Racial and Ethnic Disparities in Outpatient Treatment of COVID-19 ― United States, January–July 2022

In December 2021 and early 2022, four medications received emergency use authorization (EUA) by the Food and Drug Administration for outpatient treatment of mild-to-moderate COVID-19 in patients who are at high risk for progressing to severe disease; these included nirmatrelvir/ritonavir (Paxlovid) and molnupiravir (Lagevrio) (both oral antivirals), expanded use of remdesivir (Veklury; an intraveneous antiviral), and bebtelovimab (a monoclonal antibody [mAb]).* Reports have documented disparities in mAb treatment by race and ethnicity (1) and in oral antiviral treatment by zip code-level social vulnerability (2); however, limited data are available on racial and ethnic disparities in oral antiviral treatment.† Using electronic health record (EHR) data from 692,570 COVID-19 patients aged ≥20 years who sought medical care during January-July 2022, treatment with Paxlovid, Lagevrio, Veklury, and mAbs was assessed by race and ethnicity, overall and among high-risk patient groups. During 2022, the percentage of COVID-19 patients seeking medical care who were treated with Paxlovid increased from 0.6% in January to 20.2% in April and 34.3% in July; the other three medications were used less frequently (0.7%-5.0% in July). During April-July 2022, when Paxlovid use was highest, compared with White patients, Black or African American (Black) patients were prescribed Paxlovid 35.8% less often, multiple or other race patients 24.9% less often, American Indian or Alaska Native and Native Hawaiian or other Pacific Islander (AIAN/NHOPI) patients 23.1% less often, and Asian patients 19.4% less often; Hispanic patients were prescribed Paxlovid 29.9% less often than non-Hispanic patients. Racial and ethnic disparities in Paxlovid treatment were generally somewhat higher among patients at high risk for severe COVID-19, including those aged ≥50 years and those who were immunocompromised. The expansion of programs focused on equitable awareness of and access to outpatient COVID-19 treatments, as well as COVID-19 vaccination, including updated bivalent booster doses, can help protect persons most at risk for severe illness and facilitate equitable health outcomes.

In December 2021 and early 2022, four medications received emergency use authorization (EUA) by the Food and Drug Administration for outpatient treatment of mild-to-moderate COVID-19 in patients who are at high risk for progressing to severe disease; these included nirmatrelvir/ritonavir (Paxlovid) and molnupiravir (Lagevrio) (both oral antivirals), expanded use of remdesivir (Veklury; an intraveneous antiviral), and bebtelovimab (a monoclonal antibody [mAb]).* Reports have documented disparities in mAb treatment by race and ethnicity (1) and in oral antiviral treatment by zip code-level social vulnerability (2); however, limited data are available on racial and ethnic disparities in oral antiviral treatment. † Using electronic health record (EHR) data from 692,570 COVID-19 patients aged ≥20 years who sought medical care during January-July 2022, treatment with Paxlovid, Lagevrio, Veklury, and mAbs was assessed by race and ethnicity, overall and among high-risk patient groups. During 2022, the percentage of COVID-19 patients seeking medical care who were treated with Paxlovid increased from 0.6% in January to 20.2% in April and 34.3% in July; the other three medications were used less frequently (0.7%-5.0% in July). During April-July 2022, when Paxlovid use was highest, compared with White patients, Black or African American (Black) patients were prescribed Paxlovid 35.8% less often, multiple or other race patients 24.9% less often, American Indian or Alaska Native and Native Hawaiian or other Pacific Islander (AIAN/NHOPI) patients 23.1% less often, and Asian patients 19.4% less often; Hispanic patients were prescribed Paxlovid 29.9% less often than non-Hispanic patients. Racial and ethnic disparities in Paxlovid treatment were generally somewhat higher among patients at high risk for severe COVID-19, including those aged ≥50 years and those who were immunocompromised. The expansion of programs focused on equitable awareness of and access to outpatient COVID-19 treatments, as well as COVID-19 vaccination, including updated bivalent booster doses, can help protect persons most at risk for severe illness and facilitate equitable health outcomes.
