COVID-19: Questions and answers - UpToDate [Link]

com/contents/covid-19-questions-and-answers/print

The content on the UpToDate website is not intended nor recommended as a substitute for
medical advice, diagnosis, or treatment. Always seek the advice of your own physician or
other qualified health care professional regarding any medical questions or conditions. The
use of UpToDate content is governed by the UpToDate Terms of Use. ©2022 UpToDate, Inc.
All rights reserved.

COVID-19: Questions and answers

Written by the physician editors at UpToDate

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

Literature review current through: December 2021. | This topic last updated: January 31, 2022.

This topic provides answers to some of the most commonly asked questions by UpToDate
users. Additional content on COVID-19 is provided separately and can be accessed through the
UpToDate COVID-19 homepage or through the links provided below. (See 'Related UpToDate
content' below.)

VIROLOGY AND TRANSMISSION

How is SARS-CoV-2 (the virus that causes COVID-19) transmitted?

Direct person-to-person respiratory transmission is the primary means of transmission of severe

acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is thought to occur mainly through
close-range contact (ie, within approximately six feet or two meters) via respiratory particles;
virus released in the respiratory secretions when a person with infection coughs, sneezes, or
talks can infect another person if it is inhaled or makes direct contact with the mucous
membranes. Infection might also occur if a person's hands are contaminated by these
secretions or by touching contaminated surfaces and then they touch their eyes, nose, or
mouth, although contaminated surfaces are not thought to be a major route of transmission.

SARS-CoV-2 can also be transmitted longer distances through the airborne route (through
inhalation of particles that remain in the air over time and distance), but the extent to which this

1 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

mode of transmission has contributed to the pandemic is unclear. Scattered reports of SARS-
CoV-2 outbreaks (eg, in a restaurant, on a bus) have highlighted the potential for longer-
distance airborne transmission in enclosed, poorly ventilated spaces.

While SARS-CoV-2 RNA has been detected in non-respiratory specimens (eg, stool, blood),
neither fecal-oral nor bloodborne transmission appear to be significant sources of infection.
SARS-CoV-2 infection has been described in animals, but there is no evidence to suggest that
animals are a major source of transmission. (See "COVID-19: Epidemiology, virology, and
prevention", section on 'Transmission'.)

What is the incubation period for COVID-19?

The incubation period for COVID-19 is thought to be within 14 days following exposure, with
most cases occurring approximately three to five days after exposure. The incubation period
also varies by viral variant. For example, the incubation period for the Omicron variant
(B.1.1.159) appears to be slightly shorter than other variants, with symptoms first appearing
around three days after exposure. (See "COVID-19: Clinical features", section on 'Incubation
period'.)

What are some of the important SARS-CoV-2 variants?

Multiple SARS-CoV-2 variants are circulating globally. Some variants contain mutations in the
surface spike protein, which mediates viral attachment to human cells and is a target for natural
and vaccine-induced immunity. Thus, these variants have the potential to be more
transmissible, cause more severe disease, and/or evade natural or vaccine-induced immune
responses. Some of the more important circulating variants are:

● Alpha (B.1.1.7 lineage), also known as 20I/501Y.V1, was first identified in the United
Kingdom in late 2020. This variant is estimated to be more transmissible than wild-type
virus. Some studies suggest this variant may cause more severe illness.

● Delta (B.1.617.2 lineage), also known as 20A/S:478K, was identified in late 2020 in India.
This variant is more transmissible than B.1.1.7 and is also associated with more severe
disease.

● Omicron (B.1.1.529 lineage) was first reported from southern Africa in November 2021,
and it was promptly identified in multiple other countries. The variant contains >30
mutations in the spike protein, including mutations that have been found in other variants
of concern and that have been associated with increased transmissibility and decreased
susceptibility to neutralizing antibodies (including therapeutic monoclonal antibodies).
Emerging data suggest that Omicron has a replication advantage over the Delta variant
and evades infection- and vaccine-induced humoral immunity to a greater extent than

2 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

prior variants. The risk of severe disease with the Omicron variant is more uncertain.

These and other variants are listed in this table ( table 1) and discussed separately. (See
"COVID-19: Epidemiology, virology, and prevention", section on 'Variants of concern' and
"COVID-19: Vaccines", section on 'Efficacy against variants of concern'.)

CLINICAL PRESENTATION

What are the clinical presentation and natural history of COVID-19?

The spectrum of illness associated with COVID-19 is wide, ranging from asymptomatic infection
to life-threatening respiratory failure. When symptoms are present, they typically arise three to
five days after exposure. Most symptomatic infections are mild. Cough, myalgias, and
headache are the most commonly reported symptoms. Other features, including diarrhea, sore
throat, and smell or taste abnormalities, are also well described ( table 2).

Pneumonia, with fever, cough, dyspnea, and infiltrates on chest imaging, is the most frequent
serious manifestation of infection. Progression from dyspnea to acute respiratory distress
syndrome (ARDS) can be rapid; thus, the onset of dyspnea is generally an indication for
hospital evaluation and management.

ARDS can be associated with an exuberant inflammatory response, which is characterized by

fever, progressive hypoxia and/or hypotension, and markedly elevated inflammatory markers.
Other complications of severe illness include thromboembolic events, acute cardiac injury,
kidney injury, and inflammatory complications.

The time to recovery is highly variable and depends on age and pre-existing comorbidities in
addition to illness severity. Individuals with mild infection are expected to recover relatively
quickly (eg, within two weeks), whereas many individuals with severe disease have a longer
time to recovery (eg, two to three months). The most common persistent symptoms include
fatigue, dyspnea, chest pain, cough, and cognitive deficits.

The overall case fatality rate in unvaccinated individuals is estimated to be between 0.15 and 1
percent, although it varies widely by age and other patient characteristics. While severe and
fatal illness can occur in anyone, the risk rises with age and the presence of chronic illnesses,
including cardiovascular disease, pulmonary disease, diabetes mellitus, kidney disease, and
cancer ( table 3). (See "COVID-19: Clinical features".)

What factors are associated with severe COVID-19?

Severe illness can occur in otherwise healthy individuals of any age, but it predominantly occurs
in adults with advanced age and/or certain underlying medical comorbidities and among those

3 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

who are not vaccinated. These comorbidities and other less common comorbidities are
compiled in a table by the United States Centers for Disease Control and Prevention (CDC); the
strength of evidence informing each association varies ( table 3). (See "COVID-19: Clinical
features", section on 'Risk factors for severe illness'.)

Is COVID-19 caused by the Omicron variant less severe than infection caused other
variants?

Early data suggest that COVID-19 caused by the Omicron variant is less severe than infection
caused by prior variants. Some studies have shown a reduced risk of hospitalization, intensive
care unit admission, and in-hospital mortality. The relative mildness of disease reported in these
studies may reflect the younger age of individuals impacted at this stage of the surge or a
higher proportion of reinfections. While illness due to the Omicron may be milder, the high
volume of cases continues to lead to high hospitalization rates and may result in excess burden
on the health care system. (See "COVID-19: Epidemiology, virology, and prevention", section
on 'Omicron (B.1.1.529 lineage)'.)

COMPLICATIONS AND ASSOCIATED SYNDROMES

What are the major cardiac complications in patients with COVID-19? And how often do
they occur?

Cardiac manifestations are common in hospitalized patients and occur most frequently in
critically ill patients. The most common complications are listed here:

● Cardiac troponin elevation, which is a biomarker of myocardial injury, occurs in

approximately 10 to 35 percent of hospitalized patients. In the majority of these patients,
cardiac signs and symptoms are not present and the cause of the troponin rise is not
acute myocardial infarction (MI). However, patients with a clinical presentation (including
history or electrocardiogram) suggestive of acute MI require prompt evaluation and
treatment.

Usually, troponin elevation in COVID-19 patients is due to other causes of myocardial

injury including stress cardiomyopathy, hypoxic injury, myocarditis, right heart strain,
microvascular dysfunction, and systemic inflammatory response syndrome. For those
without suspected acute MI, further evaluation is focused on testing expected to impact
management.

