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 to up-to-date guidance. Best practices for COVID – 19 including IPC and optimized supportive care for severely ill patients as considered essential. 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 critically ill.
1. Case definition
When to suspect
• All symptomatic individuals who have undertaken international travel in the last 14 days or
• All symptomatic contacts of laboratory confirmed cases or
• All symptomatic healthcare personnel (HCP) or
• All hospitalized patients with severe acute respiratory illness ( SARI) (fever AND cough and/or shortness of breath) or
• Asymptomatic direct and high risk contacts of a confirmed case (should be tested once between day 5 and day 14 after contact) Symptomatic refers to fever/cough/shortness of breath. Direct and high-risk contacts include those who live in the same household with a confirmed case and HCP who examined a confirmed case.
Confirmed case A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and symptoms
2. Clinical features
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 1). Early identification of those with severe manifestations (see Table 1) allows for immediate optimized supportive care treatments and safe, rapid admission (or referral) to intensive care unit .
3. Immediate implementation of appropriate IPC measures
Infection prevention control (IPC) is a critical and integral part of clinical management of patients and should be initiated at the point of entry of the patient to hospital (typically the Emergency Department). Standard precautions should always be routinely applied in all areas of health care facilities. Standard precautions include hand hygiene; use of PPE to avoid direct contact with patients’ blood, body fluids, secretions (including respiratory secretions) and non-intact skin. Standard precautions also include prevention of needle-stick or sharps injury; safe waste management; cleaning and disinfection of equipment; and cleaning of the environment.
4. Laboratory diagnosis
Guidance on specimen collection, processing, transportation, including related biosafety procedures, is available on https://mohfw.gov.in/media/disease-alerts. As per directive from MoHFW, Government of India, all suspected cases are to be reported to district and state surveillance officers.
Figure 1: Helpline for COVID-19 (MOHFW, GOI)
Sample collection: Preferred sample: Throat and nasal swab in viral transport media (VTM) and transported on ice Alternate: Nasopharyngeal swab, BAL or endotracheal aspirate which has to be mixed with the viral transport medium and transported on ice
General guidelines: • Trained health care professionals to wear appropriate PPE with latex free purple nitrile gloves while collecting the sample from the patient. Maintain proper infection control when collecting specimens • Restricted entry to visitors or attendants during sample collection • Complete the requisition form for each specimen submitted • Proper disposal of all waste generated
Respiratory specimen collection methods: A. Lower respiratory tract • Bronchoalveolar lavage, tracheal aspirate, sputum • Collect 2-3 mL into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container.
B. Upper respiratory tract • Nasopharyngeal swab AND oropharyngeal swab
Oropharyngeal swab (e.g. throat swab): Tilt patient’s head back 70 degrees. Rub swab over both tonsillar pillars and posterior oropharynx and avoid touching the tongue, teeth, and gums. Use only synthetic fiber swabs with plastic shafts. Do not use calcium alginate swabs or swabs with wooden shafts. Place swabs immediately into sterile tubes containing 2-3 ml of viral transport media.
Combined nasal & throat swab: Tilt patient’s head back 70 degrees. While gently rotating the swab, insert swab less than one inch into nostril (until resistance is met at turbinates). Rotate the swab several times against nasal wall and repeat in other nostril using the same swab. Place tip of the swab into sterile viral transport media tube and cut off the applicator stick. For throat swab, take a second dry polyester swab, insert into mouth, and swab the posterior pharynx and tonsillar areas (avoid the tongue). Place tip of swab into the same tube and cut off the applicator tip.
Nasopharyngeal swab: Tilt patient’s head back 70 degrees. Insert flexible swab through the nares parallel to the palate (not upwards) until resistance is encountered or the distance is equivalent to that from the ear to the nostril of the patient. Gently, rub and roll the swab. Leave the swab in place for several seconds to absorb secretions before removing.
Clinicians may also collect lower respiratory tract samples when these are readily available (for example, in mechanically ventilated patients). In hospitalized patients with confirmed COVID – 19 infection, repeat upper respiratory tract samples should be collected to demonstrate viral clearance.
