Coronavirus Disease 2019 (COVID-19)

Updated: Mar 27, 2020
  • Author: David J Cennimo, MD, FAAP, FACP, AAHIVS; Chief Editor: Michael Stuart Bronze, MD  more...
  • Print
Overview

Practice Essentials

Coronavirus disease 2019 (COVID-19) is defined as illness caused by a novel coronavirus now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly called 2019-nCoV), which was first identified amid an outbreak of respiratory illness cases in Wuhan City, Hubei Province, China. [1] It was initially reported to the WHO on December 31, 2019. On January 30, 2020, the WHO declared the COVID-19 outbreak a global health emergency. [2, 3] On March 11, 2020, the WHO declared COVID-19 a global pandemic, its first such designation since declaring H1N1 influenza a pandemic in 2009. [4]

Illness caused by SARS-CoV-2 was recently termed COVID-19 by the WHO, the new acronym derived from "coronavirus disease 2019." The name was chosen to avoid stigmatizing the virus's origins in terms of populations, geography, or animal associations. [5, 6] On February 11, 2020, the Coronavirus Study Group of the International Committee on Taxonomy of Viruses issued a statement announcing an official designation for the novel virus: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). [7]

2019-2020 Outbreak

As of March 27, 2020, COVID-19 has been confirmed in more than 551,000 individuals worldwide and has resulted in more than 24,000 deaths. More than 170 countries have reported laboratory-confirmed cases of COVID-19 on all continents except Antarctica. [8]

In the United States, 86,012 cases of COVID-19 have been confirmed as of March 27, 2020, resulting in 1,301 deaths. [9, 10] As of March 26, 2020, the United States has more confirmed infections than any other country in the world, including China and Italy. [11]

Current clusters of increased local transmission can be found throughout Western Europe, the United States, and Iran. The rate of newly reported infections in China has dropped precipitously.

An interactive map of confirmed cases can be found here.

COVID-19–related deaths in China have mostly involved older individuals (≥60 years) and persons with serious underlying health conditions. In the United States, attributable deaths have been most common in adults aged 85 years or older (10%-27%), followed by adults aged 65-84 years (3%-11%), adults aged 55-64 years (1%-3%), and adults aged 20-54 years (< 1%). As of March 16, 2020, no attributable fatalities have been reported in persons aged 19 years or younger. [12]

In the United States, patients aged 65 years or older have accounted for 31% of all reported COVID-19 cases, 45% of hospitalizations, 53% of admissions to the ICU, and 80% of fatalities attributable to the infection. [12]

Among 2,449 reported cases of COVID-19 in the United States in which age was known, 6% of patients were aged 85 years or older, 25% were aged 65-84 years, 18% were aged 55-64 years, 18% were aged 45-54 years, 29% were aged 20-44 years, and 5% were aged 19 years or younger. [12]

Among 508 hospitalized US patients, 9% of patients were aged 85 years or older, 26% were aged 65-84 years, 17% were aged 55-64 years, 18% were aged 45-54 years, 20% were aged 20-44 years, and persons aged 19 years or younger accounted for less than 1%. [12]

Among US patients admitted to the ICU, 7% were adults aged 85 years or older, 46% were aged 65-84 years, 36% were aged 45-64 years, and 12% were aged 20-44 years. No persons aged 19 years or younger have been admitted to the ICU. [12]

On February 26, 2020, the first case of COVID-19 not associated with travel from China or known contact with an infected traveler was reported in California. [13] Community spread of the virus has now been reported in multiple states. [14]

The Centers for Disease Control and Prevention (CDC) has stated that more cases of COVID-19 are likely to be confirmed in the United States in the near future. They also anticipate widespread SARS-CoV-2 community spread and that most of the US population will be exposed to the virus in coming months, leading to a CDC recommendation against gatherings of 50 persons or more.

