This document is intended for clinicians taking care of hospitalised adult and paediatric patients of COVID – 19. It is not meant to replace clinical judgment or specialist consultation but rather to strengthen clinical management of these patients and provide up-to-date guidance. This document aims to provide clinicians with updated interim guidance on timely, effective, and safe supportive management of patients with COVID-19, particularly those with severe acute respiratory illness and are critically ill.

COVID–19 may present with mild, moderate, or severe illness; the latter includes severe pneumonia, ARDS, sepsis and septic shock. Early recognition of suspected patients allows for timely initiation of IPC (see Table 2). Early identification of those with severe manifestations (see Table 2) allows for immediate optimized supportive care treatments and safe, rapid admission (or referral) to intensive care unit according to national protocols. For those with mild illness, hospitalization may not be required unless there is concern for rapid deterioration. All patients discharged for home should be instructed to return to hospital if they develop any worsening of illness.

Triage: Early recognition of patients with COVID-19

The purpose of triage is to recognize and sort all patients with Fever and associated symptoms that make it a possible or suspected COVID - 19 infection at first point of contact with the hospital.

Table 1: Definitions of patients with COVID-19

SARI (Severe Acute Respiratory Infection)

An ARI with history of fever or measured temperature ≥38 C° and cough; onset within the last ~10 days; and requiring hospitalization.

Surveillance case definitions for SARI

SARI in a person, with history of fever and cough requiring admission to hospital, with no other etiology that fully explains the clinical presentation; AND any of the following: ) A history of international travel in 14 days prior to symptom onset; or ) the disease occurs in a health care worker who has been working in an environment where patients with severe acute respiratory infections are being treated; or ) the person develops an unusual or unexpected clinical course, especially sudden deterioration despite appropriate treatment, even if another etiology has been identified that fully explains the clinical presentation A person with acute respiratory illness of any degree of severity who, within 14 days before onset of illness, had any of the following exposures: ) A person with acute respiratory illness of any degree of severity who, within 14 days before onset of illness, had any of the following exposures: ) a healthcare facility in a country where hospital-associated COVID-19 infections have been reported;

1- CLOSE CONTACT IS DEFINED AS:

• Health care associated exposure.
• Working together in close proximity with a COVID-19 patient
• Travelling together with COVID-19 patient in any kind of conveyance.
• Living in the same household as a COVID-19 patients.

The epidemiological link may have occurred within a 14-day period before or after the onset of illness in the case under consideration

