COVID-19 signs, symptoms and severity of disease: A clinician guide
Last updated: June 17, 2021
The information below is based on currently available scientific evidence and informed by expert clinician opinion, and is subject to change as new information becomes available. This document is meant to provide interim information to clinicians on what is presently known about the clinical features of COVID-19, including signs and symptoms, incubation period, disease severity and risk factors for severe disease, SARS-CoV-2 variants of concern and reinfection.
On this page
- Signs and symptoms
- Incubation period
- Disease severity and risk factors for severe disease
- SARS-CoV-2 variants of concern (VOC)
Signs and symptoms
COVID-19 includes clinical features that present in varying type, frequency, severity and within different age groups. Published reports often over-represent individuals who have more severe symptoms and these may differ across care settings and between different age groups. Symptoms that are absent at the onset of illness may develop over time with disease progression. To date, there is no comprehensive list of symptoms that has been validated to have high specificity or sensitivity for COVID-19. It is possible, that as new variants emerge there may be changes in the patterns of symptoms that individuals display. Clinical diagnosis should therefore always be confirmed through SARS-CoV-2 laboratory testing. Patients should always be encouraged to seek medical consultation if experiencing new or worsening symptoms. Table 1 below outlines the common, less frequent and rare symptoms in COVID-19 individuals.
|*Note: It is important to evaluate whether the patient's symptoms are new, worsening, or different from their baseline.|
Cough, fever and shortness of breath are the three most common features amongst hospitalized adult patients, while cough, fever and myalgia were the most common symptoms amongst non-hospitalized individuals.
Clinicians should be aware of signs and symptoms that warrant more urgent or emergency medical attention. Patients with mild disease should be informed to seek medical attention should they experience any of the following:
- Trouble breathing or severe shortness of breath
- Persistent pressure or pain in the chest
- New confusion or altered level of consciousness
- Inability to wake or stay awake
- Pale, gray, or blue-colored skin, lips, or nail beds
The frequency of fever varies amongst studies but remains one of the primary symptoms of COVID-19. A patient may not present with a fever, but may progress to one after a few days of experiencing other symptoms. Older adults and those with underlying comorbidities may experience fever and respiratory symptoms later during the course of illness, when compared to younger persons or those without comorbidities. A review of data from almost 25,000 adults found that fever was the most common symptom at a frequency of 78% of the cases. A study in China found that only 44% of people who stayed in the hospital for COVID-19 had fever upon admission. However, 89% experienced fever at some point during the hospitalization. In some cases, COVID-19 may occur without fever.
Cough and shortness of breath
Other more prevalent symptoms that have been reported include cough and shortness of breath. Cough is one of the most prevalent symptoms along with fever. Both dry (58%) and productive (25%) coughs have been described in the literature. Shortness of breath was more frequently reported in hospitalized patients and associated with more severe disease. A recent systematic review and meta-analysis found shortness of breath present amongst 44% of people with severe disease and 6% of people with non-severe disease.
Many other symptoms have been associated with COVID-19. Of particular note, fatigue, myalgia, and loss of taste and/or smell are experienced in about 1/3 of all cases. Some uncommon symptoms found in COVID-19, but reported during acute illness include congestion or runny nose, skin rashes and eye issues (including conjunctivitis, eye pain and light sensitivity). These other symptoms do not typically occur on their own and are found in conjunction with the more prevalent symptoms. Some of the more uncommon symptoms may also become more prevalent as new variants emerge. Two rare but important syndromes associated with SARS-CoV-2 have been described in the literature and are called Multisystem Inflammatory Syndrome - Children (MIS-C) and Multisystem Inflammatory Syndrome - Adults (MIS-A). These are described below.
Multisystem Inflammatory Syndrome - Children (MIS-C)
In early 2020, this syndrome in children was newly recognized as related to SARS-CoV-2 infection and characterized by hyperinflammation and multi-organ involvement, and presenting with clinical features similar to Kawasaki disease and toxic shock syndrome. A recent systematic review and meta-analysis looking at 27 studies on 917 MIS-C cases found that the common manifestations amongst cases were gastrointestinal symptoms (87.3%) and cardiovascular involvement such as myocardial dysfunction (55.3%), coronary artery aneurysms (21.7%) and shock (65.8%), with marked elevated inflammatory and cardiac markers.
