- Authorized assays for viral testing include those that detect SARS-CoV-2 nucleic acid or antigen.
- Viral (nucleic acid or antigen) tests check samples from the respiratory system (such as nasal swabs) and determine whether an infection with SARS-CoV-2, the virus that causes COVID-19, is present.
- When viral RNA is detected in other kinds of samples (such as stool) it should not always be presumed that the patient from whom the specimen was obtained is actively infected or presently shedding virus.
- It is typically presumed that a positive test indicates the patient is actively infected and is also capable of spreading the virus.
- Viral tests are recommended to diagnose acute infection.
- Testing the same individual more than once in a 24-hour period is not recommended.
- The CDC does not currently recommend using antibody testing as the sole basis for diagnosis of acute infection, and antibody tests are not authorized by the FDA for such diagnostic purposes.
- In certain situations, serologic assays may be used to support clinical assessment of persons who present late in their illnesses when used in conjunction with viral detection tests.
- In addition, if a person is suspected to have post-infectious syndrome (eg, multisystem inflammatory syndrome in children) caused by SARS-CoV-2 infection, serologic assays may be used.
- Clinicians should use their judgement when interpreting tests for SARS-CoV-2 infection (particularly early in the course of infection). If clinical suspicion is high, infection should not be ruled out on the basis of RT-PCR alone (especially when results are being used as a basis for removing precautions intended to prevent onward transmission.
- Studies have reported that testing people for SARS-CoV-2 too early in the course of infection may result in a false negative test, even though they may eventually test positive for the virus.
The FDA also published a web page, A Closer Look at COVID-19 Diagnostic Testing, to provide health care providers and other public health professionals, including those who might purchase COVID-19 tests, more technical information and resources.
NIH Guideline Testing Recommendations:
- Nucleic acid amplification test (NAAT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be used to diagnose acute infection (AIII).
- Serologic testing should not be used as the sole basis for diagnosis of acute SARS-CoV-2 infection (AIII).
- Serologic testing should not be used to determine whether a person is immune to SARS-CoV-2 infection (AIII).
Table 8.1 Recommendation rating scheme.
For more information see the NIH Guidelines for Testing for SARS-CoV-2 Infection.
The populations for which SARS-CoV-2 testing with viral tests is appropriate are:
- Health care personnel (HCP): Testing of HCP can be considered in four situations:
- With signs or symptoms consistent with COVID-19 — HCP with signs or symptoms of COVID-19 should be prioritized for SARS-CoV-2 testing.
- Asymptomatic with known or suspected exposure to SARS-CoV-2.
- Asymptomatic without known or suspected exposure to SARS-CoV-2 for early identification in special settings (eg, nursing homes).
- HCP diagnosed with SARS-CoV-2 infection to determine when they are no longer infectious.
- Additional information can be found at the CDC’s Interim Guidance on Testing Healthcare Personnel for SARS-CoV-2.
- HCP undergoing testing should receive clear information on:
- The purpose of the test;
- The reliability of the test and any limitations associated with the test;
- Who will pay for the test and how the test will be performed;
- How to interpret results and any next steps related to the results;
- Who will receive the results;
- How the results may be used; and
- Any consequences for declining testing.
- If you have symptoms of COVID-19:
- Symptoms are mild:
- Health care provider (physician, nurse practitioner, pharmacist, etc.) may advise a SARS-CoV-2 test.
- If you test positive for SARS-CoV-2 infection or do not get tested, you should self-isolate for at least 10 days after symptom onset and resolution of fever for at least 24 hours, without the use of fever-reducing medications, and with improvement of other symptoms.
- If you live with a person at increased risk of severe illness (eg, an elderly relative or other individuals with underlying conditions), take special precautions in the home to protect that individual according to CDC guidelines.
- If symptoms worsen while isolating, or become moderate or severe, such as shortness of breath or severe fatigue, contact your health care provider immediately or seek emergency care.
- If you test positive, you do not need to repeat a test for at least 3 months.
- You do not need a follow-up negative test to return to work or school, as long as:
- You did not require hospitalization; and
- It has been at least 10 days after symptom onset and resolution of fever for at least 24 hours, without the use of fever-reducing medications, and with improvement of other symptoms.
- If you have been in close contact, such as ≤6 ft of a person with documented SARS-CoV-2 infection for a cumulative total of ≥15 mininutes over a 24-hour period and do not have symptoms:
- You need a test.
- Pending test results, you should self-quarantine/isolate at home and stay separated from household members to the extent possible and use a separate bedroom and bathroom, if available.
- A single negative test does not mean you will remain negative at any point in time after that test.
- Even if you have a negative test, you should still self-isolate for 14 days.
- If you cannot self-isolate, or you are a critical infrastructure worker that must work, wear a mask, physically distance, avoid crowds and indoor crowded places, wash your hands frequently, and monitor yourself for symptoms.
- If you live with a person at increased risk of severe illness (eg, an elderly person or other individuals with underlying medical conditions), take special precautions in the home to protect that individual according to CDC guidelines.
- Health care providers in close contact with a person with documented SARS-CoV-2 infection while using recommended personal protective equipment, do not need to be tested.
- If you do not have COVID-19 symptoms and have not been in close contact with someone known to have SARS-CoV-2 infection (meaning being ≤6 ft of an infected person for a cumulative total of ≥15 mininutes over a 24-hour period):
- You do not need a test unless recommended or required by your health care provider or public health official.
- If you are tested, you should self-quarantine at home until your test results are known, and then adhere to your health care provider’s advice.
- A negative test does not mean you will remain negative at any point in time after that test.
