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Coronavirus disease 2019 (COVID-19)

Author: Kenneth McIntosh, MD
Section Editor: Martin S Hirsch, MD
Deputy Editor: Allyson Bloom, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2020. | This topic last updated: Apr 04, 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 epidemiology, clinical features, diagnosis, management, and prevention of
COVID-19. 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
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(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 a 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.
Route of 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 [11].
However, as the outbreak progressed, person-to-person spread became the main mode of transmission.
Person-to-person spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 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. Although one letter to the editor described a
study in which SARS-CoV-2 remained viable in experimentally generated aerosols for at least three hours, the
relevance of this to the epidemiology of COVID-19 and its clinical implications are unclear [12]. Given the
current uncertainty regarding transmission mechanisms, airborne precautions are recommended in certain
situations. (See 'Infection control for suspected or confirmed cases' below.)
SARS-CoV-2 RNA has been detected in blood and stool specimens [13-15]. Live virus has been cultured from
stool in some cases [16], but according to a joint WHO-China report, fecal-oral transmission did not appear to
be a significant factor in the spread of infection [17].
Period of infectivity — The interval during which an individual with COVID-19 is infectious is uncertain. Most
data informing this issue are from studies evaluating viral RNA detection from respiratory and other
specimens. However, 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
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with later in the illness [18-20]. 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 [20]. These findings raise the possibility that
transmission might be more likely in the earlier stage of infection, but additional data are needed to confirm
this hypothesis.
The duration of viral shedding is also variable; there appears to be a wide range, which may depend on
severity of illness. 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 [21]. In another study of 137 patients who survived COVID-19, the
median duration of viral RNA shedding from oropharyngeal specimens was 20 days (range of 8 to 37 days)
[22]. 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 [20].
The reported rates of transmission from an individual with symptomatic infection vary by location and infection
control interventions. According to a joint WHO-China report, the rate of secondary COVID-19 ranged from 1
to 5 percent among tens of thousands of close contacts of confirmed patients in China [17]. Among crew
members on a cruise ship, 2 percent developed confirmed infection [23]. In the United States, the
symptomatic secondary attack rate was 0.45 percent among 445 close contacts of 10 confirmed patients [24].
Transmission of SARS-CoV-2 from asymptomatic individuals (or individuals within the incubation period) has
also been described [25-30]. However, the extent to which this occurs remains 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 [31]. 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 one has been approved by the US Food and Drug Administration (FDA) [32,33].
Immunity — 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 [19,20,34]. 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 [34]. 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 [19]. One
preliminary study reported that rhesus macaques infected with SARS-CoV-2 did not develop reinfection
following recovery and rechallenge [35]; however, this study has not been published in a peer-reviewed
journal, and further confirmation of these findings is needed.
As above, the FDA has approved a test that qualitatively identifies immunoglobulin (Ig)M and IgG antibodies
against SARS-CoV-2 in serum or plasma [33]. Should evidence confirm that the presence of these antibodies
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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 [36-38].
In a study of 1099 patients with confirmed symptomatic COVID-19, the median incubation period was four
days (interquartile range two to seven days) [37].
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 [39]. The median incubation period in this study was 5.1
days.
Spectrum of illness severity — The spectrum of symptomatic infection ranges from mild to critical; most
infections are not severe [38,40-45]. 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
[46]:
● 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.
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 [17]. Most of the fatal cases occurred in
patients with advanced age or underlying medical comorbidities [22,46]. (See 'Risk factors for severe illness'
below.)
The proportion of severe or fatal infections may vary by location. As an example, 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 [47,48]. In contrast, the estimated case fatality
rate in mid-March in South Korea was 0.9 percent [49]. 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 [22,46,50,51]:
● Cardiovascular disease
● Diabetes mellitus
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● Hypertension
● Chronic lung disease
● Cancer
● Chronic kidney disease
The United States Centers for Disease Control and Prevention (CDC) also includes immunocompromising
conditions, severe obesity (body mass index ≥40), and liver disease as potential risk factors for severe illness
[52], 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 [48].
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 [53].
Males have comprised a disproportionately high number of deaths in cohorts from China and Italy [48,54].
Particular laboratory features have also been associated with worse outcomes. These include [22,55,56]:
● 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 [43].
Patients with severe disease have also been reported to have higher viral RNA levels in respiratory
specimens than those with milder disease [21], although this association was not observed in a different study
that measured viral RNA in salivary specimens [19].
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 [41-43]. 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 [46].
Older age was also associated with increased mortality, with case fatality rates of 8 and 15 percent among
those aged 70 to 79 years and 80 years or older, respectively. 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
[48].
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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 [57]; 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 uncommon; when it occurs, it is usually mild, although severe
cases have been reported [58-61]. In the large Chinese report described above, only 2 percent of infections
were in individuals younger than 20 years old [46]. Similarly, in South Korea, only 6.3 percent of nearly 8000
infections were in those younger than 20 years old [49]. In a small study of 10 children in China, clinical illness
was mild; 8 had fever, which resolved within 24 hours, 6 had cough, 4 had sore throat, 4 had evidence of focal
pneumonia on CT, and none required supplemental oxygen [59]. In another study of six children aged 1 to 7
years who were hospitalized in Wuhan with COVID-19, all had fever >102.2°F/39°C and cough, four had
imaging evidence of viral pneumonia, and one was admitted to the intensive care unit; all children recovered
[60].
Asymptomatic infections — Asymptomatic infections have also been described [38,62-64], but their
frequency is unknown.
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 [65]. 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 [66].
Similarly, in a smaller COVID-19 outbreak within a skilled nursing facility, 13 of the of the 23 residents who
had a positive screening test were asymptomatic at the time of diagnosis, but 10 of them ultimately developed
symptoms over the next seven days [67].
Even patients with asymptomatic infection may have objective clinical abnormalities [29,68]. 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 [29]. 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 [68].
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 [37,41-43]. There
are no specific clinical features that can yet reliably distinguish COVID-19 from other viral respiratory
infections.
In a study describing 138 patients with COVID-19 pneumonia in Wuhan, the most common clinical features at