The following complications may occur with or without troponin elevation:

● Arrhythmias have been reported in approximately 5 to 20 percent of hospitalized cases,

4 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

and most are asymptomatic. Causes may include hypoxia, electrolyte abnormalities,
myocardial injury, and drug effects (such as QT-prolonging agents).

● Heart failure is the most common symptomatic cardiac complication. Data on its
incidence are limited; however, its presence is associated with increased mortality. Heart
failure in patients with COVID-19 may be precipitated by acute illness in patients with pre-
existing known or undiagnosed heart disease (eg, coronary artery disease or hypertensive
heart disease) or incident acute myocardial injury (eg, stress cardiomyopathy or acute
MI).

(See "COVID-19: Evaluation and management of cardiac disease in adults" and "COVID-19:
Myocardial infarction and other coronary artery disease issues" and "COVID-19: Arrhythmias
and conduction system disease".)

What are the major thrombotic complications in patients with COVID-19?

COVID-19 is a hypercoagulable state associated with an increased risk of venous

thromboembolism (VTE; including deep vein thrombosis and pulmonary embolism) and arterial
thrombosis, including stroke, myocardial infarction, and possibly limb ischemia. The risk is
highest in individuals in the intensive care unit (ICU), often despite prophylactic anticoagulation.
Bleeding is not common but has been seen, especially in the setting of trauma and/or
anticoagulation. (See "COVID-19: Hypercoagulability", section on 'VTE'.)

What are the most common dermatologic syndromes associated with COVID-19?

The most common cutaneous findings reported in patients with COVID-19 include an
exanthematous (morbilliform) rash, pernio-like acral lesions, livedo-like lesions, retiform
purpura, necrotic vascular lesions, urticaria, vesicular (varicella-like) eruptions, and erythema
multiforme-like lesions. An erythematous, polymorphic rash has also been associated with a
related multisystem inflammatory syndrome in children. The frequency of cutaneous findings is
estimated to range from less than 1 percent to 20 percent of patients with COVID-19.

Uncertainty remains about the strength and mechanisms of associations between reported skin
findings and COVID-19. The timing of the appearance of cutaneous findings in relation to the
course of COVID-19 has varied, with reports describing skin changes occurring prior to,
concomitantly, or following symptoms of COVID-19. (See "COVID-19: Cutaneous
manifestations and issues related to dermatologic care".)

What is multisystem inflammatory syndrome associated with COVID-19?

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that has
been reported in patients with current or recent COVID-19 infection or exposure. It shares

5 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

clinical features with Kawasaki disease (KD), KD shock, and toxic shock syndrome. Clinical
features include persistent fever, severe illness with involvement of multiple organ systems, and
elevated inflammatory markers ( table 4). Most children with MIS-C have survived, although
some have required intensive care. Intravenous immune globulin is suggested in all patients
who meet criteria for MIS-C, along with glucocorticoids in those with moderate or severe
manifestations ( algorithm 1). (See "COVID-19: Multisystem inflammatory syndrome in
children (MIS-C) clinical features, evaluation, and diagnosis" and "COVID-19: Multisystem
inflammatory syndrome in children (MIS-C) management and outcome".)

A very similar syndrome has also been reported in adults in association with COVID-19
infection or exposure and is termed multisystem inflammatory syndrome in adults (MIS-A). (See
"COVID-19: Care of adult patients with systemic rheumatic disease", section on 'COVID-19 as a
risk factor for rheumatologic disease'.)

What is "long-COVID"?

"Long-COVID," also referred to as post-COVID conditions, post-COVID syndrome, or postacute

sequelae of SARS-CoV-2 infection (PASC), generally refers to symptoms that develop during or
after acute COVID-19 illness, continue for ≥2 months (ie, 3 months from symptom onset), and
are not explained by an alternative diagnosis. It is not yet known whether "long-COVID"
represents a new syndrome unique to COVID-19 or overlaps with recovery from similar
illnesses. (See "COVID-19: Evaluation and management of adults following acute viral illness",
section on 'Terminology and stages of recovery'.)

Persistent physical symptoms following acute COVID-19 are common and typically include
fatigue, dyspnea, chest pain, and cough. Headache, joint pain, dysgeusia, myalgias, and
diarrhea have also been reported. Common psychological and cognitive symptoms include poor
concentration, insomnia, anxiety, and depression. The time to symptom resolution depends
primarily on premorbid risk factors, the severity of the acute illness, and the spectrum of initial
symptoms. However, prolonged symptoms are common even in patients with less severe
disease who were never hospitalized. (See "COVID-19: Evaluation and management of adults
following acute viral illness", section on 'Expected recovery time course'.)

CLINICAL EVALUATION

Is there a way to distinguish COVID-19 clinically from other respiratory illnesses,

particularly influenza?

No, the clinical features of COVID-19 overlap substantially with influenza and other respiratory
viral illnesses. There is no way to distinguish among them without testing. (See "COVID-19:
Clinical features".)

6 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

When should patients with confirmed or suspected COVID-19 be advised to stay at

home? Have an in-person clinical evaluation?

Home management is appropriate for most patients with mild symptoms (eg, fever, cough,
and/or myalgias without dyspnea), provided they can be adequately isolated, monitored, and
supported in the outpatient setting. In addition, outpatients who have mild to moderate
symptoms and risk factors for severe disease ( table 3) are candidates for early treatment
with COVID-19-specific therapy. (See 'Are there any COVID-19-specific therapies available for
non-hospitalized patients?' below.)

Patients being managed at home should be educated about the potential for worsening disease
and advised to closely monitor for symptoms of more serious disease, including dyspnea or
persistent chest pain. The development of these symptoms should prompt clinical evaluation
and possible hospitalization. (See "COVID-19: Outpatient evaluation and management of acute
illness in adults", section on 'Determine if in-person evaluation warranted'.)

LABORATORY EVALUATION

What laboratory abnormalities are commonly seen in patients with COVID-19?

Common laboratory abnormalities among hospitalized patients with COVID-19 include:

● Lymphopenia
● Elevated aminotransaminase levels
● Elevated lactate dehydrogenase levels
● Elevated inflammatory markers (eg, ferritin, C-reactive protein, and erythrocyte
sedimentation rate)

Abnormalities in coagulation testing, elevated procalcitonin levels, and elevated troponin levels
have also been reported. The degree of these abnormalities tends to correlate with disease
severity. (See "COVID-19: Epidemiology, virology, and prevention".)

What are the major coagulation abnormalities in patients with COVID-19?

A number of laboratory abnormalities have been reported, including high fibrinogen and
D-dimer and mild prolongation of the prothrombin time (PT) and activated partial thromboplastin
time (aPTT). Abnormal coagulation studies are mainly used to monitor clinical status and to
help determine level of care. Very high D-dimer is associated with a high mortality rate. Atypical
findings (eg, severe thrombocytopenia) should be further evaluated. (See "COVID-19:
Hypercoagulability", section on 'Coagulation abnormalities'.)

7 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

DIAGNOSTIC TESTING

What are the different types of tests for COVID-19?

There are three major types of tests for COVID-19 ( table 5):

● Nucleic acid amplifications tests (NAATs; eg, reverse transcription polymerase chain
reaction [RT-PCR]) – RT-PCR for SARS-CoV-2 is the primary test used to diagnose active
COVID-19. The test is performed primarily on upper respiratory specimens (including
nasopharyngeal swabs, nasal swabs, and saliva) but can also be performed on lower
respiratory tract samples. Sensitivity and specificity are generally high, although
performance varies based on the specific assay used, specimen quality, and duration of
illness.

● Antigen tests – Antigen tests can also be used to diagnosis active infection. Antigen
tests are less sensitive than NAATs, and their performance varies by the specific antigen
test. These tests are typically performed on nasopharyngeal or nasal swabs.

● Serology – Serologic tests measure antibodies to SARS-CoV-2 and are primarily used to
identify patients who have had COVID-19 in the past as well as patients with current
infection who have had symptoms for three to four weeks. Sensitivity and specificity are
highly variable, and cross-reactivity with other coronaviruses has been reported.

