| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-133 |
Sentence |
denotes |
Sensitivity and specificity of 14 SARS-CoV-2 serological assays and their diagnostic potential in RT-PCR negative COVID-19 infections |
| T2 |
134-136 |
Sentence |
denotes |
E. |
| T3 |
137-156 |
Sentence |
denotes |
VAN HONACKER ET AL. |
| T4 |
157-177 |
Sentence |
denotes |
ACTA CLINICA BELGICA |
| T5 |
179-187 |
Sentence |
denotes |
Abstract |
| T6 |
188-196 |
Sentence |
denotes |
ABSTRACT |
| T7 |
197-208 |
Sentence |
denotes |
Background: |
| T8 |
209-384 |
Sentence |
denotes |
Molecular detection of SARS-CoV-2 in respiratory samples is the gold standard for COVID-19 diagnosis but it has a long turnaround time and struggles to detect low viral loads. |
| T9 |
385-467 |
Sentence |
denotes |
Serology could help to diagnose suspected cases which lack molecular confirmation. |
| T10 |
468-515 |
Sentence |
denotes |
Two case reports are presented as illustration. |
| T11 |
516-527 |
Sentence |
denotes |
Objectives: |
| T12 |
528-633 |
Sentence |
denotes |
The aim of this study was to evaluate the performance of several commercial assays for COVID-19 serology. |
| T13 |
634-749 |
Sentence |
denotes |
We illustrated the added value of COVID-19 serology testing in suspect COVID-19 cases with negative molecular test. |
| T14 |
750-763 |
Sentence |
denotes |
Study design: |
| T15 |
764-888 |
Sentence |
denotes |
Twenty-three sera from 7 patients with a confirmed molecular diagnosis of SARS-CoV-2 were tested using 14 commercial assays. |
| T16 |
889-976 |
Sentence |
denotes |
Additionally, 10 pre-pandemic sera and 9 potentially cross-reactive sera were selected. |
| T17 |
977-1019 |
Sentence |
denotes |
We calculated sensitivity and specificity. |
| T18 |
1020-1214 |
Sentence |
denotes |
Furthermore, we discuss the diagnostic relevance of COVID-19 serology in a retrospective cohort of 145 COVID-19 cases in which repetitive molecular and serological SARS-CoV-2 tests were applied. |
| T19 |
1215-1223 |
Sentence |
denotes |
Results: |
| T20 |
1224-1363 |
Sentence |
denotes |
The interpretation of the pooled sensitivity of IgM/A and IgG resulted in the highest values (range 14–71% on day 2–7; 88–94% on day 8–18). |
| T21 |
1364-1428 |
Sentence |
denotes |
Overall, the specificity of the assays was high (range 79–100%). |
| T22 |
1429-1568 |
Sentence |
denotes |
Among 145 retrospective cases, 3 cases (2%) remained negative after sequential molecular testing but positive on final SARS-CoV-2 serology. |
| T23 |
1569-1580 |
Sentence |
denotes |
Conclusion: |
| T24 |
1581-1698 |
Sentence |
denotes |
Sensitivity of COVID-19 serological diagnosis was variable but consistently increased at >7 days after symptom onset. |
| T25 |
1699-1720 |
Sentence |
denotes |
Specificity was high. |
| T26 |
1721-1889 |
Sentence |
denotes |
Our data suggest that serology can complement molecular testing for diagnosis of COVID-19, especially for patients presenting the 2nd week after symptom onset or later. |
| T27 |
1891-1901 |
Sentence |
denotes |
Background |
| T28 |
1902-2004 |
Sentence |
denotes |
In December 2019, several cases of an unidentified pneumonia occurred in the province of Hubei, China. |
| T29 |
2005-2141 |
Sentence |
denotes |
With the use of next-generation sequencing, the Wuhan Institute of Virology identified a new coronavirus as the etiological agent [1,2]. |
| T30 |
2142-2271 |
Sentence |
denotes |
This new virus, which belongs to the genus betacoronavirus, was initially acknowledged as novel coronavirus 2019 (2019-nCOV) [3]. |
| T31 |
2272-2449 |
Sentence |
denotes |
On 11 February 2020, the virus was officially renamed the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses [4]. |
| T32 |
2450-2605 |
Sentence |
denotes |
Since then the virus has rapidly spread and on the 18th of July 2020, over 14 million confirmed cases and 600 000 direct casualties have been reported [5]. |
