Covid Panel

© 2021 Beckman Coulter, Inc. All rights reserved. Company confidential; not for external distribution.
Covid Panel
A Menu That Matters For Covid-19
How can clinical guidelines and use case scenarios grow usage of COVID panel (serology and other covid related tests like PCT, IL-6)
AGENDA
• Clinical guidelines and studies for Covid Serology
• Clinical guidelines and studies for PCT and IL-6 in Covid-19
4 © 2021 Beckman Coulter, Inc. All rights reserved. Company confidential; not for external distribution.
Clinical guidelines and studies for Covid
Serology
Populations which may benefit from COVID-19 serological testing
1. Patients that have had COVID-19 compatible symptoms but have
been NAT negative.
2. Serosurveillance:
i. Populations in general to define the degree of community
exposure.
ii. Frontline healthcare workers to likewise define exposure.
• Additional testing, such as NAT testing, may be
warranted in serological positive individuals to
determine potential risk for infecting others. It is
important to reiterate that it is unknown the extent to
which antibody positivity translates to actual
immunity.
3. Convalescent patients that want to donate plasma for patients
suffering from COVID-19 infection. Further testing to define
optimal titer and overall neutralizing activity will be needed.
Role of serology in the COVID-19 pandemic, Stowell and Garner, Clin Infect Dis. 2020 Nov 5; 71(8):1935-1936.
Feb 12, 2021, https://www.cdc.gov/coronavirus/2019-ncov/covid-data/serology-surveillance/index.html
• 305 serum samples collected from hospital workers undergoing routine SARS-CoV-2 testing for whom a definitive result of
molecular test on nasopharyngeal swab was available within the previous 4 months (range, 0.5–4.0 months), which is the most
suitable diagnostic window for detecting IgG humoral immunity against SARS-CoV-2
• Total imprecision lower than ~6%
• The linearity profile was also found to be optimal, in a range of IgG antibody titers between 0.11 and over 18, which is an upper limit
of interval covering the vast majority of patient samples tested in the present study (302/305; >98%)
• Excellent LOB, LOD and functional sensitivity that would enable to obtain a clinically usable antibody titer in most patients with
ongoing or previous SARS-CoV-2 infection
8 Ruscio et al., J Lab Precis Med 2020
• AUC not significantly different from Roche
Elecsys Anti-SARS-CoV2 total, and better
than AUC of DiaSorin Liaison SARS-CoV-2
S1/S2 IgG
• Can be reliably used as a surrogate of total
antibodies within seroprevalence studies
 Abrupt and relatively rapid decline of
anti-SARs-CoV-2 IgM and IgA has
been described in patients with
COVID-19
• “Suitability for full automation, 0.74
characterized by random accessibility,
contained turnaround time and high 0.87
throughput, will enable rapid responses to 0.83
massive testing programs, so enormously
enhancing the efficiency of laboratory
diagnostics within the context of the
ongoing COVID-19 pandemic”.
Ruscio et al., J Lab Precis Med 2020

Immune Surveillance
10 Company confidential; not for external distribution.

IMMUNE PASSPORT
http://www.china-embassy.org/eng/visas/t1828184.htm
http://www.chinaembassy.org.sg/eng/gdxw/t1842963.htm
Study demonstrates Access SARS-CoV-2 IgG assay detects circulating neutralizing
antibodies

SURROGATE VIRAL NEUTRALIZATION ASSAY
GenScript cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit
https://clpmag.com/uncategorized/study-new-covid-19-serological-test-fast-effective/
Diagnostics 2021, 11, 593. https://doi.org/10.3390/diagnostics11040593
Background
• Sensitivities and specificities of different SARS-CoV-2 serology assay vary across manufacturers, population prevalence and sites.
• Currently, there is no consensus on whether the antibodies, if present, are protective
• Are previously infected individuals protected from a future infection?
Patient samples
• The blood samples were collected between days
35 and 48 following a positive PCR test result, or
the day following a negative PCR result where
clinical symptoms were present.
• It was assumed that by that point the level of IgG
antibodies in the patients who were able to
produce them would already be detectable
Aim of Study
• Compare five different immunoassays for the determination of SARS-CoV-2 antibodies.
• Comparison to the VNT in order to assess the method’s ability to predict the level of antibody neutralization which could allow the
screening of potential plasma donors.
• Dependence of the test results on age.
VIRAL NEUTRALIZATION TEST
2-fold dilutions which, after mixing with the
virus, resulted in a final serum concentration
of 1/10, 1/20 . . . up to 1/2560.
Susceptible cell line Infection of Susceptible cell line
Virus Neutralization Titer

