Rapid SARS-CoV-2 IgG Antibody Testing in High Risk Healthcare Workers

The success of Singapore, Taiwan and Hong Kong in limiting the impact of the sudden acute
respiratory syndrome coronavirus-2 (SARS-CoV-2), also know as COVID-19, has been attributed
to their preparedness but mostly to the implementation and distribution of SARS-CoV-2 fast
diagnostic tests and establishment of decentralized point-of-care (POC) testing
(https://www.nature.com/articles/d41587-020-00010-2). So far, the frontline response to the
SARS-CoV-2 outbreak has been polymerase chain reaction (PCR) testing. PCR is the gold
standard for diagnosing an infectious agent, and it has the advantage that the primers needed
for such tests can be produced with relative speed as soon as the viral sequence is known.

The first quantitative reverse-transcriptase-based PCR (RT-PCR) tests for detecting SARS-CoV2
were designed and distributed in January by the World Health Organization (WHO), soon after
the virus was identified. The test protocol is complex and expensive, however, and is mainly
suited to large, centralized diagnostic laboratories. Tests typically take 4-6 hours to
complete, but the logistical requirement to ship clinical samples means the turnaround time
is 24 hours at best. A new fast PCR test (45 min) from Cepheid has been approved by the U.S.
Food and Drug Administration on March 21st with availability at the end of the month. Rapid
POC tests are also needed to accelerate clinical decision-making and to take some of the
workload off centralized test laboratories. Most importantly, the current state of the matter
in Indiana University Health system, as well as many around the country is that healthcare
workers including from the ER and ICU are currently unable to receive adequate testing
through existing facilities. Worst, their access to appropriate personal protective equipment
(PPE) has been limited, increasing their exposure risk and causing a significant amount of
stress and anxiety for front-line healthcare providers across the country.

Back to the Singapore experience, they have used immunoassays that can provide historic
information about viral exposure, as well as diagnostic evidence. They exploited
antibody-antigen recognition, either by using monoclonal antibodies (mAbs) to detect viral
antigens in clinical samples or by using cloned viral antigens to detect patient antibodies
directed against the virus. The lateral flow assay format - essentially a dipstick encased in
a cassette - contains the capture reagents (either an mAb directed at a viral antigen or a
viral antigen that is recognized by patients' antibodies) immobilized at defined locations on
a nitrocellulose membrane, as well as labelled detector mAbs that recognize the same target.
A positive result, which is triggered by binding between the analyte and capture mAb and
binding by the detector mAb, is visible as a colored line. Two drops of blood from a pinprick
is enough to detect a virus. They're essentially the same as home pregnancy kits. Several of
these assays are available in Asia, and most European Countries have been using them too. In
US, RayBiotech has developed such a similar test using knowledge from the Asian tests
(https://www.raybiotech.com/covid-19-igm-igg-rapid-test-kit/). This product is CE marked and
certified for diagnostic use in the EU. The application for FDA Emergency Use Authorizations
of tests was submitted on March 16th, 2020. At the moment, the FDA has only approved PCR
testing. No lateral flow tests have been approved as of March 23rd, 2020. However, this
lateral flow test can be used legally in the US, for in vitro diagnostic use, as a POC test
when administered by a licensed medical practitioner. These kits were developed in-house by
Ray Biotech and validated using samples taken in hospital from patients showing clinical
symptoms in Guangzhou China (all confirmed via PCR). Current stocks of 10,000 kits are being
replenished daily at RayBiotech, with efforts to increase production ten-fold within the next
week. The CE certificate can be found here:
https://www.raybiotech.com/files/images/CG-COV_CE-Certificates.jpg.

Based on the Singapore, Taiwan, Hong Kong positive experience, and to curb the fast spread of
the virus in the US, we propose to use the POC SARS-CoV-2 IgG Antibody in high risk
healthcare workers with or without symptoms, previously quarantine or not. Indeed, we
hypothesize that the incidence of seroconversion among ER and ICU healthcare workers is high
and higher than current models predict and that several cases are asymptomatic or with mild
symptoms.

There are two additional benefits of testing seroconversion.

1. Although there are no official reports, we clearly hear and see selfies of anxiety,
stress and exhaustion from our colleagues at the front line. Thus for the healthcare
workers knowing that they have seroconverted, will help them be more confident that they
are now protected and can work in safer conditions as it has recently been shown that
reinfection could not occur in SARS-CoV-2 infected rhesus macaques
https://www.biorxiv.org/content/10.1101/2020.03.13.990226v1.

2. The healthcare workers represent an ideal pool of donors for convalescent plasma due to
their commitment and the fact that they have usually been tested to give blood or are
currently blood donors. The FDA just approved a master protocol for collection and
administration of convalescent plasma:
https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-i…
ption-ide-process-cber/investigational-covid-19-convalescent-plasma-emergency-inds

In sum, "you cannot fight a fire blindfolded, and we cannot stop this pandemic if we don't
know who is infected." (World Health Organization Director-General, 16 March 2020).

If successful and validated, we will hope to rapidly scale it up to propose the rapid
SARS-CoV-2 IgG Antibody testing to the general population as has been done in countries that
have had almost no death due to COVID-19.