In China, 87% of confirmed cases were aged 30 to 79 years and 3% were aged 80 years or older. Approximately 51% of patients were male.
In Italy, the median age and prevalence of comorbidities was higher compared with China.
In the UK, the median age of patients was 73 years and males accounted for 60% of admissions in a prospective observational cohort study of more than 20,000 hospitalised patients.
In the US, older patients (aged ≥65 years) accounted for 31% of all cases, 45% of hospitalisations, 53% of intensive care unit admissions, and 80% of deaths, with the highest incidence of severe outcomes in patients aged ≥85 years.
China: 2.1% (median age 7 years)
Italy: 1.2% (median age 4 to 5 years; higher in males but not statistically significant)
Spain: 0.8% (median age 3 years)
US: 10% (or 729 cases per 100,000 children in the population) as of 10 September.
In the UK, a prospective observational cohort study found that children and young adults represented 0.9% of all hospitalised patients at the time. The median age of children admitted to hospital was 4.6 years, 56% were male, 35% were under 12 months of age, and 42% had at least one comorbidity. In terms of ethnicity, 57% were White, 12% were South Asian, and 10% were Black. Age under 1 month, age 10 to 14 years, and Black race were risk factors for admission to critical care.
Most cases are from familial clusters, or children who have a history of close contact with an infected patient. It appears that children generally don’t spread the virus to household contacts. Unlike adults, children do not seem to be at higher risk for severe illness based on age or sex.
A meta-analysis of over 2500 pregnant women with confirmed COVID-19 found that 73.9% of women were in the third trimester; 50.8% were from Black, Asian, or minority ethnic groups; 38.2% were obese; and 32.5% had chronic comorbidities.
In the UK, the estimated incidence of admission to hospital with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is 4.9 per 1000 maternities. Most women were in the second or third trimester. Of these patients, 41% were aged 35 years or older, 56% were from Black or other ethnic minority groups, 69% were overweight or obese, and 34% had pre-existing comorbidities.
In the US, according to an analysis of 8200 infected pregnant women, Hispanic and non-Hispanic Black pregnant women appear to be disproportionately affected during pregnancy.
The overall proportion of healthcare workers who tested positive for SARS-CoV-2 among all patients with COVID-19 in a living systematic review and meta-analysis was 11% via polymerase chain reaction, and 7% via antibody screening. The most frequently affected healthcare workers were nurses. Only 5% of healthcare workers developed severe disease and 0.5% died. The incidence of severe or critical disease and mortality in healthcare workers was lower than the incidence of severe or critical disease and mortality in all patients.
US - 18%
UK - 10%
Italy - 9%
Netherlands - 6%
China - 4.2%.
The majority of healthcare workers with COVID-19 reported contact in the healthcare setting. In a study of over 9000 cases reported in healthcare workers in the US, 55% had contact only in a healthcare setting, 27% only in a household, 13% only in the community, and 5% in more than one setting.
People residing or working in an area with a high risk of transmission (e.g., closed residential settings, humanitarian setting), people residing in or travelling to an area with community transmission, and people working in a health setting (including within health facilities and households) at any time within the 14 days prior to symptom onset are at higher risk of infection.
A contact is a person who has experienced any one of the following exposures during the 2 days before and the 14 days after the onset of symptoms of a probable or confirmed case: face-to-face contact with a probable or confirmed case within 1 metre (3 feet) and for at least 15 minutes; direct physical contact with a probable or confirmed case; direct care for a patient with probable or confirmed COVID-19 without using recommended personal protective equipment; or other situations as indicated by local risk assessments.
Older age is a risk factor for infection. Data from a cross-sectional study in the UK indicate that people aged 40 to 64 years are at greatest risk of infection, followed by patients 75 years and older, and then people aged 65 to 74 years. The risk of severe illness in adults increases with age, with older people (aged 65 years and older) at highest risk. The highest mortality rate has been observed in patients 80 years and older. In the US, patients ≥65 years accounted for 31% of all cases, 45% of hospitalisations, 53% of intensive care unit admissions, and 80% of deaths, with the highest incidence of severe outcomes in patients aged ≥85 years. While age is an independent risk factor, the risk in older people is also partly related to the likelihood that older adults are more likely to have comorbidities.
