The overall ‘clinical’ false negative rate (1 – sensitivity) of rt-PCR in the detection of SAR-CoV-2 in the respiratory tract is estimated to be 30%, although estimates vary from 3.5 – 50%. This rate is higher when the technique of clinical sampling is poor, higher in nasopharyngeal and oral swabs than lower respiratory tract secretions, and higher early in the course of disease (prior to symptom development) and following the first week of symptoms.
The performance of the rt-PCR test can be maximized by:
1. Timing and collecting specimens in the optimal manner
2. Applying the test in those individuals with a high pre-test probability of having COVID-19; this includes individuals living in communities with a high prevalence of disease, those with an epidemiological history linking them to a confirmed case, and those with symptoms associated with COVID-19, potentially identified with the aid of a clinical prediction rule
3. Serial testing with a repeat rt-PCR test after a specific interval such as 24-48 hours
4. In the clinical setting, the additional assessment of blood biomarkers, IgM/IgG serology and chest CT scan
These considerations apply to the decision to conduct initial rt-PCR testing as well as to the decision to re-test individuals with an initial negative result.
Badea, A; Reeder, B; Young, C; Dalidowicz, M; Miller, L. What factors can be used to identify negative PCR tests that are ‘false negatives’? 2020 May 25; Document no.: EOC052101 RR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2020. 12 p. (CEST rapid review report)
Several references provide estimates of the proportion of HCW infected with SARS-CoV2 that range from 0.9% -20%. A recent review from Alberta Health Services that examined the COVID-19 rt-PCR test results among HCW indicates that in that province 2.4% of physicians and 0.9% of non-MD HCW who were tested were positive for SARS-CoV-2 compared to 3.5% of the general population.
In the studies reviewed, the majority of cases are confirmed by RT-PCR, while only one reference also used serology testing.
Vanstone, J; Reeder, B; Duncan, V; Howell-Spooner, B. What proportion of healthcare workers are rt-PCR positive and IgM or IgG positive? 2020 Jun 2; Document no.: LAB040802v3 RR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2020. 10 p. (CEST rapid review report)