Rapid Diagnostic Testing for SARS-CoV-2

Clinical Course and Diagnostic Testing

Pathophysiology and Timeline of Viremia, Antigenemia, and Immune Response during Acute SARS-CoV-2 Infection.

In some persons, reverse-transcriptase–polymerase-chain-reaction (RT-PCR) tests can remain positive for weeks or months after initial infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but this positivity rarely indicates replication-competent virus that can result in infection.

The pathophysiology of acute SARS-CoV-2 infection, the clinical course of Covid-19, and the host immunologic response provide a basis for diagnostic testing strategies (Figure 1).10,11 SARS-CoV-2 is predominantly a respiratory airway pathogen, and transmission occurs largely through inhalation of small droplets and aerosols.12 Novel genomic viral variants, including the B.1.617.2 (delta) variant, have higher transmissibility than the original D614G virus, leading to faster dissemination within populations, but they share the same pathophysiology of infection and disease. The WHO recently named the B.1.1.529 (omicron) variant as the sixth “variant of concern,” and available evidence suggests it is more transmissible but less virulent than previous variants.

Symptoms of Covid-19 and Signs or Symptoms of Severe Covid-19.

Symptoms of Covid-19 (Table 1) appear 2 to 14 days after exposure, with an average onset 5 to 6 days after infection.13,14 Most persons with Covid-19 have mild-to-moderate symptoms and recover at home, but some, particularly older or unvaccinated adults and those with underlying medical conditions or immunocompromise, may have serious illness.13 SARS-CoV-2 infection also occurs without causing symptoms or Covid-19, and asymptomatic persons can contribute to viral transmission.15-17 Humoral immunity wanes after initial vaccination,18 but booster immunizations have been shown to reduce the incidence of adverse outcomes.19 Viral load levels and clearance may be similar among vaccinated and unvaccinated adults,20 and adults who have not received a booster immunization have a higher risk of Covid-19–related hospitalization or death than those who have received one.21

Indications and Algorithms for Rapid Diagnostic Tests (RDTs) for SARS-CoV-2.

The Centers for Disease Control and Prevention defines a close contact as a person who was less than 6 feet away for 15 minutes or more over a 24-hour period.13,23 Potential high-risk transmission settings include an airplane, a concert or sporting event, and a crowded or poorly ventilated indoor area.13,22,23 Covid-19 denotes coronavirus disease 2019.

Three common indications for diagnostic SARS-CoV-2 testing, as recommended by the WHO22 and the Centers for Disease Control and Prevention (CDC),23 range from high to low pretest probability of infection (Figure 2). First, anyone with Covid-19 symptoms, regardless of vaccination status, should undergo testing for SARS-CoV-2. Second, asymptomatic persons, regardless of vaccination status, who are close contacts of someone with known or probable SARS-CoV-2 infection should undergo diagnostic testing. Persons who are unvaccinated or who have not received a vaccine booster within the previous 6 months have a higher pretest probability of infection than those who are fully vaccinated, whereas others have a low or moderate pretest probability of infection. Third, testing should be considered in asymptomatic persons who have been in a setting where the risk of transmission is high, such as in an airplane or at a sporting event. Use of an RDT may also be considered in persons who plan to be in a group setting, even though they may have a low pretest probability of infection; this testing should occur as close to the time of the gathering as possible.

Diagnostic testing for acute SARS-CoV-2 infection can be performed with either molecular NAATs or antigen-based assays, and both are available as RDTs.22,23 Molecular NAATs detect the presence of viral gene targets, including the N, S, and E genes and the open reading frame 1ab (ORF 1ab). Reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays are the most widely used diagnostic SARS-CoV-2 NAATs worldwide.24 Antigen-based tests, also called immunoassays, detect domains of the surface proteins, including the nucleocapsid, spike, and receptor-binding domains, that are specific to SARS-CoV-2. Although both techniques are highly specific, NAATs are generally more sensitive than antigen-based tests because they amplify target genomic sequences. Tests to detect host IgG or IgM antibodies to SARS-CoV-2 should not be used to diagnose acute infection.

The clinical performance of diagnostic SARS-CoV-2 testing extends beyond pathogen targets such as viral proteins and RNA and includes clinical characteristics (e.g., the patient’s viral load and the time since exposure or symptom onset), operational testing attributes (e.g., the specimen type, swab…

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