MIS-C signs and symptoms include:
- Kawasaki disease-like features: conjunctivitis, red eyes; red or swollen hands and feet; rash; red cracked lips, and swollen glands. In some children, coronary artery enlargement and/or aneurysms have been described. Some children presenting with Kawasaki disease-like syndrome have been noted to have a broader age range and presentation with more gastrointestinal (abdominal pain or diarrhea) and neurologic (headaches or meningitis) manifestations
- Gastrointestinal symptoms such as abdominal pain, diarrhea, nausea/vomiting (patients have presented with colitis, hepatitis, and questionable appendicitis)
- Toxic shock syndrome-like features with hemodynamic instability and poor heart function. Cytokine storm/macrophage activation or hyperinflammatory features
- Thrombosis or acute kidney injury
- Shortness of breath
Common laboratory findings in case reports have included:
- An abnormal level of inflammatory markers in the blood, including elevated ESR/CRP and ferritin, LDH
- Lymphopenia, thrombocytopenia, neutrophilia
- Elevated B-type natriuretic peptide (BNP) or NT-proBNP (pro-BNP), hyponatremia, elevated D-dimers
In children presenting with a persistent fever (≥3 days) who are moderately to severely ill with clinical signs of organ dysfunction (e.g. gastrointestinal, respiratory, cardiac, skin, or neurologic), the diagnosis of MIS-C should be considered.
Multisystem Inflammatory Syndrome - Adults (MIS-A)
Since June 2020, several case reports and series have been published reporting a similar multisystem inflammatory syndrome in adults (MIS-A) that was previously identified in children. Three studies identified 27 patients who had cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness and who also have positive test results for SARS-CoV-2 by PCR or antibody assays indicating recent infection. Clinicians should consider MIS-A in adults with similar signs and symptoms as seen with MIS-C. It is important to note that 30% of adults and 45% of children with MIS-C/A reported a negative PCR and a positive SARS-CoV-2 antibody test results, suggesting MIS-A and MIS-C might represent a post-infectious process. If suspicious of MIS-C/A and a patient has a negative PCR test, consider both antibody and viral testing to assist with diagnosis.
Symptoms in children
A recent systematic review of the signs and symptoms of laboratory-confirmed COVID-19 disease in children and youth under 19 years of age found cases of asymptomatic positive laboratory tests ranged from 15% to 42%. Fever and cough were the most common symptoms; with the proportions with fever ranging from 46% to 64% and for cough from 32% to 56%. All other signs and symptoms were present at less than 10% to 20%. Vomiting, diarrhea and abdominal ranged from 7% to 18%.
A French multi-centre hospital, as part of a screening program, found that as many as half of paediatric cases were asymptomatic when screened on entry to the hospital. One should also consider when assessing children, that the signs and symptoms of COVID-19 are similar to those of other infections and non-infectious processes, including influenza, other viral upper respiratory infections, streptococcal pharyngitis, asthma and allergies. The lack of specificity of signs or symptoms and the significant proportion of asymptomatic infections make symptom-based screening for identification of SARS-CoV-2 in children difficult.
Symptoms in older adults
Symptoms amongst older adults may be atypical or subtle. Confusion, delirium, and/or loss of movement, mobility and speech may occur in older people. Fever, cough and shortness of breath may be absent or less common.
Symptoms in older adults that differ from typical symptoms include:
- fever and other symptoms may take longer to manifest
- delirium, confusion, falls, functional decline
- decrease in blood pressure
- hypoxia without respiratory symptoms
Asymptomatic, pre-symptomatic and pauci-symptomatic infection
A person who is asymptomatic is someone with a positive SARS-CoV-2 test who never develops any symptoms, whereas a person who is pre-symptomatic is someone who is infected with SARS-CoV-2 and may have detectable virus, but is not yet showing symptoms (these individuals develop symptoms later on in the course of infection). Individuals who are pauci-symptomatic will have a positive SARS-CoV-2 test in the presence of very limited symptomatology. A systematic review and meta-analysis looking at prevalence of SAR-CoV-2 in persons who are asymptomatic from 28 studies, found that 25% of COVID-19 cases were asymptomatic (95%CI: 16-38). Asymptomatic, pre-symptomatic and pauci-symptomatic SARS-CoV-2 infection and how much each of these contributes to transmission is still unknown.
