Coronavirus disease 2019 (COVID-19): Epidemiology, virology, clinical features, diagnosis, and prevention

INTRODUCTIONCoronaviruses are important human and animal pathogens. At the end of 2019, a novel coronavirus was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China. It rapidly spread, resulting in an epidemic throughout China, followed by an increasing number of cases in other countries throughout the world. In February 2020, the World Health Organization designated the disease COVID-19, which stands for coronavirus disease 2019 [1]. The virus that causes COVID-19 is designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); previously, it was referred to as 2019-nCoV.

Understanding of COVID-19 is evolving. Interim guidance has been issued by the World Health Organization and by the United States Centers for Disease Control and Prevention [2,3]. Links to these and other related society guidelines are found elsewhere. (See 'Society guideline links' below.)

This topic will discuss the virology, epidemiology, clinical features, diagnosis, and prevention of COVID-19.

The management of COVID-19 is discussed in detail elsewhere. (See "Coronavirus disease 2019 (COVID-19): Outpatient management in adults" and "Coronavirus disease 2019 (COVID-19): Management in hospitalized adults" and "Coronavirus disease 2019 (COVID-19): Critical care issues".)

Issues related to COVID-19 in specific populations are discussed elsewhere:

●(See "Coronavirus disease 2019 (COVID-19): Pregnancy issues".)

●(See "Coronavirus disease 2019 (COVID-19): Considerations in children".)

●(See "Coronavirus disease 2019 (COVID-19): Cancer care during the pandemic".)

●(See "Coronavirus disease 2019 (COVID-19): Issues related to kidney disease and hypertension".)

Community-acquired coronaviruses, severe acute respiratory syndrome (SARS) coronavirus, and Middle East respiratory syndrome (MERS) coronavirus are discussed separately. (See "Coronaviruses" and "Severe acute respiratory syndrome (SARS)" and "Middle East respiratory syndrome coronavirus: Virology, pathogenesis, and epidemiology".)

VIROLOGYFull-genome sequencing and phylogenic analysis indicated that the coronavirus that causes COVID-19 is a betacoronavirus in the same subgenus as the severe acute respiratory syndrome (SARS) virus (as well as several bat coronaviruses), but in a different clade. The structure of the receptor-binding gene region is very similar to that of the SARS coronavirus, and the virus has been shown to use the same receptor, the angiotensin-converting enzyme 2 (ACE2), for cell entry [4]. The Coronavirus Study Group of the International Committee on Taxonomy of Viruses has proposed that this virus be designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [5].

The Middle East respiratory syndrome (MERS) virus, another betacoronavirus, appears more distantly related [6,7]. The closest RNA sequence similarity is to two bat coronaviruses, and it appears likely that bats are the primary source; whether COVID-19 virus is transmitted directly from bats or through some other mechanism (eg, through an intermediate host) is unknown [8]. (See "Coronaviruses", section on 'Viral serotypes'.)

In a phylogenetic analysis of 103 strains of SARS-CoV-2 from China, two different types of SARS-CoV-2 were identified, designated type L (accounting for 70 percent of the strains) and type S (accounting for 30 percent) [9]. The L type predominated during the early days of the epidemic in China, but accounted for a lower proportion of strains outside of Wuhan than in Wuhan. The clinical implications of these findings are uncertain.

EPIDEMIOLOGY

Geographic distribution — Globally, more than three million confirmed cases of COVID-19 have been reported. Updated case counts in English can be found on the World Health Organization and European Centre for Disease Prevention and Control websites. An interactive map highlighting confirmed cases throughout the world can be found here.

Since the first reports of cases from Wuhan, a city in the Hubei Province of China, at the end of 2019, more than 80,000 COVID-19 cases have been reported in China, with the majority of those from Hubei and surrounding provinces. A joint World Health Organization (WHO)-China fact-finding mission estimated that the epidemic in China peaked between late January and early February 2020 [10], and the rate of new cases decreased substantially by early March.

However, cases have been reported in all continents, except for Antarctica, and have been steadily rising around the world.

In the United States, COVID-19 has been reported in all 50 states, Washington DC, and at least four territories [11]. The cumulative incidence varies by state and likely depends on a number of factors, including population density and demographics, extent of testing and reporting, and timing of mitigation strategies. In the United States, outbreaks in long-term care facilities and homeless shelters have emphasized the risk of exposure and infection in congregate settings [12-14]. (See 'Risk of transmission' below.)

Transmission — Understanding of the transmission risk is incomplete. Epidemiologic investigation in Wuhan at the beginning of the outbreak identified an initial association with a seafood market that sold live animals, where most patients had worked or visited and which was subsequently closed for disinfection [15]. However, as the outbreak progressed, person-to-person spread became the main mode of transmission.

Person-to-person

Route of person-to-person transmission — The exact mode of person-to-person spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. It is thought to occur mainly via respiratory droplets, resembling the spread of influenza. With droplet transmission, virus released in the respiratory secretions when a person with infection coughs, sneezes, or talks can infect another person if it makes direct contact with the mucous membranes; infection can also occur if a person touches an infected surface and then touches his or her eyes, nose, or mouth. Droplets typically do not travel more than six feet (about two meters) and do not linger in the air.

Whether SARS-CoV-2 can be transmitted through the airborne route (through particles smaller than droplets that remain in the air over time and distance) under natural conditions has been a controversial issue. One letter to the editor described a study in which SARS-CoV-2 grown in tissue culture remained viable in experimentally generated aerosols for at least three hours [16]; some studies have identified viral RNA in ventilation systems and in air samples of hospital rooms of patients with COVID-19, but cultures for viable virus were not performed in these studies [17-19]. Other studies using high-speed imaging to visualize respiratory exhalations have suggested that respiratory droplets may get carried in a gas cloud and have horizontal trajectories beyond six feet (two meters) with speaking, coughing, or sneezing [20,21]. However, the direct relevance of these findings to the epidemiology of COVID-19 and their clinical implications are unclear. Long-range airborne transmission of SARS-CoV-2 has not clearly been documented [22], and in a few reports of health care workers exposed to patients with undiagnosed infection with only contact and droplet precautions, no secondary infections were identified despite the absence of airborne precautions [23,24]. Reflecting the current uncertainty regarding transmission mechanisms, recommendations on airborne precautions in the health care setting vary by location; airborne precautions are universally recommended when aerosol-generating procedures are performed. This is discussed in detail elsewhere. (See "Coronavirus disease 2019 (COVID-19): Infection control in health care and home settings", section on 'Patients with suspected or confirmed COVID-19'.)