The CDC has postulated that this situation could result in large numbers of patients requiring medical care concurrently, resulting in overloaded public health and healthcare systems and, potentially, elevated rates of hospitalizations and deaths. The CDC advises that nonpharmaceutical interventions (NPIs) will serve as the most important response strategy in attempting to delay viral spread and to reduce disease impact. [14]

The feasibility and implications of strategies for suppression and mitigation have been rigorously analyzed and are being encouraged or enforced by many governments in order to slow or halt viral transmission. Population-wide social distancing of the entire population plus other interventions (eg, home self-isolation, school and business closures) is strongly advised. These policies may be required for long periods to avoid rebound viral transmission. [15]

According to the CDC, individuals at high risk of infection include persons in areas with ongoing local transmission, healthcare workers caring for patients with COVID-19, close contacts of infected persons, and travelers returning from locations where local spread has been reported. [14]

Person-to-person spread of SARS-CoV-2 has been reported in the United States. [16, 17] Individuals who believe they may have been exposed to SARS-CoV-2 should immediately contact their healthcare provider.

The CDC has also provided recommendations for individuals who are at high risk of COVID-19–related complications, including older adults and persons who have serious underlying health conditions (eg, heart disease, diabetes, lung disease). Such individuals should consider the following precautions: [18]

  • Stock up on supplies.
  • Avoid close contact with sick people.
  • Wash hands often.
  • Stay home as much as possible in locations where COVID-19 is spreading.
  • Develop a plan in case of illness.

Healthcare personnel are also referred to Medscape’s Novel Coronavirus Resource Center for the latest news, perspective, and resources.

Route of transmission

Transmission is believed to occur via respiratory droplets from coughing and sneezing, as with other respiratory pathogens, including influenza and rhinovirus. [19] Virus released in respiratory secretions can infect other individuals via direct contact with mucous membranes. Droplets usually cannot travel more than 6 feet. The virus can also persist on surfaces to varying durations and degrees of infectivity. One study found that SARS-CoV-2 remained viable for up to 72 hours some surfaces despite decreasing infectivity over time. Notably, the study reported that no viable SARS-CoV-2 was measured after 4 hours on copper or after 24 hours on cardboard. [20]

The duration of viral shedding varies significantly and may depend on severity. Among 137 survivors of COVID-19, viral shedding based on testing of oropharyngeal samples ranged from 8-37 days, with a median of 20 days. [21] A different study found that repeated viral RNA tests using nasopharyngeal swabs were negative in 90% of cases among 21 patients with mild illness, whereas results were positive for longer durations in patients with severe COVID-19. [22]

Data have suggested that asymptomatic patients are still able to transmit infection. This raises concerns for the effectiveness of isolation. [23, 24] Zou et al followed viral expression through infection via nasal and throat swabs in a small cohort of patients. They found increases in viral loads at the time that the patients became symptomatic. One patient never developed symptoms but was shedding virus beginning at day 7 after presumed infection. [25]

An initial report of 425 patients with confirmed COVID-19 in Wuhan, China, attempted to describe the epidemiology. Many of the initial cases were associated with direct exposure to live markets, while subsequent cases were not. This further strengthened the case for human-to-human transmission. The incubation time for new infections was found to be 5.2 days, with a range of 4.1-7 days. The longest time from infection to symptoms seemed to be 12.5 days. At this point, the epidemic had been doubling approximately every 7 days, and the base reproductive number was 2.2 (meaning every patient infects an average of 2.2 others). [26] Further data will likely better define the clinical course, incubation time, and duration of infectivity.