| T33 |
2606-2771 |
Sentence |
denotes |
So far, implementation of strict quarantine measures have contained further exponential spreading of the virus in Europe and have flattened the first epidemic curve. |
| T34 |
2772-2942 |
Sentence |
denotes |
Considering the extent of the pandemic, its socio-economic impact, and the effect on healthcare systems worldwide, there is a high need to extend the diagnostic capacity. |
| T35 |
2943-3118 |
Sentence |
denotes |
So far, the gold standard for the diagnosis of SARS-CoV-2, implemented at the start of the outbreak, is real-time reverse transcriptase polymerase chain reaction (RT-PCR) [6]. |
| T36 |
3119-3269 |
Sentence |
denotes |
In contrast with a high specificity up to 98.8% [7], RT-PCR suffers from a rather long turnaround time when performed in batch testing (2 to 6 hours). |
| T37 |
3270-3347 |
Sentence |
denotes |
Continuous PCR testing has a faster turnaround time (1 u) but a low capacity. |
| T38 |
3348-3510 |
Sentence |
denotes |
False negative results in both the very early as well as the late phase of the disease due to low virus shedding at these stages of infection are reported [8–10]. |
| T39 |
3511-3616 |
Sentence |
denotes |
Studies have shown discrepant results between RT-PCR and chest computed tomography (CT) findings [11,12]. |
| T40 |
3617-3787 |
Sentence |
denotes |
CT imaging findings in 30 patients with suspicion of COVID-19 pneumonia were shown to have a sensitivity of 97.2% compared to 83.3% of initial nasopharyngeal RT-PCR [13]. |
| T41 |
3788-3899 |
Sentence |
denotes |
Establishing the diagnosis of COVID-19 is sometimes very challenging and does not only rely on molecular tests. |
| T42 |
3900-4062 |
Sentence |
denotes |
We report on two patients who presented at the emergency department with high suspicion of COVID-19 infection based on clinical findings and/or chest-CT findings. |
| T43 |
4063-4179 |
Sentence |
denotes |
Nevertheless, SARS-CoV-2 RT-PCR testing was repeatedly negative on repetitive nasopharyngeal, throat and anal swabs. |
| T44 |
4180-4291 |
Sentence |
denotes |
Case 1 was a 66 year old male experiencing symptoms of shortness of breath, fever and muscle pain since 8 days. |
| T45 |
4292-4341 |
Sentence |
denotes |
Lab findings showed thrombopenia (87,000/µL, ref. |
| T46 |
4342-4388 |
Sentence |
denotes |
149,000–31,9000/µL), lymphopenia (930/µL, ref. |
| T47 |
4389-4445 |
Sentence |
denotes |
1,133–3,105/µL), normal neutrophil count (2,980/µL, ref. |
| T48 |
4446-4494 |
Sentence |
denotes |
1,573–6,100/µL) low eosinophil count (0/µL, ref. |
| T49 |
4495-4541 |
Sentence |
denotes |
28–273/µL), normal basophil count (10/µL, ref. |
| T50 |
4542-4656 |
Sentence |
denotes |
6–50/µL), elevated D-dimers (1,480 ng/mL, ref. <500 ng/mL) and elevated C-reactive protein (29 mg/L, ref <5 mg/L). |
| T51 |
4657-4856 |
Sentence |
denotes |
Chest CT on the day of admission showed bilateral ground glass opacities with a crazy paving pattern suspicious for COVID-19 (CT severity score of 10 or CO-RADS classification of 4: COVID-19 likely). |
| T52 |
4857-5064 |
Sentence |
denotes |
Repetitive nasopharyngeal swabs on day 8, 9, 12 and 13 as well as anal swabs on day 9 and 13 after symptom onset were all SARS-CoV-2 RT-PCR negative using the protocol described by Corman and colleagues [6]. |
| T53 |
5065-5196 |
Sentence |
denotes |
Serology on day 13 after symptom onset indicated negative IgM but positive IgG (Prima Professional®, Point-Of-Care antibody Tests). |
| T54 |
5197-5328 |
Sentence |
denotes |
On day 13, the patient was admitted to the intensive care unit (ICU) because of type 1 respiratory insufficiency (pO2 60 mmHg, ref. |
| T55 |
5329-5361 |
Sentence |
denotes |
83–108 mm Hg; pCO2 31 mmHg, ref. |
| T56 |
5362-5388 |
Sentence |
denotes |
35–45 mm Hg; pH 7.46, ref. |
| T57 |
5389-5400 |
Sentence |
denotes |
7.35–7.45). |
| T58 |
5401-5443 |
Sentence |
