Quyết định 3351/QĐ-BYT 2020 Hướng dẫn chẩn đoán và điều trị COVID-19

DECISION

Promulgating the Guidance on diagnosis and treatment of COVID-19 caused by a new strain of Coronavirus (SARS-Cov-2)

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THE MINISTER OF HEALTH

Pursuant to the Government’s Decree No. 75/2017/ND-CP dated June 20, 2017, defining the functions, tasks, powers and organizational structure of the Ministry of Health;

According to the opinion of the Council in charge of updating and supplementing the Guidance on diagnosis and treatment of acute respiratory infections caused by the new strain of Coronavirus (nCoV) established under the Decision No. 319/QD-BYT dated February 06, 2020 by the Minister;

At the proposal of the Director of the Medical Services Administration - The Ministry of Health,

DECIDES:

Article 1.To promulgate together with this Decision the “Guidance on diagnosis and treatment of COVID-19 caused by a new strain of Coronavirus (SARS-Cov-2)”, replacing the “Guidance on diagnosis and treatment of acute respiratory infections caused by SARS-CoV-2 (COVID-19)” attached to the Decision No. 1344/QD-BYT dated March 25, 2020 of the Minister of Health.

Article 2.This Decision takes effect on the date of its signing.

Article 3.Mr. /Ms.: Chief of the Ministry Office, Director of the Medical Services Administration - the Ministry of Health; Chief Inspector; Director Generals and Directors of Directorates, Authorities and Departments under the Ministry of Health; Directors of Hospitals and Institutes under the Ministry of Health; Directors of municipal and provincial Departments of Health; Heads in charge of Healthcare of sectors shall be responsible for implementing this Decision.

GUIDANCE

On diagnosis and treatment of COVID-19 caused by new a strain of Coronavirus (SARS-Cov-2)

(Issued together with the Decision No. 3351/QD-BYT dated July 29, 2020 of the Minister of Health)

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I. OUTLINE

Coronavirus are a large family of viruses that are transmitted from animals to humans and cause illnesses ranging from common cold to more severe diseases threatening human lives, including Severe Acute Respiratory Syndrome (SARS-CoV) in 2002, and the Middle East respiratory syndrome (MERS-CoV) in 2012. Since December 2019, a new strain of Coronavirus (SARS-CoV-2) has been identified as the cause of the acute respiratory infections (COVID-19) epidemic in Wuhan City (Hubei province, China), then spread to all over China and by far most of the countries in the world. On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic. The SARS-CoV-2 strain is not only transmitted from animals to humans but also directly from person to person, mainly through respiratory droplets and contact. Such virus also may be spread by aerosols, especially at health establishments and in crowded places and in enclosed spaces. Currently, there is no evidence for the faecal-oral transmission of such virus.

Persons infected with COVID-19 has diverse clinical presentation: From asymptomatic infection, to severe medical manifestations such as severe pneumonia, respiratory distress, septic shock, multiple organ dysfunction and death, especially in the elderly, people with chronic illnesses or immunodeficiency with TCD4 cell counts decreased below 250 cells/mm3, people with elevated D-Dimer or with co-infection or superinfection of other etiologies like bacteria, fungi.

There are currently no specific drugs and vaccines available for the prevention of COVID-19, therefore the most used measures are supportive and symptomatic treatment. The main preventive measures are early detection and isolation of infected cases.

II. DIAGNOSIS

1. Case definition

1.1. Possible case:

Possible cases shall include the following cases:

A. Patients show symptoms of fever and/oracute respiratory infection that cannot be explained by other causes.

B. Patients show any respiratory symptomsANDhas traveled to/been through/residence in/back fromepidemiological areas* where ongoing community transmission of COVID-19 in the 14 days prior to onset of symptomsORin close contact(**) with a confirmed COVID-19 case in the 14 days prior to onset of symptoms.

*Epidemiological areas:are defined as countries and territories that have confirmed cases of COVID-19 transmitted domestically, or where there is an active outbreak in Vietnam according to the “Interim guidance for surveillance, prevention and control of COVID-19” provided by the Ministry of Health and updated by the General Department of Preventive Medicine.

**Close contact:includes

- Being in contact at health establishments, including: Directly providing healthcare for a confirmed COVID-19 case; working with health staff who is infected with COVID-19; visiting or living in the same room with a confirmed COVID-19 case.

