Quyết định 3351/QĐ-BYT năm 2020 về Hướng dẫn chẩn đoán và điều trị COVID-19 do chủng vi rút Corona mới (SARS-CoV-2) do Bộ trưởng Bộ Y tế ban hành

DECISION

INTRODUCING COVID-19 DIAGNOSIS AND TREATMENT GUIDELINES

MINISTER OF HEALTH

Pursuant to the Government’s Decree No. 75/2017/ND-CP dated 20/6/2017 on functions, duties, powers and organizational structure of Ministry of Health;  

Per the opinions of the specialized council for revision of COVID-19 diagnosis and treatment guidelines established according to Decision No. 319/QĐ-BYT dated 06/2/2020 by the Minister;

At the request of the Head of the Department of Medical Services Administration - Ministry of Health,

HEREBY DECIDES:

Article 1. Promulgated together with this Decision are COVID-19 diagnosis and treatment guidelines superseding the COVID-19 diagnosis and treatment guidelines promulgated together with Decision No. 1344/QD-BYT dated 25/3/2020 by the Minister of Health.

Article 2. This Decision takes effect from the date on which it is signed.

Article 3. Head of Office of the Ministry of Health, Head of the Department of Medical Services Administration; Chief Inspector of the Ministry of Health; heads of affiliates of the Ministry of Health; directors of hospitals and institutes with beds affiliated to the Ministry of Health; Directors of Departments of Health of provinces and central-affiliated cities; and heads of health units of central authorities shall implement this Decision.

GUIDELINES

COVID-19 DIAGNOSIS AND TREATMENT

(Enclosed with Decision No. 3351/QD-BYT dated July 29, 2020 by Minister of Health)

I. OVERVIEW

Coronaviruses (CoV) are a virus family capable of animal-to-human transmission, resulting in illness ranging from the common cold to severe and life-threatening conditions such as the 2002 severe acute respiratory syndrome (SARS- CoV) and 2012 Middle East respiratory syndrome (MERS-CoV). In December 2019, a new strain of coronavirus (SARS-CoV-2) was confirmed as the cause of an outbreak of acute respiratory infection (COVID-19) in Wuhan city (Hubei, China), which has spread to all of China and almost all countries around the world. On 11/3/2020, the World Health Organization (WHO) declared COVID-19 a pandemic. Besides animal-to-human transmission, SARS- CoV-2 can be spread between humans, mostly through respiratory droplets and contact. The virus can also be transmitted via aerosols, especially in healthcare establishments, crowded places and enclosed spaces. As of now, there is no clear evidence of fecal-oral transmission.

COVID-19 has diverse clinical manifestations, ranging from asymptomatic infection to severe illness such as severe pneumonia, respiratory failure, septic shock, multiorgan dysfunction and death, especially in the elderly, those with chronic diseases or immunodeficiency whose TCD4 cell count is lower than 250 cells/mm3, and those having high D-Dimer level or concurrent or secondary viral or fungal infection.

As there are no effective cure and vaccine for COVID-19, COVID-19 treatment mostly involves supportive care and symptom treatment. Main preventive measures consist of early detection and isolation of confirmed cases.

II. DIAGNOSIS

1. Definition of COVID-19 cases

1.1. Suspected cases

A suspected case involves:

A. A patient who has fever and/or acute respiratory disease that cannot be attributed to other causes.

B. A patient who has any respiratory symptom AND has traveled to/through/from or stayed in a COVID-19 infected epidemiological zone in the 14 days prior to symptom onset OR has had close contact (**) with a suspected or confirmed COVID-19 case in the 14 days prior to symptom onset.

* Epidemiological zone: a country or territory recording domestically transmitted COVID-19 cases or an active epidemic hotspot in Vietnam per the interim guidelines for COVID-19 monitoring and prevention promulgated by the Ministry of Health and updated by the General Department of Preventive Medicine.

** Close contact includes:

- Contact at healthcare establishments, including direct care of a COVID-19 case; working with a health care worker infected with COVID-19; visiting a COVID-19 case or staying in the same room as a COVID-19 case.