Both NAATs and antigen tests can be used to screen patients in congregate settings, such as
long-term care facilities. (See "COVID-19: Diagnosis", section on 'Diagnostic approach' and
"COVID-19: Epidemiology, virology, and prevention", section on 'Screening in high-risk
settings'.)

How accurate is RT-PCR for SARS-CoV-2? Should two tests be performed or one?

A positive RT-PCR for SARS-CoV-2 generally confirms the diagnosis of COVID-19. However,
false-negative tests from upper respiratory specimens have been well documented. If initial
testing is negative, but the suspicion for COVID-19 remains, and determining the presence of
infection is important for management or infection control, we suggest repeating the test. For
hospitalized patients with evidence of lower respiratory tract involvement, the repeat test can be
performed on expectorated sputum or a tracheal aspirate, if available.

In settings where testing is not readily available, the diagnosis of COVID-19 can be made
presumptively based on a compatible clinical presentation in the setting of an exposure risk,
particularly when no other cause of the symptoms is evident. (See "COVID-19: Diagnosis",
section on 'Diagnostic approach'.)

8 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

What are the indications for testing asymptomatic individuals?

Indications for testing asymptomatic individuals include close contact with an individual with
COVID-19, screening in congregate settings (eg, long-term care facilities, correctional and
detention facilities, homeless shelters), and screening hospitalized patients in high-prevalence
regions. Screening may also be indicated prior to time-sensitive surgical procedures or aerosol-
generating procedures and prior to receiving immunosuppression. If resources allow, the United
States Centers for Disease Control and Prevention (CDC) suggests serial testing of select
groups of asymptomatic individuals (eg, residents and staff in congregate settings, workers with
public interactions or large numbers of close contacts) to help prevent transmission by quickly
identifying cases so that infected individuals can be isolated and contacts quarantined. (See
"COVID-19: Diagnosis", section on 'Whom to test'.)

Can SARS-CoV-2 variants be reliably detected by available diagnostic assays?

Thus far, yes. Most circulating SARS-CoV-2 variants have mutations in the S gene, which
encodes the viral spike protein ( table 1).

While many nucleic acid amplification tests target the S gene, they also target other genes.
Thus, if a mutation alters one gene target, the other gene targets still function and the test will
detect the virus, including the Omicron variant.

Notably, the Omicron variant contains a mutation that results in S gene target failure for some
assays. S gene failure can be used as a marker for the Omicron variant; however, it is
nonspecific and can occur with other variants, such as Alpha. Most antigen tests target
nucleocapsid protein, so mutations in the spike protein would not impact the accuracy of these
tests. While the Omicron variant does contain mutations in the gene that encodes the
nucleocapsid, antigen testing is thought to be unaffected. (See "COVID-19: Diagnosis", section
on 'Impact of SARS-CoV-2 mutations/variants on test accuracy'.)

HOME CARE

Are there any COVID-19-specific therapies available for non-hospitalized patients?

Among adult outpatients with mild to moderate COVID-19 and risk factors for progression to
severe disease ( table 3), we recommend treatment with COVID-19-specific therapy. We do
not use COVID-19-specific therapy for individuals without risk factors or in those with
asymptomatic SARS-CoV-2 infection.

We recommend nirmatrelvir-ritonavir, monoclonal antibody therapy active against circulating

variants ( table 1), or remdesivir as first-line therapies. Each treatment has been

9 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

demonstrated to substantially reduce the risk of hospitalization (and with some interventions,
mortality) in outpatients with mild to moderate COVID-19 and risk factors for progression to
severe disease. The choice between therapies depends upon local availability, ease of prompt
access to treatment (as all therapies must be given early in the course of illness), susceptibility
to prevalent viral variants, and specific patient factors (eg, comorbid conditions, potential drug-
drug interactions with nirmatrelvir-ritonavir). Additionally, monoclonal antibodies and remdesivir
are administered parenterally, which may be operationally complicated in many outpatient
settings.

If nirmatrelvir-ritonavir, monoclonal antibody therapy, and remdesivir are not feasible options,
molnupiravir is an alternative. However, it may not be as effective as the other interventions,
and there are other safety considerations.

The Omicron variant appears to escape neutralization by casirivimab-imdevimab and

bamlanivimab-etesevimab but is expected to remain susceptible to sotrovimab. We agree with
the National Institutes of Health (NIH), which recommends against the use of casirivimab-
imdevimab and bamlanivimab-etesevimab in areas where Omicron is the prevalent variant, and
these two agents are no longer authorized for use where COVID-19 infection is likely due to
nonsusceptible SARS-CoV-2 variants.

When the incidence of SARS-CoV-2 infection is high, supplies of these agents (and the
resources required to administer them) may be insufficient to offer treatment to all eligible
patients. In such circumstances, these treatments should be prioritized for individuals most
likely to benefit (ie, immunocompromised individuals who are likely to have a suboptimal
response to vaccination, and unvaccinated or incompletely vaccinated individuals with the
highest risk for progression to severe disease) ( table 6). (See "COVID-19: Outpatient
evaluation and management of acute illness in adults", section on 'Treatment with COVID-19-
specific therapies'.)

What advice should be given to patients with known or presumed COVID-19 managed at
home?

For most patients with COVID-19 who are managed at home, we advise the following:

● Supportive care with antipyretics/analgesics (eg, acetaminophen) and hydration

● Close contact with their health care provider
● Monitoring for clinical worsening, particularly the development of new or worsening
dyspnea, which should prompt clinical evaluation and possible hospitalization
● Separation from other household members, including pets (eg, staying in a separate room
when possible and wearing a mask when in the same room)
● Frequent hand washing for all family members

10 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

● Frequent disinfection of commonly touched surfaces

(See "COVID-19: Outpatient evaluation and management of acute illness in adults", section on
'Management and counseling for all outpatients'.)

How long should patients cared for at home stay isolated?

The United States Centers for Disease Control and Prevention (CDC) has issued
recommendations for discontinuing home isolation in the general community. A symptom- or
time-based strategy is preferred for most patients.

For symptomatic immunocompetent patients with mild disease who are cared for at home,
isolation can usually be discontinued when the following criteria are met:

● At least five days have passed since symptoms first appeared AND

● At least one day (24 hours) has passed since resolution of fever without the use of fever-
reducing medications AND

● There is improvement in symptoms (eg, cough, shortness of breath)

After discontinuing home isolation, patients should continue to wear a well-fitting mask around
others. The total duration of isolation plus strict masking is 10 days. During this time, patients
should avoid people who are immunocompromised or at high risk for severe disease. Additional
information on restrictions (eg, travel) after the five-day isolation period can be found on the
CDC website.

For patients who did not have symptoms at the time of laboratory-confirmed SARS-CoV-2
infection, home isolation can usually be discontinued when at least five days have passed since
the positive COVID-19 test (followed by strict mask wearing for an additional five days), as long
as there was no evidence of subsequent illness.

Although this strategy can be used for many patients, home isolation should continue for a total
of 10 days if a viral test was performed toward the end of the five-day isolation and is positive, if
strict mask wearing is not possible, or if the patient had moderate disease. In addition, this
strategy should not be used for those who had severe disease or are immunocompromised; for
such patients, the duration of isolation may need to be extended and/or testing may be needed
to confirm resolution. (See "COVID-19: Infection prevention for persons with SARS-CoV-2
infection", section on 'Discontinuation of precautions'.)

What is the significance of a persistently positive RT-PCR for weeks after illness?

Patients diagnosed with COVID-19 can have detectable SARS-CoV-2 RNA in upper respiratory
tract specimens for weeks after the onset of symptoms. However, prolonged viral RNA

11 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

detection does not necessarily indicate prolonged infectiousness. According to the CDC,
isolation of infectious virus more than 10 days after illness onset is rare in patients whose
symptoms have resolved.

