Coronavirus Disease 2019 (COVID-19) 

Updated: Mar 31, 2020
Author: David J Cennimo, MD, FAAP, FACP, AAHIVS; Chief Editor: Michael Stuart Bronze, MD 

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]

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 10 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.[8]

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.[9]

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.[8]

Person-to-person spread of SARS-CoV-2 has been reported in the United States.[10, 11] 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:[12]

  • 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.

Signs and symptoms

Presentations of COVID-19 have ranged from asymptomatic/mild symptoms to severe illness and mortality. Symptoms may develop 2 days to 2 weeks following exposure to the virus.[13] 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.[14]

Wu and McGoogan 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.[15]

Common symptoms have included the following:

  • Fever
  • Cough
  • Myalgia
  • Fatigue

Less-common symptoms have included the following:

  • Headache
  • Sputum production
  • Diarrhea
  • Malaise
  • Shortness of breath/dyspnea
  • Respiratory distress

The most common serious manifestation of COVID-19 appears to be pneumonia.

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.[16]

Symptoms in children with infection appear to be uncommon, although some children with severe COVID-19 have been reported.[15]

See Clinical Presentation.

Diagnosis

COVID-19 should be considered a possibility in (1) patients with respiratory tract symptoms and newly onset fever or (2) in patients with severe lower respiratory tract symptoms with no clear cause. Suspicion is increased if such patients have been in an area with community transmission of SARS-CoV-2 or have been in close contact with an individual with confirmed or suspected COVID-19 in the preceding 14 days.

Microbiologic testing is required for definitive diagnosis. At present, such testing is of limited availability.

Patients who do not require emergency care are encouraged to contact their healthcare provider over the phone. Patients with suspected COVID-19 who present to a healthcare facility should prompt infection-control measures. They 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.[17]

See Workup.

Management

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.[18]

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.

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.[19]

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.[20] 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%).[21]

Route of Transmission

Transmission is believed to occur via respiratory droplets from coughing and sneezing, as with other respiratory pathogens, including influenza and rhinovirus.[22] 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 detectable 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.[23]

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.[24] 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.[25]

Data have suggested that asymptomatic patients are still able to transmit infection. This raises concerns for the effectiveness of isolation.[26, 27] 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.[28]

Epidemiology

Coronavirus outbreak and pandemic

As of March 31, 2020, COVID-19 has been confirmed in more than 803,000 individuals worldwide and has resulted in more than 39,000 deaths. More than 170 countries have reported laboratory-confirmed cases of COVID-19 on all continents except Antarctica.[29]

In the United States, 164,719 cases of COVID-19 have been confirmed as of March 31, 2020, resulting in 3,170 deaths.[30, 31] As of March 26, 2020, the United States has more confirmed infections than any other country in the world, including China and Italy.[32]

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.

United States data

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 had been reported in persons aged 19 years or younger.[33]

In the United States, as of March 16, 2020, patients aged 65 years or older had 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.[33]

Among 2,449 reported cases of COVID-19 in the United States as of March 16, 2020, 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.[33]

Among 508 hospitalized US patients as of March 16, 2020, 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%.[33]

Among US patients admitted to the ICU as of March 16, 2020, 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.[33]

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.[34] Community spread of the virus has now been reported in multiple states.[8]

COVID-19 in China

COVID-19–related deaths in China have mostly involved older individuals (≥60 years) and persons with serious underlying health conditions.[33]

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).[35] 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 data from China, including updates on epidemiology and clinical presentation. COVID-19 was reported to be most severe in older adults, but a marked male predominance was no longer found. 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.

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.[36]

Prognosis

Early reports have described COVID-19 as clinically milder than MERS or SARS in terms of severity and case fatality rate.[21] Thus far, the fatality rate for COVID-19 appears to be around 2%.[31]

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.[31]

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 had been reported in persons aged 19 years or younger.[33]

In China, the case-fatality rate was found to range from 5.8% in Wuhan to 0.7% in the rest of China.[37] 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).[38]

Virology

The full genome of SARS-CoV-2 was first posted by Chinese health authorities soon after the initial detection, facilitating viral characterization and diagnosis.[8] 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.[8] SARS-CoV-2 is a group 2b beta-coronavirus that has at least 70% similarity in genetic sequence to SARS-CoV.[21] Like MERS-CoV and SARS-CoV, SARS-CoV-2 originated in bats.[8]

 

Presentation

History

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.[13] Other symptoms, such as malaise and respiratory distress, have also been described.[21]

Symptoms may develop 2 days to 2 weeks following exposure to the virus.[13] 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.[14]

Wu and McGoogan 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.[15]

In an initial report of 41 patients infected in Wuhan, China, Huang et al reported that 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,[39] and ground-glass opacities are common on CT scans.[36]

Symptoms in children with infection appear to be uncommon, although some children with severe COVID-19 have been reported.[15]

Asymptomatic infections have been reported, but the incidence is unknown.[36]

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.[40]

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.[17] 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.[40]

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.[21]

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.[16]

Physical Examination

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.[17]

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.[41, 39, 42, 43]

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.[39]

ARDS is a major complication in severe cases of COVID-19, affecting 20%-41% of hospitalized patients.[43, 44] 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.[44]

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.[45]

Clinical Progression

A retrospective, single-center study from Shanghai evaluated clinical progression of COVID-19 in 249 patients. The interval from symptom onset to hospitalization averaged 4 days (range, 2-7 days) among symptomatic patients. The vast majority (94.3%) of patients developed fever. Hospitalization lasted an average of 16 days (range, 12-20 days) before discharge.

