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. (See 'Neurologic disease' below.)

The microbiology of coronaviruses and the epidemiology, clinical manifestations, diagnosis, treatment, and prevention of ccCoVs will be discussed here.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is discussed in detail separately. (See "COVID-19: Epidemiology, virology, and prevention".)

Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are also reviewed separately. (See "Severe acute respiratory syndrome (SARS)" and "Middle East respiratory syndrome coronavirus: Virology, pathogenesis, and epidemiology".)

CORONAVIRUS DISEASE 2019 (COVID-19) PANDEMIC — A novel coronavirus, previously designated 2019-nCoV, was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China, at the end of 2019. It subsequently spread throughout China and then worldwide, becoming a global health emergency. In February 2020, the World Health Organization (WHO) designated the disease COVID-19, which stands for coronavirus disease 2019 [1]. The virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the cause of COVID-19, which is discussed in detail elsewhere. (See "COVID-19: Epidemiology, virology, and prevention".)

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) [2,3].

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) [4,5]. 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 [6].

●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 [7]. 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 [8].

●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 [8,9]. Cytotoxic T lymphocytes recognizing portions of the N protein have been identified [10].

●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 [11].

●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 [12].

Viral serotypes — Coronaviruses are widespread among birds and mammals, with bats being host to the largest variety of genotypes [13]. Animal and human coronaviruses fall into four distinct genera [2,3]. 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.

●The alphacoronavirus 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 [14]. In contrast, HCoV-NL63, like SARS-CoV and SARS-CoV-2 (betacoronaviruses), uses angiotensin-converting enzyme-2 (ACE-2) [15]. Important animal alphacoronaviruses are transmissible gastroenteritis virus of pigs and feline infectious peritonitis virus. There are also several related bat coronaviruses among the alphacoronaviruses.

●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 [16]. This genus also contains several bat viruses, MERS-CoV [17,18], SARS-CoV, and SARS-CoV-2, although the last three are genetically somewhat distant from HCoV-OC43 and HCoV-HKU1.

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 [19]. HCoV-OC43 is thought to have jumped from one animal host to the other as recently as 1890 [20].

●The gammacoronavirus 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.

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

None of the common cold human coronaviruses (HCoV-OC43, HCoV-NE63, HCoV-HKU1, and HCoV-229E) replicate easily in tissue culture, and, until recently, this 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 [4,21-23]. 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 [24-26].

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 [27-30]. 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 — This section discusses the epidemiology of common cold coronaviruses (ccCoVs).

The epidemiology of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS) is discussed separately:

●(See "COVID-19: Epidemiology, virology, and prevention", section on 'Epidemiology'.)

●(See "Severe acute respiratory syndrome (SARS)", section on 'Epidemiology'.)

●(See "Middle East respiratory syndrome coronavirus: Virology, pathogenesis, and epidemiology", section on 'Epidemiology'.)

Seasonality — ccCoVs 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 [25,31,32]. The winter seasonality was confirmed in an eight-year study in 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 [33].

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 [34]. 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 [35]. 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 [36-38]. 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 [39].

In other surveys, HCoV-OC43, HCoV-NL63, HCoV-229E, and HCoV-HKU1 predominate unpredictably in certain years and in certain parts of the world [26,32,35,39].

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 aerosol droplets. 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 [33].

In hospital settings, spread among pediatric patients probably occurs through shedding by their infected caretakers [40]. Outbreaks are common in long-term care facilities for older adults [41].

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 [42].

The impact of immunity to ccCoVs on the incidence and severity of COVID-19 is uncertain. This is discussed elsewhere. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Immune responses following infection'.)

CLINICAL MANIFESTATIONS — The clinical manifestations of infections caused by common cold human coronaviruses (HCoVs) are described here.

Clinical features of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS) are discussed separately:

●(See "COVID-19: Diagnosis" and "COVID-19: Clinical features".)

●(See "Severe acute respiratory syndrome (SARS)", section on 'Clinical manifestations'.)

●(See "Middle East respiratory syndrome coronavirus: Clinical manifestations and diagnosis", section on '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 [23,43]. 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 – Common cold coronaviruses (ccCoVs) probably account for 5 to 10 percent of all acute upper respiratory tract infections in adults [26], 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 [44]. 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 [35,45]. 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 [35]. (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) [46]. 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 [47]. 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 [48].

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) [49]. They have been temporally linked to acute asthma attacks in both children and adults [50-52].

ccCoVs are also frequently associated with respiratory infection severe enough for hospitalization [53,54]. 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) [55]. 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 [53,54].

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 [56-60]. Several outbreaks of HCoV-OC43 respiratory disease in older adults living in long-term care facilities have been described [61,62], 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 [63].

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 [24,64,65]. 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 [66]. They are also an important cause of nosocomial infections in neonatal intensive care units [67]. One of the more recently discovered ccCoVs, HCoV-NL63, has been associated with croup in children [66,68,69].

ccCoVs are also found in immunocompromised hosts with pneumonia, including adults with HIV infection [70-76]. Twenty-eight HCoV-infected hematopoietic cell transplant (HCT) recipients were compared with published series of similar HCT patients with influenza virus, RSV, and parainfluenza virus infections from the same center [77]. 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 [78]. (See "Parainfluenza viruses in adults" and "Parainfluenza viruses in children" and "Viral infections following lung transplantation", section on 'Rejection'.)

Gastrointestinal manifestations — The idea that coronaviruses produce diarrhea in humans is intriguing because of their clear intestinal pathogenicity in animals. Early human studies 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 [79] or necrotizing enterocolitis in newborns [80]. In several studies, CVLPs have been purified that appear to be antigenically related to HCoV-OC43 [79].