Widespread transmission has been reported in long-term care facilities. People who live in a nursing home or long-term care facility are at higher risk for severe illness. Care home residents represent approximately one third of the total number of deaths in England and Wales; other countries have reported a similar experience. This is likely due to shortages in personal protective equipment, a vulnerable population, and a lack of testing. More than one third of care homes in England have had cases. A study across four nursing homes in the UK found that 26% of residents died over a 2-month period, with all-cause mortality increasing by 203% compared with previous years. Approximately 40% of residents tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and of these, 43% were asymptomatic and 18% had atypical symptoms.
Male sex is a risk factor for infection, more severe disease, worse prognosis, and mortality. Data from a cross-sectional study in the UK found that the adjusted odds of a positive test were greater in males (18.4%) compared with females (13.3%). It has been hypothesised that this may be due to the presence of androgens, a lower level of SARS-CoV-2 antibodies compared with females, or women mounting a stronger immune response compared with men; however, further research is required.
People from Black, Asian, and minority ethnic (BAME) groups are at a higher risk of infection and worse outcomes, including an increased risk of mortality, compared with the general population. The reasons for this are unclear and require further research. Data from a cross-sectional study in the UK found that South Asian and Black patients had 1.93 and 1.47 the odds of suspected infection, respectively. The average age of patients from ethnic minorities was significantly lower than that of White patients. Ethnic minorities in the UK (including South Asian, East Asian, Black, and other ethnic minorities) admitted to hospital were more likely to be admitted to intensive care and require invasive mechanical ventilation compared with White patients, despite similar disease severity at admission and being younger with fewer comorbidities. There is also evidence from the US that supports this. Age-adjusted data from the Centers for Disease Control and Prevention (as of 25 June) show that non-Hispanic American Indian, Alaska Native, and non-Hispanic Black people have approximately 5 times the rate of hospitalisations of non-Hispanic White people, and Hispanic or Latino people have approximately 4 times the rate of hospitalisations of non-Hispanic White people. However, a cohort study of over 11,000 patients across 12 states in the US found there was no difference in all-cause, in-hospital mortality between Black and White patients after adjusting for sociodemographic factors and comorbidities (e.g., age, sex, insurance). In a study of over 10,000 deceased patients in the US, 35% of Hispanic and 30% of non-White decedents were aged <65 years, compared with 13% of White, non-Hispanic decedents.
People with comorbidities are at higher risk for severe illness and mortality. The more comorbidities a person has, the greater their risk for severe illness. In the US, approximately 90% of hospitalised patients had at least one reported underlying medical condition (as of 5 September 2020). The most prevalent comorbidities in adults with COVID-19 are hypertension, diabetes, chronic respiratory disease, cardiovascular disease, and other chronic diseases such as cancer. In a prospective observational cohort study of more than 20,000 hospitalised patients in the UK, the most common comorbidities were chronic cardiac disease (31%), uncomplicated diabetes (21%), non-asthmatic chronic pulmonary disease (18%), and chronic kidney disease (16%). Similarly, in the US the most common comorbidities were cardiovascular disease (32%), diabetes (30%), and chronic lung disease (18%). Hospitalisations were six times higher and deaths were 12 times higher in patients with comorbidities compared with those without. It has been estimated that approximately 56% of adults in the US are at risk for requiring hospitalisation from COVID-19 because of the presence of at least one comorbidity. These underlying conditions are associated with modifiable risk factors, which, if improved through lifestyle changes, may improve a person’s risk status.
Among 345 paediatric cases with information on underlying conditions, 23% had at least one underlying condition, most commonly chronic lung disease, cardiovascular disease, or immunosuppression. Approximately 39% of hospitalised children had an underlying condition in another study. The most prevalent comorbidities were asthma, neurological disorders, diabetes, obesity, cardiovascular disease, and malignancy/haematological conditions.
