Sensitivity of PCR Assay
Currently the CDC states that a negative result does not exclude
SARS-CoV-2 infection. Sources of false negative testing include patient
misidentification, collection of inappropriate or inadequate material,
improper specimen transportation, low viral density in pre-symptomatic
patients, and lab errors. In addition to these factors, the location of
testing in the aerodigestive tract plays a large role in the sensitivity
to detect SARS-CoV-2. As was shown by Zou et al.,3viral loads in the upper respiratory tract of 18 patients varied
according to sub-site, with about 64 fold higher viral loads detected in
the nasal cavity than in the pharynx. In a study of 213 patients with
confirmed COVID-19, the authors found that sputum samples showed the
highest positive rate in both severe (88.9%) and mild (82.2%) cases,
followed by nasal swabs (73.3%, 72.1%), and then throat swabs (60.0%,
61.3%).2 In a similar study consisting of 205
patients, Wang et al. found that bronchoalveolar lavage had the highest
positive rates (93%), followed by sputum (72%), nasal swabs (63%),
bronchoscope brushings (46%), pharyngeal swabs (32%), feces (29%),
and blood (1%).1 From these studies, it appears that
the highest positive detection rate is from lower respiratory tract
specimens. A plausible explanation is that SARS-CoV-2 binds to human
angiotensin-converting enzyme 2 (ACE2), found predominantly in the lower
respiratory tract.23 However a potential confounder is
that invasive lower respiratory tract sampling would be primarily
performed on patients that have been intubated, which suggests that
these patients overall may have higher viral load. Finally, to add
further complexity to diagnosis, there may be variable viral load and
shedding over time, even when the patient is asymptomatic. There
currently is no consensus on when PCR testing should be performed, and
this is an area that needs further study.