denotes |
He did not require mechanical ventilation. |
| T59 |
5444-5500 |
Sentence |
denotes |
Based on these findings, he was diagnosed with COVID-19. |
| T60 |
5501-5648 |
Sentence |
denotes |
Case 2 was a 14 year old child presenting at the emergency room with 3 days of fever > 39°C, muscle pain, cough, sore throat, headache and fatigue. |
| T61 |
5649-5778 |
Sentence |
denotes |
The girl’s father had suffered from fever and respiratory symptoms after contact with multiple COVID-19 patients 4 weeks earlier. |
| T62 |
5779-5941 |
Sentence |
denotes |
On day 4 after symptom onset, there was a clinical deterioration to refractory shock and multi-organ failure with hypotension and respiratory and cardiac failure. |
| T63 |
5942-5991 |
Sentence |
denotes |
Lab findings showed thrombopenia (89,000/µL, ref. |
| T64 |
5992-6038 |
Sentence |
denotes |
154,000–452,000/µL), lymphopenia (162/µL, ref. |
| T65 |
6039-6095 |
Sentence |
denotes |
1,500–6,500/µL), normal neutrophil count (7,564/µL, ref. |
| T66 |
6096-6147 |
Sentence |
denotes |
2,500–8,000), normal eosinophil count (283/µL, ref. |
| T67 |
6148-6191 |
Sentence |
denotes |
100–500/µL), low basophil count (0/µL, ref. |
| T68 |
6192-6306 |
Sentence |
denotes |
10–100/µL), elevated D-dimers (4,420 ng/mL, ref. <500 ng/mL) and high C-reactive protein (308 mg/L, ref. <5 mg/L). |
| T69 |
6307-6354 |
Sentence |
denotes |
Chest CT did not show signs of viral pneumonia. |
| T70 |
6355-6417 |
Sentence |
denotes |
Echocardiography revealed decreased left ventricular function. |
| T71 |
6418-6488 |
Sentence |
denotes |
She responded well to supportive therapy and corticosteroid treatment. |
| T72 |
6489-6582 |
Sentence |
denotes |
Throat swabs on day 3 and 5 after symptom onset were negative for SARS-CoV-2 with RT-PCR [6]. |
| T73 |
6583-6685 |
Sentence |
denotes |
Serology on day 8 after symptom onset was negative for IgM but positive for IgG (Prima Professional®). |
| T74 |
6686-6799 |
Sentence |
denotes |
She was diagnosed with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS). |
| T75 |
6800-6915 |
Sentence |
denotes |
The case reports mentioned above point out the potential of serological assays to add to the diagnosis of COVID-19. |
| T76 |
6916-7021 |
Sentence |
denotes |
So far, a large number of serological assays have been developed in response to the diagnostic need [14]. |
| T77 |
7022-7138 |
Sentence |
denotes |
Data on the validation and comparison of the performance of these assays are emerging but are still limited [15–18]. |
| T78 |
7139-7315 |
Sentence |
denotes |
Since antibody production by the specific immune system is subject to delay, a lower diagnostic performance of serological assays in the early phase of the disease is expected. |
| T79 |
7316-7434 |
Sentence |
denotes |
So far, studies have revealed that antibodies could be detected as early as 3–6 days after symptom onset [9,10,19,20]. |
| T80 |
7436-7446 |
Sentence |
denotes |
Objectives |
| T81 |
7447-7777 |
Sentence |
denotes |
The main goal of this study was to evaluate the performance of 5 five Point-Of-Care antibody Tests, one chemiluminescence microparticle immunoassay (CMIA), one chemiluminescence immunoassay (CLIA) and 7 enzyme-linked immunosorbent assays (ELISA) for COVID-19 serology in an attempt to validate and select the best performing ones. |
| T82 |
7778-7949 |
Sentence |
denotes |
Secondly, we discuss the role of SARS-CoV-2 serology in the process of diagnosing COVID-19 disease in presumable COVID-19 cases with sequential negative SARS-CoV-2 RT-PCR. |
| T83 |
7951-7963 |
Sentence |
denotes |
Study design |
| T84 |
7964-8117 |
Sentence |
denotes |
The study was approved by the local ethics committee (BC-07829) of the Ghent University Hospital, a 1062-beds tertiary care teaching hospital in Belgium. |
| T85 |
8118-8339 |
Sentence |
denotes |