SARS-CoV-2 has been detected in non-respiratory specimens, including stool, blood, and ocular secretions, but the role of these sites in transmission is uncertain [25-29]. In particular, several reports have described detection of SARS-CoV-2 RNA from stool specimens, even after viral RNA could no longer be detected from upper respiratory specimens [28,29], and live virus has been cultured from stool in some cases [26]. Although it would be difficult to confirm, fecal-oral transmission has not been clinically described, and according to a joint WHO-China report, did not appear to be a significant factor in the spread of infection [30].

Detection of SARS-CoV-2 RNA in blood has also been reported in some but not all studies that have tested for it [25,26,29,31]. However, the likelihood of bloodborne transmission (eg, through blood products or needlesticks) appears low; respiratory viruses are generally not transmitted through the bloodborne route, and transfusion-transmitted infection has not been reported for SARS-CoV-2 or for the related MERS-CoV or SARS-CoV [32]. (See "Blood donor screening: Laboratory testing", section on 'Emerging infectious disease agents'.)

Viral shedding and period of infectivity — The interval during which an individual with COVID-19 is infectious is uncertain. It appears that SARS-CoV-2 can be transmitted prior to the development of symptoms and throughout the course of illness. However, most data informing this issue are from studies evaluating viral RNA detection from respiratory and other specimens, and detection of viral RNA does not necessarily indicate the presence of infectious virus.

Viral RNA levels from upper respiratory specimens appear to be higher soon after symptom onset compared with later in the illness [33-36]. Additionally, in a study of nine patients with mild COVID-19, infectious virus was isolated from naso/oropharyngeal and sputum specimens during the first week of illness, but not after this interval, despite continued high viral RNA levels at these sites [35]. One modeling study, based on the timing of infection among 77 transmission pairs in China (with a mean serial interval of 5.8 days between the onset of symptoms in each pair) and assumptions about incubation period, suggested infectiousness started 2.3 days prior to symptom onset, peaked 0.7 days before symptom onset, and declined within seven days; however, most patients were isolated following symptom onset, which would reduce the risk of transmission later in illness regardless of infectiousness [36]. These findings raise the possibility that patients might be more infectious in the earlier stage of infection, but additional data are needed to confirm this hypothesis.

Nevertheless, transmission of SARS-CoV-2 from asymptomatic individuals (or individuals within the incubation period) has been documented [37-41]. The biologic basis for this is supported by a study of a SARS-CoV-2 outbreak in a long-term care facility, in which infectious virus was cultured from reverse transcription polymerase chain reaction (RT-PCR)-positive upper respiratory tract specimens in presymptomatic and asymptomatic patients as early as six days prior to the development of typical symptoms [42]. However, the extent to which asymptomatic or presymptomatic transmission occurs and how much it contributes to the pandemic remain unknown. In an analysis of 157 locally acquired COVID-19 cases in Singapore, transmission during the incubation period was estimated to account for 6.4 percent; in such cases, the exposures occurred one to three days prior to symptom development [43]. Large-scale serologic screening may be able to provide a better sense of the scope of asymptomatic infections and inform epidemiologic analysis; several serologic tests for SARS-CoV-2 are under development, and some have been granted emergency use authorization by the US Food and Drug Administration (FDA) [44,45].

How long a person remains infectious is also uncertain. The duration of viral shedding is variable; there appears to be a wide range, which may depend on severity of illness [29,35,46-48]. In one study of 21 patients with mild illness (no hypoxia), 90 percent had repeated negative viral RNA tests on nasopharyngeal swabs by 10 days after the onset of symptoms; tests were positive for longer in patients with more severe illness [46]. In contrast, in another study of 56 patients with mild to moderate illness (none required intensive care), the median duration of viral RNA shedding from naso- or oropharyngeal specimens was 24 days, and the longest was 42 days [49]. However, as mentioned above, detectable viral RNA does not always correlate with isolation of infectious virus, and there may be a threshold of viral RNA level below which infectivity is unlikely. In the study of nine patients with mild COVID-19 described above, infectious virus was not detected from respiratory specimens when the viral RNA level was <106 copies/mL [35].

The impact of viral RNA detection on infection control precautions is discussed elsewhere. (See "Coronavirus disease 2019 (COVID-19): Infection control in health care and home settings", section on 'Discontinuation of precautions'.)

Risk of transmission — The risk of transmission from an individual with SARS-CoV-2 infection varies by the type and duration of exposure, use of preventive measures, and likely individual factors (eg, the amount of virus in respiratory secretions). Most secondary infections have been described among household contacts, in congregate or health care settings when personal protective equipment was not used (including hospitals [50] and long-term care facilities [12]), and in closed settings (eg, cruise ships [51]). However, reported clusters of cases after social or work gatherings also highlight the risk of transmission through close, non-household contact.

Contact tracing in the early stages of epidemics at various locations suggested that most secondary infections were among household contacts, with a secondary attack rate of up to 16 percent [30,52-54]. According to a joint WHO-China report, the rate of secondary COVID-19 in various locations ranged from 1 to 5 percent among tens of thousands of close contacts of confirmed patients in China; most of these occurred within households, with an in-household secondary attack rate of 3 to 10 percent [30]. In the United States, the symptomatic secondary attack rate was 0.45 percent among 445 close contacts of 10 confirmed patients; among household members, the rate was 10.5 percent [52]. In a similar study in Korea, the rates were comparable, with secondary infections in 0.55 percent of all contacts and 7.6 percent of family members [53].

Clusters of cases have also been reported following family, work, or social gatherings where close, personal contact can occur [55,56]. As an example, epidemiologic analysis of a cluster of cases in the state of Illinois showed probable transmission through two family gatherings at which communal food was consumed, embraces were shared, and extended face-to-face conversations were exchanged with symptomatic individuals who were later confirmed to have COVID-19 [55].

The risk of transmission with more indirect contact (eg, passing someone with infection on the street, handling items that were previously handled by someone with infection) is not well established and is likely low.

Environmental contamination — Virus present on contaminated surfaces may be another source of infection if susceptible individuals touch these surfaces and then transfer infectious virus to mucous membranes in the mouth, eyes, or nose. The frequency and relative importance of this type of transmission remain unclear. It may be more likely to be a potential source of infection in settings where there is heavy viral contamination (eg, in an infected individual's household or in health care settings).

