19 | CDC Yellow Book 2024 (2024)

The content of this page has been updated to reflect the CDC Respiratory Virus Guidance.

Author(s):Cria O. Gregory and Aron Hall

Infectious Agent

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is a single-stranded, positive-sense RNA virus that belongs to the familyCoronaviridae, genusBetacoronavirus. SARS-CoV-2 has continued to evolve since it first emerged in late 2019. In 2021, the World Health Organization (WHO) began labeling key variants by Greek letters. As of 2023, WHO will only assign Greek letters to variants of concern, indicating increase in disease severity, likelihood of substantially impacting the healthcare system, or significant decrease in effectiveness of vaccines in protecting against severe illness.

Transmission

SARS-CoV-2 is transmitted from person to person by airborne particles and droplets that carry infectious virus. When an infected person breathes, sings, talks, coughs, or sneezes, they release infectious aerosol particles into the air. Exposure can occur when aerosol particles and small respiratory droplets are inhaled or contact exposed mucous membranes. Indoors, fine droplets and aerosol particles can linger and accumulate, even after an infected person has left the room. The risk of infection generally increases with closer contact and with longer durations of contact with an infected person, particularly in poorly ventilated indoor or crowded settings. Activities that increase emission of respiratory fluids such as singing, cheering, or exercising can increase risk of transmission. Infection from contaminated surfaces or objects is possible but generally does not contribute significantly to new infections.

People with COVID-19 can be infectious from 1–2 days before and up to 8–10 days after symptoms begin. The majority of transmission appears to occur during the early periods of infection, particularly in the 1–2 days before symptoms start and within the first few days of symptom onset. This period of infectiousness may be reduced slightly but has been fairly consistent since SARS-CoV-2 emerged. Individuals who are asymptomatic can also transmit the virus.

Outbreaks of COVID-19 have occurred in multiple travel-related settings, including cruise ships, airplanes, hotels, and conferences. Many of these outbreaks were documented in the earlier period of the pandemic, but outbreaks still occur, even among highly vaccinated populations.

Epidemiology

The first cases of COVID-19 were reported in December 2019 in Wuhan, China, and rapidly spread to other countries. On January 30, 2020, WHO declared the outbreak a Public Health Emergency of International Concern, and on March 11, 2020, WHO declared COVID-19 a global pandemic. As of February 25, 2024, globally there have been more than 774,000,000 confirmed COVID-19 cases and over 7,000,000 deaths. These are likely significant underestimates because many cases are undiagnosed or not reported. In the United States, in 2022, COVID-19 was the fourth leading cause of death, following heart disease, cancer, and unintentional injury.

When the novel virus first emerged, none of the population had any specific protective immunity against this pathogen. At least 98% of the US population now has some degree of protective immunity from vaccination, infection, or both (hybrid immunity). Hybrid immunity has been described as providing better protection with longer durability against severe illness compared to immunity from vaccination or infection alone.

SARS-CoV-2 has had ongoing circulation, with waves of increased and decreased incidence, since it emerged. The virus has continued to evolve and has not yet settled into a predictable pattern of circulation. The dramatic shift in the virus from Delta to Omicron in late 2021 resulted in reduced vaccine effectiveness, more immune escape, and the loss of effectiveness of some therapeutics, along with a corresponding surge in infections. Broadly, SARS-CoV-2 causes less severe illness than when it first emerged, due to background immunity of the population and reduced severity of the virus itself. However, it remains a public health threat, particularly to individuals at increased risk of severe illness, and with ongoing circulation, travelers could be exposed whenever they are traveling. SARS-CoV-2 will continue to evolve, and a new variant could emerge that is more infectious or causes more severe illness.

Clinical Presentation

Signs and symptoms of SARS-CoV-2 infection can include fever, chills, cough, shortness of breath, fatigue, muscle aches, headache, loss of taste or smell, sore throat, nasal congestion or rhinorrhea, vomiting or diarrhea, or skin rashes. Illness can range from asymptomatic to severe, and many symptoms are difficult to distinguish from other infections without diagnostic testing.

Severe disease occurs more often in people who are 50 years and older, with risk increasing substantially at ages >65 years. Risk of severe illness is also increased in people who are immunocompromised (either from an immunocompromising condition or medication) or with certain underlying medical conditions. Risk is greater with increasing number of comorbidities. People who are pregnant are at increased risk of severe illness from COVID-19, and of having a preterm birth, stillbirth, or other pregnancy complications if infected with SARS-CoV-2 while pregnant. See acomprehensive list of risk factors. See Sec. 3, Ch. 1, Immunocompromised Travelers, and Sec. 7, Ch. 1, Pregnant Travelers, for additional information about these populations.