From March 12th to 31st 2020, 23 consecutive sera from 7 different patients, admitted to the hospital with a confirmed diagnosis of COVID-19 based on positive RT-PCR [6], were collected on day 2 to 18 after symptom onset. |
| T86 |
8340-8391 |
Sentence |
denotes |
The study group consisted of 2 females and 5 males. |
| T87 |
8392-8440 |
Sentence |
denotes |
The median age was 58 years (range 39–81 years). |
| T88 |
8441-8616 |
Sentence |
denotes |
The collected sera were divided into 2 groups: day 2–7 after symptom onset (7 samples) and day 8–18 after symptom onset (16 samples) in order to evaluate clinical sensitivity. |
| T89 |
8617-8807 |
Sentence |
denotes |
Specificity was evaluated using 10 pre-pandemic sera, i.e. clinical samples sent to the hospital laboratory for non-COVID-19-related serological investigations from August to September 2019. |
| T90 |
8808-9179 |
Sentence |
denotes |
Furthermore, 9 potential cross-reactive sera were included, i.e. IgM positivity against Cytomegalovirus (CMV) (n = 2), Epstein-Barr virus (EBV) (n = 2) or Toxoplasma gondii (Toxo) (n = 1); samples positive for rheumafactor (RF) (n = 1) or anti-nuclear factor (ANF) (n = 1)) and sera from patients positive for non-SARS-CoV-2 endemic coronaviruses (OC43 and NL63) (n = 2). |
| T91 |
9180-9398 |
Sentence |
denotes |
The 14 serological assays listed in Table 1 were performed on each of the 23 sera from PCR confirmed COVID-19 positive patients and the 19 pre-pandemic/cross-reactive sera, according to the manufacturer’s instructions. |
| T92 |
9399-9457 |
Sentence |
denotes |
Sensitivity and specificity were calculated for each test. |
| T93 |
9458-9675 |
Sentence |
denotes |
We calculated both the overall sensitivity (day 2–18 after symptom onset) and the sensitivity of the two subgroups (day 2–7 and day 8–18), each time for IgM/A and IgG separately and for combined IgM/A and IgG testing. |
| T94 |
9676-9684 |
Sentence |
denotes |
Table 1. |
| T95 |
9685-9716 |
Sentence |
denotes |
Overview of the included assays |
| T96 |
9717-9774 |
Sentence |
denotes |
Test Assay Company Antibody detection Recombinant antigen |
| T97 |
9775-9793 |
Sentence |
denotes |
Point-of-care test |
| T98 |
9794-9883 |
Sentence |
denotes |
Corona Virus (COVID-19) Combined IgM/IgG Rapid Test Sol Scientifics IgM+IgG Not specified |
| T99 |
9884-9986 |
Sentence |
denotes |
COVID-19 IgG/igM Rapid Test Cassette Zhejiang ORIENT GENE Biotech IgM+IgG Spike + nucleocapsid protein |
| T100 |
9987-10097 |
Sentence |
denotes |
Wantai SARS-COV-2 Ab Rapid Test Beijing Wantai Biological Pharmacy Enterprise IgM+IgG (combined) Not specified |
| T101 |
10098-10166 |
Sentence |
denotes |
COVID-19 IgG/IgM RAPID TEST PRIMA PROFESSIONAL IgM+IgG Not specified |
| T102 |
10167-10250 |
Sentence |
denotes |
Diagnostic Kit for IgG/IgM Antibody to SARS-CoV-2 WIZ BIOTECH IgM+IgG Not specified |
| T103 |
10251-10292 |
Sentence |
denotes |
Enzyme-Linked Immunosorbent Assay (ELISA) |
| T104 |
10293-10363 |
Sentence |
denotes |
Anti-SARS-CoV-2 ELISA (IgA) EUROIMMUN S1 Spike glycoprotein (S1domain) |
| T105 |
10364-10435 |
Sentence |
denotes |
Anti-SARS-CoV-2 ELISA (IgG) EUROIMMUN IgG Spike glycoprotein (S1domain) |
| T106 |
10436-10520 |
Sentence |
denotes |
Novel Coronavirus COVID-19 IgM ELISA Kit Epitope Diagnostics (EDI) IgM Not specified |
| T107 |
10521-10612 |
Sentence |
denotes |
Novel Coronavirus COVID-19 IgG ELISA Kit Epitope Diagnostics (EDI) IgG Nucleocapsid protein |
| T108 |
10613-10676 |
Sentence |
denotes |
SARS-CoV-2 IgM ELISA Kit Creative Diagnostics IgM Not specified |
| T109 |
10677-10740 |
Sentence |
denotes |
SARS-CoV-2 IgG ELISA kit Creative Diagnostics IgG Not specified |
| T110 |
10741-10817 |
Sentence |
denotes |
Human Anti-2019 nCoV(N) IgG ELISA kit Finetest, Wuhan Fine Biotech Co., Ltd. |
| T111 |
10818-10851 |
Sentence |
denotes |
IgG Spike glycoprotein (S1domain) |
| T112 |
10852-10901 |
Sentence |
denotes |
Chemiluminescent microparticle immunoassay (CMIA) |
