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Author: Kenneth McIntosh, MD

Section Editor: Martin S Hirsch, MD
Deputy Editor: Allyson Bloom, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Apr 2020. | This topic last updated: May 22, 2020.

INTRODUCTION

Coronaviruses 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 and
airway management 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".)

VIROLOGY

Full-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 five 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, cases have been reported in all continents, except for Antarctica.

In the United States, COVID-19 has been reported in all 50 states, Washington DC, and at least
four territories [10]. 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 [11-13]. (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 [14]. However, as the outbreak progressed, person-to-person spread became the main
mode of transmission.

Person-to-person

Route of person-to-person transmission — Direct person-to-person transmission is the

primary means of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
It is thought to occur through close-range contact, mainly via respiratory droplets; 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).

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 [15]; 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 [16-18].
Other studies using specialized imaging to visualize respiratory exhalations have suggested that
respiratory droplets may get aerosolized or carried in a gas cloud and have horizontal trajectories
beyond six feet (two meters) with speaking, coughing, or sneezing [19-21]. 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 while
using 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, ocular
secretions, and semen, but the role of these sites in transmission is uncertain [25-30]. 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 rare cases [26,31]. 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 [32].

Detection of SARS-CoV-2 RNA in blood has also been reported in some but not all studies that
have tested for it [25,26,29,33]. 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 [34]. (See "Blood donor screening:
Laboratory testing", section on 'Emerging infectious disease agents'.)

Viral shedding and period of infectivity — The precise 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, particularly early in the course.
However, most data informing this issue are from studies evaluating viral RNA detection from
respiratory and other specimens; detection of viral RNA does not necessarily indicate the presence
of infectious virus, and thus prolonged viral RNA detection following the resolution of illness does
not necessarily indicate infectiousness.

Largely indirect data suggest that infected individuals are more likely to be infectious in the earlier
stages of infection. Viral RNA levels from upper respiratory specimens appear to be higher soon
after symptom onset compared with later in the illness [35-39]. Additionally, in a study of nine
patients with mild COVID-19, infectious virus was isolated from naso/oropharyngeal and sputum
specimens during the first eight days of illness, but not after this interval, despite continued high
viral RNA levels at these sites [37]. 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 that 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 [38]. In another study that evaluated over
2500 close contacts of 100 patients with COVID-19 in Taiwan, all of the 22 secondary cases had
their first exposure to the index case within six days of symptom onset; there were no infections
documented in the 850 contacts whose exposure was after this interval [40].

Transmission of SARS-CoV-2 from asymptomatic individuals (or individuals within the incubation
period) has also been well documented [41-46]. 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 [47]. 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 [48]. 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 have been granted emergency use authorization
by the US Food and Drug Administration (FDA) [49,50].

How long a person remains infectious is also uncertain, but available data suggest that prolonged
viral RNA shedding after symptom resolution is not clearly associated with prolonged
infectiousness. The duration of viral RNA shedding is variable; there appears to be a wide range,
which may depend on severity of illness [29,37,51-53]. 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
[51]. 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 [54].

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 [37]. According to
information from the United States Centers for Disease Control and Prevention (CDC), when
patients continue to have detectable viral RNA in upper respiratory samples following clinical
recovery, by three days after recovery, the RNA concentrations are generally at or below the levels
at which replication-competent virus can be reliably isolated; additionally, isolation of infectious virus
from upper respiratory specimens more than nine days after illness onset has not yet been
documented [55]. Infectious virus has also not been isolated from respiratory specimens of patients
who have a repeat positive RNA test following clinical improvement and initial viral clearance [56].
(See 'Immunity and risk of reinfection' below.)

One study reported a patient with critical COVID-19 from whom replicative virus was isolated from
the stool 28 days following symptom onset; further data are needed to understand the frequency
and clinical significance of this finding [31].

The relevance of viral RNA detection to duration of 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 [57] and long-term care facilities [11]), and in
closed settings (eg, cruise ships [58]). 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 15 percent [32,59-
62]; some studies have suggested even higher household infection rates [46,63,64]. 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 [32]. 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 [59]. 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 [60].

