can rapidly progress to acute respiratory distress syndrome, septic shock, difficult to correct metabolic acidosis, coagulation dysfunction and multiple organ failure. It is worth noting that severe and critical patients may have moderate to low fever or even no obvious fever during the course of the disease.
Patients with the mild form of the disease present only as low fever, slight fatigue, and so forth, with no lung inflammation.
Judging from the current cases, most patients have a good prognosis and a minority are in critical condition. The prognosis of the elderly and those with chronic underlying diseases is more poor. The symptoms of child cases are relatively mild.
(2) Laboratory examination.
In the early stage of the disease, the total number of peripheral blood leukocytes is normal or decreased, and the lymphocyte count was decreased, and some patients may have increased liver enzyme, lactate dehydrogenase (LDH), myoenzyme and myoglobin, and some critically ill patients may have elevated troponin. C-reactive protein (CRP) and erythrocyte sedimentation rate increased in most patients, and procalcitonin was normal. In severe cases, D- dimer increased and peripheral blood lymphocytes progressively decreased. Inflammatory cytokines often increase in severe and critical patients.
Novel coronavirus nucleic acid can be detected in nasopharyngeal swabs, sputum and other lower respiratory tract secretions, blood, feces and other samples.
In order to improve the positive rate of nucleic acid detection, it is suggested that sputum be collected as much as possible, collecting secretions from the lower respiratory tract of patients undergoing tracheal intubation, and sending samples for examination as soon as possible after collection.
(3) Chest Imaging.
In the early stage, there are multiple small patches and interstitial changes, most notably in the outer lung. It further develops into multiple ground-glass opacity and infiltration shadows in both lungs; and in severe cases, consolidation of the lungs may occur, and pleural effusion is rare.
IV. Diagnostic Standards
(1) Suspected cases.
Comprehensively analyze combinations of the following epidemiological history and clinical presentations:
- Epidemiological history
(1) Within 14 days prior to onset, had history of travel or residence in Wuhan or surrounding regions, or other communities reporting cases;
2. Within 14 days before onset had a history of contact with those infected by the novel coronavirus (positive nucleic acid testing);
(3) Within 14 days prior to onset, had contact with patients who had a fever or respiratory tract symptoms that had come from Wuhan, its surrounding regions, or other communities reporting cases.
(4) Aggregated onset.
- Clinical presentation:
(1) Fever and/or respiratory tract symptoms;
(2) Having the imaging features of novel coronavirus pneumonia discussed above;
(3) The white blood cell count is normal or decreased and lymphocyte count was decreased in the early stage of the disease.
Where there are any of the epidemiologic history items, and any 2 of the clinical presentions are met. Where there is no clear epidemiological history, and at least 3 of the clinical presentations are met.
(2) Confirmed cases.
Suspected cases have one of the following pathological evidence:
- Tests positive for real-time fluorescence RT-PCR detection of novel coronavirus nucleic acid;
- The viral gene sequencing is highly homologous with the known novel coronavirus.
V. Clinical Classification
(1) Mild form.
Clinical symptoms are minor, imaging does not show signs of lung inflammation.
(2) Regular form.
Has fever and respiratory tract symptoms, imaging shows visible lung inflammation.
(3) Severe form.
Meeting any of the following:
- Shortness of breath, RR above 30 times/min;
- In resting state, oxygen saturation is less than 93%;
- Arterial oxygen partial pressure (PaO2)/ fraction of inspired oxygen (FiO2) < 300mmHg (1mmHg=0.133kPa).
For high altitude (altitude over 1000 meters), (Pa0/F10) should be corrected according to the following formula: Pa0/F10 = 2x [ atmospheric pressure (mmHg)/760]
Where lung imaging shows that the lesion has progressed significantly more than 50% within 24-48 hours, it should be re-classified as severe form.
(4) Critical form.
Meeting any of the following criteria:
- Respiratory failure occurs and mechanical ventilation is required;
- other organ failure requiring ICU monitoring;
VI. Differential diagnosis
(1) COVID-19 cases with mild presentations need to be differentiated from other virus-induced upper respiratory tract infections.