- Being in direct contact with a distance of up to 02 meters with a possible or confirmed COVID-19 case during the illness.

- Living in the same house with a possible or confirmed COVID-19 case during the illness.

- Being in the same teamwork or office with a possible or confirmed COVID-19 case during the illness.

- In the same group of travel, business, entertainment, party, meeting, etc. with a possible or confirmed COVID-19 case during the illness.

- Traveling in the same vehicle (sitting in the same row, in front or behind 02 rows of seats) with a possible or confirmed COVID-19 case during the illness.

1.2. Confirmed case

Means the possible case or any person having a positive test with SARS-CoV-2 virus that are carried out by testing establishments permitted by the ministry of Health.

III. SYMPTOMS

1. Clinical

- Incubation period: From 02 - 14 days, or from 05 - 07 days on average.

- Onset: Common symptoms are fever, dry cough, fatigue and muscle pain. Some cases show symptoms of sore throat, sniffle, runny nose, headache, chesty cough, emesis and diarrhoea.

- Development:

+ Most patients (about more than 80%) have only mild fever, cough, fatigue, no pneumonia and usually recover on their own after about 01 week. However, some cases do not show any clinical presentations.

+ About 14% of patients with severe development such as pneumonia, severe pneumonia need hospitalization, about 5% need treatment in intensive care units with acute respiratory symptoms (hyperpnea, dyspnoea, cyanosis, etc.), acute respiratory distress syndrome (ARDS), septic shock, organ dysfunction including kidney damage and myocardial damage, leading to death.

+ The average time from the initial symptom to severe development is usually about 07 - 08 days.

+ Death occurs more often in the elderly, those who are immunocompromised and have chronic diseases. In adults, old age, high sequential organ dysfunction assessment (SOFA) score upon admission and D-dimer level greater than 1 μg/mL are prognostic factors of increased risk of death.

- Recovery period: After 07 - 10 days of acute period, if there is no ARDS, the patient shall be free from fever, the clinical signs shall gradually return to normal and the patient shall recover from COVID-19.

- There is no evidence of any difference in the clinical presentations of COVID-19 in pregnant women.

- For children, most children infected with COVID-19 have milder clinical presentations compared to adults, or have no symptoms at all. The most common symptoms of COVID-19 in children are fever and cough, or manifestations of pneumonia. However, some children infected with COVID-19 have a multi-system inflammatory lesion similar to signs of Kawasaki disease: fever; erythema or corneal congestion, or swollen oral mucosa, hands, or feet; circulatory failure; manifestations of impaired cardiac function and elevated heart enzyme levels; digestive disorders; coagulopathy and an increase in acute inflammatory indicators.

2. Para-clinical test

Nonspecific hematological and serum biochemistry tests:

- The number of leukocytes in the blood may be normal or decreased; the number of lymphocytes is often decreased, especially in the group of severe development.

- C-reactive protein (CRP) levels are normal or elevated, procalcitonin (PCT) levels are often normal or slightly elevated. In some cases, ALT, AST, CK, LDH may slightly increase.

- In severe cases, the manifestations of organ function dysfunction, coagulopathy, elevated D-dimer, acid-base and electrolyte disorders.

3. X-ray and computed tomography (CT) scan of the lung

- In the early stage or only infection of the upper respiratory tract, X-ray images are normal.

- In the presence of pneumonia, lesions are usually bilateral with signs of interstitial pneumonia or diffuse circle of cloud-like ground glass shadow, in peripheral or lower lobe. Lesions can progress rapidly in ARDS. Signs of cavitation or pleural effusion, pneumothorax are rare.

4. Testing for etiology confirmation

- Detection of SARS-CoV-2 by real-time RT-PCR assay technique or sequencing genes from patient samples.

IV. CLASSIFICATION OF CLINICAL FORMS

COVID-19 disease has the following clinical infection forms:

1. Asymptomatic infection:a person infected with SARS-CoV-2 confirmed by a positive real-time RT-PCR assay, but showing no clinical symptoms.

2. Mild infection: Acute respiratory infection

- A patient infected with SARS-CoV-2 shall have non-specific clinical symptoms such as fever, dry cough, sore throat, sniffle, fatigue, headache and muscle pain.