Extensive SARS-CoV-2 contamination of environmental surfaces in hospital rooms of patients with COVID-19 has been described [17,57]. In a study from Singapore, viral RNA was detected on nearly all surfaces tested (handles, light switches, bed and handrails, interior doors and windows, toilet bowl, sink basin) in the airborne infection isolation room of a patient with symptomatic mild COVID-19 prior to routine cleaning [17]. Viral RNA was not detected on similar surfaces in the rooms of two other symptomatic patients following routine cleaning (with sodium dichloroisocyanurate). Of note, viral RNA detection does not necessarily indicate the presence of infectious virus [35].

It is unknown how long SARS-CoV-2 can persist on surfaces [16,58,59]; other coronaviruses have been tested and may survive on inanimate surfaces for up to six to nine days without disinfection. In a study evaluating the survival of viruses dried on a plastic surface at room temperature, a specimen containing SARS-CoV (a virus closely related to SARS-CoV-2) had detectable infectivity at six but not nine days [59]. However, in a systematic review of similar studies, various disinfectants (including ethanol at concentrations between 62 and 71%) inactivated a number of coronaviruses related to SARS-CoV-2 within one minute [58]. Based on data concerning other coronaviruses, duration of viral persistence on surfaces also likely depends on the ambient temperature, relative humidity, and the size of the initial inoculum [60].

These data highlight the importance of environmental disinfection in the home and health care setting. (See "Coronavirus disease 2019 (COVID-19): Infection control in health care and home settings", section on 'Environmental disinfection'.)

Uncertain risk of animal contact — SARS-CoV-2 infection is thought to have originally been transmitted to humans from an animal host, but the ongoing risk of transmission through animal contact is uncertain. There is no evidence suggesting animals (including domesticated animals) are a major source of infection in humans.

SARS-CoV-2 infection has been described in animals in both natural and experimental settings. There have been rare reports of animals with SARS-CoV-2 infection (including asymptomatic infections in dogs and symptomatic infections in cats) following close contact with a human with COVID-19 [61]. The risk of infection may vary by species. In one study evaluating infection in animals after intranasal viral inoculation, SARS-CoV-2 replicated efficiently in ferrets and cats; viral replication was also detected in dogs, but they appeared to be less susceptible overall to experimental infection [62]. Pigs and poultry were not susceptible to infection.

Given the uncertainty regarding the transmission risk and the apparent susceptibility of some animals to SARS-CoV-2 infection, the United States Centers for Disease Control and Prevention (CDC) recommends that pets be kept away from other animals or people outside of the household and that people with confirmed or suspected COVID-19 try to avoid close contact with household pets, as they should with human household members, for the duration of their self-isolation period. There have been no reports of domesticated animals transmitting SARS-CoV-2 infection to humans.

Immunity and risk of reinfection — Antibodies to the virus are induced in those who have become infected. Preliminary evidence suggests that some of these antibodies are protective, but this remains to be definitively established. Moreover, it is unknown whether all infected patients mount a protective immune response and how long any protective effect will last.

Data on protective immunity following COVID-19 are emerging [34,35,63]. A case series evaluating convalescent plasma for treatment of COVID-19 identified neutralizing activity in plasma of recovered patients that appeared to be transferred to recipients following plasma infusion [63]. Similarly, in another study of 23 patients who recovered from COVID-19, antibodies to the receptor-binding domain of the spike protein and the nucleocapsid protein were detected by enzyme-linked immunosorbent assay (ELISA) in most patients by 14 days following the onset of symptoms; ELISA antibody titers correlated with neutralizing activity [34]. One preliminary study reported that rhesus macaques infected with SARS-CoV-2 did not develop reinfection following recovery and rechallenge [64]; however, this study has not been published in a peer-reviewed journal, and further confirmation of these findings is needed.

Some studies have reported positive RT-PCR tests for SARS-CoV-2 in patients with laboratory-confirmed COVID-19 following clinical improvement and negative results on two consecutive tests [65,66]. However, these positive tests occurred shortly after the negative tests, were not associated with worsening symptoms, may not represent infectious virus, and likely did not reflect reinfection.

As above, the FDA has granted emergency use authorization for tests that qualitatively identify antibodies against SARS-CoV-2 in serum or plasma [45]. Should evidence confirm that the presence of these antibodies reflects a protective immune response, serologic screening will be an important tool to understand population immunity and distinguish individuals who are at lower risk for reinfection.

CLINICAL FEATURES

Incubation period — The incubation period for COVID-19 is thought to be within 14 days following exposure, with most cases occurring approximately four to five days after exposure [67-69].

In a study of 1099 patients with confirmed symptomatic COVID-19, the median incubation period was four days (interquartile range two to seven days) [68].

Using data from 181 publicly reported, confirmed cases in China with identifiable exposure, one modeling study estimated that symptoms would develop in 2.5 percent of infected individuals within 2.2 days and in 97.5 percent of infected individuals within 11.5 days [70]. The median incubation period in this study was 5.1 days.

Spectrum of illness severity and case fatality rates — The spectrum of symptomatic infection ranges from mild to critical; most infections are not severe [50,69,71-75]. Specifically, in a report from the Chinese Center for Disease Control and Prevention that included approximately 44,500 confirmed infections with an estimation of disease severity [76]:

●Mild (no or mild pneumonia) was reported in 81 percent.

●Severe disease (eg, with dyspnea, hypoxia, or >50 percent lung involvement on imaging within 24 to 48 hours) was reported in 14 percent.

●Critical disease (eg, with respiratory failure, shock, or multiorgan dysfunction) was reported in 5 percent.

●The overall case fatality rate was 2.3 percent; no deaths were reported among noncritical cases.

Among hospitalized patients, the proportion of critical or fatal disease is higher [77,78]. In a study that included 2634 patients who had been hospitalized for COVID-19 in the New York City area, 14 percent were treated in the intensive care unit and 12 percent received invasive mechanical ventilation, and mortality among those receiving mechanical ventilation was 88 percent [77]. However, the analysis was limited to patients who had either been discharged or died during the admission, and these patients represented fewer than half of the total population admitted with COVID-19; thus, the proportion of critically ill patients and the associated mortality rate may not accurately reflect those of the entire hospitalized population.

