Human coronaviruses (HCVs) were isolated first in human embryonic trachea organ culture. These agents and other CVs isolated from animals were characterized by electron microscopy as large, pleomorphic, spherical or elliptical, enveloped RNA viruses with a diameter of 80 to 200 nm. The envelope displays distinctive 20-nm long, petal-shaped projections that produce a solar corona appearance. The RNA genome is surrounded by a nucleoprotein that forms a helical nucleocapsid just beneath the envelope. Major antigens are the nucleocapsid and two or three envelope proteins. Based on antigenic relatedness, human isolates now are grouped into at least three serotypes: HCV-229E, HCV-OC43, and the SARS coronavirus. Two additional human strains, NL63 and HKU1, have recently been identified. The cell receptor for HCV-229E is human aminopeptidase N (CD13). Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. The cellular receptor for HCV-OC43 has not been identified.

HCVs are worldwide in distribution. Estimates of prevalence in any population vary with the sensitivity of serologic tests. Using HCV-229E and HCV-OC43 as antigens, regardless of the test used, 50% to 60% of adults older than 30 years of age have antibody to both serotypes. The most sensitive tests show prevalence rates approaching 90% to 100%. On the other hand, the SARS CV was recognized first to infect humans in southern China in late 2002; infection spread from China to other parts of southeast Asia and the rest of the world in 2003. Seroprevalence studies show no evidence of past infection in humans, suggesting that this virus has been introduced only recently into the human population.

Most HCV infections occur from midwinter to early spring. One serotype may predominate for 1 year, then may exhibit low activity for 1 year or more. Exceptions to these generalizations exist (e.g., studies in Germany and England showed the viruses to be present all during year, and a Seattle study found that both serotypes sometimes circulate in a population simultaneously).

HCVs demonstrate some age specificity. Geometric mean antibody titers tend to increase directly with age. In a Seattle study, children averaged one HCV infection per year, approximately three times as many as their parents. Many individuals experienced reinfection with the same virus, but in all cases, serial infections by the same virus were separated by at least 8 months. Thus, short-term immunity against homologous virus reinfection, but not against reinfection by the other serotypes, appears to exist. Whether infection with the SARS CV leads to short- or long-term immunity is not known.

Subclinical infection with HCVs is a common finding in healthy children and adults. In the Seattle study, the antibody titer in 40% of children and 36% of adults increased significantly without evidence of illness. Similarly, in an 8.5-year surveillance of healthy older children in Atlanta, only 38% (63 of 168) of children with HCV-229E seroconversion and 47% (44 of 93) of those with HCV-OC43 seroconversion reported any illness. Subclinical infection with the SARS CV appears to be an uncommon occurrence, although the frequency of asymptomatic infection is being evaluated.

HCVs appear to be transmitted via the respiratory route. Volunteers have been infected readily through an intranasal inoculation of virus. A natural transmission experiment in human volunteers using HCV-229E showed aerosol transmission may be the most common means, but hand-to-face transmission has not been excluded. The SARS CV is transmitted primarily by contact, although aerosol transmission probably also occurs. Other routes of CV transmission have not been documented in humans, but animal CVs can be spread by the fecal-oral route, and the SARS CV is excreted in stool.

In human volunteers, the incubation period of HCV colds ranges from 1 to 5 days, and for the SARS CV, the incubation period is as long as 10 days. HCVs replicate in the upper respiratory tract, are shed in nasal washings, and reach detectable levels at onset of symptoms. Illness generally lasts 6 to 7 days, but it can persist for 18 days. The SARS CV replicates in the lower respiratory tract, and peak titers are not detected until 7 to 10 days after the onset of symptoms.