- No signs of pneumonia or oxygenation impairment i are shown.

3. Moderate infection: Pneumonia

-Adults and children: with pneumonia (fever, cough, shortness of breath, hyperpnea) but no signs of severe pneumonia, SpO2≥ 90% when breathing in the air.

-Babies:Coughing or shortness of breath and hyperpnea. Hyperpnea is defined when the breathing rate ≥ 60 times/minute in newborns under 02 months; ≥ 50 times/minute in babies aged from 2 - 11 months; ≥ 40 times/minute in children aged from 01 - 05 years) and no signs of severe pneumonia are shown.

- Diagnosis shall be based on clinical practice, however, however, interstitial pneumonia or complications shall be detected through X-ray, ultrasound or CT images of the lung.

4. Severe infection - Severe pneumonia

-Adults and children:fever or suspected respiratory infection, accompanied by any of the following signs: the breathing rate > 30 times/minute, severe dyspnoea, or SpO2≤ 93% when breathing room air.

-Babies:Cough or shortness of breath and plus at least one of the following signs: Cyanosis or SpO2< 90%; severe respiratory distress (grunting, chest recession);

+ Or a baby is diagnosed with pneumonia and shows any of the severe signs as follows: inability to breastfeed or drink; lethargy or unconsciousness, or convulsions. Other signs of a pneumonia may be found, such as chest recession, hyperpnea (with the above-mentioned breathing rate).

- While the diagnosis is made on clinical grounds; chest imaging may identify complications.

5. Critical infection

5.1. Acute respiratory distress syndrome (ARDS)

- Onset:Within 01 week of a known clinical insult or new or worsening respiratory symptoms.

- X-ray, CT scan or ultrasound of the lungs:bilateral opacities, not fully explained by volume overload, lobar or lung collapse, or nodules.

- The origin of pulmonary edema not fully explained by cardiac failure or fluid overload. Need objective assessment (e.g. echocardiography) to exclude hydrostatic pressure if no risk factor presents.

- Oxygenation impairment:in adults, classification shall be carried out according to the PaO2/FiO2(P/F) and SpO2/FiO2(S/F) indicators in case where the PaO2is not available:

+ Mild ARDS: 200 mmHg < P/F ≤ 300 mmHg with PEEP or CPAP ≥ 5 cm H2O.

+ Moderate ARDS: 100 mmHg < P/F ≤ 200 mmHg with PEEP ≥ 5 cm H2O).

+ Severe ARDS: P/F ≤ 100 mmHg with PEEP ≥ 5 cmH2O

+ In case where PaO2is not available: S/F ≤ 315 suggests ARDS (including in non-ventilated patients)

- Oxygenation impairment:in children:Based on OI indexes (Oxygenation Index:OI=MAP*×FiO2×100/PaO2) (MAP*: mean airway pressure) or OSI (Oxygenation Index using SpO2: OSI = MAP × FiO2× 100 / SpO2) for patients require invasive mechanical ventilation, and PaO2/FiO2or SpO2/FiO2for continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV):

+ NIV BiLevel or CPAP ≥ 5 cmH2O through masks: PaO2/FiO2≤ 300 mmHg or SpO2/FiO2≤ 264

+ Mild ARDS (invasive mechanical ventilation): 4 ≤ OI < 8 or 5 ≤ OSI < 7.5

+ Moderate ARDS (invasive mechanical ventilation): 8 ≤ OI < 16 or 7.5 ≤ OSI < 12.3

+ Severe ARDS (invasive mechanical ventilation): OI ≥ 16 or OSI ≥ 12.3

5.2. Sepsis

- Adults:showing signs of organ dysfunction include:

+ Altered mental status: drowsiness, drowsiness, lethargy

+ Shortness of breath or dyspnoea, low oxygen saturation

+ Fast heart rate, weak pulse, cold extremities or low blood pressure, skin mottling

+ Oliguria or anuric

+ Laboratory evidence of coagulopathy, thrombocytopenia, acidosis, high lactate, or hyperbilirubinemia, etc.

- Children:suspected or proven infection and ≥ 2 age- based systemic inflammatory response syndrome criteria, of which one must be abnormal temperature or white blood cell count.

