Coronavirus Disease 2019 (COVID-19)
Updated: May 28, 2020
What’s New Here
Coronavirus 2019-20 Outbreak Overview
A large family of viruses that cause a variety of illness:
- Common cold
- Middle East Respiratory Syndrome (MERS-CoV)
- Severe Acute Respiratory Syndrome (SARS-CoV)
Novel Coronavirus (SARS-CoV-2; 2019-nCoV) History
- In late 2019, a new coronavirus – not seen previously in humans – was identified as the cause of human illness in China and given the name 2019-nCoV.
- By late January 2020, outbreak declared a public health emergency of international concern by WHO and US Centers for Disease Control and Prevention (CDC).,
- Categorized as a pandemic by WHO in March 2020.
Case Definition and Patient Under Investigation (PUI)
- COVID-19 name given by WHO to the disease caused by the SARS-CoV-2 (2019-nCoV) virus.
- See Case Definitions for WHO Surveillance Case Definition and CDC Patient Under Investigation (PUI) Clinical Criteria for COVID-19.
- If a PUI for COVID-19 is identified, notify your health department immediately. See Reporting COVID-19 in the United States for details.
- A detailed travel history is recommended for all patients being evaluated with fever and acute respiratory illness.
⇒ Specific COVID-19 treatments
- No treatments for COVID-19 have yet been FDA approved.
- Care is primarily supportive (see Supportive Therapy below)
- Emergency Use Authorization (EUA) have been issued for antiviral remdesivir (details below).
- Antiviral drugs commonly used in clinical practice, including ganciclovir, acyclovir and ribavirin, are not currently recommended for SARS-CoV-2.
- Treatments under study:
Median Time to Recovery (Days)
†Preliminary Results from Adaptive COVID-19 Treatment Trial (ACTT).
- The Lancet reported on a RCT (ClinicalTrials.gov NCT04257656) at ten hospitals in Hubei, China. Remdesivir was not associated with statistically significant clinical benefits, although some authors have concluded that the study was underpowered to detect a statistical difference.
- NEJM study of compassionate-use remdesivir in severe COVID-19 showed clinical improvement in 36 of 53 patients (68%). However, no conclusion about true efficacy could be made from this small and non-controlled study.
- Many additional clinical trials are underway.
- Convalescent plasma
- PNAS: In an uncontrolled case series of 10 adult patients with severe COVID-19 who were given one dose of convalescent plasma with the neutralizing antibody titers above 1:640, clinical symptoms significantly improved with an increase of oxyhemoglobin saturation within 3 d, accompanied by rapid neutralization of viremia.
- JAMA: In an uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in clinical status.
- Other Convalescent Plasma Clinical Trials are underway.
- ⇒ Hydroxychloroquine (HCQ) and chloroquine (CQ)
- Inhibits growth of SARS-CoV-2 in vitro, but no clinical trials have demonstrated conclusively their effectiveness in humans.
- ⇒ Lancet reported a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. No benefit was found and these drugs were associated with decreased in-hospital survival and increased frequency of ventricular arrythmias.
- Observational study published in JAMA showed amongst 1,438 hospitalized COVID-19 patients those receiving hydroxychloroquine, azithromycin, or both had no significant differences in mortality.
- Observational study published in NEJM showed HCQ not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death.
- An increasing number of studies have reported clinically significant QT Interval prolongation from CQ/HCQ +/- azithromycin, with some authors cautioning "first, do no harm."
- See also Chloroquine / Hydroxychloroquine in Coronavirus COVID-19.
- Lopinavir-ritonavir (AbbVie; Kaletra, Aluvia)
- Tocilizumab (Genentech; Actemra)
- Monoclonal antibody which blocks the IL-6 signalling pathway.
- Being investigated in a number of Tocilizumab Clinical Trials.
- 3-Drug Cocktail (interferon beta-1b, lopinavir–ritonavir, and ribavirin) reported in an open label, randomized trial (NCT04276688) to be safe and superior to lopinavir–ritonavir alone in alleviating symptoms and shortening hosptial stay and viral shedding in patients with mild to moderate COVID-19.
- Ibrutinib (AbbVee; Imbruvica): showed protection against pulmonary injury in a small, uncontrolled study of patients already on this agent for Waldenstrom’s Macroglobulinemia.
- Favipiravir (Toyama Chemical; Avigan), an antiviral drug under study alone and in combination with tocilizumab, see Favipiravir Clinical Trials.
