Common cold coronaviruses

INTRODUCTION — 

Coronaviruses are important human and animal pathogens.

During epidemics, common cold coronaviruses (ccCoVs) are the cause of up to one-third of community-acquired upper respiratory tract infections in adults and probably also play a role in severe respiratory infections in both children and adults. In addition, it is possible that certain ccCoVs cause diarrhea in infants and children. Their role in central nervous system diseases, except for a single case report of encephalitis in a severely immunocompromised infant, has been suggested but not proven.

The microbiology of coronaviruses in general and the epidemiology, clinical manifestations, diagnosis, treatment, and prevention of ccCoVs are discussed here.

The other human coronaviruses are:

●Severe acute respiratory syndrome coronavirus (SARS-CoV) – This betacoronavirus caused an outbreak of rapidly progressive respiratory illness that spread from southern China and Hong Kong to Vietnam, Thailand, and Singapore, and then to Europe, Canada, and the United States between 2002 and 2004. There were over 8000 reported cases and 700 deaths. Stringent infection-control practices were successful in controlling the SARS epidemic, in part because patients were not highly contagious during the prodromal period and could thus be identified and placed on precautions before the height of infectiousness. No cases of SARS have been reported since mid-2004.

●Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – This betacoronavirus is the cause of coronavirus disease 2019 (COVID-19). SARS-CoV-2 and COVID-19 are discussed in detail separately. (See "COVID-19: Epidemiology, virology, and prevention" and "COVID-19: Clinical features" and "COVID-19: Diagnosis" and "COVID-19: Evaluation and management of adults with acute infection in the outpatient setting".)

●Middle East respiratory syndrome coronavirus (MERS-CoV) – This betacoronavirus is the cause of Middle East respiratory syndrome (MERS). MERS-CoV and MERS are also reviewed separately. (See "Middle East respiratory syndrome coronavirus: Virology, pathogenesis, and epidemiology".)

CORONAVIRUS VIROLOGY — 

Coronaviruses are classified as a family within the order Nidovirales, viruses that replicate using a nested set of mRNAs ("nido-" for "nest"). The coronavirus subfamily is further classified into four genera: alpha, beta, gamma, and delta coronaviruses. The human coronaviruses (HCoVs) are in two of these genera: alpha coronaviruses (HCoV-229E and HCoV-NL63) and beta coronaviruses (HCoV-HKU1, HCoV-OC43, Middle East respiratory syndrome coronavirus [MERS-CoV], the severe acute respiratory syndrome coronavirus [SARS-CoV]), and SARS-CoV-2 (figure 1) [1,2].

Viral composition — Coronaviruses are medium-sized enveloped positive-stranded RNA viruses whose name derives from their characteristic crown-like appearance in electron micrographs (picture 1) [3,4]. These viruses have the largest known viral RNA genomes, with a length of 27 to 32 kb. The host-derived membrane is studded with glycoprotein spikes and surrounds the genome, which is encased in a nucleocapsid that is helical in its relaxed form but assumes a roughly spherical shape in the virus particle (figure 2). Replication of viral RNA occurs in the host cytoplasm by a unique mechanism in which RNA polymerase binds to a leader sequence and then detaches and reattaches at multiple locations, allowing for the production of a nested set of mRNA molecules with common 3' ends (figure 3).

The genome encodes four or five structural proteins, S, M, N, HE, and E. HCoV-229E, HCoV-NL63, and the SARS coronavirus possess four genes that encode the S, M, N, and E proteins, respectively, whereas HCoV-OC43 and HCoV-HKU1 also contain a fifth gene that encodes the HE protein [5].

●The spike (S) protein projects through the viral envelope and forms the characteristic spikes in the coronavirus "crown." It is heavily glycosylated, probably forms a homotrimer, and mediates receptor binding and fusion with the host cell membrane. The major antigens that stimulate neutralizing antibody, as well as important targets of cytotoxic lymphocytes, are on the S protein [6]. Receptor usage is discussed below. (See 'Viral serotypes' below.)

●The membrane (M) protein has a short N-terminal domain that projects on the external surface of the envelope and spans the envelope three times, leaving a long C terminus inside the envelope. The M protein plays an important role in viral assembly [7].