On March 10, 2020, Dr. Zunyou Wu of the CCDC delivered a report at the Conference on Retroviruses and Opportunistic Infections (CROI) meeting detailing the latest data from China, including updates on epidemiology and clinical presentation. COVID-19 is still most severe in older adults, but a marked male predominance no longer exists. At presentation, approximately 40% of the cases were “mild” with no pneumonia symptoms. Another 40% were “moderate” with symptoms of viral pneumonia, 15% were severe, and 5% critical. During the course of the illness, 10%-12% of cases that initially presented as mild or moderate illness progressed to severe, and 15%-20% of severe cases eventually became critical. The mean time from exposure to symptoms was 5-6 days. Patients with mild cases seem to recover within 2 weeks, while patients with severe infections may take 3-6 weeks to recover. Deaths were observed from 2-8 weeks following symptom onset. Interestingly, completely asymptomatic infection was rare (< 1%) after detailed symptom assessments. Analysis of the virology data does suggest that patients can shed virus 1-2 days before symptoms appear, raising concern for asymptomatic spread.

Diagnostic testing

The CDC has developed a diagnostic test for detection of the virus and received special Emergency Use Authorization (EUA) from the FDA on February 4, 2020, for its use. [27] The test is a real-time reverse transcription–polymerase chain reaction (rRT-PCR) assay that can be used to diagnose the virus in respiratory and serum samples from clinical specimens. [14]

Although the CDC rRT-PCR test was found to have performance issues related to manufacture of one of the reagents, the CDC has since developed an updated protocol that excludes the need for the third (problematic) component of the test without affecting accuracy. The test kits are now being shipped to US state and local public health laboratories that the CDC has determined to be qualified. [14]

The FDA has issued EUAs for several other tests, as follows: [28]

  • New York SARS-CoV-2 Real-time Reverse Transcriptase (RT)-PCR Diagnostic Panel (Wadsworth Center, NYSDOH)
  • cobas SARS-CoV-2 (Roche Molecular Systems, Inc.)
  • TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Inc.)
  • Panther Fusion SARS-CoV-2 (Hologic, Inc.)
  • COVID-19 RT-PCR Test (Laboratory Corporation of America)
  • Lyra SARS-CoV-2 Assay (Quidel Corporation)
  • Quest SARS-CoV-2 rRT-PCR (Quest Diagnostics Infectious Disease, Inc.)
  • Abbott RealTime SARS-CoV-2 assay (Abbott Molecular)

Of note, commercially available molecular tests for other respiratory viruses (even those detecting endemic coronaviruses) have not demonstrated the ability to detect SARS-CoV-2. Australian scientists have successfully grown the virus in cultures. [29]

A recent Chinese study reported that positive rates varied by sample type tested. In 205 patients with confirmed COVID-19 among 3 hospitals, pharyngeal swabs were collected 1-3 days after admission. Other types of samples were also collected throughout illness—sputum, blood, urine, feces, nasal swabs, and bronchial brush or bronchoalveolar lavage (BAL) fluid. Samples were tested with RT-PCR. Of 1070 total samples tested, types with the highest rates of positive results included BAL fluid (14/15; 93%), sputum (75/104; 72%), nasal swabs (5/8; 63%), brush biopsy (6/13; 46%), pharyngeal swabs (126/398; 32%), feces (44/153; 29%), blood (3/307; 1%), and urine (0/72; 0%). Nasal swabs were found to contain the most virus. [30]

Guo et al reported that immunoglobulin M (IgM) enzyme-linked immunoassay (ELISA) results were positive in 93% of patients with suspected COVID-19 (characteristic radiographic, clinical, and epidemiologic features) despite negative PCR results and despite negative results on plasma specimens tested before the COVID-19 outbreak. [31]

Treatment of COVID-19

No specific antiviral treatment is recommended for COVID-19. Infected patients should receive supportive care to help alleviate symptoms. Vital organ function should be supported in severe cases. [32]

No vaccine is currently available for SARS-CoV-2. Avoidance is the principal method of deterrence.

Numerous collaborative efforts to discover and evaluate effectiveness of antivirals (eg, remdesivir), immunotherapies (eg, hydroxychloroquine, sarilumab), monoclonal antibodies, and vaccines have rapidly emerged.

For more information on investigational drugs and biologics being evaluated for COVID-19, see Investigational Drugs and Biologics.