African green monkey
kidney fibroblasts Serum samples
Extracted from
clinical sample
TCID50
Only live uninfected cells were Positivity was determined by a titer of
1:10, 1:20 . . . 1:2560 stained with the neutral red dye, 20 and above
enabling a macroscopic reading
Adapted from https://mms.businesswire.com/media/20200413005181/en/784571/5/%5BCelltrion%5D-How-a-coronavirus-neutralization-test-

works.jpg?download=1
Correlation of SARS-CoV-2 Antibody with Virus Neutralization Test
• Individual immunoassays were compared to each other and VNT.
• Dependence of neutralizing antibody production on age.
• Two cut-off levels for each immunoassay corresponding to the titers 80 and 160, respectively.
Neutralizing Antibody Titers in VNT correlated significantly with age of patients
• Elderly patients have a higher proportion of people with high VNT titers than young people.
• The percentage of higher titers (≥320) increases continuously with age.
VNT titer
Correlation of SARS-CoV-2 Antibody with Virus Neutralization Test
• Assays targeted against spike protein (Diasorin, Beckman Coulter and Euroimmun) showed a correlation with each other.
• The correlation of individual immunoassays with the VNT reveals that assays targeted against the spike protein (Diasorin, Beckman
Coulter and Euroimmun) showed correlation with the VNT, and assays targeted against the nucleocapsid protein (Abbott and Roche)
exhibited less correlation.
Šimánek, V et al. Five Commercial Immunoassays for SARS-CoV-2 Antibody Determination and Their Comparison and
Correlation with the Virus Neutralization Test. Diagnostics 2021, 11, 593. https://doi.org/10.3390/diagnostics11040593
Cut-Off Values for Screening Suitable Donors of Convalescent Plasma
• Assays targeted against the nucleocapsid protein mainly provide information about the contact with the virus
• Very low sensitivity, especially for titer 160
ROC CURVE FOR DIASORIN, BECKMAN COULTER AND EUROIMMUN, TITER <80 VS.
≥80
Diasorin Beckman Coulter Euroimmun
ROC CURVE FOR DIASORIN, BECKMAN COULTER AND EUROIMMUN, TITER <160 VS.
≥160
Diasorin Beckman Coulter Euroimmun
Thoughts, Discussion and Conclusion
• “Best” serology assay depends on use case scenario for COVID-19 Management
• Concept of total antibody meant highest sensitivity for determining who had been in contact with the virus during the first wave of
the virus.
• Spike protein is the target for neutralizing antibodies, antibodies against nucleocapsid cannot directly neutralize the virus.
• Authors refer to current recommendation:
• The convalescent plasma should have at least a 160 titer of the neutralizing antibodies, although titer 80 is still acceptable as a
minimum threshold value
• Anti spike serology assays show very good correlation with VNT
• Authors conclude that anti-spike serology assays can be used to screen potential convalescent plasma donors
VACCINE DEPLOYMENT
https://medicine.nus.edu.sg/the-covid-19-chronicles/
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/facts.html
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/safety-of-vaccines.html
ANTIBODY RESPONSE INDUCED BY A SINGLE DOSE OF ASTRAZENECA
VACCINE
Ewer, K.J., Barrett, J.R., Belij-Rammerstorfer, S. et al. T cell and antibody responses induced by a single dose of
ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nat Med 27, 270–278 (2021).
https://doi.org/10.1038/s41591-020-01194-5
What are mRNA vaccines?
• Lipid nanoparticles containing prefusion-stabilized
protein–encoding mRNA (mostly encoding SARS-
CoV-2 spike protein and its receptor binding
domain)
• Administered by intramuscular injection
• Myocytes, antigen presenting cells (APCs),
dendritic cells and other immune cells in draining
lymph nodes uptake these nanoparticles and
mRNA is released into the cytoplasm, where it is
efficiently translated into mature spike protein
• Expressed at the cell surface or released in the
surrounding extracellular space after cell injury,
• Newly synthesized spike protein is presented to B
and T cells, triggering the generation of different
classes of antibodies and T cells (especially CD4+
and CD8+ cells), which are expected to elicit a
solid humoral and cellular immune response
against SARS-CoV-2 spike protein.
• Compare data of five commercial anti-SARS-CoV-2 immunoassays after administration of an mRNA vaccine.
• Venous blood (n=45) was collected from three healthcare workers (two females, aged 44 and 39 years, and one male, aged 53
years, respectively), receiving a double (30 mg) dose of BNT162b2 mRNA Covid-19 vaccine (Comirnaty, Pfizer), on the day of the
first vaccine dose and then at fixed intervals for the following 2 months.
• Anti-SARS-CoV-2 neutralizing antibody response was assayed with Roche Total Ig anti-RBD, DiaSorin TrimericS IgG, Beckman
Coulter IgG anti-RBD, SNIBE IgG anti-RBD and Technogenetics IgG anti-N/S1
• All NAATs for SARS-CoV-2 RNA detection were consistently negative in the three study subjects, nor did clinical signs or symptoms
of COVID-19 develop, such that active SARS-CoV-2 infection was excluded throughout the study period.
Overall kinetics of anti-SARS-CoV-2 antibodies following BNT162b2 mRNA Covid-19 vaccination
(Comirnaty, Pfizer).
• Serology measured 1 week after receiving the first mRNA
vaccine dose, displaying a nearly exponential increase up
to the 3rd week, when the curve tended to flatten.
• Values are shown as mean of the three individual values.
Fold increase from

