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).