The proportion of severe or fatal infections may also vary by location. According to a joint World Health Organization (WHO)-China fact-finding mission, the case fatality rate ranged from 5.8 percent in Wuhan to 0.7 percent in the rest of China [30]. A modeling study suggested that the adjusted case fatality rate in mainland China was 1.4 percent [79]. Most of the fatal cases occurred in patients with advanced age or underlying medical comorbidities [47,76]. In Italy, 12 percent of all detected COVID-19 cases and 16 percent of all hospitalized patients were admitted to the intensive care unit; the estimated case fatality rate was 7.2 percent in mid-March [80,81]. In contrast, the estimated case fatality rate in mid-March in South Korea was 0.9 percent [82]. This may be related to distinct demographics of infection; in Italy, the median age of patients with infection was 64 years, whereas in Korea the median age was in the 40s. (See 'Impact of age' below.)

Risk factors for severe illness — Severe illness can occur in otherwise healthy individuals of any age, but it predominantly occurs in adults with advanced age or underlying medical comorbidities. The impact of age is discussed elsewhere. (See 'Impact of age' below.)

Comorbidities that have been associated with severe illness and mortality include (table 1) [47,76,83-85]:

●Cardiovascular disease

●Diabetes mellitus

●Hypertension

●Chronic lung disease

●Cancer (in particular hematologic malignancies, lung cancer, and metastatic disease) [86]

●Chronic kidney disease

●Obesity

The United States Centers for Disease Control and Prevention (CDC) also includes immunocompromising conditions and liver disease as potential risk factors for severe illness [87], although specific data regarding risks associated with these conditions are limited.

In a subset of 355 patients who died with COVID-19 in Italy, the mean number of pre-existing comorbidities was 2.7, and only 3 patients had no underlying condition [81].

Among patients with advanced age and medical comorbidities, COVID-19 is frequently severe. For example, in a SARS-CoV-2 outbreak across several long-term care facilities in Washington State, the median age of the 101 facility residents affected was 83 years, and 94 percent had a chronic underlying condition; the hospitalization and preliminary case fatality rates were 55 and 34 percent, respectively [88].

Males have comprised a disproportionately high number of deaths in cohorts from China, Italy, and the United States [77,81,89].

In a number of states in the United States, black individuals also appear to comprise a disproportionately high number of infections and deaths due to COVID-19, possibly related to underlying socioeconomic disparities [90-94].

Particular laboratory features have also been associated with worse outcomes (table 2). These include [47,95,96]:

●Lymphopenia

●Elevated liver enzymes

●Elevated lactate dehydrogenase (LDH)

●Elevated inflammatory markers (eg, C-reactive protein [CRP], ferritin)

●Elevated D-dimer (>1 mcg/mL)

●Elevated prothrombin time (PT)

●Elevated troponin

●Elevated creatine phosphokinase (CPK)

●Acute kidney injury

As an example, in one study, progressive decline in the lymphocyte count and rise in the D-dimer over time were observed in nonsurvivors compared with more stable levels in survivors [50].

Patients with severe disease have also been reported to have higher viral RNA levels in respiratory specimens than those with milder disease [46], although this association was not observed in a different study that measured viral RNA in salivary specimens [34].

Impact of age — Individuals of any age can acquire severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although adults of middle age and older are most commonly affected, and older adults are more likely to have severe disease.

In several cohorts of hospitalized patients with confirmed COVID-19, the median age ranged from 49 to 56 years [50,72,73]. In a report from the Chinese Center for Disease Control and Prevention that included approximately 44,500 confirmed infections, 87 percent of patients were between 30 and 79 years old [76]. Similarly, in a modeling study based on data from mainland China, the hospitalization rate for COVID-19 increased with age, with a 1 percent rate for those 20 to 29 years old, 4 percent rate for those 50 to 59 years old, and 18 percent for those older than 80 years [79].

Older age is also associated with increased mortality [76,77,81]. In a report from the Chinese Center for Disease Control and Prevention, case fatality rates were 8 and 15 percent among those aged 70 to 79 years and 80 years or older, respectively, in contrast to the 2.3 percent case fatality rate among the entire cohort [76]. Similar findings were reported from Italy, with case fatality rates of 12 and 20 percent among those aged 70 to 79 years and 80 years or older, respectively [81].

In the United States, 2449 patients diagnosed with COVID-19 between February 12 and March 16, 2020 had age, hospitalization, and intensive care unit (ICU) information available [97]; 67 percent of cases were diagnosed in those aged ≥45 years, and, similar to findings from China, mortality was highest among older individuals, with 80 percent of deaths occurring in those aged ≥65 years.

Symptomatic infection in children appears to be relatively uncommon; when it occurs, it is usually mild, although severe cases have been reported [98-101]. Details of COVID-19 in children are discussed elsewhere. (See "Coronavirus disease 2019 (COVID-19): Considerations in children".)

Asymptomatic infections — Asymptomatic infections have been well documented [69,102-108]. Their precise frequency is unknown, but several studies performed in various settings suggest that they are common. As examples:

●In a COVID-19 outbreak on a cruise ship where nearly all passengers and staff were screened for SARS-CoV-2, approximately 17 percent of the population on board tested positive as of February 20; about half of the 619 confirmed COVID-19 cases were asymptomatic at the time of diagnosis [109]. A modeling study estimated that 18 percent were true asymptomatic cases (ie, did not go on to develop symptoms), although this was based on a number of assumptions, including the incubation period [104].

●In a smaller COVID-19 outbreak within a skilled nursing facility, 27 of the 48 residents (56 percent) who had a positive screening test were asymptomatic at the time of diagnosis, but 24 of them ultimately developed symptoms over the next seven days [42].

●Other studies have reported even higher proportions of asymptomatic cases [14,107]. As an example, in a report of a universal screening program of pregnant women presenting for delivery at two New York hospitals at the height of the pandemic there, 29 of 210 asymptomatic women without fever (14 percent) had a positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) test on a nasopharyngeal specimen [107]. Four additional women had fever or symptoms and also tested positive. Thus, of 33 women with a positive SARS-CoV-2 test, 29 (88 percent) were asymptomatic on presentation.

Even patients with asymptomatic infection may have objective clinical abnormalities [40,106]. As an example, in a study of 24 patients with asymptomatic infection who all underwent chest computed tomography (CT), 50 percent had typical ground-glass opacities or patchy shadowing, and another 20 percent had atypical imaging abnormalities [40]. Five patients developed low-grade fever, with or without other typical symptoms, a few days after diagnosis. In another study of 55 patients with asymptomatic infection identified through contact tracing, 67 percent had CT evidence of pneumonia on admission; only two patients developed hypoxia, and all recovered [106].

