Diagnostics for Coronavirus Disease 2019 (COVID-19) Patients 

Updated: Apr 23, 2020
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What is the incubation period for coronavirus disease 2019 (COVID-19)?

The incubation period for coronavirus disease 2019 (COVID-19) is believed to extend to 14 days, with a median time of 4-5 days from exposure to symptomatic onset. [1]  In one study, 97.5% of symptomatic patients developed symptoms within 11.5 days of becoming infected. [1]

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

Most patients with coronavirus disease 2019 (COVID-19) will experience the following (in descending frequency) [1] :

  • Fever

  • Cough

  • Fatigue

  • Anorexia

  • Shortness of breath

  • Sputum production

  • Myalgias

Discussion

Atypical presentations have been described, and older adults and persons with medical comorbidities may have delayed presentation of fever and respiratory symptoms.

Frequently reported signs and symptoms of patients admitted to the hospital include fever (83-99%), cough (59-82%), fatigue (44-70%), anorexia (40-84%), shortness of breath (31-40%), sputum production (28-33%), and myalgias (11-35%) at illness onset. Fever has been present in 44% of patients at hospital admission and has developed in 89% during hospitalization.

Less common symptoms (< 10%) include headache, confusion, rhinorrhea, sore throat, and hemoptysis. Some patients have experienced gastrointestinal symptoms such as diarrhea and nausea prior to developing fever and lower respiratory tract signs and symptoms. Anecdotally, anosmia or ageusia may preceed the onset of respiratory symptoms, but more information is needed to understand its role in identifying COVID-19.

Signs/symptoms in pediatric patients are similar to those of adults but are usually milder.

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What is known about asymptomatic and presymptomatic transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)?

Epidemiologic studies have documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during the presymptomatic incubation period, and asymptomatic transmission has been suggested in other reports. [1]

Virologic studies using reverse transcription polymerase chain reaction (RT-PCR) have also detected SARS-CoV-2 with low cycle thresholds, indicating larger quantities of viral RNA. Viable virus has also been cultured among persons with asymptomatic and presymptomatic SARS-CoV-2 infection. [1]

It is not yet known what exact degree of SARS-CoV-2 viral RNA shedding confers risk of transmission, but the greatest transmission risk is thought to be when patients are symptomatic, because viral shedding is greatest at the time of symptom onset and falls over the course of several days to weeks. [1] However, the proportion of SARS-CoV-2 transmission in the population due to asymptomatic or presymptomatic infection compared to symptomatic infection is unclear.

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What is the range of illness severity of patients with coronavirus disease 2019 (COVID-19)?

Patients with coronavirus disease 2019 (COVID-19) can experience a range of illness severity from mild to critical, as follows [1] :

  • 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%

Discussion

In a Chinese study of over 44,000 patients, all deaths occurred among patients with critical illness, with a 2.3% overall case fatality rate but a 49% case fatality rate among patients with critical disease. [1] In the Chinese pediatric population, there was a lower illness severity, with 94% having asymptomatic, mild or moderate disease; 5% having severe disease, and less than 1% having critical disease.

Among US COVID-19 cases with known disposition, 19% were hospitalized and 6% were admitted to the intensive care unit (ICU).

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What are characteristics of critically ill patients with coronavirus disease 2019 (COVID-19)?

Critically ill patients with coronavirus disease 2019 (COVID-19) generally have the following characteristics [2] :

  • Are older (median age 66 years)

  • Have underlying comorbid conditions (72%)

  • Need high-flow oxygen therapy (11-64%)

  • Need mechanical ventilation (47-71%)

  • Need advanced organ support with endotracheal intubation an mechanical ventilation (4-42%)

  • Need respiratory support with extracorporeal membrane oxygenation (ECMO) (3-12%)

Discussion

Among patients who developed severe disease, the medium time to dyspnea ranged from 5 to 8 days, the median time to acute respiratory distress syndrome (ARDS) ranged from 8 to 12 days, and the median time to admission to the intenstive care unit (ICU) ranged from 10 to 12 days. [1]

Note: Some patients can rapidly deteriorate 1 week after illness onset. Among all hospitalized patients, 26% to 32% of patients were admitted to the ICU. [1] Moreover, among all patients, 3% to 17% developed ARDS, compared to 20% to 42% for hospitalized patients and 67% to 85% for those admitted to the ICU. Mortality among COVID-19 ICU patients ranged from 39% to 72%. The median length of hospitalization among survivors was 10 to 13 days.

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What are complications of patients with coronavirus disease 2019 (COVID-19)?

Complications of patients with coronavirus disease 2019 (COVID-19) include the following [1, 2] :

  • Pneumonia

  • Hypoxemic respiratory failure/acute respiratory distress syndrome (ARDS)

  • Diffuse alveolar damage

  • Secondary bacterial infections

  • Sepsis and septic shock

  • Cardiac injury

  • Cardiomyopathy

  • Arrhythmia

  • Sudden cardiac death

  • Acute kidney injury

  • Liver dysfunction

  • Multiorgan failure

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What are common laboratory findings in patients with coronavirus disease 2019 (COVID-19)?

