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. 2022 Nov 17;2022(11):CD013652. doi: 10.1002/14651858.CD013652.pub2

Kohmer 2020b [A].

Study characteristics
Patient Sampling Purpose: Assessment of clinical performance of multiple COVID‐19 tests
Design: Multi‐group study estimating both sensitivity and specificity
Group [1]: Symptomatic PCR‐confirmed COVID‐19 cases (n = 45)
Group [2]: Other known infections (other coronaviruses, EBV, CMV) including some pre‐pandemic (n = 37); review team excluded 6 samples with serologically confirmed SARS‐COV‐2 infection based on PRNT)
Recruitment: Unclear
Prospective or retrospective: Not stated but likely retrospective
Sample size: 82 (45)
Further detail: No more details available
Patient characteristics and setting  
Index tests Test name:
[A] SARS‐CoV‐2 IgG
[B] Elecsys Anti‐SARS‐CoV‐2
[C] Liaison SARS‐CoV‐2 S1/S2 IgG
[D] COVID‐19 VIRCLIA IgG MONOTEST
[E] Anti‐SARS‐CoV‐2 ELISA (IgG)
[F] Virotech SARS‐CoV‐2 ELISA IgG
Manufacturer:
[A] Abbott GbmH, Wiesbaden, Germany
[B] Roche Diagnostics International AG, Rotkreuz, Switzerland
[C] DiaSorin Deutschland GmbH, Dietzenbach, Germany
[D] Vircell Spain S.L.U., Granada, Spain
[E] Euroimmun, Lubeck, Germany
[F] Virotech Diagnostics GmbH, Russelsheim, Germany
Antibody:
All tests except for [B]: IgG
[B]: total antibody
Antigen target:
[A] N‐protein
[B] N‐protein
[C] S1 and S2‐protein
[D] S1 and N‐protein
[E] S1‐protein
[F] N‐protein
Evaluation setting: All lab tests, done in lab
Test method:
[A] Chemiluminescent microparticle assay (CMIA)
[B] Electrochemiluminescence immunoassay (ECLIA)
[C] Chemiluminescent immunoassay (CLIA)
[D] Chemiluminescent immunoassay (CLIA)
[E] Enzyme‐linked immunosorbent assay (ELISA)
[F] Enzyme‐linked immunosorbent assay (ELISA)
Timing of samples: No info regarding time since symptom onset.
Group [1A]: collected 2‐49 days after PCR‐positive test. Not stated for the others.
Samples used: Serum or plasma
Test operator: Not stated
Definition of test positivity:
[A] positive if index S/C >= 1.4
[B] positive if signal sample/cut‐off >= 1.0
[C] positive if >= 15 AU/mL; equivocal if 12‐15 AU/mL
[D] positive if AI >= 1.6; equivocal if AI 1.4‐1.6
[E] positive if ratio >= 1.1; equivocal if ratio 0.8‐1.1
[F] positive if Index > 1.1; equivocal if Index 0.9‐1.1
Blinding reported: Unclear
Threshold predefined: Yes, as per manufacturer. However, specified they allocated Euroimmun equivocal as negative (post hoc)
Target condition and reference standard(s) Reference standard: Groups [1A] and [1B]: PCR (not further specified)
Samples used: Not stated
Timing of reference standard: Not stated
Blinded to index test: Yes (done earlier)
Incorporated index test: No
Definition of non‐COVID cases: Group [2] and [3]: No testing
Samples used: Group [2] and [3]: NA
Timing of reference standard: Group [2] and [3]: NA
Blinded to index test: Group [2] and [3]: NA
Incorporated index test: Group [2] and [3]: NA
Flow and timing Time interval between index and reference tests: Group [1A]: index tests done 2 to 49 days after PCR‐positivity (unknown for 4 cases)
All patients received same reference standard: No
Missing data: None (but not all index tests were used on all samples to assess specificity)
Uninterpretable results: Yes, for [B]: 2 "equivocal" results, considered as negative
Indeterminate results: None
Unit of analysis: Patients
Comparative  
Notes Funding: None reported
Publication status: Published article
Source: Academic journal
Author COI: One author received speaker’s fee from Euroimmun (manufacturer of one of the index tests).
Methodological quality
Item Authors' judgement Risk of bias Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled? Unclear    
Was a case‐control design avoided? No    
Did the study avoid inappropriate exclusions? Unclear    
Did the study avoid inappropriate inclusions? Unclear    
Could the selection of patients have introduced bias?   High risk  
Are there concerns that the included patients and setting do not match the review question?     High
DOMAIN 2: Index Test (All tests)
DOMAIN 2: Index Test (Antibody tests)
Were the index test results interpreted without knowledge of the results of the reference standard? Unclear    
If a threshold was used, was it pre‐specified? Yes    
Could the conduct or interpretation of the index test have introduced bias?   Unclear risk  
Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition? Unclear    
Were the reference standard results interpreted without knowledge of the results of the index tests? Yes    
The reference standard does not incorporate the index test Yes    
Could the reference standard, its conduct, or its interpretation have introduced bias?   Unclear risk  
Are there concerns that the target condition as defined by the reference standard does not match the question?     High
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard? Unclear    
Did all patients receive the same reference standard? No    
Were all patients included in the analysis? No    
Did all participants receive a reference standard? Unclear    
Were results presented per patient? Yes    
Could the patient flow have introduced bias?   High risk