The information included in this chapter was current as of August 2022. See the most recent information regarding coronavirus disease 2019 (COVID-19).

Author(s): Sarah Anne Guagliardo, Cindy Friedman

Infectious Agent

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is a single-stranded, positive-sense RNA virus that belongs to the family Coronaviridae, genus Betacoronavirus.

Transmission

SARS-CoV-2 is primarily transmitted from person to person following close (≤6 ft, ≈2 m) exposure to respiratory fluids carrying infectious virus. When an infected person breathes, sings, talks, coughs, or sneezes, they release infectious aerosol particles (droplet nuclei) into the air. Exposure can occur when aerosol particles and small respiratory droplets are inhaled or contact exposed mucous membranes. Infection from contaminated surfaces or objects (fomites) is possible but is unlikely to contribute significantly to new infections.

Infection through inhalation is most likely to occur at closer distances (≤6 ft), but transmission over distances >6 ft by inhalation of very fine aerosolized, infectious particles (airborne transmission) has been documented. The risk of transmission is enhanced in poorly ventilated indoor spaces.

Epidemiology

The first cases of COVID-19 were reported in December 2019 in Wuhan, China, and since then, the virus has spread to all continents. International travel has played an ongoing role in the epidemiology of the pandemic, facilitating the initial global spread of the virus as well as each successive SARS-CoV-2 variant. From January 2020 to April 2022, there were 5 major epidemic waves in the United States; as of April 2022, the most recent 3 corresponded to the Alpha, Delta, and Omicron variants.

Mortality Rates

As of April 2022, there were an estimated 400 million cases and 6 million deaths reported worldwide. Case counts and deaths are likely an underestimate, since only a small proportion of infections are diagnosed and reported; in addition, self-testing options (for which positive results might go unreported) are now widely available. Estimates of the infection fatality rate (the mortality rate in infected individuals) among unvaccinated populations range from 0.15% to 1.7% Country-specific COVID-19 mortality rates can vary between destinations for multiple reasons, including differences in population-level immunity due to previous infection, vaccination rates, age distribution, prevalence of comorbidities, viral evolution, and access to health care. With the emergence of new variants, mortality rates may change.

Travel-Associated Risk

Reported travel-associated case counts and deaths also are likely an underestimate, and overall travel-related risk is difficult to ascertain. Investigating and identifying travel-associated cases of COVID-19 has unfortunately been hampered by a lack of complete passenger data for contact tracing, limited or incomplete reporting of contact tracing outcomes among exposed passengers, and difficulties in excluding non-travel–associated exposures. Tracking levels of transmission in countries globally is only one factor in determining travel-associated risk.

Modes of Transportation & Transmission Risk

Across all modes of transportation, not wearing a well-fitting mask or respirator within 6 ft of an infected person (e.g., sitting on a plane or train, sharing a cabin on a cruise) increases the risk for infection, underscoring the importance of prevention measures before and during travel.

Air Travel

Attack rates range from 0% to 8% on flights but can be as high as 60% in subsections of an aircraft, as was observed on a 10-hour flight in a business class cabin. The individuals affected in this outbreak were all seated within 6 feet of the index case; data regarding mask use were not available. The relationship between flight duration and attack rates is difficult to quantify due to other flight-specific variables (e.g., mask use among passengers and aircrew, passenger movement during the flight) that are not captured or difficult to measure. For more information about health concerns related to commercial air travel, see Sec. 8, Ch. 1, Air Travel.

Cruise Ship Travel

Cruise ship travel facilitates the introduction and spread of respiratory viruses because of close indoor proximity and extensive social interactions between ever-changing cohorts of passengers from diverse geographic regions. Cruise ships were the source of many large COVID-19 outbreaks throughout the pandemic, with severe outcomes prior to COVID-19 vaccines.

In the earliest months of the pandemic (January–April 2020), attack rates on cruises were as high as 62%. Longer voyages were associated with more cases, and repeated outbreaks on the same ship (but different voyages) were common. Since then, the Centers for Disease Control and Prevention (CDC) has worked to develop guidance for the cruise ship industry to use to better manage risks associated with COVID-19. See Sec. 8, Ch. 6, Cruise Ship Travel, for more details on health concerns related to cruises.

Ground Transportation

COVID-19 outbreaks on buses and trains have also been described. Attack rates on buses have been as high as 36%. On trains, attack rates among passengers within 3 rows of an index patient were lower, ranging from 0% to 10%, with an overall attack rate of <1%.

