Clinical Presentation

Key points

For evidence-based treatment recommendations, visit the Infectious Diseases Society of America (IDSA) COVID-19 Treatment and Management Guidelines and the American College of Physicians (ACP) Clinical Guidelines and Recommendations on COVID-19. Also, get information on variants of the virus and COVID-19 vaccines.

About COVID-19

• COVID-19 can vary from asymptomatic infection to critical illness. Symptoms and severity can change during illness.
• Uncommon presentations of COVID-19 may vary by patient age and are a challenge to recognize.
• Infected people can transmit SARS-CoV-2, the virus that causes COVID-19, before symptom onset.

Testing

• When testing for SARS-CoV-2 infection, CDC recommends a viral test, either a molecular (polymerase chain reaction [PCR], nucleic acid amplification test [NAAT]) or antigen test, that detect SARS-CoV-2 or its components. Do not use a serologic test that detects antibodies to diagnose SARS CoV-2 infection. A chest radiograph or computed tomography (CT) images alone are not recommended to diagnose COVID-19 but might be helpful in assessing and managing patients.
• People should seek health care right away for testing and/or treatment if they believe they may have a respiratory virus (if they feel sick or tested positive for one) and they have risk factors for severe illness.

Age is the most important risk factor for severe outcomes of COVID-19. Risk factors for severe COVID-19 include:

• Age over 50 years, with risk increasing substantially at age ≥ 65 years.
• Being unvaccinated or not being up to date on COVID-19 vaccinations.
• Specific medical conditions, including immunocompromising conditions. The number of underlying medical conditions also increases risk for severe COVID-19.

Some racial and ethnic minority groups are disproportionately affected by COVID-19 because of many factors, including limited access to vaccines and healthcare. 123Healthcare providers can consider these factors when evaluating the risk for severe COVID-19 and use of therapeutics.

Treatment

• Outpatient treatment should begin within 5-7 days of symptom onset.
• Additional clinical considerations may apply for children, pregnant and recently pregnant patients, patients who are moderately or severely immunocompromised, and patients with confirmed or suspected multisystem inflammatory syndrome.
• Patients within 90 days of a previous infection may need additional testing considerations. Otherwise, strategies to diagnose and treat reinfection are the same as those for previous COVID-19.

Prevention

• Staying up to date on COVID-19 vaccines is the best way to prevent future SARS-CoV-2 infections, hospitalizations, long-term sequelae, and death.

Incubation period

Incubation periods may differ by SARS-CoV-2 variant. Meta-analyses of studies published in 2020 identified a pooled mean incubation period of 6.5 days from exposure to symptom onset. 1A study conducted during high levels of Delta variant transmission reported a period of 4.3 days, 2and during high levels of Omicron variant transmission, a median incubation period of 3–4 days. 34

Presentation

Asymptomatic and Pre-symptomatic Presentation

SARS-CoV-2 infection may not elicit symptoms in some people (asymptomatic) and may elicit symptoms after a positive test (pre-symptomatic presentation). 56It is unclear what percentage of people who initially appear asymptomatic progress to clinical disease. Children are more likely to remain asymptomatic than adults. People may have abnormalities on chest imaging consistent with COVID-19 before symptom onset or a positive COVID-19 test. 7

Symptomatic Presentation

Symptoms can be difficult to differentiate from, and can overlap with, other viral respiratory illnesses such as influenza (flu) and respiratory syncytial virus (RSV). COVID-19 can vary from asymptomatic infection to critical illness; symptoms and severity can change during the illness. Because symptoms may progress quickly, close follow-up is needed, especially for:

• Older adults
• People with disabilities
• People with immunocompromising conditions
• People with certain underlying medical conditions

The Infectious Diseases Society of America (IDSA) COVID-19 Treatment guidelines define the following groups to facilitate appropriate treatment:

• Mild to Moderate Illness: Individuals who have any of the various signs and symptoms of COVID-19 and do not need supplemental oxygen who have an oxygen saturation (SpO2) ≥94% on room air at sea level.
• Severe Illness: Individuals who have SpO2 <94% on room air at sea level or needing supplemental oxygen.
• Critical Illness: Individuals who have respiratory failure who are subcategorized as:
  • Needing high-flow oxygen or non-invasive ventilation
  • Needing mechanical ventilation and extracorporeal membrane oxygenation (ECMO)

To learn more about COVID-19 treatment, please refer to the ISDA Guidelines on the Treatment and Management of Patients with COVID-19 and the ACP Clinical Guidelines and Recommendations on COVID-19.

Radiographic Considerations and Findings

Patients with severe COVID-19 may demonstrate bilateral air-space consolidation on chest radiographs.8 Chest computed tomography (CT) images may demonstrate bilateral, peripheral ground glass opacities and consolidation. 910Less common CT findings can include intra- or interlobular septal thickening with ground glass opacities (hazy opacity) or focal and rounded areas of ground glass opacity surrounded by a ring or arc of denser consolidation (reverse halo sign). 9

Multiple studies have reported abnormalities on CT or chest radiograph in people who are asymptomatic, pre-symptomatic, or before RT-PCR detects SARS-CoV-2 RNA in nasopharyngeal specimens.10

Symptoms

Common COVID-19 symptoms 11include:

• Fever
• Cough
• Shortness of breath
• Fatigue
• Headache
• Myalgia

Some people have gastrointestinal symptoms such as:

• Nausea
• Vomiting
• Diarrhea

Gastrointestinal symptoms can occur prior to having fever or lower respiratory tract signs and symptoms. 12Loss of smell and taste can occur, although these symptoms are less common since Omicron began circulating. 13 People can experience SARS-CoV-2 infection (asymptomatic or symptomatic), even if they are up to date with COVID-19 vaccines or were previously infected. 14

Several studies report ocular symptoms 15associated with SARS-CoV-2 infection, including:

• Redness
• Tearing
• Dry eye or foreign body sensation
• Discharge or increased secreations
• Itching or pain

Dermatologic manifestations have also been associated with COVID-19 and may be associated with increased severity. 16The timing of skin manifestations in relation to other COVID-19 symptoms and signs is variable. 17Images of cutaneous findings in COVID-19 are available from the American Academy of Dermatology

Transmission

People infected with SARS-CoV-2 can transmit the virus if they are vaccinated or unvaccinated, 1819asymptomatic, pre-symptomatic, 20or symptomatic. Peak transmissibility occurs from prior to symptom onset to a few days after, but most people can shed virus up to 10 days following infection. 21

Clinicians should consider encouraging all patients to follow CDC's Respiratory Virus Guidance to help lower health risks caused by SARS-CoV-2 and other respiratory viruses. Clinicians should also recommend that patients who are infected with SARS-CoV-2 follow CDC guidance for preventing spread of respiratory viruses when they are infected.

Co-circulation of influenza, RSV, and SARS-CoV-2

Clinicians can find useful resources to help in their decision making and actions when influenza, respiratory syncytial virus (RSV), and SARS-CoV-2 are co-circulating.

• Information for Clinicians on Influenza Virus Testing: Assists clinicians with influenza testing and treatment of patients with acute respiratory illness symptoms.
• Influenza Antiviral Medications: Information on antiviral treatment of influenza.
• IDSA COVID-19 Guidelines: Information on the treatment and management of patients with COVID-19
• RSV: For Healthcare Providers: Guidance on testing, vaccines for adults 60 years and older, and prophylaxis for infants and young children.