Lymphopenia (83%) is the most common laboratory finding in hospitalized patients with coronavirus disease 2019 (COVID-19). [1]

Findings that may be associated with more illness severity include the following [1] :

  • Lymphopenia

  • Neutrophilia

  • Elevated levels of serum alanine aminotransferase and aspartate aminotransferase

  • Elevated lactate dehydrogenase

  • High C-reactive protein (CRP) level

  • High ferritin levels

Elevated D-dimer and lymphopenia have been associated with mortality.

Although procalcitonin is typically normal on admission, levels may increase among those admitted to the intensive care unit (ICU).

Critically ill patients generally have high plasma levels of inflammatory makers, suggesting potential immune dysregulation.

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What criteria guide evaluation and laboratory testing for suspected coronavirus disease 2019 (COVID-19)?

Priorities for testing

Priority 1

Ensure optimal care options for all hospitalized patients, lessen the risk of nosocomial infections, and maintain the integrity of the healthcare system. These apply to hospitalized patients and symptomatic healthcare workers.

Priority 2

Ensure that those who are at highest risk of complication of infection are rapidly identified and appropriately triaged. This applies to the following groups:

  • Symptomatic patients in long-term care facilities
  • Symptomatic patients aged 65 years of age and older
  • Symptomatic patients with underlying conditions
  • Symptomatic first responders

Priority 3

As resources allow, test individuals in the surrounding community of rapidly increasing hospital cases to reduce community spread, as well as ensure the health of essential workers, such as the following:

  • Symptomatic critical infrastructure workers
  • Symptomatic individuals who do not meet any of the above categories
  • Healthcare workers and first responders
  • Mildly symptomatic individuals in communities experiencing high coronavirus disease 2019 (COVID-19) hospitalizations

Priority 4

Asymptomatic individuals

Discussion

Clinicians should work with local and state health departments to coordinate testing for COVID-19 through public health laboratories, or work with commercial or clinical laboratories using diagnostic tests granted an Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA). [3, 4, 6]

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. [6]  Most patients with confirmed COVID-19 have developed fever and/or symptoms of acute respiratory illness (eg, cough, difficulty breathing).

Other considerations that may guide testing are epidemiologic factors such as the occurrence of local community transmission of COVID-19 infections in a jurisdiction. [6]  Clinicians are strongly encouraged to test for other causes of respiratory illness.

 

 

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What diagnostic test is used to detect coronavirus disease 2019 (COVID-19)?

Diagnosis of coronavirus disease 2019 (COVID-19) requires detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by reverse transcription polymerase chain reaction (RT-PCR), which is better using nasopharynx samples compared to throat samples. [1] Lower respiratory samples may have better yield than upper respiratory samples.

SARS-CoV-2 RNA has also been detected in stool and blood. [1] The presence of SARS-CoV-2 RNA in blood may be a marker of severe illness. Older patients and those with severe illness requiring hospitalization may shed viral RNA shedding over longer periods (median range of viral shedding among hospitalized patients: 12-20 days).

There have been reports of concurrent infection with SARS-CoV-2 and other respiratory viruses. [1] Detection of another respiratory pathogen does not rule out COVID-19.

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What is the testing procedure for coronavirus disease 2019 (COVID-19)?

Conduct all testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in consultation with a healthcare provider [3, 4] .

  • Asymptomatic persons: Nasopharyngeal (NP) swabs can be used for testing in a healthcare setting, including long-term care facilities.

  • Symptomatic persons: Anterior nares and midturbinate specimen collection are only appropriate for this group. Swab both nares.

Once it's clinically determined to pursue SARS-CoV-2 testing, the process includes the following [3, 4] :

  • Specimens should be collected as soon as possible once a decision has been made to pursue coronavirus disease 2019 (COVID-19) testing, regardless of the time of symptom onset.

  • When collecting specimens, maintain proper infection control, and use recommended personal protective equipment (PPE), which includes an N95 or higher-level respirator (or a facemask if a respirator is not available), eye protection, gloves, and a gown.

  • For initial diagnostic testing, collect and test an upper respiratory specimen.

  • An NP specimen is the preferred choice for swab-based SARS-CoV-2 testing.

  • When collection of an NP swab is not possible, acceptable alternatives include (1) an oropharyngeal (OP) specimen collected by a healthcare professional; (2) a nasal midturbinate (NMT) swab collected by a healthcare professional or by onsite self-collection (using a flocked tapered swab); (3) an anterior nares (nasal swab) (NS) specimen collected by a healthcare professional or by onsite self-collection (using a flocked or spun polyester swab); or (4) an NP wash/aspirate or nasal aspirate (NA) specimen collected by a healthcare professional.

  • For NS, a single polyester swab with a plastic shaft should be used to sample both nares. NS or NMT swabs should be placed in a transport tube containing either viral transport medium, Amies transport medium, or sterile saline.

  • If both NP and OP swabs are collected, they should be combined in a single tube to maximize test sensitivity and limit use of testing resources.

  • The Centers for Disease Control and Prevention (CDC) also recommends testing lower respiratory tract specimens, if available.

