Risk factors

An observational study of 10,926 deaths due to COVID-19 in England found that death due to COVID-19 was significantly associated with older age. The hazard ratio (HR) (compared with age 50–59) for age ≥80 was 20.60 (95% confidence interval (CI) 18.70 to 22.68), age 70–79 was 6.07 (95% CI 5.51 to 6.67) and age 60–69 was 2.40 (95% CI 2.16 to 2.67).¹¹

A case-control study of 4,272 severe COVID-19 cases and 36,948 controls in Scotland found that severe COVID-19 was significantly associated with older age. The odds ratio (OR) associated with a 10-year increase in age was 2.87 for severe disease and 3.70 for fatal disease.³³

A case-control study based on data from the UK Biobank found that although age over 70 was still a significant risk factor for severe disease, other clinical risk factors were more influential than either age or sex in determining who would develop severe disease.³⁴

Increasing age remained significantly associated with death and hospital admission after vaccination according to findings from a prospective cohort study of just under 7 million vaccinated (74% had two vaccine doses) individuals from 8 Dec 2020 to 15 June 2021.³⁵

Evidence

An observational study of over 17 million UK primary care patients looked at the risk of hospitalisation, intensive care unit (ICU) admission and death by ethnic group.⁵⁴ It found that compared with the white group, the following ethnic groups had an increased risk of COVID-19-related hospitalisation:

• South Asian group (HR 1.48, 95% CI 1.41 to 1.55)
• black group (HR 1.78, 95% CI 1.67 to 1.90)
• mixed ethnicity group (HR 1.63, 95% CI 1.45 to 1.83)
• other ethnicity group (HR 1.54, 95% CI, 1.41 to 1.69)

increased risk of COVID-19-related ICU admission:

• South Asian (HR 2.18, 95% CI 1.92 to 2.48)
• black (HR 3.12, 95% CI 2.65 to 3.67)
• mixed ethnicity (HR 2.96, 95% CI 2.26 to 3.87)
• other ethnicity (HR 3.18, 95% CI 2.58 to 3.93)
  
  

and increased risk of death:

• South Asian (HR 1.26, 95% CI 1.15 to 1.37)
• black (HR 1.51, 95% CI 1.31 to 1.71)
• mixed ethnicity (HR 1.41, 95% HR 1.11 to 1.81)
• other ethnicity (HR 1.22, 95% CI 1.00 to 1.48).

These data relate to wave 1 of the pandemic, February to August 2020.

An ecological study using Office of National Statistics (UK) data at local authority district (LAD) level in England found that in LADs with the highest deprivation quartile, where there is a 1 percentage point increase in black African (regression coefficient 2.86, 95% CI 1.08 to 4.64), black Caribbean (9.66, 95% CI 5.25 to 4.06) and Bangladeshi (1.95, 95% CI 1.14 to 2.76) populations, there is a significantly higher age-adjusted COVID-19 mortality compared to respective control populations.⁵⁵ 

Another population-level study linking census data and mortality found that people from all minority ethnic groups were at elevated risk of COVID19 mortality; HRs for black males and females were 3.13 (95% CI 2.93 to 3.34) and 2.40 (95% CI 2.20 to 2.61), respectively. However, for females, in models adjusted for a broad range of covariates including occupation and proxies for socioeconomic deprivation, the HRs were close to unity for all ethnic groups except black (1.29, 95% CI 1.18 to 1.42). For males, the mortality risk remained elevated for the black (HR 1.76, 95% CI 1.63 to 1.90), Bangladeshi/Pakistani (HR 1.35, 95% CI 1.21 to 1.49) and Indian (HR 1.30, 95% CI 1.19 to 1.43) groups.⁵⁶ 