●The nucleocapsid protein (N) associates with the RNA genome to form the nucleocapsid. It may be involved in the regulation of viral RNA synthesis and may interact with M protein during virus budding [7,8]. Cytotoxic T lymphocytes recognizing portions of the N protein have been identified [9].

●The hemagglutinin-esterase glycoprotein (HE) is found only in the betacoronaviruses, HCoV-OC43 and HKU1 (see 'Viral serotypes' below). The hemagglutinin moiety binds to neuraminic acid on the host cell surface, possibly permitting initial adsorption of the virus to the membrane. The esterase cleaves acetyl groups from neuraminic acid. The HE genes of coronaviruses have sequence homology with influenza C HE glycoprotein and may reflect an early recombination between the two viruses [10].

●The small envelope (E) protein leaves its C terminus inside the envelope and then either spans the envelope or bends around and projects its N terminus internally. Its function is not known, although, in the SARS-CoV, the E protein along with M and N are required for proper assembly and release of the virus [11].

Viral serotypes — Coronaviruses are widespread among birds and mammals, with bats being host to the largest variety of genotypes [12]. Animal and human coronaviruses fall into four distinct genera [1,2]. Seven coronavirus serotypes have been associated with disease in humans: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV, SARS-CoV-2, and MERS-CoV.

●Alphacoronavirus – This genus includes two human virus species, HCoV-229E and HCoV-NL63. HCoV-229E, like several animal alphacoronaviruses, utilizes aminopeptidase N (APN) as its major receptor [13]. In contrast, HCoV-NL63 uses angiotensin-converting enzyme-2 (ACE-2) [14]. Important animal alphacoronaviruses are transmissible gastroenteritis virus of pigs and feline infectious peritonitis virus. There are also several related bat coronaviruses among the alphacoronaviruses.

●Betacoronavirus – Two of the non-SARS human species of the betacoronavirus genus, HCoV-OC43 and HCoV-HKU1, have hemagglutinin-esterase activity and probably utilize sialic acid residues as receptors [15]. This genus also contains several bat viruses, MERS-CoV [16,17], SARS-CoV, and SARS-CoV-2, although the last three are genetically somewhat distant from HCoV-OC43 and HCoV-HKU1. SARS-CoV and SARS-CoV-2 use ACE-2 as the major receptor, and MERS-CoV uses dipeptidyl peptidase 4 (DPP4; also known as CD26).

Important animal betacoronaviruses are mouse hepatitis virus, a laboratory model for both viral hepatitis and demyelinating central nervous system disease, and bovine coronavirus, a diarrhea-causing virus of cattle. Bovine coronavirus is so similar to HCoV-OC43 that the two viruses have been merged into a single species termed betacoronavirus 1 [18]. HCoV-OC43 is thought to have jumped from one animal host to the other as recently as 1890 [19].

●Gammacoronavirus – This genus contains primarily avian coronaviruses, the most prominent of which is avian infectious bronchitis virus (AIBV), an important veterinary pathogen causing respiratory and reproductive tract disease in chickens.

●Deltacoronavirus – The deltacoronavirus genus contains recently discovered avian coronaviruses found in several species of songbirds.

HCoV-OC43, HCoV-NE63, HCoV-HKU1, and HCoV-229E are the common cold human coronaviruses. None replicate easily in tissue culture, and this limitation had previously impeded progress in their study. Both HCoV-229E and HCoV-OC43 were discovered in the 1960s and were shown in volunteer experiments to produce common colds in adults [3,20-22]. Studies in the 1970s and 1980s linked them to as much as one-third of upper respiratory tract infections during winter outbreaks, 5 to 10 percent of overall colds in adults, and some proportion of lower respiratory illness in children [23-25].

Little further information developed after this until the emergence of SARS in 2002 and the development of molecular diagnostic methods. Then HCoV-NL63 and HCoV-HKU1 were quickly discovered and found to have worldwide distribution [26-29]. The polymerase chain reaction may be used for the diagnosis of each of the four human coronaviruses, and this technique has allowed substantial investigation into their epidemiology and pathogenicity. (See 'Diagnosis' below.)