  • For patients who develop a productive cough, sputum should be collected and tested for SARS-CoV-2. The induction of sputum is not recommended.

  • When it is clinically indicated (eg, those receiving invasive mechanical ventilation), a lower respiratory tract aspirate or bronchoalveolar lavage sample should be collected and tested as a lower respiratory tract specimen.

  • Maintain proper infection control when collecting specimens. See Biosafety FAQs for handling and processing specimens from suspected case patients.

Discussion

Healthcare providers should report positive results for SARS-CoV-2 to their local/state health department. [3, 4, 6]  Clinical laboratories should NOT attempt viral isolation from specimens collected from people suspected to have COVID-19 unless this is performed in a biosafety level 3 (BSL-3) laboratory. Test for other pathogens as part of the initial evaluation, but this should not delay testing for SARS-CoV-2.

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What are general guidelines for specimens of patients with coronavirus disease 2019 (COVID-19)?

Respiratory specimens

Upper respiratory tract

For nasopharyngeal (NP) swabs/oropharyngeal (OP) swabs, use only synthetic fiber swabs with plastic shafts. Do not use calcium alginate swabs or swabs with wooden shafts, as they may contain substances that inactivate some viruses and inhibit polymerase chain reaction (PCR) testing. Place swabs immediately into sterile tubes containing 2-3 mL of viral transport media. In general, CDC now recommends collecting only the NP swab. If both swabs are used, NP and OP specimens should be combined at collection into a single vial. OP swabs remain an acceptable specimen type.

  • NP swab: Insert a flexible wire shaft minitip swab through the nares parallel to the palate (not upward) until resistance is encountered or the distances is equivalent to that from the ear to the patient's nostril, indicating contact with the nasopharynx. The swab should reach a depth equal to the distance from the nostrils to the outer ear opening. Gently rub and roll the swab. Leave the swab in place for several seconds to absorb secretions. Slowly remove the swab while rotating it.

  • OP swab (eg, throat swab): Insert the swab into the posterior pharynx and tonsillar areas. Rub the swab over both tonsillar pillars and the posterior oropharynx, avoiding touching the tongue, teeth, and gums.

For NP wash/aspirate or nasal aspirate (NA), attach a catheter to the suction apparatus. With the patient seated and head tilted slightly backward, instill 1 to 1.5 mL of nonbacteriostatic saline (pH 7.0) into one nostril. Insert the tubing into the nostril parallel to the palate (not upward). The catheter should reach a depth equal to the distance from the nostrils to the outer ear opening. Use gentle suction/aspiration and remove the catheter while rotating it gently. Collect the specimen in a sterile viral transport media tube.

For nasal midturbinate (NMT) swabs (also called deep nasal swab), use a flocked tapered swab. Tilt patient’s head back 70º. While gently rotating the swab, insert the swab less than 1 inch (about 2 cm) into the nostril (until resistance is met at the turbinates). Rotate the swab several times against the nasal wall, and repeat this process in the other nostril using the same swab.

For anterior nares (NS) specimens, use a flocked or spun polyester swab. Insert the swab at least 1 cm (0.5 inch) inside the nares and firmly sample the nasal membrane by rotating the swab and leaving in place for 10 to 15 seconds. Sample both nares with the same swab.

Lower respiratory tract

  • For bronchoalveolar lavage, tracheal aspirate, pleural fluid, or lung biopsy specimens, collect 2-3 mL into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container. Because increased technical skill and equipment is needed, collection of specimens other than sputum from the lower respiratory tract may be limited to patients who present with more severe disease, including those admitted to the hospital and/or fatal cases.

  • For sputum specimens, educate the patient about the difference between sputum and oral secretions (saliva). Have the patient rinse their mouth with water and then expectorate deep cough sputum directly into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container.

Storage and shipping

Store specimens at 2-8°C for up to 72 hours after collection. If a delay in testing or shipping is expected, store specimens at -70°C or below.

Specimens must be packaged, shipped, and transported according to the current edition of the International Air Transport Association (IATA) Dangerous Goods Regulations external icon

  • If specimens will ship without delay, store specimens at 2-8°C, and ship overnight to the Centers for Disease Control and Prevention (CDC) on an ice pack.

  • If a delay in shipping will result in the CDC receiving the specimen longer than 72 hours after collection, store specimens at -70°C or below and ship overnight to CDC on dry ice.

  • Samples may be shipped to the CDC if repeated testing results remain inconclusive or if other unusual results are obtained. Contact the CDC at respvirus@cdc.gov prior to submitting samples.

  • Label each specimen container with the patient’s identification (ID) number (eg, medical record number), unique CDC or state-generated nCoV (novel coronavirus) specimen ID (eg, laboratory requisition number), specimen type (eg, serum), and the date the sample was collected.

  • Complete a CDC Form 50.34 for each specimen submitted. In the upper left box of the form, (1) for test requested select “Respiratory virus molecular detection (non-influenza) CDC-10401” and (2) for At CDC, bring to the attention of enter “Stephen Lindstrom: 2019-nCoV PUI”.

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