Uncomplicated illness	Patients with uncomplicated upper respiratory tract viral infection, may have non-specific symptoms such as fever, cough, sore throat, nasal congestion, malaise, headache. The elderly and immunosuppressed may present with atypical symptoms. These patients do not have any signs of dehydration, sepsis or shortness of breath.
Mild pneumonia	Patient with pneumonia and no signs of severe pneumonia. Child with non-severe pneumonia has cough or difficulty in breathing/ fast breathing: (fast breathing - in breaths/min): <2 months, ≥60; 2–11 months, ≥50;1– 5 years, ≥40 and no signs of severe pneumonia
Severe pneumonia	Adolescent or adult: fever or suspected respiratory infection, plus one of the following; respiratory rate >30 breaths/min, severe respiratory distress, SpO2 <90% on room air. Child with cough or difficulty in breathing, plus at least one of the following: central cyanosis or SpO2 <90%; severe respiratory distress (e.g. grunting, chest in- drawing); signs of pneumonia with any of the following danger signs: inability to breastfeed or drink, lethargy or unconsciousness, or convulsions. Other signs of pneumonia may be present: chest indrawing, fast breathing (in breaths/min): <2 months ≥60; 2–11 months ≥50; 1–5 years ≥40. The diagnosis is clinical; chest imaging can exclude complications.
Acute Respiratory Distress Syndrome	Onset: new or worsening respiratory symptoms within one week of known clinical insult. Chest imaging (radiograph, CT scan, or lung ultrasound):bilateral opacities, not fully explained by effusions, lobar or lung collapse, or nodules. Origin of oedema: respiratory failure not fully explained by cardiac failure or fluid overload. Need objective assessment (e.g. echocardiography) to exclude hydrostatic cause of oedema if no risk factor present. Origin of oedema: Mild ARDS: 200 mmHg < PaO2/FiO2 ≤ 300 mmHg (with PEEP or CPAP ≥5 cm H2O, or non-ventilated) Moderate ARDS: 100 mmHg < PaO2/FiO2 ≤200 mmHg with PEEP ≥5 cm H2O, or non-ventilated) Severe ARDS: PaO2/FiO2 ≤ 100 mmHg with PEEP ≥5 cm H2O, or non-ventilated) When PaO2 is not available, SpO2/FiO2 ≤315 suggests ARDS(including in non-ventilated patients) Oxygenation (children; note OI = Oxygenation Index and OSI = Oxygenation Index using SpO2) Bilevel NIV or CPAP ≥5 cm H2O via full face mask: PaO2/FiO2 ≤ 300 mmHg or SpO2/FiO2 ≤264 Mild ARDS (invasively ventilated): 4 ≤ OI < 8 or 5 ≤ OSI < 7.5 Moderate ARDS (invasively ventilated): 8 ≤ OI < 16 or 7.5 ≤ OSI < 12.3 Severe ARDS (invasively ventilated): OI ≥ 16 or OSI ≥ 12.3
Sepsis	Adults: life-threatening organ dysfunction caused by a dysregulated host response to suspected or proven infection, with organ dysfunction. Signs of organ dysfunction include: altered mental status, difficult or fast breathing, low oxygen saturation, reduced urine output, fast heart rate, weak pulse, cold extremities or low blood pressure, skin mottling, or laboratory evidence of coagulopathy, thrombocytopenia, acidosis, high lactate or hyperbilirubinemia. Children: suspected or proven infection and ≥2 SIRS criteria, of which one must be abnormal temperature or white blood cell count
Septic shock	Adults: persisting hypotension despite volume resuscitation, requiring vasopressors to maintain MAP ≥65 mmHg and serum lactate level < 2 mmol/L Children: any hypotension (SBP <5th centile or >2 SD below normal for age) or 2-3 of the following: altered mental state; bradycardia or tachycardia (HR <90 bpm or >160 bpm in infants and HR <70 bpm or >150 bpm in children); prolonged capillary refill (>2 sec) or warm vasodilation with bounding pulses; tachypnea; mottled skin or petechial or purpuric rash; increased lactate; oliguria; hyperthermia or hypothermia

A. Immediate implementation of appropriate measures

Clinical management of patients and should be initiated at the point of entry of the patient to hospital (typically the Emergency Department).

Table 3: How to implement infection prevention and control measures for patients with suspected or confirmed COVID - 19 infection

At triage	●  Give suspect patient a triple layer surgical mask and direct patient to “Fever Clinic”. Keep at least 1 meter distance between suspected patients and other patients.
Apply droplet precautions	●  Triple layer surgical mask. Place patients in single rooms, or group together those with the same etiological diagnosis. If an etiological diagnosis is not possible, group patients with similar clinical diagnosis with a spatial separation. Limit patient movement within the institution and ensure that patients wear triple layer surgical masks when outside their rooms
Apply contact precautions	●  Use PPE, and if possible, disposable or dedicated equipment (e.g. stethoscopes, blood pressure cuffs and thermometers). If equipment needs to be shared among patients, clean and disinfect between each patient use. Ensure that health care workers refrain from touching their eyes, nose, and mouth with potentially contaminated gloved or ungloved hands. Avoid contaminating environmental surfaces that are not directly related to patient care (e.g. door handles and light switches). Ensure adequate room ventilation. Avoid movement of patients or transport. Perform hand hygiene.
Apply airborne precautions when performing an aerosol generating procedure	●  Ensure that healthcare workers performing aerosol-generating procedures (i.e. open suctioning of respiratory tract, intubation, bronchoscopy, cardiopulmonary resuscitation) use PPE, including gloves, long-sleeved gowns, eye protection, and fit-tested particulate respirators (N95). (The scheduled fit test should not be confused with user seal check before each use.) Whenever possible, use adequately ventilated single rooms when performing aerosol-generating procedures, meaning negative pressure rooms with minimum of 12 air changes per hour or at least 160 litres/second/patient in facilities with natural ventilation. Avoid the presence of unnecessary individuals in the room. Care for the patient in the same type of room after mechanical ventilation commences.

B. Early supportive therapy and monitoring

1. Give supplemental oxygen therapy immediately.
2. Initial Flow rate - 5 L/min.
3. Titrate flow rate to achieve SpO2 as follows - ≥90% in non-pregnant adults; ≥92-95 % in pregnant patients; SpO2 ≥94%; otherwise, the target SpO2 is ≥90% for children.
4. Monitor with pulse oximeters, functioning oxygen systems and disposable, single-use, oxygen-delivering interfaces (nasal cannula, simple face mask, and mask with reservoir bag).
5. Conservative fluid management (app. 2.5 – 3.0 litres isotonic solution in absence of clinical dehydration, cardiac failure, severe respiratory congestion, renal failure etc.). Aggressive fluid resuscitation may worsen oxygenation, especially in settings where there is limited availability of mechanical ventilation.
6. Empiric antimicrobials to all patients within 1 hour of admission, on the basis of local experience. May be de-escalated based on response
7. Do not routinely give systemic corticosteroids.
8. Closely monitor patients with SARI for signs of clinical deterioration, such as rapidly progressive respiratory failure and sepsis, and apply supportive care interventions immediately: Application of timely, effective, and safe supportive therapies is the cornerstone of therapy for patients that develop severe manifestations of COVID-19.
9. Understand the patient’s co-morbid condition(s) to tailor the management of critical illness and appreciate the prognosis: During intensive care management of SARI, determine which chronic therapies should be continued and which therapies should be stopped temporarily.
10. Communicate early with patient and family: Communicate pro-actively with patients and families and provide support and prognostic information. Understand the patient’s values and preferences regarding life-sustaining interventions.

C. Collection of specimens for laboratory diagnosis

Points to remember

• Collect blood cultures for bacteria that cause pneumonia and sepsis, ideally before antimicrobial therapy. DO NOT delay antimicrobial therapy to collect blood cultures.
• Collect specimens of nasopharyngeal and oro – pharyngeal swab for RT - PCR. Clinicians may also collect LRT (Lower Respiratory Tract) samples when these are readily available (for example, in mechanically ventilated patients).
• When collecting URT samples, use viral swabs (sterile Dacron or rayon, not cotton) and viral transport media. Do not sample the nostrils or tonsils. In a patient with suspected COVID - 19, especially with pneumonia or severe illness, a single URT sample does not exclude the diagnosis, and additional URT and LRT samples are recommended. Sputum induction should be avoided due to increased risk of increasing aerosol transmission.
• Dual infections with other respiratory viral infections have been found in SARS and MERS cases. At this stage we need detailed microbiologic studies in all suspected COVID - 19 cases. Both URT and LRT specimens can be tested for other respiratory viruses, such as influenza A and B (including zoonotic influenza A), respiratory syncytial virus, parainfluenza viruses, rhinoviruses, adenoviruses, enteroviruses (e.g. EVD68), human metapneumovirus, and endemic human coronaviruses (i.e. HKU1, OC43, NL63, and 229E). LRT specimens can also be tested for bacterial pathogens, including Legionella pneumophila.
• In hospitalized patients with confirmed COVID - 19 infection, repeat URT samples should be collected to demonstrate viral clearance. The frequency of specimen collection will depend on local circumstances but should be done at least every 2 to 4 days until there are two consecutive negative results (of URT samples) in a clinically recovered patient at least 24 hours apart.

D. Management of hypoxemic respiratory failure and ARDS

• Recognize severe hypoxemic respiratory failure when a patient with respiratory distress is failing standard oxygen therapy ie. failure to maintain SpO2 ≥ 92% at flow rates of 10-15 L/min, at an FiO2 of 0.60-0.95)
• Consider High – flow nasal catheter oxygenation (HFNO) or non – invasive mechanical ventilation (NIV)
• 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.
• NIV is to be started only when endo-tracheal intubation and mechanical ventilation can be switched to quickly. This should not be undertaken at a centre without these facilities. Patients with hemodynamic instability, multiorgan failure, or abnormal mental status should not receive NIV.
• Endotracheal intubation should be performed by a trained and experienced provider using airborne precautions. Patients with ARDS, especially young children or those who are obese or pregnant, may de-saturate quickly during intubation. Pre-oxygenate with 100% FiO₂ for 5 minutes, via a face mask with reservoir bag, bag-valve mask, HFNO, or NIV. Rapid sequence intubation is appropriate after an airway assessment that identifies no signs of difficult intubation.
• Implement mechanical ventilation using lower tidal volumes (4–8 ml/kg predicted body weight, PBW) and lower inspiratory pressures (plateau pressure <30 cmH2O). This is a strong recommendation from a clinical guideline for patients with ARDS, and is suggested for patients with sepsis-induced respiratory failure. The initial tidal volume is 6 ml/kg PBW; tidal volume up to 8 ml/kg PBW is allowed if undesirable side effects occur (e.g. dyssynchrony, pH <7.15). Hypercapnia is permitted if meeting the pH goal of 7.30-7.45. The use of deep sedation may be required to control respiratory drive and achieve tidal volume targets.
• In patients with severe ARDS, prone ventilation for >12 hours per day is recommended. Application of prone ventilation is strongly recommended for adult and paediatric patients with severe ARDS but requires sufficient human resources and expertise to be performed safely.
• In patients with moderate or severe ARDS, higher PEEP instead of lower PEEP is suggested. Tables are available to guide PEEP titration based on the FiO2 required to maintain SpO2. A related intervention of recruitment manoeuvres (RMs) is delivered as episodic periods of high continuous positive airway pressure [30–40 cm H2O], progressive incremental increases in PEEP with constant driving pressure, or high driving pressure; considerations of benefits vs. risks are similar. Higher PEEP and RMs were both conditionally recommended in a clinical practice guideline. In patients with moderatesevere ARDS (PaO2/FiO₂ <150), neuromuscular blockade by continuous infusion should not be routinely used.
• In settings with access to expertise in extracorporeal life support (ECLS/ECMO), consider referral of patients with refractory hypoxemia despite lung protective ventilation. ECLS should only be offered in expert centres with a sufficient case volume to maintain expertise and that can apply the IPC measures required for COVID – 19 patients.
• Avoid disconnecting the patient from the ventilator, which results in loss of PEEP and atelectasis. Use in-line catheters for airway suctioning and clamp endotracheal tube when disconnection is required (for example, transfer to a transport ventilator).

