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

Abbreviations: ICD-9 = International Classification of Diseases, Ninth Revision; ICD-10 = International Classification of Diseases, Tenth Revision; ICU = intensive care unit; SMD = standardized mean or proportion difference.
*Hospitalizations with a discharge code consistent with COVID-19–like illness were included, such as acute respiratory illness (e.g., COVID-19, respiratory failure, or pneumonia) or related signs or symptoms (cough, fever, dyspnea, vomiting, or diarrhea), using diagnosis codes from ICD-9 and ICD-10. Clinician-ordered molecular assays (e.g., real-time reverse transcription–polymerase chain reaction test) for SARS-CoV-2 occurring ≤14 days before to <72 hours after hospital admission were included.
^†Partners contributing data on hospitalizations were in California (range of earliest to latest hospitalization: March 1–September 5), Colorado (January 22–August 31), Indiana (January 22–September 5), Minnesota and Wisconsin (January 17–August 18), New York (January 22–September 5), Oregon and Washington (February 1–August 20), and Utah (February 1–September 5).
^§Immunocompromised status was presumed based on the presence of at least one discharge diagnosis, using ICD-9 and ICD-10 diagnosis codes for solid malignancy (ICD-10 codes: C00–C80, C7A, C7B, D3A, Z51.0, and Z51.1), hematologic malignancy (ICD-10 codes: C81–C86, C88, C90–C96, D46, D61.0, D70.0, D61.2, D61.9, and D71), rheumatologic or inflammatory disorder (ICD-10 codes: D86, E85 [except E85.0], G35, J67.9, L40.54, L40.59, L93.0, L93.2, L94, M05–M08, M30, M31.3, M31.5, M32–M34, M35.3, M35.8, M35.9, M46, and T78.40), other intrinsic immune condition or immunodeficiency (ICD-10 codes: D27.9, D61.09, D72.89, D80, D81 [except D81.3], D82–D84, D89 [except D89.2], K70.3, K70.4, K72, K74.3–K74.6 [except K74.60 and K74.69], N04, and R18), or organ or stem cell transplant (ICD-10 codes: T86 [except T86.82–T86.84, T86.89, and T86.9], D47.Z1, Z48.2, Z94, and Z98.85).
^¶Vaccination was defined as having received exactly 2 doses of an mRNA-based COVID-19 vaccine ≥14 days before the hospitalization 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 hospitalization or the hospitalization date if testing only occurred after the admission.
**An absolute standardized mean or proportion difference ≥0.10 indicates a nonnegligible difference in variable distributions between hospitalizations for vaccinated versus unvaccinated patients.
^††An absolute standardized mean or proportion difference ≥0.10 indicates a nonnegligible difference in variable distributions between hospitalizations for SARS-CoV-2–positive versus SARS-CoV-2–negative patients.
^§§Indicates the reference group used for standardized mean or proportion difference calculations for dichotomous variables.
^¶¶Chronic respiratory condition was defined as the presence of discharge code for asthma, chronic obstructive pulmonary disease, or other lung disease using diagnosis codes from ICD-9 and ICD-10.

Abbreviations: CI = confidence interval; ICD-9 = International Classification of Diseases, Ninth Revision; ICD-10 = International Classification of Diseases, Tenth Revision; Ref = referent group; VE = vaccine effectiveness.
*VE was estimated using a test-negative design, adjusted for age, geographic region, calendar time (days since January 1, 2021), and local virus circulation (percentage of SARS-CoV-2–positive results from testing within the counties surrounding the facility on the date of the hospitalization) and weighted for inverse propensity to be vaccinated or unvaccinated (calculated separately for each VE estimate) using sociodemographic characteristics, underlying medical conditions, known previous SARS-CoV-2 infection, and hospital characteristics, in addition to age, geographic region, calendar time, and local virus circulation.
^†Hospitalizations with a discharge code consistent with COVID-19–like illness were included, such as acute respiratory illness (e.g., COVID-19, respiratory failure, or pneumonia) or related signs or symptoms (cough, fever, dyspnea, vomiting, or diarrhea), using diagnosis codes from ICD-9 and ICD-10. Clinician-ordered molecular assays (e.g., real-time reverse transcription–polymerase chain reaction test) for SARS-CoV-2 occurring ≤14 days before to <72 hours after hospital admission were included.
^§Partners contributing data on hospitalizations were in California (range of earliest to latest hospitalization: March 1–September 5), Colorado (January 22–August 31), Indiana (January 22–September 5), Minnesota and Wisconsin (January 17–August 18), New York (January 22–September 5), Oregon and Washington (February 1–August 20), and Utah (February 1–September 5).
^¶VE was calculated as [1–odds ratio]x100%.
**Vaccination was defined as having received exactly 2 doses of an mRNA-based COVID-19 vaccine ≥14 days before the hospitalization 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 hospitalization or the hospitalization date if testing only occurred after the admission.
^††Immunocompromised status was presumed based on the presence of at least one discharge diagnosis, using ICD-9 and ICD-10 diagnosis codes for solid malignancy (ICD-10 codes: C00–C80, C7A, C7B, D3A, Z51.0, and Z51.1), hematologic malignancy (ICD-10 codes: C81–C86, C88, C90–C96, D46, D61.0, D70.0, D61.2, D61.9, and D71), rheumatologic or inflammatory disorder (ICD-10 codes: D86, E85 [except E85.0], G35, J67.9, L40.54, L40.59, L93.0, L93.2, L94, M05–M08, M30, M31.3, M31.5, M32–M34, M35.3, M35.8, M35.9, M46, and T78.40), other intrinsic immune condition or immunodeficiency (ICD-10 codes: D27.9, D61.09, D72.89, D80, D81 [except D81.3], D82–D84, D89 [except D89.2], K70.3, K70.4, K72, K74.3–K74.6 [except K74.60 and K74.69], N04, and R18), or organ or stem cell transplant (ICD-10 codes: T86 [except T86.82–T86.84, T86.89, and T86.9], D47.Z1, Z48.2, Z94, and Z98.85).

