Over 225.6 million cases have been reported globally, with approximately 4.6 million deaths according to the World Health Organization. The US has the highest number of reported infections and deaths in the world. India, Brazil, the UK, and Russia have the highest number of infections after the US. Brazil, India, Mexico, and Peru have the highest number of deaths after the US.
Current detailed data for the UK situation is available.
In China, 87% of confirmed cases were aged 30 to 79 years and 3% were aged 80 years or older in the first wave of the pandemic. Approximately 51% of patients were male.
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 first wave.
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 in the first wave, with the highest incidence of severe outcomes in patients aged ≥85 years.
Adolescents appear to have similar susceptibility to infection as adults.
In the US, hospitalisations in adolescents peaked at 2.1 per 100,000 in early January 2021, declined to 0.6 per 100,000 in March, and rose to 1.3 per 100,000 in April. Among hospitalised adolescents, approximately one third required admission to the intensive care unit and 5% required mechanical ventilation. This data was based on 204 adolescents who were likely hospitalised primarily for COVID-19 during January 1 to March 31 2021. The cumulative number of hospitalisations in the 5- to 17-year-old age bracket from March 2020 to June 2021 was 1909 cases.
Evidence suggests that children have a lower susceptibility to infection compared with adults, with an odds ratio of 0.56 for being an infected contact compared with adults. However, observational evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may spread more effectively and rapidly among young children, although hospitalisation rates decreased. Most cases in children are from familial clusters, or children who have a history of close contact with an infected patient. It is rare for children to be the index case in household transmission clusters. Infection rates vary according to geographical location. The mean age of children with infection was 6.5 years in the first wave. Unlike adults, children do not seem to be at higher risk for severe illness based on age or sex.
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.
In the US, a retrospective cohort study of over 135,000 children found that the mean age of infected children was 8.8 years, and 53% were male. In terms of ethnicity, 59% were White, 15% were Black, 11% were Hispanic, and 3% were Asian. Only 4% of children tested positive for SARS-CoV-2 in this population, and clinical manifestations were typically mild. Cases in children, adolescents, and young adults increased between October to December 2020; however, hospitalisations, intensive care unit admissions, and deaths remain low for these groups (2.5%, 0.8%, and <0.1% respectively, based on available data).
Globally, the case fatality rate in children appears to be higher in low- and middle-income countries compared with high-income countries.
The overall prevalence in pregnant and recently pregnant women attending or admitted to hospital for any reason has been estimated to be 10%; however, the rate varies across studies and countries. A meta-analysis of over 2500 pregnant women with confirmed disease 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 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, 118,267 cases have been reported in pregnant women (as of 6 September 2021), with 21,097 hospitalisations and 147 deaths. According to an analysis of approximately 400,000 women aged 15 to 44 years with symptomatic disease, Hispanic and non-Hispanic Black pregnant women appear to be disproportionately affected during pregnancy.
Approximately 14% of the cases reported to the World Health Organization are in healthcare workers (range 2% to 35%).
The incidence of infection in healthcare workers ranged from 0% to 49.6% (by polymerase chain reaction), and the prevalence of SARS-CoV-2 seropositivity ranged from 1.6% to 31.6%. The wide ranges are likely related to differences in settings, exposures, rates of community transmission, symptom status, use of infection control measures, and other factors. There was no consistent association between sex, age, or healthcare worker role (i.e., nurse versus physician) and risk for infection or seropositivity. However, Black or Hispanic ethnicity was significantly associated with an increased risk of infection compared with White people. Working in a hospital unit with COVID-19 patients, being a frontline worker, and direct or prolonged patient contact were also associated with an increased risk for infection. The presence of immunoglobulin G antibodies was associated with a decreased risk for reinfection.
The majority of healthcare workers 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 who have been in contact with a probable or confirmed case are at increased risk of infection.
The World Health Organization defines a contact as 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.
The US Centers for Disease Control and Prevention defines a close contact as someone who has been within 2 metres (6 feet) of an infected person for at least 15 minutes over a 24-hour period, beginning 2 days before symptom onset (or 2 days before testing in asymptomatic patients).