baseline at day 63
Roche Tot Ig anti-RBD 3.03×103
Snibe IgG anti-RBD 2.37×103
Beckman-Coulter IgG anti-RBD 0.98×103
DiaSorin TrimericS IgG 0.26×103
Technogenetics IgG anti-N/S1 0.07×103
Key takeaways
• All the immunoassays evaluated in this study appear suitable for monitoring anti-SARS-CoV-2 neutralizing antibodies response in
subjects undergoing mRNA COVID-19 vaccination
• Monitoring of neutralizing anti-SARS-CoV-2 antibody response is paramount, as it has been previously reported that the inter-
individual response to vaccination may vary widely (i.e., up to 30%)
• Anti-SARS-CoV-2 neutralizing antibodies titration before and after vaccination would be necessary for fully, though unpractically,
optimizing vaccination programs
• Commercial immunoassays reliably mirrors the humoral response.
Ongoing studies driven by customers
Description
US Studies under discussion to track immunity with the Pfizer, Moderna and maybe J&J
vaccines. Henry Ford was mentioned as one of the study sites.
Brazil Qualitative Access SARS-CoV-2 IgG is used to track immunity post vaccination with
the AstraZeneca vaccine at Diagnosticos do Brasil Laboratories in Sao Paolo.
Publication expected in Q2.
Russia Qualitative Access SARS-CoV-2 IgG is used to measure immunity after vaccination
with Sputnik V, this is an ongoing comparative study with Centaur, BioMerieux and
local manual IgG kit.
Israel Access SARS-CoV-2 IgG is used to measure immunity after vaccination with Pfizer
vaccine.
Korea Post vaccination immunity studies to be conducted with the AstraZeneca and Pfizer
vaccines at Seegene Medical Foundation.
Taiwan National Taipei University Hospital will conduct a study with Roche, Siemens and
Beckman semi quant IgG to assess for immunity post vaccination with AstraZeneca
vaccine. This will be done in conjunction with plaque reduction neutralizing test, to
compare ability of different assays to detect neutralizing antibodies post vaccination.

Covid Readiness
Access IgG 1st

Access SARS-
Access SARS- IS or Access
CoV-2 IgG
CoV-2 IgM SARS-CoV-2
(qualitative) IgG II

Clinical guidelines and studies for PCT and
IL-6 in Covid-19
Changes in biomarkers from illness
onset in patients hospitalized with
COVID-19
• Differences between survivors and non-survivors were

significant for all timepoints shown, except for day 4
after illness onset for d-dimer, IL-6, and high-sensitivity
cardiac troponin I.
• For serum ferritin (D), the median values after day 16
exceeded the upper limit of detection, as indicated by
the dashed line
Lancet 2020; 395: 1054–62

The Connection Between PCT and COVID-19
1. Zhou et al., Lancet , March 9, 2020 , https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930566-3