Clinical manifestations

Initial presentation — Pneumonia appears to be the most frequent serious manifestation of infection, characterized primarily by fever, cough, dyspnea, and bilateral infiltrates on chest imaging [50,68,72,73]. However, other features, including upper respiratory tract symptoms, myalgias, diarrhea, and smell or taste disorders, are also common (table 3). There are no specific clinical features that can yet reliably distinguish COVID-19 from other viral respiratory infections, although development of dyspnea several days after the onset of initial symptoms is suggestive. (See 'Course and complications' below.)

Most studies describing the clinical features of COVID-19 have been performed in hospitalized populations. In a study describing 138 patients hospitalized with COVID-19 pneumonia in Wuhan, the most common clinical features at the onset of illness were [50]:

●Fever in 99 percent

●Fatigue in 70 percent

●Dry cough in 59 percent

●Anorexia in 40 percent

●Myalgias in 35 percent

●Dyspnea in 31 percent

●Sputum production in 27 percent

Other cohort studies of patients with confirmed COVID-19 have reported a similar range of clinical findings [50,72,110-112]. However, fever might not be a universal finding on presentation. In one study, fever was reported in almost all patients, but approximately 20 percent had a very low grade fever <100.4°F/38°C [72]. In another study of 1099 patients from Wuhan and other areas in China, fever (defined as an axillary temperature over 99.5°F/37.5°C) was present in only 44 percent on admission but was ultimately noted in 89 percent during the hospitalization [68].

Although not highlighted in the initial cohort studies from China, smell and taste disorders (eg, anosmia and dysgeusia) have also been reported as common symptoms in patients with COVID-19 [113-115]. In a survey of 59 patients with COVID-19 in Italy, 34 percent self-reported either a smell or taste aberration and 19 percent reported both [114]. In a survey of 202 outpatients with mild COVID-19 in Italy, 64 percent reported alterations in smell or taste, and 24 percent reported very severe alterations; smell or taste changes were reported as the only symptom in 3 percent overall and preceded symptoms in another 12 percent [116]. Whether this finding is a distinguishing feature of COVID-19 is uncertain.

In addition to respiratory symptoms, gastrointestinal symptoms (eg, nausea and diarrhea) have also been reported; and in some patients, they may be the presenting complaint [50,72,112,117]. In a systematic review of studies reporting on gastrointestinal symptoms in patients with confirmed COVID-19, the pooled prevalence was 18 percent overall, with diarrhea, nausea/vomiting, or abdominal pain reported in 13, 10, and 9 percent, respectively [28].

Other reported symptoms have included headache, sore throat, and rhinorrhea [68,73]. Conjunctivitis has also been described [27].

Dermatologic findings in patients with COVID-19 are not well characterized. There have been reports of maculopapular, urticarial, and vesicular eruptions and transient livedo reticularis [118-120]. Reddish-purple nodules on the distal digits similar in appearance to pernio (chilblains) have also been described, mainly in children and young adults with documented or suspected COVID-19, although an association has not been clearly established [120-123].

Course and complications — As above, symptomatic infection can range from mild to critical. (See 'Spectrum of illness severity and case fatality rates' above.)

Some patients with initially nonsevere symptoms may progress over the course of a week. In one study of 138 patients hospitalized in Wuhan for pneumonia due to SARS-CoV-2, dyspnea developed after a median of five days since the onset of symptoms, and hospital admission occurred after a median of seven days of symptoms [50]. In another study, the median time to dyspnea was eight days [72].

Acute respiratory distress syndrome (ARDS) is a major complication in patients with severe disease and can manifest shortly after the onset of dyspnea. In the study of 138 patients described above, ARDS developed in 20 percent a median of eight days after the onset of symptoms; mechanical ventilation was implemented in 12.3 percent [50]. In another study of 201 hospitalized patients with COVID-19 in Wuhan, 41 percent developed ARDS; age greater than 65 years, diabetes mellitus, and hypertension were each associated with ARDS [95].

Other complications have included arrhythmias, acute cardiac injury, and shock [50,89,124,125]. In one study, these were reported in 17, 7, and 9 percent, respectively [50]. In a series of 21 severely ill patients admitted to the ICU in the United States, one-third developed cardiomyopathy [124]. Thromboembolic complications, including pulmonary embolism and acute stroke (even in patients younger than 50 years of age without risk factors), have also been reported [126-131]. (See "Coronavirus disease 2019 (COVID-19): Critical care issues", section on 'Clinical features in critically ill patients' and "Coronavirus disease 2019 (COVID-19): Hypercoagulability", section on 'Clinical features'.)

Some patients with severe COVID-19 have laboratory evidence of an exuberant inflammatory response, similar to cytokine release syndrome, with persistent fevers, elevated inflammatory markers (eg, D-dimer, ferritin), and elevated proinflammatory cytokines; these laboratory abnormalities have been associated with critical and fatal illnesses [72,132]. (See 'Risk factors for severe illness' above.)

Guillain-Barré syndrome has also been reported, with onset 5 to 10 days after initial symptoms [133].

According to the WHO, recovery time appears to be around two weeks for mild infections and three to six weeks for severe disease [10].

Laboratory findings — Common laboratory findings among hospitalized patients with COVID-19 include lymphopenia, elevated aminotransaminase levels, elevated lactate dehydrogenase levels, and elevated inflammatory markers (eg, ferritin, C-reactive protein, and erythrocyte sedimentation rate) [50,68,112].

Lymphopenia is especially common, even though the total white blood cell count can vary [50,72,73,134]. As an example, in a series of 393 adult patients hospitalized with COVID-19 in New York City, 90 percent had a lymphocyte count <1500/microL; leukocytosis (>10,000/microL) and leukopenia (<4000/microL) were each reported in approximately 15 percent [112].

On admission, many patients with pneumonia have normal serum procalcitonin levels; however, in those requiring ICU care, they are more likely to be elevated [50,72,73].

Several laboratory features, including high D-dimer levels and more severe lymphopenia, have been associated with mortality [73]. These are discussed elsewhere. (See 'Risk factors for severe illness' above.)

Imaging findings — Chest radiographs may be normal in early or mild disease. In a retrospective study of 64 patients in Hong Kong with documented COVID-19, 20 percent did not have any abnormalities on chest radiograph at any point during the illness [135]. Common abnormal radiograph findings were consolidation and ground glass opacities, with bilateral, peripheral, and lower lung zone distributions; lung involvement increased over the course of illness, with a peak in severity at 10 to 12 days after symptom onset.

