Effectiveness of COVID-19 mRNA Vaccines Against COVID-19–Associated Hospitalizations Among Immunocompromised Adults During SARS-CoV-2 Omicron Predominance — VISION Network, 10 States, December 2021—August 2022

Persons with moderate-to-severe immunocompromising conditions might have reduced protection after COVID-19 vaccination, compared with persons without immunocompromising conditions (1-3). On August 13, 2021, the Advisory Committee on Immunization Practices (ACIP) recommended that adults with immunocompromising conditions receive an expanded primary series of 3 doses of an mRNA COVID-19 vaccine. ACIP followed with recommendations on September 23, 2021, for a fourth (booster) dose and on September 1, 2022, for a new bivalent mRNA COVID-19 vaccine booster dose, containing components of the BA.4 and BA.5 sublineages of the Omicron (B.1.1.529) variant (4). Data on vaccine effectiveness (VE) of monovalent COVID-19 vaccines among persons with immunocompromising conditions since the emergence of the Omicron variant in December 2021 are limited. In the multistate VISION Network,§ monovalent 2-, 3-, and 4-dose mRNA VE against COVID-19-related hospitalization were estimated among adults with immunocompromising conditions¶ hospitalized with COVID-19-like illness,** using a test-negative design comparing odds of previous vaccination among persons with a positive or negative molecular test result (case-patients and control-patients) for SARS-CoV-2 (the virus that causes COVID-19). During December 16, 2021-August 20, 2022, among SARS-CoV-2 test-positive case-patients, 1,815 (36.3%), 1,387 (27.7%), 1,552 (31.0%), and 251 (5.0%) received 0, 2, 3, and 4 mRNA COVID-19 vaccine doses, respectively. Among test-negative control-patients during this period, 6,928 (23.7%), 7,411 (25.4%), 12,734 (43.6%), and 2,142 (7.3%) received these respective doses. Overall, VE against COVID-19-related hospitalization among adults with immunocompromising conditions hospitalized for COVID-like illness during Omicron predominance was 36% ≥14 days after dose 2, 69% 7-89 days after dose 3, and 44% ≥90 days after dose 3. Restricting the analysis to later periods when Omicron sublineages BA.2/BA.2.12.1 and BA.4/BA.5 were predominant and 3-dose recipients were eligible to receive a fourth dose, VE was 32% ≥90 days after dose 3 and 43% ≥7 days after dose 4. Protection offered by vaccination among persons with immunocompromising conditions during Omicron predominance was moderate even after a 3-dose monovalent primary series or booster dose. Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP recommendations. Further, additional protective recommendations for persons with immunocompromising conditions, including the use of prophylactic antibody therapy, early access to and use of antivirals, and enhanced nonpharmaceutical interventions such as well-fitting masks or respirators, should also be considered.

antivirals, and enhanced nonpharmaceutical interventions such as well-fitting masks or respirators, should also be considered. VISION Network methods to assess VE have been previously described (3,5). For this analysis, among adults aged ≥18 years, eligible medical encounters were defined as hospitalizations of patients with one or more immunocompromising conditions and a COVID-19-like illness diagnosis who underwent SARS-CoV-2 molecular testing ≤14 days before to <72 hours after the encounter date. Immunocompromising conditions were identified from electronic medical records based on International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, Tenth Revision (ICD-10) discharge diagnosis codes associated with being immunocompromised (3). Vaccination status was obtained from electronic health records or immunization registries. Two-dose vaccination was defined as receipt of a second dose of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) vaccine ≥14 days before the index date; † † 3-and 4-dose vaccinations were defined as receipt of the most recent dose ≥7 days before the index date. Persons with no documented COVID-19 vaccine doses were considered unvaccinated. Encounters for persons who received a non-mRNA COVID-19 vaccine, only 1 dose, >4 doses, dose 2 <14 days before the index date, dose 3 or 4 <7 days before the index date, or who received doses before vaccine was recommended by ACIP were excluded. § § The study period began on the date when ≥50% of sequenced specimens for each study site yielded an Omicron variant based on local surveillance data (site-specific start dates ranged from December 16 to 29, 2021) and ended August 20, 2022; start and end dates for Omicron sublineage predominance periods for BA. VE ≥7 days after receipt of dose 3 varied by immunocompromising condition, ranging from 43% among persons with an organ or stem cell transplant (with or without another condition) to 70% among those with a solid malignancy only (Table 3).