Infection control

Patients who are under investigation for COVID-19 should be evaluated in a private room with the door closed (an airborne infection isolation room is ideal) and asked to wear a surgical mask. All other standard contact and airborne precautions should be observed, and treating healthcare personnel should wear eye protection. [33]

Next:

Background

Coronaviruses comprise a vast family of viruses, 7 of which are known to cause disease in humans. Some coronaviruses that typically infect animals have been known to evolve to infect humans. SARS-CoV-2 is likely one such virus, postulated to have originated in a large animal and seafood market. Recent cases involve individuals who reported no contact with animal markets, suggesting that the virus is now spreading from person to person. [34]

Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are also caused by coronaviruses that “jumped” from animals to humans. More than 8,000 individuals developed SARS, nearly 800 of whom died of the illness (mortality rate of approximately 10%), before it was controlled in 2003. [35] MERS continues to resurface in sporadic cases. A total of 2,465 laboratory-confirmed cases of MERS have been reported since 2012, resulting in 850 deaths (mortality rate of 34.5%). [36]

The full genome of SARS-CoV-2 was first posted by Chinese health authorities soon after the initial detection, facilitating viral characterization and diagnosis. [14] The CDC analyzed the genome from the first US patient who developed the infection on January 24, 2020, concluding that the sequence is nearly identical to the sequences reported by China. [14] SARS-CoV-2 is a group 2b beta-coronavirus that has at least 70% similarity in genetic sequence to SARS-CoV. [36] Like MERS-CoV and SARS-CoV, SARS-CoV-2 originated in bats. [14]

Prognosis and Severity of COVID-19 Compared With SARS and MERS

Early reports have described COVID-19 as clinically milder than MERS or SARS in terms of severity and case fatality rate. [36] Thus far, the fatality rate for COVID-19 appears to be around 2%. [10]

Early in the outbreak, the WHO reported that severe cases in China had mostly been reported in adults older than 40 years with significant comorbidities and skewed toward men, although this pattern may be changing. [10]

COVID-19–related deaths in China have mostly involved older individuals (≥60 years) and persons with serious underlying health conditions. In the United States, attributable deaths have been most common in adults aged 85 years or older (10%-27%), followed by adults aged 65-84 years (3%-11%), adults aged 55-64 years (1%-3%), and adults aged 20-54 years (< 1%). As of March 16, 2020 no fatalities or ICU admissions have been reported in persons aged 19 years or younger. [12]

In an initial report of 41 patients infected in Wuhan, China, Huang et al reported a 78% male predominance, with 32% of all patients reporting underlying disease. The most common clinic finding was fever (98%), followed by cough (76%) and myalgia/fatigue (44%). Headache, sputum production, and diarrhea were less common. The clinical course was characterized by the development of dyspnea in 55% of patients and lymphopenia in 66%. All patients with pneumonia had abnormal lung imaging findings. Acute respiratory distress syndrome (ARDS) developed in 29% of patients, [37] and ground-glass opacities are common on CT scans. [38]

History, Symptoms of Infection, and Potential Complications

Presentations of COVID-19 have ranged from asymptomatic/mild symptoms to severe illness and mortality. Common symptoms have included fever, cough, and shortness of breath. [39] Other symptoms, such as malaise and respiratory distress, have also been described. [36]

Symptoms may develop 2 days to 2 weeks following exposure to the virus. [39] A pooled analysis of 181 confirmed cases of COVID-19 outside Wuhan, China, found the mean incubation period to be 5.1 days and that 97.5% of individuals who developed symptoms did so within 11.5 days of infection. [40]

Wu et al reported that, among 72,314 COVID-19 cases reported to the Chinese Center for disease Control and Prevention (CCDC), 81% were mild (absent or mild pneumonia), 14% were severe (hypoxia, dyspnea, >50% lung involvement within 24-48 hours), 5% were critical (shock, respiratory failure, multiorgan dysfunction), and 2.3% were fatal. [41]