(2) COVID-19 is to be differentiated from pneumonia caused by known viral agents such as influenza, adenovirus, and respiratory syncytial virus, as well as mycoplasma pneumonia. Suspected cases should be tested for common pathogens using methods such as rapid antigen test and multiplex PCR nucleic acid test as much as possible.
(3) Also consider non-infectious diseases such as vasculitis, dermatomyositis, and organizing pneumonia.
VII. Discovery and Reporting of Cases
When a suspected case is discovered by medical workers at various level or type of medical institution, the patient should receive treatment in isolation immediately. Consultations of specialists or primary care clinicians should consider differential diagnosis and report the case online within 2 hours. Samples should be collected for 2019-nCoV nucleic acid testing. The suspected case should then be transferred to designated hospitals under safe transferring conditions immediately. It's recommended that patients who tested positive for other respiratory antigens be tested also for 2019-nCoV if they have had close contact with 2019-nCoV patients.
(1) Determine the place of treatment based on the patients' conditions.
- Suspected and confirmed cases should be treated in quarantine, in designated hospitals with effective isolation and disease control capacity. Suspected cases should be treated in individual isolation. Confirmed cases can be treated with multiple patients in the same isolation room.
- Critical cases shall be put in ICU treatment as soon as possible.
(2) General treatment.
- Treatment for mild cases includes bed rest, supportive treatments, and maintenance of caloric intake. Pay attention to fluid and electrolyte balance and maintain homeostasis. Closely monitor the patient's vitals and oxygen saturation.
- As indicated by clinical presentations, monitor the hematology panel, routine urinalysis, CRP, biochemistry (liver enzymes, cardiac enzymes, kidney function), coagulation, arterial blood gas analysis, chest radiography, and so on. Cytokines can be tested if possible.
- Administer effective oxygenation measures promptly, including nasal catheter, oxygen mask, and high flow nasal cannula.
- Antiviral therapies: Interferon-alpha (adult: 5 million units or equivalent can be added to 2ml sterile water for injection and delivered with a nebulizer twice daily), lopinavir/ritonavir (adult: 200mg/50mg/tablet, 2 tablets twice daily; the length of treatment should not exceed 10 days), ribavirin (recommended in combination with interferon or lopinavir/ritonavir, adult: 500mg twice or three times daily via IV, the length of treatment should not exceed 10 days), chloroquine phosphate (adult: 500mg twice daily; the length of treatment should not exceed 10 days), umifenovir (adult: 200mg three times daily; the length of treatment should not exceed 10 days). Pay attention to the adverse effects associated with lopinavir/ritonavir, such as diarrhea, nausea, vomiting and liver dysfunction, as well as interactions with other medications. The efficacy of the current medications in use will be evaluated in clinical application. Concurrent usage of 3 or more antiviral drugs is not recommended. Corresponding medication should be discontinued should intolerable side effects appear.
- Antibiotic therapies: avoid unjustifiable or inappropriate usage of antibiotics, especially combinatory use of broad-spectrum antibiotics.
(3) Treatment of severe and critical cases.
- Treatment principles: on the basis of symptom management, proactively prevent and manage complications, treat underlying diseases, prevent secondary infections, and support organ functions promptly.
- Respiratory support:
(1) Oxygen therapy: patients with severe symptoms should be receiving oxygenation through nasal cannulas or oxygen masks. Assess the patient timely to determine whether dyspnea and/or hypoxemia have been alleviated.
(2) High flow nasal cannula or non-invasive ventilation: when patients with dyspnea and/or hypoxemia do not respond to regular oxygen therapy, consider using high flow nasal cannula or non-invasive ventilation. If the symptoms do not improve or worsen within a short period of time (1-2 hours), tracheal intubation and invasive mechanical ventilation should be used.
(3) Invasive mechanical ventilation: using lung-protective ventilation strategy (LPVS), i.e. low tidal volume of 4-8ml/kg ideal body weight, and low inspiratory pressure (plateau pressure < 30cm H2O) for mechanical ventilation in order to reduce ventilation-associated lung injury. Patient-ventilator asynchrony is common. Sedation and muscle relaxant should be used appropriately.
(4) Salvage therapy: for patients with severe ARDS, a recruitment maneuver is recommended. When resources allow, prone ventilation should be carried out for 12 hours per day. If prone ventilation is ineffective, extracorporeal membrane oxygenation (ECMO) should be considered if conditions allow.