- Systemic corticosteroids are under investigation in clinical trials. Some authors advise that they should not given routinely for the treatment of COVID-19.
- Unlicensed treatments
- Should be administered only in the context of ethically-approved clinical trials or the Monitored Emergency Use of Unregistered Interventions Framework (MEURI), with strict monitoring.
- For the latest journal research
Supportive therapy and monitoring
Mild to Moderate Disease
- Patients with a mild clinical presentation (absence of viral pneumonia and hypoxia) can often manage their illness at home.
- Outpatient or inpatient monitoring may be required, depending on:
- Clinical presentation, need for supportive care, risk factors for severe disease, and the ability to self-isolate at home.
- Risk factors for severe illness: these patients should be monitored closely given the possible risk of progression to severe illness in the second week after symptom onset.
- Inpatient management of COVID-19 is supportive and focused on the management of complications (see below). For details see NEJM review of treatment of severe COVID-19.
- WHO and the Surviving Sepsis Campaign have produced guidelines for inpatient and ICU management of patients with COVID-19:
- For management of children with COVID-19:
Front-line healthcare personnel in the United States should be prepared to evaluate patients for coronavirus disease 2019 (COVID-19). The following checklist from the CDC highlights key steps for healthcare personnel in preparation for transport and arrival of patients with confirmed or possible COVID-19.
- Stay up to date on the latest information about signs and symptoms, diagnostic testing, and case definitions for coronavirus disease 2019
- Review your infection prevention and control policies and CDC infection control recommendations for COVID-19 for:
- Assessment and triage of patients with acute respiratory symptoms
- Patient placement
- Implementation of Standard, Contact, and Airborne Precautions, including the use of eye protection
- Visitor management and exclusion
- Source control measures for patients (e.g., put face mask on suspect patients)
- Requirements for performing aerosol generating procedures
- Be alert for patients who meet the persons under investigation (PUI) definition
- Know how to report a potential COVID-19 case or exposure to facility infection control leads and public health officials
- Know who, when, and how to seek evaluation by occupational health following an unprotected exposure (i.e., not wearing recommended PPE) to a suspected or confirmed coronavirus disease 2019 patient
- Remain at home, and notify occupational health services, if you are ill
- Know how to contact and receive information from your state or local public health agency (See Reporting COVID-19 in the United States)
World Health Organization
Objectives of global surveillance
- Monitor trends in COVID-19 disease at national and global levels.
- Rapidly detect new cases in countries where the virus is not circulating, and monitor cases in countries where the virus has started to circulate.
- Provide epidemiological information to conduct risk assessments at the national, regional and global level.
- Provide epidemiological information to guide preparedness and response measures.
Surveillance Case Definitions for COVID-19
- Case and contact definitions are based on the current available information and are regularly revised as new information accumulates.
- Countries may need to adapt case definitions depending on their local epidemiological situation and other factors.
- All countries are encouraged to publish definitions used online and in regular situation reports, and to document periodic updates to definitions which may affect the interpretation of surveillance data.
The case definitions are based on the current information available and will be revised as new information accumulates. Countries may need to adapt case definitions depending on their own epidemiological situation.
*Definition of contact
A contact is a person who experienced any one of the following exposures during the 2 days before and the 14 days after the onset of symptoms of a probable or confirmed case:
†Source: Global surveillance for COVID-19 caused by human infection with COVID-19 virus. World Health Organization. Revised 20 March 2020.
1 Inconclusive being the result of the test reported by the laboratory.
Classification of transmission scenarios
- WHO recommends using the following categories to describe transmission patterns at national and sub-national levels (wherever possible) to guide decisions for preparedness, readiness and response activities.
Countries/territories/areas with no cases
Countries/territories/areas with one or more cases, imported or locally detected
Clusters of cases
Countries/territories/areas experiencing cases, clustered in time, geographic locationand/or by common exposures
Countries/area/territories experiencing larger outbreaks of local transmission defined through an assessment of factors including, but not limited to: - Large numbers of cases not linkable to transmission chains - Large numbers of cases from sentinel lab surveillance - Multiple unrelated clusters in several areas of the country/territory/area
Recommendations for laboratory testing
Any suspected case should be tested for COVID-19 infection using available molecular tests. However, depending on the intensity of the transmission, the number of cases and the laboratory capacity, only a subset of the suspect cases may prioritized for testing.
During community transmission WHO recommends prioritizing persons to be tested as indicated in the WHO global testing strategy for COVID-19.
