COVID-19 - Clinical Features - UpToDate

9/8/2021 COVID-19: Clinical features - UpToDate
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COVID-19: Clinical features

Author: Kenneth McIntosh, MD
Section Editor: Martin S Hirsch, MD
Deputy Editor: Allyson Bloom, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2021. | This topic last updated: Jun 10, 2021.
INTRODUCTION
Coronaviruses are important human and animal pathogens. At the end of 2019, a novel coronavirus was identified as the cause of a
cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China. It rapidly spread, resulting in an epidemic throughout China,
followed by an increasing number of cases in other countries throughout the world. In February 2020, the World Health Organization
designated the disease COVID-19, which stands for coronavirus disease 2019 [1]. The virus that causes COVID-19 is designated severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2); previously, it was referred to as 2019-nCoV.
Understanding of COVID-19 is evolving. Interim guidance has been issued by the World Health Organization and by the United States
Centers for Disease Control and Prevention [2,3]. Links to these and other related society guidelines are found elsewhere. (See 'Society
guideline links' below.)
This topic will discuss the clinical features of COVID-19. The epidemiology, virology, prevention, and diagnosis of COVID-19 are discussed
elsewhere. (See "COVID-19: Epidemiology, virology, and prevention" and "COVID-19: Diagnosis".)
The management of COVID-19 is also discussed in detail elsewhere:
● (See "COVID-19: Outpatient evaluation and management of acute illness in adults".)

● (See "COVID-19: Management in hospitalized adults".)
● (See "COVID-19: Infection control for persons with SARS-CoV-2 infection".)
(Related Pathway(s): COVID-19: Initial telephone triage of adult outpatients.)
Issues related to COVID-19 in pregnant women and children are discussed elsewhere:
● (See "COVID-19: Pregnancy issues and antenatal care".)

● (See "COVID-19: Clinical manifestations and diagnosis in children" and "COVID-19: Multisystem inflammatory syndrome in children
(MIS-C) clinical features, evaluation, and diagnosis".)
See specific topic reviews for details on complications of COVID-19 and issues related to COVID-19 in other patient populations.
Common cold coronaviruses, severe acute respiratory syndrome (SARS) coronavirus, and Middle East respiratory syndrome (MERS)
coronavirus are discussed separately. (See "Coronaviruses" and "Severe acute respiratory syndrome (SARS)" and "Middle East respiratory
syndrome coronavirus: Virology, pathogenesis, and epidemiology".)
ASYMPTOMATIC INFECTIONS
Asymptomatic infections have been well documented [4-12]. One review estimated that 33 percent of people with SARS-CoV-2 infection
never develop symptoms [13]. This estimate was based on four large population-based, cross-sectional surveys, among which the median
proportion of individuals who had no symptoms at the time of a positive test was 46 percent (range 43 to 77 percent), and on 14
longitudinal studies, among which a median of 73 percent of initially asymptomatic individuals remained so on follow-up. However, there
is still uncertainty around the proportion of asymptomatic infections, with a wide range reported across studies. Additionally, the
definition of "asymptomatic" may vary across studies, depending on which specific symptoms were assessed. The range of findings in
studies evaluating asymptomatic infections is reflected in the following examples:
● In a COVID-19 outbreak on a cruise ship where nearly all passengers and staff were screened for severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), approximately 19 percent of the population on board tested positive; 58 percent of the 712 confirmed
COVID-19 cases were asymptomatic at the time of diagnosis [14,15]. In studies of subsets of those asymptomatic individuals, who
were hospitalized and monitored, approximately 77 to 89 percent remained asymptomatic over time [15,16].
● In a smaller COVID-19 outbreak within a skilled nursing facility, 27 of the 48 residents (56 percent) who had a positive screening test
were asymptomatic at the time of diagnosis, but 24 of them developed symptoms over the next seven days [17].
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● Other studies, particularly those conducted among younger populations, have reported even higher proportions of infections that
are asymptomatic [10,18-22]. As an example, in an outbreak on an aircraft carrier, a quarter of the crew, among whom the mean age
was 27 years, tested positive for SARS-CoV-2 [21]. Among the 1271 cases, only 22 percent were symptomatic at the time of testing
and 43 percent remained asymptomatic throughout the observation period. High rates of asymptomatic infection have also been
reported among pregnant women presenting for delivery [10,19].
Patients with asymptomatic infection may have objective clinical abnormalities [9,23]. As an example, in a study of 24 patients with
asymptomatic infection who all underwent chest computed tomography (CT), 50 percent had typical ground-glass opacities or patchy
shadowing, and another 20 percent had atypical imaging abnormalities [23]. Five patients developed low-grade fever, with or without
other typical symptoms, a few days after diagnosis. In another study of 55 patients with asymptomatic infection identified through
contact tracing, 67 percent had CT evidence of pneumonia on admission; only two patients developed hypoxia, and all recovered [9].
As above, some individuals who are asymptomatic at the time of diagnosis go on to develop symptoms (ie, they were actually
presymptomatic). In one study, symptom onset occurred a median of four days (range of three to seven) after the initial positive RT-PCR
test [15].
The risk of transmission from patients with asymptomatic infection is discussed elsewhere. (See "COVID-19: Epidemiology, virology, and
prevention", section on 'Viral shedding and period of infectiousness'.)
SEVERITY OF SYMPTOMATIC INFECTION
Spectrum of severity and fatality rates
● Spectrum of infection severity – The spectrum of symptomatic infection ranges from mild to critical; most infections are not severe
[4,24-29]. Specifically, in a report from the Chinese Center for Disease Control and Prevention that included approximately 44,500
confirmed infections with an estimation of disease severity [30]:
• Mild disease (no or mild pneumonia) was reported in 81 percent.
• Severe disease (eg, with dyspnea, hypoxia, or >50 percent lung involvement on imaging within 24 to 48 hours) was reported in 14
percent.
• Critical disease (eg, with respiratory failure, shock, or multiorgan dysfunction) was reported in 5 percent.
• The overall case fatality rate was 2.3 percent; no deaths were reported among noncritical cases.
Similarly, in a report of 1.3 million cases reported to the United States Centers for Disease Control and Prevention (CDC) through the
end of May 2020, 14 percent were hospitalized, 2 percent were admitted to the intensive care unit (ICU), and 5 percent died [31]. The
risk of severe illness varied by age and underlying comorbidities. (See 'Risk factors for severe illness' below.)
● Infection fatality rates – The case fatality rate only indicates the mortality rate among documented cases. Since many severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are asymptomatic and many mild infections do not get diagnosed, the
infection fatality rate (ie, the estimated mortality rate among all individuals with infection) is considerably lower and has been
estimated in some analyses to be between 0.15 and 1 percent, with substantial heterogeneity by location and across risk groups [32-
35]. In a systematic review and meta-analysis of 27 studies from resource-rich settings that calculated the total number of community
infections through seroprevalence surveys or comprehensive tracing programs up to September 2020, the infection fatality rate was
estimated to increase exponentially by age (0.002 percent at age 10, 0.01 percent at age 25, 0.4 percent at age 55, 1.4 percent at age
65, 4.6 percent at age 75, 15 percent at age 85, and >25 percent at age ≥90 years) [36]. These age-related differences appeared to
account for most of the geographic variability in reported infection fatality rates (ie, locations with a higher median population age
reported higher fatality rates). Nevertheless, given the challenges in accurately assessing overall infection rates and deaths, there is a
high level of uncertainty with these estimates.
● Fatality rates among hospitalized patients – Among hospitalized patients, the risk of critical or fatal disease is high [37-43]. In a
study from early in the pandemic that included 2741 patients who were hospitalized for COVID-19 in a New York City health care
system, 665 patients (24 percent) died or were discharged to hospice [40]. Of the 647 patients who received invasive mechanical
ventilation, 60 percent died, 13 percent were still ventilated, and 16 percent were discharged by the end of the study. The in-hospital
fatality rate associated with COVID-19 has been higher than that for influenza [44-46]. As an example, in an analysis of hospital data
from the United States Veterans Health Administration, patients with COVID-19 were five times more likely to die during the
hospitalization than patients with influenza (21 versus 3.8 percent) [44].
Over the course of the pandemic, declining in-hospital fatality rates have been reported [47-50]. As an example, in a retrospective
study of a national surveillance database in England that included over 21,000 critical care patients with COVID-19, ICU survival
improved from 58 percent in late March 2020 to 80 percent by June 2020 [47]. The reasons for this observation are uncertain, but