| T113 |
10902-10948 |
Sentence |
denotes |
SARS-CoV-2 IgG Abbott IgG Nucleocapsid protein |
| T114 |
10949-10985 |
Sentence |
denotes |
Chemiluminescence immunoassay (CLIA) |
| T115 |
10986-11045 |
Sentence |
denotes |
Liaison SARS-CoV-2 S1/S2 IgG DiaSorin IgG S1 and S2 protein |
| T116 |
11046-11192 |
Sentence |
denotes |
Sensitivity and specificity were calculated by means of Excel (version 16.0, Microsoft, Washington, USA) using the following definitions in Excel: |
| T117 |
11193-11261 |
Sentence |
denotes |
Sensitivity = 100 x [True Positive/(True Positive + False Negative)] |
| T118 |
11262-11329 |
Sentence |
denotes |
Specificity = 100 x [True Negative/(True Negative +False Positive)] |
| T119 |
11330-11632 |
Sentence |
denotes |
All patients consulting at the emergency department of our hospital from the 1st of March till the 14th of May, with symptoms suggestive of COVID-19 disease that required hospital admission and for which laboratory diagnosis was performed in our institution were retrospectively included in a database. |
| T120 |
11633-11732 |
Sentence |
denotes |
In all patients a RT-PCR test on nasopharyngeal/throat swab was performed at the time of admission. |
| T121 |
11733-11857 |
Sentence |
denotes |
If the initial nasopharyngeal swab was found to be negative, a second nasopharyngeal and additional anal swab were analyzed. |
| T122 |
11858-11922 |
Sentence |
denotes |
If still negative, a bronchoalveolar lavage (BAL) was performed. |
| T123 |
11923-12169 |
Sentence |
denotes |
Patients with repetitive negative molecular testing for SARS-CoV-2 but high clinical, epidemiological and/or radiological suspicion of COVID-19 disease were subjected to serological testing using COVID-19 IgG/IgM rapid test (Prima Professional®). |
| T124 |
12170-12354 |
Sentence |
denotes |
Among this retrospective cohort of hospitalized patients clinically treated for COVID-19 disease, we calculated the number of patients that ultimately had a RT-PCR confirmed diagnosis. |
| T125 |
12355-12466 |
Sentence |
denotes |
As such, an estimation of the added diagnostic value of SARS-CoV-2 serology in this cohort could be calculated. |
| T126 |
12468-12475 |
Sentence |
denotes |
Results |
| T127 |
12476-12578 |
Sentence |
denotes |
Sensitivity on day 2–7 after symptom onset ranged from 0% to 57% for IgM/A and from 0% to 71% for IgG. |
| T128 |
12579-12684 |
Sentence |
denotes |
Sensitivity on day 8–18 after symptom onset ranged from 50% to 94% for IgM/A and from 81% to 94% for IgG. |
| T129 |
12685-12888 |
Sentence |
denotes |
If IgA/M and IgG were both available, the combined IgM/A and IgG sensitivity result was consistently higher than the separate interpretation (range 14–71% on day 2–7 and 88–94% on day 8–18; see Table 2). |
| T130 |
12889-12897 |
Sentence |
denotes |
Table 2. |
| T131 |
12898-12944 |
Sentence |
denotes |
Sensitivity and specificity of all test assays |
| T132 |
12945-13038 |
Sentence |
denotes |
Test Assay Sensitivity day 2–7 Sensitivity day 8–18 Overall sensitivity day 2-d18 Specificity |
| T133 |
13039-13109 |
Sentence |
denotes |
IgM* IgG IgM* + IgG IgM* IgG IgM* + IgG IgM* IgG IgM* + IgG IgM* IgG |
| T134 |
13110-13150 |
Sentence |
denotes |
Point-of-care test |
| T135 |
13151-13265 |
Sentence |
denotes |
Corona Virus (COVID-19) Combined IgM/IgG Rapid test (Sol scientifics) 57% 14% 57% 94% 88% 94% 83% 65% 83% 79% 100% |
| T136 |
13266-13362 |
Sentence |
denotes |
COVID-19 IgG/IgM Rapid test Cassette (Orient Gene) 43% 29% 43% 94% 88% 94% 78% 70% 78% 100% 100% |
| T137 |
13363-13406 |
Sentence |
denotes |
SARS-CoV-2 Ab rapid test (Wantai) n.a. n.a. |
| T138 |
13407-13420 |
Sentence |
denotes |
43% n.a. n.a. |
| T139 |
13421-13434 |
Sentence |
denotes |
94% n.a. n.a. |
| T140 |
13435-13443 |
Sentence |
denotes |
78% n.a. |
| T141 |
13444-13448 |
Sentence |
denotes |
100% |
| T142 |
13449-13541 |
Sentence |
denotes |