People who live or work in, or travel to, a location with a high risk of transmission are at increased risk of infection.
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.
People at risk of infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern include:
Those who have been in, or transited through, any countries with transmission of variants of concern (consult local guidance for lists of affected countries) and who develop symptoms within 10 days of departure or transit (or date of sampling for a positive SARS-CoV-2 test if asymptomatic)
Those known to be infected with a variant of concern based on sequencing results, regardless of travel history
Contacts of individuals described above.
Older people are at increased risk for infection and severe disease.
The risk of hospitalisation and death increases with age. For example, in people aged 85 years and older, the risk of hospitalisation is 15 times higher and the risk of death is 610 times higher compared with 18- to 29-year-olds according to US data.
In the UK, data from a cross-sectional study indicated 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 highest mortality rate was 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 early in the pandemic, with the highest incidence of severe outcomes in patients aged ≥85 years.
Observational studies in older adults aged ≥60 years across multiple countries found that approximately 51% of older patients had severe infection, while 22% were critically ill.
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. The higher prevalence of malnutrition in older patients may also contribute to poor outcomes.
Males are at increased risk for infection and severe disease.
In the UK, data from a cross-sectional study 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, women mounting a stronger immune response compared with men, genetic factors, or a higher prevalence of alcohol consumption and smoking; however, further research is required.
In the UK, data indicate that South Asian, Black, and mixed ethnicity populations have an increased risk for testing positive and of adverse outcomes (i.e., hospitalisation, intensive care unit admission, death) compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Race may play an important role in adverse outcomes in children as well as adults.
In the US, the proportion of hospitalised patients was highest for Hispanic or Latino patients, and these racial and ethnic disparities were largest during May–July 2020 and became less pronounced as the pandemic spread throughout the country. Cumulative age-adjusted data from the US Centers for Disease Control and Prevention (as of 7 September 2021) indicate that Hispanic or Latino people, non-Hispanic American Indian or Alaska Native people, and non-Hispanic Black people have approximately 2.8, 3.5, and 2.8 times the rate of hospitalisations and 2.3, 2.4, and 2 times the rate of deaths of non-Hispanic White people, respectively. However, cohort studies in the US have found no difference in outcomes between non-Hispanic Black and Hispanic patients compared with White patients after adjusting for sociodemographic factors (e.g., age, sex, insurance) and comorbidities. These patients may have an increased risk of mortality and morbidity due to their disproportionate representation among hospitalisations.
Racial disparities in outcomes may be partially attributed to higher rates of comorbidities in certain ethnic groups.
In the UK, care home residents represented approximately one third of the total number of deaths in England and Wales during the first wave of the pandemic; other countries reported a similar experience. This was likely due to shortages in personal protective equipment, a vulnerable population, and a lack of testing. A study across four nursing homes 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 SARS-CoV-2, and of these, 43% were asymptomatic and 18% had atypical symptoms.
In the US, the 30-day all-cause mortality rate was 21% in a cohort study of more than 5000 nursing home residents. Older age, male sex, and impaired cognitive and physical function were independently associated with mortality.
In the UK, the most common comorbidities reported in a cohort study of more than 20,000 hospitalised patients were cardiac disease (31%), uncomplicated diabetes (21%), non-asthmatic chronic pulmonary disease (18%), and chronic kidney disease (16%).
In the US, approximately 95% of hospitalised adults had at least one reported underlying medical condition, with the most common being hypertension, disorders of lipid metabolism, and obesity. Approximately 99% of patients who died had at least one underlying health condition. The strongest risk factors for death were obesity, anxiety and fear-related disorders, and diabetes, as well as the total number of underlying conditions. It has been estimated that approximately 56% of adults, and 32% of young adults (ages 18-25 years), are at risk for severe disease because of the presence of at least one comorbidity.
Globally, hypertension (21%), obesity (18%), and diabetes (18%) were the most prevalent comorbidities. Cancer, chronic kidney disease, diabetes, and hypertension were independently associated with mortality. Chronic kidney disease was statistically the most prominent comorbidity leading to death.
