Table of Contents

To the Editor

Keehner et al.1 (Sept. 30 issue) report a resurgence of SARS-CoV-2 infections, mostly with the delta variant, in vaccinated health care workers in San Diego in July. The reduction in vaccine protection was allegedly due to emergence of the delta variant, waning immunity, and the end of masking requirements in California.

SARS-CoV-2 Infection in Vaccinated HCWs at Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (February–August, 2021).

In May 2021, vaccine protection against both symptomatic and asymptomatic infection was 83% among 3720 vaccinated health care workers at Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.2 We did not observe a subsequent increase, but rather a decrease, in the frequency of breakthrough infections (Table 1). The delta variant appeared in Italy3 in April and subsequently became predominant. In line with data from England,4 our findings show a persistent vaccine effectiveness against the delta variant. Although the levels of vaccine-elicited neutralizing antibodies were reduced against the delta variant, the effect of these antibodies was not abolished.5 The discrepancy between our data and the data from California may reside in the persistence of an indoor masking requirement, broad population testing, and high vaccination coverage in Italy by August 31 (71% coverage with one dose and 61% coverage with two doses), all of which reduce the circulation of the virus.

Daniele Lilleri, M.D.
Carlo Marena, M.D.
Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
[email protected]

Fausto Baldanti, M.D.
Università degi Studi di Pavia, Pavia, Italy

No potential conflict of interest relevant to this letter was reported.

This letter was published on December 15, 2021, at

  1. 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 2021;385:13301332.

  2. 2. Rovida F, Cassaniti I, Paolucci S, et al. SARS-CoV-2 vaccine breakthrough infections with the alpha variant are asymptomatic or mildly symptomatic among health care workers. Nat Commun 2021;12:60326032.

  3. 3. Istituto Superiore di Sanita. Prevalenza e distribuzione delle varianti di SARS-CoV-2 di interesse per la sanità pubblica in Italia. September 3, 2021 (

  4. 4. Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of Covid-19 vaccines against the B.1.617.2 (delta) variant. N Engl J Med 2021;385:585594.

  5. 5. Cassaniti I, Bergami F, Percivalle E, et al. Humoral and cell-mediated response against SARS-CoV-2 variants elicited by mRNA vaccine BNT162b2 in healthcare workers: a longitudinal observational study. Clin Microbiol Infect 2021 September 25 (Epub ahead of print).


The authors reply: Lilleri et al. report that the incidence of SARS-CoV-2 infections in Pavia Province, Italy, similar to the incidence in California, had increased during July and August 2021 because of the delta variant but that the incidence among vaccinated health care workers at Fondazione IRCCS Policlinico San Matteo had not increased. Unlike the modest surge in delta variant infections in Pavia Province, a considerable surge of infections occurred in San Diego County during this period, despite a similar vaccination rate to that in Pavia; this surge allowed for the evaluation of vaccine effectiveness in our health care workforce in the context of increased exposure in the community. We minimized biases in our data by excluding previously infected, asymptomatic, and non–messenger RNA–vaccinated health care workers from the calculations of vaccine effectiveness. Because of these differences, our study populations are not comparable. Furthermore, when we analyzed vaccine effectiveness according to time interval since completion of the primary vaccine series, we observed a decreased vaccine effectiveness among health care workers who had been vaccinated earlier. Our data suggest that a confluence of factors, including the emergence of the delta variant, the end of the indoor masking mandate, and waning vaccine effectiveness, contributed to the infections in our health care workers during this time period.

Lucy E. Horton, M.D., M.P.H.
Shira R. Abeles, M.D.
Francesca J. Torriani, M.D.
UC San Diego Health, San Diego, CA
[email protected]

Since publication of their letter, the authors report no further potential conflict of interest.

This letter was published on December 15, 2021, at

SARS-CoV-2 Infection in Vaccinated HCWs at Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (February–August, 2021).*

Variable February March April May June July August
Fully vaccinated HCWs — no. 3269 3657 3720 3720 3720 3720 3720
Vaccinated HCWs with infection — no. (%) 5 (0.15) 14 (0.38) 14 (0.38) 1 (0.03) 1 (0.03) 4 (0.11) 0
SARS-CoV-2 variant among vaccinated HCWs with infection — no.
Alpha 1 8 13 1 0 0 0
Delta 0 0 0 0 0 3 0
Could not be determined 4 6 1 0 1 1 0
SARS-CoV-2 variant among infected persons in Pavia Province — no.
Alpha 39 36 49 58 25 9 0
Delta 0 0 0 1 11 189 358
Other 29 7 8 17 13 5 0
Could not be determined 15 9 3 27 38 26 32