There is no standardized approach to management of patients with persistently positive reverse

transcription polymerase chain reaction (RT-PCR) 10 days or more after resolution of
symptoms. However, such patients are generally felt to have low infectiousness, particularly
after mild to moderate disease and in the absence of immunocompromise. This is why
symptom- and time-based approaches for discontinuation of precautions are recommended for
most patients. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Viral
shedding and period of infectiousness'.)

HOSPITAL CARE

What is the preferred approach to oxygenation?

As a general approach, we target a peripheral oxygen saturation between 90 and 96 percent

using the lowest possible fraction of inspired oxygen. We also encourage patients to self-prone,
when possible, based on data that suggest improved oxygenation and minimal downside to
proning.

● For most patients, we use low-flow oxygen (eg, low-flow nasal cannula, simple face
mask), which minimizes risk of viral aerosolization. Because exertional desaturation is
common and can be profound, providing additional support with activity (eg, going to the
bathroom) may be needed.

● For those with acute hypoxemic respiratory failure and higher oxygen needs than low-flow
oxygen can provide, we suggest selective use of noninvasive measures rather than
routinely proceeding directly to intubation. Among the noninvasive modalities, we prefer
high-flow nasal cannula (HFNC) over noninvasive ventilation (NIV), unless there is
separate indication for NIV (eg, acute exacerbation of chronic obstructive pulmonary
disease, heart failure).

● We have a low threshold for intubation in patients who have any of the following: rapid
progression over a few hours; failure to improve despite HFNC >60 L/min and FiO2 >0.6;
development of hypercapnia; and/or hemodynamic instability or multiorgan failure.

● When mechanical ventilation is required, we use low tidal volume ventilation (LTVV)
targeting ≤6 mL/kg predicted body weight (PBW; range 4 to 8 mL/kg PBW ( table 7 and
table 8)) that targets a plateau pressure ≤30 cm H2O and applies positive end-
expiratory pressure (PEEP) as outlined in the table ( table 9).

12 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

● For patients with COVID-19 who fail LTVV, prone ventilation is the preferred next step (
table 10 and table 11).

● For those who fail LTVV and prone ventilation, rescue strategies include alveolar
recruitment maneuvers, high PEEP, neuromuscular blocking agents, inhaled pulmonary
vasodilators, and, rarely, extracorporeal membrane oxygenation.

(See "COVID-19: Respiratory care of the nonintubated hypoxemic adult (supplemental oxygen,
noninvasive ventilation, and intubation)" and "COVID-19: Management of the intubated adult".)

When are antiviral treatment, glucocorticoids, and other COVID-19-specific therapies

indicated? And which agents are preferred?

Our approach to COVID-19-specific therapy in hospitalized patients depends on the presence

of hypoxia (O2 saturation ≤94 percent on room air), need for oxygenation or ventilatory support,
and the patients’ clinical and laboratory risk factors for severe disease ( algorithm 2).

● For patients who do not require oxygen and do not have clinical ( table 3) or laboratory (
table 12) risk factors for severe disease, care is primarily supportive, with close
monitoring for disease progression.

● For patients who do not require oxygen but have clinical ( table 3) or laboratory (
table 12) risk factors for severe disease and were hospitalized for COVID-19, we
suggest remdesivir. Individuals who have risk factors but were hospitalized for other
reasons (ie, have incidental SARS-CoV-2 infection) may be eligible for therapies
authorized for high-risk outpatients (eg, monoclonal antibodies, nirmatrelvir-ritonavir,
remdesivir).

● For patients who are receiving low-flow supplemental oxygen, we suggest low-dose
dexamethasone and remdesivir. For those who have significantly elevated inflammatory
markers (eg, C-reactive protein [CRP] level ≥75 mg/L), have increasing oxygen
requirements despite dexamethasone, and are within 96 hours of hospitalization, we
suggest adding tocilizumab or baricitinib. If supplies of tocilizumab or baricitinib are
limited, we prioritize them for more severely ill patients on higher levels of oxygen support.
For immunocompromised patients, we also evaluate whether monoclonal antibody
therapy is available through an investigational new drug application.

● For hospitalized patients who are receiving high-flow supplemental oxygen or noninvasive
ventilation, we recommend low-dose dexamethasone. For those who are within 24 to 48
hours of admission to an intensive care unit (ICU) or receipt of ICU-level care (and within
96 hours of hospitalization), we suggest adding tocilizumab or baricitinib. We also suggest
adding remdesivir.

13 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

● For hospitalized patients who require mechanical ventilation or extracorporeal membrane

oxygenation, we recommend low-dose dexamethasone. For those who are within 24 to 48
hours of admission to an ICU (and within 96 hours of hospitalization), we suggest adding
tocilizumab. We suggest not routinely using remdesivir in this population.

● If dexamethasone is not available, other glucocorticoids at equivalent doses are

reasonable alternatives.

In addition to these therapies (or if individual patients cannot take these therapies), we refer
them to a clinical trial for other therapies when available. Other investigational therapies include
other antiviral agents, cytokine and kinase inhibitors, and other immunomodulatory agents.
Clinicians may also be able to obtain convalescent plasma for use outside a trial setting;
however, we suggest not using convalescent plasma for mechanically ventilated patients and
not using it outside the context of clinical trials for most other hospitalized patients because of
lack of clear benefit. We generally do not use other agents off label for treatment of COVID-19.
In particular, we suggest not using hydroxychloroquine, chloroquine, or ivermectin, given the
lack of benefit and potential for toxicity. (See "COVID-19: Management in hospitalized adults"
and "COVID-19: Management in hospitalized adults", section on 'COVID-19-specific therapy'.)

Is anticoagulation indicated in all hospitalized patients? And if so, how much?

Yes, all hospitalized patients with COVID-19 should receive at least prophylactic-dose
anticoagulation unless contraindicated ( algorithm 3).

● For thromboprophylaxis, we suggest standard prophylactic dosing rather than higher

intensity (intermediate- or full-dose) anticoagulation for most inpatients, including in the
ICU. Individuals already receiving full-dose anticoagulation for another indication should
continue it. Thromboprophylaxis is typically discontinued upon hospital discharge, with
rare exceptions.

● We have a low threshold for evaluating for venous thromboembolism (VTE; including
deep vein thrombosis, pulmonary embolism, or other sites). If VTE is documented or
strongly suspected, full-dose anticoagulation is used for at least three months.

Our approach to the evaluation and management of COVID-19 hypercoagulability is presented

in the table ( table 13) and discussed in detail separately. (See "COVID-19:
Hypercoagulability", section on 'Management'.)

OTHER MEDICATION CONSIDERATIONS

Should I use acetaminophen or NSAIDs when providing supportive care?

14 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been theorized to cause harm in patients
with COVID-19, but clinical data are limited. Given the uncertainty, we use acetaminophen as
the preferred antipyretic agent for most patients rather than NSAIDs. If NSAIDs are needed, we
use the lowest effective dose. We do not routinely discontinue NSAIDs in patients using them
for the management of chronic illnesses.

The US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the
World Health Organization (WHO) do not recommend that NSAIDs be avoided when clinically
indicated. (See "COVID-19: Management in hospitalized adults", section on 'NSAID use'.)

Do ACE inhibitors and ARBs increase the likelihood of severe COVID-19?

Patients receiving angiotensin-converting-enzyme (ACE) inhibitors or angiotensin receptor

blockers (ARBs) should continue treatment with these agents if there is no other reason for
discontinuation (eg, hypotension, acute kidney injury). Despite speculation that patients with
COVID-19 who are receiving these agents may be at increased risk for adverse outcomes,
accumulating evidence does not support an association of ACE inhibitors and ARBs with more
severe disease. In addition, stopping these agents in some patients can exacerbate comorbid
cardiovascular or kidney disease and increase mortality. (See "COVID-19: Issues related to
acute kidney injury, glomerular disease, and hypertension", section on 'Renin angiotensin
system inhibitors'.)

SPECIAL POPULATIONS

Asthma/COPD

Should patients using inhaled glucocorticoids for asthma or COPD be advised to stop
these medications to prevent COVID-19?

