Multistate Outbreak of SARS-CoV-2 Infections, Including Vaccine Breakthrough Infections, Associated With Large Public Gatherings, United States

Radhika Gharpure; Samira Sami; Johanna Vostok; Hillary Johnson; Noemi Hall; Anne Foreman; Rebecca T. Sabo; Petra L. Schubert; Hanna Shephard; Vance R. Brown; Ben Brumfield; Jessica N. Ricaldi; Andrew B. Conley; Lindsay Zielinski; Lenka Malec; Alexandra P. Newman; Michelle Chang; Lauren E. Finn; Cameron Stainken; Anil T. Mangla; Patrick Eteme; Morgan Wieck; Alison Green; Alexandra Edmundson; Diana Reichbind; Vernell Brown Jr.; Laura Quiñones; Allison Longenberger; Elke Hess; Megan Gumke; Alicia Manion; Hannah Thomas; Carla A. Barrios; Adrianna Koczwara; Thelonious W. Williams; Marcia Pearlowitz; Moussokoura Assoumou; Alessandra F. Senisse Pajares; Hope Dishman; Cody Schardin; Xiong Wang; Kendalyn Stephens; Nakema S. Moss; Gurpalik Singh; Christine Feaster; Lindsey Martin Webb; Anna Krueger; Kristen Dickerson; Courtney Dewart; Bree Barbeau; Amelia Salmanson; Lawrence C. Madoff; Julie M. Villanueva; Catherine M. Brown; A. Scott Laney


Emerging Infectious Diseases. 2022;28(1):35-43. 

In This Article


This investigation highlights that the Delta variant of SARS-CoV-2 can spread quickly through a highly vaccinated population and can be transmitted to others regardless of vaccination status. Although vaccination remains a key mitigation strategy to decrease illness and death associated with COVID-19,[25] the Delta variant of SARS-CoV-2 is highly transmissible,[26] and several studies have suggested lower vaccine effectiveness during Delta variant predominance compared with earlier months,[5–7,27] probably driven by waning immunity from increased time since vaccination.[28] In this outbreak, 99% of cluster-associated cases that had available sequencing were caused by the Delta variant, and 81% of cluster-associated cases were classified as vaccine breakthrough infections. The large number of breakthrough infections is probably representative of a highly vaccinated underlying population; as a greater proportion of the US population becomes fully vaccinated, vaccine breakthrough infections are likely to be more frequently observed.[27,29]

Data from this outbreak provide support for an increasing body of evidence that fully vaccinated persons can transmit SARS-CoV-2 to others, including other fully vaccinated persons, particularly during Delta variant predominance.[12,15,30] The observed examples of secondary transmission, particularly to children <12 years of age and to older persons >75 years of age, highlight that fully vaccinated persons should wear a mask indoors in public to reduce the risk for infection and prevent SARS-CoV-2 transmission, especially if they have someone in their household who is immunocompromised, at increased risk for severe disease, or not fully vaccinated.[31] The serial interval between primary and secondary case onset (median 2 days) was comparable to what has been previously described for Delta variant transmission (median 2–3 days).[21,22] However, further characterization of serial interval, particularly stratified by vaccination status, is warranted. Symptom onset of persons who had secondary cases before symptom onset of persons who had primary cases was observed in a small number of pairs, consistent with previous reports,[21,22] and could be caused by presymptomatic transmission[23,24] or variability in self-reported symptom onset date.

In this outbreak, most fully vaccinated and non–fully vaccinated persons were symptomatic, and the number of symptoms reported was similar between the 2 groups. This finding differs from those of previous studies that had limited data on Delta variant infections, which found that persons with vaccine breakthrough infections had fewer symptoms compared with persons who had non–breakthrough infections.[15,16] In addition, hospitalizations were rare for fully vaccinated and non–fully vaccinated persons during this outbreak (<1%). Previous analyses have demonstrated that high effectiveness of COVID-19 vaccines against severe disease caused by the Delta variant, including hospitalization.[27,32,33] Additional population-level surveillance of the clinical picture and outcomes of patients with Delta variant breakthrough infections is warranted to clarify differences in disease severity, including older adults and persons who have underlying conditions or other characteristics that might affect immune response to vaccination or predispose them to more severe COVID-19 illness. Additional studies are also needed to characterize the effect of vaccination on risk for reinfection with SARS-CoV-2. Previous studies have indicated that vaccination might reduce the risk for reinfection.[34] However, the number of persons who had a previous COVID-19 diagnosis was inadequate to enable comparison in our study.

The first limitation of our study is that, because the outbreak occurred among an open population that included thousands of persons who traveled to Provincetown and whose infection and vaccination status were unknown, these data cannot be used to calculate or infer vaccine effectiveness or to compare COVID-19 vaccine products. Symptoms and outcomes observed in this investigation might be affected by greater presence of older age and underlying conditions for fully vaccinated persons compared with non–fully vaccinated persons.

Second, data abstracted from public health department surveillance systems can differ in method of collection and completeness of data. Although data were cleaned and combined across jurisdictions, bias might have been introduced if data were not missing at random (e.g., if persons who had unknown vaccination data more commonly had missing data for additional variables).

Third, vaccination status was assigned through matching with an immunization information system or self-report; persons who did not have vaccination data were assigned as non–fully vaccinated, which could lead to misclassification bias. Symptom data, including date of onset, and underlying medical conditions were self-reported and might be incomplete or inaccurate.

Fourth, asymptomatic SARS-CoV-2 infections might be underrepresented; although testing recommendations in Massachusetts were changed on July 14 to encourage all persons, regardless of vaccination status, to seek testing after travel to Provincetown or close contact with a person who showed positive results for COVID-19, symptomatic persons might have been more likely to seek testing than asymptomatic persons because of previous CDC guidance that most asymptomatic vaccinated persons can refrain from testing. Consequently, the cluster was probably larger than documented, particularly underestimating asymptomatic infections. Similarly, attitudes, such as willingness to seek testing and report symptoms might have differed by vaccination status, potentially leading to greater case ascertainment and increased symptom prevalence among persons who had vaccine breakthrough cases.

Finally, the number of secondary cases might be greatly underestimated because capacity and methods for contact tracing and case follow-up varied across jurisdictions, particularly during the nationwide surge in COVID-19 cases attributed to the Delta variant. The frequency or attack rate of secondary transmission of SARS-CoV-2 cannot be inferred from these data. In addition, our investigation could not account for additional sources of SARS-CoV-2 exposure that could have led to infection among persons who had secondary cases. Furthermore, for this investigation, secondary cases only included those in persons who did not travel to Provincetown; additional chains of transmission occurring within visitors/residents in Provincetown are not described in this study.

In conclusion, major epidemiologic questions about breakthrough infections, such as the comparative infectiousness of fully vaccinated and non–fully vaccinated persons, duration of viral shedding, and duration of vaccine-derived immunity, remain. However, our findings underscore the need for persons who are fully vaccinated to take precautions to prevent transmission of SARS-CoV-2 to themselves and others, such as wearing a mask in public indoor settings or crowded outdoor settings, particularly during substantial or high transmission. Vaccination, although critical to reduce illness and death from COVID-19, should be complemented by layered mitigation strategies to address the COVID-19 pandemic.[25,31]