Interim Clinical Guidance for Management of

Patients with Confirmed Coronavirus Disease

(COVID-19)
Summary of Recent Changes
Revisions were made on March 30, 2020, to reflect the following:

 New information about asymptomatic and pre-symptomatic infections

 Non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme
inhibitors, and angiotensin receptor blockers and risk of infection or
infection severity
 Information about COVID-19 and potential for SARS-CoV-2 reinfection
 Possibility of infection with both SARS-CoV-2 and other respiratory
viruses
 Additional laboratory and imaging findings in COVID-19
 Updated guidelines from the World Health Organization and the
Surviving Sepsis Campaign
 Inclusion of new resource: Information for Clinicians on Therapeutic
Options for COVID-19 Patients

On This Page

 Clinical Presentation
 Clinical Course
 Diagnostic Testing
 Laboratory and Radiographic Findings
 Clinical Management and Treatment
 Investigational Therapeutics
 Discontinuation of Transmission-Based Precautions or Home Isolation
This interim guidance is for clinicians caring for patients with confirmed
infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-
2), the virus that causes coronavirus disease 2019 (COVID-19). CDC will
update this interim guidance as more information becomes available.

Clinical Presentation
Incubation period

The incubation period for COVID-19 is thought to extend to 14 days, with a

median time of 4-5 days from exposure to symptoms onset.  One study
1-3

reported that 97.5% of persons with COVID-19 who develop symptoms will
do so within 11.5 days of SARS-CoV-2 infection.3

Presentation

The signs and symptoms of COVID-19 present at illness onset vary, but over
the course of the disease, most persons with COVID-19 will experience the
following : 1,4-9

 Fever (83–99%)
 Cough (59–82%)
 Fatigue (44–70%)
 Anorexia (40–84%)
 Shortness of breath (31–40%)
 Sputum production (28–33%)
 Myalgias (11–35%)

Atypical presentations have been described and older adults and persons
with medical comorbidities may have delayed presentation of fever and
respiratory symptoms.  In one study of 1,099 hospitalized patients, fever
10,11

was present in only 44% at hospital admission but later developed in 89%
during hospitalization.  Headache, confusion, rhinorrhea, sore throat,
1

hemoptysis, vomiting, and diarrhea have been reported but are less common
(<10%).  Some persons with COVID-19 have experienced gastrointestinal
1,4-6

symptoms such as diarrhea and nausea prior to developing fever and lower
respiratory tract signs and symptoms.  Anosmia or ageusia preceeding the
9

onset of respiratory symptoms has been anecdotally reported, but more

information is needed to understand its role in identifying COVID-19.

Several studies have reported that the signs and symptoms of COVID-19 in
children are similar to adults and are usually milder compared to adults.
12-

 For more information on the clinical presentation and course among

16

children, see Information for Pediatric Healthcare Providers.

Asymptomatic and Pre-Symptomatic Infection

Several studies have documented SARS-CoV-2 infection in patients who
never develop symptoms (asymptomatic) and in patients not yet
symptomatic (pre-symptomatic).  Since asymptomatic persons are not
13,15,17-25

routinely tested, the prevalence of asymptomatic infection and detection of

pre-symptomatic infection is not well understood. One study found that as
many as 13% of RT-PCR-confirmed cases of SARS-CoV-2 infection in children
were asymptomatic.  Another study of skilled nursing facility residents
13

infected with SARS-CoV-2 from a healthcare worker demonstrated that half

were asymptomatic or pre-symptomatic at the time of contact tracing
evaluation and testing.  Patients may have abnormalities on chest imaging
25

before the onset of symptoms.  Some data suggest that pre-symptomatic

19,20

infection tended to be detected in younger individuals and was less likely to

be associated with viral pneumonia. 19,20

Although transmission of SARS-CoV-2 from asymptomatic or pre-

symptomatic persons has been reported , risk of transmission is thought
17,21,22

to be greatest when patients are symptomatic. Viral RNA shedding,

measured indirectly by RT-PCR cycle threshold values, is greatest at the time
of symptom onset and declines over the course of several days to
weeks.  The exact degree of SARS-CoV-2 viral RNA shedding that confers
26,27

risk of transmission is not yet clear.