The estimated median duration of fever in all febrile patients was 10 days after symptom onset.

In 163 patients (65.7%), radiological abnormalities (compared with baseline) occurred on day 7 following symptom onset, 154 (94.5%) of whom improved radiologically by day 14.

The median duration to negative results on RT-PCT using upper respiratory tract samples was 11 days. Viral clearance was more likely to be delayed in ICU patients.

The authors concluded that most cases of COVID-19 are mild. Early viral replication control and host-directed therapy applied at later stages were essential to improving outcomes.[46]

 

Workup

Approach Considerations

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.[22]

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.[40]

The FDA now recommends that nasal swabs that access just the front of the nose be used in symptomatic patients, allowing for (1) a more comfortable and simplified collection method and (2) self-collection at collection sites.[47]

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.[48]

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 Studies

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.[49] 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.[8]

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.[8]

The FDA has issued EUAs for several other tests, as follows:[50]

  • 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)
  • NxTAG CoV Extended Panel Assay (Luminex Molecular Diagnostics, Inc.)
  • ID NOW COVID-19 (Abbott Diagnostics Scarborough, Inc.)
  • Real-Time Fluorescent RT-PCR Kit for Detecting SARS-2019-nCoV (BGI Genomics Co. Ltd)
  • AvellinoCoV2 test (Avellino Lab USA, Inc.)
  • PerkinElmer New Coronavirus Nucleic Acid Detection Kit (PerkinElmer, Inc.)
  • Accula SARS-Cov-2 Test (Mesa Biotech Inc.)
  • BioFire COVID-19 Test (BioFire Defense, LLC
  • Xpert Xpress SARS-CoV-2 test (Cepheid)
  • Primerdesign Ltd COVID-19 genesig Real-Time PCR assay (Primerdesign Ltd.)
  • ePlex SARS-CoV-2 Test (GenMark Diagnostics, Inc.)
  • Simplexa COVID-19 Direct assay (DiaSorin Molecular LLC)

If laboratory testing confirms an alternate pathogen, SARS-CoV-2 can be excluded, although this recommendation may change in the future.[51]

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.[52]

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.[53]

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.[54]

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.[40]

Leukopenia, leukocytosis, and lymphopenia were common among early cases.[21, 39]

Lactate dehydrogenase and ferritin levels are commonly elevated.[39]

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.[44]

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

CT Scanning

Chest CT scanning in patients with COVID-19–associated pneumonia usually shows ground-glass opacification, possibly with consolidation. Some studies have reported that abnormalities on chest CT scans are usually bilateral, involve the lower lobes, and have a peripheral distribution. Pleural effusion, pleural thickening, and lymphadenopathy have also been reported, although with less frequency.[39, 55, 56]

Bai et al reported the following common chest CT scanning features among 201 patients with CT abnormalities and positive RT-PCR results for COVID-19:[57]

  • Peripheral distribution (80%)
  • Ground-glass opacity (91%)
  • Fine reticular opacity (56%)
  • Vascular thickening (59%)

Less-common features on chest CT scanning included the following:[57]

  • Central and peripheral distribution (14%)
  • Pleural effusion (4.1%)
  • Lymphadenopathy (2.7%)

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.[58] Wang et al reported on 55 patients with asymptomatic infection, two-thirds of whom had evidence of pneumonia as revealed by CT scanning.[59]

Progression of CT abnormalities

Mingzhi et al recommend high-resolution CT scanning and reported the following CT changes over time in patients with COVID-19 among 3 Chinese hospitals:[60]

  • Early phase: Multiple small patchy shadows and interstitial changes begin to emerge in a distribution beginning near the pleura or bronchi rather than the pulmonary parenchyma.
  • Progressive phase: The lesions enlarge and increase, evolving to multiple ground-glass opacities and infiltrating consolidation in both lungs.
  • Severe phase: Massive pulmonary consolidations occur, while pleural effusion is rare.
  • Dissipative phase: Ground-glass opacities and pulmonary consolidations are absorbed completely. The lesions begin evolving into fibrosis. [60]

Chest Radiography

Chest radiography may reveal pulmonary infiltrates.[61]

 

Treatment

Approach Considerations

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.[18]

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.

Medical Care

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

Prevention

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

General measures for prevention of viral respiratory infections include the following:[18]

  • 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.

