The use of the CoLab score in the diagnostic screening to rule out Covid-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019
[COVID-19]) is a global pandemic with millions of cases and hundreds of
thousands of deaths. (ref. WHO. Novel coronavirus (2019-nCoV) situation
reportsl 2020; CDC U. Coronavirus disease 2019 (COVID-19) cases in US; 2020))
The initial clinical symptoms for COVID-19 are nonspecific and similar to other
seasonal viral diseases, which encompasses fever, dyspnoe, dry cough and
fatigue. Reverse transcription Polymerase Chain Reaction (RT-PCR) based
methodologies have been the gold standard in confirming that the individual
presenting with COVID-19 has active viral shedding of SARS-CoV-2 (ref).
However, there are some important limitations to RT-PCR. First, current
techniques take up to 6-8 hr in order to obtain first results. Next to this,
often laboratories cannot handle the overload. A second important limitation is
that RT-PCR, on a nasopharyngeal swab, may result false negatively in the
initial phase of the disease, in spite of the presence of typical symptoms (ref
Li et al, NEJM 2020; 382(13):1199-1207; Guo et al, Clin Infect Dis 2020;
71(15):778-785; Lippi et al, Clin Chem Lab Med 2020; 58(7): 1070-1076). In
addition, the standard test used has an 80% accuracy (compared to chest CT scan
results) (Lippi et al,Clin Chem Lab Med 2020), which may depend on the specific
level of viral shedding by any individual at the time of sample test. Third,
the RT-PCR technique carries a certain cost, which could mean a considerable
financial burden weighing upon both health systems and patients (ref. Langer et
al, Sc J Traum, Res Emer Med 2020; 28(113)).
A direct consequence of these limitations is the time spent by a large number
of patients awaiting results in the emergency department (ED) before a decision
can be taken as to where admit them to, e.g. in isolation wards and intensive
care units focused on COVID-19 patients, or in *clean, non-infective* wards of
the hospital (ref Langer et al, Sc J Traum, Res Emer Med 2020; 28(113);
Grasselli et al, Lancet Resp Med 2020; 27; Chen et al, Lancet 2020; 395(10223):
507-513)).
To mitigate the burden on the healthcare system, while also providing the best
possible care for patients, efficient diagnosis and information on the
prognosis of the disease is needed. In addition, to prevent reuse of crude
limits when ED and hospital resources are exhausted during a coming wave, a
predictive model using multivariable analysis could be of great value.
Very recently, an algorithm was developed by de Boer et al, leading to the
so-called *Colab*-score. It turned out that this score had a very high negative
predictive value (99.15%). This algorithm was validated using our patient
dataset gathered during the first COVID-19 wave. The score is calculated using
the age of the patient next to the numeric values of 10 routine-laboratory
parameters that are regularly requested on the ED (CRP, albumin, total
bilirubin, gamma-glutamyltranspherase (GGT), alkaline phosphatase (AP), lactate
dehydrogenase (LDH), leukocytes, erythrocytes, absolute numbers of eosinophilic
as well as basophilic granulocytes).
This algorithm was built and validated using a dataset in which only patients
of the first COVID-19 wave were included (period February till June 2020). It
is known that the first wave occurred after the peak of other respiratory
infectious diseases (influenza etc). At the moment, we are facing the second
wave, which takes place in another period of the year. Fall and winter in the
Northern Hemisphere means inclement weather in many areas, with more people
spending time indoors. Several holidays take place around the end of the
calendar year, and people who celebrate them want to gather, travel, and visit
friends and family. From other respiratory infection diseases, it is known that
they increase in this period of the year. An explanation is that during colder
months, people gather indoors, and it is known that this is a risk for further
transmission of the virus.
Another difference in the second COVID-19 wave as opposed to the first one, is
the human behavior prompted by state and local government, and a better
compliance to these rules, such as physical distancing, handwashing and
mask-wearing,

The aim of the present study is to investigate if the high negative predictive
value of the Colab-score hold on when investigating this score in the following
cohort of persons:
- Care- and cure-personnel of Zuyderland MC who were requesting a SARS-CoV-2
RT-PCR screening because of Covid-19 related complaints, or because they were
in the neigbourhood of a SARS-CoV-2 infected person
- Patients that needed to be tested for Covid-19 in a pre-surgery screening
setting.

As secondary outcome we want to investigate if this CoLab score leads to faster
diagnostics. Also we want to investigate if this simple blood test also leads
to a responsible decrease in requested RT-PCR's

It concerns a prospective cohort study, in which we want to include in several
weeks enough persons to answer above mentioned questions:
- Cohort 1: Care and cure personnel of Zuyderland MC requesting a Covid-19
RT-PCR test because they have Covid-19 related complaints, or who were in the
near neighborhood of a Covid-19 positive person.
- Cohort 2: patients that has to be tested to exclude Covid-19 before they can
undergo surgery (pre-surgery screening)

Persons of these cohort will undergo a venipuncture when they have an
appointment for a nasopharyngeal swab (SARS-CoV-2 RT PCR assay). An heparin-
and an EDTA-anticoagulated blood container (max. 3 ml each tube) will be drawn.
In the heparin-blood the following clinical chemical tests will be performed:
CRP, albumin, LDH, GGT, AF, total Bilirubin. The EDTA-blood sample will be used
for determination of leukocytes, erythrocytes, absolute numbers of eosinophils
and basophils. The 10 numeric values of the before mentioned tests will be put
into the CoLab-algorithm, together with the age of the person.

The final result of the CoLab-score will be compared with the result of the
SARS-CoV-2 RT-PCR assay,

Natue and extent of the burden are minimal and risks are negligible, because
the load for the person is minimal (only 1 venipuncture).