To monitor the full extent of the circulation of the virus in the general population, WHO recommends implementing testing for COVID-19 via existing national sentinel surveillance sites for influenza-like illness (ILI) and severe acute respiratory infection (SARI). Guidance will be made available here:
U.S. Centers for Disease Control
- For any patient meeting criteria for evaluation for COVID-19, clinicians are encouraged to contact and collaborate with their state or local health department. See Reporting COVID-19 in the United States.
- For patients that are severely ill, evaluation for COVID-19 may be considered even if a known source of exposure has not been identified.
- Clinicians should use their judgment to determine if a patient has signs and symptoms compatible with COVID-19 and whether the patient should be tested. Asymptomatic infection with SARS-CoV-2 has been reported.
- The most common symptoms include fever (subjective or confirmed) and/or symptoms of acute respiratory illness (e.g., cough, difficulty breathing) but some people may present with other symptoms.
- Other considerations that may guide testing are epidemiologic factors such as:
- Occurrence of local community transmission of COVID-19 infections in a jurisdiction
- Known exposure to an individual who has tested positive for SARS-CoV-2
- Occurrence of local community transmission or transmission within a specific setting/facility (e.g., nursing homes) of COVID-19.
- Another population in which to prioritize testing of minimally symptomatic and even asymptomatic persons are long-term care facility residents, especially in facilities where one or more other residents have been diagnosed with symptomatic or asymptomatic COVID-19.
- Clinicians are strongly encouraged to test for other causes of respiratory illness, for example influenza, in addition to testing for SARS-CoV-2.
†Source: U.S. Centers for Disease Control and Prevention. Evaluating and Testing Persons for Coronavirus Disease 2019 (COVID-19) Revised May 3, 2020.
Recommendations for Reporting, Testing, and Specimen Collection
- Clinicians should immediately implement recommended infection prevention and control practices, including use of recommended personal protective equipment (PPE) if a patient is suspected of having COVID-19. They should also notify infection control personnel at their healthcare facility if a patient is classified as a Patient Under Investigation (PUI) for COVID-19.
- For diagnostic testing for COVID-19 see the Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from PUIs for COVID-19 and Biosafety FAQs for handling and processing specimens from possible cases and PUIs.
- Clinicians should report positive test results to their local or state health department only.
- On March 19th, WHO issued guidance on infection prevention and control strategies for healthcare workers (HCW) when COVID-19 is suspected.
- See  for full details and references.
- Infection prevention and control (IPC) strategies to prevent or limit transmission in health care settings include the following:
- Ensuring triage, early recognition, and source control (isolating patients with suspected COVID-19);
- Applying standard precautions for all patients;
- Implementing empiric additional precautions (droplet and contact and, whenever applicable, airborne precautions) for suspected cases of COVID-19;
- Implementing administrative controls;
- Using environmental and engineering controls.
Contact and droplet precautions
- In addition to using standard precautions, all individuals, including family members, visitors and HCWs, should use contact and droplet precautions before entering the room of suspected or confirmed COVID-19 patients.
- Patients should be placed in adequately ventilated single rooms. For general ward rooms with natural ventilation, adequate ventilation is considered to be 60 L/s per patient.
- When single rooms are not available, patients suspected of having COVID-19 should be grouped together.
- All patients’ beds should be placed at least 1 metre apart regardless of whether they are suspected to have COVID-19.
- Where possible, a team of HCWs should be designated to care exclusively for suspected or confirmed cases to reduce the risk of transmission.
Healthcare Worker (HCW) Protection
- HCWs should:
- Wear a medical mask.
- Wear eye protection (goggles) or facial protection (face shield) to avoid contamination of mucous membranes.
- Wear a clean, non-sterile, long-sleeved gown.
- Use gloves.
- Boots, coverall, and apron is not required during routine care.
- Carry out hand hygiene and appropriate doffing and disposal of all Personal Protective Equipment (PPE) after care of each patient.
- Refrain from touching eyes, nose, or mouth with potentially contaminated gloved or bare hands.
- Use new set of PPE when care is given to a different patient.
- Equipment should be either single-use and disposable or dedicated equipment (e.g., stethoscopes, blood pressure cuffs and thermometers).
- If equipment needs to be shared among patients, clean and disinfect it between use for each individual patient (e.g., by using ethyl alcohol 70%).
- Avoid moving and transporting patients out of their room or area unless medically necessary.
- Use designated portable X-ray equipment or other designated diagnostic equipment. If transport is required, use predetermined transport routes to minimize exposure for staff, other patients and visitors, and have the patient wear a medical mask.