the onset of illness were [43]:
● Fever in 99 percent
● Fatigue in 70 percent
● Dry cough in 59 percent
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● Anorexia in 40 percent
● Myalgias in 35 percent
● Dyspnea in 31 percent
● Sputum production in 27 percent
Other cohort studies of patients from Wuhan with confirmed COVID-19 have reported a similar range of
clinical findings [41,43,69,70]. However, fever might not be a universal finding. 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 [41].
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 [37].
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 [71,72]. 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 [72]. Whether this is a distinguishing feature of COVID-19 is uncertain.
Other, less common symptoms have included headache, sore throat, and rhinorrhea. 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 [41,43,73].
Course and complications — As above, symptomatic infection can range from mild to critical. (See
'Spectrum of illness severity' above.)
Some patients with initially mild 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 [43]. In another study, the median time to dyspnea was eight days [41].
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 [43]. 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 [55].
Other complications have included arrhythmias, acute cardiac injury, and shock [43,54,74]. In one study,
these were reported in 17, 7, and 9 percent, respectively [43]. In a series of 21 severely ill patients admitted to
the ICU in the United States, one-third developed cardiomyopathy [74]. (See "Coronavirus disease 2019
(COVID-19): Critical care issues", section on 'Clinical features in critically ill patients'.)
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 [41,75]. (See 'Risk factors for severe illness' above.)
According to the WHO, recovery time appears to be around two weeks for mild infections and three to six
weeks for severe disease [10].
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Laboratory findings — In patients with COVID-19, the white blood cell count can vary. Leukopenia,
leukocytosis, and lymphopenia have been reported, although lymphopenia appears most common [13,41-43].
Elevated lactate dehydrogenase and ferritin levels are common, and elevated aminotransferase levels have
also been described. On admission, many patients with pneumonia have normal serum procalcitonin levels;
however, in those requiring ICU care, they are more likely to be elevated [41-43].
High D-dimer levels and more severe lymphopenia have been associated with mortality [42].
Imaging findings — Chest CT in patients with COVID-19 most commonly demonstrates ground-glass
opacification with or without consolidative abnormalities, consistent with viral pneumonia [70,76]. 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.
Although 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 recommends not
using chest CT for screening or diagnosis of COVID-19 and recommends reserving it for hospitalized patients
when needed for management [77].
In a study of 1014 patients in Wuhan who underwent both reverse-transcription polymerase chain reaction
(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 [78]. 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) [79]. 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
[69]. 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 [70,80].
Among patients who clinically improve, resolution of radiographic abnormalities may lag behind improvements
in fever and hypoxia [81].
EVALUATION AND 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. Although these
syndromes can occur with other viral respiratory illnesses, the likelihood of COVID-19 is increased if the
patient:
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● 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) (see 'Geographic distribution' 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 'Infection control for suspected or
confirmed cases' below.)
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 1); high-priority individuals include hospitalized
patients (especially critically ill patients with unexplained respiratory illness), symptomatic health care
workers, and symptomatic individuals who have risk factors for severe disease [82,83].
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.
An approach to suspected cases when testing is not available is discussed elsewhere. (See 'COVID-19
testing not readily available' below.)
Laboratory testing — Patients who meet the testing criteria discussed above should undergo testing for
SARS-CoV-2 (the virus that causes COVID-19) in addition to testing for other respiratory pathogens (eg,
influenza, respiratory syncytial virus). (See "Diagnostic approach to community-acquired pneumonia in
adults", section on 'Diagnostic testing for microbial etiology'.)
In the United States, the CDC recommends collection of a nasopharyngeal swab specimen to test for SARS-
CoV-2 [84]. An oropharyngeal swab can be collected but is not essential; if collected, it should be placed in
the same container as the nasopharyngeal specimen. Oropharyngeal, nasal mid-turbinate, or nasal swabs
are acceptable alternatives if nasopharyngeal swabs are unavailable.
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 'Infection
control for suspected or confirmed cases' below.)
SARS-CoV-2 RNA is detected by reverse-transcription polymerase chain reaction (RT-PCR) [85]. In the
United States, testing is performed by the CDC, by local public health departments, by hospitals that have
developed and validated their own tests, and by certain commercial reference laboratories.
A positive test for SARS-CoV-2 generally confirms the diagnosis of COVID-19, although false-positive tests
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are possible.
False-negative tests from upper respiratory specimens have been 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 [86]. Infection control precautions for COVID-19 should continue while
repeat evaluation is being performed. (See 'Infection control for suspected or confirmed cases' below.)
The accuracy and predictive values of SARS-CoV-2 testing have not been systematically evaluated, and the
sensitivity of testing likely depends on the precise test as well as the type of specimen obtained. Negative RT-
PCR tests on oropharyngeal swabs despite CT findings suggestive of viral pneumonia have been reported in
some patients who ultimately tested positive for SARS-CoV-2 [80].
Lower respiratory tract specimens may have higher viral loads and be more likely to yield positive tests than
upper respiratory tract specimens [16,87]. 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) [16]. 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.
Serologic tests, as soon as generally available and adequately evaluated, should be able to identify patients
who have either current or previous infection but a negative PCR test [88,89]. In one study that included 58
patients with clinical, radiographic, and epidemiologic features suspicious for COVID-19 but with negative
SARS-CoV-2 PCR testing, an IgM enzyme-linked immunosorbent assay (ELISA) was positive in 93 percent
(and was negative when tested separately on plasma specimens that predated the COVID-19 outbreak) [88].
In the United States, a serologic test has been approved by the Food and Drug Administration for use by
laboratories that are certified to perform moderate- and high-complexity tests [33].
For safety reasons, specimens from a patient with suspected or documented COVID-19 should not be
submitted for viral culture.
The importance of testing for other pathogens was highlighted in a report of 210 symptomatic patients with
suspected COVID-19; 30 tested positive for another respiratory viral pathogen, and 11 tested positive for
SARS-CoV-2 [40]. In addition, coinfection with SARS-CoV-2 and other respiratory viruses, including influenza,
has been reported [90,91], and this may impact management decisions.
MANAGEMENT
Site of care
Home care — Home management is appropriate for patients with non-severe infection (eg, fever, cough,
and/or myalgias without dyspnea) who can be adequately isolated in the outpatient setting [13,92,93].
Management of such patients should focus on prevention of transmission to others and monitoring for clinical
deterioration, which should prompt hospitalization.
There should be a low threshold to clinically evaluate in person patients who have risk factors for more severe
illness, even if they have only mild symptoms, to ensure they are stable enough for home care (see 'Risk