Clinical Course

Illness Severity

The largest cohort of >44,000 persons with COVID-19 from China showed
that illness severity can range from mild to critical : 28

 Mild to moderate (mild symptoms up to mild pneumonia): 81%

 Severe (dyspnea, hypoxia, or >50% lung involvement on imaging): 14%
 Critical (respiratory failure, shock, or multiorgan system dysfunction): 5%

In this study, all deaths occurred among patients with critical illness and the
overall case fatality rate was 2.3%.  The case fatality rate among patients with
28

critical disease was 49%.  Among children in China, illness severity was lower
28

with 94% having asymptomatic, mild or moderate disease, 5% having severe

disease, and <1% having critical disease.  Only one (<0.1%) death was
13

reported in a person <18 years old.  Among U.S. COVID-19 cases with
13
known disposition, the proportion of persons who were hospitalized was
19%.  The proportion of persons with COVID-19 admitted to the intensive
29

care unit (ICU) was 6%. 29

Clinical Progression

Among patients who developed severe disease, the medium time to dyspnea
ranged from 5 to 8 days, the median time to acute respiratory distress
syndrome (ARDS) ranged from 8 to 12 days, and the median time to ICU
admission ranged from 10 to 12 days.  Clinicians should be aware of the
5,6,10,11

potential for some patients to rapidly deteriorate one week after illness
onset. Among all hospitalized patients, a range of 26% to 32% of patients
were admitted to the ICU.  Among all patients, a range of 3% to 17%
6,8,11

developed ARDS compared to a range of 20% to 42% for hospitalized

patients and 67% to 85% for patients admitted to the ICU.  Mortality
1,4-6,8,11

among patients admitted to the ICU ranges from 39% to 72% depending on
the study.  The median length of hospitalization among survivors was 10
5,8,10,11

to 13 days. 1,6,8

Risk Factors for Severe Illness

Age is a strong risk factor for severe illness, complications, and death. 1,6,8,10,11,28-

 Among more than 44,000 confirmed cases of COVID-19 in China, the case
31

fatality rate was highest among older persons: ≥80 years: 14.8%, 70–79 years:
8.0%, 60–69 years: 3.6%, 50–59 years: 1.3%, 40–49 years: 0.4%, <40 years:
0.2%.  Early U.S. epidemiologic data suggests that the case fatality was
28,32

highest in persons aged ≥85 years (range 10%–27%), followed by 3%–11%

for ages 65–84 years, 1%–3% for ages 55–64 years, and <1% for ages 0–54
years.29

Patients with no reported underlying medical conditions had an overall case

fatality of 0.9%, but case fatality was higher for patients with comorbidities:
10.5% for those with cardiovascular disease, 7.3% for diabetes, and
approximately 6% each for chronic respiratory disease, hypertension, and
cancer.  Heart disease, hypertension, prior stroke, diabetes, chronic lung
32

disease, and chronic kidney disease have all been associated with increased
illness severity and adverse outcomes.  Accounting for differences in
1,6,10,11,28,32
age and prevalence of underlying condition, mortality associated with
COVID-19 in the United States was similar to China. 29,30,33

Medications

It has been hypothesized that angiotensin-converting enzyme (ACE)

inhibitors or angiotensin receptor blockers (ARBs) may increase the risk of
SARS-CoV-2 infection and COVID-19 severity.  ACE inhibitors and ARBs
34

increase the expression of angiotensin-converting enzyme 2 (ACE2). SARS-

CoV-2 uses the ACE2 receptor to enter into the host cell. There are no data
to suggest a link between ACE inhibitors or ARBs with worse COVID-19
outcomes. The American Heart Association (AHA), the Heart Failure Society
of America (HFSA), and the American College of Cardiology (ACC) released a
statement recommending continuation of these drugs for patients already
receiving them for heart failure, hypertension, or ischemic heart disease.35

It has also been hypothesized that non-steroidal anti-inflammatory drugs

(NSAIDs) may worsen COVID-19. There are no data suggesting an
association between COVID-19 clinical outcomes and NSAID use. More
information can be found at Healthcare Professionals: Frequently Asked
Questions and Answers.