In a single hospital study with a multi-ethnic catchment area age, gender, multimorbidity and black ethnicity (OR 2.1, 95% CI 1.5 to 3.2, p<0.001), compared with white ethnicity, (absolute excess risk <1/1000) were associated with COVID-19 admission and mortality. The South Asian cohort had lower admission rates and lower mortality compared to the white group (COVID-19 admissions, (OR 0.5, 95% CI 0.3 to 0.8, p<0.01); non-COVID admissions, (OR 0.4, 95% CI 0.3 to 0.6, p <0.00) and community deaths (OR 0.5, 95% CI 0.3 to 0.7, p< 0.001). Despite many common risk factors ethnic groups had different admission rates and within-group differing association of risk factors. Deprivation impacted only the white ethnicity group, in the oldest age bracket and in a lesser (not most) deprived quintile. ⁵⁷ 

A UK observational study investigated associations between ethnicity and obesity and found that compared with white individuals without obesity, all other combinations of obesity and ethnicity had a higher risk of admission to critical care, receiving mechanical ventilation, or mortality in those admitted to hospital with COVID-19. However, the risk of all outcomes was greatest in those of black ethnicity with obesity.⁵⁸  

A case-control study of 4,272 severe COVID-19 cases and 36,948 controls in Scotland found no statistically significant association of ethnicity with severe COVID-19. The authors note that case numbers from ethnic minority backgrounds were very small so confidence intervals were wide.³³  

A single centre, retrospective study of 907 patients admitted to hospital with COVID-19 in Birmingham, UK between February and May 2020 found that, after clinical factors had been adjusted for, ethnicity and social deprivation had no statistically significant association with mortality.⁵² 

A study of admissions for COVID-19 at five East London hospitals found that compared with white patients, those from minority ethnic backgrounds were younger, with differing comorbidity profiles and less frailty. Asian and black patients were more likely to be admitted to ICU and to receive invasive ventilation (OR 1.54, 95% CI 1.06 to 2.23, p=0.023 and OR 1.80, 95% CI 1.20 to 2.71, p=0.005, respectively). After adjustment for age and sex, patients from Asian (HR 1.49, 95% CI 1.19 to 1.86, p<0.001) and black (HR 1.3, 95% CI 1.02 to 1.65, p=0.036) backgrounds were more likely to die. These findings persisted after adjustment for a range of risk factors including major comorbidities, obesity, smoking, frailty and ABO blood group.⁵⁹ 

Indian and Pakistani ethnicities remained significantly associated with death and hospital admission in a vaccinated population according to findings from a prospective cohort study of just under 7 million vaccinated individuals (74% had two vaccine doses) from 8 Dec 2020 to 15 June 2021. ³⁵ The HR for people of Indian ethnicity compared to white people was 1.59 (95% CI 1.16 to 2.18) for death and 1.32 (95% CI 1.00 to 1.75) for hospitalisation. For Pakistani compared to white ethnicity the HR was 2.28 (95% CI 1.59 to 3.27) for death and 2.49 (95% CI 1.86 to 3.33) for hospitalisation. 

Evidence

Occupation and severe COVID-19

A UK cohort study (Biobank, with exposure ascertainment from 2006- 2010) included 120,075 participants aged 49– 64.³⁶ Of these, 29.3% were classified as essential workers (healthcare (9%), social and education (11.2%) and ”other” (9.1%)). White participants made up 92.2% of the sample, South Asians 2.6% and black participants 2.7%. Woman and ethnic minority participants were more likely to be employed in essential occupations.

In comparison with non-essential workers, healthcare workers (n=10,646) had a greater risk of severe COVID-19 as measured by hospitalisation or death, (relative risk (RR) 7.43, 95% CI 5.52 to 10.00).³⁶ This association remained when adjusted for age, gender, country of birth, ethnicity socioeconomic factors of deprivation, education, shift work, health conditions and lifestyle factors. Similarly, social care workers (n=5,297) had a higher risk when compared with non-essential workers, (RR 2.46, 95% CI 1.47 to 4.14). Transport workers within the subcategory of ”other”
essential workers (n=3,279) also had a higher risk of severe COVID-19 (RR 2.20, 95% CI 1.21 to 4.00) but this association was not statistically significant when adjusted for socioeconomic status (RR 1.66, 95% CI 0.91 to 3.01). There were no strong associations between occupation and severe COVID-19 observed for police, food or education workers.