Of the 2.5 million deaths reported globally by the end of February 2021, 2.2 million were in countries where more than half the population is classified as overweight. In countries where less than half the adult population is classified as overweight, the likelihood of death is around one tenth of the level seen in countries where more than half the population is classified as overweight.
Evidence from a meta-analysis found that patients who are obese have a significantly increased risk of infection, clinically severe disease, hospitalisation, intensive care unit admission, need for mechanical ventilation, and mortality.
A cohort study in the UK found that the risk of severe outcomes (i.e., hospitalisation, intensive care unit admission, death) increased progressively above a body mass index ≥23 kg/m², independent of the excess risks of related diseases (e.g., diabetes). The relative risk was particularly notable in people <40 years of age and those with Black ethnicity.
A cohort study in the US found a non-linear relationship between body mass index and disease severity, with the lowest risk at body mass indexes near the threshold between healthy weight and overweight, then increasing with higher body mass index.
People with cardiovascular disease are at increased risk for severe disease.
Pre-existing cardiovascular disease is associated with adverse outcomes including disease severity, disease progression, and mortality.
Arrhythmias, coronary artery disease, and cardiovascular disease are significantly associated with intensive care unit admission. Heart failure, arrhythmias, coronary artery disease, and cardiovascular disease are also significantly associated with an increased risk of mortality. Pre-existing atrial fibrillation was associated with a higher risk of short-term death. Coronary heart disease has also been associated with disease progression and severe/critical disease. The association is affected by the presence of hypertension; patients with coronary heart disease and hypertension had an increased risk of poor prognosis compared with those without hypertension.
People with type 1 or type 2 diabetes are at increased risk for severe disease.
Diabetes is associated with an increased risk for disease progression, intensive care admission, acute respiratory distress syndrome, need for invasive mechanical ventilation, and mortality.
In the UK, one third of all deaths in hospitalised patients occured in patients with diabetes. An analysis of more than 19,000 patients admitted to critical care over the entire first wave of the pandemic found that type 2 diabetes is associated with a 20% increase in mortality in patients with severe disease, independent of age, sex, ethnicity, obesity, or other major comorbidity.
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/acute kidney injury, history of stroke or heart failure, poor glycaemic control prior to infection, higher glycosylated haemoglobin levels, higher body mass index, elevated C-reactive protein, diabetic ketoacidosis, hyperglycaemic hyperosmolar state, and insulin use. The higher risk of intensive care unit admission and mechanical ventilation in patients with type 1 diabetes may be accounted for by the presence of diabetic ketoacidosis. Patients with newly diagnosed diabetes have a higher risk of all-cause mortality compared with patients with known diabetes, hyperglycaemia, or normal glucose.
Use of metformin, sodium–glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, or dipeptidyl peptidase-4 inhibitors may be associated with lower mortality. However, the reduction in mortality only appears to be significant with metformin.
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.
People with chronic obstructive pulmonary disease COPD, including emphysema and chronic bronchitis, are at increased risk for severe disease. People with moderate to severe asthma, or other chronic lung diseases (e.g., interstitial lung disease, cystic fibrosis, idiopathic pulmonary fibrosis, pulmonary hypertension) may be at increased risk for severe disease; however, evidence is limited. There is no clear evidence that people with asthma or COPD are at higher risk of infection.
COPD is associated with an increased risk of hospitalisation, intensive care unit admission, and mortality. A national, multicentre prospective cohort study in the UK (75,463 patients from 258 healthcare facilities) found that patients with COPD were less likely to receive critical care than patients without an underlying respiratory condition.
