Limits of the current diagnostic approach for COVID-19
The diagnostic gold standard for COVID-19 is the naso-pharingeal (NP)
swab reverse-transcription real-time polymerase chain reaction (rRT-PCR)
detection of SARS-Cov-2. However, due to the unavailability of a shared
reference standard for COVID-19 diagnosis there are no reliable data on
NP swab sensitivity. Clerici et al. assessed nasopharyngeal swab
sensitivity in patients with known SARS-Cov-2 infection, based on the
presence of symptoms and of ≥1 positive rRT-PCR serial testing, and
found a sensitivity of 77% (95% CI, 73 to 81%).6Wang et al. evaluated SARS-Cov-2 detectability in different biological
specimens in COVID-19 patients and found a NP swab sensitivity of
63%.7 Pooled data found that the probability of a
false negative result was as high as 21% even at the optimal testing
window (3 days after symptom onset).8
Given the limits of NP swab testing, some experts propose to diagnose
suspected cases using the widely available, time-saving and non-invasive
imaging approach of chest computed tomography (CT), that could serve as
an efficient and effective way to flag, diagnose, and possibly triage
COVID-19 patients.9,10 However, as confirmed by a
recent metanalysis of 60 studies (5744 patients), CT has a low
specificity compared to NP swabs rRT-PCR, 46% (95% CI,
29-63%).11 Ongoing studies are evaluating the role of
radiomics analysis to identify a diagnostic signature for COVID-19
infection, based on standard-of-care chest CT imaging, with promising
preliminary results showing a sensitivity of 69.52%, and a specificity
of 91.63%.12
In this scenario identifying the false negative cases remains of
critical importance to properly manage patients avoiding improper
allocation of COVID-19 cases and allowing a timely treatment. Since the
early pandemic, BAL has been proposed as a potentially useful diagnostic
tool to increase COVID-19 diagnosis sensitivity. Nevertheless,
considering the high potential to aerosol exposure generate during BAL,
international bronchology societies have universally cautioned for a
limited and proper use of this tool in clinical practice during the
pandemic peaks. The role of BAL in the diagnostic algorithm of COVID-19
has been debated and explored in several studies.