No, patients with asthma or chronic obstructive pulmonary disease (COPD) who need inhaled
glucocorticoids to maintain control of their asthma or COPD should continue them at their usual
dose. When indicated, inhaled steroids help to minimize risk of an asthma or COPD
exacerbation and the associated need for interaction with the health care system. There is no
good evidence that inhaled glucocorticoids increase susceptibility to COVID-19 or have an
adverse effect on the course of infection. Stopping them may worsen asthma or COPD control
and thereby increase the risk for complications of COVID-19, if acquired. (See "An overview of
asthma management", section on 'Advice related to COVID-19 pandemic' and "Stable COPD:
Overview of management", section on 'Advice related to COVID-19'.)

Should patients with COVID-19 and an acute exacerbation of asthma or COPD be

treated with systemic glucocorticoids?

15 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

Yes, patients with COVID-19 infection and a concomitant acute exacerbation of asthma or
COPD should receive prompt treatment with systemic glucocorticoids as indicated by usual
guidelines. Delaying therapy can increase the risk of a life-threatening exacerbation. While the
World Health Organization (WHO) and United States Centers for Disease Control and
Prevention (CDC) recommend glucocorticoids not be routinely used in the treatment of
COVID-19 infection, exacerbations of asthma and COPD are considered appropriate
indications for use. Overall, the known benefits of systemic glucocorticoids for exacerbations of
asthma and COPD outweigh the potential harm in COVID-19 infection. (See "An overview of
asthma management", section on 'Advice related to COVID-19 pandemic' and "Stable COPD:
Overview of management", section on 'Advice related to COVID-19'.)

Pregnancy, delivery, and breastfeeding

What special considerations are there for pregnant and breastfeeding women?

Issues related to COVID-19 during pregnancy, delivery, and the postpartum period are
discussed separately. (See "COVID-19: Pregnancy issues and antenatal care" and "COVID-19:
Labor, birth, and postpartum issues and care" and "COVID-19 and pregnancy: Questions and
answers".)

Pediatrics

What special considerations are there for children?

Specific considerations for children, including an overview of multisystem inflammatory

syndrome, are discussed separately. (See "COVID-19: Clinical manifestations and diagnosis in
children" and "COVID-19: Management in children" and "COVID-19: Multisystem inflammatory
syndrome in children (MIS-C) clinical features, evaluation, and diagnosis" and "COVID-19:
Multisystem inflammatory syndrome in children (MIS-C) management and outcome" and
"COVID-19: Return to play or strenuous activity following infection".)

Other special populations

What considerations are there for other special populations?

Issues related to the care of other special populations during the COVID-19 pandemic are
discussed separately. Refer to the UpToDate COVID-19 homepage and the topics linked below.

● (See "COVID-19: Cutaneous manifestations and issues related to dermatologic care".)

● (See "COVID-19: Considerations in patients with cancer".)
● (See "COVID-19: Care of adult patients with systemic rheumatic disease".)
● (See "COVID-19: Evaluation and management of cardiac disease in adults".)
● (See "COVID-19: Issues related to acute kidney injury, glomerular disease, and

16 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

hypertension".)
● (See "COVID-19: Issues related to diabetes mellitus in adults".)
● (See "COVID-19: Issues related to end-stage kidney disease".)
● (See "COVID-19: Issues related to gastrointestinal disease in adults".)
● (See "COVID-19: Issues related to liver disease in adults".)
● (See "COVID-19: Issues related to solid organ transplantation".)
● (See "COVID-19: Issues related to wound care and telehealth management".)
● (See "COVID-19: Management in nursing homes".)
● (See "COVID-19: Neurologic complications and management of neurologic conditions".)
● (See "COVID-19: Psychiatric illness".)

INFECTION PREVENTION

Are any medications available to prevent COVID-19 following exposure?

In the United States, the Food and Drug Administration (FDA) has issued an emergency use
authorization (EUA) to use the monoclonal antibodies casirivimab-imdevimab and
bamlanivimab-etesevimab to prevent SARS-CoV-2 infection in select individuals over 12 years
of age. However, since these combinations are not expected to retain activity against the
Omicron variant, their distribution to states or territories that have >80 percent prevalence of the
Omicron variant has been paused. Although the monoclonal antibody sotrovimab may retain
activity against Omicron, it has not been studied for post-exposure prophylaxis and should not
be used for this purpose.

Other agents (eg, hydroxychloroquine, ivermectin, tixagevimab-cilgavimab [another monoclonal

antibody combination]) have not been shown to be effective. (See "COVID-19: Epidemiology,
virology, and prevention", section on 'Post-exposure prophylaxis for select individuals'.)

What PPE is recommended for health care personnel taking care of patients with
suspected or confirmed COVID-19?

Any personnel entering the room of a patient with suspected or confirmed COVID-19,
regardless of COVID-19 vaccination status, should wear the appropriate personal protective
equipment (PPE): gown, gloves, eye protection (full face shield preferred rather than goggles or
a surgical mask with an attached eye shield), and a respirator (eg, an N95 respirator). If the
supply of respirators is severely limited, medical masks are an acceptable alternative, except
during aerosol-generating procedures (eg, tracheal intubation and extubation, tracheotomy,
bronchoscopy, noninvasive ventilation, cardiopulmonary resuscitation).

Health care personnel should be aware of the appropriate sequence of putting on ( figure 1)
and taking off ( figure 2) PPE to avoid contamination. (See "COVID-19: Infection prevention

17 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

for persons with SARS-CoV-2 infection".)

What type of room should patients with known or suspected COVID-19 be placed in?

Most hospitalized patients should be placed in a well-ventilated, single-occupancy room with a

closed door and dedicated bathroom. When this is not possible, patients with confirmed
COVID-19 can be housed together. (See "COVID-19: Infection prevention for persons with
SARS-CoV-2 infection", section on 'Type of room'.)

Patients undergoing aerosol-generating procedures (eg, tracheal intubation and extubation,

tracheotomy, bronchoscopy, noninvasive ventilation) should be placed in an airborne isolation
room (ie, a single-patient, negative-pressure room), except when these procedures are
performed in the operating room or when such rooms are unavailable. (See "COVID-19:
Infection prevention for persons with SARS-CoV-2 infection", section on 'Aerosol-generating
procedures/treatments'.)

Special considerations for patients undergoing aerosol-generating procedures in the operating

room are discussed elsewhere. (See "COVID-19: Perioperative risk assessment and anesthetic
considerations, including airway management and infection control".)

Outside of the operating room, patients with suspected or known COVID-19 should not be
placed in positive-pressure rooms. (See "COVID-19: Infection prevention for persons with
SARS-CoV-2 infection".)

Should individuals who are fully vaccinated continue to wear masks and physically
distance?

Although SARS-CoV-2 infection might still occur despite vaccination, the risk is substantially
lower. Recommendations on public health precautions following vaccination have evolved with
new developments in the pandemic (eg, emergence of the highly transmissible Delta and
Omicron variants), and the approach should be tailored to the overall rate of transmission in the
community.

In the United States, the Centers for Disease Control and Prevention (CDC) suggests that all
individuals wear masks in indoor public settings in areas where community transmission is
substantial (ie, ≥50 cases/100,000 people over the prior seven days or >8 percent positive
nucleic acid amplification test [NAAT] rate). Masks are also recommended on all forms of public
transportation, regardless of vaccination status. We also counsel immunocompromised
individuals to maintain personal preventive measures even if they have been vaccinated,
particularly when contact with unvaccinated individuals is possible, because they may have
suboptimal responses to COVID-19 vaccination. (See "COVID-19: Epidemiology, virology, and
prevention", section on 'Wearing masks in the community' and "COVID-19: Vaccines", section

18 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

on 'Post-vaccine public health precautions'.)

VACCINATION AND IMMUNITY

Immunity and vaccine efficacy

Does protective immunity develop after SARS-CoV-2 infection? Can reinfection occur?

Protective SARS-CoV-2-specific antibodies and cell-mediated responses are induced following

infection. Evidence suggests that some of these responses can be detected for at least a year
following infection. (See "COVID-19: Epidemiology, virology, and prevention", section on
'Immune responses following infection'.)