5. Early supportive therapy and monitoring
a. Give supplemental oxygen therapy immediately to patients with SARI and respiratory distress, hypoxaemia, or shock: Initiate oxygen therapy at 5 L/min and titrate flow rates to reach target SpO2 ≥90% in non-pregnant adults and SpO2 ≥92-95 % in pregnant patients. Children with emergency signs (obstructed or absent breathing, severe respiratory distress, central cyanosis, shock, coma or convulsions) should receive oxygen therapy during resuscitation to target SpO2 ≥94%; otherwise, the target SpO2 is ≥90%. All areas where patients with SARI are cared for should be equipped with pulse oximeters, functioning oxygen systems and disposable, single- use, oxygen-delivering interfaces (nasal cannula, simple face mask, and mask with reservoir bag). Use contact precautions when handling contaminated oxygen interfaces of patients with COVID – 19. b. Use conservative fluid management in patients with SARI when there is no evidence of shock: Patients with SARI should be treated cautiously with intravenous fluids, because aggressive fluid resuscitation may worsen oxygenation, especially in settings where there is limited availability of mechanical ventilation. c. Give empiric antimicrobials to treat all likely pathogens causing SARI. Give antimicrobials within one hour of initial patient assessment for patients with sepsis: Although the patient may be suspected to have COVID – 19, Administer appropriate empiric antimicrobials within ONE hour of identification of sepsis. Empirical antibiotic treatment should be based on the clinical diagnosis (community-acquired pneumonia, health care-associated pneumonia [if infection was acquired in healthcare setting], or sepsis), local epidemiology and susceptibility data, and treatment guidelines. Empirical therapy includes a neuraminidase inhibitor for treatment of influenza when there is local circulation or other risk factors, including travel history or exposure to animal influenza viruses. Empirical therapy should be de-escalated on the basis of microbiology results and clinical judgment d. Do not routinely give systemic corticosteroids for treatment of viral pneumonia or ARDS outside of clinical trials unless they are indicated for another reason: A systematic review of observational studies of corticosteroids administered to patients with SARS reported no survival benefit and possible harms (avascular necrosis, psychosis, diabetes, and delayed viral clearance). A systematic review of observational studies in influenza found a higher risk of mortality and secondary infections with corticosteroids; the evidence was judged as very low
to low quality due to confounding by indication. A subsequent study that addressed this limitation by adjusting for time-varying confounders found no effect on mortality. Finally, a recent study of patients receiving corticosteroids for MERS used a similar statistical approach and found no effect of corticosteroids on mortality but delayed lower respiratory tract (LRT) clearance of MERS-CoV. Given lack of effectiveness and possible harm, routine corticosteroids should be avoided unless they are indicated for another reason. See section F for the use of corticosteroids in sepsis. e. 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. f. 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. g. 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.
6. Management of hypoxemic respiratory failure and ARDS
• Recognize severe hypoxemic respiratory failure when a patient with respiratory distress is failing standard oxygen therapy. Patients may continue to have increased work of breathing or hypoxemia even when oxygen is delivered via a face mask with reservoir bag (flow rates of 10-15 L/min, which is typically the minimum flow required to maintain bag inflation; FiO2 0.60-0.95). Hypoxemic respiratory failure in ARDS commonly results from intrapulmonary ventilation-perfusion mismatch or shunt and usually requires mechanical ventilation. • High – flow nasal catheter oxygenation or non – invasive mechanical ventilation: When respiratory distress and/or hypoxemia of the patient cannot be alleviated after receiving standard oxygen therapy, high – flow nasal cannula oxygen therapy or non – invasive ventilation can be considered. If conditions do not improve or even get worse within a short time (1 – 2 hours), tracheal intubation and invasive mechanical ventilation should be used in a timely manner. Compared to standard oxygen therapy, HFNO reduces the need for intubation. Patients with hypercapnia (exacerbation of obstructive lung disease, cardiogenic pulmonary oedema), hemodynamic instability, multi-organ failure, or abnormal mental status should generally not receive HFNO, although emerging data suggest that HFNO may be safe in patients with mild-moderate and non-worsening hypercapnia25. Patients receiving HFNO should be in a monitored setting and cared for by experienced personnel capable of endotracheal intubation in case the patient acutely deteriorates or does not improve after a short trial (about 1 hr). • NIV guidelines make no recommendation on use in hypoxemic respiratory failure (apart from cardiogenic pulmonary oedema and post-operative respiratory failure) or pandemic viral illness (referring to studies of SARS and pandemic influenza). Risks include delayed intubation, large tidal volumes, and injurious transpulmonary pressures. Limited data suggest a high failure rate when MERS patients received NIV. Patients receiving a trial of NIV should be in a monitored setting and cared for by experienced personnel capable of endotracheal intubation in case the patient acutely deteriorates or does not improve after a short trial (about 1 hr). Patients with hemodynamic instability, multiorgan failure, or abnormal mental status should not receive NIV.
• Recent publications suggest that newer HFNO and NIV systems with good interface fitting do not create widespread dispersion of exhaled air and therefore should be associated with low risk of airborne transmission. • 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. Ventilator protocols are available. 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. • Use a conservative fluid management strategy for ARDS patients without tissue hypoperfusion. • In patients with moderate or severe ARDS, higher PEEP instead of lower PEEP is suggested.PEEP titration requires consideration of benefits (reducing atelectrauma and improving alveolar recruitment) vs. risks (end-inspiratory overdistension leading to lung injury and higher pulmonary vascular resistance). 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 moderate-
severe 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), 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) 7. 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 age- appropriate 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
8. 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 counseling.
9. Prevention of complications
Implement the following interventions (Table 3) to prevent complications associated with critical illness. These interventions are based on Surviving Sepsis or other guidelines, and are generally limited to feasible recommendations based on high quality evidence.
10. Specific therapy
NO SPECIFIC ANTIVIRALS have been proven to be effective as per currently available data. However, based on the available information (uncontrolled clinical trials), the following drugs may be considered as an off – label indication in patients with severe disease and requiring ICU management:
• Hydroxychloroquine (Dose 400mg BD – for 1 day followed by 200mg BD for 4 days)
In combination with • Azithromycin (500 mg OD for 5 days)
These drugs should be administered under close medical supervision, with monitoring for side effects including QTc interval.
The above medication is presently not recommended for children less than 12 years, pregnant and lactating women.
These guidelines are based on currently available information and would be reviewed from time to time as new evidence emerges.
Support to Treating Physicians: AIIMS, New Delhi is running a 24×7 helpline to provide support to the treating physicians on clinical management. The helpline number is 9971876591. The identified nodal doctor of the State, appointed for clinical management of COVID – 19 should only contact AIIMS Call Centre.