Men, South Asian and black ethnic groups, those with socioeconomic disadvantage and the least educated groups had higher risk of severe COVID-19 compared with women, white British, those with socioeconomic advantage and degree educated groups. Shift work and manual work were associated with a higher risk of severe COVID-19 as were being overweight or obese or being a previous smoker.³⁶

Occupation and deaths due to COVID-19

In records of deaths involving COVID-19 in Scotland in the 21 months to 30 November 2021, the occupation category with the highest age-standardised rate per 100,000 of population was for process, plant and machine operatives (58.2).³⁷ This compared with the rate of 24.5 for the 950 deaths across all occupations. Those whose death certified occupation related to the category of elementary occupations (which includes construction workers and cleaners) had the next highest rate of 37.5. The corresponding rate for healthcare workers was 13.5 and for social care workers it was 34.8. People in professional occupations had the lowest death rate (7.9 per 100,000 over 21 months).

Evidence

Factors associated with hospital admission

A UK cohort study of 427 pregnant women admitted to hospital for COVID-19 found that 233 (56%) were from black or other ethnic minority groups. Each of four categories of non-white ethnicity (Asian, black, Chinese/other and mixed) were associated with two to four fold increased risk of admission to hospital with COVID-19 in an observed over expected analysis based on estimated total number of maternities in each group. This analysis also found increased risk of hospital admission with body mass index (BMI) >25 and age ≥35. Most women did not have severe illness, and most were admitted in the third trimester of their pregnancy.³⁸

Outcomes for pregnant women compared with non-pregnant women

A living systematic review and meta-analysis with literature search to October 2020 identified 192 studies examining aspects of COVID-19 disease in pregnant women.³⁹ Most studies were on women who required visits to hospital, including for childbirth. This limits the generalisability of findings.

The overall rate of COVID-19 diagnosis in pregnant women attending or admitted to hospital for any reason was 10% (95% CI 7% to 12%; 73 studies, 67,271 women). Where universal screening was in place the rate was 7%, whilst for settings with testing based on symptoms it was 28%. The rate of COVID-19 positivity was 4% across asymptomatic study participants. Three quarters (73%) of the pregnant women with COVID-19 in the universal screening population were asymptomatic.³⁹ When compared with non-pregnant women with COVID-19 the odds of admission to ICU (OR 2.13, 95% CI 1.53 to 2.95) and need for invasive ventilation (OR 2.59, 95% CI 2.28 to 2.94) were higher in pregnant women. When compared with non-pregnant women, factors associated with increased risk of severe COVID-19 were age ≥35 (7 studies), BMI >30 (5 studies), chronic hypertension (2 studies) and pre-existing diabetes (3 studies).³⁹

Where pregnant women with the disease have symptoms the pattern is similar to that of the general female population with the most common symptoms being fever (40%) and cough (41%). When compared with nonpregnant women (of reproductive age) pregnant women were less likely to report symptoms of fever (OR 0.49, 95% CI 0.38 to 0.63; 11 studies, 240,324 women) and myalgia (OR 0.53, 95% CI 0.36 to 0.78; 3 studies, 240,105 women).³⁹

A case-control study from France examined the risk of ICU admission in 83 pregnant women with COVID-19 at ≥20 weeks’ gestation with 107 non- 14 pregnant controls matched for age, diabetes, hypertension and asthma. ICU admission was 2.38% in the control group and 11.08% in the pregnant COVID-19 case group (p=0.024).⁴⁰

