Population immunity of natural infection, primary-series vaccination, and booster vaccination in Qatar during the COVID-19 pandemic: An observational study

Abstract

SummaryBackgroundWaning of natural infection protection and vaccine protection highlight the need to evaluate changes in population immunity over time. Population immunity of previous SARS-CoV-2 infection or of COVID-19 vaccination are defined, respectively, as the overall protection against reinfection or against breakthrough infection at a given point in time in a given population.MethodsWe estimated these population immunities in Qatar’s population between July 1, 2020 and November 30, 2022, to discern generic features of the epidemiology of SARS-CoV-2. Effectiveness of previous infection, mRNA primary-series vaccination, and mRNA booster (third-dose) vaccination in preventing infection were estimated, month by month, using matched, test-negative, case-control studies.FindingsPrevious-infection effectiveness against reinfection was strong before emergence of Omicron, but declined with time after a wave and rebounded after a new wave. Effectiveness dropped immediately after Omicron emergence from 88.3% (95% CI: 84.8-91.0%) in November 2021 to 51.0% (95% CI: 48.3-53.6%) in December 2021. Primary-series effectiveness against infection was 84.0% (95% CI: 83.0-85.0%) in April 2021, soon after introduction of vaccination, before waning gradually to 52.7% (95% CI: 46.5-58.2%) by November of 2021. Effectiveness declined linearly by ∼1 percentage point every 5 days. After Omicron emergence, effectiveness dropped suddenly from 52.7% (95% CI: 46.5-58.2%) in November 2021 to negligible levels in December 2021. Booster effectiveness dropped immediately after Omicron emergence from 83.0% (95% CI: 65.6 -91.6%) in November 2021 to 32.9% (95% CI: 26.7-38.5%) in December 2021, and continued to decline thereafter. Effectiveness of previous infection and vaccination against severe, critical, or fatal COVID-19 were generally >80% throughout the study duration.InterpretationHigh population immunity may not be sustained beyond a year. This creates fertile grounds for repeated waves of infection to occur, but these waves may increasingly exhibit a benign pattern of infection.FundingThe Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114.Research in contextEvidence before this studySARS-CoV-2 infection induces protection against reinfection, but this protection wanes with time since last infection. Similarly, COVID-19 primary-series and booster vaccination induce protection against SARS-CoV-2 infection, but this protection also wanes with time since last dose. These immunity patterns demonstrate the need for the concept ofpopulation immunityto track evolution of overall immune protection over time in a given population. Previous-infection and vaccine population immunities in a specific country can be defined as the overall protection against infection at a given point in time in the full national population. A search of PubMed, Google Scholar, and the International Vaccine Access Center’s VIEW-hub databases up to April 21, 2023 using the keywords “vaccination”, “infection”, “immunity”, “protection”, “SARS-CoV-2”, and “COVID-19” did not identify studies that investigated this epidemiological concept for a national population throughout the COVID-19 pandemic.Added value of this studyThis study analyzed the national federated databases for SARS-CoV-2 infection and COVID-19 vaccination in Qatar, a country that experienced SARS-CoV-2 waves dominated by different pre-Omicron variants and Omicron subvariants. Using a matched, test-negative study design, population immunity against infection of each of previous infection, primary-series vaccination, and booster vaccination were characterized at the national level month by month for two calendar years to discern generic features of the epidemiology of SARS-CoV-2. The three forms of population immunity showed rapid variation over time driven by waning of protection. Vaccine-derived population immunity declined by 1 absolute percentage point every 5 days. Omicron introduction immensely reduced the three forms of population immunity within one month by about 50 absolute percentage points. Meanwhile, previous-infection and vaccine population immunities against severe COVID-19 were durable with slow waning even after Omicron emergence.Implications of all available evidenceBoth previous-infection and vaccine population immunities vary rapidly at a national level creating fertile grounds for repeated waves of infection to occur even within months of each other. High levels of population immunity may not be sustained for more than a year or so. Preventing infection/reinfection, transmission, or future waves of infection cannot sustainably be done with current vaccines nor by the entire population being infected. Timely administration of boosters for those vulnerable to severe COVID-19 may remain essential for years to come. Repeated waves of infection may also facilitate further evolution of the virus and continual immune evasion. Emergence of a new variant that is substantially different from circulating variants can suddenly and immensely reduce population immunity leading to large epidemic waves. However, the durability of population immunity against severe COVID-19 will likely curtail the severity of future waves.