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factors for severe illness' above). If such patients are cared for at home, they should remain in frequent
contact with their provider to closely monitor for any symptoms or signs suggestive of clinical worsening.
Outpatient management is mainly supportive with hydration, antipyretics, and analgesics, if necessary.
Outpatients with COVID-19 should stay at home and try to separate themselves from other people and
animals in the household. They should wear a face cover when in the same room (or vehicle) as other people
and when presenting to health care settings. Disinfection of frequently touched surfaces is also important, as
discussed elsewhere. (See 'Environmental disinfection' below.)
The optimal duration of home isolation is uncertain. The United States Centers for Disease Control and
Prevention (CDC) has issued recommendations on discontinuation of home isolation, which include both test-
based and non-test-based strategies [94,95]. The choice of strategy depends upon the patient population (eg,
immunocompromised versus nonimmunocompromised), the availability of testing supplies, and access to
testing.
● When a test-based strategy is used, patients may discontinue home isolation when there is:
• Resolution of fever without the use of fever-reducing medications AND
• Improvement in respiratory symptoms (eg, cough, shortness of breath) AND
• Negative results of a US Food and Drug Administration (FDA) emergency use-authorized molecular
assay for COVID-19 from at least two consecutive nasopharyngeal swab specimens collected ≥24
hours apart (total of two negative specimens)
● When a non-test-based strategy is used, patients may discontinue home isolation when the following
criteria are met:
• At least seven days have passed since symptoms first appeared AND
• At least three days (72 hours) have passed since recovery of symptoms (defined as resolution of
fever without the use of fever-reducing medications and improvement in respiratory symptoms [eg,
cough, shortness of breath])
In some cases, patients may have had laboratory-confirmed COVID-19, but they did not have any symptoms
when they were tested. In such patients, home isolation may be discontinued when at least seven days have
passed since the date of their first positive COVID-19 test so long as there was no evidence of subsequent
illness.
For health care workers with confirmed or suspected COVID-19, decisions about return to work should be
made in the context of the provider's local circumstances (eg, availability of testing, staffing shortages) [96].
More detailed information regarding criteria for return to work, as well as return to work practices and work
restrictions, is found on the CDC website.
The use of non-test-based strategies that use time since illness onset and time since recovery as the criteria
for discontinuing precautions is based upon findings that transmission is most likely to occur in the early stage
of infection. However, data are limited, particularly in immunocompromised patients, and this strategy may not
prevent all instances of secondary spread [94,95]. Protocols in other countries and at specific institutions may
differ on the duration of home isolation when testing for viral clearance cannot be performed; as an example,
the World Health Organization (WHO) suggests that home isolation in patients with documented COVID-19
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should continue for at least two weeks after symptom resolution [97]. (See 'Route of transmission' above.)
More detailed interim recommendations on home management of patients with COVID-19 can be found on
the WHO and CDC websites [93,98,99].
Hospital care — Some patients with suspected or documented COVID-19 have severe disease that
warrants hospital care. Management of such patients consists of ensuring appropriate infection control, as
below (see 'Infection control for suspected or confirmed cases' below), and supportive care. Investigational
approaches are also being evaluated (see 'Investigational approaches' below). Clinical guidance can be found
on the WHO and CDC websites [13,92].
Patients with severe disease often need oxygenation support. High-flow oxygen and noninvasive positive
pressure ventilation have been used, but the safety of these measures is uncertain, and they should be
considered aerosol-generating procedures that warrant specific isolation precautions. (See "Coronavirus
disease 2019 (COVID-19): Critical care issues", section on 'Respiratory care of the nonintubated patient'.)
Some patients may develop acute respiratory distress syndrome (ARDS) and warrant intubation with
mechanical ventilation. Management of ARDS in patients with COVID-19 and other critical care issues are
discussed in detail elsewhere. (See "Coronavirus disease 2019 (COVID-19): Critical care issues".)
Limited role of glucocorticoids — The WHO and CDC recommend glucocorticoids not be used in patients
with COVID-19 pneumonia unless there are other indications (eg, exacerbation of chronic obstructive
pulmonary disease) [13,92]. Glucocorticoids have been associated with an increased risk for mortality in
patients with influenza and delayed viral clearance in patients with Middle East respiratory syndrome
coronavirus (MERS-CoV) infection. Although they were widely used in management of severe acute
respiratory syndrome (SARS), there was no good evidence for benefit, and there was persuasive evidence of
adverse short- and long-term harm [100]. (See "Treatment of seasonal influenza in adults", section on
'Adjunctive therapies' and "Middle East respiratory syndrome coronavirus: Treatment and prevention", section
on 'Treatment'.)
The use of glucocorticoids among critically ill patients with COVID-19 is discussed elsewhere. (See
"Coronavirus disease 2019 (COVID-19): Critical care issues", section on 'Glucocorticoids'.)
Uncertainty about NSAID use — Some clinicians have suggested the use of non-steroidal anti-inflammatory
drugs (NSAIDs) early in the course of disease may have a negative impact on disease outcome [101,102].
These concerns are based on anecdotal reports of a few young patients who received NSAIDs early in the
course of infection and experienced severe disease. However, there have been no clinical or population-
based data that directly address the risk of NSAIDs. The European Medicines Agency (EMA) and the WHO
do not recommend that NSAIDs be avoided when clinically indicated [103,104]. Given the uncertainty, we
suggest acetaminophen as the preferred antipyretic agent, if possible, and if NSAIDs are needed, the lowest
effective dose should be used. However, we do not suggest that NSAIDs be stopped in patients who are on
them chronically for other conditions, unless there are other reasons to stop them (eg, renal injury,
gastrointestinal bleeding).
Investigational approaches — A number of investigational approaches are being explored for antiviral
treatment of COVID-19, and enrollment in clinical trials should be discussed with patients or their proxies. A
registry of international clinical trials can be found on the WHO website and at clinicaltrials.gov.
Certain investigational agents have been described in observational series or are being used anecdotally
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based on in vitro or extrapolated evidence. It is important to acknowledge that there are no controlled data
supporting the use of any of these agents, and their efficacy for COVID-19 is unknown.
● Remdesivir – Several randomized trials are underway to evaluate the efficacy of remdesivir for moderate
or severe COVID-19 [105]. Remdesivir is a novel nucleotide analogue that has activity against severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and related coronaviruses (including
SARS and MERS-CoV) both in vitro and in animal studies [106,107]. Remdesivir is an intravenous agent;
reported side effects include nausea, vomiting, and transaminase elevations. It is also prepared in a
cyclodextrin vehicle, so there is concern for potentially toxic accumulation of the vehicle in renal
impairment. Exclusion criteria vary by trials but include alanine aminotransferase level >5 times the upper
limit of normal and chronic kidney disease (creatinine clearance <30 or <50 mL/min, depending on the
trial); some trials also exclude use of a different COVID-19-targeted therapy within 24 hours prior to
remdesivir initiation. Remdesivir may be available through compassionate use for pregnant women and
children. Use of remdesivir has been described in case series [108,109]; systematic evaluation of the
clinical impact of remdesivir on COVID-19 has not yet been published.
● Chloroquine/hydroxychloroquine – Both chloroquine and hydroxychloroquine have been reported to