Abbreviations: CI = confidence interval; ICD-9 = International Classification of Diseases, Ninth Revision; ICD-10 = International Classification of Diseases, Tenth Revision; Ref = referent group; VE = vaccine effectiveness.
*VE was estimated using a test-negative design, adjusted for age, geographic region, calendar time (days since January 1, 2021), and local virus circulation (percentage of SARS-CoV-2–positive results from testing within the counties surrounding the facility on the date of the hospitalization) and weighted for inverse propensity to be vaccinated or unvaccinated (calculated separately for each VE estimate) using sociodemographic characteristics, underlying medical conditions, known previous SARS-CoV-2 infection, and hospital characteristics, in addition to age, geographic region, calendar time, and local virus circulation.
^†Hospitalizations with a discharge code consistent with COVID-19–like illness were included, such as acute respiratory illness (e.g., COVID-19, respiratory failure, or pneumonia) or related signs or symptoms (cough, fever, dyspnea, vomiting, or diarrhea), using diagnosis codes from ICD-9 and ICD-10. Clinician-ordered molecular assays (e.g., real-time reverse transcription–polymerase chain reaction test) for SARS-CoV-2 occurring ≤14 days before to <72 hours after hospital admission were included.
^§Immunocompromising condition subgroups were not mutually exclusive, and patients could be represented in more than one of the five subgroups (i.e., solid malignancy, hematologic malignancy, rheumatologic or inflammatory disorder, other intrinsic immune condition or immunodeficiency, and organ or stem cell transplant).
^¶Partners contributing data on hospitalizations were in California (range of earliest to latest hospitalization: March 1–September 5), Colorado (January 22–August 31), Indiana (January 22–September 5), Minnesota and Wisconsin (January 17–August 18), New York (January 22–September 5), Oregon and Washington (February 1–August 20), and Utah (February 1–September 5).
**VE was calculated as [1–odds ratio]x100%.
^††Solid malignancy was defined as the presence of at least one discharge diagnosis using ICD-9 and ICD-10 diagnosis codes. ICD-10 codes included C00–C80, C7A, C7B, D3A, Z51.0, and Z51.1.
^§§Vaccination was defined as having received exactly 2 doses of an mRNA-based COVID-19 vaccine ≥14 days before the hospitalization 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 hospitalization or the hospitalization date if testing only occurred after the admission.
^¶¶Hematologic malignancy was defined as the presence of at least one discharge diagnosis using ICD-9 and ICD-10 diagnosis codes. ICD-10 codes included C81–C86, C88, C90–C96, D46, D61.0, D70.0, D61.2, D61.9, and D71.
***Rheumatologic or inflammatory disorder was defined as the presence of at least one discharge diagnosis using ICD-9 and ICD-10 diagnosis codes. ICD-10 codes included D86, E85 (except E85.0), G35, J67.9, L40.54, L40.59, L93.0, L93.2, L94, M05–M08, M30, M31.3, M31.5, M32–M34, M35.3, M35.8, M35.9, M46, and T78.40.
^†††Other intrinsic immune condition or immunodeficiency was defined as the presence of at least one discharge diagnosis using ICD-9 and ICD-10 diagnosis codes. ICD-10 codes included D27.9, D61.09, D72.89, D80, D81 (except D81.3), D82–D84, D89 (except D89.2), K70.3, K70.4, K72, K74.3–K74.6 (except K74.60 and K74.69), N04, and R18.
^§§§Organ or stem cell transplant was defined as the presence of at least one discharge diagnosis using ICD-9 and ICD-10 diagnosis codes. ICD-10 codes included T86 (except T86.82–T86.84, T86.89, and T86.9), D47.Z1, Z48.2, Z94, and Z98.85.