- Direct contact within less than or equal to 2 meters with a suspected or confirmed COVID-19  case during period of illness.

- Living in the same house as a suspected or confirmed COVID-19 case during period of illness.

- Working with a confirmed or suspected COVID-19 case in the same team or office during period of illness.

- Being in a tourist group, business team, group of friends, etc. with a confirmed or suspected COVID-19 case during period of illness.

- Traveling in the same vehicle (sitting on the same row or within two rows in front of or behind) as a suspected or confirmed COVID-19  case during period of illness.

1.2. Confirmed cases

Confirmed cases are suspected cases or any person testing positive for SARS-CoV-2 confirmed by testing facilities permitted to perform such testing by the Ministry of Health.

III. SYMPTOMS

1. Clinical

- Incubation period: from 2 to 14 days, from 5 to 7 days on average.

- Onset: common symptoms include fever, dry cough, fatigue and muscle pain. Some may experience throat pain, stuffy nose, runny nose, headache, productive cough, vomiting and diarrhea.

- Development:

+ Most patients (more than 80%) have only mild fever and fatigue without pneumonia and usually recover after about 1 week. However, some cases do not develop any clinical symptom.

+ About 14% of patients develop serious complications such as pneumonia or severe pneumonia, requiring hospitalization; about 5% of patients need to be admitted to intensive care units for treatment of acute respiratory manifestations (rapid breathing, dyspnea, cyanosis, etc.), acute respiratory distress syndrome (ARDS), septic shock, organ dysfunction, including kidney injury and heart muscle injury, leading to death.

+ It takes an average of 7 to 8 days after symptom onset for serious complications to develop.

+ The elderly and those with immunodeficiency and underlying chronic diseases are at higher risk of dying. In adult patients, old age, high sequential organ failure assessment (SOFA) score upon hospitalization and D-dimer level > 1 μg/L are associated with a worse prognosis.

- Recovery period: from 7 to 10 days after the period of illness, if without ARDS, patients will no longer have fever, clinical signs will gradually disappear and patients will make a recovery.

- There is no evidence of different clinical manifestations of COVID-19 in pregnant women.

- In pediatric patients, most of them have milder clinical manifestations compared to adult patients or no symptom. Common signs include fever and coughing or manifestations of pneumonia. However, some pediatric patients suffer from multiorgan dysfunction similar to Kawasaki disease; fever; hyperemic eye or erythema, or swelling of the oral mucosa, hands, feet; circulatory failure; manifestations of heart dysfunction and high cardiac enzymes level; digestive disorders; coagulation disorders and high inflammatory marker levels.

2. Paraclinical tests

Non-specific blood tests and biochemical tests:

- Leukocyte count is normal or decreases; lymphocyte count usually decreases, especially in severe cases.

- C-reactive protein (CRP) level is normal or increases, procalcitonin (PCT) level is usually normal or increases slightly. ALT, AST, CK, LDH may increase slightly in some cases.

- Severe cases may develop organ dysfunction, coagulation disorders, D-dimer level increase, electrolyte and acid-base imbalance.

3. Lung X-ray and CT scan

- In the early phase of the disease or if there is only upper respiratory tract infection, radiographs look normal.

- When pneumonia develops, there are usually signs of bilateral interstitial pneumonia or diffuse ground-glass opacity in peripheral or lower areas of the lungs. The injury can progress rapidly in ARDS. Signs of cavity formation, pneumothorax or pleural effusions are rare.

4. Confirmatory testing

- SARS-CoV-2 may be detected via Real time RT-PCR or next-generation sequencing.

IV. CLINICAL FORM CLASSIFICATION

COVID-19 can be classified into the following clinical forms:

1. Asymptomatic form: patients test positive for SARS-CoV-2 via realtime RT-PCR but have no clinical symptom.

2. Mild cases: acute upper respiratory tract infection

- Patients have non-specific clinical symptoms such as fever, dry cough, throat pain, stuffy nose, fatigue, headache, muscle pain.

- There are no signs of pneumonia or oxygen deprivation.