inhibit SARS-CoV-2 in vitro, although hydroxychloroquine appears to have more potent antiviral activity
[110].
Clinical data evaluating hydroxychloroquine or chloroquine are limited, and their efficacy against SARS-
CoV-2 is unknown. Nevertheless, given the lack of clearly effective interventions and the in vitro antiviral
activity, some clinicians think it is reasonable to use hydroxychloroquine in hospitalized patients with
severe disease or risk for severe disease who are not eligible for clinical trials. In the United States, the
FDA issued an emergency use authorization to allow the use of these agents in adolescents or adults
hospitalized for COVID-19 when participation in clinical trials is not feasible [111]. However, if these
agents are used outside of a clinical trial, the possibility of drug toxicity (including QTc prolongation, in
particular, as well as cardiomyopathy and retinal toxicity) and drug interactions should be considered
prior to use, especially in individuals who may be more susceptible to these effects, and the patients
should be monitored closely for adverse effects during use. The American College of Cardiology has
suggested QTc monitoring parameters in this setting [112]. Optimal dosing is uncertain; the FDA
suggests hydroxychloroquine 800 mg on day 1 then 400 mg daily and chloroquine 1 g on day 1 then 500
mg daily, each for four to seven days total depending on clinical response [111]. Other
hydroxychloroquine regimens used include 400 mg twice daily on day 1 then daily for five days, 400 mg
twice daily on day 1 then 200 mg twice daily for four days, and 600 mg twice daily on day 1 then 400 mg
daily for four days [113].
Use of chloroquine is included in treatment guidelines from China's National Health Commission and was
reportedly associated with reduced progression of disease and decreased duration of symptoms
[114,115]. However, primary data supporting these claims have not been published [116]. A randomized
trial of patients with mild COVID-19 pneumonia and no hypoxia reported that adding hydroxychloroquine
to standard of care resulted in faster time to improvement in fever, cough, and chest imaging findings and
possibly a lower likelihood of progression to severe disease, but the trial has not been published in a
peer-reviewed journal [117], and there are concerns about concomitant co-therapies, baseline differences
between the groups, and the lack of a placebo control.
Published clinical data on either of these agents are limited. In an open-label study of 36 patients with
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COVID-19, use of hydroxychloroquine (200 mg three times per day for 10 days) was associated with a
higher rate of undetectable SARS-CoV-2 RNA on nasopharyngeal specimens at day 6 compared with no
specific treatment (70 versus 12.5 percent) [118]. In this study, the use of azithromycin in combination
with hydroxychloroquine appeared to be associated with a more rapid decline in viral RNA; however
there are methodologic concerns about the control groups for the study, the biologic basis for using
azithromycin in this setting is unclear, and another small observational study in patients with more severe
illness did not suggest rapid viral RNA clearance with the combination [119]. In a randomized trial of 30
adults with COVID-19 in Shanghai, the proportion of patients with nasopharyngeal viral clearance at day
7 was not different with hydroxychloroquine (400 mg daily for five days) compared with standard of care,
and one patient in the hydroxychloroquine group progressed to severe disease; interferon and other
antiviral agents were used in both arms, which could be confounding factors [120].
● IL-6 pathway inhibitors – Clinical features consistent with a cytokine release syndrome with elevated
interleukin (IL)-6 levels have been described in patients with severe COVID-19. Anecdotal reports have
described good outcomes with the IL-6 receptor inhibitor tocilizumab [75], but there are no published
clinical data supporting its use. Treatment guidelines from China's National Health Commission include
tocilizumab for patients with severe COVID-19 and elevated IL-6 levels. This agent, as well as sarilumab
and siltuximab, which also target the IL-6 pathway, are being evaluated in clinical trials [121].
● Convalescent plasma – In the United States, the Food and Drug Administration is accepting emergency
investigational new drug applications for use of convalescent plasma for patients with severe or life-
threatening COVID-19 [122]. A case series described administration of plasma from donors who had
completely recovered from COVID-19 to five patients with severe COVID-19 on mechanical ventilation
and persistently high viral titers despite investigational antiviral treatment [34]. The patients had
decreased nasopharyngeal viral load, decreased disease severity score, and improved oxygenation by
12 days after transfusion, but these findings do not establish a causal effect. Finding appropriate donors
and establishing testing to confirm neutralizing activity of plasma may be logistical challenges. (See
"Clinical use of plasma components", section on 'Convalescent plasma'.)
● Favipiravir – Favipiravir is an RNA polymerase inhibitor that is available in some Asian countries for
treatment of influenza and is being evaluated in clinical trials for treatment of COVID-19. In a study of
patients with non-severe disease (including oxygen saturation >93 percent), use of favipiravir was
associated with faster rates of viral clearance (median time to clearance 4 versus 11 days) and more
frequent radiographic improvement (in 91 versus 62 percent by day 14) compared with lopinavir-ritonavir
[123]. However, other therapies were administered in this non-randomized, open-label study, so the
results should be interpreted with caution given potential confounders.
● Lopinavir-ritonavir – Lopinavir-ritonavir appears to have little to no role in the treatment of SARS-CoV-2