5.3. Septic shock

- Adults:persisting hypotension despite volume resuscitation, requiring vasopressors to maintain mean arterial pressure (MAP) ≥ 65 mmHg and serum lactate level > 2 mmol/L.

- Children:septic shock is defined when there is:

+ Any hypotension: systolic blood pressure (SBP) < 5 centile or > 2 SD below normal for age, or babies under 1 year: < 70 mmHg; children from 01 - 10 years: < 70 + 2 x years; children > 10 years old: <90 mmHg).

+ Or two or three of the following signs: altered mental state; tachycardia or bradycardia (heart rate (HR) < 90 beats per minute (bpm) or > 160 bpm in infants and HR < 70 bpm or > 150 bpm in children); prolonged capillary refill (> 2 sec) or feeble pulse; tachypnoea; mottled or cool skin or petechial or purpuric rash; increased lactate; oliguria; hyperthermia or hypothermia.

5.4. Other severe or dangerous complicationspulmonary infarction, stroke, delirium. It is necessary to closely monitor and apply definitive diagnostic measures when in doubt and to take appropriate treatment.

V. DIFFERENTIAL DIAGNOSIS

- It is required to carry out a differential diagnosis of acute respiratory infections caused by SARS-CoV-2 (COVID-19) from acute respiratory infections caused by other common agents, including known severe etiological agents:

+ Seasonal influenza virus (A/H3N2, A/H1N1, B), paramyxovirus, respiratory syncytial virus (RSV),rhinovirus, myxovirrus, adenovirus.

+ Flu syndrome caused by common strains ofcoronavirus.

+ Common bacterial etiologies, including atypical bacteria such as Mycoplasmapneumoniaetc.

+ Other etiologies of severe acute respiratory infections include avian influenza (A/H5N1, A/H7N9, A/H5N6, SARS-CoV, and MERS-CoV).

- It is necessary to carry out differential diagnosis for severe conditions of the patient (respiratory distress, organ dysfunction, etc.) due to other etiologies or due to the severe condition of accompanying chronic diseases.

VI. TESTING, DIAGNOSIS, MONITORING AND REPORTING CASES

- Possible cases are required to be tested to confirm infection with SARS-CoV-2.

- Collecting specimens from the upper respiratory tract (nasopharyngeal and oropharyngeal fluids) for virus identification by real-time RT-PCR technique.

- Where clinical suspicion remains and the upper respiratory tract specimens are negative, specimens from the lower respiratory tract when readily available (expectorated sputum, endotracheal aspirate, or bronchoalveolar lavage) shall be collected.

- For ventilated patients, only specimens from the lower respiratory tract are required.

- The test for SARS-CoV-2 antibodies is not recommended for the diagnosis of COVID-19 infection.

- Possible cases, including those with known common agents, should be tested to confirm SARS-CoV-2 at least once.

- Where suspicion remains, blood cultures shall be carried out, or when there is sepsis, blood cultures should be carried out before using antibiotics. Other etiologies of bacteria and viruses should be tested if there are clinical signs of doubts.

- It is necessary to fully perform para-clinical tests and routine exploration depending on the patient s condition to diagnose, predict and monitor the patient.

- For confirmed COVID-19 cases, it is necessary to collect specimens from the respiratory fluids and carry out test every 02 - 04 days or a shorter period (if necessary) until the test result is negative.

- Cases with positive results for SARS-CoV-2 should be reported to the Ministry of Health or local Centers for Disease Control and Prevention (CDC).

- Determination of epidemiology related to SARS-CoV-2 positive cases such as: place of residence, workplace, travel, making a list of people who have been in direct contact, complying with instructions on monitoring, prevention and control of COVID-19 provided by the Ministry of Health.

VII. Immediate implementation of infection prevention measures

Infection prevention is an important step in the diagnosis and treatment of a patient infected with COVID-19, so it should be taken as soon as the patient arrives at a health establishment. Standard prevention measures should be applied in all areas of a health establishment.

1. At screening and classification areas.

- Suspected COVID-19 patients should be given a mask and directed to isolation area.

- To keep at least 02 m distance between patients.

- Patients shall be guided to cover their noses and mouths upon coughing, sneezing and wash their hands immediately after being in contact with respiratory fluids.

2. Application of droplet precautions.

-  To wear a medical mask if working within 02 m of the patient.

