SARS: Systematic Review of Treatment Effects

By Lauren J. Stockman, R. Bellamy, P. Garner. PLoS Medicine, 2006

1,171 citations recorded by the source corpus.

Background The SARS outbreak of 2002–2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO) expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. Methods and Findings In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. Conclusions Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage and timing, and to accrue data in real time during future outbreaks to monitor specific adverse effects and help inform treatment.

Subfields: Epidemiology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/1fabf8b5ddd4560d1ce7431b19642ab0e29847cc

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Citations in the corpus

Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19 (2022, background): “A systematic review [30] reported on 15 studies, 13 of which were inconclusive to any benefits of corticosteroids.”
Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2 (2008, background): “Furthermore, some patients who survived SARS display neurological/psychological sequelae that appear to be disproportionate to the extent of lung infection or expected side effects of corticosteroid therapy (11, 25, 28, 53) (steroids were used in most patients with SARS in the outbreak of 2002 to 20”
The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China (2020, neutral): “In vivo, the effectiveness of IFNs combined with ribavirin requires further evaluation [39].”
Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture (2010, background): “antivirals are currently still lacking for the effective treatment of SARS and other nidovirus-related diseases [33].”
Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations (2020, neutral): “58 Although expert guidance can be sought from local or international societies, patients treated with experimental therapies should be enrolled in a clinical study when possible.”
Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019‐nCoV (2020, result): “At best, efficacy with RBV was inconclusive, with some studies showing a worsening of patient outcomes (as reviewed by Stockman, et al).(32) Exonuclease activity by the enzyme nsp14 has been shown to be able to remove mismatches as well as incorporated nucleoside analogs, and inactivation of nsp14’s”
Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions (2020, neutral): “Evidence is mainly derived from experience with SARS-CoV and MERS-CoV infections [95].”
Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture (2014, background): “Also the merits of treating SARS patients with 106 immunomodulatory corticosteroids have remained a matter of debate (reviewed in (28-30)).”
Hypothesis for potential pathogenesis of SARS-CoV-2 infection–a review of immune changes in patients with viral pneumonia (2020, result): “This is different from the effect of high-dose of glucocorticoids described in other literature [14].”
Coronavirus Infections in Children Including COVID-19 (2020, background): “152 There is no evidence for the use of monoclonal antibodies against tumor necrosis factor alpha.”
Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome (2017, background): “inconclusive and four were classified as causing possible harm.(6) In one randomized controlled trial (RCT) that included 16 non-ICU patients, "early" (<7 days of illness) hydrocortisone therapy was associated with a higher subsequent plasma viral load.”
Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients (2020, background): “Due to its anti-inflammatory effect, glucocorticoids have been widely used to stop the progression of the acute lung injury and acute respiratory distress syndrome in SARS and COVID-19 patients by suppressing lung inflammation [4,49].”