VIDAS® SARS-COV-2 IgG & IgM

Oyon Hendrayana

PIONEERING DIAGNOSTICS
 CORONAVIRUS?

Coronaviruses pertamakali ditemukan pada

akhir 1960.

Sebagian besar menyerang saluran nafas.

Anggota dari Coronavirus family

• Infectious bronchitis (chickens)
• Common cold (humans)
• Human Coronavirus 229E
• Human Coronavirus OC43
• SARS-CoV in 2003
• HCoV NL63 in 2004
• HKU1 in 2005
• MERS-CoV in 2012
• SARS-CoV-2 in 2019 (COVID-19)
• Others

Geller C et al. Viruses. 2012 Nov; 4(11): 3044–3068.

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 COVID-19

Masa Inkubasi: 2 s/d 14 hari (rata-rata 5 hari)

Daya tular: Sangat tinggi saat ada gejala. Memungkinkan pada beberapa hari sebelum
gejala muncul.

Gejala klinis:
•> 80 % Seperti flu
•Pada kasus yang berat:
• Pneumonia
• Acute Respiratory Distress Syndrome (ARDS)
• Sepsis

Faktor risiko: lansia, kondisi co-morbid (Penyakit paru kronis, penyakit jantung, dll.)

Mortality: 2 s/d 3% (diantara kasus terkonfirmasi, terutama yang rawat inap)

Belum ada perawatan khusus, belum ada vaksin

Source: WHO, Santé Publique France

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 COVID-19; TRANSMISI DAN GEJALA

TRANSMISI
• Orang ke orang melalui droplet yang
muncul ketika kita berbicara, batuk dan
bersin.
• Droplet berada diudara hanya dalam
waktu singkat tetapi mungkin masih
dapat bertahan lama dan menular pada
permukaan metal, kaca, atau plastik.1
• Penularan melalui objek dan
permukaan yang terkontaminasi.

1. Novel coronavirus (COVID-19) – Frequently asked questions – Alerts. Health.NSW.gov.au. 27 February 2020
2. Kampf, G.et al. The Journal of Hospital Infection. 2020. 104 (3): 246–251

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 FIRST REPORT ON CHINESE COHORT
(WUHAN)

with pneumonia; lab confirmed COVID-19 (n=41), Median age 49 years; male (73%)
Comorbidities (32%)
• Diabetes (20%)
• Hypertension (15%)
• Cardiovascular disease (15%)

Symptoms
• Fever (98%), cough (76%), myalgia/fatigue (44%)
• After admission: Dyspnea(55%)

Complications
• ARDS (29%) (due to invasion of epithelial cells)
• Acute cardiac injury (12%)
• ICU admission (32%)
• Secondary infection (10%)
• Died (15%)
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 PATHOPHYSIOLOGY

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 PATOGENESIS

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 DYNAMIC OF DIAGNOSTIC TEST

Sethuraman.N., et al, Interpreting Diagnostics tests for

SARSCoV2 JAMA 12 May 2020
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 BIOLOGICALMARKERS &
PARAMETERS

Source: IFCC
https://www.ifcc.org/ifcc-news/2020-03-26-ifcc-information-guide-on-covid-19
9 See also: Lippi G, Plebani M. Clin Chem Lab Med. 2020 Mar 19.
 ANTIBODY TESTING

10 Kemenkes RI : Pedoman Pencegahan dan Pengendalian Coronavirus Disease (COVID-19), revisi ke-4
 ESTIMATED PREVALENCE OF COVID-19
IN GLOBAL POPULATION

NPV is related to sensitivity and PPV is related to specificity

and both NPV and PPV are related to prevalence.

E.g. of Spain
• Even in Spain, overall prevalence of antibody positivity is close to 5%.

Global
• At global level, let’s assume today we have 2% of the population with SARS
Cov-2 antibodies.

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 PPV AND NPV SCENARIOS OF A COVID-19 TEST WITH 95%
SPECIFICITY AND SENSITIVITY IN A GLOBAL
POPULATION WITH 5% AND 2% PREVALENCE
Sensitivity:95%

Specificity: 95%

PPV 53% NPV 100%

Important factor→ Actual Result

5% prevelance
Ab Present Ab Absent
Test Positive 50 45 95
Assesment result Test Negative 3 950 953
53 995 1,048

Sensitivity TP/(TP+FN) 95%

Specificity TN/(TN+FP) 95%
PPV TP/(TP+FP) 53% Positive result correctness
NPV TN/(TN+FN) 100%

