Comparative performance of surrogate and specific tests for SARS-CoV2
The key risk in using any POCT is of a false-negative result leading to inappropriate management of SARS-CoV2 infection. For FebriDx, an additional risk is that a positive result cannot exclude the possibility of another virus as the cause of infection.
Studies evaluating FebriDx mostly consider performance in distinguishing viral from bacterial causes of acute respiratory illnesses in toto , in secondary care. Reported sensitivities range from 64-90%, and specificities from 78-88% (13–16). However, two recent studies from the UK evaluate FebriDx specifically for screening for SARS-CoV2 in hospital: a small-scale pilot (5), and a study nested within a non-randomised clinical trial of molecular POCTs (6). These studies report impressive sensitivities and specificities of 100% and 93%, and 100% and 86% respectively. However, interpretation is limited by [i] the use of clinical diagnosis as reference standard rather than RT-PCR in the first study, [ii] evaluation in single secondary care centres in England in both cases, and [iii] the inclusion of patients in the range 2-7 days from symptom onset only in the first study. Finally, test performance in both studies may have been artificially boosted because they were conducted at times when the range of co-circulating respiratory viruses was lower than in the autumn and winter.
A comprehensive assessment of POCT field performance is beyond the scope of this paper, and available data indicate large context-dependent variations even for the same platform. However, based on data covering the first 14 days from symptom onset collated by FIND (17), SARS Co-V2-specific tests perform comparably to FebriDx (figure 1). Caveats to this assessment are that: (i) the majority of tests are antibody-based and therefore only reactive some time after symptom onset, and (ii) most studies used patient samples collected in clinical settings only. Evidence on the performance of FebriDx or any other POCT for diagnosis of SARS-CoV2 infection in key workers, care home residents, or other high-risk populations is in very short supply.