Around 32% of young adults (aged 18-25 years) in the US had underlying conditions that put them at risk for severe disease including heart conditions, diabetes, asthma, immune conditions, liver conditions, and obesity. Smoking (including e-cigarette use) in the past 30 days also increased the risk. The rate of young adults at risk for severe disease decreased to 16% when considering non-smokers only.
People with serious heart conditions (e.g., heart failure, coronary artery disease, cardiomyopathy, pulmonary hypertension) are at increased risk of severe illness. Cardiovascular disease is associated with a 3-fold increased odds of severe infection, and an 11-fold increase in all-cause mortality.
People with hypertension may be at increased risk of severe illness. Hypertension has been associated with increased poor composite outcome, including mortality, severe disease, acute respiratory distress syndrome, need for intensive care admission, and disease progression. Patients with hypertension have a 2.27-fold higher risk of severe disease, and a 3.48-fold higher risk of fatality compared with patients without hypertension.
People with type 2 diabetes are at increased risk of severe illness. People with type 1 diabetes or gestational diabetes may also be at increased risk of severe illness; however, evidence is limited for these patient groups. The pooled prevalence of diabetes in COVID-19 patients is approximately 15%. Diabetes is associated with an increased risk of disease progression, intensive care admission, acute respiratory distress syndrome, mechanical ventilation, and mortality. The risk of intensive care admission and mortality is significantly higher in patients with diabetes compared with those without diabetes (pooled risk ratio of 1.88 and 1.61, respectively). Risk factors for poor prognosis and higher mortality in patients with type 1 or type 2 diabetes include older age, male sex, non-White ethnicity, socioeconomic deprivation, renal impairment, history of stroke or heart failure, higher glycosylated haemoglobin (HbA1c) levels, higher body mass index, elevated C-reactive protein, diabetic ketoacidosis, and insulin use. However, HbA1c levels were not associated with mortality in a large US cohort of hospitalised patients with diabetes and COVID-19, while insulin treatment and obesity were strong and independent risk factors for in-hospital mortality. Hyperglycaemia is also an independent risk factor for poor prognosis in hospitalised patients with or without known diabetes. One third of all deaths in hospitalised patients in England occur in patients with diabetes. People with type 1 diabetes have 3.50 times the odds of dying in hospital with COVID-19, while people with type 2 diabetes have 2.03 times the odds. Patients with newly diagnosed diabetes have a higher risk of all-cause mortality compared with patients with known diabetes, hyperglycaemia, or normal glucose. The poor prognosis in these patients is likely due to the syndromic nature of diabetes, with factors such as hyperglycaemia, older age, and the presence of comorbidities (e.g., obesity, hypertension, cardiovascular disease) all contributing to the increased risk.
There is no clear evidence that people with asthma or chronic obstructive pulmonary disease (COPD) are at higher risk of infection. People with COPD (including emphysema and chronic bronchitis) are at increased risk of severe illness. COPD is associated with a 5-fold increased risk of severe infection. People with moderate to severe asthma may be at increased risk of severe illness; however, evidence is limited. There is no statistically significant association between asthma and a higher risk of mortality in patients with COVID-19. Asthma prevalence among hospitalised COVID-19 patients appeared to be similar to the asthma prevalence in the general population in one study, and asthma was not an independent risk factor for intubation. People with other chronic lung diseases (e.g., cystic fibrosis, idiopathic pulmonary fibrosis) may be at increased risk of severe illness; however, the evidence is limited. There are no data on whether paediatric respiratory diseases (including childhood asthma) are risk factors for infection or severity.
People with chronic kidney disease may be at higher risk of infection. Data from a cross-sectional study in the UK found that the adjusted odds of a positive test were greater in patients with chronic kidney disease (32.9%) compared with those without (14.4%). People with chronic kidney disease are also at increased risk of severe illness. The prevalence of pre-existing chronic kidney disease in COVID-19 patients was 5.2% (2.3% for end-stage kidney disease), and is an independent risk factor for developing acute kidney injury as a complication.
