COVID mortality and hybrid immunity from infection and vaccination: a global perspective

The COVID-19 pandemic claimed an estimated 20 million lives worldwide between 2020 and 2023, with the heaviest tolls in 2020-2021 and fewer deaths since [1, 2]. A combination of widespread infections and expanded vaccine coverage eventually tempered the virus’s impact, but the paths to this “hybrid immunity” varied greatly across regions.
Our analysis examines serological and mortality data from four countries – Canada, India, China, and Sierra Leone – highlighting the disparate paths to immunity and mortality outcomes.
In Canada, serial serosurveillance by the Action to Beat Coronavirus study revealed that stringent early restrictions kept infection levels under 10% – until the Omicron wave. During 2021, Canada achieved high vaccine coverage, with most adults receiving two doses. The Omicron wave eventually infected around 80% of Canadian adults, and the first Omicron wave coincided with a major vaccine booster campaign. This combination of limited early transmission and high vaccination kept excess mortality relatively low at around 50,000, or 6% [3, 4]. However, large excess deaths in nursing homes were a significant exception to Canada’s success. Other high-income countries with robust vaccination efforts showed similarly low excess deaths, though some recorded a puzzling trend of higher excess deaths among women [Patrick Brown, personal communication].
India’s experience was markedly different, best depicted as “uncontrolled transmission”. Infections rose in late 2020 (primarily with the Alpha variant) including across younger and older generations. Initial vaccine coverage was negligible. Deaths during the first waves were modest but notable. By contrast, India faced a devastating Delta wave in spring 2021. This wave likely caused 3-4 million deaths – seven to eight times the official count – resulting in 35-45% excess mortality and accounting for a third of the global discrepancy between reported COVID deaths and excess deaths [5]. On top of widespread infection, a mass vaccination campaign in late 2021 helped India avoid major resurgences in 2022-2023.
China pursued an aggressive “zero-COVID” strategy, keeping infection rates low and rolling out domestic vaccines that may have been less effective than those used in the West. But China abandoned its strict policies in fall 2022, and the Omicron wave in late 2022 resulted in a sharp mortality spike among those aged 60 and over. Total excess deaths reached 1.3 million, or 13%, in a brief period from late 2022 to early 2023 [6].
Sierra Leone’s path to hybrid immunity is perhaps the most intriguing. Various waves had swept through the country before vaccines became widely available in 2022, leaving over 70% of adults infected by the Delta wave in mid-2021. Despite high infection rates, excess mortality was modest – around 7,000 deaths or 6%, concentrated among the elderly. This unexpectedly low mortality suggests that Sierra Leone and other West African countries may possess unidentified factors mitigating severe disease despite high infection rates [7].
The COVID-19 pandemic offers valuable lessons in immunity and mortality. Future efforts to understand hybrid immunity in pandemics will depend on timely, large-scale serosurveys, and comprehensive data on vaccination and mortality [8].

DISCLOSURE

The authors report no conflict of interest.

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