During 2020–2021, all-cause excess mortality among men in the US was 18.8% (95% confidence interval (CI): 17.3, 20.5%) higher than expected, while among women it was 17.8% (16.1, 19.6%) (Fig. 1, supplementary Tables 1 and 2). The ratio of COVID-19 UC to excess mortality was 74.2% (69.2, 79.7%) for men and 68.7% (63.5, 75.0%) for women and as a CC was 6.9% (6.4, 7.4%) for men and 8.1% (7.5, 8.8%) for women. Excess mortality for males in 2020 was 16.2% (14, 18.4%), which increased to 21.5% (19.3, 23.7%) in 2021 (Fig. 1, supplementary Tables 3 and 5). The ratio of COVID-19 UC to the excess mortality rate was lower in 2021 (71.5% (66.1, 78.4%)) than 2020 (77.8% (69.7, 88.4%)), although with overlapping 95% CIs, while the COVID-19 CC ratio was steady. Excess mortality for females in 2020 was slightly lower at 13.9% (11.6, 16.3%) and also rose to be similar at 21.8% (19.3, 24.1%) in 2021 (Fig. 1, supplementary Tables 4 and 6). The ratio of COVID-19 UC to the excess mortality rate for females fell from 78.9% (68.6, 92.3%) 2020 to 62.1% (57.3, 68.8%) in 2021, and the ratio for COVID-19 CC also fell over these years. The observed and expected number of deaths for each cause, and number of COVID-19 UC, COVID-19 CC, and excess deaths for 2020 and 2021, is in supplementary Table 7.

Excess mortality and ratio of COVID-19 (UC and CC) to excess mortality, all causes, by sex, US, 2020, 2021 and 2020–21. Uncertainty intervals shown in supplementary Tables 1-6. Percentage figure refers to overall excess mortality for all causes: the sum of COVID UC, COVID CC and No COVID.

Of the 24 non-COVID-19 causes of death, for 21 causes the mortality rate in 2020–21 was higher than expected (based on MC) (supplementary Tables 1 and 2). Only influenza, suicide and lung cancer mortality was lower than expected (supplementary Figs. 1–4). During 2020–21, the highest excess mortality rate of the 24 causes was for pneumonia at 126.5% (116.6, 136.9%) for men and 103.3% (92.3, 114.3%) for women, respectively (Fig. 2, supplementary Tables 1 and 2). There was higher excess mortality from pneumonia in 2021 (149.3% (134.2, 166.7%) for males, 125.3% (109.3, 143.1%) for females) than 2020 (104.9% (91.7, 117.6%) for males, 81.2% (68, 93.7%) for females) (supplementary Fig. 1, supplementary Tables 3–6). During 2020–21, the ratio of COVID-19 UC to excess mortality for pneumonia exceeded 100% for both males and females, indicating that the age-standardized death rate of pneumonia with COVID-19 as the UC was greater than the total excess age-standardized death rate for pneumonia; this can occur because the pneumonia age-standardized death rate without COVID-19 (either as UC or CC) was lower than expected. Across the same period, COVID-19 CC accounted for less than 5% of the excess mortality in both sexes.

Excess mortality and ratio of COVID-19 (UC and CC) to excess mortality, infectious and respiratory diseases, by sex and cause of death, US, 2020–2021. Uncertainty intervals shown in supplementary Tables 1 and 2. Percentage figure refers to overall excess mortality for that cause: the sum of COVID UC, COVID CC and No COVID.

In stark contrast, the mortality rate for influenza in 2020–2021 was 79.8% lower than expected (− 86.2, − 73.8%) for men and 82.2% lower (− 88.0, − 76.5%) for women, even lower in 2021 than 2020 (Fig. 2; supplementary Fig. 1). The excess mortality rates for other respiratory diseases in 2020–21 were 45.2% (42.2, 48.2%) for men and 35.6% (32.4, 39%) for women (Fig. 2), respectively, being higher in 2021 than 2020 (supplementary Fig. 1). Excess mortality from chronic respiratory diseases was much lower, being less than 5% for each sex in 2020–21. It was over 10% for sepsis in 2020–21, being much higher in 2021 than 2020. The ratio of COVID-19 UC to excess mortality for chronic respiratory diseases exceeded 200% and for other respiratory diseases, and sepsis was greater than 100% during 2020–21.

Among non-communicable diseases, the highest excess mortality in 2020–21 was observed in other kidney disease (males 45% (37.8, 52%); females 40.7% (33.2, 47.9%)), followed by diabetes (males 33.9% (29.3, 38.5%); females 38.3% (32.8, 43.4%)), hypertensive heart disease (males 25.7% (22, 29.6%); females 28.9% (22.8, 33.9%)), and other cardiovascular diseases (males 15.8% (11.1, 21.1%); females 18.3% (11.7, 24.5%)) (Fig. 3, supplementary Tables 1 and 2). The three non-communicable diseases with the lowest excess mortality among males were chronic kidney disease (males 5.7% (0.5, 10.7%); females 5.7% (0.5, 11.6%)), all cancers (males 3.5% (1.7, 5.5%); females 3.6% (1.7, 5.5%)), and lung cancer (males − 1.7% (− 5.4, 2.0%); females − 2.5% (− 6.1, 1.2%)). Other heart diseases, stroke, IHD, Parkinson’s and Alzheimer's and other dementias had similar levels of excess mortality for males and females, being between 8% and 15%.

