SARS-CoV-2 Attack Rate and Population Immunity in Southern New England, March 2020 to May 2021 | Infectious Diseases | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

SARS-CoV-2 Attack Rate and Population Immunity in Southern New England, March 2020 to May 2021

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What proportion of individuals living in southern New England had immunity to SARS-CoV-2, either through past infection or vaccination, by May 31, 2021?

Findings  This case series analysis for Rhode Island, Massachusetts, and Connecticut revealed that two-thirds of residents were immune to SARS-CoV-2 by May 31, 2021. The population immune fraction was lower than desired because 27% of vaccines during the winter to spring 2021 vaccination campaign were administered to individuals who were already seropositive.

Meaning  These findings suggest that SARS-CoV-2 population immunity was overestimated in summer 2021 and that future emergency-setting vaccination campaigns may need to exceed traditional coverage goals.


Importance  In emergency epidemic and pandemic settings, public health agencies need to be able to measure the population-level attack rate, defined as the total percentage of the population infected thus far. During vaccination campaigns in such settings, public health agencies need to be able to assess how much the vaccination campaign is contributing to population immunity; specifically, the proportion of vaccines being administered to individuals who are already seropositive must be estimated.

Objective  To estimate population-level immunity to SARS-CoV-2 through May 31, 2021, in Rhode Island, Massachusetts, and Connecticut.

Design, Setting, and Participants  This observational case series assessed cases, hospitalizations, intensive care unit occupancy, ventilator occupancy, and deaths from March 1, 2020, to May 31, 2021, in Rhode Island, Massachusetts, and Connecticut. Data were analyzed from July 2021 to November 2021.

Exposures  COVID-19–positive test result reported to state department of health.

Main Outcomes and Measures  The main outcomes were statistical estimates, from a bayesian inference framework, of the percentage of individuals as of May 31, 2021, who were (1) previously infected and vaccinated, (2) previously uninfected and vaccinated, and (3) previously infected but not vaccinated.

Results  At the state level, there were a total of 1 160 435 confirmed COVID-19 cases in Rhode Island, Massachusetts, and Connecticut. The median age among individuals with confirmed COVID-19 was 38 years. In autumn 2020, SARS-CoV-2 population immunity (equal to the attack rate at that point) in these states was less than 15%, setting the stage for a large epidemic wave during winter 2020 to 2021. Population immunity estimates for May 31, 2021, were 73.4% (95% credible interval [CrI], 72.9%-74.1%) for Rhode Island, 64.1% (95% CrI, 64.0%-64.4%) for Connecticut, and 66.3% (95% CrI, 65.9%-66.9%) for Massachusetts, indicating that more than 33% of residents in these states were fully susceptible to infection when the Delta variant began spreading in July 2021. Despite high vaccine coverage in these states, population immunity in summer 2021 was lower than planned owing to an estimated 34.1% (95% CrI, 32.9%-35.2%) of vaccines in Rhode Island, 24.6% (95% CrI, 24.3%-25.1%) of vaccines in Connecticut, and 27.6% (95% CrI, 26.8%-28.6%) of vaccines in Massachusetts being distributed to individuals who were already seropositive.

Conclusions and Relevance  These findings suggest that future emergency-setting vaccination planning may have to prioritize high vaccine coverage over optimized vaccine distribution to ensure that sufficient levels of population immunity are reached during the course of an ongoing epidemic or pandemic.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: April 9, 2022.

Published: May 26, 2022. doi:10.1001/jamanetworkopen.2022.14171

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Tran TNA et al. JAMA Network Open.

Corresponding Author: Maciej F. Boni, PhD, Center for Infectious Disease Dynamics, Department of Biology, Pennsylvania State University, University Park, PA 16802 (

Author Contributions: Ms Tran and Dr Boni had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Ms Tran and Dr Wikle contributed equally.

Concept and design: Tran, Gentilesco, Hanage, Boni.

Acquisition, analysis, or interpretation of data: Tran, Wikle, Yang, Inam, Leighow, Chan, Albert, Strong, Pritchard, Hanks, Crawford, Boni.

Drafting of the manuscript: Tran, Yang, Albert, Strong, Hanage, Boni.

