130 participants were included into the study, with 76.9% females (n= 100) and 23.1% males (n= 30). The median age was 41 years (ranging from 19 to 64). A majority of the participants (65.4 %) were nurses, 23.8% were medical doctors, and 10.8% were employed in other fields (e.g. biomedical analysts, physiotherapists, etc.). 101 participants (77.7%) had a high-risk-exposition (category I), while 29 participants (22.3%) were classified as low-risk-exposed (category II). The mean number of days from the contact to a COVID-19 patient without personal protective equipment until sampling was 19.4 (± 13.9) days
Table 1. Baseline characteristics.
N=
|
130
|
Gender
female, n (%)
male, n (%)
|
100 (76.9)
30 (23.1)
|
Age, median (range)
|
41 (19 – 64)
|
Occupation
nurses, n (%)
medical doctors, n (%)
others, n (%)*
|
85 (65.4)
31 (23.8)
14 (10.8)
|
Category of contact to COVID-19 patients
category I, n (%)#
category II, n (%)$
|
101 (77.7)
29 (22.3)
|
Days from contact to study inclusion, mean (SD)
|
19.4 (13.9)
|
History of COVID-19:
previous RT-PCR confirmed infection
unknown COVID-19 status
|
5 (3.8)
125 (96.2)
|
* e.g. biomedical analysts, physiotherapists and others
# defined as “High-risk-exposition”, i.e. less than two meters over a prolonged period of time, or close contact while performing aerosol-generating procedure
$ defined as “Low-risk-exposition”, i.e. contact above a distance of two meters for less than 15 minutes contact time
Table 2 summarizes the results of the RT-PCR, ELISA, and the POC tests, and table 3 gives details on all participants with their respective results. Four participants were positively tested with RT-PCR (3.1% of the overall study group), one with a history of confirmed and recovered COVID-19 infection, but three with a previous unknown status and therefore newly detected infection (2.4% of the unknown status collective). These three participants failed to show IgG or IgM antibodies by any test, but later developed clinical symptoms.
Test concordance (IgM + IgG) of the NADAL® COVID-19 IgG/IgM Rapid Test for serum vs. whole blood was 96.9% and for the mö-screen 2019-NCOV Corona Virus test 97.7%. Comparison of the results of the two POC tests showed 99.2% concordance for serum and 100% for whole blood. Test concordance of the both POC tests compared to the reference standard ELISA was slightly higher when using serum instead of whole blood (NADAL® COVID-19 IgG/IgM Rapid Test 97.7% vs. 96.2%; mö-screen 2019-NCOV Corona Virus test 96.9% vs. 96.2%), however the differences were not statistically significant.
Using ELISA, five participants with a history of a COVID-19 infection (two with IgM + IgG, two with IgG only, one with IgM only), and two participants of unknown infection status were positively tested for anti-SARS-CoV-2 antibodies (one with IgM + IgG, one with IgG only). Both did not experience any clinical symptoms and therefore were defined as asymptomatically infected (= 1.6% of the participants with unknown COVID-19 status, and 1.9% of the participants with a category I high-risk exposure contact).
Table 2. Overview of the main results of RT-PCR, ELISA and both point-of-care lateral flow chromatographic immunoassay, and test concordance among different assays and specimens (blood serum vs. whole blood).
RT-PCR positive:
Overall study group (n=130), n (%)
Participants with unknown status (n=125), n (%)
Participants with previous COVID-19 (n=5), n (%)
|
4 (3.1)
3 (2.4)
1 (20.0)
|
ELISA:
Negative, n (%)
IgM, n (%)
IgG, n (%)
IgM + IgG, n (%)
|
123 (94.6)
1 (0.8)
3 (2.3)
3 (2.3)
|
POC test 1 (NADAL), whole blood:
Negative, n (%)
IgM, n (%)
IgG, n (%)
IgM + IgG, n (%)
|
124 (95.4)
1 (0.8)
2 (1.5)
3 (2.3)
|
POC test 1 (NADAL), serum:
Negative, n (%)
IgM, n (%)
IgG, n (%)
IgM + IgG, n (%)
|
123 (94.6)
1 (0.8)
0
6 (4.6)
|
POC test 2 (mö-screen), whole blood:
Negative, n (%)
IgM, n (%)
IgG, n (%)
IgM + IgG, n (%)
|
124 (95.4)
1 (0.8)
2 (1.5)
3 (2.3)
|
POC test 2 (mö-screen), serum:
Negative, n (%)
IgM, n (%)
IgG, n (%)
IgM + IgG, n (%)
|
124 (95.4)
0
0
6 (4.6)
|
Test result concordance (IgM + IgG):
POC 1: serum vs. whole blood, n (%)
POC 2: serum vs. whole blood, n (%)
POC 1 vs. POC 2: serum (n, %) / whole blood (n, %)
POC 1 vs. ELISA: serum (n, %) / whole blood (n, %)
POC 2 vs. ELISA: serum (n, %) / whole blood (n, %)
|
126 (96.9)
127 (97.7)
129 (99.2) / 130 (100)
127 (97.7) / 125 (96.2)
126 (96.9) / 125 (96.2)
|
POC = point-of-care lateral flow chromatographic immunoassay; ELISA = enzyme-linked immunosorbent assay
Table 3. Details of study participants with any positive result for SARS-CoV-2 infection and/or anti-SARS-CoV-2 antibodies.