The short-term risk of reinfection (eg, within the first several months after initial infection) is low.
Several studies estimated the risk of reinfection to be <1 percent in the subsequent six months
following initial infection. The risk of reinfection may be greater with the Omicron variant. (See
"COVID-19: Epidemiology, virology, and prevention", section on 'Risk of reinfection'.)

How efficacious is vaccination at preventing symptomatic COVID-19?

Vaccine efficacy varies by type ( table 14). Based on phase III trial data:

● BNT162b2 (Pfizer-BioNTech COVID-19 vaccine) had 95 percent efficacy in preventing

symptomatic COVID-19 at or after day 7 following completion of a two-dose series. (See
"COVID-19: Vaccines", section on 'BNT162b2 (Pfizer-BioNTech COVID-19 vaccine)'.)

● mRNA-1273 (Moderna COVID-19 vaccine) had 95 percent efficacy in preventing

symptomatic COVID-19 at or after day 7 following completion of a two-dose series. (See
"COVID-19: Vaccines", section on 'mRNA-1273 (Moderna COVID-19 vaccine)'.)

● Ad26.COV2.S (Janssen/Johnson & Johnson COVID-19 vaccine) had 66 percent efficacy

against moderate to severe COVID-19 and 85 percent efficacy against severe COVID-19
at or after 28 days following administration of a single dose. (See "COVID-19: Vaccines",
section on 'Ad26.COV2.S (Janssen/Johnson & Johnson COVID-19 vaccine)'.)

● ChAdOx1 nCoV-19/AZD1222 (AstraZeneca COVID-19 vaccine) had 70 percent efficacy in

preventing symptomatic COVID-19 at or after two weeks following completion of a two-
dose series. (See "COVID-19: Vaccines", section on 'ChAdOx1 nCoV-19/AZD1222
(University of Oxford, AstraZeneca, and the Serum Institute of India)'.)

Subsequent data suggest that immunity may wane over time and varies for viral variants;
mRNA vaccines may be slightly more effective at preventing severe disease than other vaccine

19 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

types. (See "COVID-19: Vaccines", section on 'Immunogenicity, efficacy, and safety of select
vaccines'.)

Available data and the efficacy of other vaccines types are discussed separately. (See
"COVID-19: Vaccines", section on 'Immunogenicity, efficacy, and safety of select vaccines'.)

How effective is vaccination against the Delta and Omicron variants?

Vaccine effectiveness against Delta is reduced against overall infection but largely retained
against severe disease. Preliminary evidence suggests reduced vaccine effectiveness,
particularly against overall infection, with Omicron ( table 1). (See "COVID-19: Vaccines",
section on 'Efficacy against variants of concern'.)

Have breakthrough infections been reported following vaccination?

Yes, breakthrough infection after vaccination has been reported but occurs much less frequently
than infection in unvaccinated individuals, and a high proportion of breakthrough infections may
be asymptomatic.

While the overall risk of breakthrough infections is higher for the Delta and Omicron variants,
the risk of severe breakthrough infection with the Delta variant remains low. Preliminary
evidence suggests the same for Omicron, particularly among those who received a booster
vaccine. (See "COVID-19: Vaccines", section on 'Breakthrough infections after vaccination'.)

Vaccine availability and indications for vaccination

Which vaccines are currently available in the United States? Worldwide?

In the United States, these vaccines are available:

● BNT162b2 (Pfizer-BioNTech COVID-19 vaccine)

● mRNA-1273 (Moderna COVID-19 vaccine)
● Ad26.COV2.S (Janssen/Johnson & Johnson COVID-19 vaccine)

BNT162b2 and mRNA-1273 are mRNA vaccines and are delivered in lipid nanoparticles. Once
injected and taken up into muscle cells, the mRNA expresses the SARS-CoV-2 surface spike
protein. Spike protein mediates viral attachment to human cells ( figure 3). Expression of the
spike protein induces binding and neutralizing antibody responses. (See "COVID-19: Vaccines",
section on 'BNT162b2 (Pfizer-BioNTech COVID-19 vaccine)' and "COVID-19: Vaccines",
section on 'mRNA-1273 (Moderna COVID-19 vaccine)'.)

Ad26.COV2.S is based on a replication-incompetent adenovirus 26 vector that expresses a

stabilized spike protein. (See "COVID-19: Vaccines".)

20 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

Outside of the United States, vaccine availability varies regionally. One of the most widely
available vaccines is ChAdOx1 nCoV-19/AZD1222 (University of Oxford, AstraZeneca, and the
Serum Institute of India vaccines), an adenovirus vector-based DNA vaccine that also
expresses the surface spike protein. (See "COVID-19: Vaccines", section on 'Other countries'.)

Numerous additional vaccine candidates are being evaluated for prevention of COVID-19,
including nucleic acid-based (mRNA and DNA) vaccines, viral-vector vaccines, and inactivated
or recombinant protein vaccines ( figure 4 and table 14). (See "COVID-19: Vaccines".)

Available vaccines and vaccine candidates are also catalogued on the World Health
Organization website.

What are the indications and contraindications to vaccination?

For patients in the United States, we recommend vaccination with BNT162b2 (Pfizer-BioNTech
COVID-19 vaccine), mRNA-1273 (Moderna COVID-19 vaccine), or Ad26.COV2.S
(Janssen/Johnson & Johnson COVID-19 vaccine).

● Individuals ≥5 years old are eligible for BNT162b2.

● Individuals ≥18 years old are eligible for mRNA-1273 and Ad26.COV2.S.

If availability is not an issue, we suggest one of the mRNA vaccines (BNT162b2 or

mRNA-1273) rather than Ad26.COV2.S.

Contraindications to these vaccines are:

● For the mRNA COVID-19 vaccines:

• A history of a severe allergic reaction, such as anaphylaxis, after a previous dose of an

mRNA COVID-19 vaccine or to any of its components (including polyethylene glycol).

• An immediate allergic reaction of any severity (including hives) to a previous dose of

an mRNA COVID-19 vaccine, to any of its components, or to polysorbate (with which
there can be cross-reactive hypersensitivity to polyethylene glycol). Such individuals
should not receive an mRNA COVID-19 vaccine unless they have been evaluated by
an allergy expert who determines that it can be given safely.

Components of the mRNA COVID-19 vaccines are listed on the United States Centers for
Disease Control and Prevention (CDC) website.

The United States Advisory Committee on Immunization Practices lists history of severe
allergic reaction to any other vaccine or injectable therapy (that does not share the same
components as the mRNA COVID-19 vaccines) as a precaution, but not contraindication,
to mRNA COVID-19 vaccination.

21 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

● For Ad26.COV2.S:

• A history of a severe allergic reaction, such as anaphylaxis, to the vaccine or any of its
components.

• A history of thrombosis with thrombocytopenia following an Ad26.COV2.S or any other

adenoviral vector COVID-19 vaccine.

Individuals with a precaution to vaccination, as well as any individual with a history of

anaphylaxis that does not result in a contraindication to vaccination, should be monitored for 30
minutes after vaccination. All other recipients should be monitored for 15 minutes. (See
"COVID-19: Vaccines", section on 'Indications and vaccine selection' and "COVID-19:
Vaccines", section on 'Contraindications and precautions (including allergies)'.)

Are vaccine recommendations different for immunocompromised patients?

The United States Advisory Committee on Immunizations Practices (ACIP) recommends that
patients with certain moderate to severe immunocompromising conditions receive three mRNA
vaccine doses as part of the primary series rather than two doses. Immunocompromising
conditions that warrant the third dose include active chemotherapy for cancer, hematologic
malignancies, hematopoietic cell transplantation (HCT) or solid organ transplantation, advanced
or untreated HIV infection with a CD4 count <200 cell/microL, moderate or severe primary
immunodeficiency disorder, and use of immunosuppressive medications (eg, mycophenolate
mofetil, rituximab, prednisone >20 mg/day for >14 days) ( table 15). For those who received
COVID-19 vaccination prior to HCT or CAR-T cell therapy, the CDC recommends repeat
vaccination with a full primary series at least three months after the transplant or CAR-T
administration. Such patients meet criteria for receiving a three-dose primary series with the
mRNA vaccines.