infection. This combined protease inhibitor, which has primarily been used for HIV infection, has in vitro
activity against the SARS-CoV [124] and appears to have some activity against MERS-CoV in animal
studies [125]. However, there was no difference in time to clinical improvement or mortality at 28 days in
a randomized trial of 199 patients with severe COVID-19 given lopinavir-ritonavir (400/100 mg) twice
daily for 14 days in addition to standard care versus those who received standard of care alone [126].
Institutional protocols — Several academic medical institutions in the United States have developed
COVID-19 management protocols and made them publicly available. Given the paucity of high-quality clinical
evidence on the management of COVID-19, the safety and efficacy of these strategies are uncertain:
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● Brigham and Women's Hospital

● Massachusetts General Hospital
● Michigan Medicine
● Nebraska Medicine
● Penn Medicine
● University of Washington Medicine
Partners in Health has also released resources for clinicians and organizations in resource limited settings.
PREVENTION
In the health care setting
Measures for all patients — Screening patients for clinical manifestations consistent with COVID-19 (eg,
fever, cough, dyspnea) prior to entry into a health care facility can help identify those who may warrant
additional infection control precautions. This can be done over the phone before the patient actually presents
to a facility. Routine visits should be postponed for patients with these manifestations; if they need to present
for medical care, they should be advised to wear a face cover. Separate waiting areas for patients with
respiratory symptoms should be designated, if possible, at least six feet away from the regular waiting areas.
In locations where community transmission is ongoing, postponing all elective procedures or non-urgent visits
and using virtual (eg, through video communication) visits may be useful strategies to reduce the risk of
exposure in the health care setting [127].
In some settings, such as long-term care facilities, the United States Centers for Disease Control and
Prevention (CDC) recommends that standard, contact, and droplet precautions in addition to eye protection
be used for any patient with an undiagnosed respiratory infection who is not under consideration for
COVID-19 [128]. Some institutions have instituted policies requiring health care workers to wear medical
masks in all clinical settings [129]. These strategies may help reduce the risk of spread from unsuspected
virus carriers.
Infection control precautions for suspect COVID-19 cases are discussed below.
Infection control for suspected or confirmed cases — Infection control to limit transmission is an
essential component of care in patients with suspected or documented COVID-19.
Individuals with suspected infection in the community should be advised to wear a face cover to contain their
respiratory secretions prior to seeking medical attention. (See 'Evaluation and diagnosis' above.)
In the health care setting, the World Health Organization (WHO) and CDC recommendations for infection
control for suspected or confirmed infections differ slightly:
● The WHO recommends standard, contact, and droplet precautions (ie, gown, gloves, and medical mask),
with eye or face protection [130]. The addition of airborne precautions (ie, respirator) is warranted during
aerosol-generating procedures (as detailed below).
The CDC recommends that patients with suspected or confirmed COVID-19 be placed in a single-
occupancy room with a closed door and dedicated bathroom [127]. The patient should wear a medical
mask if being transported out of the room (eg, for studies that cannot be performed in the room). An
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airborne infection isolation room (ie, a single-patient negative pressure room) should be reserved for
patients undergoing aerosol-generating procedures (as detailed below). However, patients with
suspected or confirmed COVID-19 should not be in a positive-pressure room.
Any personnel entering the room of a patient with suspected or confirmed COVID-19 should wear the
appropriate personal protective equipment (PPE): gown, gloves, eye protection, and a respirator (eg, an
N95 respirator). If supply of respirators is limited, the CDC acknowledges that medical masks are an
acceptable alternative (in addition to contact precautions and eye protection), but respirators should be
worn during aerosol-generating procedures [127].
Aerosol-generating procedures include tracheal intubation and extubation, noninvasive ventilation, manual
ventilation before intubation, bronchoscopy, administration of high-flow oxygen or nebulized medications,
tracheotomy, cardiopulmonary resuscitation, and upper endoscopy. The CDC does not consider
nasopharyngeal or oropharyngeal specimen collection an aerosol-generating procedure that warrants an
airborne isolation room, but it should be performed in a single-occupancy room with the door closed, and any
personnel in the room should wear a respirator (or if unavailable, a medical mask) [127].
Health care workers should pay special attention to the appropriate sequence of putting on (figure 1) and
taking off (figure 2) PPE to avoid contamination.
The importance of infection control in preventing the spread of severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2) in health care settings has been demonstrated in several studies. In one report of 138
patients with COVID-19 in China, it was estimated that 43 percent acquired infection in the hospital setting
[43]. In Washington State, suboptimal use of infection control procedures contributed to the spread of infection
to 81 residents, 34 staff members, and 14 visitors [131].
Exposures in health care workers — For health care workers who have had a potential exposure to
COVID-19, the CDC has provided guidelines for work restriction and monitoring. The approach depends upon
the duration of exposure, the patient's symptoms, whether the patient was wearing a medical mask, the type
of PPE used by the provider, and whether an aerosol-generating procedure was performed. Some local
health departments allow health care workers to return to work following an exposure if they adhere to cough
and hand hygiene, wear a medical mask while at the health care facility until 14 days after the exposure, and
monitor daily for fever or respiratory symptoms, the presence of which would prompt immediate self-isolation
[132].
Strategies for PPE shortages — Limited availability of personal protective equipment (PPE) has
complicated medical care of patients with suspected or documented COVID-19 (and other transmissible
conditions) worldwide.
In the United States, the CDC offers guidance on optimizing the supply of PPE when sudden increases in
patient volume threaten a facility's PPE capacity [133]. Strategies include canceling non-urgent procedures or
visits that would warrant use of PPE, prioritizing the use of certain PPE for the highest risk situations, and
cautious extended or limited reuse of PPE.
There has also been interest in decontamination of PPE for reuse, in particular for N95 respirators. The CDC
has highlighted three methods for decontamination of respirators when supplies are critically low (crisis
standards) [134]:
● Ultraviolet light – Decontamination with ultraviolet (UV) light was evaluated in the context of the H1N1
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influenza pandemic; in experimental models, UV irradiation was observed to reduce H1N1 influenza
viability on N95 respirator surfaces at doses below the threshold observed to impair the integrity of the
respirator [135-137]. Coronaviruses can also be inactivated by UV irradiation, but comparable studies
have not been performed with SARS-CoV-2, and the dose needed to inactivate the virus on a respirator
surface is unknown. Nebraska Medicine has implemented a protocol for UV irradiation of N95 respirators
in the context of the COVID-19 pandemic based on the dose generally needed to inactivate other single-
stranded RNA viruses on surfaces [138].
● Hydrogen peroxide vapor – Hydrogen peroxide vapor has been observed to inactivate other non-
coronavirus single-stranded RNA viruses on environmental surfaces [139,140]. Duke University Health
System has created an in-house protocol using hydrogen peroxide vapor for N95 decontamination [141].
In some regions, plans for large-scale decontamination (eg, tens of thousands of respirators daily) with
hydrogen peroxide vapor with proprietary machinery are underway [142].
● Moist heat – Moist heat has been observed to reduce the concentration of H1N1 influenza virus on N95
respirator surfaces [136]. In this study, moist heat was applied by preparing a container with 1 L of tap
water in the bottom and a dry horizontal rack above the water; the container was sealed and warmed in
an oven to 65°C/150°F for at least three hours; it was then opened, the respirator placed on the rack, and
the container resealed and placed back in the oven for an additional 30 minutes. No residual H1N1
infectivity was found. The optimal time and temperature to inactivate SARS-CoV-2 are uncertain; several
studies observed inactivation of SARS-CoV after 30 to 60 minutes at 60°C/140°F [143-145].
Equipment used for protection in other industries is also being explored as an alternative to standard health
care PPE, such as elastometric half-mask respirators in place of N95 respirators [146].
Discontinuation of precautions — The decision to discontinue infection control precautions for