EPIDEMIOLOGY

Seasonality — ccCoVs HCoV-OC43, HCoV-NE63, HCoV-HKU1, and HCoV-229E are ubiquitous; wherever investigators have looked, they have been detected. Their seasonality depends, in part, on the climate.

In temperate climates, coronavirus respiratory infections occur primarily in the winter, although smaller peaks are sometimes seen in the fall or spring, and infections can occur at any time of the year [24,30-32]. The winter seasonality was observed in a seven-year study of the ccCoVs in the United States from 2014 to 2021 [33]. In all, the seasonality was remarkably consistent from year to year, with season onset in late-October to mid-November and peak in early-January to mid-February. The only exception was the 2020 to 2021 season, during which peak activity occurred 11 weeks later than prior seasons, likely because of population-based preventive strategies during the COVID-19 pandemic. While the cadence of the yearly epidemics was strikingly similar, the predominant species varied from year to year. Similar observations were made in an eight-year study from Michigan in the United States, in which ccCoV infections were identified between December and May, with a peak in January and February; only 2.5 percent of infections were identified between June and September [34].

A large study from Scotland, in which molecular testing for respiratory viruses was performed in over 74,000 acute respiratory illnesses among adults and children from 2005 to 2017, gives some idea of the age incidence and seasonality of ccCoV infections (OC43, 229E, and NL63) in relation to other respiratory viruses in a temperate climate [35]. The samples were obtained in general practitioner offices and hospital in- or out-patient facilities. ccCoV infections were most common in the winter during influenza season (accounting for approximately 7 percent of all respiratory viral detections), were distributed across all age groups, and were less common than those caused by rhinovirus (15 to 46 percent), influenza (13 to 34 percent), or respiratory syncytial virus (10 to 22 percent). Coinfections were relatively common, particularly in young children. The three species differed in their age incidence patterns: OC43 (the most common overall) was found most often in infants, young (one to five years old) children, and older adults; 229E was most common in adults (>17 years old) of all ages; NL63 was found most often in infants under a year of age, with a gradual decrease in frequency throughout child- and adulthood.

A nine-year survey of all children under 16 years of age admitted for acute respiratory illness at the only hospital in Sør-Trøndelag County, Norway, a region with approximately 59,000 children, found that both HCoV-OC43 and HCoV-NL63 were detected most frequently and were epidemic every other winter, that HCoV-HKU-1 usually prevailed every other winter during the years when HCoV-OC43 and HCoV-NL63 did not, and that detection of 229E was unusual [36]. HCoV-associated lower respiratory tract infection hospitalization rates for the population under five years were calculated at 1.5 per 1000 children per year.

Seasonality in China has not been thoroughly studied, but from preliminary data, ccCoVs are seen most often in June, July, and August in northern China and in the province of Qinghai in northwestern China [37-39]. A seven-year study of hospitalized children in Guangzhou, China, described the seasonality in a subtropical region, with outbreaks at almost any time of year but predominantly in the spring and fall [40].

In other surveys, HCoV-OC43, HCoV-NL63, HCoV-229E, and HCoV-HKU1 predominate unpredictably in certain years and in certain parts of the world [25,31,36,40].

In almost all these surveys, HCoV-OC43 is the most common of the four strains, followed by HCoV-NL63, but the prevalence of the various strains in any particular year and place is often unpredictable.

Routes and risk of transmission — ccCoVs probably spread in a fashion similar to that of rhinoviruses, via direct contact with infected secretions or large respiratory particles. Thus, they can spread easily through a household. In one study, the secondary infection rate among household members was 7 to 12 percent, depending on the serotype, with an average serial interval of 3.2 to 3.6 days between the index and secondary infection [34].

In hospital settings, spread among pediatric patients probably occurs through shedding by their infected caretakers [41]. Outbreaks are common in long-term care facilities for older adults [42].

Immunity and reinfection — Immunity develops soon after infection but wanes gradually over time. Reinfection is common, presumably because of waning immunity, but possibly because of antigenic variation within species [43].

Although ccCoVs share common features, the immune response to the different ccCoVs appears to be virus specific. In a cohort of children followed from birth to four years of age, in which 345 endemic coronavirus (representing the four ccCoVs) infections were detected, immunity against the identified species (ie, homotypic immunity) occurred frequently, yet no heterotopic or cross-protective immunity was observed [44].