- Ensure that HCWs who are transporting patients perform hand hygiene and wear appropriate PPE as described in this section.
- Notify the area receiving the patient of any necessary precautions as early as possible before the patient’s arrival.
- Routinely clean and disinfect surfaces with which the patient is in contact.
- Limit the number of HCWs, family members, and visitors who are in contact with suspected or confirmed COVID-19 patients.
- Maintain a record of all persons entering a patient’s room, including all staff and visitors.
Airborne precautions for aerosol-generating procedures
- Some aerosol-generating procedures, such as tracheal intubation, non-invasive ventilation, tracheotomy, cardiopulmonary resuscitation, manual ventilation before intubation, and bronchoscopy, have been associated with an increased risk of transmission of coronaviruses.
- Ensure that HCWs performing aerosol-generating procedures:
- Perform procedures in an adequately ventilated room – that is, natural ventilation with air flow of at least 160 L/s per patient or in negative- pressure rooms with at least 12 air changes per hour and controlled direction of air flow when using mechanical ventilation.
- Use a particulate respirator at least as protective as a US National Institute for Occupational Safety and Health (NIOSH)-certified N95, European Union (EU) standard FFP2, or equivalent.
- When HCWs put on a disposable particulate respirator, they must always perform the seal check.Note that facial hair (e.g. a beard) may prevent a proper respirator fit.
- Use eye protection (i.e., goggles or a face shield).
- Wear a clean, non-sterile, long-sleeved gown and gloves. If gowns are not fluid-resistant, HCWs should use a waterproof apron for procedures expected to create high volumes of fluid that might penetrate the gown.
- Limit the number of persons present in the room to the absolute minimum required for the patient’s care and support.
- For abbreviations used below see Glossary of Coronavirus terms.
- Syndromes range from mild upper respiratory infection to severe pneumonia, ARDS and death.
- All age groups are susceptible to the virus, but elderly patients with comorbidities are more likely to experience severe illness.
- Major risk factors for severe illness and mortality from COVID-19:
- Comorbidities: heart disease, hypertension, prior stroke, diabetes, chronic lung disease, and chronic kidney disease have all been associated with increased illness severity and adverse outcomes.
†Source: Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020. MMWR Morb Mortal Wkly Rep. ePub: 18 March 2020.
Chronic respiratory disease
†Source: The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China.
Mortality associated with COVID-19 in the United States has been reported to be similar to China.
Less common (< 10%)
- Anosmia or ageusia preceeding the onset of respiratory symptoms has been reported anecdotally, but more information is needed to understand its role in identifying COVID-19.
Asymptomatic and Pre-Symptomatic Infection
- Several studies have documented SARS-CoV-2 infection in patients who never develop symptoms (asymptomatic) and in patients not yet symptomatic (pre-symptomatic).,,,,
- Since asymptomatic persons are not routinely tested, the prevalence of asymptomatic infection and detection of pre-symptomatic infection is not well understood.
- One study found that as many as 13% of RT-PCR-confirmed cases of SARS-CoV-2 infection in children were asymptomatic.
- Patients may have abnormalities on chest imaging before the onset of symptoms.,
- Although transmission of SARS-CoV-2 from asymptomatic or pre-symptomatic persons has been reported, risk of transmission is thought to be greatest when patients are symptomatic.
- Viral RNA shedding, measured indirectly by RT-PCR cycle threshold values, is greatest at the time of symptom onset and declines over the course of several days to weeks.,
- The exact degree of SARS-CoV-2 viral RNA shedding that confers risk of transmission is not yet clear.
In 44,600 COVID-19 cases from China, disease severity was classified as:
- Mild to moderate (mild symptoms up to mild pneumonia): 81%
- Severe (dyspnea, hypoxia, or >50% lung involvement on imaging): 14%
- Critical (respiratory failure, shock, or multiorgan system dysfunction): 5%
- Case fatality rate was 49% among patients in this group and 2.3% overall.
Among 2,143 pediatric patients studied in China
- 94% had asymptomatic, mild or moderate disease
- 5% had severe disease
- < 1% had critical disease
- Only one (< 0.1%) death was reported in a person under 18 years old.
Among U.S. COVID-19 cases with known disposition
- Hospitalized: 19%
- Admitted to the intensive care unit (ICU): 6%
- Among patients who developed severe disease, the mean duration to develop the following conditions: 
- Dyspnea: 5–8 days
- Acute respiratory distress syndrome (ARDS): 8–12 days
- ICU admission: 10–12 days.