39 2. Lippi, G., &confidential;
Company Plebani, M. (2020).
notProcalcitonin in patients
for external with severe coronavirus disease 2019 (COVID-19): A meta-analysis. Clinica chimica acta; international journal of clinical chemistry, 505,
distribution.
190–191. https://doi.org/10.1016/j.cca.2020.03.004
© 20213. Beckman Coulter, Inc. All rights reserved. Company confidential; not for external
https://www.ifcc.org/ifcc-news/2020-03-26-ifcc-information-guide-on-covid-19/ distribution.
(accessed last April 4, 2020)
Disclaimer
• Currently, the only intended use claim for Access PCT is to “aid in the risk assessment
of critically ill patients for progression to severe sepsis and septic shock.”
PCT ACCURATELY PREDICTS BACTERIAL INFECTIONS
20%
Positive blood cultures (%)
10%
0%
PCT < 0.1 ng/mL PCT 0.1-0.25 PCT 0.25-0.5 PCT 0.5-1.0 PCT > 1.0 ng/mL
ng/mL ng/mL ng/mL
PCT level >1.0 ng/mL indicates higher possibility of bacterial infections
Muller F., et al. 2010 Chest; 138(1):121-129.

*
PCT CAN DETECT SEPSIS EARLIER.
AUC with PCT: 0.94

AUC without PCT: 0.74
Harbarth et al. Am J Respir Crit Care Med Vol 164. pp 396–402, 2001
https://acphospitalist.org/archives/2018/08/procalcitonin-promise-and-pitfalls.htm
INTERPRETATION OF PCT RESULTS
Critically ill patients with COVID-19 often develop septic
shock.
 There may be clinical utility in developing a COVID-19 test panel
• PCT can address potential progression to sepsis through
bacteria infection.
Patients who have recovered from sepsis may be more
vulnerable to re-infection
• 4 studies were included in meta-analysis. The
pooled OR of these studies shows that increased
procalcitonin values are associated with a nearly 5-
fold higher risk of severe SARS-CoV-2 infection
(OR, 4.76; 95% CI, 2.74–8.29).
• The results of this meta-analysis of the literature
would suggest that serial procalcitonin measurement
may play a role for predicting evolution towards a
more severe form of disease.

PCT LEVELS IN COVID-19 PATIENTS
Hu et al., International Journal of Antimicrobial Agents 56 (2020) 106501

HOW DO THE SEPSIS BIOMARKERS COMPARE?
PCT
1. Peaks earlier than CRP
2. More stable
Brunkhorst et al. Int Care Med 24: 888-892 1998
CHEM / IA
Access PCT Assay Problem Quantifiable
Results
Customer needs:
Random-access with an extensive

PCT levels correlate with the severity of
bacterial infections and the probability of a
HIGH assay menu and 50-test reagent pack
Throughput
positive blood culture1, 2, 3
HIGH
20% CV LoQ of 0.05 ng/mL and CV
Access PCT offers state-of-the-art precision and ≤8% at concentrations of ≥0.150
low-end sensitivity for high confidence in Sensitivity ng/mL
procalcitonin results Physicians need a fast
and efficient way to Assay characteristics:
identify patients at • Time to result: 20 minutes
increased risk for • Sample size: 35 μL
• Calibration Stability: 28 days
sepsis.
• Open Pack Stability: 28 days
Access PCT is a clinically useful diagnostic assay

to assess patients with suspected sepsis or life-
Solution threatening septic shock.
1. https://www.ifcc.org/ifcc-news/2020-03-26-ifcc-information-guide-on-covid-19/
(accessed last April 4, 2020) Laboratories can experience greater
2. Wacker, C, Prkno, A, Brunkhorst, FM, Schlattmann, P. “Procalcitonin as a diagnostic
marker for sepsis: a systematic review and meta-analysis.” Lancet Infect Dis. 13(5):426– efficiency when you consolidate PCT
435.
3. Schuetz, P, Bretscher, C, Bernasconi, L, and Mueller, B. “Overview of procalcitonin testing into your routine workflow on
assays and procalcitonin-guided protocols for the management of patients with infections
and sepsis.” Expert Rev Mol Diagn, 2017. vol. 17, No. 6, 593–601. Access immunoassay systems.
PROGRESSION OF COVID-19 INFECTION
Sidiqi, H.K. and M.R. Mehra, COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal. J Heart Lung Transplant, 2020. *Seroconversion is an individualized process, typically, seroconversion of IgG and/or IgM is
49 © 2021 Beckman Coulter, Inc. All rights reserved. Company confidential; not for external distribution. observed 7 – 14 days post symptom onset but this may vary across individuals
The Connection Between TnI and COVID-19
1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 2020; 395: 497–506.
2. Guo T, Fan Y, Chen M, et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. Epub ahead of print 27 March 2020. DOI:
10.1001/jamacardio.2020.1017.
3. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet 2020; 395: 1054–1062.
4. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020;
S2213260020300795.
5. Shi S, Qin M, Shen B, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. Published online March 25, 2020. doi:10.1001/jamacardio.2020.0950
6. https://www.mdedge.com/cardiology/article/220765/coronavirus-updates/troponins-touted-ally-covid-19-triage-message-nuanced [Accessed: June 11, 2020]
CHEM / IA
Problem Quantifiable
Results
Access hsTnI Assay Customer needs:
Improved diagnostic
accuracy
A high-sensitivity troponin HIGH Assay imprecision:

assay is needed to detect Precision 3.4% at 18 ng/L
circulating troponin earlier

in disease progression and
provide improved
diagnostic clarity. ≥94% Accurately identifies ≥94% of AMI
patients in as little as 1 hour after
True AMI
Patients presentation
Solution
Access hsTnI is a true high-sensitivity troponin
assay that demonstrates <10% CV at the upper
reference limits (URL) for men and women and
detects troponin in >50% of the healthy
© 2021 Beckman Coulter, Inc. All rights reserved. Company confidential; not for external distribution. population.
COMMON CHALLENGES LABORATORIES FACE TODAY
Top 3 Needs
Patient Safety
Consolidate STAT Panel with Access PCT Enhancements

Laboratory Workflow
and hsTnI
Efficiency
Comparable, Reliable
Results
Increase Increase Reliability Show Value

Lab Efficiency and Impact to TAT Within the
Institution
Improve patient
care
Grow and Minimize

Future-Proof Costs and
Your Address
Laboratory Budget
Concerns
Offer the
Right Menu
to Address Health Issues
Did you know?
Accumulating evidence suggests that a

subgroup of patients with severe COVID-19
might have a cytokine storm syndrome (CSS)1.
CSS
CSS occurs when large numbers
of white blood cells are activated
and release inflammatory
Source: The Lancet cytokines, which in turn activate
yet more white blood cells2, 3, 4.
1. Mehta P, McAuley F et al. "COVID-19: consider cytokine storm syndromes and immunosuppression." The Lancet. VOLUME 395, ISSUE 10229, P1033-1034, MARCH 28, 2020. doi:
https://doi.org/10.1016/S0140-6736(20)30628-0.
2. https://www.nature.com/articles/s41584-020-0451-z [Accessed: June 25, 2020]
3. https://www.nature.com/articles/s41392-020-0191-1 [Accessed: June 25, 2020]
53 Company
4. Lee DW,confidential;
Gardner R, PorternotDL,for external
Louis distribution.
CU, Ahmed N, Jensen M, et al. (July 2014). "Current concepts in the diagnosis and management of cytokine release syndrome". Blood. 124 (2): 188–95.
doi:10.1182/blood-2014-05-552729.
© 2021 Beckman PMC
Coulter, Inc. All rights reserved. 4093680.
Company PMID 24876563.
confidential; not for external distribution.
WHAT IS CYTOKINE STORM?
• Cytokine storm is a general term applied to maladaptive cytokine release in

response to infection and other stimuli
• The pathogenesis is complex but includes loss of regulatory control of

proinflammatory cytokine production, both at local and systemic levels
• A rapid and well-coordinated immune response is the first line of defense

against viral infection
• Dysregulated and excessive immune responses may cause immune damage
• Release of cytokines occurs in respiratory cells at the early stage of SARS-CoV

infection
• In later stages, the cells secrete high levels of proinflammatory cytokines

interleukin (IL)-1β, IL-6
• IL-6 is produced by lymphoid and nonlymphoid cells and is an important

mediator of fever and of the acute phase response
https://www.knowablemagazine.org/article/health-disease/2020/what-cytokine-storm [Accessed: June 11, 2020]