Investigational Drugs and Biologics

No drugs or biologics have been proven to be effective for the prevention or treatment of COVID-19. Numerous antiviral agents, immunotherapies, and vaccines are being investigated and developed as potential therapies. Searching for effective therapies for COVID-19 infection is a complex process. Gordon et al identified 332 high-confidence SARS-CoV-2 human protein-protein interactions. Among these, they identified 66 human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials, and/or preclinical compounds. As of March 22, 2020, these researchers are in the process of evaluating the potential efficacy of these drugs in live SARS-CoV-2 infection assays.[62]

McCreary and Pogue’s “Review of Early and Emerging Options” for COVID-19 treatment provides a comprehensive review of potential beneficial therapies and adjunctive treatments.[63]

An international collaborative publication offers guidance for sepsis management in critically ill adults with COVID-19 and includes evidence-based recommendations.[64]

Examples of prospective treatments are discussed below.

Antiviral Agents

Remdesivir

The broad-spectrum antiviral agent remdesivir (GS-5734; Gilead Sciences, Inc) is a nucleotide analog prodrug. It was studied in clinical trials for Ebola virus infections but showed limited benefit.[65] Remdesivir has been shown to inhibit replication of other human coronaviruses associated with high morbidity in tissue cultures, including severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. Efficacy in animal models has been demonstrated for SARS-CoV and MERS-CoV.[66]

Several phase 3 clinical trials are testing remdesivir for treatment of COVID-19 in the United States, South Korea, and China. An adaptive randomized trial of remdesivir coordinated by the National Institute of Health (NCT04280705) was started first against placebo, but additional therapies can be added to the protocol as evidence emerges. The first experience with this study involved passengers of the Diamond Princess cruise ship in quarantine at the University of Nebraska Medical Center after returning to the United States from Japan following an on-board outbreak of COVID-19.[67] Positive results were seen with remdesivir after use by the University of Washington in the first case of COVID-19 documented on US soil.[68] The drug was prescribed under an open-label Compassionate Use protocol, but the US FDA has since moved to allow Expanded access to remdesivir, permitting approved sites to prescribe the investigational product for multiple patients under protocol without requesting permission for each.[69]

An in vitro study showed that the antiviral activity of remdesivir plus interferon beta (IFNb) was superior to that of lopinavir/ritonavir (LPV/RTV; Kaletra, Aluvia; AbbVie Corporation). Prophylactic and therapeutic remdesivir improved pulmonary function and reduced lung viral loads and severe lung pathology in mice, whereas LPV/RTV-IFNb slightly reduced viral loads without affecting other disease parameters. Therapeutic LPV/RTV-IFNb improved pulmonary function but did not reduce virus replication or severe lung pathology.[70]

Lopinavir/ritonavir

A combination of lopinavir/ritonavir plus IFNb treatment improved clinical parameters in marmosets and mice infected with MERS-CoV.[66]

In a randomized, controlled, open-label trial of hospitalized adults (n=199) with confirmed SARS-CoV-2 infection, recruited patients had an oxygen saturation of 94% or less on ambient air or PaO2 of less than 300 mm Hg and were receiving a range of ventilatory support modes (eg, no support, mechanical ventilation, extracorporeal membrane oxygenation [ECMO]). These patients were randomized to receive lopinavir/ritonavir 400 mg/100 mg PO BID for 14 days added to standard care (n=99) or standard care alone (n=100). Results showed that time to clinical improvement did not differ between the two groups (median, 16 days). The mortality rate at 28 days was numerically lower for lopinavir/ritonavir compared with standard care (19.2% vs 25%) but did not reach statistical significance.[71] An editorial accompanies this study that is informative in regard to the extraordinary circumstances of conducting such a study in the midst of the outbreak.[72] Average wholesale price (AWP) for a course of lopinavir/ritonavir at this dose is $575.

Other investigational antivirals

Other investigational antivirals being tested for efficacy against COVID-19 include rintatolimod (toll-like receptor 3 [TLR-3] agonist), azvudine (nucleoside reverse transcriptase inhibitor), danoprevir (NS3/4A HCV protease inhibitor), plitidepsin (targets EF1A), and favipiravir (viral RNA polymerase inhibitor).

The TLR-3 agonist rintatolimod (Poly I:Poly C12U; Ampligen; AIM ImmunoTech) is being tested as a potential treatment for COVID-19 by the National Institute of Infectious Diseases (NIID) in Japan and the University of Tokyo.[73] It is a broad-spectrum antiviral agent.[74]

Plitidepsin (Aplidin; PharmaMar) is a member of the compound class known as didemnins. In vitro studies from Spain report plitidepsin potentially targets EF1A, which is key to multiplication and spread of the virus.[75]

Preliminary results of favipiravir’s moderate antiviral effect on COVID-19 have emerged from a study in China, although the parent company of the drug (Fujifilm Pharmaceuticals, Japan) has not confirmed the drug’s efficacy.[76] Favipiravir (Avigan) is approved in Japan and China for influenza and is investigational for use in COVID-19.