age
|
gender
|
time since contact (days)
|
RT-PCR
|
POC 1 NADAL (WB)
|
POC 2
mö-screen
(WB)
|
POC 1 NADAL (S)
|
POC 2 mö-screen (S)
|
ELISA
|
35
|
m
|
5
|
pos
|
neg
|
neg
|
neg
|
neg
|
neg
|
42
|
f
|
4
|
pos
|
neg
|
neg
|
neg
|
neg
|
neg
|
53
|
f
|
5
|
pos
|
neg
|
neg
|
neg
|
neg
|
neg
|
55
|
m
|
47
|
neg
|
IgG
|
IgG
|
IgM/IgG
|
IgM/IgG
|
IgM/IgG
|
52
|
f
|
47
|
neg
|
IgG
|
IgG
|
IgM/IgG
|
IgM/IgG
|
IgG
|
61
|
f
|
23
|
neg
|
IgM/IgG
|
IgM/IgG
|
IgM/IgG
|
IgM/IgG
|
IgG
|
43
|
f
|
40
|
neg
|
IgM/IgG
|
IgM/IgG
|
IgM/IgG
|
IgM/IgG
|
IgM/IgG
|
36
|
m
|
34
|
neg
|
IgM
|
IgM
|
IgM/IgG
|
IgM/IgG
|
IgM/IgG
|
45
|
f
|
50
|
pos
|
neg
|
neg
|
IgM
|
neg
|
IgM
|
59
|
f
|
46
|
neg
|
IgM/IgG
|
IgM/IgG
|
IgM/IgG
|
IgM/IgG
|
IgG
|
RT-PCR = real-time polymerase chain reaction; POC = point-of-care lateral flow chromatographic immunoassay; ELISA = enzyme-linked immunosorbent assay; WB = whole blood; S = serum
Table 4 and 5 depict the performance of the two POC tests compared to ELISA, when using blood serum. The NADAL® COVID-19 IgG/IgM Rapid Test showed a sensitivity (IgM/ IgG) of 100% (100%/ 100%), a specificity (IgM/ IgG) of 98.8% (97.6%/ 100%), a PPV of 76.9% (57.1%/ 100%), an NPV of 100% (100%/ 100%), and a diagnostic accuracy of 98.8% (97.7%/ 100%). The mö-screen 2019-NCOV Corona Virus test had a sensitivity (IgM/IgG) of 90.9% (80%/ 100%), a specificity (IgM/IgG) of 98.8% (97.6%/ 100%), a PPV of 76.9% (57.1%/ 100%), an NPV of 99.6% (99.2%/ 100%), and a diagnostic accuracy of 98.5% (96.9%/ 100%).
Table 4. Comparison of lateral flow chromatographic immunoassay (point-of-care antibody tests: NADAL® COVID-19 IgG/IgM Rapid Test; mö-screen 2019-NCOV Corona Virus test) and reference standard for anti-SARS-CoV-2 antibodies (ELISA), using blood serum, in seven participants with detected SARS-CoV-2 antibodies.
ELISA
|
Positive
|
Negative
|
POC 1 (NADAL)
|
Positive
|
Negative
|
POC 2
(mö-screen)
|
Positive
|
Negative
|
IgM
|
4
|
3
|
IgM
|
7
|
0
|
IgM
|
6
|
1
|
IgG
|
6
|
1
|
IgG
|
6
|
1
|
IgG
|
6
|
1
|
POC = point-of-care lateral flow chromatographic immunoassay; ELISA = enzyme-linked immunosorbent assay
Table 5. Result overview: Diagnostic accuracy of lateral flow chromatographic immunoassay (point-of-care antibody tests: NADAL® COVID-19 IgG/IgM Rapid Test; mö-screen 2019-NCOV Corona Virus test) vs. reference standard for anti-SARS-CoV-2 antibodies (ELISA), using blood serum.
|
NADAL® COVID-19 IgG/IgM Rapid Test
|
mö-screen 2019-NCOV Corona Virus test
|
|
IgM
|
IgG
|
IgM
|
IgG
|
Sensitivity (95% CI)
|
1.0 (0.39 – 1.0)
|
1.0 (0.54 – 1.0)
|
0.8 (0.23 – 0.99)
|
1.0 (0.54 – 1.0)
|
Specificity (95% CI)
|
0.97 (0.93 – 0.99)
|
1.0 (0.97 – 1.0)
|
0.97 (0.93 – 0.99)
|
1.0 (0.97 – 1.0)
|
PPV (95% CI)
|
0.57 (0.30 – 0.80)
|
1.0
|
0.57 (0.28 – 0.81)
|
1.0
|
NPV (95% CI)
|
1.0
|
1.0
|
0.99 (0.95 – 0.99)
|
1.0
|
Accuracy (95% CI)
|
0.97 (0.93 – 0.99)
|
1.0 (0.97 – 1.0)
|
0.43 (0.92 - 0.99)
|
1.0 (0.97 – 1.0)
|
PPV = positive predictive value; NPV = negative predictive value