Study Population

The cohort comprised 167 183 nonhospitalized patients 12 years and older. Patients were included if they had a laboratory-confirmed positive COVID-19 polymerase chain reaction or antigen test collected in the noninpatient setting between November 9, 2020, and January 31, 2022, or if they were referred to the health care system specifically for nMAb treatment. All patients in the cohort met at least 1 of the following Food and Drug Administration EUA criteria for high risk of a poor outcome: 65 years or older, pregnant, and/or having obesity or overweight, chronic kidney disease, diabetes, immunosuppressive disease or immunosuppressive treatment, cardiovascular disease or hypertension, chronic lung diseases, sickle cell disease, neurodevelopmental disorders (eg, cerebral palsy), and/or medical-related technological dependence.¹⁸ The patient index date was the date of the first positive test result (99.4% of population) or the date of referral (0.6% of population). Patient index dates were categorized into the following variant epochs: pre-Delta (November 9, 2020, to June 30, 2021), Delta (July 1 to November 30, 2021), Delta and Omicron BA.1 (December 1 to 31, 2021), and Omicron BA.1 (January 1 to 31, 2022).

Patients were excluded from analyses if they died on the index date, had clinical COVID-19 before the index date, received another COVID-19 outpatient therapy within the outcome window of 30 days, or received nMAb treatment more than 10 days after the index date or during a hospitalization (Figure 1). Clinical COVID-19 was defined as having a previously recorded International Statistical Classification of Diseases, Tenth Revision, Clinical Modification code U07.1 diagnosis without a positive laboratory test. COVID-19 immunization records were obtained from EHR and state vaccine registries. Patients were considered partially vaccinated if they received 1 mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) vaccine dose and fully vaccinated if they received 1 Ad26.COV2.S (Janssen) vaccine dose or 2 mRNA or BNT162b2 vaccine doses. Patients were considered boosted if they had 1 additional vaccine dose after being fully vaccinated. Patients were considered immunocompromised if they received immunosuppressant medications within the previous 90 days or a diagnosis of immune deficiency or solid organ or hematopoietic stem cell transplant.¹⁹ Immunosuppressive medications were defined using systemic corticosteroid and immunosuppressant value sets,^20,21 which were updated to include drugs available after the version date of the value sets. To characterize the representativeness of the study population, race (American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or other Pacific Islander, White, other, and not specified) and ethnicity (Hispanic or Latino, Non-Hispanic or non-Latino, and not specified) categories were abstracted from the EHRs.

nMAb indicates neutralizing monoclonal antibody.