The dramatic variation in the national rates of COVID-19 infection and fatality since the onset of the pandemic led researchers to determine the conditions linked with this cross-country variation as these may guide investment in more effective preparedness and response for future pandemics.

• The Institute for Health Metrics and Evaluation's modelling database was assessed to retrieve daily SARS-CoV-2 infections and COVID-19 deaths for 177 countries and territories and 181 subnational locations.

• The most variation in cumulative rates of SARS-CoV-2 infection between Jan 1, 2020, and Sept 30, 2021, could be explained by the following factors: the proportion of the population living below 100 m (5·4% [4·0–7·9] of variation), GDP per capita (4·2% [1·8–6·6] of variation), and the proportion of infections attributable to seasonality (2·1% [95% uncertainty interval 1·7–2·7] of variation).

• No explanation could be provided for most cross-country variation in cumulative infection rates.

• The most variation in COVID-19 infection-fatality ratio (IFR) over the same period could be explained by the following factors: the age profile of the country (46·7% [18·4–67·6] of variation), GDP per capita (3·1% [0·3–8·6] of variation), and national mean BMI (1·1% [0·2–2·6] of variation).

• No explanation could be provided for 44·4% (29·2–61·7) of the cross-national variation in IFR.

• Standardized infection rates or IFRs did not correlate meaningfully with pandemic-preparedness indices, which aim to measure health security capacity.

• Larger, statistically significant associations of measures of trust in the government and interpersonal trust, as well as less government corruption, were observed with lower standardized infection rates.

• In addition, among middle-income and high-income countries where vaccine availability was more widespread, there was higher COVID-19 vaccine coverage in correlation with high levels of government and interpersonal trust, as well as less government corruption, and lower corruption was linked with greater reductions in mobility.

• Based on findings, they support greater investment in risk communication and community engagement strategies to boost the confidence that individuals have in public health guidance, in order to enhance efforts to improve pandemic preparedness and response for the next pandemic.

• Increasing health promotion for key modifiable risks is suggested to be linked with a decrease in fatalities in such a scenario.