This study used EHR data from 30 sites (each representing one or more health care systems) participating in PCORnet, or Lagevrio prescription or Veklury or mAb administration. ¶ ¶ High-risk patient groups were defined based on age (50-64, 65-79, and ≥80 years) and immunocompromise (previous organ transplant, active cancer treatment, corticosteroid use, and immunosuppressive medication use).*** The percentage of COVID-19 patients treated with each medication was calculated by age group, sex (male and female), race (White, Black, Asian, AIAN/NHOPI, multiple or other race, and missing), ethnicity (Hispanic, non-Hispanic, and other or missing), † † † immunocompromise, and underlying medical conditions. § § § Disparities were assessed using absolute differences (percentage treated in the racial or ethnic minority group minus the percentage treated in the majority group [i.e., White race and non-Hispanic ethnicity, respectively]) and relative differences (absolute difference divided by the percentage treated in the majority group). Statistical differences in the percentage treated by race and ethnicity were quantified using Pearson's chi-square tests comparing patients in the minority groups with those in the majority group. Disparities in percentage treated overall and by age group were assessed during April-July 2022, when Paxlovid use was highest; disparities by immunocompromise could only be assessed during January-July 2022 because of restrictions in the PCORnet distributed data infrastructure. P-values <0.05 were considered statistically significant. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy. ¶ ¶ ¶ During January-July 2022, a total of 692,570 COVID-19 patients aged ≥20 years were identified.**** Among these, 22.2% were aged ≥65 years, 60.5% were female, 68.2% were White, and 79.6% were non-Hispanic (Table 1). Overall, 11.7% of COVID-19 patients were treated with Paxlovid, 2.7% with mAbs, 1.0% with Lagevrio, and 0.7% with Veklury. The percentage treated with Paxlovid exceeded the overall average of 11.7% for the following patient groups: aged ≥50 years, White, non-Hispanic, † † † † active cancer treatment, corticosteroid use, immunosuppressive medication use, and presence of underlying medical conditions (except chronic kidney disease, cirrhosis, congestive heart failure, and dementia). mAb treatment was more common than Paxlovid treatment among patients with a previous organ transplant.
Racial and ethnic disparities existed for treatment with other medications, but absolute differences were small, given the low treatment percentages. Racial and ethnic minority patients were ¶ ¶ Treatment groups were not mutually exclusive. For example, among 81,373 patients prescribed Paxlovid, 579 (0.7%) were also treated with mAbs (491 bebtelovimab), 619 (0.8%) with Lagevrio, and 203 (0.2%) with Veklury. Among patients prescribed Paxlovid, 71% had either a diagnostic code for COVID-19 or a documented positive SARS-CoV-2 viral test (NAAT/PCR or rapid antigen); 28% had a documented positive viral test, and 66% had a diagnostic code. There were no systematic differences in age, sex, race, or ethnicity between patients prescribed Paxlovid who had a diagnostic code or positive test compared with those who did not. *** The presence of immunocompromise was based on available information in the patients' EHR before COVID-19: previous organ transplant (one or more ICD-10-CM codes at any time before COVID-19); active cancer treatment (three or more ICD-10-CM codes for cancer during the 6 months preceding COVID-19); corticosteroid use (two or more prescriptions during the year preceding COVID-19); and immunosuppressive medication use (one or more prescriptions or administrations in the year preceding COVID-19, not including corticosteroids

TABLE 1. (Continued) Demographic and clinical characteristics of patients with COVID-19* and those treated with four outpatient medications † and the percentage of COVID-19 patients treated with each medication among adults aged ≥20 years -PCORnet, the National Patient-Centered Clinical Research Network, 30 U.S. sites, January-July 2022
treated with mAbs and Lagevrio less often than were White and non-Hispanic patients (Supplementary Table 1, https:// stacks.cdc.gov/view/cdc/121865). AIAN/NHOPI, Asian, and Hispanic patients received Veklury less often than did White and non-Hispanic patients; Black patients received Veklury more often than White patients.
