Results
The study was conducted at Kettering General Hospital, Kettering England, between the 26th of March and 7th of April 2020. A total of 75 consecutive patients were screened for eligibility and 26 patients were deemed ineligible due to history of symptoms being longer than 7 days in duration (n=25) and immunosuppression (n=1). FebriDx testing was performed on 49 patients, test results were obtained for 48/49 patients and testing was not possible in 1/49 patients due to an inability to obtain enough blood on the first attempt. A second attempt was not possible as the patient was elderly, frail and clinically unstable at the time of testing. Data from 48 patient were included for final analysis (Figure 2). Of the 48 patients enrolled, 66.7% (32/48) males and 33.3% (16/68) female and 54.2% (26/48) were older than 65 years with a median age of 67 years. Enrolled patients reported symptoms for 2-7 days with a mean, median of 3.8 days and 3-day symptom onset, respectively. Fever was present at the time of testing in 85.4% (41/48) of patients. The final disposition amongst the cohort was 75% (36/48) of patients were discharged home, 25% (12/48) died while hospitalised. Cohort characteristics are described in Table 1.
Of the 48 subjects enrolled, 8.3% (4/48) had a final diagnosis categorised as non-infectious, 16.7% (8/48) bacterial infection, 2.1% (1/48) as non-COVID-19 viral infection and 72.9% (35/48) COVID-19 infection based on the Case Definitions30,31 (Figure 3). The overall prevalence of COVID-19 infection in the cohort was 72.9% (35/48) and the FebriDx test results were positive for a viral infection in all cases that had a final diagnosis of COVID-19 Viral infection. FebriDx was positive for bacterial infection in 22.9% (11/48) of cases and 100% (8/8) had a final diagnosis of Bacterial Infection (Sensitivity 100% [95% CI 63.1-100.0], Specificity 92.5% [95% CI 79.6-98.4], NPV 100% [95% CI 90.5-100.0], PPV 72.7% [95% CI 39.0-94.0] (Table 2). In all cases where FebriDx was negative for a viral infection (13/48), SARS-CoV-2 rRT-PCR was also negative. In one case of lower respiratory tract infection (LRTI), it was not possible to determine the exact cause of infection and a viral infection could not be excluded despite negative viral tests (FebriDx test, rRT-PCR for SARS-CoV-2, influenza and RSV were negative). Therefore, this patient was classified as having a final diagnosis of Non-COVID-19 Viral. Including this patient, in primary endpoint analysis, FebriDx demonstrated a diagnostic sensitivity 97.2% [95% CI 85.5 - 99.9], specificity of 100% [95% CI 73.5 - 100.0], PPV of 100% [95% CI 90.0 - 100.0], and NPV of 92.3% [95% CI 64.0 - 99.8] for viral infection (COVID-19 and Non-COVID-19) (Table 2).
In secondary endpoint analysis, SARS-CoV-2 was detected by rRT-PCR in (31/35) cases with a final diagnosis of COVID-19 Viral infection; 82.9% (29/35) were detected on the first rRT-PCR test (test to confirmation, 48 hours), 5.7% (2/35) were detected on the second rRT-PCR test (test to confirmation, 96 hours), and 11.5% (4/35) SARS-CoV-2 were not detected by rRT-PCR despite clear clinical evidence of COVID-19 that was consistent with Case Definition30,31. Of the 4 patients that met the Case Definition for COVID-19, but where SARS-CoV-2 was not detected using rRT-PCR, one had a positive SARS-CoV-2 IgM/IgG antibody test 14 days after the initial negative rRT-PCR test. FebriDx was viral positive in this patient.
FebriDx demonstrated a diagnostic sensitivity of 100% [95% CI 90.0-100], specificity of 100% [95% CI 75.3-100.0], PPV of 100% [95% CI 90.0-100], and NPV of 100% [95% CI 75.3-100.0] for identifying COVID-19 infection in a setting in which most ARIs were expected to be caused by SARS-CoV-2 (i.e. a high prevalence of SARS-CoV-2 infection was expected). Initial rRT-PCR (i.e. the very first rRT-PCR result obtained from patients) demonstrated a diagnostic sensitivity of 82.9% [95% CI 66.4-93.4], specificity of 100% [95% CI 75.3-100], PPV of 100% [95% CI 88.1-100], and NPV of 68.4% [43.4-87.4] when compared to the COVID-19 Case Definition30,31 (Table 2).