3. Moderate cases: pneumonia

- Adult and older pediatric patients: have pneumonia (fever, cough, rapid breathing) and no signs of severe pneumonia, SpO₂ ≥ 90% when breathing in outdoor air.

- Young pediatric patients: have cough or dyspnea and rapid breathing (rapid breathing refers to a respiratory rate of ≥ 60 breaths/minute in children under 2 months of age; ≥ 50 breaths/minute in children from 2 to 11 months of age; ≥ 40 breaths/minute in children from 1 to 5 years of age) and no signs of severe pneumonia.

- Diagnosis is made based on clinical signs, however, interstitial pneumonia or complications is/are detected via lung X-ray, ultrasound or CT scans.

4. Severe cases: severe pneumonia

- Adult and older pediatric patients: have fever or are suspected of respiratory infection, accompanied by any of the following signs: respiratory rate of > 30 breaths/minute, severe dyspnea, or SpO₂ ≤ 93% when breathing in room air.

- Young pediatric patients: have cough or dyspnea and at least one of the following signs: cyanosis or SpO₂ < 90%; severe respiratory failure (grunting noises when breathing, retractions);

+ Or the child is diagnosed with pneumonia and has any of the following severe signs: inability to drink/nurse; altered level of consciousness (lethargic or comatose); convulsions. Other pneumonia signs such as retractions or rapid breathing may be present (with the abovementioned respiratory rate).

- Diagnosis is made based on clinical signs; complications are detected via lung X-ray.

5. Critical cases

5.1. Acute respiratory distress syndrome (ARDS)

- Onset: respiratory symptoms appear or worsen within one week starting from onset of clinical symptoms.

- Lung X-rays, CT scans or ultrasound images: ground-glass opacity in both lungs that is not caused by pleural effusion, lobar atelectasis or lung nodules.

- Pneumochysis is not caused by heart failure or fluid overload. Subjective assessment (heart ultrasound) is needed to exclude pneumochysis caused by hydrostatic pressure if there are no risk factors.

- Hypoxemia: in adult patients, classification is done based on PaO₂/FiO₂ (P/F) ratio and SpO₂/FiO₂ (S/F) ratio if PaO₂ value is unavailable:

+ 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 cmH2O).

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

+ When PaO₂ value is unavailable: S/F ≤315 suggests ARDS (including patients not put on mechanical ventilators)

- Hypoxemia: in pediatric patients, classification is done based on OI (oxygenation index: OI = MAP* × FiO2 × 100 / PaO2) (MAP*: mean airway pressure) or OSI (oxygen saturation index: SpO₂: OSI = MAP × FiO₂ × 100 / SpO₂) for patients put on invasive ventilators, and PaO₂/FiO₂ or SpO₂/FiO₂ ratio for patients put on CPAP machines or non-invasive ventilators (NIV):

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

+ Mild ARDS (invasive ventilation): 4 ≤OI<8 or 5≤OSI<7,5

+ Moderate ARDS (invasive ventilation): 8 ≤OI<16 or 7,5≤OSI<12,3

+ Severe ARDS (invasive ventilation): OI ≥16 or OSI ≥12,3

5.2. Sepsis

- In adult patients: there are signs of organ dysfunction:

+ Altered level of consciousness: somnolence, stupor, coma

+ Dyspnea or rapid breathing, low oxygen saturation level

+ Fast heart rate, weak pulse, cold extremities, or low blood pressure, livedo reticularis

+ Low urine output or no urine output

+ Laboratory tests show coagulation disorders, thrombocytopenia, acidosis, high lactate level, high bilirubin level, etc.

- Pediatric patients: when sepsis is suspected or confirmed and at least 2 criteria for systemic inflammatory response syndrome (SIRS) are met and one of them must be change to body temperature or abnormal leukocyte count.

5.3. Septic shock

- In adult patients: prolonged low blood pressure despite volume resuscitation, use vasoactive drugs to maintain mean arterial pressure (MAP) at ≥65 mmHg and serum lactate levels at >2 mmol/L.

- In pediatric patients: septic shock is confirmed upon the presence of:

+ Any form of low blood pressure: when systolic pressure < 5th centile or > 2SD below the normal value for age, or (children < 1 year of age: < 70 mmHg; children from 1 to 10 years of age: < 70 + 2 x age; children > 10 years of age: <90 mmHg).

