INTRODUCTION — Coronaviruses are important human and animal pathogens. During epidemics, they 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 coronaviruses 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, epidemiology, clinical manifestations, diagnosis, treatment, and prevention of community-acquired coronaviruses will be discussed here. Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are reviewed separately. (See “Severe acute respiratory syndrome (SARS)” and “Middle East respiratory syndrome coronavirus: Virology, pathogenesis, and epidemiology”.)

NOVEL CORONAVIRUS (2019-NCOV) OUTBREAK IN CHINA

Epidemiology — A novel coronavirus, 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. By late January 2020, thousands of laboratory-confirmed cases in China had been reported, and the case count has been rising daily; the majority of reports are from Hubei and surrounding provinces, but numerous cases have been reported in other provinces and municipalities throughout China, including Beijing [1,2]. Sporadic but increasing cases have also been reported in other countries globally (including countries in Asia and Europe, as well as Australia, the United States [Washington state, Illinois, California, and Arizona], and Canada), mainly among travelers from China [3-6]. Updated case counts in English can be found on the World Health Organization and the European Centre for Disease Prevention and Control websites.

Epidemiologic investigation in Wuhan identified an initial association with a seafood market where most patients had worked or visited and which was subsequently closed for disinfection [7]. The seafood market also sold live rabbits, snakes, and other animals. However, as the outbreak progressed, most laboratory-confirmed cases had no contact with this market, and cases were identified among health care workers and other contacts of patients with 2019-nCoV infection. Human-to-human transmission has been confirmed in China [8] and has also been identified in other countries [9], including the United States. Understanding of the transmission risk is incomplete. One report of a small cluster of five cases suggested transmission from asymptomatic individuals during the incubation period; all patients in this cluster had mild illness [10].

Virology — Full-genome sequencing and phylogenic analysis indicated that 2019-nCoV is a betacoronavirus, in a distinct clade from the betacoronaviruses associated with human severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) [11,12]. It has close similarity to bat coronaviruses, and it is likely that bats are the primary source, but whether 2019-nCoV is transmitted directly from bats or through some other mechanism (eg, through an intermediate host) is unknown [13]. (See ‘Viral serotypes’ below.)

Clinical features — The illness is characterized primarily by fever, cough, dyspnea, and bilateral infiltrates on chest imaging [1,2,7,14]. The incubation period of 2019-nCoV is thought to be within 14 days following exposure. Although many of the reported infections are not severe, approximately 20 percent of confirmed patients have had critical illness (including respiratory failure, septic shock, or other organ failure requiring intensive care). Most of the fatal cases have occurred in patients with underlying medical comorbidities.

In a study describing 41 of the initial cases identified in the outbreak, 73 percent of cases were males, and the median age was 49 (interquartile range 41 to 58 years) [14]. Nearly all (98 percent) reported fever, 76 percent had cough, and 44 percent had myalgias/fatigue. Dyspnea developed in 55 percent after a median of eight days of illness. Lymphopenia was common and all patients had parenchymal lung abnormalities on computed tomography (CT) of the chest, including ground glass opacities, subsegmental consolidation, and multilobular consolidation. Acute respiratory distress syndrome developed in 30 percent, and mechanical ventilation was implemented in 10 percent. Similar clinical features were described in a cohort of 99 patients with confirmed 2019-nCoV infection admitted to an infectious disease specialty hospital in Wuhan [15].

In a family cluster of infections, the onset of fever and respiratory symptoms occurred approximately three to six days after presumptive exposure [16]. Similarly, in an analysis of 10 patients with confirmed 2019-nCoV-associated pneumonia, the estimated mean incubation period was five days [8].

Clinical suspicion, evaluation, diagnosis, and management — The approach to management should focus on early recognition of suspect cases, immediate isolation and institution of infection control measures, and supportive care. The possibility of 2019-nCoV should be considered in patients with fever and/or lower respiratory tract symptoms who reside in or have recently (within the prior 14 days) traveled to the Wuhan area of China or who have had recent close contact with a confirmed or suspected case of 2019-nCoV.

When 2019-nCoV is suspected, infection control measures should be implemented and public health officials notified. In the United States, the Centers for Disease Control and Prevention (CDC) recommends a cautious approach to infection control in the clinical setting and advises standard, contact, and airborne precautions (table 1), as well as eye protection [17]. In addition to testing for other respiratory pathogens, the CDC recommends collection of specimens from the lower respiratory tract (sputum, tracheal aspirate, or bronchoalveolar lavage), upper respiratory tract (nasopharyngeal/oropharyngeal swab or nasopharyngeal wash), and serum.