Long COVID and multisystem inflammatory syndrome

Long COVID is broadly defined as signs, symptoms, or conditions that continue or develop after acute COVID-19 infection. Symptoms or conditions can be persistent, stop and then reemerge, or begin after the acute infection resolves, and can last weeks, months, or years. Long COVID, also referred to as post-COVID conditions or post-acute sequelae of COVID-19, can affect different body systems (e.g., neurologic, respiratory, digestive). Common reported symptoms include tiredness or fatigue that interferes with daily life, symptoms that get worse with physical or mental effort, difficulty thinking or concentrating (sometimes called “brain fog”), cough, shortness of breath, and heart palpitations. Long COVID is more common among women, people with more severe acute COVID-19 illness, and people with underlying health conditions. The best way to protect against Long COVID is to prevent infection and severe acute COVID-19. Vaccination can reduce the risk of Long COVID, while data are mixed on whether antivirals during acute infection may reduce the risk of Long COVID.

Multisystem inflammatory syndrome (MIS) is a rare but serious condition associated with COVID-19 in which different parts of the body become inflamed, typically 2–6 weeks after acute infection. MIS was first recognized and has been more widely reported in children (MIS-C) but has also been reported among adults (MIS-A). Incidence of MIS-C is much lower compared to earlier in the pandemic, but cases do still occur. This overall decline is likely due to multiple factors, including an increase in population immunity from both infection and vaccination, as well as differences in development of MIS-C associated with different SARS-CoV-2 variants.

Diagnosis

Viral tests that detect current infection with SARS-CoV-2 are used for COVID-19 diagnosis and include nucleic acid amplification tests (NAATs) and antigen tests.Tests that detect antibody to SARS-CoV-2can be used to identify previous infection and might be useful for surveillance purposes but are not typically used for diagnosis except for MIS-C. All tests should be performed as specified by the manufacturer and authorized or approved by the US Food and Drug Administration (FDA).

Nucleic Acid Amplification Testing

NAATs detect SARS-CoV-2 RNA and are highly sensitive and specific, typically performed in a laboratory or clinical setting, with results usually taking 1–3 days. The most common NAAT is the polymerase chain reaction (PCR) test. A positive NAAT provides evidence of current infection. Residual shedding of non-infectious viral RNA can result in a positive test result beyond when an individual is infectious. Most immunocompetent people are not infectious after 8–10 days, but a NAAT can be positive for longer. People with immunocompromising conditions can test positive for longer durations, although this does not necessarily indicate they are infectious.

Antigen Tests

Antigen tests are sometimes called rapid tests or point-of-care tests because they can be used almost anywhere and can yield results in 15–30 minutes. These tests detect the presence of viral proteins (antigens). In general, they are less sensitive than NAATs, particularly among asymptomatic people. A single negative antigen test cannot rule out an infection. FDA recommends repeat testing following a negative antigen test for a total of 2 antigen tests for people with symptoms or 3 antigen tests for people without symptoms, each performed 48 hours apart. A single positive antigen test is typically reliable, especially if the person is symptomatic.

Consider encouraging patients to travel with several antigen tests, particularly if they are at increased risk of severe illness and would be eligible for treatment. Most COVID-19 antigen tests need to be stored between 2°C (36°F) and 30°C (86°F), so will not be appropriate for all travel conditions or locations.

Treatment

Before travel, encourage patients to have a healthcare contingency plan in place, should they test positive for COVID-19 while abroad (see Travel Insurance, Travel Health Insurance, and Medical Evacuation Insurance chapter). For mild disease, medications that are typically available over the counter can be used to alleviate symptoms. Patients also should rest and stay well-hydrated.

For people at greater risk for progression to severe disease, several antiviral medications (Table 5-08-1) have been approved or authorized for treatment of mild to moderate COVID-19. As of March 2024, preferred antiviral medications, in order of preference, are oral nirmatrelvir + ritonavir (Paxlovid) and intravenous remdesivir (Velkury). If neither of these drugs is available or clinically appropriate, molnupiravir (Lagevrio) is the recommended alternative therapy. As of March 2024, no monoclonal antibodies are authorized for use in non-hospitalized patients because they are not effective against circulating variants of SARS-CoV-2. This may change as new monoclonal antibodies are developed, or if variants begin circulating that are susceptible to previous monoclonal antibodies and approval is reinstated. For maximal efficacy, medications should be given as soon as possible after symptom onset. Emergence of future variants might impact treatment options. The National Institutes of Health has developedCOVID-19 treatment guidelines.

Travelers who are at high risk for progression to severe COVID-19 (e.g., severely immunocompromised persons, frail older adults with serious co-morbid conditions) should be counseled on the importance of ensuring they are up to date on COVID-19 vaccination, reviewing when and where to seek medical care, and considering potential treatment options if symptoms occur during travel. COVID-19 antivirals can be taken safely even with many other medications. Clinicians shouldevaluate drug-drug interactionsbecause some medications may need to be stopped or changed.