potential explanations include improvements in hospital care of COVID-19 and better allocation of resources when hospitals were not
overburdened.
In resource-limited settings, in-hospital mortality rates may be higher than those reported elsewhere. As an example, in a study from
10 countries in Africa, where there was a median of two intensive care specialists in each hospital and a minority of facilities did not
have pulse oximetry, the in-hospital 30-day mortality rate following critical care admission was 48 percent [51]. Mortality was
associated with underlying comorbidities as well as resource shortages.
● Excess deaths during the pandemic – Neither the case fatality rate nor the infection fatality rate account for the full burden of the
pandemic, which includes excess mortality from other conditions because of delayed care, overburdened health care systems, and
social determinants of health [52,53].
Risk factors for severe illness — Severe illness can occur in otherwise healthy individuals of any age, but it predominantly occurs in
adults with advanced age or certain underlying medical comorbidities. Specific demographic features and laboratory abnormalities have
also been associated with severe disease. These are discussed in detail in the sections that follow.
Several prediction tools have been proposed to identify patients who are more likely to have severe illness based on epidemiologic,
clinical, and laboratory features; however, most of the studies evaluating these tools are limited by risk of bias, and none has been
prospectively evaluated or validated for clinical management [54].
Increasing age — Individuals of any age can acquire SARS-CoV-2 infection, although adults of middle age and older are most
commonly affected, and older adults are more likely to have severe disease.
In several cohorts of hospitalized patients with confirmed COVID-19, the median age ranged from 49 to 56 years [25-27]. In a report from
the Chinese Center for Disease Control and Prevention that included approximately 44,500 confirmed infections, 87 percent of patients
were between 30 and 79 years old [30]. Similarly, in a modeling study based on data from mainland China, the hospitalization rate for
COVID-19 increased with age, with a 1 percent rate for those 20 to 29 years old, 4 percent rate for those 50 to 59 years old, and 18 percent
for those older than 80 years [55].
Older age is also associated with increased mortality [30,37,56,57]. In a report from the Chinese Center for Disease Control and
Prevention, case fatality rates were 8 and 15 percent among those aged 70 to 79 years and 80 years or older, respectively, in contrast to
the 2.3 percent case fatality rate among the entire cohort [30]. In an analysis from the United Kingdom, the risk of death among
individuals 80 years and older was 20-fold that among individuals 50 to 59 years old [57].
In the United States, 2449 patients diagnosed with COVID-19 between February 12 and March 16, 2020, had age, hospitalization, and ICU
information available [58]; 67 percent of cases were diagnosed in those aged ≥45 years, and, similar to findings from China, mortality was
highest among older individuals, with 80 percent of deaths occurring in those aged ≥65 years. In contrast, individuals aged 18 to 34 years
accounted for only 5 percent of adults hospitalized for COVID-19 in a large health care database study and had a mortality rate of 2.7
percent; morbid obesity, hypertension, and male sex were associated with mortality in that age group [59].
Symptomatic infection in children and adolescents appears to be relatively uncommon; when it occurs, it is usually mild, although a small
proportion (eg, <2 percent) experience severe and even fatal disease. Details of COVID-19 in children are discussed elsewhere. (See
"COVID-19: Clinical manifestations and diagnosis in children", section on 'Frequency of severe disease in children'.)
Comorbidities — Comorbidities and other conditions that have been associated with severe illness and mortality include [30,40,57,59-
62]:
● Cardiovascular disease
● Diabetes mellitus
● Chronic obstructive pulmonary disease and other lung diseases
● Cancer (in particular hematologic malignancies, lung cancer, and metastatic disease) [63]
● Chronic kidney disease
● Solid organ or hematopoietic stem cell transplantation
● Obesity [64-66]
● Smoking [67]
The United States CDC has created a list of certain comorbidities that have been associated with severe disease (defined as infection
resulting in hospitalization, admission to the ICU, intubation or mechanical ventilation, or death) and notes that the strength of evidence
informing the associations varies [68]. These comorbidities are outlined in the table ( table 1).
In a report of 355 patients who died with COVID-19 in Italy, the mean number of pre-existing comorbidities was 2.7, and only 3 patients
had no underlying condition [56].