- Possible cases shall be given priority to be placed in single rooms, or a group of those with the same etiological diagnosis shall be placed in the same room. If an etiological diagnosis is not possible, group patients with similar clinical diagnosis and based on epidemiological risk factors, with a spatial separation. Rooms for patients must be well ventilated.

- When providing care in close contact with a patient with respiratory symptoms (e.g. coughing or sneezing), eye protection should be used.

- To limit patient movement within the health establishment and ensure that patients wear medical masks when leaving their rooms.

3. Application of contact precautions.

- Health staff must use personal protection equipment (such as medical masks, eye protection goggles, gloves, gown) when entering patient rooms and remove personal protection equipment when leaving patient rooms and avoid getting dirty hands in their eyes, nose and mouth.

- Equipment (such as stethoscopes, thermometers) must be cleaned and disinfected before using on each patient.

- To avoid contaminating environmental surfaces such as door, light and fan switches, etc.)

- Patient rooms must be well ventilated, windows (if any) should be opened.

- To avoid movement or transport of patients.

- To perform hand hygiene.

4. Application of airborne transmission precautions

- Health staff must use the appropriate personal protection equipment, including gloves, gowns, eye protection, and N95 masks or equivalent when examining, providing healthcare for confirmed or diagnosed cases, or/and performing procedures such as open suctioning of respiratory tract, intubation, bronchoscopy, cardiopulmonary resuscitation.

- If possible, to perform the procedure in a separate room, or a negative pressure room.

- To avoid the presence of unnecessary persons individuals in the room when carrying out such procedures.

VIII. TREATMENT

1. General treatment principles

- To classify the patient and determine where to treat him/her according to the severity of the disease:

+ Possible cases (may be considered as emergency cases):  Shall be examined, monitored and isolated at a separate room at health establishments, specimens should be collected in an appropriate manner for testing for definitive diagnosis.

+ Confirmed cases should be monitored and treated completely isolated.

+ Mild cases (upper respiratory tract infections, mild pneumonia) shall be treated at normal departments and rooms.

+ Severe cases (severe pneumonia and sepsis) should be treated at emergency departments or intensive care units.

+ Severe - critical cases: (Severe respiratory distress, ARDS, septic shock, multiple organ dysfunction) require intensive resuscitation.

- There are currently no specific drugs, therefore the most used measures are supportive and symptomatic treatment.

- To individualize treatments for each case, especially severe - critical cases.

- Some research regimens approved by the Ministry of Health may be used.

- To monitor, detect and handle promptly severe cases and complications.

2. General monitoring and treatment measures

- To rest on beds, patient rooms must be well ventilated, air purification systems or other preventive measures such as ultraviolet light (if any) may be used.

- To clean the nose and throat, the nose moist may be kept with normal saline solution, to rinse the mouth and throat with normal oral cleaning solutions.

- To keep warm.

- To drink adequate water, ensure fluid and electrolyte balance.

- To be careful when infusing patients suffering pneumonia without any signs of shock.

- To ensure nutrition and improve health, supplement vitamins if necessary. For severe - critical cases, to apply nutrition instruction issued by the Association of Emergency, Intensive Care Medicine and Clinical Toxicology.

- In case of high temperature, to reduce fever by paracetamol with a dose of 10 - 15 mg/kg/time, but not more than 60 mg/kg/day for children and no more than 2 grams/day for adults.

- To relieve/block the cough by common antitussives if needed.

- To evaluate, treat, and predict associated chronic medical conditions (if any).

- To counsel, provide psychological support, and motivate the patient.

- To closely monitor clinical signs, progression of lung lesions on chest X-ray and/or chest CT, especially around 07 - 10 days of disease, to detect signs of severe progression such as respiratory distress, circulatory failure to take timely intervention measures.

- There should be minimal first aid equipment and tools at treatment establishments, such as oxygen saturation monitor, oxygen supply system/bottle, oxygen breathing device (nasal cannula, simple masks, and masks with reservoir bags), squeeze ball, masks, and equipment for endotracheal intubation that are appropriate for all ages.

3. Treatment of respiratory distress syndrome

3.1. Oxygen therapy and monitoring

- To give supplemental oxygen therapy immediately to patients with severe acute respiratory infection and respiratory distress, hypoxaemia or shock and target SpO2> 94%.