Sentinel Surveillance

In the context of declining global testing and reporting, determining country-level risk has become more challenging. Sentinel surveillance of international travelers may therefore be an important contribution to the global picture of disease burden and variant emergence. In September 2021, CDC launched a voluntary traveler-based SARS-CoV-2 genomic surveillance program to detect variants among travelers arriving at major US international airports. Through this program, CDC scientists detected Omicron subvariants BA.2 and BA.3 in the United States 7 and 45 days earlier, respectively, than any other US report.

Clinical Presentation

SARS-CoV-2 infection can present with an array of clinical findings, ranging from asymptomatic to severe (e.g., multiorgan involvement, respiratory failure, death). Most infections are mild, however; about 40% of people are asymptomatic. Among cases that do not result in severe disease or hospitalization, fatigue, headache, muscle aches, rhinitis, and sore throat are reported most often. Other reported symptoms and signs include fever, chills, cough, shortness of breath, loss of taste and smell, nausea, vomiting, and diarrhea.

There is evidence that clinical presentation and illness severity differ depending on the SARS-CoV-2 variant. For example, 34% of patients infected with the Delta variant experienced loss of taste and smell, as compared to 13% of patients infected with the Omicron variant. Omicron was also associated with proportionally less pneumonia and severe disease. For pre-Omicron variants, the median incubation period is 5 days with a range of 2–14 days after initial exposure; studies of the Omicron variant have estimated the incubation period to be 2–3 days.

Age and underlying medical conditions increase a person’s risk for severe disease and death. The risk of severe disease and death increases significantly with age (≥50 years old), pregnancy, obesity, and with an increasing number of comorbidities (e.g., diabetes, hypertension, HIV infection). See a comprehensive 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

People infected with SARS-CoV-2 can continue to experience symptoms ≥4 weeks after initial infection. Reported symptoms include shortness of breath, fatigue, headache, and difficulty thinking or concentrating. Commonly known as “long COVID,” this condition goes by several other names, including post-COVID syndrome or condition, post-acute sequelae of COVID-19 (PASC), and chronic COVID Syndrome (CCS). See the most up-to-date definition of long COVID and an associated list of symptoms. Researchers are investigating risk factors and manifestations of long COVID.

In addition to the above, there is growing evidence of long-term cardiovascular consequences of the disease, including cerebrovascular disorders, dysrhythmias, heart failure, ischemic and non-ischemic heart disease, myocarditis, pericarditis, and thromboembolic disease.

Diagnosis

Viral tests that detect current infection with SARS-CoV-2 are used for COVID-19 diagnosis, and include nucleic acid amplification tests (NAATs, e.g., reverse transcription PCR [RT-PCR]) and antigen tests. Tests that detect antibody to SARS-CoV-2 can be used to identify previous infection and might be useful for surveillance purposes, but are not typically used for diagnosis, except for multisystem inflammatory syndrome in children and adults.

Nucleic Acid Amplification Testing

NAATs detect SARS-CoV-2 RNA and are highly sensitive and specific. The most common NAAT is the RT-PCR test. A positive RT-PCR provides evidence of current infection. Residual shedding of non-infectious viral RNA also can result in a positive test result, as demonstrated by reports of patients whose RT-PCR tests remain positive ≥3 months post-infection.

Acceptable specimens for SARS-CoV-2 RT-PCR tests include saliva and swab samples collected from the upper respiratory tract (e.g., nasopharynx, nasal mid-turbinate, anterior nasal, oropharynx). As new tests are developed, other specimen types might be identified as being suitable for testing. Each test should be performed as specified by the manufacturer and authorized or approved by the US Food and Drug Administration (FDA). NAAT results usually take 1–3 days, but some rapid tests available in the United States can be useful for travelers who need proof of a negative test for entry to international destinations; travelers should confirm with their air carrier and their destination in advance to ensure the acceptability of the test used.

Antigen Testing

Antigen tests detect the presence of viral proteins (antigens). In general, they are less sensitive than NAATs but are less expensive and can yield rapid results (≈15 minutes). Antigen tests can be used in a laboratory, at the point of care, or self-administered. See more information on antigen testing.

Treatment

Before travel, encourage patients to have a health care contingency plan in place, should they test positive for COVID-19 while abroad; some countries require proof of travel insurance for COVID-19 (see Sec. 6, Ch. 1, Travel Insurance, Travel Health Insurance & Medical Evacuation Insurance). For mild disease, medications such as acetaminophen or ibuprofen can provide symptomatic relief. Patients also should rest and stay well hydrated.