It is unclear whether asthma increases the risk of infection or severe outcomes (i.e., hospitalisation, intensive care unit admission, mortality). Systematic reviews and meta-analyses do not detect a clear increase in risk, and high-quality primary studies report conflicting results. People with asthma who have comorbid COPD, and people with non-allergic asthma, appear to have worse outcomes. According to meta-analyses, asthma is not associated with an increased risk for infection, severe disease, hospitalisation, intensive care unit admission, worse prognosis, mortality, or a higher risk of intubation or mechanical ventilation. Clinical outcomes were similar between patients with asthma and patients without asthma. Patients with asthma may have a lower risk of infection and death compared with non-asthmatic patients. However, a national, multicentre prospective cohort study in the UK (75,463 patients from 258 healthcare facilities) found that patients with asthma were more likely to receive critical care than patients without an underlying respiratory condition. Severe asthma was associated with increased mortality compared with patients with non-severe asthma in patients aged 16 years and older. Inhaled corticosteroid use in patients with asthma was associated with lower mortality compared with patients without an underlying respiratory condition in patients aged 50 years and older.
People with obstructive sleep apnoea may be at increased risk for severe disease, intensive care admission, mechanical ventilation, and mortality; however, evidence is limited. Obstructive sleep apnoea has not been associated with an increased risk of infection.
People with cystic fibrosis do not appear to be at increased risk of infection; however, there is evidence that some patients may experience a more severe clinical course (e.g., post-transplantation).
People with tuberculosis appear to be at an increased risk of severe disease and mortality.
There are no data on whether paediatric respiratory diseases (including childhood asthma) are risk factors for infection or severity.
Patients with chronic kidney disease had a significantly higher risk of hospitalisation and all-cause mortality compared with people without chronic kidney disease. Patients with chronic kidney disease also had a higher risk of progressing to critical illness in the pooled analysis of included studies and subgroup analyses of studies with multivariable adjustment, although neither result achieved statistical significance.
Incidence appears to be higher in patients receiving dialysis compared with those not requiring renal replacement therapy. Patients with end-stage renal disease who were on renal replacement therapy also had an increased risk of intensive care unit admission, need for mechanical ventilation, and mortality.
In the UK, data from a cross-sectional study 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%).
Pre-existing chronic kidney disease is an independent risk factor for developing acute kidney injury as a complication.
Pregnant women are at increased risk for severe disease.
According to an analysis of approximately 400,000 women aged 15 to 44 years with symptomatic disease, pregnant women were more likely to be hospitalised, be admitted to the intensive care unit, receive invasive mechanical ventilation or extracorporeal membrane oxygenation, and die compared with non-pregnant women.
Pregnant women and neonates are more vulnerable to adverse outcomes in low- to middle-income countries compared with high-income countries.
See the Complications section for more information on pregnancy-related complications.
People who are current or former smokers are at increased risk for severe disease.
Smoking is associated with severe or critical outcomes, and an increased risk of intensive care unit admission and mortality. The association appears to be more significant in former smokers compared with current smokers, and in younger people. Current smokers are at higher risk of developing severe disease compared with non-smokers. Smokers have double the mortality risk compared with non-smokers. 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.
Patients with cancer have an increased risk of severe disease, increased ventilatory requirements, and mortality compared with the general population. Intensive care unit admission rates were not statistically significant between the two groups. Haematological malignancies were associated with the highest risk of mortality (possibly explained by the greater degree of immunosuppression used in the treatment of these patients), followed by lung cancer. There is no clear association between treatment modality and mortality. A higher risk of infection is likely due to immunosuppressive treatments and/or recurrent hospital visits. The pooled in-hospital mortality risk in patients with cancer is 14.1%. The pooled mortality in cancer patients admitted to the intensive care unit was 60.2%.
Mortality in cancer patients is affected by pre-existing non-cancer comorbidities, and is significantly higher in people with hypertension, cardiovascular disease, chronic obstructive pulmonary disease, and diabetes.
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. In the largest international cohort study to date, 20% of children with cancer developed severe or critical disease, but most patients recovered without advanced support. Approximately 35% of children were asymptomatic. Lymphopenia and neutropenia were associated with more severe disease. Overall survival in children with cancer is very high (99.4%), and there was no significant difference in the risk of hospitalisation or intensive care unit admission between haematological malignancies and solid tumours in children.
People with cerebrovascular disease are at increased risk for severe disease.
Patients with a history of cerebrovascular disease were more likely to progress to adverse outcomes compared with patients without a history of cerebrovascular disease. Patients with pre-existing cerebrovascular disease had 2.67-fold higher odds of poor outcomes including intensive care admission, mechanical ventilation, and mortality.