hospitalized patients with COVID-19 should be made on a case-by-case basis in consultation with experts in
infection prevention and control and public health officials. In the United States, the CDC recommends that
hospitalized patients meet all of the following criteria before discontinuation of precautions: resolution of fever
(without antipyretics), improvement in respiratory symptoms, and two negative reverse-transcription
polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 on sequential nasopharyngeal specimens
collected ≥24 hours apart [147]. Although a non-test-based strategy (ie, that allows discontinuation of
precautions after specific time intervals since symptom onset and symptom resolution) may be appropriate for
patients managed at home, this test-based strategy is preferred for hospitalized patients and those being
transferred to a long-term care facility. If patients are ready to be discharged home prior to meeting criteria for
discontinuation of precautions, they can be sent home with instructions to self-isolate until they meet either
test-based or non-test-based criteria. (See 'Home care' above.)
Whether a test-based strategy reliably identifies patients who are no longer infectious is unknown. Positive
RT-PCR tests for SARS-CoV-2 RNA were reported in laboratory-confirmed COVID-19 patients after they had
clinically improved and tested negative on two consecutive tests [148]. Another report described 22 patients
with COVID-19 who had detectable viral RNA in fecal and/or sputum specimens for up to 13 and 39 days,
respectively, even though the viral RNA was no longer detectable in pharyngeal specimens [149]. The clinical
significance of these findings is uncertain; it is unknown whether these individuals continued to shed
infectious virus.
Environmental disinfection — To help reduce the spread of COVID-19 virus, environmental infection
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control procedures should also be implemented [93,99,127,130,150]. In United States health care settings,
the CDC states routine cleaning and disinfection procedures are appropriate for COVID-19 virus [127].
Products approved by the Environmental Protection Agency (EPA) for emerging viral pathogens should be
used; a list of EPA-registered products can be found here. Specific guidance on environmental measures,
including those used in the home setting, is available on the CDC and WHO websites. Additional information
is also found in a separate topic review. (See "Coronaviruses", section on 'Treatment and prevention'.)
The importance of environmental disinfection was illustrated in a study from Singapore, in which 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 [151]. 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.
It is unknown how long SARS-CoV-2 can persist on surfaces [12,150,152]; 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 [152].
However, in a systematic review of similar studies, various disinfectants (including ethanol at concentrations
between 62 and 71 percent) inactivated a number of coronaviruses related to SARS-CoV-2 within one minute
[150].
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).
● 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 [2,153,154]. Recommendations on use of masks by
healthy members of the community vary by country [155].
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
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to achieve, especially in areas with substantial community transmission [156]. 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 CDC has included recommended measures to prevent spread in the community on its website.
Managing asymptomatic non-health care workers 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 [157]. 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 suggests [157,158]:
● 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 'Home care' above.)
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 [159,160]. Many countries also perform entry screening (eg, temperature,
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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 [161]. Because risk of travel changes rapidly, travelers
should check United States government websites for possible restrictions.
Investigational approaches — Numerous vaccine candidates are being evaluated for prevention of
COVID-19. The first vaccine to undergo preliminary study in humans in the United States uses a messenger
RNA platform to result in expression of the viral spike protein in order to induce an immune response [162].
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 [163,164]. 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".)
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), it is reasonable to advise the patient to self-isolate at home (if hospitalization is not
warranted) and alert the clinician about worsening symptoms. The optimal duration of home isolation in such
cases is uncertain. A discussion of when home isolation can be discontinued in patients with confirmed
COVID-19 can be found above. (See 'Home care' above.)
Managing chronic medications
Patients receiving ACE inhibitors/ARBs — Patients receiving angiotensin-converting enzyme (ACE)