The incubation period for COVID-19 has been estimated to range from 2 to 14 days, with a median of 5-6 days from exposure to symptom onset. Of all individuals who develop symptoms, 97.5% of the symptoms occur within 11.5 days of exposure. Note that SARS-CoV-2 RNA may be detectable in the upper or lower respiratory tract for weeks after illness onset. However, detection of viral RNA does not necessarily mean that the patient can transmit the virus. The time period in which an individual with COVID-19 can transmit the virus is said to be at a maximum of 10 days after symptom onset for immunocompetent people who have COVID-19. Evidence has shown that an individual may be infectious for up to 3 days prior to any presentation of symptoms. The levels of viral RNA from nasopharyngeal, saliva/sputum samples, upper respiratory specimens, and stool samples appear to be highest soon after symptom onset. A recent systematic review and meta-analysis found that SARS-CoV-2 cases with serial upper respiratory tract samples showed peak viral loads within the first week of symptom onset. The highest viral loads were reported soon after or at the time of symptom onset or at day 3-5 of illness, followed by a consistent decline.
Disease severity and risk factors for severe disease
There is a spectrum of COVID-19 disease severity, ranging from asymptomatic to mild, to moderate, severe and critical disease. Severe disease more often occurs in those with increasing age and those with underlying medical conditions, with the risk increasing with the number of underlying conditions.
Two large cohort studies in the USA and the UK found the most common comorbidities were hypertension (46.7%), hyperlipidemia (28.9%), diabetes (27.9%), and chronic pulmonary disease (16.1%). High risk for mortality was associated with increasing number of comorbid conditions. A comprehensive CDC scientific evidence review process and a Canadian rapid review have recently been published to update the list of underlying medical conditions associated with more severe COVID-19 disease. The conditions identified in these reviews are listed below:
Underlying medical conditions associated with more severe COVID-19 disease:
- asthma (moderate to severe)
- chronic kidney and end-stage disease
- chronic lung diseases
- cystic fibrosis
- dementia or other neurological conditions
- diabetes (type 1 or type 2)
- Down syndrome
- heart conditions
- such as heart failure, coronary artery disease, cardiomyopathies or hypertension
- HIV infection
- immunocompromised state
- interstitial lung disease
- liver disease
- motor neuron diseases
- overweight and obesity*
- pulmonary hypertension
- sickle cell disease or thalassemia
- smoking, current or former
- solid organ or blood stem cell transplant
- stroke or cerebrovascular disease
- substance use disorders
*Overweight = body mass index (BMI) > 25 kg/m2 but < 30 kg/m2), obesity (BMI ≥30 kg/m2 but < 40 kg/m2), or severe obesity (BMI of ≥40 kg/m2)
Patients with certain medical and/or social vulnerabilities, including people experiencing intellectual and developmental disabilities, persons who use substances regularly, people experience cognitive disabilities, mental health conditions or experiencing homelessness or are unhoused, may make it more difficult for the patient to recognize, clearly communicate, or act on symptom progression. These patients need closer attention and monitoring.
SARS-CoV-2 variants of concern (VOC)
Viruses naturally mutate or change over time. Mutations do not always increase transmissibility or virulence, or lead to suboptimal immune or therapeutic responses compared to non-variant viruses. Multiple SARS-CoV-2 variants have emerged in recent months and have shown increased transmissibility when compared with the original strain of SARS-CoV-2. These have been labeled variants of concern (VOCs). The reason for the increased transmissibility of some SARS-CoV-2 variants has not been fully determined, though it may be related to changes in receptor binding or viral load.
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