Did you know?
15%
Immediate initial evaluation of IL-6 level
should be performed upon hospital
admission of COVID-19 patients, due to its
potential benefits to assess worsening of individuals infected with
clinical features and disease progression in COVID-19 are sick enough to
necessitate hospitalization in the
COVID-19. US, with a subset of patients
requiring intensive care
Source: Médecine et Maladies Infectieuses
Ulhaq, Z. S., & Soraya, G. V. (2020). Interleukin-6 as a potential biomarker of COVID-19 progression. Medecine et maladies infectieuses, 50(4), 382–383. https://doi.org/10.1016/j.medmal.2020.04.002
Nakamichi, K., Shen, J.Z., Lee, C.S. et al. Hospitalization and mortality associated with SARS-CoV-2 viral clades in COVID-19. Sci Rep 11, 4802 (2021). https://doi.org/10.1038/s41598-021-82850-9
IL-6 MAY HELP TRIAGE COVID-19 PATIENTS
Ulhaq, Z. S., & Soraya, G. V. (2020). Interleukin-6 as a potential biomarker of COVID-19 progression. Medecine et maladies infectieuses, 50(4), 382–383. https://doi.org/10.1016/j.medmal.2020.04.002
THE CONNECTION BETWEEN IL-6 AND COVID-19
29
150
Physicians in Wuhan found
that IL-6 was higher in those
PATIENT who died than in those who
STUDY survived3.
PATIENT
Physicians in Wuhan reported that higher levels STUDY
of the cytokines IL-6 were found in more severe
Covid-19 infections1.
239
Elevated IL-6 was found to
be statistically significant
11
predictor of clinical
deterioration4 in a study
PATIENT
STUDY conducted in Lombardi,
PATIENT IL-6 was also an early indicator Italy.
STUDY of a cytokine storm-like
condition in an analysis by
physicians in Guangdong2.
1. https://europepmc.org/article/med/32026671 [Accessed: June 11, 2020]; 2. https://www.medrxiv.org/content/10.1101/2020.02.26.20026989v1 [Accessed: June 11, 2020]
3. https://link.springer.com/article/10.1007/s00134-020-05991-x [Accessed: June 11, 2020]; 4. Maurizio, C at al. "Early Predictors of Clinical Deterioration in a Cohort of 239 Patients Hospitalized for Covid-19 Infection in Lombardy, Italy." Journal of Clinical
57 © 2021 BeckmanPublished:
Medicine. Coulter, Inc. All rights
20 May 2020. reserved. Company confidential; not for external distribution.
Access IL-6: Intended Use
• The Access IL-6 assay is an in vitro
diagnostic test for the quantitative
measurement of IL-6 in human serum and
plasma (heparin).
• Used to assist in identifying severe
inflammatory response in patients with
confirmed COVID-19 illness to aid in
determining the risk of intubation with
mechanical ventilation, in conjunction with
clinical findings and the results of other
laboratory testing.
• Used to aid in the study of inflammatory
disease.
CHEM / IA
Problem Quantifiable
Results
Customer needs:
Access IL-6 Assay

≤ 35 Time to first result
Identify associated min

risk for intubation
with mechanical 28 Calibration and open pack stability
days
ventilation in COVID-
19 patients Assay characteristics:
• Sample type: Serum or plasma
• Sample size: 110 μL
• Calibration Stability: 28 days
• Open Pack Stability: 28 days
Solution
Identify severe inflammatory response earlier and recognize associated risk for intubation with
mechanical ventilation in COVID-19 patients with Access IL-6. Adding this objective tool to your
laboratory in conjunction with clinical findings and other laboratory testing can aid clinicians and hospitals
to:
• more effectively assess and triage COVID-19 patients earlier
© 2021 Beckman Coulter, Inc. All rights reserved. Company confidential; not for external distribution. • better manage both critical patients and valuable resources
https://www.cdc.gov/library/covid19/pdf/public_pdfs/2020_10_30_Science-Update_Final-Public_v2.pdf
HIGH SERUM IL-6 VALUES INCREASE THE RISK OF MORTALITY AND THE SEVERITY OF
PNEUMONIA IN PATIENTS DIAGNOSED WITH COVID-19
• IL-6 serum concentrations above 35 pg/mL were associated with a higher risk of:
– More severe pneumonia (OR = 4.47, 95% CI 1.15-17.45, p = 0.031).
– Increased risk of mortality (OR = 20.00, 95% CI 4.21-94.91, p = 0.0001).
– ICU admission (OR = 12.75, 95% CI 2.16-75.33, p = 0.005).
Guirao et al., Dec 2020, Molecular Immunology, (128) 64 – 68