Every 2 +ve results one is only 1 correct

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 PPV AND NPV SCENARIOS OF A COVID-19 TEST WITH 95%
SPECIFICITY AND SENSITIVITY IN A GLOBAL
POPULATION WITH 5% AND 2% PREVALENCE
Sensitivity:95%

Specificity: 95%

PPV 29% NPV 100%

Important factor→ Actual Result

2% prevelance
Ab Present Ab Absent
Test Positive 20 50 70
Assesment result Test Negative 1 980 981
21 1030 1,051

Sensitivity TP/(TP+FN) 95%

Specificity TN/(TN+FP) 95%
PPV TP/(TP+FP) 29% Positive result correctness
NPV TN/(TN+FN) 100%

Every 3 +ve results one is only 1

correct
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 SARS- COV-2 STRUCTURE

Protein Spike S1&S2-protein

descrided as the target of
Neutralizing Ab Spike Glycoprotein

E-protein
Envelope protein

M-protein
Membrane protein

RNA
The Lancet 4 April 2020

N-protein
Nucleoprotein
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 VIDAS® SARS-COV-2 IGM (9COM)
VIDAS® SARS-COV-2 IGG (9COG)

Qualitative assay : index

Semi quantitative

60 Tests
Stability 12 months

Calibration every 28 days

S1 S1 C1 C2

Human serum or plasma (lithium heparin)

Sample volume 100µL***

Time to result : 27 min

***VIDAS®3 : Manual pipetting of Standard & Controls

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VIDAS® SARS-COV-2 IGM: INDIRECT SANDWICH

Solid Phase Patient sample ALP + monoclonal Substrate

Sub domain anti-human IgM Ab
of Protein S

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VIDAS® SARS-COV-2 IGG: INDIRECT SANDWICH

4MUP
ALP 4MP

Solid Phase
Patient sample ALP +monoclonal Substrate
Sub domain
anti-human IgG Ab
of Protein S

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 VIDAS® SARS-COV-2 IGM (9COM)
VIDAS® SARS-COV-2 IGG (9COG)

100µL

9COM -9COG (compatible MINIVIDAS VIDAS VIDAS 3)

27 minutes

TV index = patient RVF/ Standard RFV

Qualitative test - No equivocal zone

_ 1 +

Negative Result does not exclude the possibility of exposure or infection with CoVID19.
Results between 0.80 and 1.2 must be interpreted with caution.
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.
 VIDAS® SARS-COV-2
IGM: PERFORMANCES

Positive Percent
Period after Agreement***
Positive PCR

SENSITIVITY ≤ 7 days
IgM
52,9%
100%
8 – 15 days 90,6% >=D16
≥ D16 100%

SPECIFICITY
99.4%

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VIDAS® SARS-COV-2
IGM: PPV-NPV

Positive and Negative Predictive Values (PPV-NPV)

Positive and negative predictive values are directly related to the

prevalence of the disease in the population. The calculation was
done with the assumption of 5% prevalence.

PPV and NPV were computed using results obtained from 7 days
post symptoms onset.

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 INTERPRETING DIAGNOSTIC TESTS FOR SARS-COV-2
ESTIMATED VARIATION OVER TIME FOR DETECTION OF SARS-
COV-2 INFECTION RELATIVE TO SYMPTOM ONSET*

*JAMA Network, From: Interpreting Diagnostic Tests for SARS-CoV-2

JAMA. Published online May 06, 2020. doi:10.1001/jama.2020.8259
Estimated Variation Over Time in Diagnostic Tests for Detection of SARS-CoV-2 Infection Relative to Symptom Onset Estimated time intervals and rates of viral detection are based on data from several
published reports.

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Because of variability in values among studies, estimated time intervals should be considered approximations and
the probability of detection of SARS-CoV-2 infection is presented qualitatively. SARS-CoV-2 indicates severe acute respiratory syndrome coronavirus 2; PCR, polymerase chain reaction.
A Detection only occurs if patients are followed up proactively from the time of exposure.
B More likely to register a negative than a positive result by PCR of a nasopharyngeal swab.*
VIDAS SARS-COV-2 (IGM)
The following figure shows the distribution of VIDAS SARS-COV-IgM results (index) for 60
patients, according to the number of days post symptons onset

DISTRIBUTION OF IgM Index Post Symptoms Onset

VIDAS SARS-COV-2 IgM

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VIDAS® SARS-COV-2
IGG : PERFORMANCES

Positive Percent
Period after Agreement***
Positive PCR
IgM
SENSITIVITY ≤ 7 days 45,3% 96,6%
8 – 15 days 88,6% >=D16
≥ D16 96,6%

SPECIFICITY 100%

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VIDAS® SARS-COV-2
IGG: PPV-NPV

Positive and Negative Predictive Values (PPV-NPV)

Positive and negative predictive values are directly related to the prevalence
of the disease in the population. The calculation was done with the
assumption of 5% prevalence.

