Coronavirus Confirmed as SARS Agent
Laurie Barclay, MD
April 9, 2003 ÃƒÂ¯Ã‚Â¿Ã‚Â½ Within just two months, investigators have found what may be the causative agent of severe acute respiratory syndrome (SARS), according to a report published online April 8 by The Lancet. A coronavirus that has never been described before was isolated from two patients and then confirmed through polymerase chain reaction (PCR) in 45 of 50 patients but in no controls. According to the commentators, the progress is truly “remarkable and unprecedented.” A separate article in The Lancet also provides guidelines for management.
“This report provides evidence that a virus in the coronavirus family is the etiological agent of SARS,” lead author Malik Peiris, from the University of Hong Kong, says in a news release. “However, it remains possible that other viruses act as opportunistic secondary invaders to enhance the disease progression, a hypothesis that needs to be investigated further.”
The Hong Kong University SARS Study Group reviewed records and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters, and ranging in age from 23 to 74 years. Evaluation included chest radiography and double-blinded laboratory testing of nasopharyngeal aspirates and serum samples.
The most frequent symptoms were fever, chills, myalgia, and cough. Fewer than 25% of patients had upper respiratory tract symptoms, but 10% had gastrointestinal symptoms. Respiratory symptoms and auscultatory findings were milder than would be expected from chest x-ray findings.
Predictors of severity were household contact with other infected individuals, older age, lymphopenia, and liver dysfunction. In two patients, a virus belonging to the family Coronaviridae was isolated. Serological and reverse-transcriptase PCR specific for this virus was positive in 45 of 50 patients with SARS, but in no controls. Of 32 patients from whom acute and convalescent sera were available, all had rising antibody titers to this coronavirus.
Because this virus is not one of the two known human coronaviruses, nor is it exactly like any of the known animal coronaviruses, the investigators believe that it may be a new virus which may have originated from animals. Additional genetic analysis may confirm this hypothesis.
“The high incidence of altered liver function, leukopenia, severe lymphopenia, thrombocytopenia, and subsequent evolution into adult respiratory distress syndrome suggests a severe systemic inflammatory damage induced by this human pneumonia-associated coronavirus,” they write. “Thus immunomodulation by steroid treatment may be important to complement the empirical antiviral treatment with ribavirin.”
They describe a “window of opportunity” of around eight days from symptom onset to respiratory failure, and they note that severe complicated cases are associated with underlying disease and delayed use of ribavirin and steroid treatment. The epidemiologic data suggest that spread is by droplets or by direct and indirect contact, although airborne spread and fecal-oral transmission cannot be ruled out.
“These findings significantly strengthen the tentative etiological association reported by other investigators who have also isolated a novel coronavirus from patients with SARS,” Ann Falsey and Edward Walsh, from the University of Rochester in New York, write in an accompanying commentary. “As other pathogens, such as human metapneumovirus and Chlamydia spp, are identified in SARS patients, it will be important to use control groups to determine their role in causality or as cofactors for severe disease.”
They note that nearly 40% of the patients developed respiratory failure requiring assisted ventilation, and that the lack of untreated control patients prevents definite conclusions about the efficacy of treatment.
In a second commentary, William Ho, from the Hospital Authority Building in Kowloon, Hong Kong, reports that the first index case in Hong Kong was admitted on Feb. 22, 2003. As of April 6, 842 cases with 22 deaths were identified in Hong Kong. The Hospital Authority of Hong Kong and the Department of Health have implemented public health measures and hospital policies for diagnosis and management of patients with SARS, which are available online at http://www.ha.org.hk.
Algorithms consider whether a suspected case has had close or social contact with a patient with SARS, whether there are classic symptoms of fever, cough, and shortness of breath, and whether chest x-ray reveals a new pulmonary infiltrate. Management may consist of outpatient monitoring or admission to hospital or designated medical center.
Coronavirus Confirmed as SARS Agent