2019-nCoV is detected by polymerase chain reaction; in the United States, testing is performed by the CDC.

Management of documented cases consists of supportive care.

Understanding of this novel coronavirus is evolving rapidly. The World Health Organization (WHO) has issued interim guidance on surveillance case definitions, laboratory diagnosis, and clinical management. The CDC has also issued interim guidance.

Links to these and other related society guidelines are found elsewhere. (See ‘Society guideline links’ below.)

Global public health measures — On January 30, 2020, WHO declared the 2019-nCoV outbreak a public health emergency of international concern.

The WHO does not recommend international travel restrictions but does acknowledge that movement restriction may be temporarily useful in some settings. WHO advises exit screening for international travelers from areas with ongoing transmission of 2019-nCoV to identify individuals with fever, cough, or potential high-risk exposure [18].

In China, health officials announced a restriction of public transportation within and a halt of air and rail traffic out of Wuhan and other surrounding areas [1]. In the United States, the CDC recommends that individuals avoid all nonessential travel to China [19]; airports in some major cities (including San Francisco, Los Angeles, and New York City) had begun screening air travelers from Wuhan for signs of illness on arrival.

WHO also advises general measures to reduce transmission of infection, including diligent hand washing and respiratory hygiene and avoiding close contact with live or dead animals and ill individuals.

VIROLOGY — Coronaviruses are classified as a family within the Nidovirales order, 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], and the severe acute respiratory syndrome coronavirus [SARS-CoV]) (figure 1) [20,21].

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) [22,23]. 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 [24].

●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 [25]. 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 [26].

●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 [26,27]. Cytotoxic T lymphocytes recognizing portions of the N protein have been identified [28].

●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 [29].

●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 [30].

Viral serotypes — Coronaviruses are widespread among birds and mammals, with bats being host to the largest variety of genotypes [31]. Animal and human coronaviruses fall into four distinct genera (figure 1) [20,21]. There are five non-SARS coronavirus serotypes that have been associated with disease in humans: HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, and a novel coronavirus (MERS-CoV) that emerged in 2012.

●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 [32]. In contrast, HCoV-NL63, like the SARS-CoV (a betacoronavirus), uses angiotensin-converting enzyme-2 (ACE-2) [33]. 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 [34]. This genus also contains several bat viruses, MERS-CoV [35,36], and SARS-CoV, although the last two are genetically somewhat distant from HCoV-OC43 and HCoV-HKU1 (figure 1).

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 [37]. HCoV-OC43 is thought to have jumped from one animal host to the other as recently as 1900 [38].

●The gammacoronavirus genus contains primarily avian coronaviruses, the most prominent of which is infectious bronchitis virus of chickens. This is 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 community-acquired 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 [22,39-41]. 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 [42-44].

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 [45-48]. 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 — Community-acquired coronaviruses are ubiquitous; wherever investigators have looked, they have been detected. 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 [43,49,50]. 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 [51]. In other surveys, HCoV-OC43, HCoV-NL63, HCoV-229E, and HCoV-HKU1 predominate unpredictably in certain years and in certain parts of the world [44,50-52]. In almost all such 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 is often unpredictable.

A large polymerase chain reaction (PCR)-based study of viruses in adults and children with acute respiratory illness was performed in Scotland, with sampling in over 44,000 episodes over nine years and gives some idea of the incidence and seasonality of community-acquired HCoV infections in relation to other respiratory viruses in a temperate climate [53]. HCoV infections were most common in the winter, were distributed across all age groups, and were less common than those caused by rhinovirus, influenza, or respiratory syncytial virus but more common than other respiratory viruses; coinfections were relatively common, particularly in young children.

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 [52]. HCoV-associated lower respiratory tract infection hospitalization rates for the population under five years were calculated at 1.5 per 1000 children per year.

Routes of transmission — Respiratory coronaviruses probably spread in a fashion similar to that of rhinoviruses, via direct contact with infected secretions or large aerosol droplets. 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 [54]. In hospital settings, spread among pediatric patients probably occurs through shedding by their infected caretakers [55]. Outbreaks are common in long-term care facilities for older adults [56].

Middle East respiratory syndrome and severe acute respiratory syndrome are both zoonoses. Animals implicated in these infections are discussed in detail separately. (See “Middle East respiratory syndrome coronavirus: Virology, pathogenesis, and epidemiology”, section on ‘Possible sources and modes of transmission’ and “Severe acute respiratory syndrome (SARS)”, section on ‘Intermediate host and reservoir’.)