A comprehensive guideline published in November 2021 by the Royal College of Midwives and the Royal College of Obstetricians and Gynaecologists reported that pregnant women were more likely to be admitted to ICU but that this may reflect lower thresholds for admission rather than greater severity of disease.⁴¹ It also found that pregnant women have higher needs for ventilation and extracorporeal membrane oxygenation which may indicate that pregnant women have an increased risk of severe disease. This guideline was based on a literature review to June 2021 and expert opinion. The guideline reported that pregnant women who required hospitalisation had overall worse maternal outcomes, including an increased risk of death, although the risk of death remains very low (the UK maternal mortality rate from COVID-19 is 2.4/100,000 maternities). It also reported that pregnant women may be at increased risk of complications in the third trimester when compared to earlier in pregnancy. The full guideline can be found here https://www.rcog.org.uk/globalassets/documents/guidelines/2022-01-11- coronavirus-covid-19-infection-in-pregnancy-v14.3.pdf

COVID pregnancy outcomes compared with non-COVID pregnancy outcomes

The odds of preterm birth were higher in pregnant women with COVID-19 when compared with pregnant women without COVID-19 (OR 1.47, 95% CI 1.14 to 1.91; 18 studies, 8,459 women).³⁹

Neonates born to women with COVID-19 had a higher risk of neonatal ICU admission (OR 4.89, 95% CI 1.87 to 12.81; 10 studies, 5,873 neonates).³⁹

Evidence

An observational study of 10,926 deaths due to COVID-19 in England found that death due to COVID-19 was significantly associated with male sex (HR 1.59, 95% CI 1.53 to 1.65).¹¹

A case-control study of 4,272 severe COVID-19 cases and 36,948 controls in Scotland found that severe COVID-19 was significantly associated with male sex. The OR associated with male sex was 1.63 for all severe disease and 1.58 for fatal disease.³³ A systematic review of international data suggests that this association is maintained across all age groups.⁴⁶

A case-control study based on UK Biobank data found that other factors, including a genetics-based score and clinical risk factors were more influential than age or sex in determining who would develop severe disease.³⁴

A large matched cohort study of UK women found that oestrogen exposure had a protective effect for COVID-19 status and severity.⁴⁷

Male sex remains significantly associated with death and hospital admission in a vaccinated population according to findings from a prospective cohort study of just under 7 million vaccinated individuals (74% had two vaccine doses) from 8 Dec 2020 to 15 June 2021.35 Hazard ratio for death was 1.89 (95% CI 1.72 to 2.08), and for hospitalisation 1.31 (95% CI 1.20 to 1.44).³⁵

Evidence

A meta-analysis of 19 peer-reviewed papers showed that smoking is associated with disease progression and severe disease, with smokers having greater odds of progression in COVID-19 severity compared with people who never smoked (OR 1.91, 95% CI 1.42 to 2.59, p=0.001). ⁴²

A systematic review of peer-reviewed studies carried out by the World Health Organization suggested that smoking is associated with increased severity of disease and death in hospitalised COVID-19 patients. The authors note that although likely related to severity, there is no evidence to quantify the risk to smokers of COVID-19-related hospitalisation.⁴³

An observational study of 10,926 deaths due to COVID-19 in England found that death due to COVID-19 was significantly associated with former smoking (HR 1.19, 95% CI 1.14 to 1.24) but not current smoking (HR 0.89, 95% CI 0.82 to 0.97).¹¹

A prospective cohort analysis of UK Biobank data found that amongst participants >69 years, once infected, smokers were twice as likely to die from COVID-19 compared with non-smokers (RR 2.15, 95% CI 1.11 to 4.16) whereas there was no statistically significant difference for those under the age of 69 (RR 1.22, 95% CI 0.83 to 1.79).⁴⁴ Similar patterns 15 were observed for previous smokers. The impact of smoking was similar in men and women.

A prospective cohort study linked vaccination status, primary care records, COVID-19 testing, hospitalisation and mortality data in Scotland to assess the frequency of adverse COVID-19 outcomes in people receiving at least one vaccine dose. Data from December 2020 to April 2021 were included. Being a smoker was associated with increased risk of the composite outcome of COVID-19-related hospitalisation or death. When compared with non-smokers, smokers and ex-smokers had increased risk of adverse outcome (RR 1.14, 95% CI 0.97 to 1.33, RR 1.18, 95% CI 1.01 to 1.38, respectively), but this was only statistically significant for ex-smokers.⁴⁵

