Evaluation of COVID-19 vaccination strategies with a delayed second dose

• Published in: PLoS biology 2021-04, Vol.19 (4), p.e3001211-e3001211
• Main Authors: Moghadas, Seyed M, Vilches, Thomas N, Zhang, Kevin, Nourbakhsh, Shokoofeh, Sah, Pratha, Fitzpatrick, Meagan C, Galvani, Alison P
• Format: Article
• Language: English
• Subjects: Age groups; Asymptomatic; Biology and Life Sciences; Clinical trials; Coronaviruses; COVID-19; COVID-19 - epidemiology; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 vaccines; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - supply & distribution; Disease transmission; Dosage; Drug dosages; Evaluation; Hospitalization; Hospitalization - statistics & numerical data; Humans; Immunization Schedule; Immunization, Secondary; Infections; Medical personnel; Medicine and Health Sciences; Methods; Models, Statistical; Mortality; People and places; Population; Public health; SARS-CoV-2 - immunology; Schedules; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; United States - epidemiology; Vaccination; Vaccination - methods; Vaccination - statistics & numerical data; Vaccines; Viral diseases
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3001211

Two of the Coronavirus Disease 2019 (COVID-19) vaccines currently approved in the United States require 2 doses, administered 3 to 4 weeks apart. Constraints in vaccine supply and distribution capacity, together with a deadly wave of COVID-19 from November 2020 to January 2021 and the emergence of highly contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose or to continue with the recommended 2-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these 2 vaccination strategies, while varying the temporal waning of vaccine efficacy following the first dose and the level of preexisting immunity in the population. Our results show that for Moderna vaccines, a delay of at least 9 weeks could maximize vaccination program effectiveness and avert at least an additional 17.3 (95% credible interval [CrI]: 7.8-29.7) infections, 0.69 (95% CrI: 0.52-0.97) hospitalizations, and 0.34 (95% CrI: 0.25-0.44) deaths per 10,000 population compared to the recommended 4-week interval between the 2 doses. Pfizer-BioNTech vaccines also averted an additional 0.60 (95% CrI: 0.37-0.89) hospitalizations and 0.32 (95% CrI: 0.23-0.45) deaths per 10,000 population in a 9-week delayed second dose (DSD) strategy compared to the 3-week recommended schedule between doses. However, there was no clear advantage of delaying the second dose with Pfizer-BioNTech vaccines in reducing infections, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the characteristics and durability of vaccine-induced protection after the first dose in order to determine the optimal time interval between the 2 doses.