The third dose should be given at least 28 days after the second dose. Individuals >5 years of
age are eligible for BNT162b2 (Pfizer-BioNTech COVID-19 vaccine), and individuals >18 years
of age are eligible for mRNA-1273 (Moderna COVID-19 vaccine). Immunocompromised
individuals who received three doses of a primary mRNA vaccine series may also receive a
booster dose five months later. Patients who received Ad26.COV2.S (Janssen/Johnson &
Johnson COVID-19 vaccine) should receive a booster vaccine dose after the primary series.
(See "COVID-19: Vaccines", section on 'Immunocompromised individuals'.)

Who is eligible for a booster dose? And when should it be administered?

Because of the possibility of waning immunity and decreased efficacy against variants that
might escape the immune response directed against spike proteins targeted by the original
vaccines, several countries have initiated or announced plans to administer a booster vaccine

22 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

for individuals who have been fully vaccinated. (See "COVID-19: Vaccines".)

In the United States, the Food and Drug Administration (FDA) has authorized and the CDC
recommends a booster dose be given for individuals 12 years of age or older.

● For those who previously received BNT162b2 [Pfizer COVID-19 vaccine]), the CDC
recommends a booster dose at least five months after completion of the primary series.

● For those who previously received mRNA-1273 (Moderna COVID-19 vaccine), the CDC
recommends a booster dose at least five months after completion of the primary series.

● For those who previously received Ad26.COV2.S (Janssen/Johnson & Johnson

COVID-19 vaccine), the CDC recommends a booster dose at least two months after
completion of the primary series.

Any one of the vaccines can be given as a booster dose. However, we prefer one of the mRNA
vaccines. (See "COVID-19: Vaccines", section on 'Role of booster vaccinations/waning efficacy'
and "COVID-19: Vaccines", section on 'Mixing vaccine types'.)

Booster doses following a primary vaccine series are a distinct issue from administering a third
dose of an mRNA vaccine for the primary series in certain immunocompromised patients. (See
"COVID-19: Vaccines", section on 'Immunocompromised individuals'.)

Adverse effects

What adverse effects are associated with vaccination?

The more common adverse effects for all vaccine types include local injection site reactions,
fever, headache, fatigue, chills, myalgias, and arthralgias ( table 14). These reactions are
more common in younger individuals and after the second dose (when a two-dose series is
given).

Anaphylaxis is a rare adverse event reported following receipt of mRNA vaccines. Most cases
evaluated to date have been determined not to be caused by IgE-mediated reactions, and
some patients have successfully received the second dose of the same vaccine without
incident. Patients with apparent anaphylaxis to a first dose of an mRNA vaccine should be
referred to an allergy specialist if possible. Alternatively, a non-mRNA vaccine could be given in
place of the second dose of mRNA vaccine, followed by 30 minutes of observation. (See
"COVID-19: Allergic reactions to SARS-CoV-2 vaccines".)

The potential associations between thromboembolism and ChAdOx1 nCoV-19/AZD1222

(AstraZeneca COVID-19 vaccine) and Ad26.COV2.S (Janssen/Johnson & Johnson COVID-19
vaccine) are discussed below and in detail in the UpToDate text. (See "COVID-19: Vaccines",

23 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

section on 'Thrombosis with thrombocytopenia' and "COVID-19: Vaccine-induced immune

thrombotic thrombocytopenia (VITT)".)

There are rare reports of myocarditis and pericarditis following receipt of the mRNA vaccines,
BNT162b2 (Pfizer vaccine) and mRNA-1273 (Moderna vaccine), though not following receipt of
Ad26.COV2.S (Janssen/Johnson & Johnson vaccine). Most reported cases were mild and
occurred more commonly in males and in adolescents and young adults. Onset was generally
within the first week after vaccine receipt, more commonly after the second dose. (See
"COVID-19: Vaccines", section on 'Myocarditis'.)

There is also a possible association between Ad26.COV2.S (Janssen/Johnson & Johnson

vaccine) and Guillain-Barre syndrome. (See "COVID-19: Vaccines", section on 'Guillain-Barre
syndrome'.)

A detailed list of adverse event rates and how they vary by vaccine type and patient age can be
found on the CDC website. (See "COVID-19: Vaccines", section on 'Approach to vaccination'
and "COVID-19: Allergic reactions to SARS-CoV-2 vaccines", section on 'mRNA vaccines'.)

How does the risk-benefit ratio for COVID-19 vaccination differ in children?

The individual benefit of COVID-19 vaccination in young children may be somewhat less than in
adults because COVID-19 tends to be less severe in children than in adults.

Nevertheless, there are several compelling reasons to vaccinate children, including the
potential to reduce risk of the following:

● Multisystem inflammatory syndrome in children (MIS-C) following acute COVID-19

● Other potential sequelae (eg, "long COVID-19" and indirect effects on mental health and
education)
● Severe disease in children with underlying medical conditions
● Acute COVID-19 of any severity

Furthermore, even with the lower risk of severe disease among children, the number of
COVID-19 deaths among those 5 to 11 years old from 2020 to 2021 exceeds the prevaccination
era mortality rates of infections for which childhood vaccines are routinely provided (eg,
rotavirus, meningococcal disease, varicella).

The risks of vaccination in children are less clearly defined than in adults and adolescents.
Concern about the risk of myocarditis in children has been raised because of the association of
mRNA COVID-19 vaccines with myocarditis, particularly in adolescents and young adults. While
the precise risk of vaccine-associated myocarditis among 5- to 11-year-olds is unknown, based
on the historical age distribution of myocarditis in the pre-COVID-19 era, it is expected to be

24 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

lower than that among adolescents and young adults, which is already low. In addition, most
myocarditis cases following receipt of a COVID-19 mRNA vaccine are mild and short lived. The
benefits of COVID-19 vaccination in children are estimated to exceed this risk.

Given the hypothesis that MIS-C is associated with immune dysregulation precipitated by
SARS-CoV-2 infection, similar immune-related side effects following vaccination in children are
another concern. Vaccine trials in this age group have not identified a potential signal, although
rare case reports of MIS in adults following vaccination highlight the importance of monitoring
for this possible adverse effect. (See "COVID-19: Vaccines", section on 'Children'.)

Are COVID-19 vaccines associated with thrombotic complications? If so, which

vaccines?

Extremely rare cases of thrombotic events (eg, deep vein thrombosis, pulmonary embolism,
arterial thrombosis, cerebral venous sinus thrombosis) associated with thrombocytopenia have
been reported 5 to 30 days following vaccination with ChAdOx1 nCoV-19/AZD1222
(AstraZeneca COVID-19 vaccine) and Ad26.COV2.S (Janssen/Johnson & Johnson COVID-19
vaccine), a syndrome referred to as vaccine-induced immune thrombotic thrombocytopenia
(VITT). The mechanism is similar to autoimmune heparin-induced thrombocytopenia (HIT).
There are no known risk factors; individuals with risk factors for or a history of venous or arterial
thromboembolism do not appear to be at increased risk for VITT.

The features suggestive of VITT are summarized in the table and diagnostic algorithm (
table 16 and algorithm 4). (See "COVID-19: Vaccine-induced immune thrombotic
thrombocytopenia (VITT)".)

Because of the rarity of VITT and the potential severity of COVID-19, the overall benefit of
vaccination outweighs the risk of VITT for most individuals. Nevertheless, several countries
have suspended use of ChAdOx1 nCoV-19/AZD1222 pending additional data, and some are
limiting it to individuals over a certain age. (See "COVID-19: Vaccines", section on 'Thrombosis
with thrombocytopenia'.)

Can analgesics or antipyretics be taken for side effects following vaccination?

Analgesics or antipyretics (eg, nonsteroidal anti-inflammatory drugs [NSAIDs] or

acetaminophen) can be taken for local or systemic side effects following vaccination. However,
pre-emptive use of these agents prior to vaccination is not recommended because of the
uncertain impact on immune response to the vaccine. (See "COVID-19: Vaccines", section on
'Expected adverse effects and their management'.)