Immunomodulators and Other Investigational Therapies

Interleukin-6 inhibitors

Interleukin-6 (IL-6) inhibitors may ameliorate severe damage to lung tissue caused by cytokine release in patients with serious COVID-19 infections. Several studies have indicated a “cytokine storm” with release of IL-6, IL-1, IL-12, and IL-18, along with tumor necrosis factor alpha (TNFα) and other inflammatory mediators. The increased pulmonary inflammatory response may result in increased alveolar-capillary gas exchange, making oxygenation difficult in patients with severe illness.

On March 16, 2020, Sanofi and Regeneron announced initiation of a phase 2/3 trial of the IL-6 inhibitor sarilumab (Kevzara). The United States–based component of the trial will be initiated in New York. The multicenter, double-blind, phase 2/3 trial has an adaptive design with two parts and is anticipated to enroll up to 400 patients. The first part will recruit patients with severe COVID-19 infection across approximately 16 US sites, and will evaluate the effect of sarilumab on fever and the need for supplemental oxygen. The second, larger, part of the trial will evaluate improvement in longer-term outcomes, including preventing death and reducing the need for mechanical ventilation, supplemental oxygen, and/or hospitalization.[77]

Genentech, maker of another IL-6 inhibitor, tocilizumab (Actemra), is working with the FDA to initiate a randomized, double-blind, placebo-controlled phase III clinical trial in collaboration with BARDA to evaluate the safety and efficacy of tocilizumab plus standard of care in hospitalized adult patients with severe COVID-19 pneumonia compared to placebo plus standard of care. The goal is to begin in early April 2020, with a target of approximately 330 patients globally. The primary and secondary endpoints of the study include clinical status, mortality, mechanical ventilation, and ICU variables.[78]

An open label, non-controlled, non–peer reviewed study was conducted in China in 21 patients with severe respiratory symptoms related to COVID-19. All had a confirmatory diagnosis of SARS-CoV-2 infection. The patients in the trial had a mean age of 56.8 years (18 of 21 were male). Although all patients met enrollment criteria of (1) respiratory rate of 30 breaths/min or more, (2) SpO2 of 93% or less, and (3) PaO2/FiO2 of 300 mm Hg or less, only two of the patients required invasive ventilation. The other 19 patients received various forms of oxygen delivery, including nasal canula, mask, high-flow oxygen, and noninvasive ventilation. All patients received standard of care, including lopinavir and methylprednisolone. Patients received a single dose of 400 mg tocilizumab via intravenous infusion. In general, the patients improved with lower oxygen requirements, lymphocyte counts returned to normal, and 19 patients were discharged with a mean of 15.5 days after tocilizumab treatment. The authors concluded that tocilizumab was an effective treatment in patients with severe COVID-19.[79]

Nonetheless, these conclusions should be viewed with extreme caution. No controls were used in this study, and only one patient was receiving invasive mechanical ventilation. In addition, all patients were receiving standard therapy for at least a week before tocilizumab was started. AWP for 400 mg of tocilizumab is $2765.

An anti-interleukin-6 receptor monoclonal antibody (TZLS-501; Tiziana Life Sciences and Novimmune) is currently being developed.[80]

Hydroxychloroquine and chloroquine

Hydroxychloroquine and chloroquine are widely used antimalarial drugs that elicit immunomodulatory effects and are therefore also used to treat autoimmune conditions (eg, systemic lupus erythematosus, rheumatoid arthritis). As inhibitors of heme polymerase, they are also believed to have additional antiviral activity via alkalinization of the phagolysosome, which inhibits the pH-dependent steps of viral replication. Wang et al reported that chloroquine effectively inhibits SARS-CoV-2 in vitro.[81] The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2–infected Vero cells. Physiologically based pharmacokinetic models (PBPK) were conducted for each drug. Hydroxychloroquine was found to be more potent than chloroquine in vitro. Based on PBPK models, the authors recommend a loading dose of hydroxychloroquine 400 mg PO BID, followed by 200 mg BID for 4 days.[82]

Published reports stemming from the worldwide outbreak of COVID-19 have evaluated the potential usefulness of these drugs in controlling cytokine release syndrome in critically ill patients.[82, 83]

According to a consensus statement from a multicenter collaboration group in China, chloroquine phosphate 500 mg (300 mg base) twice daily in tablet form for 10 days may be considered in patients with COVID-19 pneumonia.[84] While no peer-reviewed treatment outcomes are available, Gao and colleagues profess that 100 patients have demonstrated significant improvement with this regimen without documented toxicity.[83] It should be noted this is 14 times the typical dose of chloroquine used per week for malaria prophylaxis and 4 times that used for treatment. Cardiac toxicity should temper enthusiasm for this as a widespread cure for COVID-19. It should also be noted that chloroquine was previously found to be active in vitro against multiple other viruses but has not proven fruitful in clinical trials, even resulting in worse clinical outcomes in human studies of Chikungunya virus infection (a virus unrelated to SARS-CoV-2).

