POCT modalities and SARS-CoV2 in theory
There are four POC testing approaches for SARS-CoV2 with different decision-making implications:
POCT utility varies according to time from symptom onset. PCR-based tests offer better sensitivity in the first few days but performance declines from as early as day 5 (8). Class III POCTs likely offer value only from day 7-8 because of the time taken to generate a detectable antibody response (9–11). All POCTs are, for now, used to guide interim decision-making pending final diagnosis via RT-PCR.
While class I, II and III modalities test for SARS-CoV2-specific antigens, RNA or antibodies respectively, FebriDx is a composite tool that detects both Myxovirus resistance protein A (MxA – elevated in acute viral infections) and C-reactive protein (CRP – elevated in either viral or bacterial infections). The test uses fixed thresholds for “positive” MxA and CRP levels; any positive MxA result, with or without positive CRP, indicates viral infection (4). These markers are used because: [i] CRP production is stimulated by Interleukin-6 (IL-6), produced in higher quantities in bacterial infections; [ii] MxA expression is exclusively driven by Type 1 Interferons (IFN-1), secreted in response to detection of viral signatures by host intracellular receptors. IFN-1, and consequently MxA, are thought to be specific to viral infection (4).
There may be grounds for caution in interpreting FebriDx results at the extremes of the clinical course. Early SARS-CoV infection appears not to activate MxA and IFN-1 transcription in the normal way (12), and if SARS-CoV2 similarly attenuates early MxA expression, FebriDx may have low sensitivity in at least the first few days following infection. The low MxA threshold for a positive result (40ng/mL) means FebriDx may nevertheless be positive even with weak MxA activation.