All four ccCoV species have been found by reverse-transcriptase 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) [31,81]. 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 [81,82]. 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 [83].

A study assessed the association between gastrointestinal manifestations (diarrhea, vomiting, nausea, and abdominal pain) in adults reporting to general practitioners with respiratory symptoms plus systemic symptoms or signs (fever, chills, headache, or myalgia) [84]. Viruses were sought from respiratory and stool samples and bacteria from stool samples only. Gastrointestinal symptoms, which occurred in 57 percent of patients, were more likely to occur in those with fever >39°C (102.2°F), headache, a gastrointestinal pathogen, or HCoV respiratory infection. Although a few HCoVs were found in stool samples, the authors thought that these were likely swallowed viruses. The pathogenetic mechanism of these gastrointestinal manifestations remains unclear.

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. Common cold coronaviruses (ccCoVs) can infect neural cells in vitro [85], and three-week-old mice develop generalized encephalitis after intracerebral inoculation with HCoV-OC43 [86]. HCoV-OC43 RNA sequences have been detected in the cerebrospinal fluid of a 15-year-old boy with acute demyelinating encephalomyelitis (ADEM) [87]. 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 [88].

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) [89], 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 [90]. 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-transcriptase polymerase chain reaction than in healthy individuals [91].

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 [92]. Others failed to confirm this finding, and, at the present time, it is assumed that neither ccCoVs nor SARS-CoV-2 have a role in this disease [93-95]. (See "Kawasaki disease: 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 — Since there is no effective treatment for common cold coronavirus (ccCoV) infections, establishing the diagnosis is of limited utility in patients suspected of having these infections. In contrast, diagnosing coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS) is critically important for understanding outbreak epidemiology and limiting transmission of infection. These issues are discussed elsewhere. (See "Middle East respiratory syndrome coronavirus: Clinical manifestations and diagnosis", section on 'Diagnosis' and "Severe acute respiratory syndrome (SARS)", section on 'Diagnosis' and "COVID-19: Diagnosis", section on 'Diagnostic approach'.)

Rapid techniques that have been used to detect ccCoVs from nasopharyngeal samples include reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence antigen detection assays [96-98].

Because of its utility for detecting all four of the known ccCoV strains, RT-PCR has supplanted other diagnostic methods. Although broadly reacting pan-coronavirus primers have been developed, they are less sensitive than primers designed for each of the four human strains [96,99]. The sensitivity may be further improved by using real-time RT-PCR [32]. All four common cold strains are included in many respiratory nucleic acid amplification diagnostic panels.

ccCoVs are difficult to grow in tissue culture.

TREATMENT AND PREVENTION — There is currently no treatment recommended for common cold coronavirus (ccCoV) infections except for supportive care as needed.

Chloroquine, which has potent antiviral activity against SARS-CoV [100], has been shown to have similar activity against HCoV-229E in cultured cells [101] and against HCoV-OC43 both in cultured cells and in a mouse model [102]. 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 [103]. More detailed information on prevention of coronavirus disease 2019 (COVID-19), SARS, and Middle East respiratory syndrome (MERS) is discussed separately. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Prevention' and "Severe acute respiratory syndrome (SARS)", section on 'Prevention' and "Middle East respiratory syndrome coronavirus: Treatment and prevention", section on 'Prevention'.)

The efficacy of various disinfectants was examined both on viruses in liquid suspension and on viruses dried on surfaces [104]. 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 [105-107]. Likewise, hexachlorophene [108], 2% glutaraldehyde [105] and 1% povidone-iodine [105,107] 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 [106,107]. Coronaviruses were not killed by benzalkonium chloride or chlorhexidine unless 70% ethanol was added [105].

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 [42]. 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 [109].

Development of vaccines to prevent COVID-19, SARS, and MERS is discussed elsewhere. (See "Severe acute respiratory syndrome (SARS)", section on 'Vaccine development' and "Middle East respiratory syndrome coronavirus: Treatment and prevention", section on 'Vaccine development' and "COVID-19: Vaccines" and "COVID-19: Epidemiology, virology, and prevention", section on 'Vaccines'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: COVID-19 – Index of guideline topics" and "Society guideline links: Middle East respiratory syndrome coronavirus".)

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SUMMARY AND RECOMMENDATIONS

●Common cold coronaviruses (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, and probably also play a role in severe respiratory infections in both children and adults, particularly adults with underlying pulmonary disease and older adults. (See 'Introduction' above and 'Clinical manifestations' above.)

●Coronaviruses are medium-sized enveloped positive-stranded RNA viruses whose name derives from their characteristic crown-like appearance in electron micrographs (picture 1). (See 'Viral composition' above.)

●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.)

●Most ccCoV infections are diagnosed clinically, although reverse-transcription polymerase chain reaction applied to respiratory secretions is the diagnostic test of choice. (See 'Diagnosis' above.)

●There is currently no treatment recommended for ccCoV infections except for supportive care as needed. (See 'Treatment and prevention' above.)

●In late 2019, a novel coronavirus was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in China. It subsequently spread throughout China and elsewhere, becoming a global health emergency. In February 2020, the World Health Organization designated the disease COVID-19, which stands for coronavirus disease 2019. Previously, this virus was referred to as 2019-nCoV. COVID-19 is discussed in detail elsewhere. (See "COVID-19: Epidemiology, virology, and prevention".)

●Severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus are also discussed in detail separately. (See "Severe acute respiratory syndrome (SARS)" and "Middle East respiratory syndrome coronavirus: Virology, pathogenesis, and epidemiology".)