Approach
There are currently no specific treatments shown to be effective against SARS. A variety of pharmacologic interventions have been used, but their efficacy remains inconclusive.[44] Therefore, treatment is focused on the alleviation of symptoms, the prevention and treatment of complications, and the aggressive support of vital functions if these are threatened or compromised.
Isolation procedures
Once a clinical suspicion of SARS has been established, all appropriate protective measures must be initiated to minimize the risk of transmission, with immediate implementation of the strict contact and airborne precautions set out by the Centers for Disease Control and Prevention (CDC).[45] These measures must be further intensified when diagnostic or therapeutic aerosol-generating procedures are carried out.
An assessment of the clinical severity allows the most appropriate location for management to be established. The CDC advises that patients with SARS-CoV disease who do not require hospitalization for medical reasons may be isolated at home.[46] Stable patients should be placed in isolation and nursed in a negative pressure room where one is available. More severe cases (i.e., those presenting with or developing acute respiratory failure) should be admitted to the intensive care unit or an intermediate care unit under airborne transmission precautions.
Supportive care
Supportive care is the mainstay of treatment. This includes administration of adequate supplemental oxygen to correct hypoxemia, replacement of fluid deficits caused by diarrhea or fever, correction of electrolyte disturbances, and antipyretics and analgesics to control fever and pain.
Impending or established respiratory failure
Patients with impending or established respiratory failure should be admitted to the ICU or an intermediate care unit. About 14% to 26% of all SARS cases and about 50% to 85% of patients admitted to the ICU will require either invasive (preferred) or noninvasive mechanical ventilation.[19][24][25][37][47][48][49] Intubation and mechanical ventilation are instituted if the patient is clinically deteriorating and cannot maintain an SaO₂ >90% with spontaneous ventilation despite maximal oxygen therapy.[50]
Noninvasive mechanical ventilation[51]
The role of noninvasive positive pressure ventilation (NIPPV) is controversial.
Although it appears to reduce mortality and the need for intubation, there are concerns regarding the possibility of viral transmission.
High rates of pneumothorax as well as subcutaneous and mediastinal emphysema are also noted with NIPPV.
In order to decrease the risk of transmission during mechanical ventilation, the following precautions must be taken.
Avoidance of nebulized humidity and utilization of Venturi masks without humidification.[52]
Avoidance of bag-mask ventilation and utilization of masks that permit filtration of exhaled gas.
Utilization of adequate sedation during intubation.
Utilization of closed suction systems and submicron filters in the exhalation outlet of mechanical ventilators.
Utilization of sedation or paralysis to minimize coughing.
Turning ventilator to standby and positive end expiratory pressure (PEEP) to off when disconnecting the circuit.
Avoidance of bronchoscopy if possible.
Empiric therapy for community-acquired pneumonia ± influenza
Due to the initial uncertainty regarding diagnosis, empiric antibiotic therapy against both typical (including drug-resistant strains) and atypical community-acquired respiratory pathogens is a prudent first-line therapy.
An appropriate beta-lactam combined with a macrolide or monotherapy with a respiratory fluoroquinolone are reasonable options. Possible examples of intravenous combinations in hospitalized patients include ceftriaxone or ceftaroline plus azithromycin or clarithromycin. Monotherapy with levofloxacin or moxifloxacin is an alternative.[53] Antibiotic therapy should be discontinued as soon as a definite diagnosis of SARS is documented.
When epidemiologically indicated (i.e., during a seasonal epidemic of influenza), influenza virus should also be covered with a 5-day course of either zanamivir or oseltamivir.
Antiviral therapy upon confirmation of the diagnosis
Randomized controlled trial (RCT) data on the efficacy of antivirals in the treatment of SARS are limited, although the consensus is that antiviral therapy should be given to all confirmed cases as early as possible. The combination of the antiproteases lopinavir/ritonavir should be given for 14 days.[54]
Although not effective as a monotherapy, ribavirin can be given with the antiprotease lopinavir/ritonavir combination.[16]
Severe infection
In addition to the above measures, patients with severe infection (deteriorating radiographic consolidation, increasing oxygen requirement [SpO₂<90%/Oxygenation Index <300 mmHg/PaO₂ <10 kpa], and a respiratory rate of ≥30 breaths/minute) should receive corticosteroids with the possible addition of immunoglobulin, interferon, and convalescent plasma.
Corticosteroids have been reported to have some efficacy in severe cases (critical SARS).[55] Although various regimens have been tried, the most commonly used is 3 to 6 days of pulsed methylprednisolone. Corticosteroids added to lopinavir/ritonavir and/or ribavirin early in the course of the infection have been shown to reduce the progression to acute respiratory distress syndrome as well as the death rate.[16]
Immunoglobulin, interferon, or convalescent plasma should be added in patients who do not show a favorable response to treatment with pulsed methylprednisolone and ribavirin.
Although not available in the US or the UK, a 5-day course of IgM-enriched immunoglobulin (Pentaglobin®), has been found to be beneficial in the treatment of SARS in other countries.[56]
Interferon has shown promising results in in vitro and animal models. Interferon alfa-2b has been shown to inhibit growth of SARS in vitro.[57]
The efficacy of convalescent plasma administration as a treatment of SARS has not been documented.[58][59]
Psychological support and counseling
Patients, as well as their relatives, may require consultation with a specialist in psychological therapy and counseling for specialized treatment.
In addition, healthcare workers report higher levels of burn-out, psychological distress associated with quarantine, fear of contagion, concern for family, and perceived stigma as well as post-traumatic stress, which limit their ability to provide high-quality patient care. Psychological and moral support for healthcare workers should be established in the acute phase and, ideally, in the prepandemic period in order to provide adequate preparation for future outbreaks.[60][61]
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