The impact of immunity to ccCoVs on the incidence and severity of COVID-19 is uncertain, though prior infection with ccCoVs does not appear to offer protection against SARS-CoV-2 infection, consistent with the data discussed above suggesting that ccCoVs induce homotypic, rather than heterotypic, immunity. In a study evaluating transmission between household contacts, presence of antibodies specific for any of the ccCoVs was not associated with protection against infection with SARS-CoV-2 [45]. Further, infection with one variant of SARS-CoV-2 does not necessarily provide protective immunity against other variants. This is discussed elsewhere. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Immune responses following infection'.)

CLINICAL MANIFESTATIONS

Respiratory syndromes — HCoV-229E and HCoV-OC43 have been proven to have pathogenicity in humans in volunteer studies where they, along with other less well-characterized coronavirus strains, reproducibly induced colds very similar to those induced by rhinoviruses, characterized by an incubation period of three days followed by upper respiratory tract symptoms such as nasal congestion and rhinorrhea [22,46]. It is assumed that HCoV-NL63 and HCoV-HKU1 have similar pathogenicity, but proof of this is lacking. Moreover, when tested by polymerase chain reaction (PCR), asymptomatic individuals of all ages periodically carry coronaviruses.

●Upper respiratory tract infections – ccCoVs probably account for 5 to 10 percent of all acute upper respiratory tract infections in adults [25], with outbreaks during which 25 to 35 percent of respiratory infections can be attributed to a single species. Like rhinoviruses, ccCoVs can be detected in middle ear effusions and have been implicated as important viral causes of acute otitis media in children [47]. Respiratory tract infection surveys that include asymptomatic babies and children indicate that coronaviruses, like rhinoviruses, are often coinfections with other respiratory viruses and are also often found in the absence of respiratory symptoms [36,48]. In one large study, when the concentration of viral RNA found in nasopharyngeal aspirates was measured (using the PCR cycle threshold value), multivariate analysis showed a significant association between a high ccCoV RNA concentration (cycle threshold <28) and both respiratory tract disease (compared with asymptomatic controls) and lack of coinfection [36]. (See "Epidemiology, clinical manifestations, and pathogenesis of rhinovirus infections" and "Acute otitis media in children: Epidemiology, microbiology, and complications", section on 'Viral pathogens'.)

●Lower respiratory tract infections – ccCoVs infections have also been linked to more severe respiratory diseases.

In adults with community-acquired pneumonia, ccCoVs are detected by PCR at frequencies similar to or somewhat lower than those of other respiratory viruses such as influenza virus, rhinovirus, and respiratory syncytial virus. Their etiologic role is not clear, in part because copathogens are often found. In three studies, simultaneous sampling of healthy adults was carried out. In one study, ccCoVs were detected more frequently in those with pneumonia (13 percent) than in healthy controls (4 percent), although coronaviruses were also detected in a substantial proportion of patients with nonpneumonic lower respiratory tract infection (10 percent) [49]. In a second study, which included 3104 adults in Europe spanning two and a half years, patients with lower respiratory tract infection (which included community-acquired pneumonia as well as cough without evidence of pneumonia) were sampled [50]. ccCoVs were the third most common viruses detected (after rhinoviruses and influenza viruses) and were found significantly more often than in matched healthy controls. In a third study, the numbers were small and the difference in detection of ccCoVs in adults with community-acquired pneumonia compared with asymptomatic individuals was not significant [51].

ccCoVs are also associated with exacerbations of airway disease. They have been found in 4 to 6 percent of adults with exacerbations of chronic obstructive pulmonary disease (less frequent than rhinoviruses and respiratory syncytial virus; equally frequent or somewhat less frequent than influenza; and more frequent than parainfluenza viruses, human metapneumovirus, and adenoviruses) [52]. They have been temporally linked to acute asthma attacks in both children and adults [53-55].

ccCoVs are also frequently associated with respiratory infection severe enough for hospitalization [56,57]. A two-year (2017 to 2019) population-based study of respiratory viruses in acutely hospitalized adults in New York City found that ccCoVs were the third most common virus, detected in 14 percent, following rhinoviruses (37 percent) and influenza virus (20 percent) [58]. These were detected most frequently among patients >80 years old. All other viruses were each found in fewer than 10 percent. In other studies, HCoV-OC43 has been the predominant ccCoV detected in hospitalized patients, suggesting that HCoV-OC43 may have greater clinical impact [56,57].