Discussion
In this multistate analysis of over 34,000 hospitalizations for COVID-19-like illness among adults with immunocompromising conditions, 2 doses of monovalent mRNA COVID-19 vaccine were 36% effective against COVID-19-associated hospitalization during a period of Omicron variant predominance. VE increased to 67% with the addition of a third dose of monovalent vaccine during BA. 1  Although protection increased after receipt of a third monovalent vaccine dose (compared with 2 doses), estimated 3-dose VE was lower in this study than in other similar studies among immunocompetent persons during Omicron predominance, including recent VISION Network analyses (6,7). Consistent with previous studies restricted to persons with immunocompromising conditions, VE in this study was lower among persons with certain immunocompromising conditions that might be associated with being more severely immunocompromised, particularly solid organ or stem cell transplant recipients.
Estimated VE among persons with immunocompromising conditions during Omicron predominance was lower than VE in comparable studies during Delta variant predominance (2). Protection was also lower during Omicron BA.2/BA.2.12.1 and BA.4/BA.5 than during BA.1 predominance, although the median interval since receipt of last vaccine dose was lower during BA.1, and waning effectiveness over time might have also contributed to the lower VE observed during these later sublineage periods. In either case, these findings suggest that the newly authorized bivalent booster vaccines, which target BA.4/BA.5 might offer additional benefit to persons with immunocompromising conditions (8).
Given the moderate protection observed even after monovalent booster doses, persons with immunocompromising conditions might also benefit from other recommended protective measures including preexposure prophylaxis with the antibody treatment tixagevimab/cilgavimab (Evusheld), ¶ ¶ ¶ ¶ which was authorized in December 2021 for persons with moderate-to-severe immunocompromising conditions and was associated with a reduction in risk for both symptomatic and severe COVID-19 in clinical trials (9). However, recent in vitro data suggest protection against emerging Omicron sublineages might be reduced and additional clinical data are needed (10).
The findings in this report are subject to at least four limitations. First, immunocompromising conditions were based on discharge diagnosis codes and a range of immune suppression is associated with each code. Second, residual confounding in VE models is possible. For example, history of previous infection could not be accurately ascertained, but might have differed between vaccinated and unvaccinated persons, which could affect VE estimates. Third, data on the use of outpatient   . † Hospitalizations with a discharge code consistent with COVID-19-like illness and molecular testing for SARS-CoV-2 ≤14 days before to <72 hours after the encounter date were included. COVID-19-like illness diagnoses included acute respiratory illness (e.g., respiratory failure or pneumonia) or related signs or symptoms (cough, fever, dyspnea, vomiting, or diarrhea) using ICD-9 and ICD-10 diagnosis codes. § mRNA COVID-19 vaccination status was defined as having received the listed number of doses of an mRNA COVID-19 vaccine within the specified range of number of days before the encounter index date, which was the date of respiratory specimen collection associated with the most recent positive or negative SARS-CoV-2 test result before the hospital admission or the admission date if testing only occurred after the admission. days before the hospital admission date. † † † Chronic respiratory condition was defined by corresponding discharge codes for asthma, chronic obstructive pulmonary disease, or other lung disease using ICD-9 and ICD-10 diagnosis codes. § § § In-hospital death was defined as death while hospitalized within 28 days after admission. treatments such as nirmatelvir/ritonavir (Paxlovid) or prophylaxis with Evusheld were not available. Finally, SARS-CoV-2 genomic sequencing data were unavailable for individual encounters, and date of testing was used to assign likely sublineage ecologically.

TABLE 1. (Continued) Characteristics of hospitalizations among immunocompromised* adults aged ≥18 years with COVID-19-like illness, † by mRNA COVID-19 vaccination status and SARS-CoV-2 test result -VISION Network, 10 states, December 2021-August 2022
Persons with immunocompromising conditions have been disproportionately affected by the COVID-19 pandemic. Whereas monovalent vaccination remains moderately protective in persons with immunocompromising conditions, VE has decreased compared with that during pre-Omicron periods, most notably during recent Omicron sublineage predominance periods, despite expanded dosing recommendations. Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent boosters that target BA.4/BA.5 sublineages. In addition, other

Summary
What is already known about this topic? COVID-19 vaccine effectiveness (VE) data among immunocompromised persons during SARS-CoV-2 Omicron variant predominance are limited.
What is added by this report?
What are the implications for public health practice?
Monovalent COVID-19 vaccine protection among persons with immunocompromising conditions during Omicron predominance was moderate after a 3-dose primary series or booster dose. Persons with immunocompromising conditions might benefit from updated bivalent boosters that target circulating BA.4/BA.5 sublineages.
protective measures recommended for persons with immunocompromising conditions, including prophylactic antibody treatments, early access to and use of antivirals, and nonpharmaceutical interventions, such as the use of well-fitting masks or respirators, should also be considered. Further study of VE of updated vaccines in persons with immunocompromising conditions is warranted.