The French have embraced hydroxychloroquine as a potentially more potent therapy with an improved safety profile to treat and prevent the spread of COVID-19.[85] If it is effective, the optimal regimen of hydroxychloroquine is unknown, although some experts have recommended higher doses, such as 600-800 mg per day. A study of hydroxychloroquine for postexposure prophylaxis in healthcare workers or household contacts is underway.[86]

One study in France recently evaluated patients treated with hydroxychloroquine against a control group who received standard of care. After dropping 6 patients from the analysis for having incomplete data, the 20 remaining patients receiving hydroxychloroquine had improved nasopharyngeal clearance of the virus on day 6 (70% [14/20] vs 12.5% [2/16]).[87] This is an unusual approach to reporting results because the clinical correlation with nasopharyngeal clearance on day 6 is unknown and several patients changed status within a few days of that endpoint (converting from negative back to positive). The choice of that particular endpoint was also not explained by the authors, yet 4 of the 6 excluded patients had adverse outcomes (admission to ICU or death) at that time but were not counted in the analysis. Furthermore, patients who refused to consent to the study group were included in the control arm, indicating unorthodox study enrollment.

Azithromycin

The small open-label study of hydroxychloroquine in France included azithromycin in 6 patients for potential bacterial superinfection. These patients were reported to have 100% clearance of SARS-CoV-2. While intriguing, these results warrant further analysis. The patients receiving combination therapy had lower viral loads, and, when compared with patients receiving hydroxychloroquine alone with similar viral burden, the results are fairly similar (6/6 vs 7/9).[87] Hydroxychloroquine and azithromycin each carry the warning of QT prolongation and can be associated with an increased risk of cardiac death when used in a broader population.[88]

Corticosteroids

Corticosteroids are not generally recommended for treatment of COVID-19 or any viral pneumonia.[89] The benefit of corticosteroids in septic shock results from tempering the host immune response to bacterial toxin release. The incidence of shock in patients with COVID-19 is relatively low (5% of cases). It is more likely to produce cardiogenic shock from increased work of the heart need to distribute oxygenated blood supply and thoracic pressure from ventilation. Corticosteroids can induce harm through immunosuppressant effects during the treatment of infection and have failed to provide a benefit in other viral epidemics, such as respiratory syncytial virus (RSV) infection, influenza infection, SARS, and MERS.[90]

Early guidelines for management of critically ill adults with COVID-19 specify when to use low-dose corticosteroids and when to refrain from using corticosteroids. The recommendations depend on the precise clinical situation (eg, refractory shock, mechanically ventilated patients with ARDS); however, these particular recommendations are based on evidence listed as weak.[64]

Nonetheless, a study describing clinical outcomes of patients diagnosed with COVID-19 was conducted in Wuhan China (N = 201). Eighty-four patients (41.8%) developed ARDS, and of those, 44 (52.4%) died. Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72).[44]

An open-label prospective trial is planned to study clinical improvement in patients treated with methylprednisolone IV.[91]

Convalescent plasma

The FDA is facilitating access to convalescent plasma, antibody-rich products that are collected from eligible donors who have recovered from COVID-19. Use of this product in patients with serious or immediately life-threatening COVID-19 may shorten the duration or severity of illness.[92]

The FDA has posted information for investigators wishing to study convalescent plasma for use in patients with serious or immediately life-threatening COVID-19 through the process of single-patient emergency Investigational New Drug (IND) applications for individual patients. The FDA is also actively engaging with researchers to discuss the possibility of collaboration on the development of a master protocol for use of convalescent plasma, with the goal of reducing duplicative efforts.

Nitric oxide

Published findings from the 2004 SARS-CoV infection suggest the potential role of inhaled nitric oxide (iNO; Mallinckrodt Pharmaceuticals, plc) as a supportive measure for treating infection in patients with pulmonary complications. Treatment with iNO reversed pulmonary hypertension, improved severe hypoxia, and shortened the length of ventilatory support compared with matched control patients with SARS.[93]

A phase 2 study of iNO is underway in patients with COVID-19 with the goal of preventing disease progression in those with severe ARDS.[94] The Society of Critical Care Medicine recommends against the routine use of iNO in patients with COVID-19 pneumonia. Instead, they suggest a trial only in mechanically ventilated patients with severe ARDS and hypoxemia despite other rescue strategies.[64] The cost of iNO is reported as exceeding $100/hour.

Other immunomodulators and investigational therapies

Table 1. Additional Immunomodulators and Other Investigational Therapies (Open Table in a new window)