Although chest CT may be more sensitive than chest radiograph and some chest CT findings may be characteristic of COVID-19, no finding can completely rule in or rule out the possibility of COVID-19. In the United States, the American College of Radiology (ACR) recommends not using chest CT for screening or diagnosis of COVID-19 and recommends reserving it for hospitalized patients when needed for management [136]. If CT is performed, the Radiological Society of North America has categorized features as typical, indeterminate, or atypical for COVID-19, and has suggested corresponding language for the interpretation report (table 4) [137].

Chest CT in patients with COVID-19 most commonly demonstrates ground-glass opacification with or without consolidative abnormalities, consistent with viral pneumonia [111,138]. Case series have suggested that chest CT abnormalities are more likely to be bilateral, have a peripheral distribution, and involve the lower lobes. Less common findings include pleural thickening, pleural effusion, and lymphadenopathy.

In a study of 1014 patients in Wuhan who underwent both RT-PCR testing and chest CT for evaluation of COVID-19, a "positive" chest CT for COVID-19 (as determined by a consensus of two radiologists) had a sensitivity of 97 percent, using the PCR tests as a reference; however, specificity was only 25 percent [139]. The low specificity may be related to other etiologies causing similar CT findings. In another study comparing chest CTs from 219 patients with COVID-19 in China and 205 patients with other causes of viral pneumonia in the United States, COVID-19 cases were more likely to have a peripheral distribution (80 versus 57 percent), ground-glass opacities (91 versus 68 percent), fine reticular opacities (56 versus 22 percent), vascular thickening (59 versus 22 percent), and reverse halo sign (11 versus 1 percent), but less likely to have a central and peripheral distribution (14 versus 35 percent), air bronchogram (14 versus 23 percent), pleural thickening (15 versus 33 percent), pleural effusion (4 versus 39 percent), and lymphadenopathy (2.7 versus 10 percent) [140]. A group of radiologists in that study was able to distinguish COVID-19 with high specificity but moderate sensitivity.

In one report of 21 patients with laboratory-confirmed COVID-19 who did not develop severe respiratory distress, lung abnormalities on chest imaging were most severe approximately 10 days after symptom onset [110]. However, chest CT abnormalities have also been identified in patients prior to the development of symptoms and even prior to the detection of viral RNA from upper respiratory specimens [111,141].

Among patients who clinically improve, resolution of radiographic abnormalities may lag behind improvements in fever and hypoxia [142].

DIAGNOSIS

Clinical suspicion and criteria for testing — The possibility of COVID-19 should be considered primarily in patients with new onset fever and/or respiratory tract symptoms (eg, cough, dyspnea). It should also be considered in patients with severe lower respiratory tract illness without any clear cause. Other consistent symptoms include myalgias, diarrhea, and smell or taste aberrancies (table 3) (see 'Initial presentation' above). Although these syndromes can occur with other viral respiratory illnesses, the likelihood of COVID-19 is increased if the patient:

●Resides in or has traveled within the prior 14 days to a location where there is community transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; ie, large numbers of cases that cannot be linked to specific transmission chains); in such locations, residence in congregate settings or association with events where clusters of cases have been reported is a particularly high risk for exposure. (See 'Geographic distribution' above and 'Risk of transmission' above.)

or

●Has had close contact with a confirmed or suspected case of COVID-19 in the prior 14 days, including through work in health care settings. Close contact includes being within approximately six feet (about two meters) of a patient for a prolonged period of time while not wearing personal protective equipment (PPE) or having direct contact with infectious secretions while not wearing PPE.

Patients with suspected COVID-19 who do not need emergency care should be encouraged to call prior to presenting to a health care facility for evaluation. Many patients can be evaluated regarding the need for testing over the phone. For patients in a health care facility, infection control measures should be implemented as soon as the possibility of COVID-19 is suspected. (See "Coronavirus disease 2019 (COVID-19): Infection control in health care and home settings", section on 'Patients with suspected or confirmed COVID-19'.)

The diagnosis cannot be definitively made without microbiologic testing, but limited capacity may preclude testing all patients with suspected COVID-19. Local health departments may have specific criteria for testing. In the United States, the Centers for Disease Control and Prevention (CDC) and the Infectious Diseases Society of America have suggested priorities for testing (table 5); high-priority individuals include hospitalized patients (especially critically ill patients with unexplained respiratory illness) and symptomatic individuals who are health care workers or first responders, work or reside in congregate living settings, or have risk factors for severe disease [143,144].

Testing criteria suggested by the World Health Organization (WHO) can be found in its technical guidance online. These are the same criteria used by the European Centre for Disease Prevention and Control.

In many cases, because of the limited availability of testing, the diagnosis of COVID-19 is made presumptively based on a compatible clinical presentation in the setting of an exposure risk, particularly when no other cause of the symptoms is evident. The management of suspected cases when testing is not available is discussed elsewhere. (See 'COVID-19 testing not readily available' below.)

Microbiologic diagnosis

RT-PCR to diagnose current infection — The diagnosis of COVID-19 is made by detection of SARS-CoV-2 RNA by reverse transcription polymerase chain reaction (RT-PCR) [145]. Various RT-PCR assays are used around the world; different assays amplify and detect different regions of the SARS-CoV-2 genome. Common gene targets include nucleocapsid (N), envelope (E), spike (S), and RNA-dependent RNA polymerase (RdRp), as well as regions in the first open reading frame [146].

In the United States, the Food and Drug Administration (FDA) has granted emergency use authorization for many different RT-PCR assays [45]; testing is performed by the CDC, local public health departments, hospital laboratories, and certain commercial reference laboratories.

Specimen collection — Upper respiratory samples are the primary specimens for SARS-CoV-2 RT-PCR testing. In the United States, the CDC recommends collection of one of the following specimens [147]:

●Nasopharyngeal swab specimen, collected by a health care professional

●Oropharyngeal swab specimen, collected by a health care professional

●Nasal swab specimen from the anterior nares, collected by a health care professional or by the patient on-site or at home (in the United States, the FDA has granted emergency use authorization for a home-collection testing kit that can be mailed to the laboratory for testing [148])

●Nasal or nasopharyngeal wash/aspirate, collected by a health care professional

Expectorated sputum should be collected from patients with productive cough; induction of sputum is not recommended. A lower respiratory tract aspirate or bronchoalveolar lavage should be collected from patients who are intubated. Additional information on testing and handling of clinical specimens can be found on the CDC website.

Infection control practices during specimen collection are discussed elsewhere. (See "Coronavirus disease 2019 (COVID-19): Infection control in health care and home settings", section on 'Patients with suspected or confirmed COVID-19'.)