+ Or 2-3 of the following signs: altered level of consciousness, fast or slow heart rate (< 90 beats/minute or > 160 beats/minute in children < 1 year of age, and < 70 beats/minute or > 150 beats/minute in young children); prolonged capillary refill (> 2 seconds); or warm vasodilation with bounding pulses; tachypnea; mottled skin or petechial or purpuric rash; increased lactate; oliguria; hyperthermia or hypothermia.

5.4. Other severe-critical complications: lung infarction, stroke, delirium. They require close monitoring, diagnostic testing upon suspicion and suitable treatments.

V. DIFFERENTIAL DIAGNOSIS

- COVID-19 needs to be differentiated from acute respiratory infection caused by other pathogens, including known pathogens:

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

+ Influenza caused by common coronavirus strains.

+ Common bacterial pathogens, including atypical bacteria such as Mycoplasma pneumonia etc.

+ Other causes of severe acute respiratory infection (SARI) such as A/H5N1, A/H7N9, A/H5N6, SARS-CoV, and MERS-CoV.

- Differential diagnosis of a patient’s critical condition (respiratory failure, organ dysfunction, etc.) is necessary to ascertain whether it results from other causes or comorbid chronic diseases.

VI. DIAGNOSTIC TESTING, MONITORING AND CASE REPORT

- Suspected cases need to undergo confirmatory testing for SARS-CoV-2.

- Collect upper respiratory tract fluids (nasopharyngeal swab & nasal and throat swab) for confirmatory testing by realtime RT- PCR.

- For cases whose upper respiratory tract specimens test negative for the virus but there are suspicious clinical signs, their lower respiratory tract fluids should be collected (sputum, bronchial fluid, tracheal wash).

- For patients put on ventilators, only lower respiratory tract fluids are needed.

- SARS-CoV-2 antibody tests are not recommended for confirmation of COVID-19 infection.

- Suspected cases, including cases whose illness has been attributed to other common causes, must undergo confirmatory testing for SARS-CoV-2 at least once.

- Blood cultures should be taken if sepsis is suspected or confirmed, which should be done before antibiotics administration. The patient needs to undergo testing for other bacterial and viral pathogens if there are suspicious clinical signs.

- Patients should undergo all necessary paraclinical tests and regular functional exploration depending on their specific conditions for diagnosis, prognosis and monitoring purposes.

- Confirmed COVID-19 cases must have respiratory fluid specimens taken and undergo testing every 2-4 days or sooner if necessary until they test negative for the virus.

- Positive SARS-CoV-2 cases must be reported to the Ministry of Health or local CDC.

- Identify epidemiological factors related to positive SARS-CoV-2 cases such as their place of residence, workplace and places visited, draw up list of persons having direct contact, and comply with guidelines for COVID-19 monitoring and prevention from the Ministry of Health.

VII. IMMEDIATE PRECAUTIONS AGAINST TRANSMISSION

As transmission prevention is a crucial step in COVID-19 diagnosis and treatment, precautions shall be taken immediately upon patient arrival in healthcare establishments. Standard precautions must be observed in all areas in a healthcare establishment.

1. In patient screening and classifying area

- Ask suspected cases to wear a face mask and guide them to the isolated zone.

- Ensure that patients stay at least 2 meters away from each other.

- Give instructions on how to cover the nose and mouth when coughing or sneezing and wash hands immediately after coming into contact with respiratory fluids to patients.

2. Precautions against droplet transmission

- Wear a medical face mask if being under 2 meters away from a patient.

- Prioritize isolating suspected cases in separate rooms, or group patients with the same cause of illness in one room. If unable to identify the cause of illness, group patients with similar clinical symptoms and epidemiological factors in one room. Patient rooms must be well ventilated.

- Wear eye protection when taking care of patients with respiratory symptoms (coughing, sneezing).

- Avoid moving patients in the healthcare establishment and patients must wear a face mask when they leave their room.

