What is a PCR test?
A PCR (polymerase chain reaction) test is a type of viral diagnostic test that detects genetic material from a virus, such as SARS-CoV-2, the virus that causes COVID-19. The test uses a technique called reverse transcription polymerase chain reaction (RT-PCR) to amplify and detect even tiny amounts of viral RNA in a sample collected from the respiratory tract, such as from a nasopharyngeal swab.
During PCR testing, the sample is first heated to allow any viral RNA present to be converted into DNA, which is then amplified millions of times through repeated heating and cooling cycles. Fluorescent probes in the test solution will bind to any of the amplified viral DNA sequences present, indicating a positive result. Because even tiny amounts of viral genetic material can be exponentially amplified, PCR tests are extremely sensitive and can detect active infections earlier than antigen or antibody testing.
When should you get a PCR test?
The CDC recommends PCR testing for:
– Anyone with symptoms of COVID-19, including fever, cough, shortness of breath, fatigue, body aches, headache, loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, or diarrhea. Symptomatic testing should be performed immediately at symptom onset.
– Anyone who has had a known exposure to COVID-19, such as through close contact with someone who tested positive. Testing is recommended 5-7 days after exposure or immediately if symptoms develop.
– Screening testing in certain high-risk groups such as healthcare workers, residents of long-term care facilities or shelters, travelers, and in areas of moderate or high community transmission.
– Individuals who have recovered from COVID-19 to determine if they still harbor viral RNA, since some RNA shedding can persist for weeks. Testing is usually performed at least 10 days after onset of symptoms and after symptoms have improved.
– Individuals who have previously tested positive using an antigen test, to confirm the result with a more accurate PCR test.
What does a negative PCR test mean?
A negative PCR test indicates that viral RNA was not detected in your sample. There are a few reasons you may get a negative test result:
– You are not currently infected with SARS-CoV-2. This is the best outcome of a negative result.
– You are infected, but are very early or late in the disease course. PCR tests can only detect active infection during the window when viral load is high enough, which can miss those just developing or waning illness.
– You have a low viral load in your sample. The sample was collected improperly or there wasn’t enough sputum collected to detect a low viral titer.
– Technical issues affected the sample analysis, shipping, or lab processing. Problems with reagents or equipment can occasionally lead to invalid test runs.
– You have an unusual SARS-CoV-2 variant that wasn’t detected accurately. Some mutated viral strains may not be identified by the primers or probes used.
So while a negative PCR result is reassuring, it is not a guarantee that you are not infected or could not still develop COVID-19 after testing. This is why confirmatory testing with a repeat PCR is sometimes needed.
When should you repeat a negative COVID PCR test?
In certain situations, repeating a negative COVID PCR test with a second confirmatory PCR test is recommended:
– You have symptoms suggestive of COVID-19 but an initial PCR test was negative. Because of the potential for false negatives, the CDC says a second test within 24-48 hours can be considered for symptomatic individuals.
– You have had a known exposure or high-risk contact but tested negative during quarantine. Experts suggest retesting 5-7 days after exposure or immediately if symptoms develop.
– You are routinely screened for work or travel purposes. Some organizations and travel programs recommend repeat testing every 3-7 days during sustained exposures.
– You are immunocompromised. Those who are severely immunodeficient may not mount an immune response to infection, thus requiring repeat testing.
– You are being extremely cautious. For those at high-risk or seeking extra reassurance, serial testing every 3-10 days may provide added peace of mind.
– You have tested positive previously. Repeat PCR testing is often needed to demonstrate viral clearance after infection, requiring two negatives spaced 24 hours apart.
– It has been a long time since symptom onset. Viral RNA shedding can persist for weeks after acute illness, so an additional test after this period provides more definitive negative results.
In contrast, repeat testing is NOT necessary in those with a previous negative who remain asymptomatic without new exposures. A single negative result is sufficient in most routine screening or surveillance testing scenarios.
What factors can affect the accuracy of PCR tests?
While PCR tests for SARS-CoV-2 are the gold standard, no test is perfect. Certain circumstances can impact the sensitivity, which may require repeat testing:
Sample collection technique
Improperly collected samples contain less respiratory secretions and fewer infected cells to detect. Nasopharyngeal swabs must reach deep into the nasopharynx and rotate to collect cells and fluids. Self-collected samples have lower viral loads.
Sample timing during infection
Viral loads peak in the first week of symptoms, declining thereafter. Samples collected very early or late in infection may have less detectable virus.
Inadequate sample storage or shipping can degrade RNA. Delays in transporting samples to the lab can reduce viral titers.
Not all PCR assays have the same sensitivities due to differences in reagents, primers, probes, and instruments. Some labs may lack robust quality controls.
Viral mutations in primer or probe targets can inhibit amplification and cause false negatives. Updates to tests are required to detect emerging variants.
Low total viral load
Those with mild or early illness often have lower viral concentrations than hospitalized patients, making the virus harder to detect.