Reinfection

There are no data concerning the possibility of reinfection with SARS-CoV-2

after recovery from COVID-19. Viral RNA shedding declines with resolution
of symptoms, and may continue for days to weeks.  However, the
11,26,27

detection of RNA during convalescence does not necessarily indicate the

presence of viable infectious virus. Clinical recovery has been correlated with
the detection of IgM and IgG antibodies which signal the development of
immunity. 36,37

Diagnostic Testing

Diagnosis of COVID-19 requires detection of SARS-CoV-2 RNA by reverse

transcription polymerase chain reaction (RT-PCR). Detection of SARS-CoV-2
viral RNA is better in nasopharynx samples compared to throat
samples.  Lower respiratory samples may have better yield than upper
27,38

respiratory samples. . SARS-CoV-2 RNA has also been detected in stool and
27,38
blood.  Detection of SARS-CoV-2 RNA in blood may be a marker of
12,26,37,39

severe illness.  Viral RNA shedding may persist over longer periods among
40

older persons and those who had severe illness requiring hospitalization.
(median range of viral shedding among hospitalized patients 12–20
days).11,26,27,36,41

Infection with both SARS-CoV-2 and with other respiratory viruses has been
reported, and detection of another respiratory pathogen does not rule out
COVID-19. 42

For more information about testing and specimen collection, handling and
storage, visit Evaluating and Testing Persons for Coronavirus Disease 2019
(COVID-19) and Frequently Asked Questions on COVID-19 Testing at
Laboratories.

Laboratory and Radiographic Findings

Laboratory Findings

Lymphopenia is the most common lab finding in COVID-19 and is found in

as many as 83% of hospitalized patients.  Lymphopenia, neutrophilia,
1,5

elevated serum alanine aminotransferase and aspartate aminotransferase

levels, elevated lactate dehydrogenase, high CRP, and high ferritin levels may
be associated with greater illness severity.  Elevated D-dimer and
1,5,6,8,11,43

lymphopenia have been associated with mortality.  Procalcitonin is typically

8,11

normal on admission, but may increase among those admitted to the ICU. 4-

6
 Patients with critical illness had high plasma levels of inflammatory makers,
suggesting potential immune dysregulation. 5,44

Radiographic Findings

Chest radiographs of patients with COVID-19 typically demonstrate bilateral

air-space consolidation, though patients may have unremarkable chest
radiographs early in the disease.  Chest CT images from patients with
1,5,45

COVID-19 typically demonstrate bilateral, peripheral ground glass

opacities.  Because this chest CT imaging pattern is non-specific and
4,8,28,45-54

overlaps with other infections, the diagnostic value of chest CT imaging for
COVID-19 may be low and dependent upon interpretations from individual
radiologists.  One study found that 56% of patients who presented within 2
46,55
days of diagnosis had a normal CT . Conversely, other studies have also
47

identified chest CT abnormalities in patients prior to the detection of SARS-

CoV-2 RNA.  Given the variability in chest imaging findings, chest
45,56

radiograph or CT alone is not recommended for the diagnosis of COVID-19.

The American College of Radiology also does not recommend CT for
screening or as a first-line test for diagnosis of COVID-19. (See American
College of Radiology Recommendationsexternal icon).

Clinical Management and Treatment

Mild to Moderate Disease

Patients with a mild clinical presentation (absence of viral pneumonia and

hypoxia) may not initially require hospitalization, and many patients will be
able to manage their illness at home. The decision to monitor a patient in
the inpatient or outpatient setting should be made on a case-by-case basis.
This decision will depend on the clinical presentation, requirement for
supportive care, potential risk factors for severe disease, and the ability of
the patients to self-isolate at home. Patients with risk factors for severe
illness (see Risk Factors for Severe Illness above) should be monitored closely
given the possible risk of progression to severe illness in the second week
after symptom onset. 5,6,10,11

For information regarding infection prevention and control

recommendations, please see Interim Infection Prevention and Control
Recommendations for Patients with Suspected or Confirmed Coronavirus
Disease 2019 (COVID-19) in Healthcare Settings.