3. Precautions against contact transmission

- Healthcare workers shall use personal protective equipment (medical mask, safety goggles, gloves, robe) when entering a patient room, discard it after leaving a patient room and avoid touching the eyes, nose and mouth with dirty hands.

- Clean and disinfect tools (stethoscopes, thermometers) before using them on a patient.

- Avoid contaminating surrounding surfaces such as room doors, light switches, fan switches, etc.

- Ensure that patient rooms are well ventilated, open windows of patient rooms (if any).

- Avoid moving patients

- Hand hygiene

4. Airborne precautions

- When examining and/or taking care of confirmed cases, and/or performing procedures such as endotracheal intubation, respiratory tract suctioning, bronchoscopy, CPR, etc., healthcare workers must use personal protective equipment, including gloves, robe, eye protection and N95 mask or an equivalent.

- If possible, procedures should be performed in a separate room or a negative pressure room.

- Irrelevant persons should not be present in a room where a procedure is being performed.

VIII. TREATMENT

1. General treatment principles

- Classify patients and identify the location where a patient will receive treatment depending on level of severity:

+ Suspected cases (may be regarded as an emergency condition): need to be examined, monitored and isolated in a separate area in healthcare establishments, and have their specimens taken properly for confirmatory testing.

+ Confirmed cases must be monitored and treated in complete isolation.

+ Mild cases (upper respiratory tract infection, mild pneumonia) shall be treated in normal departments.

+ Severe cases (severe pneumonia, sepsis) shall be treated in emergency rooms of departments or intensive care units.

+ Severe-critical cases (severe respiratory failure, ARDS, septic shock, multiorgan dysfunction) shall be treated in intensive care units.

- As there is no effective cure, treatment mostly involves supportive care and symptom treatment.

- Treatments shall be individualized for each case, especially for severe-critical cases.

- Some treatment and research regimens permitted by the Ministry of Health may be administered.

- Severe conditions and complications must be monitored, detected and handled promptly.

2. General monitoring and treatment measures

- Patients shall be on bed rest, patient rooms must be well ventilated, air filtration systems or other patient room disinfection measures such as ultraviolet light (if any) may be used.

- Clean the nose and throat, can keep the nose moisturized with saline, gargle with regular mouth wash.

- Keep the body warm.

- Drink enough water, ensure fluid and electrolyte balances.

- Be careful when administering IV fluids to pneumonia patients who have no signs of shock.

- Ensure a balanced diet, improve the body’s condition and administer vitamin supplements if necessary. For severe - critical patients, follow the diet guidelines promulgated by Vietnam National Association of Emergency, Intensive Care Medicine and Clinical Toxicology.

- If there is high fever, reduce fever, may use paracetamol with a dose of 10-15 mg/kg/dose, no more than 60 mg/kg/day for children and no more than 2 grams/day for adults.

- Reduce cough using common cough medications if necessary.

- Evaluate, treat and give a prognosis of comorbid chronic conditions (if any).

- Give advice and encouragement to patients.

- Closely monitor clinical signs and progress of lung injury on lung X-Rays and/or CT scans, especially from the 7th to the 10th day of illness, to detect and promptly handle worsening signs such as respiratory failure and circulatory failure.

- Treating establishments shall be equipped with minimum emergency aid equipment and tools such as pulse oximeters, oxygen supply systems/tanks, oxygen-delivering interfaces (nasal cannula, simple face mask, and mask with reservoir bag), bag valve masks, oxygen masks, and endotracheal intubation equipment for different age groups.

3. Treatment of respiratory failure

3.1. Oxygen therapy and monitoring

- Give supplemental oxygen therapy immediately to patients with SARI and respiratory failure, hypoxemia, or shock to reach SpO2 > 94%.

- In adult patients, if there are emergency signs (labored breathing, retractions, cyanosis, reduced lung ventilation), clear the patient’s airway and give oxygen therapy immediately to reach SpO2 ≥ 94 % during the resuscitation process. Administer oxygen via nasal cannula (1-4 liters/minute), or simple face mask, or mask with reservoir bag, with an initial flow of 5 liters/minute, which can be increased to 10-15 liters/minute if necessary. When the patient is in a more stable condition, adjust the flow to reach SpO₂ ≥ 90 % in adults and SpO₂ ≥ 92-95% in pregnant women.