CLINICAL MANIFESTATIONS — The clinical manifestations of infections caused by community-acquired human coronaviruses (HCoVs) are described here; Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) are discussed separately. (See “Severe acute respiratory syndrome (SARS)”, section on ‘Clinical manifestations’ and “Middle East respiratory syndrome coronavirus: Clinical manifestations and diagnosis”, section on ‘Clinical manifestations’.)

Respiratory — 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 upper respiratory tract symptoms such as nasal congestion and rhinorrhea [41,57]. 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.

Human coronaviruses probably account for 5 to 10 percent of all acute upper respiratory tract infections in adults [44], with outbreaks during which 25 to 35 percent of respiratory infections can be attributed to a single species. Like rhinoviruses, coronaviruses can be detected in middle ear effusions and have been implicated as important viral causes of acute otitis media in children [58]. 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, suggesting that, although common, their pathogenicity in healthy infants and children may be low [52,59]. 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 HCoV RNA concentration (cycle threshold <28) and both respiratory tract disease (compared with asymptomatic controls) and lack of coinfection [52]. (See “Epidemiology, clinical manifestations, and pathogenesis of rhinovirus infections” and “Acute otitis media in children: Epidemiology, microbiology, clinical manifestations, and complications”, section on ‘Viral pathogens’.)

Coronavirus infections have also been linked to more severe respiratory diseases. In adults with community-acquired pneumonia, coronaviruses 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, coronaviruses 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) [60]. In a third 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 [61]. HCoV was the third most common virus detected (after rhinovirus and influenza virus) and was found significantly more often than in matched healthy controls. In another study, the numbers were small and the difference in detection of coronaviruses in adults with community-acquired pneumonia compared with asymptomatic individuals was not significant [62].

The ratio of HCoV-OC43 outpatient infections to inpatient infections was threefold lower than that for HCoV-229E, suggesting that HCoV-OC43 may have greater clinical impact. Another survey of severe acute respiratory infections from 2010 to 2014 in Arizona in the United States found influenza virus most frequently (50 cases), followed by human metapneumovirus (25 cases), parainfluenza viruses (20 cases), coronaviruses (16 cases), and respiratory syncytial virus (11 cases); among coronaviruses, HCoV-OC43 predominated [63]. Further information on the role of coronaviruses in acute respiratory illness in adults comes from a four-year cohort study comparing HCoV-229E with HCoV-OC43 [64].

Among older adult patients, there is increasing evidence that coronaviruses are important causes of influenza-like illness, acute exacerbations of chronic bronchitis, and pneumonia, where their frequency is below those of influenza and respiratory syncytial virus but similar to that of rhinoviruses [65-68]. Several outbreaks of HCoV-OC43 respiratory disease in older adults living in long-term care facilities have been described [69,70], 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 mono-infection with HCoV-NL63 has also been reported [71].

In children hospitalized in New York City with HCoV 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 [72].

Coronaviruses 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) [73]. They have been temporally linked to acute asthma attacks in both children and adults [74-76]. They have been found in variable proportions, ranging from 2 to 8 percent, of neonates, infants, and young children hospitalized with community-acquired pneumonia, and have been identified even more frequently in lower respiratory tract disease in outpatients [42,77,78]. They are also an important cause of nosocomial infections in neonatal intensive care units [79]. One of the more recently discovered human coronaviruses, HCoV-NL63, has been associated with croup in children [72,80,81].

Coronaviruses also probably cause pneumonia in immunocompromised hosts, including adults with HIV infection [82-85]. 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 [86]. 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 [87]. (See “Parainfluenza viruses in adults” and “Parainfluenza viruses in children” and “Viral infections following lung transplantation”, section on ‘Rejection’.)

The clinical manifestations of MERS-CoV and SARS-CoV are discussed separately. (See “Severe acute respiratory syndrome (SARS)”, section on ‘Clinical manifestations’ and “Middle East respiratory syndrome coronavirus: Clinical manifestations and diagnosis”, section on ‘Clinical manifestations’.)

Enteric — 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 [88] or necrotizing enterocolitis in newborns [89]. In several studies, CVLPs have been purified that appear to be antigenically related to HCoV-OC43 [88].

All four HCoV 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) [49,90]. 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 [90,91]. In a study that used RT-PCR to investigate the frequency of coronaviruses 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 [92].

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) [93]. 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. Community-acquired human coronaviruses (HCoVs) can infect neural cells in vitro [94], and three-week-old mice develop generalized encephalitis after intracerebral inoculation with HCoV-OC43 [95]. HCoV-OC43 RNA sequences have been detected in the cerebrospinal fluid of a 15-year-old boy with acute demyelinating encephalomyelitis (ADEM) [96]. 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 [97].

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) [98], investigators have sought to link coronaviruses 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 [99]. 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 [100].