Due to these limitations, the CDC estimates actual PCR sensitivity to be 70-75% during the first 5 days of symptoms when viral loads are rising, declining to 50-55% late in disease. Thus, repeat testing with an additional sample is warranted if initial results are negative but suspicion remains high.
How soon after a negative test should you retest?
For those with a higher suspicion of having COVID-19 despite a first negative result, the optimal timing for a repeat PCR test is:
– Within 24-48 hours for symptomatic individuals. The CDC specifically advises reconsidering testing within this time frame if the original result is negative but clinical suspicion is high.
– At least 5 days after exposure or close contact with an infected person. This allows time for viral incubation and levels to rise for detection.
– Immediately if symptoms develop after an earlier negative test. Symptom onset likely corresponds with peak transmissibility.
– Every 3-7 days for those with ongoing exposures, such as frontline workers. Frequent repeat testing increases chances of detecting any infection.
– Every 3-10 days for extra-cautious individuals seeking reassurance. This accounts for the outer limits of the PCR detection window.
– At least 10 days after onset of symptoms before checking for clearance. By this time, viral loads have usually dropped enough to result in a negative.
Retesting too soon, such as the very next day, is unlikely to change the result in most cases. Allowing a few days ensures the next sample reflects a different stage of infection and a new opportunity for detection.
How many times should you repeat a negative COVID PCR test?
Most experts advise performing up to two repeat PCR tests when the pre-test probability is high and initial results are negative:
– One retest 24-48 hours after a first negative is reasonable for symptomatic patients to rule out a false result.
– A second retest 5-7 days after exposure covers the end of the incubation period in those with high-risk contacts but no symptoms.
However, there are certain situations that may warrant more frequent serial testing:
– Weekly screening of healthcare personnel and first responders. This provides ongoing surveillance for workplace exposures.
– Testing every 3-5 days for immunocompromised individuals who may not develop antibodies or have prolonged viral shedding.
– In extremely high-risk congregate settings like long-term care facilities, prisons, shelters, or dormitories. This helps identify asymptomatic spread.
– When managing serious illness in hospitalized patients to monitor for nosocomial infections.
– Among athletes, performers, and travelers undergoing mandatory repeat testing protocols.
In most other situations, repeat testing more than two times is not recommended unless new exposures or symptoms occur. Resources should be prioritized for initial diagnostic and clearance testing based on clinical judgement.
What other types of COVID tests could you use?
In some circumstances, alternative COVID tests may be warranted if repeat PCR testing remains negative but suspicion of infection persists:
Rapid antigen tests detect viral proteins rather than RNA, offering results in about 15 minutes. They may identify infections when viral loads are peaking.
These diagnose past infection by detecting antibodies generated in response to the virus. However, antibodies take 1-3 weeks to develop.
Saliva-based PCR and antigen testing is easier to perform repeatedly, but may be less sensitive than nasopharyngeal swabs.
Lab culturing of the live virus is very specific but less sensitive than PCR and requires days to obtain results.
While not definitive, CT scans and chest x-rays can sometimes reveal lung abnormalities associated with COVID-19 before other test results become positive.
Combining PCR with other testing modalities may allow for detection of infection in suspected cases where repeat PCR results remain stubbornly negative.
What precautions should you take while awaiting repeat test results?
Waiting for the results of repeat COVID testing can cause anxiety. Here are some ideal precautions you should take while in this uncertain phase:
– Continue isolating at home while symptomatic and avoid contact with others, especially high-risk individuals. Stay home from work or school if sick.
– Tell close contacts about symptoms and exposure risk, and encourage them to test as well. Limit interactions with others until confirmatory results arrive.
– Wear a well-fitting mask or respirator whenever around others at home or if you must go out for essential reasons, such as to seek medical care.
– Practice good respiratory hygiene, including covering coughs and sneezes, washing hands frequently, and avoiding touching your face. Disinfect high-touch surfaces.
– Monitor for worsening symptoms like high fever, difficulty breathing, chest pain, or bluish lips or face. Seek prompt medical care if these or other concerning symptoms develop.
– Stay hydrated, get plenty of rest, and take over-the-counter medications as needed to manage symptoms. Good nutrition and sleep support immunity.
– Cooperate with public health contact tracing efforts if they reach out to you so exposed individuals can isolate and get tested. Provide details on close contacts if your test comes back positive.
– Get tested again as advised and continue isolating if the PCR test remains negative but COVID-19 is still suspected based on symptoms or exposures. The virus could still be detected with an additional test.
Exercising caution until repeat test results confirm the initial negative PCR maximizes the chances of detecting infection early and prevents viral transmission. Always follow the latest isolation and quarantine guidelines issued by your local health department while awaiting repeat test results.
While negative results from PCR testing for SARS-CoV-2 are encouraging, they are not foolproof. Due to the potential for inaccurate or false negative test results, repeat PCR testing is often recommended if COVID-19 remains strongly suspected based on symptoms or exposures. By retesting high-probability individuals, the likelihood of detecting the infection improves, allowing for earlier treatment and containment of spread through proper isolation precautions.