Among patients with advanced age and medical comorbidities, COVID-19 is frequently severe. For example, in a SARS-CoV-2 outbreak
across several long-term care facilities in Washington state, the median age of the 101 facility residents affected was 83 years, and 94
percent had a chronic underlying condition; the hospitalization and preliminary case fatality rates were 55 and 34 percent, respectively
[69]. In an analysis of nearly 300,000 confirmed COVID-19 cases reported in the United States, the mortality rate was 12 times as high
among patients with reported co-morbidities compared with those with none [31].
Socioeconomic background and sex — Certain demographic features have also been associated with more severe illness.
Males have comprised a disproportionately high number of critical cases and deaths in multiple cohorts worldwide [37,40,56,70-72].
Black, Hispanic, and South Asian individuals comprise a disproportionately high number of infections and deaths due to COVID-19 in the
United States and United Kingdom, likely related to underlying disparities in the social determinants of health [57,73-77]. Some analyses
that have controlled for comorbidities and socioeconomic status have not found an association between African-American origin or
Hispanic ethnicity and adverse COVID-19 outcomes in hospitalized patients [78,79].
Laboratory abnormalities — Particular laboratory features have also been associated with worse outcomes ( table 2). These
include [60,80-83]:
• Lymphopenia
• Thrombocytopenia
• Elevated liver enzymes
• Elevated lactate dehydrogenase (LDH)
• Elevated inflammatory markers (eg, C-reactive protein [CRP], ferritin) and inflammatory cytokines (ie, interleukin 6 [IL-6] and
tumor necrosis factor [TNF]-alpha)
• Elevated D-dimer (>1 mcg/mL)
• Elevated prothrombin time (PT)
• Elevated troponin
• Elevated creatine phosphokinase (CPK)
• Acute kidney injury
As an example, in one study, progressive decline in the lymphocyte count and rise in the D-dimer over time were observed in
nonsurvivors compared with more stable levels in survivors [27].
Deficiencies in certain micronutrients, in particular vitamin D [84,85], have been associated with more severe disease in observational
studies, but multiple confounders likely impact the observed associations. There is also no high-quality evidence that reversing
micronutrient deficiencies with supplementation improves COVID-19 outcomes.
Viral factors — Patients with severe disease have also been reported to have higher viral RNA levels in respiratory specimens than
those with milder disease [86,87], although some studies have found no association between respiratory viral RNA levels and disease
severity [88,89]. Detection of viral RNA in the blood has been associated with severe disease, including organ damage (eg, lung, heart,
kidney), coagulopathy, and mortality [90-92].
Genetic factors — Host genetic factors are also being evaluated for associations with severe disease [93,94].
As an example, one genome-wide association study identified a relationship between polymorphisms in the genes encoding the ABO
blood group and respiratory failure from COVID-19 (type A associated with a higher risk) [93]. Type O has been associated with a lower
risk of both infection and severe disease [95]. (See "Red blood cell antigens and antibodies", section on 'Disease predisposition (including
COVID-19)'.)
CLINICAL MANIFESTATIONS
Incubation period — The incubation period for COVID-19 is generally within 14 days following exposure, with most cases occurring
approximately four to five days after exposure [4,96,97].
In a study of 1099 patients with confirmed symptomatic COVID-19, the median incubation period was four days (interquartile range two
to seven days) [97]. Using data from 181 confirmed cases in China with identifiable exposure, one modeling study estimated that
symptoms would develop in 2.5 percent of infected individuals within 2.2 days and in 97.5 percent of infected individuals within 11.5 days
[98]. The median incubation period in this study was 5.1 days.
However, determinations of the incubation period can be imprecise and may differ by the method of assessing exposure and the specific
calculations used for the estimate. Another study estimated incubation period using data from 1084 patients who had traveled or resided
in Wuhan and were subsequently diagnosed with COVID-19 after leaving Wuhan [99]. This study suggested a longer median incubation
period of 7.8 days, with 5 to 10 percent of individuals developing symptoms 14 days or more after exposure.

Initial presentation — Among patients with symptomatic COVID-19, 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 3).
Pneumonia is the most frequent serious manifestation of infection, characterized primarily by fever, cough, dyspnea, and bilateral
infiltrates on chest imaging [25-27,97]. Although some clinical features (in particular smell or taste disorders) are more common with
COVID-19 than with other viral respiratory infections [100], there are no specific symptoms or signs that can reliably distinguish COVID-19
[101]. However, development of dyspnea approximately one week after the onset of initial symptoms may be suggestive of COVID-19.
(See 'Acute course and complications' below.)
The range of associated symptoms was illustrated in a report of over 370,000 confirmed COVID-19 cases with known symptom status
reported to the CDC in the United States [31]:
● Cough in 50 percent
● Fever (subjective or >100.4°F/38°C) in 43 percent
● Myalgia in 36 percent
● Headache in 34 percent
● Dyspnea in 29 percent
● Sore throat in 20 percent
● Diarrhea in 19 percent
● Nausea/vomiting in 12 percent
● Loss of smell or taste, abdominal pain, and rhinorrhea in fewer than 10 percent each
Other cohort studies of patients with confirmed COVID-19 have reported a similar range of clinical findings [25,27,102-105]. Notably, fever
is not a universal finding on presentation, even among hospitalized cohorts. In one study, fever was reported in almost all patients, but
approximately 20 percent had a very low grade fever <100.4°F/38°C [25]. In another study of 1099 patients from Wuhan and other areas
in China, fever (defined as an axillary temperature over 99.5°F/37.5°C) was present in only 44 percent on admission but was ultimately
noted in 89 percent during the hospitalization [97]. In a study of over 5000 patients who were hospitalized with COVID-19 in New York,
only 31 percent had a temperature >100.4°F/38°C at presentation [37].
In some studies, smell and taste disorders (eg, anosmia and dysgeusia) have been more frequently reported [106-110]. In a meta-analysis
of observational studies, the pooled prevalence estimates for smell or taste abnormalities were 52 and 44 percent, respectively (although
rates ranged from 5 to 98 percent across studies) [109]. In one survey of 202 outpatients with mild COVID-19 in Italy, 64 percent reported
alterations in smell or taste, and 24 percent reported very severe alterations; smell or taste changes were reported as the only symptom
in 3 percent overall and preceded symptoms in another 12 percent [111]. However, the rate of objective smell or taste anomalies may be
lower than the self-reported rates. In another study, 38 percent of the 86 patients who reported total lack of smell at the time of
evaluation had a normal smell function on objective testing [112]. Most subjective smell and taste disorders associated with COVID-19 do
not appear to be permanent; in a follow-up survey of the 202 patients in Italy with COVID-19, 89 percent of those who noted smell or
taste alterations reported resolution or improvement by four weeks [113].
Although not noted in the majority of patients, gastrointestinal symptoms (eg, nausea and diarrhea) may be the presenting complaint in
some patients [25,27,104,114]. In a systematic review of studies reporting on gastrointestinal symptoms in patients with confirmed
COVID-19, the pooled prevalence was 18 percent overall, with diarrhea, nausea/vomiting, or abdominal pain reported in 13, 10, and 9
percent, respectively [115].
Conjunctivitis has also been described [116,117]. Nonspecific signs and symptoms, such as falls, general health decline, and delirium,
have been described in older adults, particularly those over 80 years old and those with underlying neurocognitive impairments [118].
Dermatologic findings in patients with COVID-19 are not well characterized. There have been reports of maculopapular, urticarial, and
vesicular eruptions and transient livedo reticularis [119-121]. Reddish-purple nodules on the distal digits similar in appearance to pernio
(chilblains) have also been described, mainly in children and young adults with documented or suspected COVID-19, although an
association has not been clearly established [121-124]. Some are calling this finding "COVID toes." (See "COVID-19: Cutaneous
manifestations and issues related to dermatologic care", section on 'Cutaneous manifestations of COVID-19'.)
Acute course and complications — As above, symptomatic infection can range from mild to critical. (See 'Spectrum of severity and
fatality rates' above.)
Some patients with initially nonsevere symptoms may progress over the course of a week [125]. In one study of 138 patients hospitalized
in Wuhan for pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), dyspnea developed after a median of five
days since the onset of symptoms, and hospital admission occurred after a median of seven days of symptoms [27]. In another study, the
median time to dyspnea was eight days [25].
Several complications of COVID-19 have been described:

● Respiratory failure – Acute respiratory distress syndrome (ARDS) is the major complication in patients with severe disease and can
manifest shortly after the onset of dyspnea. In the study of 138 patients described above, ARDS developed in 20 percent a median of
eight days after the onset of symptoms; mechanical ventilation was implemented in 12.3 percent [27]. In large studies from the
United States, 12 to 24 percent of hospitalized patients have required mechanical ventilation [37,40]. (See "COVID-19: Epidemiology,
clinical features, and prognosis of the critically ill adult", section on 'Clinical features in critically ill patients'.)
● Cardiac and cardiovascular complications – Other complications have included arrhythmias, myocardial injury, heart failure, and
shock, as discussed in detail elsewhere [27,70,126,127]. (See "COVID-19: Cardiac manifestations in adults", section on 'Spectrum of
clinical presentations'.)
● Thromboembolic complications – Venous thromboembolism (VTE), including extensive deep vein thrombosis (DVT) and pulmonary
embolism (PE), is common in severely ill patients with COVID-19, particularly among patients in the intensive care unit (ICU), among
whom reported rates have ranged from 10 to 40 percent [128-131]. Arterial thrombotic events, including acute stroke (even in
patients younger than 50 years of age without risk factors) and limb ischemia, have also been reported [132-135]. These are
discussed in detail elsewhere. (See "COVID-19: Hypercoagulability", section on 'Clinical features' and "COVID-19: Neurologic
complications and management of neurologic conditions", section on 'Cerebrovascular disease' and "COVID-19: Acute limb
ischemia".)
● Neurologic complications – Encephalopathy is a common complication of COVID-19, particularly among critically ill patients; as an
example, in one series of hospitalized patients, encephalopathy was reported in one-third [136]. Stroke, movement disorders, motor
and sensory deficits, ataxia, and seizures occur less frequently. (See "COVID-19: Neurologic complications and management of
neurologic conditions".)
● Inflammatory complications – Some patients with severe COVID-19 have laboratory evidence of an exuberant inflammatory
response, with persistent fevers, elevated inflammatory markers (eg, D-dimer, ferritin), and elevated proinflammatory cytokines;
these laboratory abnormalities have been associated with critical and fatal illnesses [25,137,138]. Although these features had been
likened to cytokine release syndrome (eg, in response to T cell immunotherapy), the levels of proinflammatory cytokines in COVID-19
are substantially lower than those seen with cytokine release syndrome as well as with sepsis [139]. (See 'Risk factors for severe
illness' above.)
Other inflammatory complications and auto-antibody-mediated manifestations have been described [140,141]. Guillain-Barré
syndrome may occur, with onset 5 to 10 days after initial symptoms [142]. A multisystem inflammatory syndrome with clinical
features similar to those of Kawasaki disease and toxic shock syndrome has also been described in children with COVID-19 ( table 4
). In the rare adults in whom it has been reported, this syndrome has been characterized by markedly elevated inflammatory markers
and multiorgan dysfunction (in particular cardiac dysfunction), but minimal pulmonary involvement [143]. These are discussed in
detail elsewhere. (See "COVID-19: Neurologic complications and management of neurologic conditions", section on 'Guillain-Barré
syndrome' and "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis" and
"COVID-19: Care of adult patients with systemic rheumatic disease", section on 'COVID-19 as a risk factor for rheumatologic disease'.)
● Secondary infections – Secondary infections do not appear to be common complications of COVID-19 overall [144-146]. In a review
of nine studies, mainly from China, the reported rate of bacterial or fungal coinfections was 8 percent (in 62 of 806); these included
mainly respiratory infections and bacteremia [144]. Several reports have described presumptive invasive aspergillosis among
immunocompetent patients with ARDS from COVID-19, although the frequency of this complication is uncertain [147-150]. In one
prospective study of 108 patients on mechanical ventilation for COVID-19 in Italy, probable aspergillosis was diagnosed in 30 (28
percent) based on elevated serum or bronchoalveolar lavage (BAL) galactomannan levels, growth of Aspergillus on BAL cultures, or a
cavitary infiltrate without other cause [150]. Cases of mucormycosis in patients with acute and recent COVID-19 have been reported
in India; the incidence is uncertain, but some reports suggest that nearly 15,000 cases had occurred by the end of May 2021 [151]. In
a retrospective study from 16 health care centers in India, there were 187 cases of mucormycosis among approximately 12,000
patients hospitalized with COVID-19 between September and December 2020 (prevalence 0.27 percent overall and 1.6 percent among
ICU patients); most cases involved the rhino-orbital region [152]. In this study and published case reports, diabetes mellitus and
glucocorticoid receipt have been common risk factors [153-155]. The diagnosis and management of mucormycosis are discussed in
detail elsewhere. (See "Mucormycosis (zygomycosis)".)
Autopsy studies have noted detectable SARS-CoV-2 RNA (and, in some cases, antigen) in the kidneys, liver, heart, brain, and blood in
addition to respiratory tract specimens, suggesting that the virus disseminates systemically in some cases; whether direct viral cytopathic
effects at these sites contribute to the complications observed is uncertain [156-159].
Recovery and long-term sequelae — The time to recovery from COVID-19 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 ( table 5). Data also suggest the potential for ongoing

respiratory impairment [160-163] and cardiac sequelae [164,165]. These issues are discussed in detail elsewhere. (See "COVID-19:
Evaluation and management of adults following acute viral illness", section on 'COVID-19 recovery'.)
Some patients who have recovered from COVID-19 have persistently or recurrently positive nucleic acid amplification tests (NAATs) for
SARS-CoV-2. Although recurrent infection or reinfection cannot be definitively ruled out in these settings, evidence suggests that these
are unlikely. This is discussed elsewhere. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Immune responses
following infection'.)
LABORATORY FINDINGS
Common laboratory findings 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), and abnormalities in coagulation tests [27,97,104].
Lymphopenia is especially common, even though the total white blood cell count can vary [25-27,166]. As an example, in a series of 393
adult patients hospitalized with COVID-19 in New York City, 90 percent had a lymphocyte count <1500/microL; leukocytosis
(>10,000/microL) and leukopenia (<4000/microL) were each reported in approximately 15 percent [104].
On admission, many patients with pneumonia have normal serum procalcitonin levels; however, in those requiring ICU care, they are
more likely to be elevated [25-27].
Several laboratory features, including high D-dimer levels and more severe lymphopenia, have been associated with critical illness or
mortality [26]. These are discussed elsewhere. (See 'Risk factors for severe illness' above and "COVID-19: Epidemiology, clinical features,
and prognosis of the critically ill adult", section on 'Rate and risk of progression to critical illness'.)
Abnormalities in coagulation testing are also discussed in detail elsewhere. (See "COVID-19: Hypercoagulability", section on 'Coagulation
abnormalities'.)
IMAGING FINDINGS
Chest radiographs — Chest radiographs may be normal in early or mild disease. In a retrospective study of 64 patients in Hong Kong
with documented COVID-19, 20 percent did not have any abnormalities on chest radiograph at any point during the illness [167].
Common abnormal radiograph findings were consolidation and ground-glass opacities, with bilateral, peripheral, and lower lung zone
distributions; lung involvement increased over the course of illness, with a peak in severity at 10 to 12 days after symptom onset.
Spontaneous pneumothorax has also been described, although it is relatively uncommon [168,169]. In a retrospective review of over
70,000 patients with COVID-19 evaluated in emergency departments throughout Spain, spontaneous pneumothorax was identified in 40
patients (0.56 percent) [169].
Chest CT — Although chest computed tomography (CT) may be more sensitive than chest radiograph and some chest CT findings may be
characteristic of COVID-19, no finding can completely rule in or rule out the possibility of COVID-19. In the United States, the American
College of Radiology (ACR) recommends not using chest CT for screening or diagnosis of COVID-19 and recommends reserving it for
hospitalized patients when needed for management [170]. If CT is performed, the Radiological Society of North America has categorized
features as typical, indeterminate, or atypical for COVID-19, and has suggested corresponding language for the interpretation report (
table 6) [171].
Chest CT in patients with COVID-19 most commonly demonstrates ground-glass opacification with or without consolidative abnormalities,
consistent with viral pneumonia ( image 1) [103,172,173]. As an example, in a systematic review of studies evaluating the chest CT
findings in over 2700 patients with COVID-19, the following abnormalities were noted [174]:
● Ground-glass opacifications – 83 percent

● Ground-glass opacifications with mixed consolidation – 58 percent
● Adjacent pleural thickening – 52 percent
● Interlobular septal thickening – 48 percent
● Air bronchograms – 46 percent
Other less common findings were a crazy paving pattern (ground-glass opacifications with superimposed septal thickening),
bronchiectasis, pleural effusion, pericardial effusion, and lymphadenopathy.
Chest CT abnormalities in COVID-19 are often bilateral, have a peripheral distribution, and involve the lower lobes.
Although these findings are common in COVID-19, they are not unique to it and are frequently seen with other viral pneumonias (
image 2) [175,176]. In a study of 1014 patients in Wuhan who underwent both RT-PCR testing and chest CT for evaluation of COVID-19,
a "positive" chest CT for COVID-19 (as determined by a consensus of two radiologists) had a sensitivity of 97 percent, using the PCR tests
as a reference; however, specificity was only 25 percent [177]. The low specificity may be related to other etiologies causing similar CT
findings. In another study comparing chest CTs from 219 patients with COVID-19 in China and 205 patients with other causes of viral
pneumonia in the United States, COVID-19 cases were more likely to have a peripheral distribution (80 versus 57 percent), ground-glass
opacities (91 versus 68 percent), fine reticular opacities (56 versus 22 percent), vascular thickening (59 versus 22 percent), and reverse
halo sign (11 versus 1 percent), but less likely to have a central and peripheral distribution (14 versus 35 percent), air bronchogram (14
versus 23 percent), pleural thickening (15 versus 33 percent), pleural effusion (4 versus 39 percent), and lymphadenopathy (2.7 versus 10
percent) [178].
As with chest radiographs, chest CT may be normal soon after the onset of symptoms, with abnormalities more likely to develop over the
course of illness [102,179]. However, chest CT abnormalities have also been identified in patients prior to the development of symptoms
and even prior to the detection of viral RNA from upper respiratory specimens [103,180].
Among patients who clinically improve, resolution of radiographic abnormalities may lag behind improvements in fever and hypoxia
[181].
Lung ultrasound — Point-of-care lung ultrasonography has been described for evaluation of lung involvement in patients with suspected
COVID-19 when other imaging resources are not readily available. Findings on lung ultrasound in patients with documented COVID-19
have included thickening, discontinuation, and interruption of the pleural line; B lines visible under the pleura that appear discrete,
multifocal, or confluent; patchy, strip, and nodular consolidations; and air bronchogram signs in the consolidations [182-184]. Although
ultrasound appears to be relatively sensitive for the diagnosis of COVID-19, some studies have reported low specificity. In a systematic
review of five studies, the pooled sensitivity and specificity were 86 and 55 percent, respectively [185].
SPECIAL POPULATIONS
Pregnant and breastfeeding women — The general approach to prevention, evaluation, diagnosis, and treatment of pregnant women
with suspected COVID-19 is largely similar to that in nonpregnant individuals. Issues specific to pregnant and breastfeeding women are
discussed elsewhere. (See "COVID-19: Pregnancy issues and antenatal care".)
Children — Symptomatic infection in children appears to be relatively uncommon; when it occurs, it is usually mild, although severe
cases have been reported [186-189]. Details of COVID-19 in children are discussed elsewhere. (See "COVID-19: Clinical manifestations and
diagnosis in children".)
People with HIV — The impact of HIV infection on the natural history of COVID-19 is uncertain. The clinical features appear the same as
in the general population. In several large observational studies, HIV infection has been associated with more severe COVID-19, higher
rates of hospitalization, and in some cases, higher mortality from COVID-19 [190-193]. As an example, in a multicenter cohort study from
Spain, the age- and sex-adjusted mortality rate of patients with HIV and COVID-19 was 3.7 per 10,000 people compared with 2.1 per
10,000 for the general Spanish population [190]. COVID-19 outcomes in patients with HIV had been largely similar to those seen in the
general population in smaller cohort studies [194-198].
Many of the comorbid conditions associated with severe COVID-19 (eg, cardiovascular disease) occur frequently among persons with HIV
[199,200], and it is unclear whether these or other potential confounding features, rather than HIV infection itself, contribute to the risk.
Low CD4 cell count may be associated with critical illness and death in patients with HIV and COVID-19 [201].
Issues specific to the management of patients with HIV and COVID-19 are discussed elsewhere. (See "COVID-19: Management in
hospitalized adults", section on 'People with HIV'.)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately.
(See "Society guideline links: COVID-19 – Index of guideline topics".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are
written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about
a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond
the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade
reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients.
(You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: COVID-19 overview (The Basics)" and "Patient education: COVID-19 and pregnancy (The Basics)"
and "Patient education: COVID-19 and children (The Basics)" and "Patient education: COVID-19 vaccines (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Asymptomatic infection – The clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection ranges
from asymptomatic infection to critical and fatal illness. The proportion of infections that are asymptomatic is uncertain, as the
definition of "asymptomatic" varies across studies and longitudinal follow-up to identify those who ultimately develop symptoms is
often not performed. Nevertheless, some estimates suggest that up to 40 percent of infections are asymptomatic. (See
'Asymptomatic infections' above.)
● Risk of severe disease – Most symptomatic infections are mild. Severe disease (eg, with hypoxia and pneumonia) has been reported
in 15 to 20 percent of symptomatic infections; it can occur in otherwise healthy individuals of any age, but predominantly occurs in
adults with advanced age or certain underlying medical comorbidities ( table 1). In North America and Europe, Black, Hispanic, and
South Asian individuals are also more likely to have severe disease, likely related to underlying disparities in the social determinants
of health. (See 'Severity of symptomatic infection' above.)
● Incubation period – The incubation period from the time of exposure until the onset of symptoms is four to five days on average,
but may be as long as 14 days. (See 'Incubation period' above.)
● Initial presentation – 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 3). Pneumonia, with fever, cough, dyspnea,
and infiltrates on chest imaging, is the most frequent serious manifestation of infection. There are no specific clinical features that
can yet reliably distinguish COVID-19 from other viral respiratory infections. (See 'Initial presentation' above.)
Certain laboratory features, such as lymphopenia, elevated D-dimer, and elevated inflammatory markers have been associated with
severe COVID-19 ( table 2). (See 'Laboratory abnormalities' above.)
● Complications – Acute respiratory distress syndrome (ARDS) is the major complication in patients with severe disease and can
manifest shortly after the onset of dyspnea. Other complications of severe illness include thromboembolic events, acute cardiac
injury, kidney injury, and inflammatory complications. (See 'Acute course and complications' above and "COVID-19:
Hypercoagulability" and "COVID-19: Evaluation and management of cardiac disease in adults" and "COVID-19: Multisystem
inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis" and "COVID-19: Epidemiology, clinical
features, and prognosis of the critically ill adult", section on 'Clinical features in critically ill patients'.)
Persistent symptoms following acute COVID-19 are discussed in detail elsewhere. (See "COVID-19: Evaluation and management of
adults following acute viral illness", section on 'COVID-19 recovery'.)
● Clinical suspicion – The possibility of COVID-19 should be considered primarily in patients with compatible symptoms ( table 3), in
particular fever and/or respiratory tract symptoms, who reside in or have traveled to areas with community transmission or who have
had recent close contact with a confirmed or suspected individual with COVID-19. All symptomatic patients with suspected SARS-CoV-
2 infection should undergo testing. Testing for and diagnosis of COVID-19 are discussed in detail elsewhere. (See "COVID-19:
Diagnosis", section on 'Diagnostic approach'.)
When COVID-19 is suspected, infection control measures should be implemented. Infection control in the home and in health care
settings is discussed in detail elsewhere. (See "COVID-19: Infection control for persons with SARS-CoV-2 infection", section on
'Infection control in the health care setting'.)
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 128323 Version 35.0