People with cancer are at a higher risk of infection, likely due to immunosuppressive treatments and/or recurrent hospital visits. People with cancer are also at increased risk of severe illness. The overall pooled prevalence of cancer in COVID-19 patients is approximately 2.3%, and it is significantly associated with severe disease. Patients with cancer are 76% more likely to get severe disease compared with those without cancer. They also have an increased risk of worse clinical outcomes including intensive care unit admission and all-cause mortality (particularly those with metastatic disease, haematological cancer, or lung cancer), and appear to deteriorate more quickly compared with patients without cancer. Patients with haematological malignancies (in particular, leukaemia) have a higher risk of severe or critical disease and a high mortality rate compared with patients with solid tumours. The odds ratio of intensive care admission rates and mortality rates between cancer and non-cancer groups was 2.88 and 2.25, respectively. Factors associated with an increased mortality rate in adults include older age, male sex, smoking status, number of comorbidities, Eastern Cooperative Oncology Group performance status of 2 or more, receiving chemotherapy within 4 weeks before symptom onset, cancer surgery, and active cancer. The all-cause mortality rate in patients with cancer is significantly associated with increasing age. Children with cancer may be no more vulnerable to infection compared with children without cancer. Limited data show that the overall morbidity in paediatric patients with cancer is low, with only 5% requiring hospitalisation for symptoms. Pooled case fatality rates of between 6.8% and 21% have been reported in adults with cancer, although these rates should be interpreted with caution.
People with obesity are at increased risk of severe illness. A pooled analysis found that people with obesity are at a 46% higher risk of infection, a 113% higher risk of hospitalisation, a 74% higher risk of intensive care admission, and 48% higher risk of mortality. Data from a cross-sectional study in the UK found that the adjusted odds of a positive test were greater in patients with obesity (20.9%) compared with those without (13.2%). Data from France estimates that the prevalence of obesity is 1.35 times higher in patients with severe disease compared with the general population. Obesity plays a significant role in the risk of death from COVID-19, particularly in males and younger people (<60 years of age). Increased body mass index is a significant risk factor for severe disease in pregnant women. Obesity was the most common comorbidity in children, and was significantly associated with mechanical ventilation in children 2 years and older in a single-centre retrospective study in New York.
People with sickle cell disease are at increased risk of severe illness. Among 178 patients with sickle cell disease and COVID-19 in the US (mean patient age <40 years), 69% were hospitalised, 11% were admitted to intensive care, and 7% died. Infection can cause acute chest syndrome in patients with sickle cell disease.
People with an immunocompromised state from solid organ transplant are at increased risk of severe illness. Organ transplant recipients may be at higher risk of severe illness or complications, more rapid clinical progression, and a prolonged clinical course compared with the general population due to chronic immunosuppression and the presence of co-existing conditions. Hospitalisation and mortality rates in liver transplant recipients are disproportionately high compared with non-transplant patients regardless of age or time after transplant. Older age and diabetes are significant risk factors for death among these patients.
People who are current or former smokers may be at increased risk of severe illness; however, evidence is limited. Current smokers have an increased risk of severe or critical disease. Patients with any smoking history have a significantly increased risk of severe or critical disease, in-hospital mortality, disease progression, and need for mechanical ventilation. This may be due to increased airway expression of the angiotensin-converting enzyme-2 receptor in smokers. The World Health Organization has reviewed the available evidence and concluded that smoking is associated with increased severity of disease and death in hospitalised patients.
People with cerebrovascular disease may be at increased risk of severe illness; however, evidence is limited. The pooled prevalence of pre-existing cerebrovascular disease in COVID-19 patients is 4.4%. Patients with pre-existing cerebrovascular disease have 2.67-fold higher odds of poor outcomes including intensive care admission, mechanical ventilation, and mortality.
People with chronic liver disease, especially cirrhosis, may be at increased risk of severe illness; however, evidence is limited. The prevalence of chronic liver disease in COVID-19 patients is approximately 3%. The presence of chronic liver disease is associated with more severe disease and overall mortality. The 30-day mortality rate is higher in patients with cirrhosis, with the main causes of death being respiratory complications and sudden worsening of liver function leading to end-stage liver disease.
Dyslipidaemia appears to be associated with an increased risk of severe disease according to one meta-analysis.