- In pediatric patients, if the child shows emergency signs such as labored breathing, cyanosis, shock, coma, convulsions, etc., give oxygen therapy during the resuscitation process to reach SpO₂ ≥ 94%. When the child is in a more stable condition, adjust the oxygen flow to reach SpO₂ ≥ 90 %.

- Closely monitor each patient's condition to detect worsening signs or poor response to oxygen therapy for timely handling.

3.2. Treatment of critical respiratory failure and ARDS

- When low flow oxygen therapy is not effective against hypoxemia, SpO₂ ≤ 92%, or/and there is labored breathing, consider administration of high flow nasal oxygen, CPAP, or BiPAP.

- Do not put patients with hemodynamic disorders, multiorgan dysfunction and altered level of consciousness on non-invasive ventilators.

- Closely monitor patients to detect poor response to low flow oxygen therapy for timely handling. If non-invasive breathing support is not effective against oxygen deprivation, administer endotracheal intubation and invasive ventilation.

- Endotracheal intubation should be performed by a trained and experienced provider using airborne precautions.

- Breathing support regimens for ARDS in adults and children shall be implemented with the following recommendations:

+ Mechanical ventilation: administer lung protective mechanical ventilation using lower tidal volumes (4–8 ml/kg predicted body weight, PBW) and lower inspiratory pressures (plateau pressure or Pplateau <30 cmH₂O, in children, maintain Pplateau < 28 cmH₂O). The initial tidal volume is 6 ml/kg, adjusted based on the patient’s response and treatment purpose.

+ CO₂ increase is permitted if meeting the pH goal of ≥ 7.20.

+ In adult patients with severe ARDS, prone ventilation for 12-16 hours per day is recommended (if possible).

+ High PEEP strategy may be applied to moderate and severe ARDS cases. PEEP settings shall be adjusted based on lung compliance.

+ Avoid disconnecting the patient from the ventilator, resulting in PEEP loss and atelectasis. Closed endotracheal intubation suction system is recommended.

+ In children and infants, high frequency oscillatory ventilation (HFOV) may be administered early on (if any) or upon poor response to normal ventilation. Do not administer HFOV to adult patients.

+ Give tranquillizers and analgesics as appropriate to mechanically ventilated patients. For moderate - severe ARDS cases, muscle relaxants may be used but not regularly.

- Strictly control fluid balance, avoid fluid overload, especially when not performing volume resuscitation.

- In case of severe and prolonged oxygen deprivation not responding to common therapies, consider indication and use of extracorporeal membrane oxygenation (ECMO) techniques on each case where qualified to perform such techniques.

- As ECMO can only be performed at some large healthcare establishments, upon consideration of ECMO indication, the treating establishment should contact a qualified establishment, transport the patient early and follow the patient transport procedure from the Ministry of Health.

4. Treatment of septic shock

Treatment regimens for septic shock in adult and pediatric patients shall be applied with the following recommendations:

4.1. Volume resuscitation

- Use isotonic crystalloid fluids such as saline or lactated Ringer solution. Avoid using hypotonic crystalloid fluids, Haes-steril solution or gelatin for volume resuscitation.

- Dosage:

+ Adults: give 250-500 ml as a rapid bolus in the first 15-30 minutes, and evaluate signs of fluid overload after each bolus.

+ Children: give 10-20 ml/kg as a rapid intravenous dose in the first 30-60 minutes, repeat if necessary, and evaluate signs of fluid overload after each dose.

- Monitor for signs of fluid overload in volume resuscitation such as worsening respiratory failure, hepatomegaly, tachycardia, jugular vein distention, moist pulmonary rales, pneumochysis, etc. If these signs appear, reduce or stop fluid transfusion.

- Monitor for signs of perfusion improvement: average blood pressure > 65 mgHg in adults and normal for age in children; urine volume (>0.5 ml/kg/hour for adults, and >1 ml/kg/hour for children), improvement of capillary refill time, skin color, level of consciousness and blood lactate level.

