Factors Associated With Severe Outcomes Among Immunocompromised Adults Hospitalized for COVID-19

COVID-NET, 10 States, March 2020-February 2022

Jason Robert C. Singson, MPH; Pam Daily Kirley, MPH; Huong Pham, MPH; Gretchen Rothrock, MPH; Isaac Armistead, MD; James Meek, MPH; Evan J. Anderson, MD; Libby Reeg, MPH; Ruth Lynfield, MD; Susan Ropp, PhD; Alison Muse, MPH; Christina B. Felsen, MPH; Melissa Sutton, MD; H. Keipp Talbot, MD; Fiona P. Havers, MD; Christopher A. Taylor, PhD; Arthur Reingold, MD; Shua J. Chai, MD

Disclosures

Morbidity and Mortality Weekly Report. 2022;71(27):878-884. 

In This Article

Abstract and Introduction

Introduction

Immunocompromised persons are at increased risk for severe COVID-19–related outcomes, including intensive care unit (ICU) admission and death.[1] Data on adults aged ≥18 years hospitalized with laboratory-confirmed COVID-19 from 10 U.S. states in the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET) were analyzed to assess associations between immunocompromise and ICU admission and in-hospital death during March 1, 2020–February 28, 2022. Associations of COVID-19 vaccination status with ICU admission and in-hospital death were also examined during March 1, 2021–February 28, 2022. During March 1, 2020–February 28, 2022, among a sample of 22,345 adults hospitalized for COVID-19, 12.2% were immunocompromised. Among unvaccinated patients, those with immunocompromise had higher odds of ICU admission (adjusted odds ratio [aOR] = 1.26; 95% CI = 1.08–1.49) and in-hospital death (aOR = 1.34; 95% CI = 1.05–1.70) than did nonimmunocompromised patients. Among vaccinated patients,* those with immunocompromise had higher odds of ICU admission (aOR = 1.40; 95% CI = 1.01–1.92) and in-hospital death (aOR = 1.87; 95% CI = 1.28–2.75) than did nonimmunocompromised patients. During March 1, 2021–February 28, 2022, among nonimmunocompromised patients, patients who were vaccinated had lower odds of death (aOR = 0.58; 95% CI = 0.39–0.86) than did unvaccinated patients; among immunocompromised patients, odds of death between vaccinated and unvaccinated patients did not differ. Immunocompromised persons need additional protection from COVID-19 and using multiple known COVID-19 prevention strategies, including nonpharmaceutical interventions, up-to-date vaccination of immunocompromised persons and their close contacts,§ early testing, and COVID-19 prophylactic (Evusheld) and early antiviral treatment, can help prevent hospitalization and subsequent severe COVID-19 outcomes among immunocompromised persons.

COVID-NET is a CDC-funded collaboration for population-based surveillance of laboratory-confirmed COVID-19–associated hospitalization in 99 U.S. counties in 14 states. A COVID-NET case is defined as a positive real-time reverse transcription–polymerase chain reaction or rapid antigen test result for SARS-CoV-2 (the virus that causes COVID-19) within 14 days before or during hospitalization in a person who lived in the surveillance catchment area. Medical chart abstraction and representative sampling methods have been described previously.[2] Data collected on sampled adults hospitalized during March 1, 2020–February 28, 2022, across 10 participating states** were examined. Patients whose hospitalization was not likely related to COVID-19†† and those without a completed chart review were excluded. Immunocompromised patients were defined as those having one or more predefined immunocompromising conditions.§§ COVID-19 vaccination definitions for immunocompromised persons changed during the study period¶¶; in this analysis, a vaccinated patient was defined as one who had received both doses of a 2-dose COVID-19 vaccination series or 1 dose of a single-dose COVID-19 vaccine with or without additional or booster doses ≥14 days before their positive SARS-CoV-2 test result, per state immunization information system records. Vaccinated patients with additional or booster doses were not analyzed separately. Patients were considered unvaccinated if no COVID-19 vaccination was recorded before the positive test result; patients who were documented to have received only the first dose of a 2-dose series or their last vaccination series dose <14 days before receiving a positive SARS-CoV-2 test result were excluded.

Demographic and clinical characteristics of hospitalized patients were assessed; Pearson's chi-square tests were used to compare differences between immunocompromised and nonimmunocompromised patients. Bivariate and multivariable logistic regression analyses were used to assess associations between immunocompromise and both ICU admission and in-hospital death among vaccinated and unvaccinated patients in separate models. Associations between each individual immunocompromising condition and death were assessed using multivariable analyses, adjusting only for age and sex to improve model convergence. Bivariate and multivariable analyses were used to assess the association between vaccination status and both ICU admission and in-hospital death among immunocompromised and nonimmunocompromised patients in separate models, using data beginning March 1, 2021, when immunocompromised patients first reported receiving vaccine doses, through February 28, 2022. Multivariable analyses were adjusted for age, sex, site (entered as a fixed effect), SARS-CoV-2 variant–predominant period,*** and other factors with documented or potential association and a p-value <0.10 in bivariate analyses. Statistical analyses used SAS (version 9.4; SAS Institute) survey procedures to account for sampling weights, with statistical significance set at alpha = 0.05. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.†††

During March 1, 2020–February 28, 2022, a representative sample of 24,625 (11.0%, unweighted) of 223,069 COVID-NET cases had complete chart review, including 22,345§§§ (90.7%, unweighted) that met inclusion criteria. Among the 22,345 patients included, 12.2% were immunocompromised, including 11.1%, 10.9%, and 17.3% of patients hospitalized during the pre-Delta, Delta, and Omicron variant–predominant periods, respectively. Overall, immunocompromised patients were more likely to be older and to be non-Hispanic White (Table 1). Compared with nonimmunocompromised patients, those with immunocompromise had a statistically significantly higher prevalence of all underlying medical conditions except diabetes and neurologic disease.

