SARS: where are the pediatric cases?

May 2003

---Philip A. Brunell, MD

In November the first cases of Severe Acute Respiratory Syndrome (SARS) appeared in Guangdong province in China. This syndrome consisted of fever, systemic and respiratory signs. In a few of the patients, the illness evolved into severe pneumonia and in some, rapid deterioration of respiratory function and death.

Although there is no established therapy, some patients have received ribavirin and steroids. At this writing, there are upwards of 5,400 cases and 350 deaths globally. In Canada (almost all in Toronto) there are over 145 cases — of which there are two probable and three suspected cases in children. In Singapore only 2.4% of cases had been in children. There have been few cases in children in Hong Kong and none reported from the largest children’s hospital in southern China, the epicenter of the epidemic. The number of cases in the United States has also been low, following the recent adoption of the World Health Organization case definition by the CDC. In any case, the age distribution for a respiratory virus is rather unusual.

Respiratory illnesses are common in children and many of the parents of our pediatric patients probably are concerned about whether their children may have SARS. One could likely fit a good number of our patients into the CDC definition of fever of 100.4° F and “one of more of the clinical findings of respiratory illness (eg, cough, shortness of breath, difficulty breathing, hypoxia or radiographic findings of either pneumonia or acute respiratory distress syndrome).”

The most reassuring answer to parents, at this time, is the requirement in the case definition that there must be a history of recent travel to an endemic area or contact with a person who has traveled to such an area who has a respiratory illness or contact with a patient with SARS. (www.cdc.gov/ncidod/sars/casedefinition.htm).

The clinical findings may fulfill the clinical findings but the criterion of an epidemiologic link is lacking. No one wants to miss the first case in their community.

During influenza epidemics almost half of susceptible children become infected. In fact, children are a major “vector” in spreading the disease to adults. During the season when influenza is prevalent, other respiratory viruses (eg, respiratory syncytial virus [RSV]) are circulating. Many respiratory viruses may produce a clinical syndrome similar to influenza. If SARS does become a problem in the pediatric community, it may be indistinguishable from illnesses caused by other respiratory viruses. Studies of children with respiratory illness have indicated that coronaviruses do infect them but are relatively minor players compared to other known respiratory viruses. However the agent putatively responsible for SARS is different from the two coronaviruses known to cause respiratory illnesses in humans.

Proper case definition

Most pediatricians looking at the epidemiologic data would suspect that we might be using the wrong case definition in children. As is true of so many viral diseases, both adults and children are infected but adults get sicker. Envision chickenpox without the rash with adults developing pneumonia and children being spared. We are sensitive to the fact that the same virus may cause different clinical manifestations at different ages. RSV, for example, may cause apnea in the newborn, bronchiolitis in infants and upper respiratory disease in older children and adults. It would be helpful to have serologic data on children in affected communities particularly those children who live in households with a known case of SARS. It would be of great interest to study the children in the apartment complex in which there appears to be an outbreak remembering, however, that the number of children in Chinese families will be much smaller than in American families.

Doing serologic studies necessitates having a virus in hand, with which one can prepare antigens required for such testing. Coronaviruses have been identified by independent laboratories in patients with SARS. The virus appears to be quite different than the two coronaviruses known to cause respiratory infections in humans. These two corona- viruses are causes of the common cold and less commonly associated with lower respiratory disease. Some have reported an association between coronavirus and development of wheezing in patients with asthma.

The recognition that coronaviruses were associated with the common cold dates from the 1960s. David Tyrell, an English investigator was first to establish this relationship. He used a unique and technically demanding system for isolating the virus, namely human fetal tracheal organ cultures, which were inoculated with respiratory secretions from patients with upper respiratory infections. He then used the isolates from these cultures to reproduce the symptoms in volunteers. I heard him describe the illness, which he referred to as “streamers,” when I was working in an adjoining laboratory at the Clinical Research Centre in England. Subsequently others were able to confirm his findings. Although others have developed different systems to isolate the virus and study the immune response, it remains a difficult agent with which to work. This has lead to slow progress in understanding coronavirus epidemiology.

The speed with which coronavirus was associated with SARS has been characterized as dazzling. Some Canadian investigators who were among those unable to reproduce the coronavirus results cautioned that the rush may have lead us down a blind alley. In the April 8 online edition of Lancet, a group from Hong Kong reported that they had obtained two isolates from the 50 cases studied and obtained polymerase chain reaction (PCR) evidence of infection in 44. The low rate of isolation from confirmed PCR cases is indicative of how difficult it is to isolate this agent. All of the 32 patients from whom appropriate serum specimens were obtained seroconverted. What obviously is needed is the exchange of reagents and specimens between laboratories. Animal inoculation studies already have been initiated in attempts to fulfill Koch’s postulates.

Where has this virus been?

A question which has been asked is where has this virus been? Is it a new agent? Its origin in Guangdong province brings to mind that a number of new strains of influenza virus have emanated from this part of the world. It is believed that the proximity of people, fowl and swine provide an optimal situation for influenza viruses to cross species and exchange genetic material. We recently witnessed this phenomenon in Hong Kong with the appearance of the new H5N1 influenza “chicken” virus. One traveling through this area on a train to Hong Kong and witnessing the urbanization would wonder where the farms are. Both influenza and coronavirus are RNA viruses but the differences in the organization of the genome and mechanism of replication of the viruses should make us cautious about extrapolating from influenza. Coronavirus tends to be much less promiscuous than influenza viruses. The temptation to extrapolate derives from the knowledge that the first coronavirus isolated was infectious bronchitis virus from chickens. Coronaviruses are found in a variety of avian and animal species and of agricultural importance.

Source: CDC/Dr. Fred Murphy

The rapid spread of SARS is rather frightening. Recognition of what was happening was not fully appreciated until cases started to appear in Hong Kong, other parts of China, Singapore, Vietnam, Toronto and the United States.

Almost all of the early cases either had a history of travel to China or Hong Kong or were exposed health care workers. The infection was believed to be spread by small droplets via the respiratory route requiring fairly close contact.

Precautions for managing suspected cases have been published by CDC at www.cdc.gov/ncidod/sars/index.htm.

“Personal protective equipment appropriate for standard, contact, and airborne precautions (eg, hand hygiene, gown, gloves and N95 respirator) in addition to eye protection, have been recommended for health care workers to prevent transmission of SARS in healthcare settings,” reported on the CDC Web site.

One lesson learned from the epidemic is the need for meticulous infection control practices. A significant number of the cases and deaths have been in health care workers who contracted the disease from contact with infected individuals. To date however, there is no evidence to support the thesis that there is widespread unrecognized illness in children. At this time, it is safe to say that our pediatric patients with respiratory illnesses without an epidemiologic link do not have SARS. That does not means we should stop looking.