- If you are in a high SARS-CoV-2 transmission zone and attended a public or private gathering of more than 10 people (without universal mask wearing and/or physical distancing):
- Your health care provider or public health official may advise a SARS-CoV-2 test.
- If you are tested, you should self-isolate at home until your test results are known, and then adhere to your health care provider’s advice.
- A negative test does not mean you will remain negative at any point in time after that test.
- Even if you have a negative test, you should wear a mask, physically distance, avoid crowds and indoor crowded places, wash your hands frequently, and monitor yourself for symptoms.
- Take special precautions in the home to protect any persons with increased risk of severe illness according to CDC guidelines.
Table 8.2 COVID-19 case investigation hierarchy.
- Individuals being tested to determine resolution of infection (ie, test-based strategy for Discontinuation of Transmission-Based Precautions, HCP Return to Work, and Discontinuation of Home Isolation): A test-based strategy, which requires serial tests and improvement of symptoms, can be used, as an alternative to a symptom-based or time-based strategy, to determine when a person with SARS-CoV-2 infection no longer requires isolation or work exclusion. This strategy could be considered in three situations:
- Discontinuation of Transmission-Based Precautions and Disposition of Patients with COVID-19 in Healthcare Settings;
- Discontinuation of Isolation for Persons with COVID-19 Not in Healthcare Settings; and
- Assessing Criteria for Return to Work for Healthcare Personnel with Suspected or Confirmed COVID-19 (see Section on Return to Work Criteria With Confirmed or Suspected COVID-19). Additional information can also be found at the CDC’s guidance on Assessing Criteria for Return to Work for Healthcare Personnel with Suspected or Confirmed COVID-19.
- Individuals being tested for purposes of public health surveillance for SARS-CoV-2
- Tests are used in community, outpatient, and hospital-based surveillance systems to identify cases of SARS-CoV-2 infection.
- Additionally, certain settings can experience rapid spread of SARS-CoV-2. This is particularly true for settings with vulnerable populations in close quarters for extended periods of time.
- Local, territorial, tribal, and state health departments can help with informed decision-making about testing at these or other settings.
Additional information can be found at the CDC’s Overview of Testing for SARS-CoV-2.
The FDA has also published the Comparative Performance Data for COVID-19 Molecular Diagnostic Tests. The tables in the publications show the Limit of Detection (LoD) of more than 55 authorized molecular diagnostic COVID-19 tests against a standardized sample panel provided by the FDA.
- A lower LoD represents a test’s ability to detect a smaller amount of viral material in a given sample, signaling a more sensitive test.
- However, the data does not indicate how sensitive a particular test is, and, therefore, cannot be used by itself to determine whether to authorize a test or other regulatory action.
Health care providers should contact their local and state health department immediately to notify them of patients with fever and lower respiratory illness who they suspect may have COVID-19, and local and state public health staff will determine if the patient meets the criteria for testing for COVID-19.
- Sethuraman N, Jeremiah SS, Ryo A. Interpreting Diagnostic Tests for SARS-CoV-2. JAMA. 2020;323(22):2249–2251. DOI:10.1001/jama.2020.8259
- Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. [published online ahead of print, 2020 April 1] Nature. 2020. DOI:10.1038/s41586-020-2196-x
- Hadaya J, Schumm M, Livingston EH. Testing individuals for coronavirus disease 2019 (COVID-19) [published online ahead of print, 2020 Apr 1]. JAMA. 2020;10.1001/jama.2020.5388. doi:10.1001/jama.2020.5388
- Nandini Sethuraman N, Jeremiah SS, Ryo A. Interpreting Diagnostic Tests for SARS-CoV-2. [published online ahead of print, 2020 May 6]. JAMA. 2020;323(22):2249-2251. doi:10.1001/jama.2020.8259
- Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure. [published online ahead of print, 2020 May 13]. Annals of Internal Medicine. https://doi.org/10.7326/M20-1495
Table 8.3 Questions to ask individuals being tested for COVID-19.
Brief Reminder Regarding Diagnostic Test Interpretation
Author: Jessica Whittle, MD, PhD, FACEP, Director of Research, Department of Emergency Medicine, University of Tennessee College of Medicine
Most clinicians understand the value of sensitivity and specificity when considering the utility of a diagnostic test. These characteristics are inherent to the test itself and independent of the prevalence of the disease being considered.
- Sensitivity (also called the true positive rate, the epidemiological/clinical sensitivity, the recall, or probability of detection in some fields) measures the proportion of actual positives that are correctly identified as such (eg, the percentage of sick people who are correctly identified as having the condition).
- Specificity (also called the true negative rate) measures the proportion of actual negatives that are correctly identified as such (eg, the percentage of healthy people who are correctly identified as not having the condition).
- A test that is 95% sensitive and 95% specific would be considered a good test by most clinicians. This means that if samples taken from 100 people with disease are tested, 95 of them will test positive. Conversely, if samples taken from 100 people without disease are tested, 95 of them will test negative.
- However, the challenge comes when there is only a single patient before you, not 100. To know if the positive sample in front of you is one of the true positives, or one of the false positives, prevalence must be considered. Positive predictive value allows the clinician to consider this.
- Utilizing the example above, in an area in which 2% of the population is infected we find the positive predictive value (PPV) is 28%. If you tell a patient their positive test is a true positive in this circumstance, you could be wrong as many as 72 times out of 100.
- However, when the disease prevalence is 25% in the population, you will find that the PPV is 87%. In this instance, if you tell the patient that their positive test is a true positive, you will be correct 87% of the time. You could be wrong as many as 13 times out of 100.
For more information on how to best consider and relay test information to your patients, please look to the resources developed by our colleagues: