TABLE 2. Estimated vaccine effectiveness against hospitalization with COVID-19 after previous SARS-CoV-2 infection* — United States, June 2021–February 2022.

Variant period/Vaccination status	No. of case-patients† (N = 3,761)	No. of control-patients† (N = 7,522)	VE§ (95% CI)
			Unadjusted	Adjusted
Overall
Unvaccinated (Ref)	2,303	3,571	—	—
Any mRNA vaccine, 1 dose¶,**	161	413	41.6 (29.3–51.8)	41.9 (29.5–52.1)
Any mRNA vaccine, 2 doses¶,**	1,038	2,496	38.2 (32.2–43.7)	39.4 (33.3–45.0)
Pfizer-BioNTech¶	588	1,432	40.8 (33.1–47.5)	42.7 (35.0–49.4)
Moderna¶	450	1,064	37.1 (27.6–45.3)	38.7 (29.1–46.9)
Any mRNA vaccine, booster dose¶,**	259	1,042	66.4 (60.7–71.3)	67.0 (61.3–71.9)
Delta predominant
Unvaccinated (Ref)	950	1,468	—	—
Any mRNA vaccine, 1 dose¶	45	171	61.0 (44.7–72.5)	58.8 (41.3–71.1)
Any mRNA vaccine, 2 doses¶	415	1,209	50.7 (42.9–57.5)	47.5 (38.8–54.9)
Pfizer-BioNTech¶	234	678	52.8 (42.8–61.1)	50.0 (39.0–59.0)
Moderna¶	181	531	47.9 (35.3–58.1)	44.0 (29.9–55.2)
Any mRNA vaccine, booster dose¶	27	100	60.2 (36.4–75.0)	57.8 (32.1–73.8)
Omicron predominant
Unvaccinated (Ref)	1,353	2,103	—	—
Any mRNA vaccine, 1 dose¶	116	242	27.3 (8.14–42.5)	33.0 (15.0–47.2)
Any mRNA vaccine, 2 doses¶	623	1,287	26.9 (17.4–35.4)	34.6 (25.5–42.5)
Pfizer-BioNTech¶	354	754	29.2 (16.9–39.7)	37.3 (25.8–46.9)
Moderna¶	269	533	26.2 (10.8–39.0)	35.9 (21.7–47.4)
Any mRNA vaccine, booster dose¶	232	942	64.6 (58.1–70.2)	67.6 (61.4–72.8)
Relative VE of booster dose compared with primary series ††
Overall
≥5 months after second dose (Ref)††	697	1,536	—	—
Any mRNA vaccine, booster dose††	259	1,042	56.5 (44.6–65.9)	55.9 (43.6–65.5))

Abbreviations: NAAT = nucleic acid amplification test; Ref = referent group; VE = vaccine effectiveness.

* Initial diagnosis was based on a previous positive SARS-CoV-2 NAAT or clinical diagnosis of COVID-19 >90 days before the date of the NAAT associated with subsequent hospitalization. COVID-19 was defined as a clinical encounter with any of the following International Classification of Diseases, Tenth Revision diagnostic codes: U07.1, J12.81, or J12.82.

^† Case-patients had a positive NAAT performed 10 days before through 3 days after the date of hospitalization with a diagnosis of COVID-19-like illness; control-patients had a negative NAAT result. COVID-19–like illness diagnoses were defined based on other methods (https://www.nejm.org/doi/full/10.1056/nejmoa2110362, Supplement Table S2) and included acute respiratory illness (e.g., COVID-19, respiratory failure, or pneumonia) or related signs or symptoms (e.g., cough, fever, dyspnea, vomiting, or diarrhea) using diagnostic codes from the International Classification of Diseases, Tenth Revision. Patients were eligible for inclusion if the hospitalization-associated SARS-CoV-2 NAAT was performed during June 20, 2021–February 24, 2022.

^§ VE was calculated as [1 − odds ratio] x 100, estimated using conditional logistic regression in a test-negative design after matching by 2-week calendar period of NAAT associated with hospital admission, 10-year age group, and state of residence. Adjusted estimates accounted in addition for measured differences in sex, race/ethnicity (White non-Hispanic race: yes/no and Hispanic ethnicity: yes/no), number of clinical encounters during 2019 (0, 1–9, or ≥10), number of underlying conditions (0, 1, or >1), and days since previous infection (as a continuous variable). Underlying conditions were extracted from EHR clinical encounter data and based on a CDC list of conditions associated with the highest risk for COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html, accessed March 23, 2022), including the following diagnoses: alcoholic liver disease, autoimmune hepatitis, bronchiectasis, bronchopulmonary dysplasia, cancer, cardiomyopathy, cerebrovascular disease, chronic kidney disease, cirrhosis, chronic obstructive pulmonary disease, coronary artery disease, current smoker, administration or prescription of nontopical glucocorticoids within the previous 12 months, heart failure, HIV, immune deficiency, administration or prescription of immunosuppressive medications within the previous 12 months, interstitial lung disease, nonalcoholic fatty liver disease, obesity, pulmonary arterial hypertension, pulmonary embolus, pregnancy, solid organ transplant, tuberculosis, and type 1 or 2 diabetes.

^¶ Patients were categorized on the date of NAAT associated with hospitalization as unvaccinated if no COVID-19 vaccine had been received; after dose 1 if ≥14 days had elapsed since receipt of the first dose of an mRNA COVID-19 vaccine and before any second dose; after dose 2 if ≥14 days had elapsed since receipt of the second dose of an mRNA COVID-19 vaccine and no subsequent dose was received; and after a booster dose if ≥14 days had elapsed since receipt of an mRNA booster dose administered ≥5 months after a second dose. Patients were excluded from the analysis if they received a non-mRNA COVID-19 vaccine; the day of the NAAT-associated hospitalization was <14 days after dose 1, dose 2, or a booster dose; dose 2 was received <14 days after dose 1; any booster dose was <5 months after dose 2, they received >3 doses of vaccine, or the previous positive NAAT result or COVID-19 diagnosis was after the date of the most recent vaccine dose.

** Among persons with a previous infection, adjusted VE <90 days after dose 1 was 42.0% (95% CI = 16.8%–59.5%) and ≥90 days after dose 1 was 42.2% (95% CI = 26.0%–54.8%); adjusted VE <90 days after dose 2 was 44.6% (95% CI = 28.6%–56.9%) and ≥90 days after dose 2 was 39.3% (95% CI = 32.4%–45.4%); and adjusted VE <90 days after dose 3 was 67.9% (95% CI = 60.3%–74.0%) and ≥90 days after dose 3 was 62.4% (95% CI = 48.6%–72.5%).

^†† For estimation of relative VE after a booster dose, the referent group had received dose 2 (but not a booster dose) ≥5 months previously.