Critical revision of the manuscript for important intellectual content: Tran, Wikle, Inam, Leighow, Gentilesco, Chan, Pritchard, Hanage, Hanks, Crawford, Boni.

Statistical analysis: Tran, Wikle, Inam, Leighow, Albert, Strong, Hanks, Crawford.

Obtained funding: Pritchard, Crawford.

Administrative, technical, or material support: Leighow, Gentilesco, Pritchard, Crawford, Boni.

Supervision: Pritchard, Hanage, Hanks, Boni.

Conflict of Interest Disclosures: Dr Pritchard reported receiving personal fees from Theseus Pharmaceuticals, Moma Therapeutics, and Third Rock Ventures; grants from Theseus Pharmaceuticals; and owning stock in Theseus Pharmaceuticals and Moma Therapeutics outside the submitted work. Dr Hanage reported receiving personal fees from Biobot Analytics outside the submitted work. Dr Crawford reported receiving personal fees from Global Diagnostic Systems, Revelar Biotherapeutics, and Whitespace outside the submitted work. Dr Boni reported receiving personal fees from a financial services company outside the submitted work. No other disclosures were reported.

Funding/Support: Dr Boni and Ms Tran are funded by grant No. INV-005517 from the Bill and Melinda Gates Foundation. Ms Yang is supported by contract No. HHS N272201400007C from the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases Center of Excellence in Influenza Research and Surveillance. Dr Hanage is funded by award No. U54 GM088558 from the National Institute of General Medical Sciences. Ms Albert is funded by grant No. NSF DMR-1420620 from the Penn State Materials Research Science and Engineering Center, Center for Nanoscale Science. Dr Hanks was partially supported by grant No. DMS-2015273 from the National Science Foundation. Dr Crawford is supported by Cooperative Agreement No. 6NU50CK000524-01 from the Centers for Disease Control and Prevention, funds from the COVID-19 Paycheck Protection Program and Health Care Enhancement Act, NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development grant No. 1DP2HD091799-01, and the Pershing Square Foundation.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Larry Madoff, MD, and Catherine Brown, DVM, MSc, MPH (Massachusetts Department of Public Health), helped in interpretation of the COVID-19 epidemic in Massachusetts. David Kennedy, PhD (Department of Biology, Pennsylvania State University), provided information on behavioral heterogeneity and the correlation between vaccination and past infection. They did not received any compensation for these contributions.