In China, the case-fatality rate was found to range from 5.8% in Wuhan to 0.7% in the rest of China. [42] In most cases, fatality occurs in patients who are older or who have underlying health conditions (eg, diabetes, cardiovascular disease, chronic pulmonary disease, cancer, hypertension). [43]

Symptoms in children with infection appear to be uncommon, although some children with severe COVID-19 have been reported. [41]

Asymptomatic infections have been reported, but the incidence is unknown. [38]

Clinicians evaluating patients with fever and acute respiratory illness should obtain information regarding travel history or exposure to an individual who recently returned from a country or US state experiencing active local transmission. [44]

Patients with suspected COVID-19 should be reported immediately to infection-control personnel at their healthcare facility and the local or state health department. Current CDC guidance calls for the patient to be cared for with airborne and contact precautions (including eye shield) in place. [33] Patient candidates for such reporting include those with fever and symptoms of lower respiratory illness who have travelled from Wuhan City, China, within the preceding 14 days or who have been in contact with an individual under investigation for COVID-19 or a patient with laboratory-confirmed COVID-19 in the preceding 14 days. [44]

Early in the outbreak, one patient with COVID-19 (a 61-year-old man with an underlying abdominal tumor and cirrhosis) was admitted with severe pneumonia and respiratory failure. Complications of infection included severe pneumonia, septic shock, acute respiratory distress syndrome (ARDS), and multiorgan failure, resulting in death. [36]

A complete or partial loss of the sense of smell (anosmia) has been reported as a potential history finding in patients eventually diagnosed with COVID-19, but this has not been a distinguishing feature in published studies, so its clinical importance is questionable. [45]

Clinical Manifestations

The most common serious manifestation of COVID-19 upon initial presentation is pneumonia. Fever, cough, dyspnea, and abnormalities on chest imaging are common in these cases. [46, 37, 47, 48]

Huang et al found that, among patients with pneumonia, 99% had fever, 70% reported fatigue, 59% had dry cough, 40% had anorexia, 35% experienced myalgias, 31% had dyspnea, and 27% had sputum production. [37]

ARDS is a major complication in severe cases of COVID-19, affecting 20%-41% of hospitalized patients. [48, 49] Wu et al reported that, among 200 patients with COVID-19 who were hospitalized, older age, neutrophilia, and elevated lactate dehydrogenase and D-dimer levels increased the risks of ARDS and death. [49]

Arentz et al, in a study of 21 patients with severe COVID-19 admitted to the ICU in Washington State, reported that 33% had cardiomyopathy. [50]

At least two studies have reported on manifestations of infection in apparently asymptomatic individuals. Hu et al reported on 24 asymptomatic infected persons in whom chest CT scanning revealed ground-glass opacities/patchy shadowing in 50% of cases. [51] Wang et al reported on 55 patients with asymptomatic infection, two-thirds of whom had evidence of pneumonia as revealed by CT scanning. [52]

Diagnostic Testing and Workup

Currently, diagnostic testing for SARS-CoV-2 infection can be conducted by the CDC, state public health laboratories, hospitals using their own developed and validated tests, and some commercial reference laboratories. [19]

State health departments with a patient under investigation (PUI) should contact CDC’s Emergency Operations Center (EOC) at 770-488-7100 for assistance with collection, storage, and shipment of clinical specimens for diagnostic testing. Specimens from the upper respiratory tract, lower respiratory tract, and serum should be collected to optimize the likelihood of detection. [44]

Please see CDC Interim Guidance on Coronavirus Disease 2019 (COVID-19) for testing recommendations by the CDC.