- Circulatory support: starting with sufficient fluid resuscitation and improve microcirculation. Use vasoactive drugs, and monitor hemodynamics when necessary.
- Use of convalescent plasma collected from recovered patients: indicated for patients with rapid disease progression, and severe or critical cases For usage and dosage, see "COVID-19 Clinical Treatment Plan Using Convalescent Plasma Collected from Recovered Patients (Provisional 1st edition)".
- Other treatment measures
For patients with progressively deteriorating oxygenation index, rapid imaging progression, and overactive inflammatory responses, short-term (3-5 days) glucocorticoid treatment may be used at the clinician's discretion. It's recommended that the dosage should not exceed the equivalence of methylprednisolone at 1-2mg/kg/day, since the immunosuppressive function of high-dose glucocorticoid may delay the clearance of coronavirus from the system. Xuebijing may be given intravenously at 100ml twice a day. Probiotics can be given to maintain intestinal microbiome balance and to prevent secondary bacterial infection. For severe and critical cases with hyper-inflammation, extracorporeal blood purification techniques such as plasma exchange, plasma absorption, plasma perfusion, and hemofiltration may be considered.
Patients often have anxiety and fear, and psychological counseling should be strengthened.
(4) Treatment by Traditional Chinese Medicine.
- Period of Medical Observation
Clinical manifestation 1: lack of energy accompanied by gastrointestinal discomfort
Clinical Manifestation 2: Fatigue with Fever
- Clinical treatment period (confirmed cases)
如有条件,每次服完药可加服大米汤半碗,舌干津液亏虚者可多服至一碗。 (注:如患者不发热则生石膏的用量要小,发热或壮热可加大生石膏用量)。 若症状好转而未痊愈则服用第二个疗程,若患者有特殊情況或其他基础病,第二疗程可以根据实际情况修改处方,症状消失则停药。
2.2 Mild Form
2.4 Serious Form
推荐中成药:喜炎平注射液、血必净注射液、热毒宁注射液、痰热清注射液、醒脑静注射液。 功效相近的药物根据个体情况可选择一种,也可根据临床症状联合使用两种。 中药注射剂可与中药汤剂联合使用。
推荐中成药:血必净注射液、热毒宁注射液、痰热清注射液、醒脑静注射液、参附注射液、生脉注射液、参麦注射液。 功效相近的药物根据个体情况可选择一种,也可根据临床症状联合使用两种。 中药注射剂可与中药汤剂联合使用。
Note: Suggested use of Traditional Chinese Medicine Injections for Severe and Critical Cases
2.6 Recovery Period
IX. Matters for attention after release from isolation or hospital.
(1) Criteria for release from isolation and hospital discharge
1. Temperature returned to normal for 3 days or more;
- Respiratory symptoms have a clear turn for the better;
- Chest radiology findings show substantial improvement of acute exudative lesions.
- Two consecutive negative nucleic acid tests using respiratory tract samples (taken at least 24 hours apart).
Those meeting the requirements above may be released from isolation or hospital.
(2) Matters for attention after hospital discharge.
- Designated hospitals should communicate with primary care facilities at the patient's place of residence and share medical records. Information on the discharged patients should be forwarded to the relevant neighbourhood committees and primary care facilities in a timely manner.
- Discharged patients are at increased risk of acquiring other pathogens due to their reduced immune functions during recovery. It's recommended that the patients: continue to self-monitor for 14 days, wear masks, live in well-ventilated individual suites if possible, reduce close contact with family members, eat separately, practice good hand hygiene, and avoid going outside.
- Follow-up visits are recommended at 2 and 4 weeks after discharge.
X. Transport Priniciples
Implement in accordance with the "Work Plan for Transport of Novel Coronavirus Pneumonia Cases (Provisional)" released by our Commission.
XI. Prevention and Control of Infection in Medical Establishments
Copy sent to：The joint mechanism (leading group, command department) for the prevention and control of the novel coronavirus pneumonia epidemic of each province, autonomous region, and directly governed municipality, as well as for the Xinjiang Construction and Production Corps.
General Office of the National Health Commission
Released February 18, 2020
Proofread: Qingyang Du