Therapy Proposed Use Description/Comments
Ifenprodil (NP-120; Algernon Pharmaceuticals) [95] ARDS/lung injury N-methyl-d-aspartate (NDMA) receptor glutamate receptor antagonist. NMDA is linked to inflammation and lung injury. An injectable and long-acting oral product are under production to begin clinical trials for COVID-19 and acute lung injury.
Remestemcel-L (Mesoblast Ltd) [96] ARDS/lung injury Allogeneic mesenchymal stem cell (MSC) product candidate being investigated as a treatment for ARDS associated with COVID-19.
Inhaled therapy (MannKind and Immix) [97] ARDS/lung injury Dry powder inhaled formulation with potential to treat ARDS caused by COVID-19.
TJM2 (I-MAB Biopharma) [98] Cytokine storm TJM2 is a neutralizing antibody against human granulocyte-macrophage colony stimulating factor (GM-CSF), an important cytokine that plays a critical role in acute and chronic inflammation.
Gimsilumab (Roivant) [99] Cytokine storm Monoclonal antibody that targets GM-CSF, a proinflammatory cytokine that is up-regulated in patients with COVID-19.
Anti-SARS-CoV-2 polyclonal hyperimmune globulin [100] Immunoglobulin Under development to treat high-risk patients.
CEL-SCI Corporation [101] Immunotherapy Preferentially directed immunotherapy using ligand antigen epitope presentation system (LEAPS) peptide technology to reduce COVID-19 viral load and consequent lung damage.
Brilacidin (Innovation Pharmaceuticals) [102] Immunotherapy Defensin-mimetic that mimics the immune system and disrupts the pathogen membrane, leading to cell death. It is undergoing clinical-stage testing at a US regional biocontainment laboratory. Also see Table 2 for potential use as a vaccine adjuvant.
Monoclonal antibodies (Regeneron) [103] Antibody-directed therapy Mab cocktail slated by mid-April, with the goal of initiating human trials by early summer.
Vir Biotechnology and NIH [104] Antibody-directed therapy Human monoclonal antibodies against coronaviruses, including COVID-19.
TAK-888 (Takeda) [105] Antibody-directed therapy Concentrated virus-specific antibodies from plasma collected from people who have already recovered from COVID-19.
Antibodies (Eli Lilly and AbCellera) [106] Antibody-directed therapy Antibody treatment from more than 500 unique antibodies isolated from one of the first US patients to recover from COVID-19.
Vascular leakage therapy [107] Reduction of endothelial dysfunction Targets the angiopoietin-Tie2 signaling pathway to reduce endothelial dysfunction.

Vaccines

Table 2. Investigational Vaccines (Open Table in a new window)

Vaccine Comments
INO-4800 (Inovio Pharmaceuticals) [108] Phase 1 human clinical trials are expected to begin in April 2020. In addition, Inovio has received a grant from the Bill and Melinda Gates Foundation to accelerate testing and scale up a smart device (Cellectra 3PSP) for large-scale intradermal vaccine delivery.
mRNA-1273 (Moderna Inc) [109, 110] A phase 1 study has been initiated in 45 healthy volunteers as of March 16, 2020 at Kaiser Permanente Washington Health Research Instituted in Seattle.
mRNA vaccine (CureVac) [111] Vaccine is in development and not yet ready for human testing as of March 16, 2020.
mRNA vaccine BNT162 (BioNTech and Pfizer) [112] Joint development of BioNTech’s mRNA-based vaccine candidate initiated.
COVID-19 S-Trimer (GlaxoSmithKline [GSK] and Clover Biopharmaceuticals) [113] Preclinical development is underway using GSK’s adjuvants (compounds that enhance vaccine efficacy) and Clover’s proprietary proteins, which stimulate an immune response.
SARS-CoV-2 vaccine (Johnson & Johnson [J&J]) [114] Partnering with the Biomedical advanced Research and Development Authority (BARDA) to utilize Janssen’s AdVac and PER.C6 technologies, which provide rapid upscale production of an optimal vaccine candidate.
rDNA vaccine (Sanofi) [115] Collaborating with BARDA to develop a vaccine using their recombinant DNA platform.
Saponin-based Matrix-M adjuvant vaccine (Novavax) [116] Stimulates the entry of antigen-presenting cell into the injection site and enhances antigen presentation in local lymph nodes to boost the immune response.
Live-attenuated vaccine (Codagenix) [117] Codagenix, a clinical-stage biotechnology company, is collaborating with the Serum Institute of India to co-develop a live-attenuated vaccine.
PCR-based DNA vaccine (Applied DNA Sciences and Takis Biotech) [118] The collaboration has designed four COVID-19 vaccine candidates utilizing PCR-based DNA manufacturing systems for preclinical testing in animals.
Intranasal COVID-19 vaccine (Altimmune, Inc) [119] Design and synthesis has been completed and is advancing toward animal testing.
Brilacidin adjuvant vaccine (Innovation Pharmaceuticals) [120] Material Transfer Agreement (MTA) signed with a leading public health-focused US university and top coronavirus expert to evaluate the potential antiviral properties as a defensing adjuvant. Also see Table 1.

Renin Angiotensin System Blockade and COVID-19

SARS-CoV-2 is known to utilize angiotensin-converting enzyme 2 (ACE2) receptors for entry into target cells.[121]

Concern arose regarding appropriateness of continuation of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with COVID-19 after early reports noted an association between disease severity and comorbidities such as hypertension, cardiovascular disease, and diabetes, which are often treated with ACEIs and ARBs. The reason for this association remains unclear.[122, 123]

The speculated mechanism for detrimental effect of ACEIs and ARBs is related to ACE2. It was therefore hypothesized that any agent that increases expression of ACE2 could potentially increase susceptibility to severe COVID-19 by improving viral cellular entry;[122] however, physiologically, ACE2 converts angiotensin 2 to angiotensin 1-7, which leads to vasodilation and may protect against lung injury.[123, 124] It is therefore uncertain whether an increased expression of ACE2 receptors would worsen or mitigate the effects of SARS-CoV-2 in human lungs.

