False positive test results may occur due to cross-reactivity from pre-existing antibodies to other coronaviruses. Downloaded from https://www.covid19treatmentguidelines.nih.gov/ on 7/6/2022 COVID-19 Treatment Guidelines 20 Serologic Testing and Immunity to SARS-CoV-2 Infection The FDA has issued EUAs for more than 80 SARS-CoV-2 serologic tests since the start of the pandemic. However, these tests are not currently authorized for routine use in making individual medical decisions.30 SARS-CoV-2 serologic tests are authorized for detecting antibodies, but their ability to predict protective immunity has not been validated. The majority of these tests are not standardized. Furthermore, as SARS-CoV-2 is not a well-conserved virus, mutations in the receptor binding domain of the virus could lead to decreased binding affinity between antibodies and SARS-CoV-2-specific antigens. Given the available information, there is insufficient evidence for the Panel to recommend either for or against the use of SARS-CoV-2 serologic testing to assess for immunity or to guide clinical decisions about using COVID-19 vaccines or anti-SARS-CoV-2 monoclonal antibodies in certain people. If a serologic test is performed, the result should be interpreted with caution. It remains unclear how long SARS-CoV-2 antibodies persist following either infection or vaccination. A negative serologic test result also does not preclude prior SARS-CoV-2 infection or vaccination against COVID-19. Some people who are infected with SARS-CoV-2 or who are vaccinated against COVID-19 may not develop measurable antibodies (e.g., those who are immunocompromised). It is presumed that those who do not have measurable antibodies after vaccination are at higher risk of SARS-CoV-2 infection. In communities that have a low prevalence of SARS-CoV-2 infection, the proportion of positive test results that are false positives may be quite high. In these situations, performing confirmatory testing with a distinct antibody assay, ideally an assay that uses a different antigenic target (e.g., the nucleocapsid phosphoprotein if the first assay targeted the spike protein), can substantially reduce false positives. Assuming that the test is reliable, serologic tests that identify recent or prior SARS-CoV-2 infection may be used to: • Differentiate between SARS-CoV-2 antibody responses to natural infection and vaccine-induced antibody responses to the SARS-CoV-2 spike protein antigen. Because nucleocapsid protein is not a constituent of the vaccines that are currently approved by the FDA, available through EUAs, or in late-stage clinical trials, serologic tests that detect antibodies by recognizing nucleocapsid proteins can be used to distinguish between antibody responses to natural infection and vaccine-induced antibody responses. • Determine who may be eligible to donate convalescent plasma • Define multisystem inflammatory syndrome in children (MIS-C) and multisystem inflammatory syndrome in adults (MIS-A) • Estimate the proportion of the population that has been exposed to SARS-CoV-2 Based on current knowledge, serologic tests should not be used to (AIII): • Make decisions about how to group persons in congregate settings; • Determine whether someone may return to the workplace; or • Assess for immunity to SARS-CoV-2 following vaccination in immunocompetent individuals, except in clinical trials4. Centers for Disease Control and Prevention. Nucleic acid Treatment Guidelines 23 Prevention of SARS-CoV-2 Infection Last Updated: April 29, 2022 Summary Recommendations • The COVID-19 Treatment Guidelines Panel (the Panel) recommends COVID-19 vaccination as soon as possible for everyone who is eligible according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (AI). • The Panel recommends using tixagevimab 300 mg plus cilgavimab 300 mg (Evusheld) administered as 2 consecutive 3-mL intramuscular injections (BIII) as SARS-CoV-2 pre-exposure prophylaxis (PrEP) for adults and adolescents (aged ≥12 years and weighing ≥40 kg) who do not have SARS-CoV-2 infection, who have not been recently exposed to an individual with SARS-CoV-2 infection, AND who: • Are moderately to severely immunocompromised and may have an inadequate immune response to COVID-19 vaccination; or • Are not able to be fully vaccinated with any available COVID-19 vaccines due to a history of severe adverse reactions to a COVID-19 vaccine or any of its components. • The Food and Drug Administration Emergency Use Authorization states that individuals who received tixagevimab 150 mg plus cilgavimab 150 mg should be given a second dose as soon as possible. The specific dose of tixagevimab plus cilgavimab that an individual should receive depends on the amount of time that has passed since the first dose was administered: • If the initial dose was administered ≤3 months prior, the second dose should be tixagevimab 150 mg plus cilgavimab 150 mg. • If the initial dose was administered >3 months prior, the second dose should be tixagevimab 300 mg plus cilgavimab 300 mg. • Tixagevimab plus cilgavimab is not a substitute for COVID-19 vaccination and should not be used in unvaccinated individuals for whom COVID-19 vaccination is recommended. • If