Among older adult patients, there is increasing evidence that ccCoVs are important causes of influenza-like illness, acute exacerbations of chronic bronchitis or chronic obstructive pulmonary disease, and pneumonia, where their frequency is below those of influenza and respiratory syncytial virus but similar to that of rhinoviruses [59-63]. Several outbreaks of HCoV-OC43 respiratory disease in older adults living in long-term care facilities have been described [64,65], with case-fatality rates of 8 percent. A fatal case of acute respiratory distress syndrome in a 76-year-old woman with no underlying diseases and monoinfection with HCoV-NL63 has also been reported [66].

Among neonates, infants and young children hospitalized with community-acquired pneumonia, ccCoVs have been found in variable proportions, ranging from 2 to 8 percent, and have been identified even more frequently in lower respiratory tract disease in outpatient children [23,67,68]. In children hospitalized in New York City with ccCoV infection and respiratory disease, a majority were under five years of age and had some underlying condition such as heart disease, chronic lung disease, or congenital abnormalities [69]. They are also an important cause of nosocomial infections in neonatal intensive care units [70]. One of the more recently discovered ccCoVs, HCoV-NL63, has been associated with croup in children [69,71,72].

ccCoVs are also found in immunocompromised hosts with pneumonia, including adults with HIV infection [73-79]. Twenty-eight HCoV-infected hematopoietic cell transplant (HCT) recipients were compared with published series of similar HCT patients with influenza virus, respiratory syncytial virus (RSV), and parainfluenza virus infections from the same center [80]. All viruses were detected in bronchoalveolar lavage specimens. In multivariable models, no differences in survival were seen between the HCoV-infected patients and those infected with the other respiratory viruses. There is also some evidence of an association between coronavirus infection and acute rejection and bronchiolitis obliterans syndrome in lung transplant recipients, although the association is less clear than for other respiratory viruses [81]. (See "Parainfluenza viruses in adults" and "Parainfluenza viruses in children" and "Viral infections following lung transplantation", section on 'Rejection'.)

Gastrointestinal manifestations — Diarrhea, nausea, vomiting, and abdominal pain are common features in patients with ccCoV respiratory infection. In a study of 331 patients with acute respiratory illness and systemic features (fever, chills, headache, or myalgia), identification of ccCoV on nasopharyngeal testing was associated with a higher likelihood of self-reported gastrointestinal symptoms compared with other respiratory pathogens or negative testing (documented in 22 of 28 patients with ccCoV) [82]. In another study of 13 adults with HCoV-HKU1 respiratory infection, 5 (38 percent) also reported gastrointestinal symptoms [83].

The idea that coronaviruses produce diarrhea in humans is intriguing because of their clear intestinal pathogenicity in animals. Early human studies evaluating gastrointestinal pathogenicity depended on finding "coronavirus-like particles" (CVLPs) by electron microscopy in stool samples. The most convincing studies showed a strong association between the presence of CVLPs and diarrhea in infants [84] or necrotizing enterocolitis in newborns [85,86]. As an example, in a case series from Texas of infants with necrotizing enterocolitis who had CVLPs identified in stool specimens by electron microscopy, a coronavirus was isolated and successfully passaged from the stool of two infants [86]. Infants in whom this virus was identified developed a specific antibody response to the major proteins of the virus. The identity of this virus was unknown (genetic methods were not applied). In other studies, human coronaviruses that appear to be antigenically related to HCoV-OC43 have been purified from the stool of infants with diarrhea [84].

All four ccCoV species have also been found by reverse-transcription polymerase chain reaction (RT-PCR) in the stools of a small proportion of infants and children hospitalized with diarrhea (often with respiratory symptoms as well) [30,87]. Three surveys of diarrhea used molecular methods to screen for all four HCoV species known to cause community-acquired infections. In one study, all four species were found in stools from 2.5 percent of 878 children with diarrhea and 1.8 percent of 112 asymptomatic children by RT-PCR; however, in this and other surveys, most diarrhea-associated coronavirus-positive stools also contained other known pathogens, such as rotavirus or norovirus [87,88]. In a study that used RT-PCR to investigate the frequency of ccCoVs in stool samples from children and adults with gastrointestinal illness, CoV-HKU1 was found in 4 of 479 patients (0.8 percent), and no other HCoV species were found [89].