- Adults with emergency signs (physical exertion, chest recession, cyanosis, or hypoventilation) should receive airway management and oxygen therapy during resuscitation to target SpO2≥ 94%. - To give oxygen through the nasal cannulas (1-4 liters/minute), or simple masks, or masks with reservoir bags with initiate oxygen therapy at 5 liters/minute and increase to 10 - 15 liters/minute if necessary.  Once patient is stable, the target is ≥ 90% SpO2in adults and ≥ 92 - 95% in pregnant patients.

- Children with emergency signs such as obstructed or absent breathing, cyanosis, shock, coma or convulsions, etc. should receive oxygen therapy during resuscitation to target SpO2≥ 94%. Once patient is stable, the target SpO2is ≥ 90%.

- To closely monitor the patient conditions to detect severe signs, or failure with oxygen therapy for timely intervention measures.

3.2. Treatment of critical respiratory distress and ARDS

- In case where oxygen therapy fails to alleviate hypoxemia SpO2≤ 92% or/and respiratory effort: The High Flow Nasal Oxygen, Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP) can be considered.

- Not to use the method of non-invasive positive pressure ventilation for patients with hemodynamic disorder, multiple organ dysfunction, and impaired consciousness.

- It is necessary to closely monitor the patient to detect signs of failure for timely intervention. After using non-invasive respiratory support measures, if the hypoxia does not improve, endotracheal intubation and invasive mechanical ventilation should be used.

- Endotracheal intubation must be performed by experienced persons, measures to prevent airborne transmission when placing the endotracheal tube must be applied.

- Respiratory support: Applying respiratory support regimen in ARDS treatment for adults and children. Attention:

+ Mechanical ventilation: To apply the mechanical ventilation strategy for lung protection, with low tidal volume (4-8 ml/kg ideal body weight) and low inlet pressure (to keep plateau pressure or Pplateau <30 cmH2O, for children, to keep Pplateau <28 cmH2O). Initial tidal volume 6 ml/kg, adjusted according to response of patient and treatment goals.

+ To increase CO2, to keep the pH target of ≥ 7.20.

+ In cases of severe ARDS cases in adults, to consider applying mechanical ventilation in prone position for 12-16 hours/day (if possible).

Higher PEEP can be applied for severe and medium ARDS cases. It depends on the compliance of the lung to set a suitable PEEP.

To avoid disconnecting the patient from the ventilator, leading to loss of PEEP and atelectasis. A closed endotracheal suction system should be used.

For children and infants, it is possible to use High Frequency Oscillatory Ventilation-HFOV early (if any), or when it fails to use conventional mechanical ventilation. Not to use HFOV for adults.

+ To ensure appropriate sedation, pain relief upon mechanical ventilation. In the case of medium to severe ARDS, muscle relaxants can be used, but should not be used routinely.

- To tightly control fluid balance, avoid fluid overload, especially outside the period of rehydration and cardiopulmonary resuscitation.

- In cases of severe, persistent hypoxemia, failing with conventional treatments, to consider indication and use extracorporeal membrane oxygenation (ECMO) for each specific case and carry out in which this technique is available.

ECMO can only be performed in a few large medical facilities. Therefore, if ECMO is considered, it is necessary for establishments to contact, transport patients early, and comply with the patient transportation procedure specified by the Ministry of Health.

4. Treatment of septic shock

To apply treatment regimens for septic shock for adults and children. Attention:

4.1. Fluid resuscitation

- To use a type of isotonic crystalloid solution such as physiological saline or Ringer s lactate. To avoid using hypotonic crystalloid solutions such as HAES-steril or Gelatin for fluid resuscitation.

- Dosage:

+ For adults: To give 250-500 ml crystalloid fluid as rapid bolus, in the first 15-30 minutes, to evaluate signs of fluid overload after each bolus.

+ For children: To give 10-20 ml/kg crystalloid fluid as a bolus in the first 30–60 minutes and to evaluate for signs of fluid after each bolus.

- It is necessary to closely monitor signs of fluid overload during fluid resuscitation such as more severe respiratory failure, enlarged liver, tachycardia, jugular venous distension, moist rales in lungs, pulmonary edema, etc. If the above signs present, to reduce or discontinue fluid administration.