The Infectious Diseases Society of America (IDSA) has also issued testing recommendations in terms of tier-based priority groups. [53]

According to the IDSA, the following patients should be considered highest priority for testing:

  • Patients who are critically ill or who have unexplained viral pneumonia or respiratory failure
  • Individuals with fever or signs/symptoms of lower respiratory tract illness who have had close contact with an individual with laboratory-confirmed COVID-19 within 14 days of symptom onset
  • Individuals with fever or signs/symptoms of lower respiratory tract illness who have traveled within 14 days of symptom onset to areas where sustained community transmission has been reported
  • Persons with fever or signs/symptoms of lower respiratory tract illness who are immunosuppressed, are older, or have underlying chronic health issues
  • Persons with fever or signs/symptoms of lower respiratory tract illness who are critical for the pandemic response, including healthcare workers, public health officials, and other essential leaders

Patients considered for second-priority testing include symptomatic residents of long-term care and hospitalized patients not in the ICU.

Patients considered for third-priority testing include those being treated in outpatient settings who meet criteria for influenza testing, including persons with certain comorbidities (eg, diabetes, COPD, CHF); pregnant women; and symptomatic pediatric patients with additional risk factors.

Finally, individuals considered for fourth-priority testing include persons who are undergoing monitoring for data collection and epidemiologic studies by health authorities.

Laboratory testing

If laboratory testing confirms an alternate pathogen, SARS-CoV-2 can be excluded, although this recommendation may change in the future. [54]

The CDC has developed a diagnostic test for detection of the virus and has received special emergency authorization from the FDA for its use. [27] The test is a real-time reverse transcription–polymerase chain reaction (rRT-PCR) assay that can be used to diagnose the virus in respiratory and serum samples from clinical specimens. [14]

Although the CDC rRT-PCR test was found to have performance issues related to manufacture of one of the reagents, the CDC has since developed an updated protocol that excludes the need for the third (problematic) component of the test without affecting accuracy. The test kits are now being shipped to US state and local public health laboratories that the CDC has determined to be qualified. [14]

Please see CDC Interim Guidance on Coronavirus Disease 2019 (COVID-19) for additional testing recommendations by the CDC.

In patients with suspected COVID-19, virus isolation in cell culture or initial characterization of viral agents recovered in cultures of specimens is not recommended for biosafety reasons. [44]

Leukopenia, leukocytosis, and lymphopenia were common among early cases. [36, 37]

Lactate dehydrogenase and ferritin levels are commonly elevated. [37]

Wu et al reported that, among 200 patients with COVID-19 who were hospitalized, older age, neutrophilia, and elevated lactate dehydrogenase and D-dimer levels increased the risks of ARDS and death. [49]

Chest radiography

Chest radiography may reveal pulmonary infiltrates. [55]

CT scanning

CT scan may reveal ground-glass infiltrates or consolidation, almost always bilateral. [37]

Treatment and Prevention of COVID-19

No specific antiviral treatment is recommended for COVID-19. Infected patients should receive supportive care to help alleviate symptoms. Vital organ function should be supported in severe cases. [32]

No vaccine is currently available for SARS-CoV-2. Avoidance is the principal method of deterrence.

Numerous collaborative efforts to discover and evaluate effectiveness of antivirals (eg, remdesivir), immunotherapies (eg, hydroxychloroquine, sarilumab), monoclonal antibodies, and vaccines have rapidly emerged.

For more information on investigational drugs and biologics being evaluated for COVID-19, see Investigational Drugs and Biologics.

General measures for prevention of viral respiratory infections include the following: [32]

  • Handwashing with soap and water for at least 20 seconds. An alcohol-based hand sanitizer may be used if soap and water are unavailable.
  • Individuals should avoid touching their eyes, nose, and mouth with unwashed hands.
  • Individuals should avoid close contact with sick people.
  • Sick people should stay at home (eg, from work, school).
  • Coughs and sneezes should be covered with a tissue, followed by disposal of the tissue in the trash.
  • Frequently touched objects and surfaces should be cleaned and disinfected regularly.

Infection control

Patients who are under investigation for COVID-19 should be evaluated in a private room with the door closed (an airborne infection isolation room is ideal) and asked to wear a surgical mask. All other standard contact and airborne precautions should be observed, and treating healthcare personnel should wear eye protection. [33]

Previous