Abstract
Background
While a 3-dose mRNA-1273 primary series is recommended for moderately or severely immunocompromised (IC) individuals in the U.S., some IC individuals do not complete the 3-dose series. We conducted a matched cohort study to evaluate the relative vaccine effectiveness (rVE) of the 3-dose mRNA-1273 primary series vs. 2 doses of mRNA-1273 in preventing SARS-CoV-2 infection and severe COVID-19 disease in IC individuals.
Methods
IC individuals aged ≥18 years with ≥12 months of Kaiser Permanente Southern California membership who received 3 doses of mRNA-1273 ≥24 days apart were 1:1 matched with randomly selected IC 2-dose recipients on age, sex, race/ethnicity, and 2nd dose date. Third doses were accrued from 08/12/2021 to 12/31/2021, with follow-up through 1/31/2022, spanning the delta and omicron periods. Outcomes were SARS-CoV-2 infection (positive molecular test or diagnosis code), COVID-19 hospitalization, and COVID-19 hospital death. Adjusted hazard ratios (aHR) with confidence intervals (CI) were estimated by Cox proportional hazards models. Adjusted rVE (%) was calculated as (1-aHR) x 100.
Results
Our study included 21,942 3-dose and 21,942 2-dose mRNA-1273 IC recipients. Adjusted rVE of 3 doses compared to 2 doses of mRNA-1273 against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death were 55.0% (95% CI: 50.8–58.9%), 83.0% (75.4–88.3%), and 87.1% (30.6–97.6%), respectively (Table 1). Adjusted rVE against SARS-CoV-2 infection ranged from 43.0% to 59.1% across subgroups of age, sex, race/ethnicity, history of SARS-CoV-2 infection, pregnancy, and comorbidities (Table 2). Point estimates of the 3-dose rVE were higher against COVID-19 infection and hospitalization in the first 3 months, compared to 3–6 months after the 3rd dose (Table 3).
Table 1.
Incidence rate and relative vaccine effectiveness of the mRNA-1273 3-dose primary series in preventing SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death among immunocompromised population, with 2-dose vaccinated comparison
a-Adjusted for covariates age, sex, race/ethnicity, index date (in months), time between second dose and index date, number of outpatient and virtual visits, preventive care, Charlson comorbidity score, and immunocompromising sub-conditions*.
b-Adjusted for covariates age, sex, index date (in months), time between second dose and index date, and immunocompromising sub-conditions* (except HIV/AIDS).
*Leukemia, lymphoma, congenital immunodeficiencies, asplenia/hyposplenia, HIV/AIDS, transplant (hematopoietic stem cell and solid organ), and/or receipt of immunosuppressive medications.
Table 2.
Incidence rate and relative vaccine effectiveness of the mRNA-1273 3-dose primary series in preventing SARS-CoV-2 infection by subgroups among immunocompromised population, with 2-dose vaccinated comparison
a-Adjusted for covariates age, sex, race/ethnicity, index date (in months), time between second dose and index date, number of outpatient and virtual visits, preventive care, Charlson comorbidity score, and immunocompromising sub-conditions (leukemia, lymphoma, congenital immunodeficiencies, asplenia/hyposplenia, HIV/AIDS, transplant [hematopoietic stem cell and solid organ], and/or receipt of immunosuppressive medications).
Table 3.
Incidence rate and relative vaccine effectiveness of the mRNA-1273 3-dose primary series in preventing SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death by month after index date among immunocompromised population, with 2-dose vaccinated comparison
a-Adjusted for covariates age, sex, race/ethnicity, index date (in months), time between second dose and index date, number of outpatient and virtual visits, preventive care, Charlson comorbidity score, and immunocompromising sub-conditions*
b-Adjusted for covariates age, sex, index date (in months), preventive care, Charlson comorbidity score, and immunocompromising sub-conditions*
c-Adjusted for covariates age, sex, index date (in months), time between second dose and index date, and immunocompromising sub-conditions* (except HIV/AIDS)
Vaccine effectiveness (%) was calculated as (1 – hazard ratio) × 100 when the hazard ratio was less than or equal to 1; vaccine effectiveness (%) was calculated as ([1/hazard ratio] – 1) × 100 when the hazard ratio was greater than 1.
*Leukemia, lymphoma, congenital immunodeficiencies, asplenia/hyposplenia, HIV/AIDS, transplant (hematopoietic stem cell and solid organ), and/or receipt of immunosuppressive medications
Conclusion
Three doses of mRNA-1273 provide additional protection against SARS-CoV-2 infection and severe outcomes for IC individuals, compared to 2 doses, highlighting the importance of completing 3-doses for IC populations. However, possible waning of protection against SARS-CoV-2 infection and severe outcomes after 3 months supports the ACIP recommendation of a booster dose at least 3 months after the 3rd primary series dose for adequate protection of IC individuals.
Disclosures
Jennifer H. Ku, PhD MPH, GSK: Grant/Research Support|Moderna: Grant/Research Support Lina S. Sy, MPH, Dynavax: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Seqirus: Grant/Research Support Lei Qian, PhD, Dynavax: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support Bradley Ackerson, MD, Dynavax: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Seqirus: Grant/Research Support Yi Luo, PhD, Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Seqirus: Grant/Research Support Julia Tubert, MPH, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Gina Lee, MPH, Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support Ana Florea, PhD MPH, Gilead: Grant/Research Support|GSK: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Carla Talarico, PhD, Moderna: Employee of and a shareholder in Moderna Inc. Sijia Qiu, MS, Dynavax: Grant/Research Support|Moderna: Grant/Research Support Yun Tian, MS, Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support Hung Fu Tseng, PhD MPH, GSK: Grant/Research Support|Janssen: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Seqirus: Grant/Research Support.