https://www.cdc.gov/library/covid19/pdf/public_pdfs/2020_10_30_Science-Update_Final-Public_v2.pdf
FAQ
What is the PaO2/FiO2 ratio and why is it important?
• The PaO2/FiO2 ratio, also known as the P/F ratio, is defined as the ratio of partial pressure of oxygen in blood
(PaO2), in millimeters of mercury, and the fraction of oxygen in the inhaled air (FIO2) — the PaO2/FiO2 ratio.
• It is a quick calculation often used to determine the severity of ARDS or assess lung function in patients,
particularly those on ventilators. It is useful for evaluating the extent of damage to the lungs.
In healthy lungs, this ratio depends on age and usually falls between 350 and 450.
For ARDS
Mild: 200 mm Hg < PaO2/FIO2 ≤ 300 mmHg
Moderate: 100 mm Hg < PaO2/FIO2 ≤ 200 mmHg
Severe: PaO2/FIO2 ≤ 100 mmHg
A value below 150 mmHg is considered indicative of patients at risk for intubation with mechanical ventilation.
When used in conjunction with other clinical findings, Access IL-6 can aid physicians in
identifying severe inflammatory response in Covid-19 patients to aid in determining the
risk for intubation with mechanical ventilation.
The clinical study below was conducted retrospectively in seventy-five (75) confirmed SARS-CoV-2 patients who presented
to the Emergency Department (ED) of a public research hospital in Spain. The data shown were calculated based on a cutoff
of 35 pg/mL and patients who had PaO2/FiO2 ratio < 150 mmHg, which is indicative of the risk for intubation with
mechanical ventilation*.
Clinical Evaluation Statistics
PaO2/FiO2 Ratio < PaO2/FiO2 Ratio ≥ Total Estimate (95% C.I)
150 mmHg 150 mmHg patients
Sensitivity 85.4% (71.6 to 93.1%)
IL-6 > 35 pg/mL 35 12 47
Specificity 64.7% (47.9 to 78.5%)
IL-6 ≤ 35 pg/mL 6 22 28
PPV 74.5% (60.5 to 84.8%)
Total patients 41 34 75 NPV 78.6% (60.5 to 89.8%)
PCR confirmed COVID-19 patients that have Access IL-6 concentration > 35 pg/mL at ED presentation are at increased risk
for mechanical ventilation during their hospitalization. Based on analysis of the data, an IL-6 level above 35 pg/mL accurately
identified 85.4% of patients who had PaO2/FiO2 ratio < 150 mmHg, indicative of the risk for mechanical ventilation.
*Herold T et al, Elevated levels of interleukin-6 and CRP predict the need for mechanical ventilation in COVID-19, Journal of Allergy and Clinical Immunology (2020)
ACCESS IL-6 AIDS IN UNDERSTANDING RISK FOR MECHANICAL VENTILATION
IN COVID-19 PATIENTS
• Demonstrated clinical sensitivity of 85.4% to

identify COVID-19 patients who are at risk for
intubation with mechanical ventilation
• Efficient assessment and triage of COVID-19

patients by identifying patients who are at risk for
respiratory failure and intubation
• Helping physicians better define appropriate

treatment and allocate critical resources (including
mechanical ventilators)
ACCESS IL-6 ANALYTICAL PERFORMANCE
Assay Attributes Assay Specifications
Format One-step sandwich
Sample Type / Volume Serum and plasma (heparin) / 110 µL
Time to First Result ≤ 35 minutes

0.5 -1500 pg/mL
Dynamic Range up to 4500 pg/mL with onboard dilution
Analytical Sensitivity 0.5 pg/mL (0.0535 IU/mL)
Imprecision < 12% @ concentrations greater than 2 pg/mL
Open Pack Stability 28 days
Cal Curve Stability 28 days
The assay is not susceptible to biotin interference as assay does not use streptavidin-
biotin particle chemistry
ACCESS IL-6 IMPRECISION
IFU claim: The Access Il-6 assay exhibits total imprecision < 12% at concentrations greater than 2 pg/mL.
Grand Mean Total