People with an immunocompromised state from solid organ or blood stem cell transplant may be at increased risk for severe disease; however, evidence is limited.
Solid organ transplant recipients are at increased risk for hospitalisation, intensive care unit admission, and mortality. However, the increased rate of hospitalisation may reflect a preferred management strategy of closer inpatient monitoring in these patients rather than being an indicator of disease severity. Overall mortality in solid organ transplant recipients was 20%. Solid organ transplant recipients had a 1.4-fold increased odds of mortality compared with the general population.
People with Down's syndrome or learning disability may be at increased risk for severe disease; however, evidence is limited.
In the UK, a cohort study found a 4-fold increased risk for hospitalisation and a 10-fold increased risk for for mortality in people with Down's syndrome. This may possibly be due to the presence of immune dysfunction, congenital heart disease, and pulmonary pathology.
Another study in the UK found that adults with learning disability and those with Down's syndrome or cerebral palsy have markedly increased risks of hospital admission and death over and above the risks observed for non-COVID-19 causes of death.
People with sickle cell disease or thalassaemia may be at increased risk for severe disease; however, evidence is limited.
In the UK, patients with sickle cell disease were found to have a 4-fold increased risk for hospitalisation and a 2.6-fold increased risk for death. Sickle cell trait was also associated with increased risks for both outcomes, albeit to a lesser extent.
In the US, among 178 patients with sickle cell disease (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 hypertension may be at increased risk for severe disease; however, evidence is limited.
Almost all available evidence suggests that hypertension increases the risk of severe disease or mortality, although it was sometimes unclear whether this was independent of other risk factors. There were no systematic reviews or meta-analyses studying whether people with hypertension were at greater risk of infection.
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 2.98-fold higher risk of severe disease, a 1.82-fold higher risk of critical disease, and a 2.17 to 2.88-fold higher risk of fatality compared with patients without hypertension.
Initially, there was a concern that people on ACE inhibitors or angiotensin-II receptor antagonists may be at increased risk for infection or severe disease due to upregulation of ACE2 receptor expression. However, high-certainty evidence suggests that use of these drugs is not associated with severe disease, and there is no association between the use of these medications and a positive SARS-CoV-2 test result among symptomatic patients.
Older adults with dementia are at a higher risk of mortality in the short term. Dementia patients are more likely to be vulnerable to having diseases such as hypertension, diabetes, and pneumonia, and be immunocompromised. The pooled mortality rate of patients with dementia was 39% compared with 20% in older adults without dementia.
In the UK, over one quarter of people who died with COVID-19 from March to June 2020 had dementia. Dementia and Alzheimer's disease was the most common main pre-existing health condition in deaths involving COVID-19 between March and June 2020.
A retrospective case-control study of electronic patient health records in the US found that patients with dementia were at increased risk of infection compared with patients without dementia. They also had significantly worse outcomes (6‐month hospitalisation risk and mortality risk) compared with patients with dementia but no COVID‐19 and patients with COVID‐19 but no dementia. The highest risk was seen in patients with vascular dementia.
People who are immunocompromised may be at increased risk for severe disease; however, evidence is limited.
This includes people with a history of primary immune deficiencies or prolonged use of corticosteroids or other immunosuppressant medications.
Current data do not strongly suggest that medications associated with the treatment of immune-mediated inflammatory diseases increase the risk of infection or severe disease, with the exception of corticosteroids and rituximab.
Glucocorticoid exposure of ≥10 mg/day (prednisolone) has been associated with a higher odds of hospitalisation in patients with rheumatological disease. Patients treated with ciclosporin/tacrolimus also had an increased risk for hospitalisation; however, it was not clear whether the increased risk is related to the drug itself, the underlying condition for which the patient is treated, or other factors.
Immunosuppressed patients are not at significantly increased risk of infection compared with the general population.
Also see HIV infection and Autoimmune disease below.
People living with HIV may be at increased risk for severe disease; however, evidence is limited.