Vaccine administration

25 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

Can other vaccines be given with COVID-19 vaccine?

Although there are no data regarding safety and efficacy when COVID-19 vaccines are
coadministered with other vaccines, the CDC has stated that COVID-19 vaccines can be
administered at any time in relation to other non-COVID-19 vaccines, and if needed, can be
administered on the same day as other vaccines. It is unknown if local and systemic side effects
are more frequent or more intense with coadministration on the same day, but this will be
monitored. The Advisory Committee on Immunization Practices (ACIP) had previously
suggested that non-COVID-19 vaccines not be administered within 14 days of COVID-19
vaccination, but the recommendation was revised because of concerns of resulting delays in
vaccination. The updated approach was also influenced by experience with other vaccines that
suggests that coadministration does not compromise safety or immunogenicity. (See
"COVID-19: Vaccines", section on 'Timing with relation to non-COVID-19 vaccines'.)

What if the second dose of an mRNA vaccine cannot be given because of a prior
reaction?

For individuals who received a first dose of an mRNA vaccine but cannot receive either mRNA
vaccine for the second dose (eg, because of contraindications), Ad26.COV2.S
(Janssen/Johnson & Johnson COVID-19 vaccine) can be given as long as there is not also a
contraindication to Ad26.COV2.S.

The CDC suggests giving Ad26.COV2.S at least 28 days after the mRNA vaccine dose. Such
individuals should be considered to have received a complete AD26.COV2.S vaccine regimen.
(See "COVID-19: Vaccines", section on 'Administration'.)

Should people who have had SARS-CoV-2 infection be vaccinated? If so, when? What if
a patient acquires COVID-19 after the first dose?

Yes, most individuals with a history of SARS-CoV-2 infection should be vaccinated. However,
for individuals who had SARS-CoV-2 infection complicated by multisystem inflammatory
syndrome (MIS), the decision to vaccinate should weigh the risk of exposure, reinfection, and
severe disease with infection against the uncertain safety of vaccination in such individuals.
Given the hypothesis that MIS is associated with immune dysregulation precipitated by SARS-
CoV-2 infection, it is unknown if a SARS-CoV-2 vaccine could trigger a similar dysregulated
response.

In general, vaccination can be given as soon as the individual has recovered from acute
infection (if symptomatic) and meets criteria for discontinuation of isolation precautions. Pre-
vaccination serologic screening is not recommended. If infection is diagnosed after receipt of
the first vaccine of a two-dose series (eg, with the mRNA COVID-19 vaccines), the second dose
should still be given.

26 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

Delaying vaccination for 90 days from the time of infection is also reasonable; the risk of
reinfection during this time period is low, and delaying vaccination allows other people to
receive the vaccination sooner. Delaying vaccination for 90 days is also suggested for
individuals who were treated with monoclonal antibodies or convalescent plasma. (See
"COVID-19: Vaccines", section on 'History of SARS-CoV-2 infection'.)

When administering a third dose of an mRNA vaccine to eligible individuals as part of

the primary series, should the same vaccine type as the initial two doses be used?

Yes, the same mRNA vaccine type should be used when possible. For example, individuals
who received mRNA-1273 (Moderna COVID-19 vaccine) for their first two doses should receive
mRNA-1273 for their third dose. If the initial vaccine formulation is not available or not known,
either mRNA COVID-19 vaccine type can be given. (See "COVID-19: Vaccines", section on
'Immunocompromised individuals' and "COVID-19: Vaccines", section on 'Mixing vaccine
types'.)

BLOOD DONATION

What should I tell patients about donating blood or plasma during the pandemic?

Blood donation is particularly important during the pandemic due to concerns that the supply
could become critically low. Having a history of COVID-19 is not an exclusion to donation as
long as the illness resolved at least 14 days prior to donation. (See "Blood donor screening:
Medical history", section on 'COVID-19 pandemic considerations'.)

Vaccination for COVID-19 is also not a contraindication to blood donation. Individuals who have
received an mRNA vaccine or other noninfectious vaccine (nonreplicating, inactivated) can
donate immediately; those who have received a live-attenuated viral vaccine (or who are
unsure if they have) should refrain from donating blood for a short waiting period (eg, 14 days)
after receiving the vaccine.

Most blood donation facilities are no longer collecting convalescent plasma. (See "COVID-19:
Convalescent plasma and hyperimmune globulin".)

REFERENCES

Supporting references can be found in the linked UpToDate topics.

RELATED UPTODATE CONTENT

27 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

Additional UpToDate content on COVID-19 is linked to below and can also be found through the
COVID-19 homepage.

● (See "COVID-19 and pregnancy: Questions and answers".)

● (See "COVID-19: Epidemiology, virology, and prevention".)
● (See "COVID-19: Clinical features".)
● (See "COVID-19: Diagnosis".)
● (See "COVID-19: Management in hospitalized adults".)
● (See "COVID-19: Management in nursing homes".)
● (See "COVID-19: Outpatient evaluation and management of acute illness in adults".)
● (See "COVID-19: Vaccines".)
● (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)
● (See "COVID-19: General approach to infection prevention in the health care setting".)
● (See "COVID-19: Occupational health issues for health care personnel".)
● (See "COVID-19: Management of the intubated adult".)
● (See "COVID-19: Intensive care ventilation with anesthesia machines".)
● (See "COVID-19: Extracorporeal membrane oxygenation (ECMO)".)
● (See "COVID-19: Issues related to diabetes mellitus in adults".)
● (See "COVID-19: Issues related to acute kidney injury, glomerular disease, and
hypertension".)
● (See "COVID-19: Issues related to liver disease in adults".)
● (See "COVID-19: Issues related to solid organ transplantation".)
● (See "COVID-19: Issues related to gastrointestinal disease in adults".)
● (See "COVID-19: Issues related to wound care and telehealth management".)
● (See "COVID-19: Pregnancy issues and antenatal care".)
● (See "COVID-19: Arrhythmias and conduction system disease".)
● (See "COVID-19: Myocardial infarction and other coronary artery disease issues".)
● (See "COVID-19: Evaluation and management of cardiac disease in adults".)
● (See "COVID-19: Perioperative risk assessment and anesthetic considerations, including
airway management and infection control".)
● (See "COVID-19: Hypercoagulability".)
● (See "COVID-19: Convalescent plasma and hyperimmune globulin".)
● (See "COVID-19: Considerations in patients with cancer".)
● (See "COVID-19: Gastrointestinal symptoms and complications".)
● (See "COVID-19: Psychiatric illness".)
● (See "COVID-19: Neurologic complications and management of neurologic conditions".)
● (See "COVID-19: Care of adult patients with systemic rheumatic disease".)
● (See "COVID-19: Cutaneous manifestations and issues related to dermatologic care".)
● (See "COVID-19: Acute limb ischemia".)

28 of 29 2/2/2022, 9:57 PM
COVID-19: Questions and answers - UpToDate [Link]

● (See "COVID-19: Clinical manifestations and diagnosis in children".)

● (See "COVID-19: Management in children".)
● (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical
features, evaluation, and diagnosis".)
● (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) management
and outcome".)
● (See "COVID-19: Return to play or strenuous activity following infection".)

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately.

● (See "Society guideline links: COVID-19 – Index of guideline topics".)

COVID-19 content for patient education is also provided separately.

● (See "Patient education: COVID-19 overview (The Basics)".)

● (See "Patient education: COVID-19 vaccines (The Basics)".)
● (See "Patient education: COVID-19 and children (The Basics)".)
● (See "Patient education: COVID-19 and pregnancy (The Basics)".)
● (See "Patient education: Recovery after COVID-19 (The Basics)".)

EDITORIAL PROCESS

This topic is written by the doctors and editors at UpToDate based upon content in the linked
UpToDate topics. Contributor disclosures can be found in the linked topics. All topics are
updated as new evidence becomes available and our peer review process is complete.

Topic 127454 Version 191.0

29 of 29 2/2/2022, 9:57 PM