There are also conflicting data regarding whether ACEIs and ARBs increase ACE2 levels. Some studies in animals have suggested that ACEIs and ARBs increase expression of ACE2,[125, 126, 127] while other studies have not shown this effect.[128, 129]

As controversy remains regarding whether ACEIs and/or ARBs increase ACE2 expression and how this effect may influence outcomes in patients with COVID-19, cardiology societies have largely recommended against initiating or discontinuing these medications based solely on active SARS-CoV-2 infection.[130]

Two clinical trials are currently in development at the University of Minnesota evaluating the use of losartan in patients with COVID-19 in inpatient and outpatient settings.[131, 132] Results from these trials will provide insight into the potential role of ARBs in the treatment of COVID-19.

 

Guidelines

CDC Interim Guidance on Coronavirus Disease 2019 (COVID-19)

The CDC has issued interim guidance for the COVID-19 outbreak, including evaluation and testing of persons under investigation (PUIs) for COVID-19.[133]

Information regarding COVID-19 is rapidly emerging and evolving. For the latest information, see the following:

Criteria to guide evaluation and testing of patients under investigation for COVID-19

Clinicians should work with state and local health departments to coordinate testing. The FDA has authorized COVID-19 diagnostic testing to be made available in clinical laboratories, expanding the capacity for clinicians to consider testing symptomatic patients.

The decision to administer COVID-19 testing should be based on clinical judgment, along with the presence of compatible signs and symptoms. The CDC now recommends that COVID-19 be considered a possibility in patients with severe respiratory illness regardless of travel history or exposure to individuals with confirmed infection. The most common symptoms in patients with confirmed COVID-19 have included fever and/or symptoms of acute respiratory illness, including breathing difficulties and cough.

Patient groups in whom COVID-19 testing may be prioritized include the following:

  1. Hospitalized patients with compatible signs and symptoms in the interest of infection control
  2. High-risk symptomatic patients (eg, older patients and patients with underlying conditions that place them at higher likelihood of a poor outcome)
  3. Symptomatic patients who have had close contact with an individual with suspected or confirmed COVID-19 or who have traveled from affected geographic areas within 14 days of symptom onset

Clinicians should also consider epidemiologic factors when deciding whether to test for COVID-19. Other causes of respiratory illness (eg, influenza) should be ruled out.

Patients with mild illness who are otherwise healthy should stay home and coordinate clinical management with their healthcare provider over the phone. Patients with severe symptoms (eg, breathing difficulty) should seek immediate care. High-risk patients (older individuals and immunocompromised patients or those with underlying medical conditions) should be encouraged to contact their healthcare provider in the case of any illness, even if mild.[133]

Reporting, testing, and specimen collection

In the event that a patient is classified a PUI for COVID-19, infection-control personnel at the healthcare facility should immediately be notified. Upon identification of a PUI, state health departments should immediately complete a PUI and Case Report form and can contact CDC’s Emergency Operations Center (EOC) at 770-488-7100 for assistance.

Currently, diagnostic testing for COVID-19 is being performed at state public health laboratories and the CDC. Testing for other respiratory pathogens should not delay specimen testing for COVID-19.

The CDC recommends collecting and testing upper respiratory specimens (oropharyngeal and nasopharyngeal swabs) and lower respiratory specimens (sputum, if possible) in patients with a productive cough for initial diagnostic testing. Sputum induction is not indicated. If clinically indicated, a lower respiratory tract aspirate or bronchoalveolar lavage sample should be collected and tested. Once a PUI is identified, specimens should be collected as soon as possible.[133]

 

Questions & Answers

Overview

What is coronavirus?

What is novel coronavirus?

What is COVID-19?

How did the coronavirus outbreak start?

Where did the coronavirus outbreak start?

Why is coronavirus infection called COVID-19?

What are the signs and symptoms of coronavirus disease 2019 (COVID-19)?

What is the CDC risk assessment for coronavirus disease 2019 (COVID-19) in the US?

Who is at highest risk of contracting coronavirus disease 2019 (COVID-19)?

Can coronavirus disease 2019 (COVID-19) spread from person to person?

Which precautions should high-risk persons take to prevent coronavirus disease 2019 (COVID-19)?

What is the process for diagnosing coronavirus disease 2019 (COVID-19)?

How is coronavirus disease 2019 (COVID-19) treated?

What are coronaviruses?

How does coronavirus disease 2019 (COVID-19) spread?

Can asymptomatic people spread coronavirus disease 2019 (COVID-19)?

What is the duration of viral shedding in persons with coronavirus disease 2019 (COVID-19)?

Which patient groups in the US have the highest risk of dying of coronavirus disease 2019 (COVID-19)?