GRAPHICS
Comorbidities the CDC classifies as risk factors for severe COVID-19* [1,2]
1. Established and probable risk factors (comorbidities that have been associated with severe COVID-19 in at least 1 meta-analysis or systematic review [starred conditions], or in observational
studies)
Cancer*
Cerebrovascular disease*
Children with certain underlying conditions ¶
Chronic kidney disease*
COPD* and other lung disease (including interstitial lung disease, pulmonary fibrosis, pulmonary hypertension)
Diabetes mellitus, type 1* and type 2*
Down syndrome
Heart conditions (such as heart failure, coronary artery disease, or cardiomyopathies)*
HIV
Neurologic conditions, including dementia
Obesity* (BMI ≥30 kg/m 2) and overweight (BMI 25 to 29 kg/m 2)
Pregnancy*
Smoking* (current and former)
Sickle cell disease
Solid organ or blood stem cell transplantation
Substance use disorders
Use of corticosteroids or other immunosuppressive medications
2. Possible risk factors (supported by mostly case series, case reports, or, if other study design, the sample size is small)
Cystic fibrosis
Thalassemia
3. Possible risk factors but evidence is mixed (comorbidities have been associated with severe COVID-19 in at least 1 meta-analysis or systematic review, but other studies had reached
different conclusions)
Asthma
Hypertension
Immune deficiencies
Liver disease
COVID-19: coronavirus disease 2019; CDC: Centers for Disease Control and Prevention; COPD: chronic obstructive pulmonary disease; BMI: body mass index.
* These comorbidities are associated with severe COVID-19 in adults of all ages. Risk of severe disease also rises steadily with age, with more than 80% of deaths occurring in adults older than age 65.
People of color are also at increased risk of severe disease and death, often at a younger age, due to systemic health and social inequities.
¶ Underlying medical conditions are also associated with severe illness in children, but evidence implicating specific conditions is limited. Children with the following conditions might be at increased
risk for severe illness: medical complexity; genetic, neurologic, or metabolic conditions; congenital heart disease; obesity; diabetes; asthma or other chronic lung disease; sickle cell disease;
immunosuppression.
References:
1. Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: Information for healthcare providers. Available at:
https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html (Accessed on April 5, 2021).
2. Centers for Disease Control and Prevention. Science brief: Evidence used to update the list of underlying medical conditions that increase a person's risk of severe illness from COVID-19. Available at:
https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlying-evidence-table.html (Accessed on April 5, 2021).
Graphic 127477 Version 8.0

Laboratory features associated with severe COVID-19 [1-6]
Abnormality Possible threshold
Elevations in:
D-dimer >1000 ng/mL (normal range: <500 ng/mL)
CRP >100 mg/L (normal range: <8.0 mg/L)
LDH >245 units/L (normal range: 110 to 210 units/L)
Troponin >2× the upper limit of normal (normal range for troponin T high sensitivity: females 0 to 9 ng/L; males 0 to 14 ng/L)
Ferritin >500 mcg/L (normal range: females 10 to 200 mcg/L; males 30 to 300 mcg/L)
CPK >2× the upper limit of normal (normal range: 40 to 150 units/L)
Decrease in:
Absolute lymphocyte count <800/microL (normal range for age ≥21 years: 1800 to 7700/microL)
Although these laboratory features are associated with severe disease in patients with COVID-19, they have not been clearly demonstrated to have prognostic value. We use the
thresholds listed above to identify patients who may be at risk for severe disease; they are extrapolated from published cohort data and individualized to the reference values used at our
laboratory. However, the specific thresholds are not well established and may not be applicable if laboratories use other reference values.
COVID-19: coronavirus disease 2019; CRP: C-reactive protein; LDH: lactate dehydrogenase; CPK: creatine phosphokinase.
References:
1. Guan WY, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020.
2. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395:497.
3. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395:1054.
4. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020.
5. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72,314 cases from the Chinese Center for Disease
Control and Prevention. JAMA 2020.
6. Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020.

Symptoms associated with coronavirus disease 2019 (COVID-19) [1]
Symptoms that may be seen in patients with COVID-19
Cough
Fever
Myalgias
Headache
Dyspnea (new or worsening over baseline)
Sore throat
Diarrhea
Nausea/vomiting
Anosmia or other smell abnormalities
Ageusia or other taste abnormalities
Rhinorrhea and/or nasal congestion
Chills/rigors
Fatigue
Confusion
Chest pain or pressure
Most patients with confirmed COVID-19 have fever and/or symptoms of acute respiratory illness. However, various other symptoms have been associated with COVID-19; this list is not
inclusive of all reported symptoms. These symptoms are also not specific for COVID-19, and the predictive value of a single symptom in the diagnosis of COVID-19 is uncertain.
COVID-19: coronavirus disease 2019.
Reference:
1. Centers for Disease Control and Prevention. Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19). Available at: https://www.cdc.gov/coronavirus/2019-
ncov/hcp/clinical-guidance-management-patients.html.