Clusters of cases have also been reported following family, work, or social gatherings where close,
personal contact can occur [65,66]. 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 [65]. A report
of an outbreak among a choir group, with 33 confirmed and 20 probable cases identified among 61
members who attended a practice session, raised the possibility of a high transmission risk through
singing in close proximity [67].

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 [16,68]. 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 [16]. 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 [37].

It is unknown how long SARS-CoV-2 can persist on surfaces [15,69,70]; 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 [70]. 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 [69]. 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 [71].

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 [72,73]. Moreover, asymptomatic, experimentally infected domestic cats may transmit
SARS-CoV-2 to cats they are caged with [74]. 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 [75]. 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 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 [36,37,76]. 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 [76].
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 [36]. Animal studies have suggested that the
immune response to infection may offer some protection against reinfection, at least in the short
term. In one study of nine rhesus macaques experimentally infected with SARS-CoV-2, all animals
developed neutralizing antibodies; upon rechallenge with the same viral dose 35 days later, all had
anamnestic immune responses and, on nasal swab, had lower viral RNA levels and more rapid viral
RNA decline compared with the initial challenge and with challenged naïve control animals [77].
Studies evaluating SARS-CoV-2 vaccine candidates in macaques have also suggested that immune
responses to vaccination result in lower levels of viral RNA in respiratory tract specimens following
viral challenge compared with unvaccinated controls [78,79].

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
[80,81]. 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.
Specifically, in a report from the Korea Centers for Disease Control and Prevention of patients with
COVID-19 who had a repeat positive RNA test after being previously cleared from isolation,
infectious virus could not be isolated in cell culture in any of the 108 patients tested [56]. Among 790
contacts, there were no newly confirmed cases that were traced to exposure during the period of
the repeat positive test.

As above, the FDA has granted emergency use authorization for tests that identify antibodies
against SARS-CoV-2 in serum or plasma [50]. 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 [82-84].

In a study of 1099 patients with confirmed symptomatic COVID-19, the median incubation period
was four days (interquartile range two to seven days) [83].

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 [85]. 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 [57,84,86-90]. 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 [91]:

● 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 [92-94]. 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 [92].
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 [32]. A modeling study suggested that the
adjusted case fatality rate in mainland China was 1.4 percent [95]. Most of the fatal cases occurred
in patients with advanced age or underlying medical comorbidities [52,91]. 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 [96,97]. In contrast, the
estimated case fatality rate in mid-March in South Korea was 0.9 percent [98]. 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 and other conditions that have been associated with severe illness and mortality
include (table 1) [52,91,99-102]:

● Cardiovascular disease
● Diabetes mellitus
● Hypertension
● Chronic lung disease
 ● Cancer (in particular hematologic malignancies, lung cancer, and metastatic disease) [103]
● Chronic kidney disease
● Obesity
● Smoking

The United States Centers for Disease Control and Prevention (CDC) also includes
immunocompromising conditions and liver disease as potential risk factors for severe illness [104],
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 [97].

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 [105].

Males have comprised a disproportionately high number of deaths in cohorts from China, Italy, and
the United States [92,97,106].

In a number of states in the United States, black and Latino individuals also appear to comprise a
disproportionately high number of infections and deaths due to COVID-19, possibly related to
underlying socioeconomic disparities [107-111].

Particular laboratory features have also been associated with worse outcomes (table 2). These
include [52,112,113]:

● 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 [57].
Patients with severe disease have also been reported to have higher viral RNA levels in respiratory
specimens than those with milder disease [51], although this association was not observed in a
different study that measured viral RNA in salivary specimens [36].

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 [57,87,88]. 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 [91]. 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 [95].

Older age is also associated with increased mortality [91,92,97]. 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 [91]. 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 [97].

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 [114]; 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 [115-118]. 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 [84,119-125].

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 [126]. 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 [121].
 ● 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 [47].

● Other studies have reported even higher proportions of asymptomatic cases [13,124]. 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 [124]. 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 [44,123]. 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 [44]. 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 [123].

