Severe Acute Respiratory Syndrome (SARS) Treatment & Management
- Author: Faustine Ong, MD; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM more...
Currently, no definitive medication protocol specific to SARS has been developed, although various treatment regimens have been tried without proven success.[11, 12] The CDC recommends that patients suspected of or confirmed as having SARS receive the same treatment that would be administered if they had any serious, community-acquired pneumonia.
Isolate confirmed or suspected patients and provide aggressive treatment in a hospital setting. Mechanical ventilation and critical care treatment may be necessary during the illness.[11, 12] No benefit has been shown with prone ventilation. An infectious disease specialist, a pulmonary specialist, and/or a critical care specialist should direct the medical care team. Communication with local and state health agencies, the CDC, and WHO is critical.
Various steroid regimens have been used around the world as part of the initial SARS treatment cocktail. In the initial Hong Kong cohort of patients, corticosteroids were first given (with ribavirin) because of the similarity of the clinical and radiographic findings of SARS to those of bronchiolitis obliterans-organizing pneumonia. Despite anecdotal reports of success, the efficacy of steroids has not been confirmed in a clinical trial.[58, 59]
During phase 2 of the clinical course, intravenous (IV) administration of steroids has been shown to suppress cytokine-induced lung injury. It was also associated with favorable clinical improvement, with resolution of fever and lung opacities within 2 weeks.[59, 60]
However, a retrospective analysis showed an increased risk of 30-day mortality. Carefully designed studies will be needed to clarify the optimal role systemic steroids in the treatment SARS. Findings show that local pulmonary inflammation may be reduced with systemic glucocorticoid therapy.
The most widely used of these to date is ribavirin (usually in conjunction with steroids). Despite early anecdotal reports of patients with SARS improving with a combination of ribavirin and steroids, ribavirin does not have proven activity against Coronaviridae. It does have significant adverse effects, including hemolysis. It is unlikely that ribavirin is of any clinical benefit in SARS.
Lopinavir/ritonavir was shown to have in vitro effects against the SARS-CoV. Some synergistic benefits with ribavirin were also demonstrated.[61, 62] However, the outcome of the subgroup that received lopinavir/ritonavir as rescue therapy after receiving pulsed methylprednisolone treatment for worsening respiratory symptoms was not better than that for the matched cohort.
Type 1 IFNs inhibit a wide range of RNA and DNA viruses, including SARS-CoV, and these effects have been demonstrated in vitro, as well as in some human and animal cell lines. In experimentally infected cynomolgus macaques, prophylactic treatment with pegylated IFN-alfa significantly reduced viral replication and excretion, viral antigen expression by type 1 pneumocytes, and pulmonary damage. However, the results of post exposure treatment with pegylated IFN-alfa were not as impressive.
In patients, use of IFN-alfacon1 plus corticosteroids was associated with improved oxygenation, more rapid resolution of radiographic lung opacities, and lower levels of creatine phosphokinase (CPK). These findings, although encouraging, need to be supported by further studies.
A high-affinity human monoclonal antibody (huMab) to the SARS-CoV S protein, known as 80 R, has potent neutralizing activity in vitro and in vivo. This antibody was shown to neutralize SARS-CoV and inhibit syncytia formation between cells expressing the S protein and those expressing the SARS-CoV receptor ACE2. It reduced replication of SARS-CoV in the lungs of infected ferrets, decreased viral secretion, and prevented macroscopic lung pathology. This may be a useful viral entry inhibitor for the emergency prophylaxis and treatment of SARS.
Intravenous immunoglobulin (IVIG) was used in particular in Singapore during the SARS outbreak. However, its use was associated with a hypercoagulable state, and as many as one third of the patients who received IVIG were diagnosed with venous thromboembolism, including some cases of pulmonary embolism.
Pentaglobulin (immunoglobulin-M [IgM]-enriched immunoglobulin) was also used in a small study, with encouraging results, but its use was also complicated by embolic events. The use of convalescent plasma was also attempted in some centers.