Patients with severe COVID-19 may be more likely to have metabolic dysfunction-associated fatty liver disease (MAFLD; also called non-alcoholic fatty liver disease) compared with patients who have non-severe COVID-19. MAFLD is associated with a 4- to 6-fold increase in severity of COVID-19. Severity of COVID-19 has been associated with younger age (<60 years) and intermediate or high fibrosis-4 (FIB-4) scores in patients with MAFLD.
Surgical mortality and complications are higher in patients with COVID-19 compared with patients without COVID-19. A retrospective study of 34 patients in China who underwent elective surgeries during the incubation period of COVID-19 found that all patients developed pneumonia after surgery. Approximately 44% of these patients required admission to the intensive care unit, and 20% died. Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection, and are associated with higher mortality, particularly in men and those aged 70 years and over.
Pregnant women may be at increased risk of severe illness and adverse pregnancy outcomes. According to an analysis of 8200 infected pregnant women, pregnant women were more likely to be hospitalised, to be admitted to the intensive care unit, and to receive mechanical ventilation compared with non-pregnant women; however, mortality rates did not differ.
People who are immunocompromised (e.g., blood or bone marrow transplant, immune deficiencies, prolonged use of corticosteroids or other immunosuppressant medications) may be at increased risk of severe illness; however, evidence is limited. Patients with inflammatory bowel disease who were on long-term biologicals or other immunomodulatory therapies did not have a higher risk of poor outcomes; however, recent corticosteroid use may be related to worse outcomes. Glucocorticoid exposure of ≥10 mg/day (prednisolone) has been associated with a higher odds of hospitalisation in patients with rheumatological disease. Also see HIV infection, below.
Evidence suggests that there may be an association between long-term exposure to ambient air pollution and COVID-19. The highest numbers of cases were recorded in the most polluted regions of Italy, with patients presenting with more severe disease requiring intensive care. The mortality was 2-fold higher in polluted regions compared with other regions. One study found that of deaths from COVID-19 across 66 administrative regions in Italy, Spain, France, and Germany, 78% of deaths occurred in just five regions, and these regions were the most polluted in terms of nitrogen dioxide levels. A preprint study from Harvard University found that people who live in US regions with high levels of air pollution were more likely to die from COVID-19 than those who live in less polluted areas. The researchers found that an increase of 1 microgram/m³ in fine particulate matter is associated with an 8% increase in the COVID-19 death rate.
Distribution of community outbreaks along restricted latitude, temperature, and humidity measurements are consistent with the behaviour of a seasonal respiratory virus. Evidence suggests that cold and dry conditions may increase transmission, and warm and humid conditions may reduce the rate of infections; however, evidence is not yet sufficient to prove causation. However, there is other evidence that suggests ambient temperature has no significant impact on transmission, especially during the pandemic stage of an emerging pathogen. Further research is required on how weather conditions influence transmission as colder temperatures have been associated with increased transmission of other coronaviruses. Higher latitude may also be associated with an increased risk of cases and deaths in some countries. A positive correlation has been found between lower death rates and a country’s proximity to the equator, suggesting a correlation between sunlight exposure (and vitamin D levels) and reduced mortality.
Data from a cross-sectional study in the UK found that the adjusted odds of a positive test were greater in people living in urban areas (26.2%) compared with people living in rural areas (5.6%), and in people living in more deprived areas (29.5%) compared with people living in less deprived areas (7.7%).
A single-centre, retrospective cohort study suggests that vitamin D deficiency plays a role in the risk of infection. A population-based study in Israel found that patients who tested positive for COVID-19 had significantly lower plasma vitamin D levels compared with those who tested negative. Univariate analysis demonstrated an association between low plasma vitamin D level and increased likelihood of hospitalisation. The study concluded that low plasma vitamin D level appears to be an independent risk factor for COVID-19 infection and for hospitalisation. A small retrospective observational preprint study (not peer reviewed) also suggests a link between vitamin D insufficiency and COVID-19 severity. Further research is needed.
There was originally concern that people on these drugs may be at increased risk of infection or more severe disease due to upregulation of angiotensin-converting enzyme-2 (ACE2) receptor expression. However, high-certainty evidence suggests that use of these drugs is not associated with severe disease, and moderate-certainty evidence suggests that there is no association between the use of these medications and a positive SARS-CoV-2 test result among symptomatic patients. Despite this reassuring evidence, another meta-analysis found that the use of angiotensin-II receptor antagonists, and not ACE inhibitors, may augment the risk of SARS-CoV-2 infection in adults <60 years of age. A prospective cohort study of over 19,000 patients in England found that these drugs were associated with a significantly reduced risk of COVID-19, and were not associated with an increased risk of intensive care. However, variations between ethnic groups raise the possibility of ethnic-specific effects. The UK National Institute for Health and Care Excellence states that conclusion cannot be drawn on whether these drugs increase or decrease the risk of developing COVID-19 or severe disease based on the current available evidence. Professional societies recommend that patients who are already on these drugs continue to take them.
There is concern that people on these drugs may be at increased risk of infection or more severe disease as statins have been shown to increase the expression of ACE2 in laboratory animals, and may promote the activation of the inflammatory pathway in acute respiratory distress syndrome leading to more severe disease. However, a retrospective study of nearly 14,000 patients found that statin use was associated with a lower risk of all-cause mortality in patients with COVID-19, possibly due to the immunomodulatory effects of statins. A meta-analysis of four retrospective studies also suggests a reduced risk for fatal or severe disease among statin users. Further research into the potential therapeutic or detrimental effects of statins is required.
Proton-pump inhibitors (PPIs) are known to increase the risk of infections due to hypochlorhydria. There is evidence of an independent, dose-response relationship between the use of antisecretory medications and COVID-19 positivity. People taking PPIs had significantly increased odds for reporting a positive COVID-19 test when compared with those not taking PPIs. People taking H2 antagonists were not at elevated risk. Patients taking PPIs may also be at increased risk of severe clinical outcomes.
It is still unclear whether HIV infection influences infection and disease course. However, males affected by antiretroviral therapy-related complications may be at greater risk of severe disease.
Autoimmune disease, in general, does not appear to be associated with a higher risk of infection. Patients with autoimmune rheumatic disease may be more susceptible to infection compared with the general population, although data are scarce. Autoimmune disease has been associated with a slightly increased risk of disease severity and mortality; however, this was not statistically significant. Risk of mortality appears to be associated with older age and the presence of comorbidities even in patients with autoimmune disease, rather than the autoimmune disease itself or use of immunosuppressive medications. In patients with multiple sclerosis, neurological disability, age, and obesity were risk factors for severe disease. Weak evidence suggests that people with inflammatory bowel disease may be somewhat protected from infection, likely due to their ongoing treatment for the condition. Further research is required as there is concern about the risk of infection in these patients.
People with neurological conditions (e.g., dementia) may be at increased risk of severe illness; however, evidence is limited.
People with thalassaemia may be at increased risk of severe illness; however, evidence is limited.
Children may be at increased risk of severe illness if they have certain conditions (e.g., obesity, diabetes, asthma and chronic lung disease, immunosuppression); are medically complex; have serious genetic, neurological, or metabolic disorders; or have congenital heart disease. However, evidence is limited.
People with blood group A appear to be at increased risk of infection, while people with blood group O have a decreased risk (blood groups B and AB were not significantly associated with infection). A genome-wide association study found that patients with blood group A are at 45% increased risk of respiratory failure compared with other blood groups. It also found a protective effect in blood group O. Two chromosomal loci were associated with respiratory failure, and one of these coincided with the ABO blood group locus.
There is some emerging evidence that gut microbiota dysfunction may be implicated in the pathogenesis of COVID-19, although this is yet to be confirmed. Patients appear to have a depletion of beneficial commensals (Eubacterium ventriosum, Faecalibacterium prausnitzii, Roseburia and Lachnospiraceae taxa) and an overgrowth of opportunistic pathogens (Clostridium hathewayi, Actinomyces viscosus, Bacteroides nordii) during hospitalisation. Gut microbiome configuration has been associated with disease severity.
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