Recommendations for use of antigenic tests in the diagnosis of acute SARS-CoV-2 infection in the second pandemic wave: attitude in different clinical settings

Abstract

The high transmissibility of SARS-CoV-2 before and shortly after the onset of symptoms suggests that only diagnosing and isolating symptomatic patients may not be sufficient to interrupt the spread of infection; therefore, public health measures such as personal distancing are also necessary. Additionally, it will be important to detect the newly infected individuals who remain asymptomatic, which may account for 50% or more of the cases. Molecular techniques are the "gold standard" for the diagnosis of SARS-CoV-2 infection. However, the massive use of these techniques has generated some problems. On the one hand, the scarcity of resources (analyzers, fungibles and reagents), and on the other the delay in the notification of results. These two facts translate into a lag in the application of isolation measures among cases and contacts, which favors the spread of the infection. Antigen detection tests are also direct diagnostic methods, with the advantage of obtaining the result in a few minutes and at the very "pointof-care". Furthermore, the simplicity and low cost of these tests allow them to be repeated on successive days in certain clinical settings. The sensitivity of antigen tests is generally lower than that of nucleic acid tests, although their specificity is comparable. Antigenic tests have been shown to be more valid in the days around the onset of symptoms, when the viral load in the nasopharynx is higher. Having a rapid and real-time viral detection assay such as the antigen test has been shown to be more useful to control the spread of the infection than more sensitive tests, but with greater cost and response time, such as in case of molecular tests. The main health institutions such as the WHO, the CDC and the Ministry of Health of the Government of Spain propose the use of antigenic tests in a wide variety of strategies to respond to the pandemic. This document aims to support physicians involved in the care of patients with suspected SC2 infection, in the context of a growing incidence in Spain since September 2020, which already represents the second pandemic wave of COVID-19.

Keywords: COVID-19; PCR; SARS-CoV2; antigenic test; diagnosis; emergency departments; microbiology; nursing home and long-term facilities; pediatrics; primary care.

Figure 1

Confirmed cases by age group along the second wave in he Community of Madrid (https://www.comunidad.madrid/servicios/salud/2019-nuevocoronavirus#situacion-epidemiologica-actual)

Figure 2

Distribution of severe cases and deaths by age group in the Community of Madrid (https://www.comunidad.madrid/servicios/salud/2019-nuevocoronavirus#situacion-epidemiologica-actual).

Figure 3

Cumulative incidence of confirmed cases in the previous 14 days in the Community of Madrid, as of October 6, 2020 (https://www.comunidad.madrid/servicios/salud/2019-nuevo-coronavirus#situacion-epidemiologica-actual).

Figure 4

Pre-test and post-test probability of infection according to results of test with 83.8% sensitivity and 97% specificity

Figure 5

Nasopharyngeal smear technique to perform the antigenic test against SARS-COV-2. A: The swab must reach the posterior wall of the nasopharynx or cavum. Once there, it should be turned on its own axis to collect as many epithelial cells as possible. B: The swab must be stirred well in order to get a good emulsion in the medium and break at the notch.

Figure 6

Work-up algorithm for the study of suspected cases of acute SC2 infection in Primary Care. ^aDone in the previous 3 months, except in special cases; ^bOr not done; ^cPositive antigen test does not require confirmation with PCR; ^dNew symptoms or worsening of previous ones, without severity criteria (severe dyspnea, tachypnea ≥30 rpm, Sat O2≤93%, and/or pulmonary infiltrates ≥50%) [34]

Figure 7

Work-up algorithm for the study of close contacts of SC2 infection in Primary Care. ^aDone in the previous 3 months, except in special cases; ^bOr not done; ^cConsider PCR in health or social care personnel

Figure 8

Work-up algorithm for the study of suspected cases of acute SC2 infection in Primary Pediatric Care. ^aDone in the previous 3 months, except in special cases; ^bOr not done; ^cWith positive antigenic test no PCR confirmation is required. The presence of fever, cough, odynophagia, respiratory distress, ageusia, anosmia, gastrointestinal symptoms are considered suggestive symptoms of COVID-19. Isolated rhinorrhea would not be considered clinically suggestive (also take into account the family epidemic environment and context); ^dIf the patient already had an infection confirmed by PCR or presents positive SC2-IgG in the previous 3 months, it is not recommended to perform the antigenic test or PCR, except in special cases (immunosuppressed or at-risk cohabitants or need for admission); ^eConsider PCR if there is no improvement, persisting clinical or epidemiological suspicion.

Figure 9

Work-up algorithm for the study of suspected cases of acute SC2 infection in Pediatric Emergency Room. ^aDone in the previous 3 months, except in special cases; ^bOr not done; ^cWith positive antigenic test, no PCR confirmation is required. The presence of fever, cough, odynophagia, respiratory distress, ageusia, anosmia, and gastrointestinal symptoms are considered suggestive symptoms of COVID-19. Isolated rhinorrhea would not be considered clinically suggestive (also take into account the family epidemic environment and context); ^dIf the patient already had a confirmed infection by PCR or presents positive SC2-IgG in the previous 3 months, it is not recommended to perform the antigenic test or PCR, except in special cases (immunosuppressed or cohabitants at risk or need for admission).

Figure 10

Work-up algorithm for the study of close contacts of SC2 infection in the pediatric field, including schools. ^aDone in the previous 3 months, except in special cases; ^bOr not done; ^cPositive antigenic test does not require PCR confirmation;^dIf the patient already had a confirmed infection by PCR or presents positive SC2-IgG in the previous 3 months, it is not recommended to perform the antigenic test or PCR, except in special cases (immunosuppressed or cohabitants at risk or need for admission). In case of close contact at school test not generally indicated, but a test is to be done if the patient develops symptoms during quarantine, vulnerable people according to the criteria of their pediatrician or family doctor, or in situations of special risk, prior public health indication.

Figure 11

Work-up algorithm for the study of suspected cases of acute SC2 infection in Emergency Services. ^aDone in the previous 3 months, except in special cases; ^bOr not done; ^cPositive antigenic test does not require PCR confirmation.

Figure 12

Work-up algorithm for the study of suspected cases of acute SC2 infection in sociosanitary centers (residents or professionals). ^aDone in the previous 3 months, except in special cases; ^bOr not done; ^cPositive antigenic test does not require PCR confirmation.

Figure 13

Work-up algorithm for the study of close contacts of SC2 infection in sociosanitary centers. ^aDocumented history of COVID-19 in the previous 3 months; ^bDone in the previous 3 months, except in special cases; ^cOr not done; ^dAntigenic test or PCR depending on the availability of the tests. If the lag for PCR result is expected to be less than 24 hours, it is preferable to perform a baseline PCR. Otherwise, it will be preferable to chose antigen test, having to confirm negative results with PCR; ^ePositive antigenic test does not require PCR confirmation.

Figure 14

Work-up algorithm for the screening of SC2 infection in personnel in sociosanitary centers.