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.