POSSIBLE DISEASE ASSOCIATIONS

Neurologic disease — The clear involvement of several animal coronaviruses in acute and chronic neurologic disease has stimulated a search for similar pathogenicity of human coronaviruses. ccCoVs can infect neural cells in vitro [90], and three-week-old mice develop generalized encephalitis after intracerebral inoculation with HCoV-OC43 [91]. HCoV-OC43 RNA sequences have been detected in the cerebrospinal fluid of a 15-year-old boy with acute demyelinating encephalomyelitis (ADEM) [92]. In another report, full-length HCoV-OC43 RNA was recovered from the brain, with widespread cerebral immunohistochemical staining at autopsy, in an 11-month-old boy with severe combined immunodeficiency and acute encephalitis following umbilical cord blood transplantation [93].

With the observation that rats and mice infected with certain strains of mouse hepatitis virus (MHV) developed a severe demyelinating encephalitis similar to multiple sclerosis (MS) [94], investigators have sought to link ccCoVs with MS. Currently available evidence is inconclusive. T cell clones from patients with MS have been shown to react both with HCoV-229E antigens and myelin basic protein, suggesting molecular mimicry as a basis of pathogenesis [95]. Some, but not all, investigators have detected RNA of the human coronaviruses, HCoV-OC43 and HCoV-229E, more frequently in brain tissue from MS patients by reverse-transcription polymerase chain reaction (RT-PCR) than in healthy individuals [96].

Despite these findings, an etiologic connection between ccCoVs and MS or other demyelinating diseases remains tentative and unproven. (See "Manifestations of multiple sclerosis in adults".)

Kawasaki disease — An association of ccCoV infection with Kawasaki disease was reported by one group of investigators and stimulated a flurry of investigation worldwide [97]. However, others failed to confirm this finding, and, thus it is assumed that ccCoVs do not have a role in this disease [98-100]. (See "Kawasaki disease: Pathogenesis, epidemiology, and etiology", section on 'Infectious etiology'.)

There have been reports of a multisystem inflammatory syndrome in children associated with coronavirus disease 2019 (COVID-19) that has clinical features similar to those of Kawasaki disease and/or toxic shock syndrome. This is discussed in detail elsewhere. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis".)

DIAGNOSIS — 

Specific microbiologic diagnosis of ccCoVs in patients with acute respiratory infections is generally unnecessary, since there is no specific management or preventive approach, and identification of a ccCoV does not preclude the possibility of other respiratory pathogens (eg, influenza, respiratory syncytial virus [RSV], or SARS-CoV-2).

However, reverse-transcription polymerase chain reaction (RT-PCR) assays that can detect all four of the known ccCoV strains are included in many respiratory nucleic acid amplification diagnostic panels, and these are the test of choice for ccCoV. These are performed on nasopharyngeal specimens. Although broadly reacting pan-coronavirus primers have been developed, they are less sensitive than primers designed for each of the four human strains [101,102]. The sensitivity may be further improved by using real-time RT-PCR [31].

Other rapid techniques that have been used to detect ccCoVs from nasopharyngeal samples include immunofluorescence antigen detection assays [101,103,104]. ccCoVs are difficult to grow in tissue culture.

DIFFERENTIAL DIAGNOSIS — 

Other respiratory pathogens (eg, rhinovirus, adenovirus, metapneumovirus, parainfluenza virus, respiratory syncytial virus [RSV], SARS-CoV-2, and influenza virus) can share the same clinical features of ccCoV. Clinical features alone are insufficient to reliably distinguish these infections.

The differential diagnosis of syndromes associated with ccCoV is discussed in detail elsewhere:

●(See "The common cold in children: Clinical features and diagnosis" and "The common cold in adults: Diagnosis and clinical features".)