inhibitors or angiotensin receptor blockers (ARBs) should continue treatment with these agents. This
approach is supported by multiple guideline panels [165-169].
There has been speculation that patients with COVID-19 who are receiving these agents may be at increased
risk for adverse outcomes [170,171]. Angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2
[172,173], and renin-angiotensin-aldosterone system inhibitors have been shown to increase ACE2 levels in
some, but not all, animal and human studies [173,174]. Although patients with cardiovascular disease,
hypertension, and diabetes may have a more severe clinical course in the setting of infection with SARS-
CoV-2, there is no evidence to support an association with these agents. In addition, stopping these agents in
some patients may exacerbate comorbid cardiovascular or kidney disease and lead to increased mortality
[175].
Patients receiving immunomodulatory agents — Immunocompromised patients with COVID-19 are at
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increased risk for severe disease, and the decision to discontinue prednisone, biologics, or other
immunosuppressive drugs in the setting of infection must be determined on a case-by-case basis. (See
'Management' above.)
For individuals with underlying conditions who require treatment with these agents and are without evidence
of COVID-19, there is no evidence that routinely discontinuing treatment is of any benefit. In addition,
discontinuing these medications may result in loss of response when the agent is reintroduced. This approach
is supported by statements from American and other dermatology, rheumatology, and gastroenterology
societies [176-179].
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".)
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 topic (see "Patient education: Coronavirus disease 2019 (COVID-19) overview (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 a 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
21 of 40 4/7/2020, 12:52 AM
possibility of COVID-19 in patients with severe respiratory illness when no other etiology can be
identified. Limitations in testing capacity may preclude testing all patients with suspected infection;
suggested priorities include hospitalized patients, symptomatic health care workers, and symptomatic
individuals who have risk factors for severe disease (table 1). (See 'Clinical features' above and
'Evaluation and diagnosis' above.)
● In addition to testing for other respiratory pathogens, a nasopharyngeal swab specimen should be
collected for reverse-transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. (See
'Evaluation and diagnosis' above.)
● Upon suspicion of COVID-19, infection control measures should be implemented and public health
officials notified. In health care settings in the United States, the Centers for Disease Control and
Prevention (CDC) recommends a single-occupancy room for patients and gown, gloves, eye protection,
and a respirator (or medical mask as an alternative) for health care personnel (figure 1 and figure 2).
(See 'Infection control for suspected or confirmed cases' above.)
● Management consists of supportive care, although investigational approaches are being evaluated.
Home management may be possible for patients with mild illness who can be adequately isolated in the
outpatient setting. (See 'Management' above.)
● 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 'Preventing exposure in the
community' 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.)
Use of UpToDate is subject to the Subscription and License Agreement.
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18, 2020).
Topic 126981 Version 45.0
35 of 40 4/7/2020, 12:52 AM
GRAPHICS
Suggested priorities for SARS-CoV-2 (COVID-19) testing
Priority CDC guidance [1] IDSA guidance [2]
First Hospitalized patients Critically ill patients receiving ICU-level care with unexplained viral
Symptomatic health care pneumonia or respiratory failure (regardless of travel or exposure history)
workers Any individual (including health care workers) with fever or features of a
lower respiratory tract illness and close contact with patients with
laboratory-confirmed COVID-19 within 14 days of symptom onset
(including all residents of long-term care facilities with a confirmed case)
Individuals with fever or features of a lower respiratory tract illness who
are also immunosuppressed (including patients with HIV), older, or have
underlying chronic health conditions
Individuals with fever or features of a lower respiratory tract illness who
are critical to the pandemic response, including health care workers,
public health officials, and other essential leaders
Second Patients in long-term care Non-ICU hospitalized patients and long-term care residents with
facilities with symptoms unexplained fever and features of a lower respiratory tract illness* ¶
Patients 65 years of age
and older with symptoms
Patients with underlying
conditions with symptoms
First responders with
symptoms
Third Critical infrastructure Outpatients who meet criteria for influenza testing (eg, symptoms such as
workers with symptoms fever, cough, and other suggestive respiratory symptoms plus comorbid
Individuals who do not conditions, such as diabetes mellitus, chronic obstructive pulmonary
meet any of the above disease, congestive heart failure, age >50 years, immunocompromising
categories with symptoms conditions); testing of outpatient pregnant women and symptomatic
Health care workers and children with similar risk factors is also included in this priority level*
first responders without
symptoms
Individuals with mild
symptoms in communities
experiencing high
COVID-19 hospitalizations
Fourth Individuals without Community surveillance as directed by public health and/or infectious
symptoms (non-priority) diseases authorities
SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; COVID-19: coronavirus disease 2019; CDC: United States Centers for
Disease Control and Prevention; IDSA: Infectious Diseases Society of America; ICU: intensive care unit.
* The number of confirmed COVID-19 cases in the community should be considered.
¶ As testing becomes more widely available, routine testing of hospitalized patients may be important for infection prevention and
management at discharge.
References:
1. Centers for Disease Control and Prevention. Evaluating and Testing Persons for Coronavirus Disease 2019 (COVID-19). Available
at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-criteria.html (Accessed on March 26, 2020).
2. Infectious Diseases Society of America. COVID-19 Prioritization of Diagnostic Testing. Available at: http://www.idsociety.org
/globalassets/idsa/public-health/covid-19-prioritization-of-dx-testing.pdf (Accessed on March 26, 2020).
Graphic 127515 Version 2.0
36 of 40 4/7/2020, 12:52 AM
Putting on personal protective equipment
Sequence for putting on personal protective equipment.
Reproduced from: Centers for Disease Control and Prevention. Protecting Healthcare Personnel: Sequence for
Donning and Removing Personal Protective Equipment. Available at: https://www.cdc.gov/hai/prevent
/ppe.html (Accessed on March 20, 2020).
37 of 40 4/7/2020, 12:52 AM
Taking off personal protective equipment
38 of 40 4/7/2020, 12:52 AM
Reproduced from: Centers for Disease Control and Prevention. Protecting Healthcare Personnel: Sequence for Donning and Removing
Personal Protective Equipment. Available at: https://www.cdc.gov/hai/prevent/ppe.html (Accessed on March 20, 2020).
39 of 40 4/7/2020, 12:52 AM
Contributor Disclosures
Kenneth McIntosh, MD Nothing to disclose Martin S Hirsch, MD Nothing to disclose Allyson Bloom, MD Nothing to
disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by
vetting through a multi-level review process, and through requirements for references to be provided to support the
content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy
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Coronavirus disease 2019 (COVID-19) - UpToDate https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19...