Excess mortality and ratio of COVID-19 (UC and CC) to excess mortality, non-communicable diseases, by sex and cause of death, US, 2020–2021. Uncertainty intervals shown in supplementary Tables 1 and 2. Percentage figure refers to overall excess mortality for that cause: the sum of COVID UC, COVID CC and No COVID.

Also for non-communicable diseases in 2020–21, the ratio of COVID-19 UC to excess mortality for Alzheimer's and other dementias and chronic kidney disease was over 100% in males but only for chronic kidney disease in females. The ratio of COVID-19 UC to excess mortality was over 50% for other kidney disease, diabetes, hypertensive heart disease (males only), other heart disease, stroke (males only), IHD (males only) and all cancers (Fig. 3, supplementary Tables 1 and 2). For all non-communicable diseases, except Parkinson’s disease, Alzheimer’s disease and chronic kidney disease (males only), there was higher excess mortality in 2021 than 2020 (supplementary Figs. 2–3). The ratio of COVID-19 UC to excess mortality rates did not show significant changes between 2020 and 2021, except for a decline for other kidney diseases for males, a notable increase for male Parkinson’s disease, and a significant decline for both male and female all cancers. In 2020–21, the ratios of COVID-19 CC to excess mortality for Parkinson’s disease (males only), Alzheimer's and other dementias (males only), chronic kidney disease, all cancers and lung cancer exceeded 20%, and were lower for other causes.

Among the six other causes in 2020–21, the highest excess mortality was observed for homicide (males 22.8% (17.0, 28.7%); females 11.7% (6.6, 16.7%)). This was followed by alcohol-related conditions (males 18.0% (15.3, 20.6%); females 16.1% (12.8, 19.3%)), drug use disorders (males 13.2% (8.9, 17.9%); females 11.9% (7.6, 16.1%)), and transport accidents (males 10.0% (7.7, 12.0%); females 6.3% (3.8, 9.1%)). For falls, both males and females had an excess mortality rate of 2.8% (males (− 3.3, 9.9%); females (− 5.4, 11.4%)). Suicide had less deaths than expected (males − 4.4% (− 5.9, − 2.6%); females − 16.7% (− 19.3, − 14.1%)) (Fig. 4, supplementary Tables 1 and 2). The ratio of COVID-19 UC to excess mortality was over 30% for falls among males and exceeded 20% for females. For alcohol-related causes, the ratio exceeded 15% for both males and females. For homicide, drug use disorders, transport accidents, and suicide, the ratios were all below 7%.

Excess mortality and ratio of COVID-19 (UC and CC) to excess mortality, other causes, by sex and cause of death, US, 2020–2021. Uncertainty intervals shown in supplementary Tables 1 and 2. Percentage figure refers to overall excess mortality for that cause: the sum of COVID UC, COVID CC and No COVID.

Table 1 shows that, following an increase in home deaths relative to hospitals deaths in the pre-pandemic period, there was a sharp increase in hospital deaths and decline in hospice/nursing home deaths in 2020–21. All-cause mortality rates in 2020–21 were higher for hospital (males 33.2% (31.4, 35.1%), females 29.8% (27.9, 31.7%)) than home deaths (males 20.2% (18.4, 22.1%), females 21.4% (19.1, 23.6%)), and COVID-19 UC made a much greater contribution to excess mortality rates for hospital deaths (males 92.9% (89.1, 96.9%), females 90.7% (86.6, 95.5%)) than for home deaths (males 15.6% (14.5, 16.9%), females 12.5% (11.6, 13.8%)) (Figs. 5, 6). Excess mortality from pneumonia, other kidney diseases, other respiratory diseases and diabetes was far higher in hospitals than in homes, being more than double for some causes. For most causes of death, the ratio of COVID-19 UC to excess mortality in hospitals was over 90%, whereas for all causes for home deaths, except for pneumonia and other respiratory diseases, it was less than 20% of excess home deaths. Regardless of whether deaths occurred in hospitals or at home, COVID-19 CC was less than 10% of excess mortality for most causes, with the exception of pneumonia.

Top 10 causes of death according to highest excess mortality, hospital deaths and home deaths, males, US, 2020–2021. Uncertainty intervals shown in supplementary Tables 8 and 10. Percentage figure refers to overall excess mortality for that cause: the sum of COVID UC, COVID CC and No COVID.

Top 10 causes of death according to highest excess mortality, hospital deaths and home deaths, females, US, 2020–2021. Uncertainty intervals shown in supplementary Tables 9 and 11. Percentage figure refers to overall excess mortality for that cause: the sum of COVID UC, COVID CC and No COVID.