PPV and NPV were computed using results obtained from 7 days post
symptoms onset.

26
 INTERPRETING DIAGNOSTIC TESTS FOR SARS-COV-2
ESTIMATED VARIATION OVER TIME FOR DETECTION OF SARS-
COV-2 INFECTION RELATIVE TO SYMPTOM ONSET*

*JAMA Network, From: Interpreting Diagnostic Tests for SARS-CoV-2

JAMA. Published online May 06, 2020. doi:10.1001/jama.2020.8259
Estimated Variation Over Time in Diagnostic Tests for Detection of SARS-CoV-2 Infection Relative to Symptom Onset Estimated time intervals and rates of viral detection are based on data from several
published reports.

25
Because of variability in values among studies, estimated time intervals should be considered approximations and
the probability of detection of SARS-CoV-2 infection is presented qualitatively. SARS-CoV-2 indicates severe acute respiratory syndrome coronavirus 2; PCR, polymerase chain reaction.
A Detection only occurs if patients are followed up proactively from the time of exposure.
B More likely to register a negative than a positive result by PCR of a nasopharyngeal swab.*
VIDAS SARS-COV-2 (IGG)
The following figure shows the distribution of VIDAS SARS-COV-IgG results (index) for 67
patients, according to the number of days post symptons onset

DISTRIBUTION OF IgG Index Post Symptoms Onset

VIDAS SARS-COV-2 IgG

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 VIDAS SARS-COV-2 (IGM & IGG)
PERFORMANCES FOR OUR TESTS

SPECIFICTY* SENSITIVITY**

Positive Percent Agreement***

IgM IgG Period after
Positive PCR IgM+ or
IgM IgG
IgG+
99,4% 99,9%
308 989 ≤ 7 days 52,9% 45,3% 59,3%

8 – 15 days 90,6% 88,6% 96,4%

≥ D16 100% 96,6% 100%

HAS**** Recommendation
• Specifity (>98%) RESULTS
• Sensitivity (>90-95%) Index Interpretation
i < 1,00 Negative
*Specificity: True Negative Rate
** Sensitivity = True Positive Rate
***PPA = Positive Percent Agreement
i ≥ 1,00 Positive
**** HAS = Haute Autorité de Santé (French)
Differentiation factors – Ratio Index vs signal
To better follow the antibody responses

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 COMPETITION

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VIDAS SARS-COV-2 (IGM & IGG)
COMPETITION DIAGNOSTIC OFFER
ANALYSIS

Automated solutions

Low performance
Rapi test solutions Many player

Microplate solutions

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 COMPETITION LANDSCAPE

High
Volume

Low

Performance High
 VIDAS SARS-COV-2 (IgG & IgM)
VIDAS BENEFITS VS AFIAS CLINICAL OFFER*

AFIAS
NEGATIVE POINTS VIDAS ASSETS
• Low performances for PPA and NPA • 2 different kits available IgM & IgG
• Combo (IgG+IgM) • Lower calibration frequency: every 28 days
• 95.8% PPA (@ what prevalence no
information) • Results within 28 min.
• 96.7% NPA (@ what prevalence no • Performances:
information) • Sensitivity: 100% for IgM, 96.6% for IgG
• Data of performance is not robust • Specificity : 99.4% for IgM, 100% for IgG
enough. No clear information about • Spike Ag used better for future vaccination follow
sensitivity and specificity.
• Rapid test format:
• Not true automation like VIDAS
• Ag used not described (nucleocapsid or
Spike Ag) TAKE HOME MESSAGE
POSITIVE POINTS
• Duration of assay: 10 minutes. • VIDAS offer is for low/ mid volume testing
• Perceived automation
• VIDAS provides accurate results
• Low price ??