COVID-19 IgG/IgM RAPID TEST (PRIMA PROFESSIONAL) 0% 29% 29% 50% 81% 88% 35% 65% 70% 95% 100% |
| T143 |
13542-13650 |
Sentence |
denotes |
Diagnostic Kit for IgG/IgM Antibody to SARS-CoV-2 (WIZ BIOTECH) 14% 14% 14% 94% 94% 94% 70% 70% 70% 95% 100% |
| T144 |
13651-13714 |
Sentence |
denotes |
Enzyme-Linked Immunosorbent Assay (ELISA) |
| T145 |
13715-13788 |
Sentence |
denotes |
Anti-SARS-CoV-2 (EUROIMMUN)* 57% 29% 57% 94% 88% 94% 83% 70% 83% 95% 100% |
| T146 |
13789-13881 |
Sentence |
denotes |
Novel Coronavirus COVID-19 (Epitope Diagnostics) 29% 71% 71% 69% 94% 94% 57% 87% 87% 95% 89% |
| T147 |
13882-13975 |
Sentence |
denotes |
SARS-CoV-2 IgG ELISA Kit (Creative Diagnostics) 29% 14% 29% 94% 88% 94% 74% 65% 74% 100% 100% |
| T148 |
13976-14029 |
Sentence |
denotes |
Human Anti-2019 nCoV(N) IgG ELISA kit (Finetest) n.a. |
| T149 |
14030-14043 |
Sentence |
denotes |
29% n.a. n.a. |
| T150 |
14044-14057 |
Sentence |
denotes |
88% n.a. n.a. |
| T151 |
14058-14071 |
Sentence |
denotes |
70% n.a. n.a. |
| T152 |
14072-14075 |
Sentence |
denotes |
83% |
| T153 |
14076-14145 |
Sentence |
denotes |
Chemiluminescent microparticle immunoassay (CMIA) |
| T154 |
14146-14174 |
Sentence |
denotes |
SARS-CoV-2 IgG (Abbott) n.a. |
| T155 |
14175-14188 |
Sentence |
denotes |
29% n.a. n.a. |
| T156 |
14189-14202 |
Sentence |
denotes |
88% n.a. n.a. |
| T157 |
14203-14216 |
Sentence |
denotes |
70% n.a. n.a. |
| T158 |
14217-14221 |
Sentence |
denotes |
100% |
| T159 |
14222-14280 |
Sentence |
denotes |
Chemiluminescence immunoassay (CLIA) |
| T160 |
14281-14325 |
Sentence |
denotes |
Liaison SARS-CoV-2 S1/S2 IgG (DiaSorin) n.a. |
| T161 |
14326-14338 |
Sentence |
denotes |
0% n.a. n.a. |
| T162 |
14339-14352 |
Sentence |
denotes |
81% n.a. n.a. |
| T163 |
14353-14366 |
Sentence |
denotes |
59% n.a. n.a. |
| T164 |
14367-14371 |
Sentence |
denotes |
100% |
| T165 |
14372-14401 |
Sentence |
denotes |
Anti-SARS-CoV-2 (EUROIMMUN)*: |
| T166 |
14402-14442 |
Sentence |
denotes |
IgA instead of IgM; n.a.: not applicable |
| T167 |
14443-14530 |
Sentence |
denotes |
Overall the specificity for SARS-CoV-2 IgG was excellent (100%) for all but two assays: |
| T168 |
14531-14788 |
Sentence |
denotes |
The Novel Coronavirus COVID-19 (Epitope Diagnostics) kit showed cross reaction with Toxo IgM+ sample and one pre-pandemic sample and the Human Anti-2019 nCoV(N) IgG ELISA kit (Finetest) showed cross reaction with Toxo IgM+ sample and 2 pre-pandemic samples. |
| T169 |
14789-14947 |
Sentence |
denotes |
For IgM, only two assays showed a specificity of 100%: COVID-19 IgG/IgM Rapid test Cassette (Orient Gene) and SARS-CoV-2 IgG ELISA Kit (Creative Diagnostics). |
| T170 |
14948-15550 |
Sentence |
denotes |
The other assays cross reacted with one or more samples: the combined IgM/IgG Rapid Test IgM (Sol scientific®) showed cross-reaction with CMV IgM+ sample, ANF+ sample, RF+ sample and Tox IgM+ sample, the COVID-19 IgG/IgM RAPID TEST IgM (PRIMA PROFESSIONAL®) showed cross-reaction with EBV IgM+, the Diagnostic Kit for IgG/IgM Antibody to SARS-CoV-2 IgM (WIZ BIOTECH) showed cross-reaction with RF+ sera, the Anti-SARS-CoV-2 ELISA IgA (EUROIMMUN®) showed cross-reaction with CMV IgM+ sample and the Novel Coronavirus COVID-19 IgM (Epitope Diagnostics®) had a cross-reaction with one pre-pandemic sample. |
| T171 |
15551-15669 |
Sentence |
denotes |
In our institution a total of 145 patients were hospitalized with an in-house laboratory confirmed COVID-19 diagnosis. |
| T172 |
15670-15808 |
Sentence |
denotes |
In this group, the presence of SARS-CoV-2 was confirmed using RT-PCR on the first nasopharyngeal and/or throat swab in 132 patients (91%). |
| T173 |
15809-15904 |
Sentence |
denotes |
Another 4 patients were diagnosed with a second nasopharyngeal and 1 patient with an anal swab. |
| T174 |
15905-15963 |
Sentence |
denotes |
Next, 5 patients were found to be positive on BAL samples. |