Among unvaccinated patients, those who were immunocompromised had higher odds of ICU admission (aOR = 1.26) and death (aOR = 1.34) than did nonimmunocompromised patients¶¶¶ (Table 2). Similarly, among vaccinated patients, those who were immunocompromised also had higher odds of ICU admission (aOR = 1.40) and in-hospital death (aOR = 1.87) compared with nonimmunocompromised patients.**** Among patients with a specific immunocompromising condition compared with patients without that condition (irrespective of immunocompromise status), the odds of in-hospital death were higher for those with AIDS or low CD4+ count (aOR = 2.03), immunosuppressive therapy use (aOR = 1.65), multiple myeloma (aOR = 5.28), or solid organ transplant (aOR = 2.12) and lower for patients with immunoglobulin deficiency (aOR = 0.16) (Supplementary Table 1, https://stacks.cdc.gov/view/cdc/118606).

Among immunocompromised patients, those who were vaccinated did not have statistically significantly different odds of ICU admission or in-hospital death†††† compared with unvaccinated patients (Table 3). Among nonimmunocompromised patients, those who were vaccinated had lower odds of death (aOR = 0.58) than did unvaccinated patients.§§§§

During the pre-Delta and Delta variant–predominant periods, immunocompromised patients generally had higher odds of death, irrespective of vaccination status compared with nonimmunocompromised patients, and nonimmunocompromised patients who were vaccinated had lower odds of death compared with unvaccinated patients (Supplementary Table 2, https://stacks.cdc.gov/view/cdc/118607). However, in the Omicron variant–predominant period, odds of death, irrespective of immunocompromise or vaccination status, were not statistically significantly different.

*Vaccinated patients were defined as those with a positive SARS-CoV-2 test result from a specimen collected ≥14 days after either the second dose of a 2-dose vaccination series or after 1 dose of a single-dose vaccine. When not otherwise specified, vaccinated patients include those who might have received additional or booster doses. Vaccinated patients without additional or booster doses include both those eligible and those not yet eligible for an additional or booster dose. Vaccinated patients with additional booster doses received additional or booster doses on or after August 13, 2021, with a positive SARS-CoV-2 test result from a specimen collected ≥14 days after receipt of additional or booster doses.
https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html
§ https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html
https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html; https://www.covid19treatmentguidelines.nih.gov/overview/prioritization-of-therapeutics/
**California, Colorado, Connecticut, Georgia, Michigan, Minnesota, New Mexico, New York, Oregon, and Tennessee. Data from four other states in COVID-NET were not available for this analysis.
††Excluded admissions for labor/obstetrics, trauma, psychiatric conditions, or inpatient surgery.
§§Standardized COVID-NET medical chart abstraction identified the following immunocompromising conditions: AIDS or CD4+ count <200, complement deficiency, graft versus host disease, HIV infection, immunoglobulin deficiency/immunodeficiency, immunosuppressive therapy (within 12 months before admission), leukemia, Hodgkin or non-Hodgkin lymphoma, metastatic cancer, multiple myeloma, solid organ malignancy, steroid therapy (within 2 weeks of admission), and transplant history involving hematopoietic stem cells or solid organs.
¶¶ https://www.cdc.gov/media/releases/2021/s0813-additional-mRNA-mrna-dose.html
***Pre-Delta variant–predominant period = March 1, 2020–June 26, 2021; Delta variant–predominant period = June 27–December 18, 2021; Omicron variant–predominant period = December 19, 2021–February 28, 2022. https://www.cdc.gov/mmwr/volumes/71/wr/mm7116e1.htm
†††45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.
§§§ A total of 2,280 patients were excluded: 80 (3.5%) had incomplete chart review, 107 (4.7%) had missing discharge date, 1,441 (63.2%) had a non–COVID-19 related admission (labor/obstetrics [15], inpatient surgery [376], psychiatric condition [509], and trauma [541]), and 652 (28.6%) whose vaccination status did not meet the study's vaccinated or unvaccinated definition.
¶¶¶ICU admission among unvaccinated patients was adjusted for age, sex, site, variant predominant period, race/ethnicity, hypertension, diabetes, chronic lung disease, cardiovascular disease, renal disease, and obesity. Death among unvaccinated patients was adjusted for age, sex, site, variant predominant period, race/ethnicity, long-term care facility, hypertension, diabetes, chronic lung disease, cardiovascular disease, renal disease, blood disorders, neurologic disease, and rheumatologic/autoimmune condition.
****ICU admission among vaccinated patients was adjusted for age, sex, site, variant predominant period, race/ethnicity (American Indian or Alaska Native and Asian or Pacific Islander were reclassified to other/unknown because of small numbers), chronic metabolic disease, liver disease, and rheumatologic/autoimmune condition. Death among vaccinated patients was adjusted for age, sex, site, variant predominant period, race/ethnicity, cardiovascular disease, renal disease, and rheumatologic/autoimmune condition.
††††ICU admission among immunocompromised patients was adjusted for age, sex, site, variant predominant period, rheumatologic/autoimmune condition, and obesity. Death among immunocompromised patients was adjusted for age, sex, site, variant predominant period, hypertension, renal disease, and rheumatologic/autoimmune condition.
§§§§Death among nonimmunocompromised patients was adjusted for age, sex, site, variant predominant period, hypertension, diabetes mellitus, chronic metabolic disease, cardiovascular disease, renal disease, and neurologic disease.

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