During January-July 2022, racial and ethnic disparities also existed for the four immunocompromised patient groups. In general, immunocompromised Black, multiple or other race, and Hispanic patients were treated with Paxlovid and mAbs less often than were immunocompromised White and non-Hispanic

Discussion
In this study of nearly 700,000 COVID-19 patients who sought medical care, the proportion who were treated with an outpatient COVID-19 medication increased substantially over time, primarily driven by increased Paxlovid use; however, treatment gaps exist among racial and ethnic minority groups. During April-July 2022, Paxlovid treatment was 35.8% lower among Black patients relative to White patients and 29.9% lower among Hispanic patients relative to non-Hispanic patients. This study corroborates previous reports of inequitable outpatient COVID-19 treatment (1,2) and documents the persistence of racial and ethnic disparities through July 2022. Disparities in pharmacy dispensing of oral antiviral medications between zip codes with high and with low social vulnerability began narrowing during July-August 2022, after the current study ended (3). Additional analyses can determine whether this recent ecological trend will result in reduced racial and ethnic disparities.
Multiple factors likely contributed to the observed disparities. Persons living in counties that are both high-poverty areas and majority Black, Hispanic, or American Indian or Alaska Native are less likely to have access to COVID-19 treatment facilities. § § § § Limited access to treatment is particularly detrimental when patients need timely services, as is required for COVID-19 medications that must be initiated soon after symptom onset (5 days for oral antivirals, 7 days for mAbs and Veklury, as authorized by EUAs). In addition, minority patients' previous negative experiences with health care services could influence their decisions regarding use of treatments (4), or racism and implicit biases among health care providers might have contributed to treatment disparities (5). Race and ethnicity also could be proxies for other barriers, such as limited knowledge of treatment options, lack of internet access for telemedicine services (6), limited transportation, and language barriers (7).
Lessons learned from the COVID-19 pandemic ¶ ¶ ¶ ¶ offer opportunities to reduce outpatient treatment disparities (8), including prioritizing medication distribution to and raising awareness about treatment options among local health care providers and members of disproportionately affected communities. Communication campaigns, especially those that use trusted messengers, have been effective in reaching racial and ethnic minority populations and might facilitate increased awareness and use of COVID-19 treatments (9). Several initiatives have been implemented at the federal and state levels to improve equitable dispensing of COVID-19 medications (3). One example is the federal Test-to-Treat initiative that provides COVID-19 testing, medical evaluation, and treatment at a single location and was expanded in May 2022 to better reach vulnerable communities.***** The findings in this report are subject to at least six limitations. First, the aggregate data structure did not allow for adjustment of demographic or clinical factors that might be correlated with race and ethnicity or for assessment of combined race and ethnicity over time. Second, this study assessed treatment disparities among COVID-19 patients who sought medical care; the percentage treated and magnitude of disparities among COVID-19 patients who are eligible for treatment or among all persons with COVID-19 is unknown. Third, patients treated with oral antiviral medications at community treatment programs (e.g., Test-to-Treat) were not captured in this study; thus, actual disparities could be lower than those reported if community treatment programs were differentially used by racial and ethnic minority groups. Fourth, the reasons for nontreatment (e.g., too long since symptom onset, not at risk for severe illness, treatment not offered, or § § § § h t t p s : / / w w w. k f f . o r g / c o r o n a v i r u s -c o v i d -1 9 / i s s u e -b r i e f / how-equitable-is-access-to-covid-19-treatments ¶ ¶ ¶ ¶ https://www.cdc.gov/vaccines/covid-19/downloads/guide-communitypartners.pdf ***** https://aspr.hhs.gov/TestToTreat/Pages/default.aspx treatment refused) are unknown. Fifth, small sample sizes for some race and immunocompromised patient groups led to unstable estimates. Finally, PCORnet data are derived from a convenience sample of health care facilities and captured approximately 2% of COVID-19 patients reported to CDC during January-July 2022; thus, the results might not be nationally generalizable.
Early access to effective COVID-19 treatments and staying up to date with COVID-19 vaccination, including use of updated bivalent boosters, † † † † † are critical components of the public health response to the pandemic, especially for protecting persons most at risk for severe illness (10). Racial and ethnic disparities persist in outpatient COVID-19 treatment, even among older adults and patients with immunocompromise. Expansion of programs focused on equitable outpatient COVID-19 treatment, including raising patient awareness using trusted sources, educating clinicians and other prescribers, and expanding patient access to prescribers, can facilitate equitable health outcomes.