What is the optimal timing of coronavirus disease 2019 (COVID-19) diagnostic testing?

Updated: Apr 02, 2021
  • Author: James J Dunn, PhD, D(ABMM), MT(ASCP); more...
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The timing of patient testing in the course of the disease can also impact the sensitivity of nucleic acid analysis. Viral RNA present in URT specimens from patients infected with SARS-CoV-2 is highest at the onset of symptoms. [21, 22, 23]

The viral loads for pre-symptomatic patients and those with subclinical infections are currently a topic of intense research. Viral loads in patients who are pre-symptomatic (ie, who are asymptomatic at the time of the test but who subsequently develop symptoms) do not appear to be significantly different than those in individuals with subclinical or symptomatic infections. [24, 25, 26] This would likely indicate that the sensitivity of nucleic acid testing would be the highest earlier in the course of the infection and should be equally effective prior to or at the onset of symptoms, though how soon after exposure to the virus that an NAAT can readily detect SARS-CoV-2 RNA is in question. [27]

After the first week of symptoms, which correlates with diminishing severity of symptoms in patients with a mild presentation of COVID-19, SARS-CoV-2 RNA levels in URT specimens begin to decrease but are still frequently detectable by NAAT. [21, 22, 23] However, some studies did not observe a sharp decrease after this first week. [24, 28] This phenomenon may be linked to the immune status of the patients in question; immunocompromised patients, as well as individuals with asymptomatic infections, have been noted to shed the virus for longer periods of time than immunocompetent or symptomatic patients, as measured by RNA detection. [29, 30, 31] Virus shedding decreases in subsequent weeks, but a low percentage of specimens may have detectable RNA for 6 weeks or longer after symptom onset. [32] Moreover, RNA in LRT specimens, such as sputum, may peak later and be detectable longer than URT-specimen RNA would. [26]  Likewise, in some patients, saliva has been shown to have higher viral loads and RNA that persists longer than do paired NP specimens. [33]  Saliva may provide a suitable alternative to NP specimens given the scarcity of swab supplies and does not necessarily need to be collected by HCP, which can reduce PPE usage.

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