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
[57,83,87,88]. 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 [57]:

● Fever in 99 percent (note that fever on presentation is not this common in all studies; see
below)
● 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 [57,87,127-129]. However, fever is not 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 [87]. 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 [83]. In a study of over
5000 patients who were hospitalized with COVID-19 in New York, only 31 percent had a
temperature >100.4°F/38°C at presentation [92].

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
[130-132]. 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 [131]. 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 [133]. 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 [57,87,129,134]. 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 [83,88].
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 [135-
137]. 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 [137-140]. Some are calling this finding
"COVID toes."

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 [57]. In another study, the median time to
dyspnea was eight days [87].

Several complications of COVID-19 have been described:

● Acute respiratory distress syndrome (ARDS) is the 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 [57]. 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 [112].
(See "Coronavirus disease 2019 (COVID-19): Critical care and airway management issues",
section on 'Clinical features in critically ill patients'.)

● Other complications have included arrhythmias, acute cardiac injury, and shock
[57,106,141,142]. In one study, these were reported in 17, 7, and 9 percent, respectively [57].
In a series of 21 severely ill patients admitted to the ICU in the United States, one-third
developed cardiomyopathy [141]. (See "Coronavirus disease 2019 (COVID-19): Myocardial
injury", section on 'Clinical features' and "Coronavirus disease 2019 (COVID-19): Arrhythmias
and conduction system disease", section on 'Clinical manifestations'.)

● Thromboembolic complications, including pulmonary embolism and acute stroke (even in

patients younger than 50 years of age without risk factors), have also been reported [143-148].
(See "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 [87,149,150]. (See 'Risk
factors for severe illness' above.)

● Other inflammatory complications have been described. Guillain-Barré syndrome may occur,
with onset 5 to 10 days after initial symptoms [151]. A multisystem inflammatory syndrome with
clinical features similar to those of Kawasaki disease and toxic shock syndrome has also been
described in children with COVID-19. This is discussed in detail elsewhere. (See "Coronavirus
disease 2019 (COVID-19): Multisystem inflammatory syndrome in children".)
 ● Secondary infections do not appear to be common complications of COVID-19 overall,
although data are limited [152,153]. In a review of nine studies, mainly from China, the reported
rate of bacterial or fungal coinfections was 8 percent (in 62 of 806); these included mainly
respiratory infections and bacteremia [152]. Several reports have described presumptive
invasive aspergillosis among immunocompetent patients with ARDS from COVID-19, although
the frequency of this complication is uncertain [154-156].

Autopsy studies have noted detectable SARS-CoV-2 RNA (and, in some cases, antigen) in the
kidneys, liver, heart, brain, and blood in addition to respiratory tract specimens, suggesting that the
virus disseminates systemically in some cases; whether direct viral cytopathic effects at these sites
contribute to the complications observed is uncertain [157,158].

According to the WHO, recovery time appears to be around two weeks for mild infections and three
to six weeks for severe disease [159].

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) [57,83,129].

Lymphopenia is especially common, even though the total white blood cell count can vary
[57,87,88,160]. 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 [129]. Abnormalities in
coagulation testing have also been observed; these are discussed in detail elsewhere. (See
"Coronavirus disease 2019 (COVID-19): Hypercoagulability", section on 'Coagulation
abnormalities'.)

On admission, many patients with pneumonia have normal serum procalcitonin levels; however, in
those requiring ICU care, they are more likely to be elevated [57,87,88].

Several laboratory features, including high D-dimer levels and more severe lymphopenia, have
been associated with critical illness or mortality [88]. 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 [161]. 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 [162]. 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) [163].

Chest CT in patients with COVID-19 most commonly demonstrates ground-glass opacification with
or without consolidative abnormalities, consistent with viral pneumonia [128,164]. 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 [165]. 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) [166]. A group of radiologists in that study was able to distinguish COVID-19 with high
specificity but moderate sensitivity.

As with chest radiographs, chest CT may be normal soon after the onset of symptoms, with
abnormalities more likely to develop over the course of illness [127,167]. 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 [128,168].

Among patients who clinically improve, resolution of radiographic abnormalities may lag behind
improvements in fever and hypoxia [169].
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 the individual with COVID-19 for more than a few
minutes 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'.)

If possible, all symptomatic patients with suspected infection should undergo testing; the diagnosis
cannot be definitively made without microbiologic testing. However, 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 (IDSA) 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 [170,171].
Testing certain asymptomatic individuals may also be important for public health or infection control
purposes (eg, in congregate settings where COVID-19 cases have been identified, prior to time-
sensitive surgical procedures, and prior to time-sensitive aerosol-generating procedures if PPE
supplies are limited, and in hospitalized patients at locations where prevalence is high [eg, ≥10
percent]). The IDSA also recommends SARS-CoV-2 testing for asymptomatic immunocompromised
patients who require hospitalization and for asymptomatic individuals prior to receiving
immunosuppressive therapy [172]. (See "Coronavirus disease 2019 (COVID-19): Issues related to
solid organ transplantation", section on 'Pretransplantation screening'.)

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

NAAT (RT-PCR) to diagnose current infection — The diagnosis of COVID-19 is made by

direct detection of SARS-CoV-2 RNA by nucleic acid amplification tests (NAATs), primarily reverse
transcription polymerase chain reaction (RT-PCR) [173]. Various RT-PCR assays are used around
the world; different assays amplify and detect different regions of the SARS-CoV-2 genome. Most
target two or more genes, including the nucleocapsid (N), envelope (E), and spike (S) genes, and
regions in the first open reading frame, including the RNA-dependent RNA polymerase (RdRp)
gene [174].

In the United States, the Food and Drug Administration (FDA) has granted emergency use
authorization for many different RT-PCR assays [50]; testing is performed by the CDC, local public
health departments, hospital laboratories, and certain commercial reference laboratories. These
tests have different performance characteristics and times to result (ranging from 15 minutes to
several hours) and require different specimen types. The turnaround time for clinicians to receive a
result also depends on how often the laboratory performs the test. Point-of-care NAATs have also
been developed, although some are less sensitive than laboratory-based tests [175].

Specimen collection — Upper respiratory samples are the primary specimens for SARS-
CoV-2 NAAT. In the United States, the CDC recommends collection of one of the following
specimens [176]:
 ● Nasopharyngeal swab specimen, collected by a health care professional

● Oropharyngeal swab specimen, collected by a health care professional

● Nasal swab specimen from both 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 home-collection testing kits that can be mailed to a laboratory for testing
[177,178])

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

However, there is uncertainty regarding the optimal upper respiratory tract specimen. The IDSA
suggests nasopharyngeal, mid-turbinate, or nasal specimens rather than an oropharyngeal
specimen (or saliva) because of limited data suggesting lower sensitivity with oropharyngeal
specimens and lack of data on accuracy of saliva specimens [172].

Lower respiratory tract specimens are also an option for testing; the IDSA suggests reserving these
for hospitalized patients who have an initial negative test on an upper respiratory tract specimen but
for whom suspicion for lower respiratory tract SARS-CoV-2 infection remains [172]. For lower
respiratory tract specimens, expectorated sputum should be collected from patients with productive
cough, and tracheal aspirate or bronchoalveolar lavage should be collected from patients who are
intubated. Induction of sputum is not recommended. 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'.)

Data comparing the accuracy of testing from various sites are limited but suggest that test sensitivity
may vary by type of specimen. Lower respiratory tract specimens may have higher viral loads and
be more likely to yield positive tests than upper respiratory tract specimens [26,33]. 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.

Similarly, in another study in which 117 pairs of nasopharyngeal and oropharyngeal specimens from
12 patients were tested simultaneously, 32 pairs were discordant with one test positive and the
other negative: the nasopharyngeal specimen tested positive in 66 percent of those pairs compared
with 34 percent for the oropharyngeal specimen [39]. However, other studies have not identified
higher viral RNA levels in nasopharyngeal compared with oropharyngeal specimens [37].

Interpretation — A positive NAAT 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. Repeat testing is performed 24 to 48 hours after the initial test. In such cases, the WHO and
IDSA recommend testing a lower respiratory tract specimen if the patient has evidence of lower
respiratory tract illness [172,179]. 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 a
negative SARS-CoV-2 NAAT, 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 NAATs.

The interpretation of an inconclusive or indeterminate result depends on the specific NAAT

performed; the clinician should confer with the performing laboratory about additional testing.

The accuracy and predictive values of SARS-CoV-2 NAAT have not been systematically evaluated,
and the sensitivity of testing likely depends on the precise 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 [180]. In a similar study of 70 patients in Singapore,
initial nasopharyngeal testing was negative in 8 patients (11 percent) [181]. In both studies, rare
patients were repeatedly negative and only tested positive after four or more tests.

The likelihood of detectable SARS-CoV-2 RNA may also vary by the duration of illness [182,183]. In
an analysis of seven studies (including two unpublished reports) that evaluated RT-PCR
performance by time since symptom onset or exposure, the estimated rates of false-negative results
were 100 percent on the day of exposure, 38 percent on day 5 (estimated as the first day of
symptoms), 20 percent at day 8, and 66 percent at day 21 [182]. Heterogeneity across studies and
assumptions made in the analysis (eg, about incubation period and time of exposure) reduce
confidence in these results. One of the studies included in the analysis used a combination of RT-
PCR and an immunoglobulin (Ig)M serologic test to make the diagnosis of COVID-19 and
suggested that RT-PCR negative rates were <10 percent on days 1 to 3 of illness, >20 percent at
day 6, and >50 percent after day 14; however, these results should also be interpreted with caution,
since the serologic test used was not validated for detection of acute infection and IgM tests are
frequently falsely positive [183]. Other studies have suggested that viral RNA levels are higher early
in the course of infection but that some individuals have detectable viral RNA for several weeks
following the onset of symptoms, as discussed elsewhere. (See 'Viral shedding and period of
infectivity' above.)

There are also differences in the limit of detection among the major commercial laboratory RT-PCR
assays, and retesting samples on different platforms may yield conflicting results [184]. Additionally,
point-of-care NAAT assays may not be as sensitive as laboratory-based tests [175].

Test performance by specimen type (eg, nasopharyngeal, oropharyngeal, and lower respiratory
tract) is discussed elsewhere. (See 'Specimen collection' above.)

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 [183,185-187]. Additionally, individual results should be interpreted with caution in settings of
low seroprevalence, in which even serologic tests that have high specificity still have a low positive
predictive value (ie, a positive test may be as likely to reflect a false positive as a true positive)
[188].

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 [50]. 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 [185]. 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. Rapid antigen tests are easy
to use and can be performed at the point of care, but for respiratory pathogens, they are
typically less sensitive than nucleic acid amplification testing (see "Diagnosis of seasonal
influenza in adults", section on 'Rapid antigen tests'). Several manufacturers are selling rapid,
point-of-care antigen tests, and in the United States, the FDA has started to issue emergency
use authorizations on such tests [189]. Clinicians should be aware of the possibility of false
negatives with antigen tests. The WHO had previously cautioned against the use of rapid tests
based on antigen testing or antibody detection that have not undergone adequate validation
because of concerns regarding false-positive or false-negative results [190].

● For safety reasons, specimens from a patient with suspected or documented COVID-19 should
not be submitted to clinical laboratories for viral culture. Viral culture is mainly reserved for
research purposes. (See 'Viral shedding and period of infectivity' above.)

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
[92,191-193].

MANAGEMENT
Home management is appropriate for patients with mild infection (eg, fever, cough, and/or myalgias
without dyspnea) or asymptomatic infection who can adequately self-isolate 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 and airway management 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'.)

Personal preventive measures — 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 [194].

● Cleaning and disinfecting objects and surfaces that are frequently touched. The CDC has
issued guidance on disinfection in the home setting; a list of Environmental Protection Agency-
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 [195]. Recommendations on use of
masks by healthy members of the community vary by country [196].

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
[197]. 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 (away from other individuals and pets in the
household) 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 and "Coronavirus disease 2019 (COVID-19): Infection control in health care and home
settings", section on 'Isolation at home'.)