Official reprint from UpToDate®

Coronavirus disease 2019 (COVID-19)

Route of transmission — Understanding of the transmission risk is incomplete. Epidemiologic investigation

Person-to-person spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is thought to

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

EVALUATION AND DIAGNOSIS

• Resolution of fever without the use of fever-reducing medications AND

• Improvement in respiratory symptoms (eg, cough, shortness of breath) AND

● Chloroquine/hydroxychloroquine – Both chloroquine and hydroxychloroquine have been reported to

● Lopinavir-ritonavir – Lopinavir-ritonavir appears to have little to no role in the treatment of SARS-CoV-2

● Brigham and Women's Hospital

In the health care setting

Discontinuation of precautions — The decision to discontinue infection control precautions for

Preventing exposure in the community — If community transmission of SARS-CoV-2 is present, residents

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

Managing chronic medications

Patients receiving ACE inhibitors/ARBs — Patients receiving angiotensin-converting enzyme (ACE)

Patients receiving immunomodulatory agents — Immunocompromised patients with COVID-19 are at

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

Use of UpToDate is subject to the Subscription and License Agreement.

3. World Health Organization. Novel Coronavirus (2019-nCoV) technical guidance. https://www.who.int/em

7. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus:

8. Perlman S. Another Decade, Another Coronavirus. N Engl J Med 2020; 382:760.

Lancet Infect Dis 2020.

29. Hu Z, Song C, Xu C, et al. Clinical characteristics of 24 asymptomatic infections with COVID-19

33. US Food and Drug Administration. https://www.fda.gov/media/136622/download (Accessed on April 03,

e-print. https://www.biorxiv.org/content/10.1101/2020.03.13.990226v1.full.pdf (Accessed on March 26, 2

49. KCDC. Updates on COVID-19 in Korea. March 14, 2020. https://www.cdc.go.kr/board/board.es?mid=a3

Euro Surveill 2020; 25.

71. https://www.entnet.org/content/coronavirus-disease-2019-resources (Accessed on March 23, 2020).

019 (COVID-19) https://www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html (Accessed on Ma

unocompromised persons with COVID-19 (Interim Guidance). https://www.cdc.gov/coronavirus/2019-nc

Engl J Med 2020; 382:929.

111. US Food and Drug Administration. https://www.fda.gov/media/136534/download (Accessed on March 3

121. https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=IL-6&cntry=&state=&city=&dist= (Accessed o

ess-cber/investigational-covid-19-convalescent-plasma-emergency-inds (Accessed on March 29, 2020).

132. https://www.doh.wa.gov/Portals/1/Documents/1600/coronavirus/HealthCareworkerReturn2Work.pdf (Ac

Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From a

162. https://clinicaltrials.gov/ct2/show/NCT04283461 (Accessed on March 23, 2020).

163. https://clinicaltrials.gov/ct2/show/NCT04308668 (Accessed on March 23, 2020).

166. European Society of Hypertension. ESH Statement on COVID-19. https://www.eshonline.org/spotlights/

174. Vaduganathan M, Vardeny O, Michel T, et al. Renin-Angiotensin-Aldosterone System Inhibitors in

178. The American Academy of Dermatology. https://assets.ctfassets.net/1ny4yoiyrqia/PicgNuD0IpYd9MSO

179. American College of Rheumatology. https://www.rheumatology.org/announcements (Accessed on March

Topic 126981 Version 45.0

Suggested priorities for SARS-CoV-2 (COVID-19) testing

Priority CDC guidance [1] IDSA guidance [2]

Graphic 127515 Version 2.0

Putting on personal protective equipment

Sequence for putting on personal protective equipment.

Graphic 127473 Version 1.0

Taking off personal protective equipment

Graphic 127474 Version 1.0

Conflict of interest policy

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