To monitor signs of improvement of perfusion: mean arterial pressure> 65 mgHg for adults and age-appropriate targets in children; urine output (> 0.5 ml/kg/hr in adults, and> 01 ml/kg/hr in children), and improvement of duration of capillary refill, skin color, status of consciousness and the concentration of blood lactate.

4.2. Vasopressors

If hemodynamic status, perfusion have not been improved, to early give vasopressors.

-For adults: Noradrenaline is the initial choice. To adjust the dosage for the target of mean arterial pressure (MAP) ≥ 65 mmHg and improvement of perfusion. If signs of blood pressure and poor perfusion persist or there arises cardiac dysfunction despite achieving MAP target with fluids and vasopressors, to consider dobutamine.

-For children: Adrenalin is the initial choice. Dopamine or dobutamine can be given. To consider adding noradrenaline in cases of vasodilator shock (pulse pressure or the difference between the maximum and minimum blood pressure >40 mmHg). To adjust vasopressors to achieve the target of MAP > 50thpercentile by age.

- To use the central venous catheter to administer vasopressors. If the central venous catheter is not available, either peripherally inserted central catheter or intraosseous line can be used. To monitor signs of rhexis and necrosis.

Depending on the conditions of each establishment, either invasive or non-invasive hemodynamic probes can be used to assess and monitor the hemodynamic status to adjust fluid and vasopressors according to the patient s condition.

4.3. Blood culture and empirical broad-spectrum antibioticswithin 01 hour from the determination of septic shock.

4.4. To controlblood sugar, (to keep blood sugar from 8-10 mmol/L), calcemia, albumin concentration, (to give albumin when albumin concentration <30 g/L, to keep albumin concentration ≥ 35 g/L).

4.5. If there are risk factorsfor acute adrenal insufficiency, or catecholamine-dependent shock: May give low-dose Hydrocortisone: For adults: to give Hydrocortisone 50 mg every 06 hours, using intravenous therapy; for children: to give 02 mg/kg/first dose, then 0.5-1.0 mg/kg every 06 hours.

4.6. Transfusion of packed red cells as needed, to keep hemoglobin concentration ≥ 10 g/dl.

5. Treatment to support organ function

Depending on the specific situation of each patient to give appropriate support measures.

- To support kidney function:

+ To ensure hemodynamics, fluid and electrolyte balance, diuretics when necessary.

+ In cases of severe renal impairment, multiple organ dysfunction and/or fluid overload, to indicate the application of alternative kidney measures such as continuous dialysis, intermittent hemodialysis, or peritoneal dialysis, depending on conditions of the treatment establishment.

- To support liver function: In cases of liver failure

- To adjust coagulopathy: To transfuse platelet, fresh plasma, coagulation factors if necessary. If D-Dimer increases from 500 to 1000 µg/L, to use enoxaparine with prophylactic doses; If D-Dimer increases to above 1000 µg/L, to use enoxaparin with therapeutic doses.

6. Other treatment therapies

6.1. Antibiotics

- Not to use routine antibiotics for simple upper respiratory tract infections.

- For cases of pneumonia, to conduct blood cultures and bacterial sputum cultures and consideration of appropriate antibiotic use based on experience in working with bacterial agents that can cause pneumonia co-infection (depending on age, epidemiology for etiology). To adjust the appropriate antibiotic according to antimicrobial susceptibility pattern when the bacterial isolation result is available.

- If there arises sepsis, empirical broad-spectrum antibiotics should be early given within one hour after determining the sepsis. To adjust the appropriate antibiotic upon results of bacteria and antimicrobial susceptibility pattern.

- For cases of secondary infection, depending on the etiology, epidemiological characteristics, and antibiotic resistance to select appropriate antibiotics.

6.2. Antiviral drugs

Recently, there is no specific drug for SARS-CoV-2 treatment and evidence of effect and safety of reverse transcriptase inhibitors (Antiretroviral or ARV) or of other antiviral drugs (such as Chloroquine/Hydroxychloroquine, Remdesivir, Ribavirin). The Ministry of Health shall give relevant recommendation after considering clinical trial results of Vietnam and the global

6.3. Systemic corticosteroids

- Not to use routine systemic corticosteroids for upper respiratory tract infections or viral pneumonia unless otherwise indicated.

- For septic shock cases, to use low-dose Hydrocortisone if indicated (to see the treatment of septic shock).

