Effectiveness of 2-Dose Vaccination With mRNA COVID-19 Vaccines Against COVID-19–Associated Hospitalizations Among Immunocompromised Adults

Nine States, January-September 2021

Peter J. Embi, MD; Matthew E. Levy, PhD; Allison L. Naleway, PhD; Palak Patel, MBBS; Manjusha Gaglani, MBBS; Karthik Natarajan, PhD; Kristin Dascomb, MD, PhD; Toan C. Ong, PhD; Nicola P. Klein, MD, PhD; I-Chia Liao, MPH; Shaun J. Grannis, MD; Jungmi Han; Edward Stenehjem, MD; Margaret M. Dunne, MSc; Ned Lewis, MPH; Stephanie A. Irving, MHS; Suchitra Rao, MBBS; Charlene McEvoy, MD; Catherine H. Bozio, PhD; Kempapura Murthy, MBBS; Brian E. Dixon, PhD; Nancy Grisel, MPP; Duck-Hye Yang, PhD; Kristin Goddard, MPH; Anupam B. Kharbanda, MD; Sue Reynolds, PhD; Chandni Raiyani, MPH; William F. Fadel, PhD; Julie Arndorfer, MPH; Elizabeth A. Rowley, DrPH; Bruce Fireman, MA; Jill Ferdinands, PhD; Nimish R. Valvi, DrPH; Sarah W. Ball, ScD; Ousseny Zerbo, PhD; Eric P. Griggs, MPH; Patrick K. Mitchell, ScD; Rachael M. Porter, MPH; Salome A. Kiduko, MPH; Lenee Blanton, MPH; Yan Zhuang, PhD; Andrea Steffens, MPH; Sarah E. Reese, PhD; Natalie Olson, MPH; Jeremiah Williams, MPH; Monica Dickerson, MPH; Meredith McMorrow, MD; Stephanie J. Schrag, DPhil; Jennifer R. Verani, MD; Alicia M. Fry, MD; Eduardo Azziz-Baumgartner, MD; Michelle A. Barron, MD; Mark G. Thompson, PhD; Malini B. DeSilva, MD


Morbidity and Mortality Weekly Report. 2021;70(44):1553-1559. 

In This Article


In a multistate analysis of approximately 89,000 hospitalizations of adults with COVID-19–like illness during January 17–September 5, 2021, receipt of 2 doses of mRNA COVID-19 vaccine was effective in preventing laboratory-confirmed COVID-19 hospitalizations among patients who were immunocompromised (VE = 77%) and those who were immunocompetent (VE = 90%). Nonetheless, immunocompromised patients were significantly less protected from severe COVID-19 outcomes compared with immunocompetent patients, supporting the recommendation for administration of a third dose of mRNA vaccine to further enhance protection of moderately to severely immunocompromised persons against severe COVID-19 outcomes.[5]

This study also found that VE was lower among certain subgroups of immunocompromised adults, such as solid organ or stem cell transplant recipients, than among others. These findings are consistent with other studies suggesting that certain immunocompromised persons experience an attenuated immune response to COVID-19 vaccines and make up a large proportion of hospitalizations for infections after vaccination.[3,4] The prevalence of SARS-CoV-2 infection was approximately two times greater among unvaccinated immunocompetent patients compared with unvaccinated immunocompromised patients. Because the study sample was restricted to patients hospitalized with COVID-19–like illness, this difference might be related to a variation in the prevalence of other respiratory virus infections between the two groups, although this is unable to be confirmed. A strength of the test-negative design is that such a difference is not expected to influence the validity of VE estimates stratified by immunocompromised status.

The findings in this report are subject to at least six limitations. First, the use of selected discharge diagnoses as surrogates for presumed immunocompromised status and the absence of medication and other relevant data might have led to classification of persons as immunocompromised who were not; the opposite is also possible but is less likely. Second, selection bias might be possible if vaccination status influences the likelihood of receiving testing although a previous VISION Network study indicated that vaccination status did not affect receipt of testing.[6] Third, despite the high specificity of COVID-19 vaccination status from these data sources, misclassification might be possible. Fourth, although inverse weights balanced unvaccinated and vaccinated hospitalized patients on sociodemographic and health characteristics, and further adjustments for age, geographic region, calendar time, and local virus circulation were made, unmeasured and residual confounding (e.g., mask-wearing and waning immunity) in this observational study might have biased these estimates. Fifth, the study only assessed mRNA COVID-19 vaccines and not the Janssen vaccine and included health care systems in only nine states, limiting the potential for the findings of this study to be extrapolated. Finally, immunocompromising conditions were not mutually exclusive, and sparse data in smaller immunocompromised subgroups reduced VE precision, so it was not possible to determine the independent effect of each subgroup on VE.

Immunocompromised persons benefit from and should receive COVID-19 vaccines. Given that VE is lower compared to immunocompetent patients, immunocompromised persons receiving mRNA vaccines should receive 3 doses and a booster 6 months after the third dose, consistent with CDC recommendations.[5] In addition to vaccination, immunocompromised persons should implement nonpharmaceutical prevention strategies such as masking to help prevent SARS-CoV-2 infection, and, if infected with SARS-CoV-2, be monitored closely and considered early for proven therapies that might prevent progression to severe illness (e.g., monoclonal antibodies). Additional studies are needed to further characterize variation in VE among immunocompromised subpopulations and across geographic regions, determine the degree of improvements in VE conferred by additional COVID-19 vaccine doses in immunocompromised populations, evaluate whether different approaches to vaccine administration might improve VE (e.g., dosage timing or temporarily withholding immunosuppressants), and further evaluate possible differences in VE between vaccine products.

**45 C.F.R. part 46; 21 C.F.R. part 56.