4.2. Vasoactive drugs

If signs of poor hemodynamics/perfusion persist, administer vasoactive drugs early.

- In adult patients: nor-adrenaline is the initial choice, adjust dose to achieve a MAP target of ≥ 65 mmHg and improve perfusion. If signs of poor hemodynamics and perfusion persist or heart dysfunction develops although MAP target is met using intravenous fluids and vasoactive drugs, administer dobutamine.

- In pediatric patients: adrenaline is the initial choice, may add dopamine or dobutamine. In case of vasodilatory shock (pulse pressure or difference between maximum and minimum blood pressures >40 mmHg), consider administration of nor-adrenaline. Adjust vasoactive drug dosage to achieve a MAP target of > 50^th centile normal for age.

- Administer vasoactive drugs via central IV line, or peripheral IV line or intraosseous infusion if infusion via central line is not possible. Monitor for signs of venous rupture and gangrene.

- Implement invasive or non-invasive hemodynamic monitoring measures depending on each establishment’s capacity to evaluate and monitor hemodynamic condition so as to make change to the fluids and vasoactive drugs administered as appropriate to the patient’s condition.

4.3. Blood cultures and broad-spectrum antibiotics should be used based on previous experience within one hour after septic shock is confirmed.

4.4. Control blood glucose (maintain at 8-10 mmol/L), blood calcium, blood albumin (administer albumin via intravenous route when albumin level < 30 g/L, maintain blood albumin at ≥ 35 g/L).

4.5. Cases with acute adrenal failure or catecholamine-dependent septic shock shall be administered low-dose hydrocorticone with an intravenous injection dose of 50 mg every 6 hours for adults; and a first dose of 2 mg/kg and then a dose of 0,5-1,0 mg/kg every 6 hours for children.

4.6. Transfuse red blood cells if necessary, maintain hemoglobin level at ≥ 10 g/dl.

5. Supportive care for organ dysfunction

Supportive care shall be provided as appropriate to each patient’s condition.

- Supportive care for kidney dysfunction:

+ Ensure hemodynamics and water and electrolyte balance, and administer diuretics when necessary.

+ In case of severe renal failure, multiorgan dysfunction and/or fluid overload, prescribe renal replacement therapies such as continuous renal replacement therapy, intermittent renal replacement therapy or peritoneal dialysis depending on the treating establishment's capacity.

- Supportive care for liver dysfunction: in case of liver failure

- Treatment of coagulation disorders: transfuse fresh plasma, platelets and coagulation factors if necessary. If D-dimer level increases to 500- 1000 µg/L, administer prophylactic enoxaparine dosage; if D-dimer level is higher than 1000 µg/L, administer treatment enoxaparine dosage.

6. Other treatment measures

6.1. Antibiotics

- Do not administer antibiotics regularly to cases with simple upper respiratory tract infection.

- For pneumonia patients, collect blood cultures and sputum cultures and consider administering suitable antibiotics to eliminate bacterial co-pathogens for pneumonia based on previous experience (find the cause based on age group and epidemiological factors). Make change to antibiotics used as appropriate to susceptibility test results when bacteria isolation results are available.

- If sepsis develops, administer broad-spectrum antibiotics based on previous experience early, within one hour after sepsis is confirmed. Make change to antibiotics used as appropriate when bacteria isolation results and susceptibility test results are available.

- Select suitable antibiotics for treatment of secondary infections based on their causes, epidemiological characteristics and antibiotic resistance.

6.2. Antiviral drugs

Currently, there is no drug effective against SARS-CoV-2 or evidence of the safety and effectiveness of antiretroviral drugs and other antiviral drugs (such as Chloroquine/Hydroxychloroquine, Remdesivir, Ribavirin). (The Ministry of Health will give its recommendations after assessing clinical trial results from other countries and Vietnam).

6.3. Systemic corticosteroids

- Do not administer systemic corticosteroids regularly to cases with upper respiratory tract infection or viral pneumonia unless otherwise indicated.

- Use low-dose hydrocortisone for septic shock if indicated (see Treatment of septic shock).