- Depending on clinical progression and chest X-ray images of each severe pneumonia cases, Dexamethasone may be used within 5-10 days.

6.4. Haemodialysis

Severe ARDS cases and/or severe septic shock cases that do not respond or respond poorly to conventional treatments.  Continuous haemodialysis shall be considered by dialyzers that absorb cytokines.

6.5. Intravenous immunoglobulin (IVIG)

Depending on specific cases, IVIG may be considered for severe cases and/or system inflammatory syndrome in children.

6.6. Interferon

Case-specific use of interferon (if any) or endogenous interferon stimulants may be considered.

6.7. Respiratory rehabilitation

To consider early rehabilitation treatment for patients with respiratory distress.

6.8. Detection and management of neurological and psychiatric manifestations.

- To evaluate and treat delirium, especially in severe cases: to apply delirium assessment scores, identify and treat the cause and take appropriate measures to treat delirium.

- To evaluate signs of anxiety and depression; take appropriate psychosocial support and intervention measures.

- To detect and treat sleep disturbance problems.

- To provide basic mental health and psychosocial support for all possible or confirmed COVID-19 cases.

7. Complication prevention

For severe cases treated in intensive care units, it is necessary to prevent the following common complications:

7.1. Ventilator-associated pneumonia

To apply and comply with measures to prevent ventilator-associated pneumonia:

- An oral endotracheal tube should be placed.

- To keep patient in semi-recumbent position (head of bed elevation 30 - 45º).

- To ensure dental hygiene.

- To use a closed suctioning system; periodically drain and discard condensate intubing.

- To use a new ventilator circuit for each patient; once patient is ventilated, change circuit if it is soiled or damaged, but not routinely.

- To change heat moisture exchanger when it malfunctions, when soiled, or every 5 - 7 days.

7.2. Reduce incidence of venous thromboembolism

- For Adults or children requiring admission, low molecular-weight heparin (dose according to age and weight) shall be used to inject under the skin, twice daily if there are no contraindications.

- For those with contraindications, to use mechanical prophylaxis.

- To monitor patients with COVID-19 if there are signs of suspicion of embolism such as stroke, deep embolism, pulmonary infarction, acute coronary syndrome. If there are signs of doubt, appropriate diagnostic and treatment measures should be taken.

7.3. Catheter-related bloodstream infection

To use a checklist to monitor the application of prophylactic packets when catheter insertion and care. To remove catheter if no longer needed.

7.4. Pressure ulcers

To regularly turn patients.

7.5. Stress ulcers and gastrointestinal (GI) bleeding

- To give early enteral nutrition (within 24 - 48 hours of admission).

- Administer histamine-2 receptor blockers or proton-pump inhibitors in patients with risk factors for GI bleeding. Risk factors for GI bleeding include mechanical ventilation for ≥ 48 hours, coagulopathy, renal replacement therapy, liver disease, multiple comorbidities, and multi-organ dysfunction.

7.6. Intensive care unit-acquired weakness

To actively mobilize the patient early in the course of illness when safe to do so.

8. Some special populations

8.1. Pregnant women:

When SARS-CoV-2 infection is suspected or confirmed, pregnant women shall be treated in accordance with the above-mentioned measures, however, attention should be paid to physiological changes during pregnancy.

8.2. The elderly:

The elderly with underlying medical conditions are at increased risk of serious illness and death. It is required coordination of specialists when providing care and treatment, physiological changes in the elderly, as well as drug interactions during treatment should be paid attention.

IX. HOSPITAL DISCHARGE STANDARDS

1. Patients shall be discharged from hospitals if they satisfy the following standards:

- Patients ends in at least 03 days.

- Clinical symptoms improved, overall good condition, stable vital signs, normal organ function, blood test returned to normal, chest X-ray improved.

- Three specimens (specimens taken at least 01 day apart) show negative test result for SARS-CoV-2 by real-time RT-PCR method.

2. Post-discharge follow-up

Patients should continue to be adequately isolated at home under the supervision of local health facilities and local CDCs for an additional 14 days and monitored their temperature 2 times/day at home. If their temperature is higher than 38°C for two consecutive measurements or other abnormal symptoms, the patients must be promptly examined at health establishments.

* All Appendices are not translated herein.