Interpretation — A positive test for SARS-CoV-2 generally confirms the diagnosis of COVID-19. However, false-negative tests from upper respiratory specimens have been well documented. If initial testing is negative but the suspicion for COVID-19 remains and determining the presence of infection is important for management or infection control, we suggest repeating the test. In such cases, the WHO also recommends testing lower respiratory tract specimens, if possible [149]. Infection control precautions for COVID-19 should continue while repeat evaluation is being performed. (See "Coronavirus disease 2019 (COVID-19): Infection control in health care and home settings", section on 'Patients with suspected or confirmed COVID-19'.)

In many cases, because of the limited availability of testing and concern for false-negative results, the diagnosis of COVID-19 is made presumptively based on a compatible clinical presentation in the setting of an exposure risk (residence in or travel to an area with widespread community transmission or known contact). In such cases, particularly for hospitalized patients who have negative SARS-CoV-2 RNA tests, characteristic laboratory or imaging findings can further support the clinical diagnosis of COVID-19 and be reasons to maintain infection control precautions. Nevertheless, other potential causes of symptoms should also be considered in patients with negative SARS-CoV-2 RNA tests.

The interpretation of an inconclusive or indeterminate result depends on the specific RT-PCR assay performed; the clinician should confer with the performing laboratory about additional testing.

The accuracy and predictive values of SARS-CoV-2 tests have not been systematically evaluated, and the sensitivity of testing likely depends on the precise RT-PCR assay, the type of specimen obtained, the quality of the specimen, and duration of illness at the time of testing. In a study of 51 patients who were hospitalized in China with fever or acute respiratory symptoms and ultimately had a positive SARS-CoV-2 RT-PCR test (mainly on throat swabs), 15 patients (29 percent) had a negative initial test and only were diagnosed by serial testing [150]. In a similar study of 70 patients in Singapore, initial nasopharyngeal testing was negative in 8 patients (11 percent) [151]. In both studies, rare patients were repeatedly negative and only tested positive after four or more tests.

The likelihood of a positive upper respiratory RT-PCR may be higher early in the course of illness. One study using a combination of RT-PCR and an immunoglobulin (Ig)M serologic test to make the diagnosis of COVID-19 suggested that RT-PCR positivity rates were >90 percent on days 1 to 3 of illness, <80 percent at day 6, and <50 percent after day 14; however, these results should be interpreted with caution, since the serologic test used was not validated for detection of acute infection and IgM tests are generally prone to false positivity [152].

Lower respiratory tract specimens may have higher viral loads and be more likely to yield positive tests than upper respiratory tract specimens [26,31]. In a study of 205 patients with COVID-19 who were sampled at various sites, the highest rates of positive viral RNA tests were reported from bronchoalveolar lavage (95 percent, 14 of 15 specimens) and sputum (72 percent, 72 of 104 specimens), compared with oropharyngeal swab (32 percent, 126 of 398 specimens) [26]. Data from this study suggested that viral RNA levels are higher and more frequently detected in nasal compared with oral specimens, although only eight nasal swabs were tested.

Serology to identify prior infection — Serologic tests detect antibodies to SARS-CoV-2 in the blood, and those that have been adequately validated can help identify patients who have had COVID-19. Serologic tests may also be able to identify some patients with current infection (particularly those who present late in the course of illness), but they are less likely to be reactive in the first several days to weeks of infection, and thus may have less utility for diagnosis in the acute setting [152-154]. In the United States, several serologic tests have been granted emergency use authorization by the FDA for use by laboratories certified to perform moderate- and high-complexity tests [45]. The FDA highlights that serologic tests should not be used as the sole test to diagnose or exclude active SARS-CoV-2 infection. The sensitivity and specificity of many of these serologic tests are uncertain; a catalog of these tests can be found at centerforhealthsecurity.org.

Detectable antibodies generally take several days to weeks to develop. In a study of 173 patients with COVID-19, the median time from symptom onset to antibody detection (with an enzyme-linked immunosorbent assay [ELISA] that detects antibodies to the receptor-binding domain of the spike protein) was 12 days for IgM and 14 days for IgG [153]. In the first week since symptom onset, fewer than 40 percent had detectable antibodies; by day 15, IgM and IgG were detectable in 94 and 80 percent, respectively.

The accuracy and time to antibody detection vary with the particular test used. Studies evaluating the specificity of serologic tests in a broad population are lacking; in particular, the rate of cross-reactivity with other coronaviruses is a potential concern, and IgM tests are prone to false-positive results.

Large-scale serologic screening with validated tests may be able to provide a better sense of the scope of the burden of disease (by identifying people who were not diagnosed by PCR or who may have had asymptomatic or subclinical infection) and also identify individuals who may have immunity to infection; serologic correlates of protective immunity, however, have not been defined. (See 'Viral shedding and period of infectivity' above and 'Immunity and risk of reinfection' above.)

Other tests

●Tests that identify SARS-CoV-2 antigen are under development, although rapid antigen tests for respiratory pathogens are typically less sensitive than PCR in detecting viral nucleic acid (see "Diagnosis of seasonal influenza in adults", section on 'Rapid antigen tests'). Several manufacturers are selling rapid, point-of-care tests based on antigen testing or antibody detection, but the WHO does not recommend these tests because of accuracy concerns in the absence of validation studies [155].

●For safety reasons, specimens from a patient with suspected or documented COVID-19 should not be submitted for viral culture.

Testing for other pathogens — If influenza is circulating in the community, it is reasonable to also test for influenza when testing for SARS-CoV-2, as this could have management implications.

However, detection of another viral (or bacterial) pathogen does not necessarily rule out SARS-CoV-2 in locations where there is widespread transmission. Coinfection with SARS-CoV-2 and other respiratory viruses, including influenza, has been described, but the reported frequency is variable [77,156-158].

MANAGEMENTHome management is appropriate for patients with mild infection (eg, fever, cough, and/or myalgias without dyspnea) or asymptomatic infection who can be adequately isolated in the outpatient setting. Management of such patients should focus on prevention of transmission to others and monitoring for clinical deterioration, which should prompt hospitalization. Management of patients who warrant hospitalization consists of ensuring appropriate infection control and supportive care (including oxygenation and potentially ventilatory support for acute respiratory distress syndrome). Investigational approaches are also being evaluated, and should be used in the setting of a clinical trial, whenever available. Management of COVID-19 is discussed in detail elsewhere:

●(See "Coronavirus disease 2019 (COVID-19): Management in hospitalized adults".)