It is still unclear whether HIV infection influences infection and disease course. Observational studies report conflicting results. A retrospective cohort study in the UK found that people with HIV appear to be at increased risk for mortality. A retrospective cohort study in New York found that while people with HIV do not appear to be at increased risk of infection, they are at increased risk for poor outcomes (mainly higher rates of severe disease requiring hospitalisation) compared with people living without diagnosed HIV infection. Hospitalisation risk increased with progression of HIV disease stage. HIV infection was not independently associated with poor outcomes among hospitalised patients in Zambia; however, patients with severe HIV disease were more likely to develop severe disease or die compared with those with controlled HIV disease.
Evidence from meta-analyses is conflicting. One meta-analysis found that HIV infection was not associated with composite poor outcome. However, other meta-analyses have found that people living with HIV infection have an increased risk for infection and mortality compared with people without HIV. People on tenofovir disoproxil-based regimens may have a lower risk of infection and poor outcomes; however, evidence is inconclusive.
There is evidence that suggests that HIV patients at advanced stages (stage 3 or 4) manifest less severe symptoms and have reduced mortality. This may be due to the inability of HIV-positive individuals' immune systems to provoke the cytokine storm that usually causes poor clinical outcomes in COVID-19 patients.
Despite the conflicting evidence, the World Health Organization states that HIV infection appears to be a significant independent risk factor for severe or critical disease at hospital admission and in-hospital mortality. HIV infection was independently associated with a higher risk of mortality compared with the HIV-negative population after adjusting for age, sex, disease severity, and underlying conditions. Age >65 years, male sex, and the presence of diabetes or hypertension were risk factors for severe or critical illness at hospital admission, as well as in-hospital mortality. Data were predominantly from South Africa, which may limit the generalisability of the results.
People with substance use disorders may be at increased risk for severe disease; however, evidence is limited. This includes alcohol, opioid, or cocaine use disorder.
People with substance abuse disorders, especially those using drugs that affect the respiratory and cardiovascular systems, may be vulnerable to the adverse respiratory effects of COVID-19. Cohort studies have found substance use disorders were associated with increased hospitalisation, intensive care unit admission, ventilator use, and mortality.
People with opioid use disorder had higher odds of hospitalisation, maximum length of hospital stay, and invasive mechanical ventilation compared with those without an opioid use disorder. However, patients did not appear to have an increased risk of mortality. Patients treated with methadone or buprenorphine appeared to have worse outcomes in terms of hospitalisation and length of hospital stay, but better outcomes in terms of mortality risk and need for invasive mechanical ventilation compared with patients not receiving opioid agonist treatment.
Children with certain underlying conditions may be at increased risk for severe disease; however, evidence is limited.
These conditions include obesity, diabetes, asthma and chronic lung disease, immunosuppression, and sickle cell disease. Children may also be at risk if they are medically complex; have serious genetic, neurological, or metabolic disorders; or have congenital heart disease.
A cross-sectional study of over 43,000 children in the US found that the most commonly documented underlying conditions were obesity, asthma, neurodevelopmental disorders, anxiety and fear-related disorders, and depressive disorders. Children with type 1 diabetes, cardiac and circulatory congenital anomalies, obesity, hypertension, epilepsy, neuropsychiatric disorders, and asthma as well as children with chronic disease had higher risk of hospitalisation and severe disease. Limited data suggest that children with congenital heart disease might be at increased risk of severe disease.
People with chronic liver disease, especially cirrhosis, may be at increased risk for severe disease; however, evidence is limited.
Chronic liver disease has been associated with an increased risk for severe disease and 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.
People with metabolic dysfunction-associated fatty liver disease (nonalcoholic fatty liver disease) are at increased risk for severe disease. Disease severity has been associated with age <60 years and intermediate or high fibrosis-4 (FIB-4) scores.
Meta-analyses have found that low serum vitamin D level is significantly associated with a higher risk of infection, and increased risk for severe disease, hospitalisation, and mortality in both adults and children. However, it is unclear whether these associations were statistically significant and the certainty of evidence is very low.
People taking proton-pump inhibitors (PPIs) may be at increased risk for severe disease; however, evidence is limited.