For people at greater risk for progression to severe disease, the FDA has issued Emergency Use Authorization for several postexposure treatments, including antiviral medications and monoclonal antibodies. As of August 2022, preferred antiviral medications include oral nirmatrelvir + ritonavir (Paxlovid) and intravenous remdesivir. If neither of these drugs is available or clinically appropriate, alternative therapeutic options include prophylaxis with the oral antiviral molnupiravir or with monoclonal antibodies. For maximal efficacy, administer medications as soon as possible after diagnosis. Emergence of future variants might impact future treatment options.

The National Institutes of Health regularly updates COVID-19 treatment guidelines.

Prevention

During the initial months of the pandemic, global travel virtually halted, with many countries closing their borders to international travelers. Since then, travel has gradually returned to near pre-pandemic levels. In response to newly emerging variants of concern, many countries instituted measures (e.g., mask use, testing, isolation, quarantine, vaccination requirements) to slow travel-associated transmission. Several countries, including the United States, instituted travel bans, although evidence is limited that these are an effective prevention measure.

Inhalation of virus particles and deposition of virus on mucous membranes can be prevented by wearing a well-fitting mask or respirator and avoiding crowded indoor spaces with poor ventilation. Handwashing can help prevent transmission from contact with contaminated surfaces (fomite transmission). Used in combination, layered interventions (e.g., mask wearing, avoiding crowded indoor spaces with poor ventilation, testing, isolation, quarantine, vaccination) are measures that can reduce risk of transmission.

Coronavirus Disease 2019 Information by Destination

Because the situation continues to evolve, travelers and health care providers should review the travel restrictions, requirements, recommendations, and resources for all destination countries and the United States before departure. Knowing the most up-to-date information about COVID-19 by destination can help travelers and clinicians make informed decisions about travel based on COVID-19 levels, the travelers’ risk for developing severe illness, and the health care capacity at the destination.

CDC’s COVID-19 travel page provides guidance for travelers. Each country’s ministry of health website is another source for information about COVID-19 levels at the destination as well as current entry requirements, including proof of vaccination.

Vaccination

As of August 2022, everyone ≥6 months old in the United States is eligible and recommended to receive COVID-19 vaccination (see, and Sec. 7, Ch. 4, Vaccine Recommendations for Infants & Children). At present, there are 4 vaccines authorized for use in the United States: 2 mRNA-based vaccines (Moderna, Pfizer-BioNTech), a DNA-based, adenovirus-vectored vaccine (Johnson & Johnson’s Janssen), and a protein vaccine (Novavax). In most circumstances the 2 mRNA vaccines are preferred.

All eligible travelers should be up to date with their COVID-19 vaccines before travel. Interim clinical considerations for the use of COVID-19 vaccines in the United States provide additional details regarding vaccine schedules, vaccine safety, and vaccination recommendations for people who are moderately to severely immunocompromised.

Testing

Conducting both a pretravel and posttravel test is estimated to reduce the risk of viral spread by up to 75%. Predeparture testing results in the greatest reduction of risk when a specimen is collected closest to the time of travel. Conducting a posttravel test 3–5 days after return can help prevent spread in the community. For the most up-to-date testing guidance for travelers, see International Travel to and from the United States, and Domestic Travel.

Isolation

Isolation is the physical separation of a person with a confirmed or suspected infectious disease from people who are not infected. People who have symptoms or who test positive for COVID-19 should follow the latest CDC guidance regarding isolating themselves from others and the precautions to take after ending isolation. If a person is symptomatic, they should avoid travel for 10 days after symptom onset; if asymptomatic, they should avoid travel for 10 days after the date the positive test was collected. Immunocompromised travelers (Sec. 3, Ch. 1, Immunocompromised Travelers) can be infectious for longer than 10 days and should consider longer isolation periods. See the most up-to-date information and guidance on isolation and travel.

Quarantine

Quarantine is the physical separation from other people of a person who has had close contact with someone with confirmed or suspected infectious disease. A fundamental public health approach to disease containment, quarantine has been used throughout the COVID-19 pandemic (). For the most up-to-date information and guidance on quarantine and travel.

Masks

Wearing a well-fitting mask or respirator that completely covers the nose and mouth reduces SARS-CoV-2 transmission. A properly fitted and appropriately worn respirator (e.g., N95 filtering facepiece respirator approved by the National Institute for Occupational Safety and Health) protects the wearer from inhaling airborne droplet nuclei. KN95s also offer a high level of protection. Well-fitting disposable surgical masks provide source control by helping reduce transmission from a person infected with SARS-CoV-2 to others within a shared space. Masks made from layered finely woven products afford some protection, with the least amount of protection being offered by loosely woven cloth products. See more details about types of masks and respirators.

CDC website: www.cdc.gov/coronavirus/2019-ncov/index.html