Special considerations
rRT-PCR vs. antigen test
rRT-PCR is the recommended initial test for diagnosing SAR-CoV-2 in
symptomatic patients in international guidelines (Pan American Health
Organization, 2020) (2019-nCoV Working Group. Communicable Diseases
Network Australia., 2020) (CDC, 2020c). However, as the number of
patients presenting with COVID-19 symptoms increases, there has been a
shortage of diagnostic resources, such as swabs, PCR reagents, and RNA
isolation kits, and a growing demand for rapid, onsite diagnostics (Ravi
et al., 2020).
Point-of-care (POC) tests, including rapid antigen detection tests, are
also recommended as an initial test by the CDC (CDC, 2020b),
particularly in the early days of symptoms or in cases of close contacts
in high-risk congregate settings. Infection prevalence at the time of
testing and clinical context both impact pre-test probability (CDC,
2020b) (Table 1) and should be taken into account before and after test
results. Testing of asymptomatic contact cases may be considered after
5–7 days of contact, even if the antigen detection tests are not
explicitly authorized for this use. Asymptomatic cases have been
demonstrated to have viral loads similar to symptomatic cases. A
negative antigen detection test should not remove a close contact
individual from quarantine requirements (World Health Organization,
2020).
Compared with rRT-PCR, antigen detection tests are cheaper, have a
similar specificity, and usually deliver results faster, but have a
lower sensitivity (CDC, 2020b). The choice of test also depends on the
availability of tests and trained personnel, along with the above
factors.
Types and results of immunological
tests
Antibody tests available for laboratory use include ELISA, more advanced
CLIA, and laboratory-independent POC lateral flow assays for rapid
detection of antibodies (such as CGIA), among others (Deeks et al.,
2020).
CLIA methods appear more sensitive (97.5%, 95% CI 94.0–99.0) than
ELISA (90.7%, 95% CI 83.3–95.0) or CGIA‐based lateral flow assays
(90.7%, 95% CI 82.7–95.2) for IgG/IgM (Deeks et al., 2020). Tests
that detect antibodies with a high affinity for the SARS-CoV-2 virus are
more likely to indicate neutralizing antibodies (Jayamohan et al.,
2020).
Negative rRT-PCR or antigen detection tests and the need
for
quarantine
In the case that an individual was only in close contact with an
infected patient and has not developed symptoms, they should complete 14
days of isolation. No tests are necessary, except for particular cases
such as hospitalized patients or for other epidemiological reasons
(World Health Organization, 2020b).
Image studies
Chest computed tomography (CT) is considered the primary imaging
diagnostic modality for examining patients with COVID-19 (Güneyli et
al., 2020). A Cochrane review of radiologic tests (Salameh et al., 2020)
showed that the pooled sensitivity of CT was 86.2% (95% CI 71.9–93.8
[13 studies, 2,346 participants]) and specificity was 18.1% (95%
CI 3.71–55.8). In patients with negative RT-PCR tests, Ai et
al. (Ai et al., 2020) suggested that a combination of exposure history,
clinical symptoms, typical CT imaging features, and chest CT dynamic
changes should be used to identify COVID-19 cases.
Conclusions
COVID-19 diagnosis is always a cause for uncertainty among physicians,
health professionals, and public health authorities. Our methodology,
involving 24 questions answered by Latin American experts, resulted in a
simplified algorithm involving symptomatic people or close contacts in 3
windows of time (≤7 days, 8–13 days, and ≥14 days).
Even considering the high disparities in healthcare access within the
region, we regard rRT-PCR tests as the standard diagnostic tests for
SARS-CoV-2 infection, from the onset of symptoms until 13 days
afterward. This recommendation is consistent with all main published
guidelines (Pan American Health Organization, 2020) (World Health
Organization, 2020a). Sample pooling should be used in low-resource and
low-prevalence (<30%) settings (CDC, 2020a).
We also recommend tests for antigen detection from upper respiratory
tract samples as a simple POC diagnostic test in high-prevalence
settings up to 5–7 days after onset of symptoms (World Health
Organization, 2020). We consider antigen testing a good alternative to
rRT-PCR in this setting, particularly where the molecular tests are not
readily available. Antigen detection tests also appear as a reasonable
option in the CDC guidelines for SARS-CoV-2 detection (CDC, 2020c).
Immunologic assays are not ideal for diagnosis in the early days of
SARS-CoV-2 infection according to WHO and PAHO guidelines (World Health
Organization, 2020a) (Pan American Health Organization, 2020). However,
we suggest that they can be used from 14 days after symptom onset or 21
days after close contact, if asymptomatic, for epidemiological and
contact tracing purposes. Or in some exceptional situations when the
other direct diagnostic tests are repeatedly negative in a patient with
high clinical suspicion and the individual diagnosis is necessary before
that period above mentioned, we recommend the use of antibody assay from
Day 8 onward as an aid to the diagnosis.
Depending on local epidemiology and clinical symptoms, for all suspected
COVID-19 patients, diagnostic testing for other conditions such as
malaria, dengue, typhoid, influenza, and other respiratory diseases
should also be considered (Chi et al., 2020) (United Nations. Department
of Healthcare Management and Occupational Safety and Health,
2020).
In summary, the proposed simplified algorithm aims to support medical
decision-making in Latin America, taking into account published
international guidelines and the region’s health access inequalities.
Limitations
Although based on well-established consensus formation techniques and
drawing on panelists’ expertise, these recommendations do not constitute
a statement from the institutions or associations to which these
professionals are affiliated. The main limitations of this expert panel
consensus are selection bias, observer bias, confirmation bias,
publication bias, and cohort effects (different features and pace of the
COVID-19 pandemic in each country of Latin America).
Implications
The proposed algorithm may support COVID-19 diagnosis decision-making in
Latin America, taking into account published international guidelines
and the region’s health access inequalities.
Acknowledgments
Roche Diagnostics LATAM supported the elaboration of this article. Data
was collected by the sponsor and third-party consultants (Within3, OH,
USA, and Conscient Scientific Consultants, SP, Brazil). All authors
contributed to the writing, revision, and approval of the article.
Mariangela Correa from Conscient Scientific Consultants provided medical
writing support.