Nitric oxide (NO)
Nitric oxide use was associated with improved oxygenation and weaning from ventilator support in a small study.
In vitro replication of the virus was shown to be inhibited by glycyrrhizin. A study showed that the use of traditional Chinese medicine was more effective than Western medicine in reducing hypoxemia in patients with phase 1 SARS, although it was unclear what components of the traditional medicine contributed to this effect.
Chinese researchers began testing a SARS vaccine in humans in May 2004. The Chinese vaccine trial used an inactivated SARS virus vaccine developed through conventional vaccine technology.
The first US SARS vaccine trial began at the NIH in December 2004. The NIH vaccine is composed of a small, circular piece of deoxyribonucleic acid (DNA) that encodes the viral spike protein.
Vaccine containing recombinant surface Spike (S) protein of SARS-CoV nucleocapsid has been shown to induce high levels of SARS-neutralizing antibody in animal models.[73, 74] However, there was a concern about the safety of these vaccines. Several studies reported that SARS vaccine exacerbated lung eosinophilic immunopathology and paradoxically manifested as a severe disease upon subsequent exposure to SARS-CoV infection.[75, 76] To solve this problem, Honda-Okubo et al proposed a new vaccine design that used recombinant S protein with Delta inulin adjuvants. This design was shown to achieve long-lived immunity and prevented lung eosinophilic immunopathology upon SARS-CoV reexposure.
Currently, SARS DNA vaccine encoding S glycoprotein has been investigated in a phase I clinical trial. Although it was shown to be well tolerated in that study, further studies need to be performed before an optimal yet safe vaccine can be implemented clinically.
Activity and Isolation
The CDC has issued guidelines governing the activity and isolation of patients with SARS, their immediate contacts, and the healthcare professionals who treat SARS.[3, 52]
Patients with SARS pose a risk of transmission to close household contacts and healthcare personnel. In household or residential settings, infection control measures, as described below, are recommended.
Patients with SARS should limit interactions outside the home and should not go to work, school, out-of-home child-care facilities, or other public areas until 10 days after the fever resolves, provided that respiratory symptoms are absent or improving. During this time, infection control precautions should be used to minimize the potential for transmission.
All members of a household of a patient with SARS should carefully follow recommendations for hand hygiene (eg, frequent hand washing, use of alcohol-based hand rubs), particularly after contact with body fluids (eg, respiratory secretions, urine, feces).
Disposable gloves should be used for any direct contact with the body fluids of a patient with SARS. However, gloves are not intended to replace proper hand hygiene. Immediately after activities involving contact with body fluids, gloves should be removed and discarded, and hands should be cleaned. Gloves must never be washed or reused.
Each patient with SARS should be advised to cover his or her mouth and nose with a facial tissue when coughing or sneezing. If possible, patients with SARS should wear surgical masks during close contact with uninfected persons in order to prevent the spread of infectious droplets. If a patient with SARS cannot wear a surgical mask, his or her household members should wear surgical masks when in close contact.
Sharing of eating utensils, towels, and bedding between patients with SARS and others should be avoided, although such items can be used by others after routine cleaning (eg, washing with soap and hot water). Environmental surfaces soiled by body fluids should be cleaned with a household disinfectant according to the manufacturer's instructions; gloves should be worn during this activity.
Household waste soiled with body fluids of patients with SARS, including facial tissues and surgical masks, may be discarded as normal waste.
Precautions by close patient contacts
Household members and other close contacts of patients with SARS should be actively monitored by local health departments.
Household members or other close contacts of patients with SARS should be vigilant for the development of fever or respiratory symptoms and, if these develop, should seek a healthcare evaluation. Prior to the evaluation, healthcare providers should be informed that the individual is a close contact of a patient with SARS so that necessary arrangements can be made to prevent transmission of the disease in the healthcare setting. Household members or other close contacts who have symptoms of SARS should follow the precautions recommended for patients with SARS.
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