E. Management of septic shock

• Recognize septic shock in adults when infection is suspected or confirmed AND vasopressors are needed to maintain mean arterial pressure (MAP) ≥65 mmHg AND lactate is < 2 mmol/L, in absence of hypovolemia. Recognize septic shock in children with any hypotension (systolic blood pressure [SBP] <5th centile or >2 SD below normal for age) or 2-3 of the following: altered mental state; tachycardia or bradycardia (HR <90 bpm or >160 bpm in infants and HR <70 bpm or >150 bpm in children); prolonged capillary refill (>2 sec) or warm vasodilation with bounding pulses; tachypnea; mottled skin or petechial or purpuric rash; increased lactate; oliguria; hyperthermia or hypothermia.
• In the absence of a lactate measurement, use MAP and clinical signs of perfusion to define shock. Standard care includes early recognition and the following treatments within 1 hour of recognition: antimicrobial therapy and fluid loading and vasopressors for hypotension. The use of central venous and arterial catheters should be based on resource availability and individual patient needs. Detailed guidelines are available for the management of septic shock in adults and children.
• In resuscitation from septic shock in adults, give at least 30 ml/kg of isotonic crystalloid in adults in the first 3 hours. In resuscitation from septic shock in children in well- resourced settings, give 20 ml/kg as a rapid bolus and up to 40-60 ml/kg in the first 1 hr. Do not use hypotonic crystalloids, starches, or gelatins for resuscitation.
• Fluid resuscitation may lead to volume overload, including respiratory failure. If there is no response to fluid loading and signs of volume overload appear (for example, jugular venous distension, crackles on lung auscultation, pulmonary oedema on imaging, or hepatomegaly in children), then reduce or discontinue fluid administration. This step is particularly important where mechanical ventilation is not available. Alternate fluid regimens are suggested when caring for children in resource-limited settings.
• Crystalloids include normal saline and Ringer’s lactate. Determine need for additional fluid boluses (250-1000 ml in adults or 10-20 ml/kg in children) based on clinical response and improvement of perfusion targets. Perfusion targets include MAP (>65 mmHg or ageappropriate targets in children), urine output (>0.5 ml/kg/hr in adults, 1 ml/kg/hr in children), and improvement of skin mottling, capillary refill, level of consciousness, and lactate. Consider dynamic indices of volume responsiveness to guide volume administration beyond initial resuscitation based on local resources and experience. These indices include passive leg raises, fluid challenges with serial stroke volume measurements, or variations in systolic pressure, pulse pressure, inferior vena cava size, or stroke volume in response to changes in intrathoracic pressure during mechanical ventilation.
• Administer vasopressors when shock persists during or after fluid resuscitation. The initial blood pressure target is MAP ≥65 mmHg in adults and age-appropriate targets in children.
• If central venous catheters are not available, vasopressors can be given through a peripheral IV, but use a large vein and closely monitor for signs of extravasation and local tissue necrosis. If extravasation occurs, stop infusion. Vasopressors can also be administered through intraosseous needles.
• If signs of poor perfusion and cardiac dysfunction persist despite achieving MAP target with fluids and vasopressors, consider an inotrope such as dobutamine

F. Other Therapeutic Measures:

For patients with progressive deterioration of oxygenation indicators, rapid worsening on imaging and excessive activation of the body’s inflammatory response, glucocorticoids can be used for a short period of time (3 to 5 days). It is recommended that dose should not exceed the equivalent of methylprednisolone 1 – 2mg/kg/day. Note that a larger dose of glucocorticoid will delay the removal of coronavirus due to immunosuppressive effects. For pregnant severe and critical cases, pregnancy should be preferably terminated. Consultations with obstetric, neonatal, and intensive care specialists (depending on the condition of the mother) are essential. Patients often suffer from anxiety and fear and they should be supported by psychological counselling.

G. Prevention of complications

Table 4: Prevention of complications

Anticipated Outcome	Interventions
Reduce days of invasive mechanical ventilation	Use weaning protocols that include daily assessment for readiness to breathe spontaneously. Minimize continuous or intermittent sedation, targeting specific titration endpoints (light sedation unless contraindicated) or with daily interruption of continuous sedative infusions
Reduce incidence of ventilator associated pneumonia	Oral intubation is preferable to nasal intubation in adolescents and adults Keep patient in semi-recumbent position (head of bed elevation 30-45º) Use a closed suctioning system; periodically drain and discard condensate in tubing Use a new ventilator circuit for each patient; once patient is ventilated, change circuit if it is soiled or damaged but not routinely Change heat moisture exchanger when it malfunctions, when soiled, or every 5–7 days
Reduce incidence of venous thromboembolism	Use pharmacological prophylaxis (low molecular-weight heparin [preferred if available] or heparin 5000 units subcutaneously twice daily) in adolescents and adults without contraindications. For those with contraindications, use mechanical prophylaxis (intermittent pneumatic compression devices).
Reduce incidence of catheter related bloodstream infection	Use a checklist with completion verified by a real-time observer as reminder of each step needed for sterile insertion and as a daily reminder to remove catheter if no longer needed
Reduce incidence of pressure ulcers	Turn patient every two hours
Reduce incidence of stress ulcers and gastrointestinal bleeding	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 gastrointestinal bleeding include mechanical ventilation for ≥48 hours, coagulopathy, renal replacement therapy, liver disease, multiple co-morbidities, and higher organ failure score
Reduce incidence of ICU-related weakness	Actively mobilize the patient early in the course of illness when safe to do so.