Clinical manifestations of COVID-19-associated multisystem inflammatory syndrome in children and adolescents
Frequency * (%)
Presenting symptoms
Persistent fevers (median duration 4 to 6 days) 100
Gastrointestinal symptoms (abdominal pain, vomiting, diarrhea) 60 to 100
Rash 45 to 76
Conjunctivitis 30 to 81
Mucous membrane involvement 27 to 76
Neurocognitive symptoms (headache, lethargy, confusion) 29 to 58
Respiratory symptoms (tachypnea, labored breathing) 21 to 65
Sore throat 10 to 16
Myalgias 8 to 17
Swollen hands/feet 9 to 16
Lymphadenopathy 6 to 16
Clinical findings
Shock 32 to 76
Criteria for complete Kawasaki disease met 22 to 64
Myocardial dysfunction (by echocardiogram or elevated troponin/BNP) 51 to 90
Arrhythmia 12
Acute respiratory failure requiring noninvasive or invasive ventilation 28 to 52
Acute kidney injury 8 to 52
Serositis (small pleural, pericardial, and ascitic effusions) 24 to 57
Hepatitis or hepatomegaly 5 to 21
Encephalopathy, seizures, coma, or meningoencephalitis 6 to 7
Laboratory findings
Abnormal blood cell counts
Lymphocytopenia 80 to 95
Neutrophilia 68 to 90
Mild anemia 70
Thrombocytopenia 31 to 80
Elevated inflammatory markers
C-reactive protein 90 to 100
Erythrocyte sedimentation rate 75 to 80
D-dimer 67 to 100
Fibrinogen 80 to 100
Ferritin 55 to 76
Procalcitonin 80 to 95
Interleukin-6 80 to 100
Elevated cardiac markers
Troponin 50 to 90
BNP or NT-pro-BNP 73 to 90
Hypoalbuminemia 48 to 95
Mildly elevated liver enzymes 62 to 70
Elevated lactate dehydrogenase 10 to 60
Hypertriglyceridemia 70
Imaging findings
Echocardiogram
Depressed LV function 31 to 58
Coronary artery dilation/aneurysm 8 to 38
Other findings can include mitral regurgitation and pericardial effusion --
Chest radiograph
Normal in many patients --
Abnormal findings included small pleural effusions, patchy consolidations, focal consolidation, and atelectasis --
Chest CT
Findings generally similar to those on chest radiograph --
A few patients had nodular ground-glass opacification --

Abdominal imaging (ultrasound and/or CT)
Findings are nonspecific, including free fluid, ascites, bowel and mesenteric inflammation, including terminal ileitis, mesenteric --
adenopathy/adenitis, and pericholecystic edema
COVID-19: coronavirus disease 2019; BNP: brain natriuretic peptide; NT-pro-BNP: N-terminal pro-BNP; LV: left ventricular; CT: computed tomography.
* The frequencies listed in this table represent the proportion of patients with each finding among those tested or assessed for the finding. Not all patients were tested or assessed for each.

Type, proportion, and duration of persistent COVID-19 symptoms*
Proportion of patients
Persistent symptom ¶ Approximate time to symptom resolution Δ

affected by symptom
Common physical symptoms
Fatigue 15 to 87% [1,2,6,9,14] 3 months or longer
Dyspnea 10 to 71% [1,2,6-9,14] 2 to 3 months or longer
Chest discomfort 12 to 44% [1,2] 2 to 3 months
Cough 17 to 34% [1,2,9,12] 2 to 3 months or longer
Anosmia 10 to 13% [1,3-5,9,11] 1 month, rarely longer
Less common physical symptoms
Joint pain, headache, sicca syndrome, rhinitis, dysgeusia, <10% [1,2,8,9,11] Unknown (likely weeks to months)
poor appetite, dizziness, vertigo, myalgias, insomnia,
alopecia, sweating, and diarrhea
Psychologic and neurocognitive
Post-traumatic stress disorder 7 to 24% [6,10, 14] 6 weeks to 3 months or longer
Impaired memory 18 to 21% [6,15] weeks to months
Poor concentration 16% [6] Weeks to months
Anxiety/depression 22 to 23% [2,7,8,10, 12,13, 14] Weeks to months
Reduction in quality of life >50% [8] Unknown (likely weeks to months)
COVID-19: coronavirus disease 2019.
* These data are derived from an earlier period in the pandemic; information on patient recovery and persistent symptoms is evolving, and these figures may change as longer-term data emerge.
¶ More than a third of patients with COVID-19 experience more than one persistent symptom.
Δ Time course for recovery varies depending on premorbid risk factors and illness severity and may be shorter or longer than that listed. Hospitalized patients, and in particular critically ill patients,
are more likely to have a more protracted course than those with mild disease.
References:
1. Carfì A, Bernabei R, Landi F, et al. Persistent Symptoms in Patients After Acute COVID-19. JAMA 2020; 324:603.
2. Xiong Q, Xu M, Li J, et al. Clinical sequelae of COVID-19 survivors in Wuhan, China: a single-centre longitudinal study. Clin Microbiol Infect 2020.
3. Hopkins C, Surda P, Whitehead E, Kumar BN. Early recovery following new onset anosmia during the COVID-19 pandemic - an observational cohort study. J Otolaryngol Head Neck Surg 2020; 49:26.
4. Cho RHW, To ZWH, Yeung ZWC, et al. COVID-19 Viral Load in the Severity of and Recovery From Olfactory and Gustatory Dysfunction. Laryngoscope 2020; 130:2680.
5. Meini S, Suardi LR, Busoni M, et al. Olfactory and gustatory dysfunctions in 100 patients hospitalized for COVID-19: sex differences and recovery time in real-life. Eur Arch Otorhinolaryngol 2020;
277:3519.
6. Halpin SJ, McIvor C, Whyatt G, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation. J Med Virol 2020.
7. Bowles KH, McDonald M, Barrón Y, et al. Surviving COVID-19 After Hospital Discharge: Symptom, Functional, and Adverse Outcomes of Home Health Recipients. Ann Intern Med 2020.
8. Wong AW, Shah AS, Johnston JC, et al. Patient-reported outcome measures after COVID-19: a prospective cohort study. Eur Respir J 2020; 56.
9. Nehme M, Braillard O, Alcoba G, et al. COVID-19 Symptoms: Longitudinal Evolution and Persistence in Outpatient Settings. Ann Intern Med 2020.
10. Taquet M, Luciano S, Geddes JR, Harrison PJ. Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA. Lancet Psychiatry
2020.
11. Logue J K; Franko N M; McCulloch D J; et al. Sequelae in Adults at 6 Months After COVID-19 Infection JAMA Network Open. 2021;4(2):e210830.
12. Mandal S, Barnett J, Brill S, et al. 'Long-COVID': a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19. Thorax 2020; PMID
33172844.
13. Bellan M, Soddu D, Balbo PE, et al. Respiratory and Psychophysical Sequelae Among Patients With COVID-19 Four Months After Hospital Discharge. JAMA Netw Open. 2021;4(1):e2036142.
14. Writing Committee for the COMEBAC Study Group, Morin L, Savale L, Pham T, et al. Four-Month Clinical Status of a Cohort of Patients After Hospitalization for COVID-19. JAMA. 2021; PMID 33729425.
15. Del Brutto OH, Wu S, Mera A, Recalde et al. Cognitive decline among individuals with history of mild symptomatic SARS‐CoV‐2 infection: A longitudinal prospective study nested to a population cohort. Eur
J Neurol 2021; PMID 33576150.