Severe Disease

Some patients with COVID-19 will have severe disease requiring

hospitalization for management. Complications of severe COVID-19 include
pneumonia, hypoxemic respiratory failure/ARDS, sepsis and septic shock,
cardiomyopathy and arrhythmia, acute kidney injury, and complications from
prolonged hospitalization including secondary bacterial infections.  No
1,4-6,10,11,28

specific treatment for COVID-19 is currently FDA approved. Corticosteroids

have been widely used in hospitalized patients with severe illness in
China ; however, the benefit of corticosteroid use cannot be determined
6,8,10,11

based upon uncontrolled observational data. By contrast, patients with

MERS-CoV or influenza who were given corticosteroids were more likely to
have prolonged viral replication, receive mechanical ventilation, and have
higher mortality.  Therefore, corticosteroids should be avoided unless
57-61

indicated for other reasons, such as management of chronic obstructive

pulmonary disease exacerbation or septic shock. More information can be
found at Healthcare Professionals: Frequently Asked Questions and Answers.

Inpatient management of COVID-19 revolves around the supportive

management of the most common complications of severe COVID-19:
pneumonia, hypoxemic respiratory failure/ARDS, shock, multiorgan failure,
and the complications associated with prolonged hospitalization including
secondary nosocomial infection, thromboembolism, gastrointestinal
bleeding, and critical illness polyneuropathy/myopathy.

The World Health Organization and the Surviving Sepsis Campaign have
both released comprehensive guidelines for the inpatient and ICU
management of patients with COVID-19, including those who are critically ill.
For more information visit: Interim Guidance on Clinical management of
severe acute respiratory infection when novel coronavirus (nCoV) infection is
suspected (WHO)external icon and Surviving Sepsis Campaign: Guidelines on
the Management of Critically Ill Adults with Coronavirus Disease 2019
(COVID-19)pdf iconexternal icon.

For more information on the management of children, see Information for

Pediatric Healthcare Providers and the Surviving Sepsis Campaign
International Guidelines for the Management of Septic Shock and Sepsis-
Associated Organ Dysfunction in Childrenexternal icon.

Investigational Therapeutics

No FDA-approved drugs have demonstrated safety and efficacy in

randomized controlled trials for patients with COVID-19. Use of
investigational therapies for treatment of COVID-19 should ideally be done
in the context of enrollment in randomized controlled trials. Several clinical
trials are underway testing multiple drugs with in-vitro antiviral activity
against SARS-CoV-2 and/or immunomodulatory effects that may have
clinical benefit. For the latest information, see Information for Clinicians on
Therapeutic Options for COVID-19 Patients. For the information on
registered trials in the U.S., see ClinicalTrials.govexternal icon.

Discontinuation of Transmission-Based Precautions or Home Isolation

Patients who have clinically recovered and are able to discharge from the
hospital but who have not been cleared from their Transmission-Based
Precautions may continue isolation at their place of residence until cleared.
For recommendations on discontinuation of Transmission-Based Precautions
or home isolation for patients who have recovered from COVID-19 illness,
please see: Interim Guidance for Discontinuation of Transmission-Based
Precautions and Disposition of Hospitalized Patients with COVID-19, Interim
Guidance for Discontinuation of In-Home Isolation for Patients with COVID-
19, and Discontinuation of In-Home Isolation for Immunocompromised
Persons with COVID-19.

Additional resources:

 Information for Pediatric Healthcare Providers

 Evaluating and Testing Persons for Coronavirus Disease 2019 (COVID-
19)
 Frequently Asked Questions on COVID-19 Testing at Laboratories
 Healthcare Professionals: Frequently Asked Questions and Answers
 Interim Infection Prevention and Control Recommendations for Patients
with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19) or in
Healthcare Settings
 World Health Organization. Interim Guidance on Clinical management of
severe acute respiratory infection when novel coronavirus (nCoV)
infection is suspectedexternal icon
 Surviving Sepsis Campaign: Guidelines on the Management of Critically
Ill Adults with Coronavirus Disease 2019 (COVID-19) pdf iconexternal
icon
 Surviving Sepsis Campaign: International Guidelines for Management of
Sepsis and Septic Shock: 2016external icon
 Surviving Sepsis Campaign International Guidelines for the Management
of Septic Shock and Sepsis-Associated Organ Dysfunction in
Childrenexternal icon
  Diagnosis and Treatment of Adults with Community-acquired
Pneumonia. An Official Clinical Practice Guideline of the American
Thoracic Society and Infectious Diseases Society of America external icon
 ACR Recommendations for the use of Chest Radiography and Computed
Tomography (CT) for Suspected COVID-19 Infectionexternal icon

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