Wikle  NB , Tran  TNA , Gentilesco  B ,  et al.  SARS-CoV-2 epidemic after social and economic reopening in three U.S. states reveals shifts in age structure and clinical characteristics.   Sci Adv. 2022;8(4):eabf9868. doi:10.1126/sciadv.abf9868PubMedGoogle ScholarCrossref
Yang  W , Kandula  S , Huynh  M ,  et al.  Estimating the infection-fatality risk of SARS-CoV-2 in New York City during the spring 2020 pandemic wave: a model-based analysis.   Lancet Infect Dis. 2021;21(2):203-212. doi:10.1016/S1473-3099(20)30769-6PubMedGoogle ScholarCrossref
Ehrmann  S , Li  J , Ibarra-Estrada  M ,  et al; Awake Prone Positioning Meta-Trial Group.  Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.   Lancet Respir Med. 2021;9(12):1387-1395. doi:10.1016/S2213-2600(21)00356-8PubMedGoogle ScholarCrossref
Beigel  JH , Tomashek  KM , Dodd  LE ,  et al; ACTT-1 Study Group Members.  Remdesivir for the treatment of COVID-19—final report.   N Engl J Med. 2020;383(19):1813-1826. doi:10.1056/NEJMoa2007764PubMedGoogle ScholarCrossref
Sterne  JAC , Murthy  S , Diaz  JV ,  et al; WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group.  Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis.   JAMA. 2020;324(13):1330-1341. doi:10.1001/jama.2020.17023PubMedGoogle ScholarCrossref
Horby  P , Lim  WS , Emberson  JR ,  et al; RECOVERY Collaborative Group.  Dexamethasone in hospitalized patients with COVID-19.   N Engl J Med. 2021;384(8):693-704. doi:10.1056/NEJMoa2021436PubMedGoogle ScholarCrossref
Schultes  O , Clarke  V , Paltiel  AD , Cartter  M , Sosa  L , Crawford  FW .  COVID-19 in Connecticut institutions of higher education during the 2020-2021 academic year.   medRxiv. Preprint posted online August 13, 2021. doi:10.1101/2021.08.11.21261732Google Scholar
Di Domenico  L , Pullano  G , Sabbatini  CE , Boëlle  PY , Colizza  V .  Modelling safe protocols for reopening schools during the COVID-19 pandemic in France.   Nat Commun. 2021;12(1):1073. doi:10.1038/s41467-021-21249-6PubMedGoogle ScholarCrossref
Goldhaber-Fiebert  JD , Studdert  DM , Mello  MM .  School reopenings and the community during the COVID-19 pandemic.   JAMA Health Forum. 2020;1(10):e201294. doi:10.1001/jamahealthforum.2020.1294Google ScholarCrossref
Bajema  KL , Wiegand  RE , Cuffe  K ,  et al.  Estimated SARS-CoV-2 seroprevalence in the US as of September 2020.   JAMA Intern Med. 2021;181(4):450-460. doi:10.1001/jamainternmed.2020.7976PubMedGoogle ScholarCrossref
Anand  S , Montez-Rath  M , Han  J ,  et al.  Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA: a cross-sectional study.   Lancet. 2020;396(10259):1335-1344. doi:10.1016/S0140-6736(20)32009-2PubMedGoogle ScholarCrossref
Havers  FP , Reed  C , Lim  T ,  et al.  Seroprevalence of antibodies to SARS-CoV-2 in 10 sites in the United States, March 23-May 12, 2020.   JAMA Intern Med. 2020;180(12):1576-1586. doi:10.1001/jamainternmed.2020.4130PubMedGoogle ScholarCrossref
Monod  M , Blenkinsop  A , Xi  X ,  et al; Imperial College COVID-19 Response Team.  Age groups that sustain resurging COVID-19 epidemics in the United States.   Science. 2021;371(6536):eabe8372. doi:10.1126/science.abe8372PubMedGoogle ScholarCrossref
Unwin  HJT , Mishra  S , Bradley  VC ,  et al.  State-level tracking of COVID-19 in the United States.   Nat Commun. 2020;11(1):6189. doi:10.1038/s41467-020-19652-6PubMedGoogle ScholarCrossref
Russell  TW , Golding  N , Hellewell  J ,  et al; CMMID COVID-19 working group.  Reconstructing the early global dynamics of under-ascertained COVID-19 cases and infections.   BMC Med. 2020;18(1):332. doi:10.1186/s12916-020-01790-9PubMedGoogle ScholarCrossref
Davis  JT , Chinazzi  M , Perra  N ,  et al.  Cryptic transmission of SARS-CoV-2 and the first COVID-19 wave.   Nature. 2021;600(7887):127-132. doi:10.1038/s41586-021-04130-wPubMedGoogle ScholarCrossref
Reed  C , Angulo  FJ , Swerdlow  DL ,  et al.  Estimates of the prevalence of pandemic (H1N1) 2009, United States, April-July 2009.   Emerg Infect Dis. 2009;15(12):2004-2007. doi:10.3201/eid1512.091413PubMedGoogle ScholarCrossref
Reese  H , Iuliano  AD , Patel  NN ,  et al.  Estimated incidence of coronavirus disease 2019 (COVID-19) illness and hospitalization—United States, February-September 2020.   Clin Infect Dis. 2021;72(12):e1010-e1017. doi:10.1093/cid/ciaa1780PubMedGoogle ScholarCrossref
Lewnard  JA , Liu  VX , Jackson  ML ,  et al.  Incidence, clinical outcomes, and transmission dynamics of severe coronavirus disease 2019 in California and Washington: prospective cohort study.   BMJ. 2020;369:m1923. doi:10.1136/bmj.m1923PubMedGoogle ScholarCrossref
Levin  AT , Hanage  WP , Owusu-Boaitey  N , Cochran  KB , Walsh  SP , Meyerowitz-Katz  G .  Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications.   Eur J Epidemiol. 2020;35(12):1123-1138. doi:10.1007/s10654-020-00698-1PubMedGoogle ScholarCrossref
Davies  NG , Klepac  P , Liu  Y , Prem  K , Jit  M , Eggo  RM ; CMMID COVID-19 working group.  Age-dependent effects in the transmission and control of COVID-19 epidemics.   Nat Med. 2020;26(8):1205-1211. doi:10.1038/s41591-020-0962-9PubMedGoogle ScholarCrossref
Boni  MF , Chau  NVV , Dong  N ,  et al.  Population-level antibody estimates to novel influenza A/H7N9.   J Infect Dis. 2013;208(4):554-558. doi:10.1093/infdis/jit224PubMedGoogle ScholarCrossref
Wu  JT , Leung  K , Perera  RA ,  et al.  Inferring influenza infection attack rate from seroprevalence data.   PLoS Pathog. 2014;10(4):e1004054. doi:10.1371/journal.ppat.1004054PubMedGoogle ScholarCrossref
Vinh  DN , Nhat  NTD , de Bruin  E ,  et al.  Age-seroprevalence curves for the multi-strain structure of influenza A virus.   Nat Commun. 2021;12(1):6680. doi:10.1038/s41467-021-26948-8PubMedGoogle ScholarCrossref
Centers for Disease Control and Prevention. Nationwide blood donor seroprevalence survey. Accessed August 12, 2021.
Centers for Disease Control and Prevention. Nationwide commercial laboratory seroprevalence survey. Accessed August 12, 2021.
Jones  JM , Stone  M , Sulaeman  H ,  et al.  Estimated US infection- and vaccine-induced SARS-CoV-2 seroprevalence based on blood donations, July 2020-May 2021.   JAMA. 2021;326(14):1400-1409. doi:10.1001/jama.2021.15161PubMedGoogle ScholarCrossref
Shioda  K , Lau  MSY , Kraay  ANM ,  et al.  Estimating the cumulative incidence of SARS-CoV-2 infection and the infection fatality ratio in light of waning antibodies.   Epidemiology. 2021;32(4):518-524. doi:10.1097/EDE.0000000000001361PubMedGoogle ScholarCrossref
Department of Health and Human Services. 45 CFR 46. Accessed August 12, 2021.
Tran  TNA , Wikle  NB , Albert  E ,  et al.  Optimal SARS-CoV-2 vaccine allocation using real-time attack-rate estimates in Rhode Island and Massachusetts.   BMC Med. 2021;19(1):162. doi:10.1186/s12916-021-02038-wPubMedGoogle ScholarCrossref
Massachusetts Department of Public Health. Archive of COVID-19 vaccination reports. Accessed August 12, 2021.
Connecticut Department of Public Health. COVID-19 vaccination status by residence in a SVI priority zip code. Accessed August 12, 2021.
Rhode Island Department of Health. COVID-19 Rhode Island data. Accessed August 12, 2021.
Connecticut Department of Public Health. COVID-19 vaccinations by age group. Accessed August 12, 2021.
Morozova  O , Li  ZR , Crawford  FW .  One year of modeling and forecasting COVID-19 transmission to support policymakers in Connecticut.   Sci Rep. 2021;11(1):20271. doi:10.1038/s41598-021-99590-5PubMedGoogle ScholarCrossref
Moghadas  SM , Sah  P , Shoukat  A , Meyers  LA , Galvani  AP .  Population immunity against COVID-19 in the United States.   Ann Intern Med. 2021;174(11):1586-1591. doi:10.7326/M21-2721PubMedGoogle ScholarCrossref
Centers for Disease Control and Prevention. Estimated COVID-19 burden. Accessed November 16, 2021.
COVID-19 Forecast Hub. Weekly forecast summaries. Accessed July 13, 2021.
