SARS: Systematic Review of Treatment Effects

Abstract

BackgroundThe 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 FindingsIn 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.ConclusionsDespite 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.

What are our pharmacotherapeutic options for MERS-CoV?

“…The studies were observational in design and the conclusions should be taken in this context. In a systematic review of the use of convalescent plasma in SARSCoV, the effect of this modality was inconclusive as other factors may have played a role, such as patient comorbidities, extent of the disease or effect of other concomitant treatments [5]. The presence of MERS-CoV-specific antibodies was reported in two patients from Germany with a titer of 1:640 [6,7].…”

Pathogenic viruses of the respiratory tract – A review

“…Influenza infection can spread globally in the pandemic form through the spread of novel virus types. These novel types of influenza viruses emerge following genetic reassortment of the haemagglutinin (HA) and neuraminidase (NA) genes [39].…”

Middle East Respiratory Syndrome

“…These differences in accessory proteins, with presumed differential effects on induction and signaling of Type 1 interferon (IFN), may explain why MERS-CoV is more sensitive to IFN than is SARS-CoV 15,16 . This difference in IFN sensitivity has therapeutic implications since Type 1 IFN has been used to treat patients infected with SARS-CoV or MERS-CoV 17,18 .…”