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 [198]. 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 [198,199]:

● 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 'Management and counseling for all outpatients'.)

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 [200].

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'.)

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. Throughout the world, countries have employed various
nonpharmaceutical interventions to reduce transmission. In addition to personal preventive
measures (eg, hand hygiene, respiratory etiquette and face covers, environmental disinfection),
transmission reduction strategies include:

● Social/physical distancing orders

● Stay-at-home orders
● School, venue, and nonessential business closure
● Bans on public gatherings
● Travel restriction with exit and/or entry screening
● Aggressive case identification and isolation (separating individuals with infection from others)
 ● Contact tracing and quarantine (separating individuals who have been exposed from others)

These measures have been associated with reductions in the incidence of SARS-CoV-2 infection
over time, although the relative contribution of each is difficult to assess, as most countries have
employed a combination of interventions. As an example, in an epidemiologic study in Wuhan, a
number of these 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 [201]. In another study from China, cities in which combined control
measures were preemptively implemented prior to identification of COVID-19 cases recorded 33
percent fewer laboratory-confirmed cases during the first week of the outbreak compared with cities
that implemented control measures later [202]. In a study from the United States evaluating incident
cases in bordering counties in Illinois, which issued a stay-at-home order, and Iowa, which did not,
the counties in Iowa experienced a more rapid increase in cases following implementation of the
order in Illinois, estimated to result in 217 excess cases after one month [203].

For countries where incidence has declined and relaxation of transmission reduction measures is
being considered, the WHO has issued interim guidance on implementation, which includes a step-
wise approach that is adjusted according to local circumstances and prioritizes protecting vulnerable
populations; it recommends that personal preventive measures be maintained and that public health
efforts to detect cases for isolation and to identify contacts for quarantine be strengthened
[204,205].

Specific recommendations on global travel are 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 [206]. Because the risk of
travel changes rapidly, travelers should check United States government websites for restrictions.

Investigational approaches

Vaccines — Numerous vaccine candidates are being evaluated for prevention of COVID-19
[207]. These include various types of vaccines, including nucleic acid-based (mRNA and DNA)
vaccines, viral-vector vaccines, and inactivated or recombinant protein vaccines [208]. The different
vaccine platforms vary in their potential safety and immunogenicity, speed and cost of
manufacturing, and other features important for meeting global demand.
There is also interest in Bacille-Calmette-Guerin (BCG) immunization for prevention of COVID-19,
and clinical trials are underway to evaluate its use among health care workers [209]. Studies have
suggested that, although its primary purpose is prevention of tuberculosis, BCG immunization
induces a nonspecific immune response that may have protective effects against non-
mycobacterial, including viral, infections [210,211]. Any impact of BCG immunization on COVID-19
is unknown. The WHO recommends BCG vaccination not be used for prevention or lessening the
severity of COVID-19, pending further data [212].

Post-exposure prophylaxis — Clinical trials are also being conducted in the United States and
elsewhere to evaluate the safety and efficacy of post-exposure drug prophylaxis against COVID-19
[213,214]. No agent is known to be effective in preventing infection; we suggest post-exposure
prophylaxis not be attempted outside a clinical trial.

SPECIAL SITUATIONS

Pregnant and breastfeeding women — The general approach to prevention, evaluation,

diagnosis, and treatment of pregnant women with suspected COVID-19 is largely similar to that in
nonpregnant individuals. Issues specific to pregnant and breastfeeding women are discussed
elsewhere. (See "Coronavirus disease 2019 (COVID-19): Pregnancy issues".)

Children — Symptomatic infection in children appears to be relatively uncommon; when it occurs, it

is usually mild, although severe cases have been reported [115-118]. Details of COVID-19 in
children are discussed elsewhere. (See "Coronavirus disease 2019 (COVID-19): Considerations in
children".)

COVID-19 testing not readily available — In some cases, testing for COVID-19 may not be
accessible, particularly for individuals who have a compatible but mild illness that does not warrant
hospitalization and do not have a known COVID-19 exposure or high-risk travel history.

