Resurgence of COVID-19 Infection in a Large Highly Vaccinated U.S. Health System Workforce

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In a letter to the editor in The New England Journal of Medicine, Jocelyn Keehner, MD, of the University of California San Diego Health (UCSDH), and colleagues describe a marked resurgence of COVID-19 infections among fully vaccinated workers in the UCSDH workforce in July 2021.1 The resurgence appears to be driven by the confluence of emergence of the SARS–CoV-2 delta variant, the ending of California’s mask mandate, and waning immunity after completed vaccination.

Study Details

The study involved data from the UCSDH workforce, which comprised between 18,964 and 19,035 health workers from March through July 2021. Vaccination with mRNA vaccines began in mid-December 2020. In 2021, the percentage of fully vaccinated workers was 76.3% in March (6,608 with Moderna mRNA-1273 and 7,862 with Pfizer–BioNTech BNT162b2); 81.7% in April (7,005 and 8,505); 85.0% in May (7,340 and 8,817); 86.3% in June (7,451 and 8,975); and 86.7% in July (7,464 and 9,028). Numbers of unvaccinated workers were 3,230, 2,509, 2,187, 2,059, and 1,895 in the corresponding months.

In the UCSDH health system, SARS–CoV-2 testing is triggered by the presence of at least one symptom during daily screening or by an identified exposure regardless of vaccination status.

Infection Rates

The numbers of symptomatic COVID-19 infections among fully vaccinated vs unvaccinated workers were 3 vs 11 in March (21.4% of cases in vaccinated workers); 4 vs 17 in April (19.0%); 3 vs 10 in May (23.1%); and 5 vs 10 in June (33.3%). California’s mask mandate ended on June 15, although an increasing dominance of the delta variant was observed; the variant first emerged in mid-April and by the end of July, it accounted for more than 95% of UCSDH isolates. Concurrent with these factors, the number of cases in July increased to 94 among fully vaccinated workers and 31 among unvaccinated workers, with cases in vaccinated workers accounting for 75.2% of all cases.

“Our findings underline the importance of rapidly reinstating nonpharmaceutical interventions … in addition to continued efforts to increase vaccinations … during the spread of this formidable variant.”
— Jocelyn Keehner, MD

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Attack rates per 1,000 population among fully vaccinated vs unvaccinated workers were 0.21 (95% confidence interval [CI] = 0.21–0.47) vs 3.4 (95% CI = 2.1–5.9) in March; 0.26 (95% CI = 0.26–0.50) vs 6.8 (95% CI = 4.5–10.6) in April; 0.19 (95% CI = 0.21–0.40) vs 4.6 (95% CI = 2.6–8.2) in May; 0.30 (95% CI = 0.31–0.53) vs 4.9 (95% CI = 2.9–8.7) in June; and 5.7 (95% CI = 5.4–6.2) vs 16.4 (95% CI = 11.8–22.9) in July.

Analysis of cases in July according to the month of completion of the vaccination series showed attack rates per 1,000 population of 6.7 (95% CI = 5.9–7.8) in workers completing vaccination in January or February, compared with 3.7 (95% CI = 2.5–5.7) among those completing vaccination in March through May. As noted, the attack rate in July was 16.4 (95% CI = 11.8–22.9) per 1,000 among unvaccinated workers.

Overall, during the 5 months, 227 workers tested positive for SARS–CoV-2, including 130 (57.3%) who were fully vaccinated. Symptoms were present in 109 of the 130 (83.3%) fully vaccinated workers and in 80 of the 90 (88.9%) unvaccinated workers; the remaining 7 workers were only partially vaccinated. One unvaccinated worker was hospitalized for infection. No deaths were reported.

Vaccine Effectiveness

Vaccine effectiveness was calculated for each month, with the case definition being a positive polymerase chain reaction test and one or more symptoms among workers with no previous COVID-19 infection. Vaccine efficacy rates were 93.9% (95% confidence interval [CI] = 78.2%–97.9%) in March, 96.2% (95% CI = 88.7%–98.3%) in April, 95.9% (95% CI =85.3%–98.9%) in May, and 94.3% (83.7%–98.0%) in June, dropping to 65.5% (95% CI = 48.9%–76.9%) in July.


  • Compared with 3 to 5 cases of symptomatic infection per month from March through June 2021 among fully vaccinated workers, 94 occurred in July.
  • Vaccine effectiveness was estimated to decrease from ≥ 94% in March through June to 65.5% in July, with infection rates in July being higher among those with earlier vs later completion of vaccination.

The investigators stated: “The dramatic change in vaccine effectiveness from June to July is likely to be due to both the emergence of the delta variant and waning immunity over time, compounded by the end of masking requirements in California and the resulting greater risk of exposure in the community. Our findings underline the importance of rapidly reinstating nonpharmaceutical interventions, such as indoor masking and intensive testing strategies, in addition to continued efforts to increase vaccinations, as strategies to prevent avoidable illness and deaths and to avoid mass disruptions to society during the spread of this formidable variant. Furthermore, if our findings on waning immunity are verified in other settings, booster doses may be indicated.” 

DISCLOSURE: Dr. Keehner reported no conflicts of interest.


1. Keehner J, Horton LE, Binkin NJ, et al: Resurgence of SARS-CoV-2 infection in a highly vaccinated health system workforce. N Engl J Med. September 1, 2021 (early release online).