What is the global and US prevalence of coronavirus disease 2019 (COVID-19)?

Which age groups are most likely to develop coronavirus disease 2019 (COVID-19)?

Which age groups are most likely to be hospitalized with coronavirus disease 2019 (COVID-19)?

Which age groups are most likely to be admitted to the ICU for coronavirus disease 2019 (COVID-19)?

Is coronavirus spreading in the US?

What was the epidemiology of coronavirus disease 2019 (COVID-19) in Wuhan, China?

What were the epidemiologic and clinical features of the coronavirus disease 2019 (COVID-19) outbreak in China?

Which age groups are most likely to die of coronavirus disease 2019 (COVID-19)?

Is coronavirus disease 2019 (COVID-19) more severe than SARS and MERS?

Which patient groups were more likely to develop severe coronavirus disease 2019 (COVID-19) in China?

What were the mortality risk factors for coronavirus disease 2019 (COVID-19) in China?

Is the genome of SARS-CoV-2 (coronavirus) known?

Presentation

What are the possible symptoms of coronavirus disease 2019 (COVID-19)?

How long do coronavirus disease 2019 (COVID-19) symptoms take to develop?

What is the incubation period for coronavirus disease 2019 (COVID-19)?

Are symptoms of coronavirus disease 2019 (COVID-19) in children common?

How common is asymptomatic coronavirus disease 2019 (COVID-19)?

What are important history details when evaluating a patient for coronavirus disease 2019 (COVID-19)?

What were the most common presentations of coronavirus disease 2019 (COVID-19) in China?

What is the most common serious symptom of coronavirus disease 2019 (COVID-19)?

How common is acute respiratory distress syndrome (ARDS) in patients with coronavirus disease 2019 (COVID-19)?

Are cardiac complications common in coronavirus disease 2019 (COVID-19)?

How should a patient under investigation for coronavirus disease 2019 (COVID-19) be evaluated in healthcare settings?

What is the clinical progression of coronavirus disease 2019 (COVID-19)?

Workup

Where are diagnostic tests for coronavirus disease 2019 (COVID-19) processed?

What are the IDSA recommendations for prioritizing patients to be tested for coronavirus disease 2019 (COVID-19)?

Can viral culture be used to diagnose coronavirus disease 2019 (COVID-19)?

What are common lab features in patients with coronavirus disease 2019 (COVID-19)?

What type of test is used to evaluate for coronavirus disease 2019 (COVID-19)?

Which tests are available for coronavirus disease 2019 (COVID-19)?

Which clinical specimen samples are best for coronavirus disease 2019 (COVID-19) testing?

Are there any signs of coronavirus disease 2019 (COVID-19) in seemingly asymptomatic patients?

What is the role of CT scanning in the diagnosis of coronavirus disease 2019 (COVID-19)?

What is the role of chest radiography in the diagnosis of coronavirus disease 2019 (COVID-19)?

Treatment

How is coronavirus disease 2019 (COVID-19) treated?

Is a coronavirus disease 2019 (COVID-19) vaccine available?

What are the general measures for prevention of viral respiratory infections, including coronavirus disease 2019 (COVID-19)?

Which drugs and biologics are proven effective for the treatment of coronavirus disease 2019 (COVID-19)?

What is the role of the antiviral drug remdesivir in the treatment of coronavirus disease 2019 (COVID-19)?

What is the role of the antivirals lopinavir/ritonavir in the treatment of coronavirus disease 2019 (COVID-19)?

What is the role of convalescent plasma in the treatment of coronavirus disease 2019 (COVID-19)?

What other antiviral drugs are being investigated for the treatment of coronavirus disease 2019 (COVID-19)?

What is the role of interleukin-6 (IL-6) inhibitors in the treatment of coronavirus disease 2019 (COVID-19)?

What is the role of the IL-6 inhibitor sarilumab (Kevzara) in the treatment of coronavirus disease 2019 (COVID-19)?

What is the role of the IL-6 inhibitor tocilizumab (Actemra) in the treatment of coronavirus disease 2019 (COVID-19)?

What are the roles of hydroxychloroquine and chloroquine in the treatment of coronavirus disease 2019 (COVID-19)?

What is the role of corticosteroids (such as methylprednisolone) in the treatment of coronavirus disease 2019 (COVID-19)?

What is the role of nitric oxide (methylprednisolone) in the treatment of coronavirus disease 2019 (COVID-19)?

What other immunomodulators and investigational therapies are being evaluated for the treatment of coronavirus disease 2019 (COVID-19)?

Which vaccines are being investigated for coronavirus disease 2019 (COVID-19) prevention?

What is the role of azithromycin in the treatment of coronavirus disease 2019 (COVID-19)?

What are considerations for using ACE inhibitors (ACEIs) and ARBs in patients with coronavirus disease 2019 (COVID-19)?

Guidelines

What are the CDC criteria to guide evaluation and testing of patients under investigation for coronavirus disease 2019 (COVID-19)?

What are the CDC guidelines for reporting, testing, and specimen collection for coronavirus disease 2019 (COVID-19)?