In the United States, there is limited official guidance for this situation, and the approach may
depend on the prevalence of COVID-19 in the area. If the clinician has sufficient concern for
possible COVID-19 (eg, there is community transmission and there is no other apparent cause for
the symptoms), it is reasonable to assume the patient had COVID-19 and advise the patient to self-
isolate at home (if hospitalization is not warranted) and alert the clinician about worsening
symptoms. Outpatient management of COVID-19 is discussed in detail elsewhere. (See
"Coronavirus disease 2019 (COVID-19): Outpatient management in adults", section on
'Management and counseling for all outpatients' and "Coronavirus disease 2019 (COVID-19):
Infection control in health care and home settings", section on 'Infection control in the home
setting'.)
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: Coronavirus disease 2019 (COVID-
19) – International and government guidelines for general care" and "Society guideline links:
Coronavirus disease 2019 (COVID-19) – Guidelines for specialty care" and "Society guideline links:
Coronavirus disease 2019 (COVID-19) – Resources for patients".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for patients
who want in-depth information and are comfortable with some medical jargon.

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 topics (see "Patient education: Coronavirus disease 2019 (COVID-19) overview (The
Basics)" and "Patient education: Coronavirus disease 2019 (COVID-19) and pregnancy (The
Basics)" and "Patient education: Coronavirus disease 2019 (COVID-19) and children (The
Basics)")

SUMMARY AND RECOMMENDATIONS

● In late 2019, a novel coronavirus, now designated SARS-CoV-2, was identified as the cause of
an outbreak of acute respiratory illness in Wuhan, a city in China. In February 2020, the World
Health Organization (WHO) designated the disease COVID-19, which stands for coronavirus
disease 2019. (See 'Introduction' above.)

● Since the first reports of COVID-19, infection has spread to include more than five million
confirmed cases worldwide, prompting the WHO to declare a public health emergency in late
January 2020 and characterize it as a pandemic in March 2020. (See 'Epidemiology' above.)
● The possibility of COVID-19 should be considered primarily in patients with fever and/or
respiratory tract symptoms who reside in or have traveled to areas with community
transmission or who have had recent close contact with a confirmed or suspected case of
COVID-19. Clinicians should also be aware of the possibility of COVID-19 in patients with
severe respiratory illness when no other etiology can be identified. Other symptoms have also
been associated with COVID-19 (table 3). Limitations in testing capacity may preclude testing
all patients with suspected infection; suggested priorities include hospitalized patients 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 (table 5). (See 'Clinical
features' above and 'Diagnosis' above.)

● The microbiologic diagnosis is made by a positive nucleic acid amplification test (eg, reverse
transcription polymerase chain reaction [RT-PCR]) for SARS-CoV-2. An upper respiratory tract
specimen is the preferred initial test specimen. If possible, all symptomatic patients with
suspected infection should undergo testing. However, because of limited testing capacity and
concern for false-negative testing, the diagnosis is often presumptively made based on
consistent clinical and epidemiologic features. Serologic tests can help identify individuals with
prior infection but have less utility in the first weeks of infection. (See 'Microbiologic diagnosis'
above.)

● Upon suspicion of COVID-19, infection control measures should be implemented. Infection

control in the home and in health care settings 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'.)

● Home management is appropriate for patients with mild illness who can adequately self-isolate
in the outpatient setting. A minority of patients need critical care. Home, hospital, and intensive
care unit management of patients with COVID-19 is discussed in detail elsewhere. (See
"Coronavirus disease 2019 (COVID-19): Management in hospitalized adults" and "Coronavirus
disease 2019 (COVID-19): Critical care and airway management issues".)

● To reduce the risk of transmission in the community, individuals should be advised to wash
hands diligently, practice respiratory hygiene (eg, cover their cough), and avoid crowds and
close contact with ill individuals, if possible. Social distancing is recommended in locations that
have community transmission. In some locations, face coverings are advised in public settings.
(See 'Personal preventive measures' above.)

● Interim guidance has been issued by the WHO and by the CDC. These are updated on an
ongoing basis. (See 'Society guideline links' above.)
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