| T175 |
15964-16017 |
Sentence |
denotes |
Three patients remained negative on repetitive swabs. |
| T176 |
16018-16171 |
Sentence |
denotes |
These patients were not eligible for a BAL sampling procedure or did not present with respiratory symptoms and as such serological testing was performed. |
| T177 |
16172-16263 |
Sentence |
denotes |
All 3 patients were found to be positive for IgG SARS-CoV-2 serology (Prima Professional®). |
| T178 |
16264-16463 |
Sentence |
denotes |
Given the high pre-test probability for SARS-Cov-2 in this prospective cohort and repetitive testing, the added diagnostic value of SARS-CoV-2 serology in providing a diagnosis in this cohort was 2%. |
| T179 |
16465-16475 |
Sentence |
denotes |
Discussion |
| T180 |
16476-16595 |
Sentence |
denotes |
In this study, we evaluated the detection of SARS-CoV-2 antibodies (IgM/A or IgG) with 14 different serological assays. |
| T181 |
16596-16748 |
Sentence |
denotes |
As expected, we found that sensitivity was higher if the test was performed starting from day 8 after symptom onset, as compared to earlier time points. |
| T182 |
16749-16923 |
Sentence |
denotes |
With the exception of one assay (Liaison SARS-CoV-2 S1/S2 IgG (DiaSorin), all tests resulted in a sensitivity for IgG higher than 87% starting from day 8 after symptom onset. |
| T183 |
16924-16957 |
Sentence |
denotes |
Specificity ranged from 79%-100%. |
| T184 |
16958-17052 |
Sentence |
denotes |
Recently, the first studies evaluating several commercial serology assays have been published. |
| T185 |
17053-17167 |
Sentence |
denotes |
Geurts van Kessel et al [17]. studied three rapid tests, four ELISAs and a high throughput chemiluminescent assay. |
| T186 |
17168-17289 |
Sentence |
denotes |
Sensitivity ranging from 81–100% was calculated by using a total of 187 sera from 107 RT-PCR confirmed COVID-19 patients. |
| T187 |
17290-17463 |
Sentence |
denotes |
Specificity was determined using 147 serum and plasma samples from individuals exposed to human coronaviruses and other respiratory viruses with values ranging from 85–100%. |
| T188 |
17464-17680 |
Sentence |
denotes |
Similar to our findings, the performance of the Liaison SARS-CoV-2 S1/S2 IgG (DiaSorin) was worst with a sensitivity of 81% (compared to 59% in our results) and specificity of 90% (compared with 100% in our results). |
| T189 |
17681-17926 |
Sentence |
denotes |
The group of Haselmann et al [16]. evaluated the performance of two IgG ELISA assays and one IgG electrochemiluminescence immunoassay (ECLIA) based on 51 serum samples from 26 COVID-19 patients and another 51 serum samples from control patients. |
| T190 |
17927-17990 |
Sentence |
denotes |
They report a sensitivity of 92–100% and specificity of 84–96%. |
| T191 |
17991-18314 |
Sentence |
denotes |
The Austrian Red Cross Blood Service [15] evaluated 100 SARS-CoV-2 convalescent plasma donors and SARS-CoV-2 antibodies were characterized using three different IgG-ELISAs (EUROIMMUN IgG and NCP-IgG ELISA, Wantai ELISA), two CLIA (Elecsys, LIAISON) and two lateral flow tests (MEDsan IgM/IgG-Rapid-Test, Wantai Rapid Test). |
| T192 |
18315-18425 |
Sentence |
denotes |
The Wantai ELISA and the Elecsys provided the highest sensitivities in this sample (98 and 95 % respectively). |
| T193 |
18426-18638 |
Sentence |
denotes |
Serrano et al [18]. compared the performance of 3 lateral flow immunoassays (IgM/IgG combined) to 2 ELISAs (IgA and IgG) in serum samples from 109 RT-PCR confirmed patients in different weeks after symptom onset. |
| T194 |
18639-18713 |
Sentence |
denotes |
The IgA ELISA was most sensitive the first week after symptom onset (71%). |
| T195 |
18714-18779 |
Sentence |
denotes |
The sensitivity improved to 97% for IgA ELISA in the second week. |
| T196 |
18780-18881 |
Sentence |
denotes |
In the third week IgA ELISA, IgG ELISA and 2 out 3 IgG lateral flow tests had a sensitivity of > 96%. |