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

Kawasaki disease — An association of coronavirus infection with Kawasaki disease was reported by one group of investigators and stimulated a flurry of investigation worldwide [101]. Others failed to confirm this finding, and, at the present time, it is assumed that known coronaviruses have no role in this disease [102,103]. (See “Kawasaki disease: Epidemiology and etiology”, section on ‘Infectious etiology’.)

DIAGNOSIS — Since there is no effective treatment for coronavirus infections, establishing the diagnosis is of limited utility in patients suspected of having community-acquired coronavirus infections. In contrast, diagnosing Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) is critically important for understanding outbreak epidemiology and limiting transmission of infection. (See “Severe acute respiratory syndrome (SARS)”, section on ‘Diagnosis’ and “Middle East respiratory syndrome coronavirus: Clinical manifestations and diagnosis”, section on ‘Diagnosis’.)

Until recently, no sensitive, rapid method existed to detect all of the known human coronavirus strains. Rapid techniques that can be used to detect coronaviruses from nasopharyngeal samples include reverse-transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence antigen detection assays [104-106].

Because of its utility for detecting all four of the known human coronavirus strains to cause community-acquired infections, 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 [104,107]. The sensitivity may be further improved by using real-time RT-PCR [50]. (See “Severe acute respiratory syndrome (SARS)”, section on ‘Diagnosis’.)

Community-acquired coronaviruses are difficult to replicate in tissue culture.

TREATMENT AND PREVENTION — There is currently no treatment recommended for coronavirus infections except for supportive care as needed. Several antivirals and other agents were used during the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak, but the efficacy of these drugs has not been established. (See “Severe acute respiratory syndrome (SARS)”, section on ‘Treatment’.)

Chloroquine, which has potent antiviral activity against the SARS-CoV [108], has been shown to have similar activity against HCoV-229E in cultured cells [109] and against HCoV-OC43 both in cultured cells and in a mouse model [110]. 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. Several antiseptic/disinfectant solutions used commonly in hospitals and households, including chloroxylenol, benzalkonium chloride, and cetrimide/chlorhexidine, have been shown to be ineffective against coronaviruses [111].

There has been little interest in developing vaccines for the non-SARS community-acquired coronaviruses 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 [54]. 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 [112]. There has been interest in the development of a SARS-CoV vaccine and a MERS-CoV vaccine. (See “Severe acute respiratory syndrome (SARS)”, section on ‘Vaccine development’ and “Middle East respiratory syndrome coronavirus: Treatment and prevention”, section on ‘Vaccine development’.)

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: Novel coronavirus” and “Society guideline links: Middle East respiratory syndrome coronavirus”.)

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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topic

SUMMARY AND RECOMMENDATIONS

●Coronaviruses 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.)

●Community-acquired coronaviruses are ubiquitous; wherever investigators have looked, they have been detected. 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. (See ‘Epidemiology’ above.)

●Most community-acquired coronavirus infections are diagnosed clinically, although reverse-transcriptase polymerase chain reaction applied to respiratory secretions is the diagnostic test of choice. (See ‘Diagnosis’ above and “Middle East respiratory syndrome coronavirus: Clinical manifestations and diagnosis”, section on ‘Diagnosis’.)

●There is currently no treatment recommended for coronavirus infections except for supportive care as needed. (See ‘Treatment and prevention’ above and “Middle East respiratory syndrome coronavirus: Treatment and prevention”, section on ‘Treatment’.)

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

●In late 2019, a novel coronavirus, designated 2019-nCoV, was identified as the cause of an outbreak of acute respiratory illness and has spread to include thousands of cases in China and scattered but increasing cases worldwide, prompting the World Health Organization (WHO) to declare a public health emergency in late January 2020. The possibility of 2019-nCoV should be considered in patients with fever and/or lower respiratory tract symptoms who reside in or have recently (within 14 days) traveled to the Wuhan area of China or who have had recent close contact with a confirmed or suspected case of 2019-nCoV.

Upon suspicion, infection control measures should be implemented and public health officials notified; in the United States, the Centers for Disease Control and Prevention (CDC) recommends standard, contact, and airborne precautions, as well as eye protection. In addition to testing for other respiratory pathogens, upper and lower respiratory tract specimens and serum should be collected for 2019-nCoV testing. Management consists of supportive care.

WHO has issued interim guidance on surveillance case definitions, laboratory diagnosis, and clinical management. The CDC has also issued interim guidance. (See ‘Novel coronavirus (2019-nCoV) outbreak in China’ above.)

from Up To Date

Author: Kenneth McIntosh, MD

Section Editor: Martin S Hirsch, MD

Deputy Editor: Allyson Bloom, MD