(n=40) Within Run Within Run Imprecision
Sample (pg/mL) (SD) (%CV) Total SD (%CV)
1 1.6 0.07 4.6 0.19 12.0
2 2.5 0.09 3.8 0.28 11.4
3 4.0 0.12 2.8 0.29 7.2
4 8.0 0.20 2.5 0.33 4.2
5 107.3 2.02 1.9 5.42 5.1
6 322.7 5.41 1.7 10.05 3.1
7 712.1 18.27 2.6 32.40 4.6
C1 10.0 0.27 2.7 0.35 3.6
C2 186.5 4.29 2.3 7.45 4.0
C3 852.5 14.19 1.7 29.94 3.5
PROGRESSION OF COVID-19 INFECTION
Sidiqi, 67 © M.R.
H.K. and 2021Mehra,
Beckman Coulter,Illness
COVID-19 Inc. All
in rights
Native reserved. Company confidential;
and Immunosuppressed States: Anot for external distribution.
Clinical-Therapeutic Staging Proposal. J Heart Lung Transplant, 2020.
CONCLUSIONS
• In various stages of infection, COVID-19 patients may
experience Cytokine Storm, sepsis and cardiac events
• Measurements of circulating IL-6 levels, CRP, PCT, D-
dimer, ferritin, lactate and TnI may be important in
identifying disease progression among COVID-19-infected
patients
• An increasing number of publications suggest that the
elevation of IL-6 is associated with the severity and
clinical outcome of patients with COVID-19
• A SARS-CoV-2 infection may result in an elevated
response of IL-6-induced severe respiratory distress

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© 2021 Beckman Coulter, Inc. All rights reserved. Company confidential; not for external distribution.

Ruscio et al., J Lab Precis Med 2020

10 Company confidential; not for external distribution.

12 Company confidential; not for external distribution.

GenScript cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit

Susceptible cell line Infection of Susceptible cell line

Virus Neutralization Titer

Adapted from https://mms.businesswire.com/media/20200413005181/en/784571/5/%5BCelltrion%5D-How-a-coronavirus-neutralization-test-

Diasorin Beckman Coulter Euroimmun

Diasorin Beckman Coulter Euroimmun

Fold increase from

Snibe IgG anti-RBD 2.37×103

Beckman-Coulter IgG anti-RBD 0.98×103

DiaSorin TrimericS IgG 0.26×103

Technogenetics IgG anti-N/S1 0.07×103

35 Company confidential; not for external distribution.

Access IgG 1st

36 Company confidential; not for external distribution.

• Differences between survivors and non-survivors were

Lancet 2020; 395: 1054–62

1. Zhou et al., Lancet , March 9, 2020 , https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2930566-3

Positive blood cultures (%)

PCT level >1.0 ng/mL indicates higher possibility of bacterial infections

Muller F., et al. 2010 Chest; 138(1):121-129.

AUC with PCT: 0.94

45 Company confidential; not for external distribution.

Hu et al., International Journal of Antimicrobial Agents 56 (2020) 106501

Brunkhorst et al. Int Care Med 24: 888-892 1998

Access PCT Assay Problem Quantifiable

Random-access with an extensive

Access PCT is a clinically useful diagnostic assay

A high-sensitivity troponin HIGH Assay imprecision:

circulating troponin earlier

Consolidate STAT Panel with Access PCT Enhancements

Increase Increase Reliability Show Value

Grow and Minimize

Accumulating evidence suggests that a

• Cytokine storm is a general term applied to maladaptive cytokine release in

• The pathogenesis is complex but includes loss of regulatory control of

• A rapid and well-coordinated immune response is the first line of defense

• Dysregulated and excessive immune responses may cause immune damage

• Release of cytokines occurs in respiratory cells at the early stage of SARS-CoV

• In later stages, the cells secrete high levels of proinflammatory cytokines

• IL-6 is produced by lymphoid and nonlymphoid cells and is an important

https://www.knowablemagazine.org/article/health-disease/2020/what-cytokine-storm [Accessed: June 11, 2020]

Access IL-6 Assay

Identify associated min

Guirao et al., Dec 2020, Molecular Immunology, (128) 64 – 68

• Demonstrated clinical sensitivity of 85.4% to

• Efficient assessment and triage of COVID-19

• Helping physicians better define appropriate

Format One-step sandwich

Sample Type / Volume Serum and plasma (heparin) / 110 µL

Time to First Result ≤ 35 minutes

Analytical Sensitivity 0.5 pg/mL (0.0535 IU/mL)

Imprecision < 12% @ concentrations greater than 2 pg/mL

Open Pack Stability 28 days

Cal Curve Stability 28 days