- Some patients can rapidly deteriorate one week after illness onset.
- Mortality among patients admitted to the ICU: 39%–72%
- Median length of hospitalization among survivors: 10–13 days
- There are no current data concerning reinfection with SARS-CoV-2 after recovery from COVID-19.
- Viral RNA shedding declines with resolution of symptoms, and may continue for days to weeks. However, the detection of RNA during convalescence does not necessarily indicate the presence of viable infectious virus.
- Clinical recovery has been correlated with the detection of IgM and IgG antibodies which signal the development of immunity.,
COVID-19 Diagnostic Tests
Samples to be collected
- Respiratory material
- Nasopharyngeal and oropharyngeal (URT) swab in ambulatory patients and sputum (if produced) and/or endotracheal aspirate or bronchoalveolar lavage (LRT) in patients with more severe respiratory disease.
- Send for SARS-CoV-2 testing by reverse transcription polymerase chain reaction (RT-PCR).
- In hospitalized patients with confirmed SARS-CoV-2 infection
- Repeat URT and LRT samples should be collected to demonstrate viral clearance.
- Frequency of specimen collection will depend on local circumstances but should be at least every 2 to 4 days until there are two consecutive negative results (both URT and LRT samples if both are collected) in a clinically recovered patient at least 24 hours apart.
- If local infection control practice requires two negative results before removal of droplet precautions, specimens may be collected as often as daily. 
- Serum for serological testing, acute sample and convalescent sample (this is additional to respiratory materials and can support the identification of the true agent, once serologic assay is available). Serology for diagnostic purposes is recommended only when RT-PCR is not available.
- Blood cultures for bacteria that cause pneumonia and sepsis, when indicated, ideally before antimicrobial therapy.
- Detection of SARS-CoV-2 RNA by RT-PCR
- Diagnostic for COVID-19
- Detection better in nasopharynx compared to throat samples and lower compared to upper respiratory samples
- Detection in blood may be a marker of severe illness
- A single negative RT-PCR result, particularly if this is from an upper respiratory specimen, does not exclude infection. Repeat sampling and testing or lower respiratory tract specimen is strongly recommended in severe or progressive disease.
- Viral RNA shedding
- 7–12 days in moderate cases
- My be longer for older persons and those who had severe illness requiring hospitalization (12–20 days).
- U.S. FDA issued Emergency Use Authorization (EUA) for the first serologic test for SARS-CoV-2 immunoglobulins (Cellex; qSARS-CoV-2 IgG/IgM Rapid Test) on April 1 and additional serologic test have received EUA status.
- Serology among 173 patients in an early study from China:
- Median seroconversion time for Total Antibody (Ab), IgM and then IgG were day-11, day-12 and day-14 from symptom onset.
- Presence of antibodies was < 40% among patients within 1-week from symptom onset, and rapidly increased to 100.0% (Ab), 94.3% (IgM) and 79.8% (IgG) at day-15 after onset.
- A higher titer of Ab was independently associated with a worse clinical classification (p=0.006).
Days after Symptom Onset
RNA by RT-PCR
Adapted from: Zhao J et al. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clin Infect Dis. 2020 Mar 28.
- Most common: lymphopenia (83% of hospitalized patients).
- Associated with greater illness severity: 
- Lymphopenia, neutrophilia
- ↑ serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)
- ↑ C-reactive protein (CRP), ferritin.
- Associated with greater mortality: ↑ D-dimer and lymphopenia.
- Chest X-ray (CXR)
- Bilateral air-space consolidation
- May be unremarkable early in the disease
- Chest CT
- Bilateral, peripheral ground glass opacities – a non-specific pattern seen in other infections
- Role of radiologic imaging in COVID-19 diagnosis
- Because radiologic findings are non-specific, the American College of Radiology does not recommend CXR or CT for screening or as a first-line test for diagnosis of COVID-19.
Discontinuation of Precautions or Isolation
Recommendations on discontinuation of Transmission-Based Precautions or home isolation for patients who have recovered from COVID-19 (all from CDC):
For health professionals
- Coronavirus COVID-19 Outbreak | What’s New
- Reporting COVID-19 in the United States
- Epidemic (Epi) Curves for Coronavirus COVID-19
- Specimen Collection and Testing for Coronavirus COVID-19
- PubMed Searches for Coronavirus COVID-19
- VIDEO | Coronavirus: What Nurses Need to Know
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