| T197 |
18882-18941 |
Sentence |
denotes |
The lateral flow immunoassays showed variable performances. |
| T198 |
18942-19073 |
Sentence |
denotes |
Pieri et al. also found that IgA detected by the ELISA assay might be a more reliable and stable early serological marker than IgM. |
| T199 |
19074-19160 |
Sentence |
denotes |
Instead, IgG, as expected, showed stable level after 10 days from symptoms onset [21]. |
| T200 |
19161-19217 |
Sentence |
denotes |
These findings are in accordance with our study results. |
| T201 |
19218-19278 |
Sentence |
denotes |
Serological tests could be useful in some clinical settings. |
| T202 |
19279-19392 |
Sentence |
denotes |
In our database, we found an added diagnostic value of serological assays in 2% of the COVID-19 suspect patients. |
| T203 |
19393-19541 |
Sentence |
denotes |
Although the detection of SARS-CoV-2 antibodies does not provide information on the presence of the viral RNA, it confirms recent or past infection. |
| T204 |
19542-19677 |
Sentence |
denotes |
This is especially relevant in clinical cases where high clinical suspicion for COVID-19 which cannot be confirmed with SARS-CoV-2 PCR. |
| T205 |
19678-19853 |
Sentence |
denotes |
The availability of these serological tests might avoid the need for more invasive sampling methods like BAL in the pursuit of diagnostic confirmation of COVID-19, especially. |
| T206 |
19854-19919 |
Sentence |
denotes |
Furthermore, serology can aid in infection prevention management. |
| T207 |
19920-20126 |
Sentence |
denotes |
Nuccetelli et al. suggest screening flowcharts for asymptomatic workers that is based on serological assays, workers that have already overcome the disease are subjected to molecular screening methods [22]. |
| T208 |
20127-20261 |
Sentence |
denotes |
Next the development of antigen detection assays are underway, which have the potential to rapidly detect active SARS-CoV-2 infection. |
| T209 |
20262-20384 |
Sentence |
denotes |
As the pandemic evolves, more and more insights will be gained in the value of serology as well as antigen detection [23]. |
| T210 |
20385-20468 |
Sentence |
denotes |
The main limitation of the current study is the limited number of samples included. |
| T211 |
20469-20636 |
Sentence |
denotes |
Nevertheless, this study has evaluated the performance of 14 different serological assays and therefore could provide useful information in this stage of the pandemic. |
| T212 |
20637-20782 |
Sentence |
denotes |
In conclusion, our findings show that sensitivity was variable but increased in a later stage of infection (at least 8 days after symptom onset). |
| T213 |
20783-20875 |
Sentence |
denotes |
Interpretation of the combination of IgM or IgA and IgG resulted in the highest sensitivity. |
| T214 |
20876-21087 |
Sentence |
denotes |
Our data suggest that virus-specific antibody detection for SARS-CoV-2 can complement molecular testing for diagnosis of COVID-19, especially for patients presenting in the 2nd week or later after symptom onset. |
| T215 |
21088-21147 |
Sentence |
denotes |
Larger datasets should be used to confirm current findings. |
| T216 |
21149-21169 |
Sentence |
denotes |
Disclosure statement |
| T217 |
21170-21232 |
Sentence |
denotes |
No potential conflict of interest was reported by the authors. |
| T218 |
21234-21254 |
Sentence |
denotes |
Author contributions |
| T219 |
21255-21259 |
Sentence |
denotes |
VHE: |
| T220 |
21260-21357 |
Sentence |
denotes |
Conceptualization, Methodology, Investigation, Data Curation, Writing-Original draft preparation. |
| T221 |
21358-21387 |
Sentence |
denotes |
CL, BJ, VBE, BF, DBL, SP, WJ: |
| T222 |
21388-21418 |
Sentence |
denotes |
Writing-Reviewing and Editing. |
| T223 |
21419-21430 |
Sentence |
denotes |
VB, VS, PE: |
| T224 |
21431-21474 |
Sentence |
denotes |
Writing-Reviewing and Editing, Supervision. |