Boni  MF , Nguyen  TD , de Jong  MD , van Doorn  HR .  Virulence attenuation during an influenza A/H5N1 pandemic.   Philos Trans R Soc Lond B Biol Sci. 2013;368(1614):20120207. doi:10.1098/rstb.2012.0207PubMedGoogle ScholarCrossref
Bootsma  MCJ , Ferguson  NM .  The effect of public health measures on the 1918 influenza pandemic in U.S. cities.   Proc Natl Acad Sci U S A. 2007;104(18):7588-7593. doi:10.1073/pnas.0611071104PubMedGoogle ScholarCrossref
Ball  F .  Deterministic and stochastic epidemics with several kinds of susceptibles.   Adv Appl Probab. 1985;17(1):1-22. doi:10.2307/1427049Google ScholarCrossref
Gart  JJ .  The mathematical analysis of an epidemic with two kinds of susceptibles.   Biometrics. 1968;24(3):557-566. doi:10.2307/2528318PubMedGoogle ScholarCrossref
Peluso  MJ , Takahashi  S , Hakim  J ,  et al.  SARS-CoV-2 antibody magnitude and detectability are driven by disease severity, timing, and assay.   medRxiv. Preprint posted online March 5, 2021. doi:10.1101/2021.03.03.21251639Google Scholar
Lumley  SF , Wei  J , O’Donnell  D ,  et al; Oxford University Hospitals Staff Testing Group.  The duration, dynamics, and determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses in individual healthcare workers.   Clin Infect Dis. 2021;73(3):e699-e709. doi:10.1093/cid/ciab004PubMedGoogle ScholarCrossref
Ward  H , Cooke  G , Atchison  C ,  et al.  Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults.   medRxiv. Preprint posted online October 27, 2020. doi:10.1101/2020.10.26.20219725Google Scholar
Lau  EHY , Tsang  OTY , Hui  DSC ,  et al.  Neutralizing antibody titres in SARS-CoV-2 infections.   Nat Commun. 2021;12(1):63. doi:10.1038/s41467-020-20247-4PubMedGoogle ScholarCrossref
Levin  EG , Lustig  Y , Cohen  C ,  et al.  Waning immune humoral response to BNT162b2 COVID-19 vaccine over 6 months.   N Engl J Med. 2021;385(24):e84. doi:10.1056/NEJMoa2114583PubMedGoogle ScholarCrossref
Shrotri  M , Navaratnam  AMD , Nguyen  V ,  et al; Virus Watch Collaborative.  Spike-antibody waning after second dose of BNT162b2 or ChAdOx1.   Lancet. 2021;398(10298):385-387. doi:10.1016/S0140-6736(21)01642-1PubMedGoogle ScholarCrossref
Zhong  D , Xiao  S , Debes  AK ,  et al.  Durability of antibody levels after vaccination with mRNA SARS-CoV-2 vaccine in individuals with or without prior infection.   JAMA. 2021;326(24):2524-2526. doi:10.1001/jama.2021.19996PubMedGoogle ScholarCrossref
Bayart  JL , Douxfils  J , Gillot  C ,  et al.  Waning of IgG, total and neutralizing antibodies 6 months post-vaccination with BNT162b2 in healthcare workers.   Vaccines (Basel). 2021;9(10):1092. doi:10.3390/vaccines9101092PubMedGoogle ScholarCrossref
Pegu  A , O’Connell  SE , Schmidt  SD ,  et al; mRNA-1273 Study Group§.  Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants.   Science. 2021;373(6561):1372-1377. doi:10.1126/science.abj4176PubMedGoogle ScholarCrossref
Boni  MF , Mølbak  K , Krogfelt  KA . Inferring the time of infection from serological data. In: Held  L , Hens  N , O’Neill  P , Wallinga  J , eds.  Handbook of Infectious Disease Data Analysis. CRC Press; 2020:287-303.
Pulliam  JRC , van Schalkwyk  C , Govender  N ,  et al.  Increased risk of SARS-CoV-2 reinfection associated with emergence of the Omicron variant in South Africa.   medRxiv. Preprint posted online December 2, 2021. doi:10.1101/2021.11.11.21266068Google Scholar
Center for Infectious Disease Dynamics. COVID. Accessed April 22, 2022.
Riley  S , Ainslie  KEC , Eales  O ,  et al.  REACT-1 round 6 updated report: high prevalence of SARS-CoV-2 swab positivity with reduced rate of growth in England at the start of November 2020.   medRxiv. Preprint posted online November 20, 2020. doi:10.1101/2020.11.18.20233932Google Scholar
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience

Lookup An Activity



My Saved Searches

You currently have no searches saved.


My Saved Courses

You currently have no courses saved.

With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right