Authors and Disclosures

Peter J. Embi, MD^1,2, Matthew E. Levy, PhD³, Allison L. Naleway, PhD⁴, Palak Patel, MBBS⁵, Manjusha Gaglani, MBBS⁶, Karthik Natarajan, PhD^7,8, Kristin Dascomb, MD, PhD⁹, Toan C. Ong, PhD¹⁰, Nicola P. Klein, MD, PhD¹¹, I-Chia Liao, MPH⁶, Shaun J. Grannis, MD^2,12, Jungmi Han⁷, Edward Stenehjem, MD⁹, Margaret M. Dunne, MSc³, Ned Lewis, MPH¹¹, Stephanie A. Irving, MHS⁴, Suchitra Rao, MBBS¹⁰, Charlene McEvoy, MD¹³, Catherine H. Bozio, PhD⁵, Kempapura Murthy, MBBS⁶, Brian E. Dixon, PhD^12,14, Nancy Grisel, MPP⁹, Duck-Hye Yang, PhD³, Kristin Goddard, MPH¹¹, Anupam B. Kharbanda, MD¹⁵, Sue Reynolds, PhD⁵, Chandni Raiyani, MPH⁶, William F. Fadel, PhD^12,14, Julie Arndorfer, MPH⁹, Elizabeth A. Rowley, DrPH³, Bruce Fireman, MA¹¹, Jill Ferdinands, PhD⁵, Nimish R. Valvi, DrPH¹², Sarah W. Ball, ScD³, Ousseny Zerbo, PhD¹¹, Eric P. Griggs, MPH⁵, Patrick K. Mitchell, ScD³, Rachael M. Porter, MPH⁵, Salome A. Kiduko, MPH³, Lenee Blanton, MPH⁵, Yan Zhuang, PhD³, Andrea Steffens, MPH⁵, Sarah E. Reese, PhD³, Natalie Olson, MPH⁵, Jeremiah Williams, MPH⁵, Monica Dickerson, MPH⁵, Meredith McMorrow, MD⁵, Stephanie J. Schrag, DPhil⁵, Jennifer R. Verani, MD⁵, Alicia M. Fry, MD⁵, Eduardo Azziz-Baumgartner, MD⁵, Michelle A. Barron, MD¹⁰, Mark G. Thompson, PhD⁵ and Malini B. DeSilva, MD<sup>13

1</sup>Regenstrief Institute, Indianapolis, Indiana; ²Indiana University School of Medicine, Indianapolis, Indiana; ³Westat, Rockville, Maryland; ⁴Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon; ⁵CDC COVID-19 Response Team; ⁶Baylor Scott & White Health, Texas A&M University College of Medicine, Temple, Texas; ⁷Department of Biomedical Informatics, Columbia University, New York, New York; ⁸New York Presbyterian Hospital, New York, New York; ⁹Division of Infectious Diseases and Clinical Epidemiology, Intermountain Healthcare, Salt Lake City, Utah; ¹⁰School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado; ¹¹Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, California; ¹²Center for Biomedical Informatics, Regenstrief Institute, Indianapolis, Indiana; ¹³HealthPartners Institute, Minneapolis, Minnesota; ¹⁴Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana; ¹⁵Children's Minnesota, Minneapolis, Minnesota.

Corresponding author
Peter J. Embi, pembi@regenstrief.org.

All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Allison L. Naleway reports institutional support from Pfizer outside the submitted work. Anupam B. Kharbanda reports institutional support through HealthPartners to Children's Minnesota for VISION. Charlene McEvoy reports institutional support from AstraZeneca for the AZD1222 COVID-19 vaccine trial. Jill Ferdinands reports travel support from Institute for Influenza Epidemiology, funded in part by Sanofi Pasteur. Nicola P. Klein reports institutional support from Pfizer for COVID-19 vaccine clinical trials and institutional support from Pfizer, Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Sciences (now Sanofi Pasteur) outside the submitted work. Suchitra Rao reports grant support from GlaxoSmithKline and Biofire Diagnostics. No other potential conflicts of interest were disclosed.

Sidebar

Summary

What is already known about this topic?

Studies suggest that immunocompromised persons who receive COVID-19 vaccination might not develop high neutralizing antibody titers or be as protected against severe COVID-19 outcomes as are immunocompetent persons.

What is added by this report?

Effectiveness of mRNA vaccination against laboratory-confirmed COVID-19–associated hospitalization was lower (77%) among immunocompromised adults than among immunocompetent adults (90%). Vaccine effectiveness varied considerably among immunocompromised patient subgroups.

What are the implications for public health practice?

Immunocompromised persons benefit from COVID-19 mRNA vaccination but are less protected from severe COVID-19 outcomes than are immunocompetent persons. Immunocompromised persons receiving mRNA COVID-19 vaccines should receive 3 doses and a booster, consistent with CDC recommendations, practice nonpharmaceutical interventions, and, if infected, be monitored closely and considered early for proven therapies that can prevent severe outcomes.