*Information comes from Package inserts, Commercial brochure, website

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 VIDAS SARS-COV-2 (IGM & IGG)
VIDAS BENEFITS VS ABBOTT DIAGNOSTIC OFFER*

VIDAS ASSETS
NEGATIVE POINTS
• Reagent stability 7 days on board
• Risk of Scrap • Longer stability for reagent: 12 months
• 100 or 500 tests per kit (Architect i systems)
• Lower recalibration frequency: every 28 days
• 200 or 1000 tests per kit (Alinity)

• Recalibration every 7 days (triplicate) • Pos / Neg controls & Cal included in the kit
• Separate ref for cal and controls  additional • 2 different kits available IgM & IgG
cost
• Spike Ag used  better for future vaccination follow up
• Only IgG available
• Nucleocapsid Ag used
• Questionable choice for future vaccination
follow up
POSITIVE POINTS

• Performance of the IgG test TAKE HOME MESSAGE

• Sensitivity 100%
• Specificity 99,6% • VIDAS offer is for low/ mid volume testing
• Already EUA (US- May)
• VIDAS: All In One (Pos / Neg controls & Cal included in the kit)
• Huge USA installed base platforms

*Information comes from Package inserts, Commercial brochure, website

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 VIDAS SARS-COV-2 (IGM & IGG)
VIDAS BENEFITS VS ROCHE DIAGNOSTIC OFFER*

NEGATIVE POINTS VIDAS ASSETS

• Reagent stability 3 days on board
• Risk of scrap • Longer stability for reagent: 12 months
• 200 tests/kit for Cobas 411 & 601/602 analysers
• 300 tests/kit for Cobas for 801 analysers • Separate antibody response with 2 different kits
• Total Antibodies detection (IgG+IgM+IgA) available: IgM & IgG
• No distinction of IgM & IgG  additional
testing? • Spike Ag used  better for future vaccination follow up
• Nucleocapsid Ag used: • Low calibration frequency: every 28 days
• With Total no possible to follow the • Pos / Neg controls & Cal included in the kit
vaccination follow up
• No control available on the kit
• Need to realize a pool of pos/neg control

POSITIVE POINTS

• Performance of the combo TAKE HOME MESSAGE

• Sensitivity 100%
• Specificity 99,8%
• VIDAS offer is for low/ mid volume testing
• Duration of assay
• 18 minutes • VIDAS: All In One (Pos / Neg controls & Cal included in the kit)

*Information comes from Package inserts, Commercial brochure, website

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 VIDAS SARS-COV-2 (IGG & IGM)
VIDAS BENEFITS VS MINDRAY CLINICAL OFFER*

VIDAS ASSETS
NEGATIVE POINTS • Performances:
• Low performances** • Sensitivity: 100% for IgM, 96.6% for IgG
• IgM sensi: 83.9%, Specif: 93.4% • Specificity : 99.4% for IgM, 100% for IgG
• IgG sensi: 82.2%, Specif: 93.1% • Pos / Neg controls & Cal included in the kit
• Controls not included and not • Lower calibration: every 28 days
provided as a separate reference
• Spike Ag used better for future vaccination follow
• Recalibration frequency (7 days) • 2 different kits available IgM & IgG
• On board stability (7 days)
POSITIVE POINTS

• Spike Ag used TAKE HOME MESSAGE

• better for future vaccination follow

• 2 different kits available (IgG & IgM) • VIDAS provides accurate results
• COVID 19 molecular tests available ( notfor
mindray)

* Information comes from Package inserts, Commercial brochure, website

** Performances are different between pack insert & commercial brochure
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 Calibrator 4 4 8
Controls 2 2 4
Controls 1 per day +ve and -ve 28
Total tests 40
VIDAS VS HIGH THROUGHPUT SYSTEMS
Pack Size 200
Paitent tests 160
Important factor→ Min Sample/Day 11

VIDAS D28
E411 D1 D3 at D3 Calibrator 2
Calibrator 4 4 8
Controls 2 2 4 Controls 2
Controls 1 per day +ve and -ve 6 Controls Once in 28 Days 2
Total tests 18
Pack Size 200 Total tests 4
Paitent tests 182 Pack Size 60
Important factor→ Min Sample/Day 61
Paitent tests 56
E411 D1 D14 at D14 Min Sample/Day 2
Calibrator 4 4 8
Controls 2 2 4
Controls 1 per day +ve and -ve 28
Total tests 40
Pack Size 200
Paitent tests 160
Important factor→ Min Sample/Day 11

E411 D1 D3 at D3
Calibrator 4 4 8
Controls 2 2 4
Controls 1 per day +ve and -ve 6
Total tests 18
Pack Size 200
Paitent tests 182
Important factor→ Min Sample/Day 61

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 PTC UPDATE

Package
Insert

PTC Brosur

Clinic

VIDAS

SARS
COV
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PIONEERING DIAGNOSTICS