Results of a test-negative case-control study found that the mRNA-based COVID-19 vaccines were highly effective at preventing symptomatic SARS-CoV-2 infection among health care workers. These findings were published in The New England Journal of Medicine.

Health care personnel (N=109,865) were recruited at 33 sites in 25 states across the United States between December 2020 and May 2021. Of 4931 patients included in the final analysis, 1482 (cases) were positive for SARS-CoV-2 infection on polymerase chain reaction and antibody testing and 3449 (controls) were negative for SARS-CoV-2 infection. The rate of positive PCR or antibody tests were assessed among subgroups of patients and on the basis of vaccination status.

Among patients included in the study, 69% were employed at acute care hospitals, 31% were employed at outpatient or specialty clinics, 1% were employed at urgent care clinics, and 1% were employed at long-term care facilities. A total of 7.6% of patients tested positive for SARS-CoV-2 infection during the study period. Among patients with a positive test, 1485 had at least 1 COVID-19-related symptoms.

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Of patients in both the positive and negative infection groups, the median ages were 37 (range, 18-69) and 37 (range, 18-78) years, 82% and 83% were women, and 66% and 73% were White, respectively.

Overall, the researchers found that patients in the negative infection group were more likely to have been vaccinated against SARS-CoV-2 infection compared with those in the positive infection group: 74% of patients in the negative group had received at least vaccine dose vs 45% of those in the positive group. Of vaccinated patients in both the positive and negative infection groups, 78% and 79% received the BNT162b2 vaccine; 21% and 20% received the mRNA-1273 vaccine; 8 and 28 received the Ad26.COV2.S vaccine; and 2 and 1 received the ChAdOx1 vaccine, respectively.

Symptomatic breakthrough infections were detected among 167 fully vaccinated and 140 partially vaccinated patients. In regard to patients in the positive infection group, the researchers noted that the risk for hospitalization and severe symptoms was increased among those who were unvaccinated vs those who were either fully or partially vaccinated.

The adjusted effectiveness of partial vaccination was 79.7% for any vaccine (95% CI, 74.1-84.1), 77.6% for the BNT162b2 vaccine (95% CI, 70.9-82.7), and 88.9% for the mRNA-1273 vaccine (95% CI, 78.7-94.2). Of note, the adjusted effectiveness of any vaccine increased to 90.4% (95% CI, 87.0-92.9) after full vaccination.

After stratification by subgroups, the researchers found that the effectiveness of full vaccination was decreased among patients with diabetes (80.2%; 95% CI, 45.8-92.7). In addition, the effectiveness of both partial and full vaccination was decreased among patients who were immunocompromised (39.1%; 95% CI, -45.0 to 74.4) and those who were pregnant (77.1%; 95% CI, 32.2-92.2).

Among patients with underlying conditions, full vaccination was found to be highly effective among those with hypertension (91.8%; 95% CI, 83.9-95.8) and those without COVID-19 risk factors (91.1%; 95% CI, 85.5-94.6).

This study may have been limited by its lack of a standardized protocol for SARS-CoV-2 infection testing and its short follow-up duration.

These findings, the researchers noted, “sh

owed that vaccination with either the BNT162b2 or mRNA-1273 vaccine was highly effective in preventing symptomatic COVID-19, a finding that is consistent with the results of phase 3 trials.” In addition, “the long-term duration of protection and the effectiveness of these vaccines against emerging [SARS-CoV-2] variants is unknown and should be monitored to indicate whether changes to vaccine composition or vaccine policy are needed,” the researchers concluded.

Disclosure: Some author(s) declared affiliations with industry. Please see the original reference for a full list of disclosures.


Pilishvili T, Gierke R, Fleming-Dutra KE, et al. Effectiveness of mRNA Covid-19 vaccine among U.S. health care personnel. N Engl J Med. 2021;NEJMoa2106599. doi:10.1056/NEJMoa2106599