●(See "Coronavirus disease 2019 (COVID-19): Critical care issues".)

PREVENTION

Infection control in the health care setting — In locations where community transmission is widespread, preventive strategies for all individuals in a health care setting are warranted to reduce potential exposures. Additional measures are warranted for patients with suspected or confirmed COVID-19. Infection control in the health care setting is discussed in detail elsewhere. (See "Coronavirus disease 2019 (COVID-19): Infection control in health care and home settings", section on 'Infection control in the health care setting'.)

Preventing exposure in the community — If community transmission of SARS-CoV-2 is present, residents should be encouraged to practice social distancing by staying home as much as possible and maintaining six feet (two meters) distance from others when they have to leave home. In particular, individuals should avoid crowds and close contact with ill individuals.

The following general measures are additionally recommended to reduce transmission of infection:

●Diligent hand washing, particularly after touching surfaces in public. Use of hand sanitizer that contains at least 60 percent alcohol is a reasonable alternative if the hands are not visibly dirty.

●Respiratory hygiene (eg, covering the cough or sneeze).

●Avoiding touching the face (in particular eyes, nose, and mouth). The American Academy of Ophthalmology suggests that people not wear contact lenses, because they make people touch their eyes more frequently [159].

●Cleaning and disinfecting objects and surfaces that are frequently touched. The CDC has issued guidance on disinfection in the home setting; a list of EPA-registered products can be found here.

These measures should be followed by all individuals, but should be emphasized for older adults and individuals with chronic medical conditions, in particular.

For people without respiratory symptoms, the WHO does not recommend wearing a medical mask in the community, since it does not decrease the importance of other general measures to prevent infection and may result in unnecessary cost and supply problems; the WHO also emphasizes that medical masks should be prioritized for health care workers [160]. Recommendations on use of masks by healthy members of the community vary by country [161].

In the United States, the CDC updated its recommendations in early April to advise individuals to wear a cloth face covering (eg, homemade masks or bandanas) when in public settings where social distancing is difficult to achieve, especially in areas with substantial community transmission [162]. Individuals should be counseled to avoid touching the eyes, nose, and mouth when removing the covering, practice hand hygiene after handling it, and launder it routinely. Clinicians should emphasize that the face covering does not diminish the importance of other preventive measures, such as social distancing and hand hygiene. The rationale for the face covering is primarily to contain secretions of and prevent transmission from individuals who have asymptomatic or presymptomatic infection. The CDC also reiterates that the face covering recommendation does not include medical masks, which should be reserved for health care workers.

Individuals who are caring for patients with suspected or documented COVID-19 at home should also wear a face cover when in the same room as that patient (if the patient cannot wear a face cover).

Individuals who develop an acute respiratory illness (eg, with fever and/or respiratory symptoms) should be encouraged to self-isolate at home for the duration of the illness and wear a face cover if they have to be around other people. Some may warrant evaluation for COVID-19. (See 'Clinical suspicion and criteria for testing' above.)

The efficacy of masks in containing SARS-CoV-2 is uncertain. (See "Coronavirus disease 2019 (COVID-19): Infection control in health care and home settings", section on 'Patients with suspected or confirmed COVID-19'.)

The CDC has included recommended measures to prevent spread in the community on its website.

Managing asymptomatic individuals with potential exposure — In areas where SARS-CoV-2 is prevalent, all residents should be encouraged to stay alert for symptoms and practice social distancing by staying home as much as possible and maintaining six feet (two meters) distance from others when they have to leave the home.

In the United States, the CDC suggests this approach for all residents [163]. For those returning from international travel (including cruise ship travel) and those who have had close contact with a patient with suspected or confirmed COVID-19 (including during the 48 hours prior to that patient developing symptoms), the CDC also suggests [163,164]:

●Self-quarantine at home for 14 days following the last exposure, with maintenance of at least six feet (two meters) from others at all times.

●Avoiding contact with individuals at high risk for severe illness (unless they are household members with the same exposure). (See 'Risk factors for severe illness' above.)

●Twice-daily temperature checks with monitoring for fever, cough, or dyspnea. If they develop such clinical manifestations, they should continue to stay at home away from other household members and contact their medical providers. (See "Coronavirus disease 2019 (COVID-19): Outpatient management in adults", section on 'Outpatient management and counseling for all patients'.)

For asymptomatic individuals who are critical infrastructure workers, the CDC has provided guidance on returning to work during the 14-day post-exposure period with symptom and temperature monitoring, mask use, social distancing, and workspace disinfection [165].

Management of health care workers with a documented exposure is discussed in detail elsewhere. (See "Coronavirus disease 2019 (COVID-19): Infection control in health care and home settings", section on 'Return to work for health care workers'.)

Global public health measures — On January 30, 2020, the WHO declared the COVID-19 outbreak a public health emergency of international concern and, in March 2020, began to characterize it as a pandemic in order to emphasize the gravity of the situation and urge all countries to take action in detecting infection and preventing spread. The WHO has indicated three priorities for countries: protecting health workers, engaging communities to protect those at highest risk of severe disease (eg, older adults and those with medical comorbidities), and supporting vulnerable countries in containing infection [10].

The WHO does not recommend international travel restrictions but does acknowledge that movement restriction may be temporarily useful in some settings. The WHO advises exit screening for international travelers from areas with ongoing transmission of COVID-19 virus to identify individuals with fever, cough, or potential high-risk exposure [166,167]. Many countries also perform entry screening (eg, temperature, assessment for signs and symptoms). More detailed travel information is available on the WHO website.

In the United States, the CDC currently recommends that individuals avoid all nonessential international travel and nonessential travel from some domestic locations [168]. Because risk of travel changes rapidly, travelers should check United States government websites for possible restrictions.

Other public health measures that have been variably employed in different countries include social distancing and stay-at-home ordinances, aggressive contact tracing and quarantine, restricting traffic to or from areas of very high prevalence, and policies on face masks or coverings in public. In an epidemiologic study, a number of interventions (implementation of travel restrictions in and around Wuhan with home quarantine and compulsory mask-wearing in public, followed by centralized quarantine for all cases and contacts, followed by proactive symptom screening for all residents) were associated with progressive reductions in the incidence of confirmed cases in Wuhan and a decrease in the effective reproduction number (ie, the average number of secondary cases for each case in a population made up of both susceptible and nonsusceptible individuals) from >3 prior to the interventions to 0.3 after them [169].