Proposed reporting language for CT findings related to COVID-19
Routine screening CT for diagnosis or exclusion of COVID-19 is currently not recommended by most professional organizations or the US Centers for
Disease Control and Prevention
COVID-19
pneumonia imaging Rationale CT findings Suggested reporting language
classification
Typical appearance Commonly reported Peripheral, bilateral, GGO with or without consolidation or "Commonly reported imaging features of (COVID-19) pneumonia
imaging features of visible intralobular lines ("crazy-paving") are present. Other processes such as influenza pneumonia and
greater specificity for Multifocal GGO of rounded morphology with or without organizing pneumonia, as can be seen with drug toxicity and
COVID-19 pneumonia. consolidation or visible intralobular lines ("crazy-paving") connective tissue disease, can cause a similar imaging pattern."
Reverse halo sign or other findings of organizing pneumonia
(seen later in the disease)
Indeterminate Nonspecific imaging Absence of typical features AND "Imaging features can be seen with (COVID-19) pneumonia,
appearance features of COVID-19 Presence of: though are nonspecific and can occur with a variety of infectious
pneumonia. Multifocal, diffuse, perihilar, or unilateral GGO with or and noninfectious processes."
without consolidation lacking a specific distribution and
are non-rounded or non-peripheral.
Few very small GGO with a non-rounded and non-
peripheral distribution.
Atypical appearance Uncommonly or not Absence of typical or indeterminate features AND "Imaging features are atypical or uncommonly reported for
reported features of Presence of: (COVID-19) pneumonia. Alternative diagnoses should be
COVID-19 pneumonia. Isolated lobar or segmental consolidation without GGO considered."
Discrete small nodules (centrilobular, "tree-in-bud")

Lung cavitation
Smooth interlobular septal thickening with pleural
effusion
Negative for pneumonia No features of No CT features to suggest pneumonia. "No CT findings present to indicate pneumonia. (NOTE: CT may
pneumonia. be negative in the early stages of COVID-19.)"
NOTES:
1. Inclusion in a report of items noted in parenthesis in the Suggested reporting language column may depend upon clinical suspicion, local prevalence, patient status as a PUI, and local
procedures regarding reporting.
2. CT is not a substitute for RT-PCR, consider testing according to local recommendations and procedures for and availability of RT-PCR.
Proposed reporting language for CT findings related to COVID-19, including rationale, CT findings, and suggested reporting language for each category. Associated CT findings for each
category are based upon available literature at the time of writing in March 2020, noting the retrospective nature of many reports, including biases related to patient selection in cohort
studies, examination timing, and other potential confounders.
COVID-19: coronavirus disease 2019; CT: computed tomography; GGO: ground-glass opacity; PUI: person under investigation; RT-PCR: reverse transcription polymerase chain reaction.
From: Simpson S, Kay FU, Abbara S, et al. Radiological Society of North America Expert Consensus Statement on Reporting Chest CT Findings Related to COVID-19. Endorsed by the Society of Thoracic Radiology,
the American College of Radiology, and RSNA. Radiology: Cardiothoracic Imaging 2020. Copyright © 2020 Radiological Society of North America. Available at: https://pubs.rsna.org/doi/10.1148/ryct.2020200152
(Accessed on April 6, 2020). Reproduced under the terms of the Creative Commons Attribution License.

Chest CT findings related to COVID-19
Typical CT imaging features for COVID-19. Unenhanced thin-section axial images of the lungs in a 52-year-old man with a positive RT-PCR (A to D) show bilateral, multifocal rounded (asterisks)
and peripheral GGO (arrows) with superimposed interlobular septal thickening and visible intralobular lines ("crazy-paving"). Routine screening CT for diagnosis or exclusion of COVID-19 is
currently not recommended by most professional organizations or the United States Centers for Disease Control and Prevention.
COVID-19: coronavirus disease 2019; CT: computed tomography; RT-PCR: reverse-transcription polymerase chain reaction; GGO: ground-glass opacity.
From: Simpson S, Kay FU, Abbara S, et al. Radiological Society of North America Expert Consensus Document on Reporting Chest CT Findings Related to COVID-19: Endorsed by the Society of Thoracic Radiology, the
American College of Radiology, and RSNA. Radiology: Cardiothoracic Imaging 2020; 2:2. Available at: https://pubs.rsna.org/doi/full/10.1148/ryct.2020200152. Copyright © 2020. The Authors. Reproduced under the
terms of the Creative Commons Attribution License 4.0.

Chest CT findings related to COVID-19 (2)
Typical CT imaging features for COVID-19 and other diseases with similar findings. Posterior, peripheral, and rounded GGO and
consolidation in axial images of four patients; COVID-19 (A, B), organizing pneumonia secondary to dermatomyositis (C), and influenza A
pneumonia (D). Organizing pneumonia and influenza pneumonia can be indistinguishable from COVID-19 by CT. Routine screening CT
for diagnosis or exclusion of COVID-19 is currently not recommended by most professional organizations or the United States Centers
for Disease Control and Prevention.
COVID-19: coronavirus disease 2019; CT: computed tomography; GGO: ground-glass opacity.
From: Simpson S, Kay FU, Abbara S, et al. Radiological Society of North America Expert Consensus Document on Reporting Chest CT Findings Related to
COVID-19: Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA. Radiology: Cardiothoracic Imaging 2020; 2:2.
Available at: https://pubs.rsna.org/doi/full/10.1148/ryct.2020200152. Copyright © 2020. The Authors. Reproduced under the terms of the Creative
Commons Attribution License 4.0.

Contributor Disclosures
Kenneth McIntosh, MD Nothing to disclose Martin S Hirsch, MD Nothing to disclose Allyson Bloom, MD Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level
review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
Conflict of interest policy

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COVID-19: Clinical features

The management of COVID-19 is also discussed in detail elsewhere:

● (See "COVID-19: Outpatient evaluation and management of acute illness in adults".)

● (See "COVID-19: Pregnancy issues and antenatal care".)

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SEVERITY OF SYMPTOMATIC INFECTION

Spectrum of severity and fatality rates

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

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Several complications of COVID-19 have been described:

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● Ground-glass opacifications – 83 percent

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

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SUMMARY AND RECOMMENDATIONS

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Graphic 127477 Version 8.0

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Laboratory features associated with severe COVID-19 [1-6]

Abnormality Possible threshold

D-dimer >1000 ng/mL (normal range: <500 ng/mL)

CRP >100 mg/L (normal range: <8.0 mg/L)

LDH >245 units/L (normal range: 110 to 210 units/L)

Graphic 127820 Version 2.0

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Symptoms associated with coronavirus disease 2019 (COVID-19) [1]

Symptoms that may be seen in patients with COVID-19

Dyspnea (new or worsening over baseline)

Anosmia or other smell abnormalities

Ageusia or other taste abnormalities

Rhinorrhea and/or nasal congestion

Chest pain or pressure

COVID-19: coronavirus disease 2019.

Graphic 127890 Version 8.0

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Clinical manifestations of COVID-19-associated multisystem inflammatory syndrome in children and adolescents

Persistent fevers (median duration 4 to 6 days) 100

Gastrointestinal symptoms (abdominal pain, vomiting, diarrhea) 60 to 100

Mucous membrane involvement 27 to 76

Neurocognitive symptoms (headache, lethargy, confusion) 29 to 58

Respiratory symptoms (tachypnea, labored breathing) 21 to 65

Sore throat 10 to 16

Criteria for complete Kawasaki disease met 22 to 64

Myocardial dysfunction (by echocardiogram or elevated troponin/BNP) 51 to 90

Acute respiratory failure requiring noninvasive or invasive ventilation 28 to 52

Acute kidney injury 8 to 52

Serositis (small pleural, pericardial, and ascitic effusions) 24 to 57

Encephalopathy, seizures, coma, or meningoencephalitis 6 to 7

Abnormal blood cell counts

Elevated inflammatory markers