●(See "Acute otitis media in children: Epidemiology, microbiology, and complications", section on 'Microbiology'.)

●(See "Acute bronchitis in adults", section on 'Microbiology'.)

●(See "Role of viruses in wheezing and asthma: An overview".)

●(See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults" and "Pneumonia in children: Epidemiology, pathogenesis, and etiology".)

TREATMENT AND PREVENTION — 

There is currently no treatment recommended for ccCoV infections except for supportive care as needed.

Chloroquine, which has potent antiviral activity against SARS-CoV [105], has been shown to have similar activity against HCoV-229E in cultured cells [106] and against HCoV-OC43 both in cultured cells and in a mouse model [107]. However, there have been no studies of efficacy in humans.

Preventive measures are the same as for rhinovirus infections, which consist of handwashing and the careful disposal of materials infected with nasal secretions. The use of surface disinfectants is also an important issue in infection control, since coronaviruses appear to survive for one or more days after drying on surfaces such as stainless steel, plastic, or cloth [108].

The efficacy of various disinfectants was examined both on viruses in liquid suspension and on viruses dried on surfaces [109]. Human coronaviruses, including CoV-229E and SARS-CoV, as well as several animal coronaviruses (eg, mouse hepatitis virus and transmissible gastroenteritis virus of pigs), were studied. These viruses (both in suspension and dried on surfaces) were very susceptible to 70% ethanol, with reduction of viability by greater than 3 log within seconds [110-112]. Likewise, hexachlorophene [113], 2% glutaraldehyde [110] and 1% povidone-iodine [110,112] each produced satisfactory killing. It appears that susceptibility of coronaviruses to 6% sodium hypochlorite (the active agent in bleach) solutions has been variable, but satisfactory killing was achieved with concentrations of 1:40 or higher [111,112]. Coronaviruses were not killed by benzalkonium chloride or chlorhexidine unless 70% ethanol was added [110].

There has been little interest in developing vaccines for the ccCoVs for several reasons. First, four separate species have been described and there is evidence within at least one of these species of clinically significant antigenic variation [43]. In addition, vaccine enhancement of disease has been shown for one animal coronavirus, feline coronavirus; hypersensitivity was induced in some animals by prior exposure to a vaccine containing the S protein, with the production of an immunologically mediated severe disease, feline infectious peritonitis, upon reinfection with a coronavirus [114].

SUMMARY AND RECOMMENDATIONS

●Coronavirus virology – Coronaviruses are medium-sized enveloped positive-stranded RNA viruses whose name derives from their characteristic crown-like appearance in electron micrographs (picture 1) The common cold coronaviruses (ccCoVs) include the alphacoronaviruses HCoV-229E and HCoV-NL63 and the betacoronaviruses HCoV-OC43 and HcoV-HKU1. (See 'Coronavirus virology' above.)

Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV) are all betacoronaviruses. SARS-CoV-2 and MERS are discussed in detail elsewhere. (See "COVID-19: Epidemiology, virology, and prevention" and "Middle East respiratory syndrome coronavirus: Virology, pathogenesis, and epidemiology".)

●Geographic and seasonal distribution – ccCoVs are ubiquitous; wherever investigators have looked, they have been detected. In temperate climates, ccCoV respiratory infections occur primarily in the winter, although smaller peaks are sometimes seen in the fall or spring, and infections can occur at any time of the year. (See 'Epidemiology' above.)

●Clinical features – ccCoVs are the cause of 5 to 10 percent of community-acquired upper respiratory tract infections in adults, occurring sporadically or in outbreaks of variable size. They probably also play a role in more severe respiratory infections in both children and adults (eg, influenza-like illness, community-acquired pneumonia, exacerbation of chronic airway disease), particularly adults with underlying pulmonary disease and older adults. (See 'Introduction' above and 'Clinical manifestations' above.)

●Diagnosis – Most ccCoV infections are diagnosed clinically, although reverse-transcription polymerase chain reaction (RT-PCR) testing on nasopharyngeal specimens is the diagnostic method of choice. (See 'Diagnosis' above.)

●Treatment – There are no therapies for ccCoV infection beyond supportive care. (See 'Treatment and prevention' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Kenneth McIntosh, MD, who contributed to earlier versions of this topic review.