Evidence

An observational study of 10,926 deaths due to COVID-19 in England found that death due to COVID-19 was significantly associated with living in the most deprived quintile (HR 1.79, 95% CI 1.68 to 1.91) compared with the least deprived quintile. The associations were adjusted for comorbidity, age, sex but not adjusted for employment or housing density.¹¹

An English cohort study of over 45,000 patients with hypertension and suspected COVID-19 found that increasing deprivation was significantly associated with death due to COVID-19. ⁴⁸ 

A case-control study of 4,272 severe COVID-19 cases and 36,948 controls in Scotland found that severe disease was significantly associated with socioeconomic deprivation (RR 0.54, 95% CI 0.48 to 0.62) for the least deprived quintile compared to most deprived. ³³ 

Based on data to 14 February 2022, COVID-19 cases in people coded by postcode to the most deprived quintile made up 21.8% of all positive tests.⁴⁹ People in the least deprived quintile made up 19.5% of all cases. For hospital admissions, those people in the most deprived quintile made up 30.9% of cases whilst those in the least deprived quintile contributed 12.5% of admissions.

A national audit of demographics, activity and outcomes for patients with laboratory-confirmed COVID-19 disease admitted to Scottish ICUs between 1 March and 19 September 2021 reported that the proportion of patients living in the two most deprived quintiles of area deprivation rose from 52.7% in waves one and two to 55.1% in wave three. During the third wave (1 August 2021 to 19 September 2021) the proportion of patients admitted from the two most deprived quintiles was nearly three times that from the two least deprived quintiles (65.1% compared with 22.3%). Overall estimated 30-day mortality for all patients admitted to ICU in wave three was 25.7%, with a higher estimate of death among those in the highest quintile of deprivation compared with those in the lowest quintile (30.7% compared with 28.8%).⁵⁰ 

In Scotland, the age-standardised rate of deaths involving COVID-19 between 1 March 2020 and 31 January 2022 in the most deprived quintile (213.7 per 100,000 population) was 2.47 times higher than in the least deprived quintile (86.59 per 100,000 population).³⁷ 

A study using UK Biobank data found those allocated to the least advantaged quartile of the Townsend index to be at greater risk of being tested, testing positive and testing positive in hospital.⁵¹ 

A single centre, retrospective study of 907 patients admitted to hospital with COVID-19 in Birmingham, UK between February and May 2020 found that, after clinical factors had been adjusted for, ethnicity and social deprivation had no statistically significant association with mortality.⁵² 

A prospective cohort study of admissions to three Scottish acute hospitals on one day in April 2020 found that socioeconomic deprivation had no impact on health outcomes, although it did negatively impact length of hospital stay.⁵³ This study compared the five most deprived deciles of the Scottish index for multiple deprivation with the five least deprived deciles which may have resulted in a reduction in perceived effect.

Socioeconomic deprivation remains significantly associated with death and hospital admission in a vaccinated population according to findings from a prospective cohort study of just under 7 million vaccinated individuals (74% had two vaccine doses) from 8 Dec 2020 to 15 June 2021.³⁵ Hazard ratio for death was 1.27 (95% CI 1.17 to 1.37) per 5 unit increase in the Townsend deprivation score (a greater Townsend score implies a greater level of deprivation). The corresponding HR for hospitalisation was 1.41 (95% CI 1.30 to 1.53).

A prospective cohort study linked vaccination status, primary care records, COVID-19 testing, hospitalisation and mortality data in Scotland to assess the frequency of adverse COVID-19 outcomes in people receiving at least one vaccine dose. Data from December 2020 to April 2021 were included. Socioeconomic deprivation was associated with increased risk of the composite outcome of COVID-19-related hospitalisation or death. When compared with people from the least deprived Scottish Index of Multiple Deprivation (SIMD) quintile, the relative risks for those in the most deprived and second most deprived group were RR 1.57 (95% CI 1.30 to 1.90) and RR 1.40 (95% CI 1.16 to 1.70) respectively.⁴⁵