- For severe pneumonia cases, Dexamethasone may be used for 5-10 days depending on clinical progression and lung X-rays of each case.

6.4. Hemofiltration

This is indicated for cases with severe ARDS and/or severe septic shock unresponsive or poorly responsive to normal therapies. Consider use of continuous hemofiltration with cytokine-adsorbing hemofilters.

6.5. Intravenous immunoglobulin (IVIG)

Consider use of IVIG on severe cases and/or systemic inflammatory response syndrome in children.

6.6. Interferons

Consider use of interferons in each case (if any) or endogenous interferon inducing agents.

6.7. Pulmonary rehabilitation

Consider providing pulmonary rehabilitation for respiratory failure patients early.

6.8. Detection and handling of neurological and mental manifestations

- Evaluate and treat delirium, especially in severe patients: use delirium assessment scales, identify and treat the cause and provide suitable delirium treatments.

- Evaluate anxiety and depression signs; provide social support for psychological health and undertake suitable interventions.

- Detect and handle sleep disorders.

- Provide basic social support for psychological health and support for mental health for all suspected or confirmed COVID-19 cases.

7. Complication prevention

For severe cases receiving treatment in intensive care units, take preventive measures against the following common complications:

7.1. Ventilator-associated pneumonia

Apply and comply with the bundle of interventions for the prevention of ventilator-associated pneumonia:

- Insert endotracheal tube via oral route.

- Elevate the head of the bed to 30-45 degrees.

- Maintain oral hygiene.

- Use closed endotracheal suctioning system, and drain subglottic secretion periodically.

- Use new circuits for each patient; change the circuits only if they become soiled or damaged when the patient is put on the ventilator.

- Change heat and moisture exchangers when they are soiled or damaged or every 5-7 days.

7.2. Venous thrombosis prevention

- For hospitalized adult and pediatric patients, give low-molecular-weight heparin via subcutaneous injection twice a day as appropriate to age and weight if there is no contraindication.

- Provide mechanical therapies if there is any contraindication.

- Monitor COVID-19 patients if there are suspicious signs of vascular occlusion such as stroke, deep vein thrombosis, lung infarction, acute coronary syndrome. If there are suspicious signs, adopt suitable diagnosis and treatment measures.

7.3. Central line-associated bloodstream infection

Use a monitoring checklist, implement CVC insertion bundles and take care of the central line. Remove the central line when it is not needed.

7.4. Pressure ulcers

Regularly change patient’s position

7.5. Stress-induced stomach ulcers and gastrointestinal hemorrhage

- Feed via gastronomy tube early (within 24-48 hours after hospitalization).

- Give H2 blockers or proton-pump inhibitors to patients at risk of gastrointestinal hemorrhage such as those mechanically ventilated ≥ 48 hours, patients with coagulation disorders, renal replacement therapies, liver diseases, multiple underlying conditions and multiorgan dysfunction.

7.6. Intensive care unit acquired muscle weakness

When possible, mobilize patients actively and early during the treatment process.

8. Some special populations

8.1. Pregnant women:

Pregnant women with suspected or confirmed SARS-CoV-2 infection should be treated as abovementioned with due attention paid to physiological changes during pregnancy.

8.2. Elderly patients

Elderly patients with underlying conditions have higher risk of severe illness and death. Interdisciplinary care and treatment should be given to elderly patients with due attention paid to physiological changes in the elderly as well as drug interaction during the treatment process.

IX. DISCHARGE CRITERIA

1. A COVID-19 patient may be discharged when all of the following criteria are satisfied:

- No fever for at least 3 days.

- Improved clinical symptoms, good general appearance, stable vital signs, normal organ functions, normal blood test results and better lung X-rays.

- 03 specimens (collected at least 1 day apart) testing negative for SARS-CoV-2 via realtime RT-PCR.

2. Post-discharge monitoring

The patient shall self-quarantine under the supervision of grassroots health unit and local CDC for 14 days and take temperature twice a day; if their temperature is higher than 38 degrees Celsius in two consecutive checks or there is any other abnormal sign, visit a healthcare establishment for examination immediately.