April 23, 2020
There are at
least three circumstances in which the SARS-CoV-2 antibody test can be used to
help deal with the COVID-19 pandemic. These three circumstances are as follows:
during the treatment / clinical handling of patients in hospitals or medical
clinics; in epidemiological surveillance to monitor the pandemic; to issue an
immunity certificate (or “passport”). In this post we will discuss the
usefulness of this type of test in each of these circumstances. The other type
of test, the one that detects the presence of the virus, will be considered
briefly and only in the clinical handling of patients.
PATIENT TREATMENT
Diagnosis of patients in hospitals or medical clinics
to assist in clinical handling
(Not useful)
To assist in
the clinical management of patients with suspected clinical signs and symptoms
of COVID-19, the indicated test is the one that seeks to detect the presence of
the virus at that specific time, as infected patients must be isolated from
other patients to avoid contagion and be recruited to participate in clinical
trials and receive treatments.
In this
situation, the test for antibody detection is not useful, because if the result
in this test is negative, it may be that the patient is infected, but has not
yet had time to produce the antibodies; if it is positive, it may be that he
has already produced antibodies, but there has not yet been time to get rid of
the viruses and therefore still be contagious.
EPIDEMIOLOGICAL MONITORING
Monitoring the percentage of the population with
SARS-CoV-2 antibodies, the speed of the epidemic's expansion over time and the
percentage of people who had asymptomatic infections
(It is very useful; essential)
The purpose
of the test in this case is to screen for people with possible immunity, i.e., people who have
already been infected and have produced antibodies against SARS-CoV-2. This
constant epidemiological surveillance is essential to help us make decisions
about the need to apply broader and stricter physical distance measures, such
as school closures and quarantine for the entire population, as well as
opportunities to reduce physical distance measures. Household surveys being
conducted in Brazil at this time, using this rapid serological test, are, initially,
scheduled to occur in four phases, with a two-week interval between the phases.
In this way, it will be possible to estimate the spread of SARS-CoV-2 in the
country at this time (EPICOVID19 -
These surveys
will also be useful to reveal something very important, which is the number of
people who were infected, but did not notice, that is, they were asymptomatic.
In addition to the tests, researchers will interview participants and be able
to inquire about recent symptoms typical of COVID-19. People who test positive
and report absence of recent symptoms will be classified as cases of
asymptomatic infections. This is important to investigate the role of asymptomatic
people as disseminators of this pandemic. This investigation will be possible,
because in the phases subsequent to the first phase, the researchers will apply
the test and interview neighbours of the participants who were included in the
previous phase.
These
epidemiological surveys with rapid serological tests for antibody detection are
likely to be the key instrument to help us deal with this pandemic, which may
last until 2022 (and even resurface in 2025) (https://science.sciencemag.org/content/early/2020/04/14/science.abb5793/tab-pdf).
These tests are likely to act as the speedometer that
will indicate the speed of contagion, to help us accelerate or step on the
brake, by applying measures to reduce or increase physical distance
(confinement), such as closing (or opening) schools and trade, and home
confinement (or relaxation) of the entire population.
In the medium
/ long term, these tests will be useful to detect when we are approaching the
threshold of herd immunity that will signal the end of this pandemic. For
example, if the basic reproduction number of SARS-CoV-2 is 3 (R0 = 3), when the
population reaches 67% of people with antibodies, we can assume that the epidemic
will not be sustained and will soon be eliminated.
CERTIFICATE (OR “PASSPORT”) OF IMMUNITY
Identification of people in the population who are
able to leave home confinement and speed up the resumption of economic and
social activities
(Usefulness
depends on the prevalence of people with antibodies)
Let's
imagine three scenarios to understand the effect of this type of test in
practice, in order to issue (or obtain) an immunity certificate. The rapid test
for antibodies to SARS-CoV-2 tends to have high specificity, but relatively low
sensitivity. The test that was used in the household survey in Rio Grande do
Sul and that is being used in household surveys in all states in Brazil (with
samples of people in 133 sentinel cities) has a specificity of 99% (percentage
of negative results among people without antibodies) and sensitivity of 86%
(percentage of positive results among those with antibodies).
Let's say
(first scenario) that in a population of 10,000 people there are,
hypothetically, 100 (1%) with antibodies to SARS-CoV-2 (Figure 1). The tree
(flowchart) clearly shows that in this scenario the number of true-positive
results (86) is less than that of false-positive results (99). Even with a very
good specificity (99%) a positive result is more likely to be false than true.
This means that, for a person with a positive result, the probability of not having
antibodies is greater than that of having antibodies. In possession of an
"immunity certificate" like this, the person should not feel
reassured, as she is more likely to be susceptible than immunized.
Figure 1) The rapid serological test for antibodies to SARS-CoV-2. Scenario 1: Prevalence of immunized patients = 1%; Specificity = 99%; Sensitivity = 86%. For every 100 true positives, there are 115 false positives. Only 46% of the positives are true.
Now, in a
population with 10% or 20% of people with antibodies (second and third
scenarios), a positive result in this test shows a high probability that the
person actually has antibodies (Figures 2 and 3). The number of true-positive
results is much greater than that of false-positive results; for every 100
true-positive results there are only 10 and 5 false-positive results, when the
prevalence is 10% and 20%, respectively.
Figure 2) The rapid serological test for antibodies to SARS-CoV-2. Scenario 2: Prevalence of immunized patients = 10%; Specificity = 99%; Sensitivity = 86%. For every 100 true positives, there are 10 false positives. 90% of the positives are true.
Figure 3) The rapid serological test for antibodies to SARS-CoV-2. Scenario 3: Prevalence of immunized patients = 20%; Specificity = 99%; Sensitivity = 86%. For every 100 true positives, there are 5 false positives. 95% of the positives are true.
Prevalence of
1% or less is common at this time in most populations and 10% or more is rare.
In the region of Italy where there were a large number of deaths from COVID-19
the prevalence of infected people is no more than 15%. The usefulness of this
test may be greater for subpopulations very exposed to the virus, such as physicians,
nurses and nursing technicians, who are constantly in close contact with
infected people. It can also be useful for people who are recent
"contacts" of infected people; it would be as if these people belong
to populations with a high prevalence of people with antibodies (there are
reports that among physicians, nurses, nursing technicians and hospital workers
in general, the prevalence of people with antibodies is around 20%).
The numbers
in the three scenarios are based on the aggregate population and ignore clinical history which would modify the prior probabilities. Within the general
population and among special populations such as healthcare workers, there are
individuals with and without a history of what sounds like COVID-19 including those
with no, atypical, mild, moderate and a severe history. In each of these there
is a different prior probability (i.e., a different prevalence of antibodies
in the figures), that could possibly vary from 2 to 80% for instance.
Summary
The rapid
serological test for antibodies to SARS-CoV-2 is essential for monitoring: the
percentage of the population with antibodies; the speed of the epidemic's
expansion over time; of the percentage of people who had asymptomatic
infections. It is useless for the diagnosis of patients in hospitals or medical
clinics with the aim of assisting in clinical handling. It is useless for the
identification of people in the population who are able to leave home
confinement and speed up the resumption of economic and social activities, when
the prevalence of people with antibodies is low (around 1%); but it is useful
when the prevalence is higher, i.e., when at least 10% of the population have
antibodies. This test is also useful for people who are often exposed to
infected people or who have been intimately exposed to an infected person.
Therefore, the test for antibody to SARS-CoV-2 is:
- Essential for epidemiological surveillance;
- Useless for clinical handling of patients;
- Useless for certificate of immunity if
prevalence of people with antibodies is low;
- Useful for certificate of immunity if
prevalence of people with antibodies is high (≥10%).
Warning: It has not
yet been proven that antibodies to SARS-CoV-2 confer immunity and if so, for
how long. Therefore, the values of specificity, sensitivity and scenarios
discussed in this post may not be relevant, if the antibodies do not confer
immunity or do it only for a short period of time. For now, based on studies
with monkeys and evidence of other viruses in humans, it is assumed that there
is immunity acquired for at least two years (https://science.sciencemag.org/content/early/2020/04/14/science.abb5793/tab-pdf).
Paulo Nadanovsky, PhD
Epidemiologist at FIOCRUZ and at the University of
the State of Rio de Janeiro
Disclaimer: I am an
epidemiologist, but not a specialist in the epidemiology of infectious
diseases. I teach epidemiological methods in the doctoral and master's courses
at the National School of Public Health at FIOCRUZ, at the Institute of Social
Medicine of the State University of Rio de Janeiro and in the undergraduate
medical course at this University.
The opinions in this article are mine, they do not
necessarily represent the opinions of other professionals in my institutions,
much less their official position.
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