Data on whether PPI use increases the risk for infection is conflicting. The largest meta-analysis to date found that PPI use was not associated with an increased risk for infection.
Patients taking PPIs may be at increased risk for secondary infections, severe clinical outcomes, and death. Current or regular users of PPIs were more likely to have severe outcomes compared with non-PPI users. Also, current PPI users were more likely to be hospitalised for longer compared with non-PPI users, although this was not statistically significant. Past use of PPIs is not associated with increased susceptibility to infection or severe outcomes.
A nationwide meta-analysis of over 80,000 cases in Denmark found that while current use of a proton-pump inhibitor may be associated with an increased risk of hospital admission, it was not associated with an increased risk for infection or severe outcomes. The authors concluded that conflicting results from previous studies may be more likely due to differences in study design and population.
People with autoimmune disease may be at higher risk for infection and severe disease; however, evidence is limited.
Current data do not strongly suggest that the presence of an immune-mediated inflammatory disease increases the risk of infection or severe disease. The increased risk reported in some studies may be due to comorbidities associated with immune-mediated inflammatory diseases or medications the patient is taking (corticosteroids, rituximab). Increased rates of hospitalisation in these patients were not associated with increased rates of death.
Inflammatory arthritis: evidence does not show a strong association between inflammatory arthritis (e.g., rheumatoid arthritis, spondyloarthritis) and risk of infection or adverse outcomes such as hospitalisation, intensive care unit admission, need for mechanical ventilation, or death. However, evidence is conflicting. Some studies do report an increased risk of adverse outcomes, but the studies had limitations.
Inflammatory bowel disease: evidence suggests that the risk profile for infection and severe disease is similar to the general population if patients have good disease control and do not use corticosteroids. Higher disease activity and flares may lead to increased susceptibility to infection and worse outcomes. Patient outcomes (hospitalisation, intensive care unit admission, and mortality) were worse in ulcerative colitis and patients on corticosteroids, thiopurines, aminosalicylates, or combination therapy. Outcomes were better in patients on biological agents.
Connective tissues diseases: several studies suggest an increased risk of infection in patients with connective tissue disorders (e.g., systemic lupus erythematosus, Sjogren syndrome, systemic sclerosis, polymyositis and dermatomyositis) compared with the general population and patients with other immune-mediated inflammatory diseases. This is possibly due to the widespread use of corticosteroids in these patients. There is a lack of data regarding outcomes and evidence is conflicting.
Psoriasis: data on risk and outcomes convincingly suggest a comparable risk profile as observed in the general population, with no increase in susceptibility to infection or severe disease reported in cohort studies.
Vasculitis: corticosteroid use and comorbid respiratory disease were associated with severe outcomes, based on limited data. Disease activity and other immunosuppressive therapies were not associated with severe outcomes.
Multiple sclerosis: neurological disability, older age, Black race, cardiovascular comorbidities, recent treatment with corticosteroids, and obesity were risk factors for severe disease and mortality. Current evidence does not suggest that multiple sclerosis significantly increases the mortality rate. Highest hospitalisation and mortality rates were in patients who were not on disease-modifying therapies, followed by those who were on B cell-depleting therapies (e.g., rituximab, ocrelizumab).
Risk factors for infection may include obesity, pulmonary disease, and hospitalisation. Vitamin D supplementation was associated with a lower risk of infection.
Parkinson's disease was associated with severe disease, poor in-hospital outcomes, and mortality in one meta-analysis. However, the evidence for an association is still unclear. The association was influenced by age, but not by sex or the presence of dementia, hypertension, or diabetes.
Patients may experience substantial worsening of parkinsonian symptoms.
Physical inactivity may be associated with a higher risk for severe disease; however, evidence is limited.
A retrospective observational study in nearly 50,000 patients found that patients with COVID-19 who were consistently inactive during the 2 years before the pandemic had a greater risk of hospitalisation, intensive care unit admission, and death compared with patients who were consistently meeting physical activity guidelines or who were doing some level of physical activity. Other than older age and a history of organ transplant, physical inactivity was the strongest risk factor for severe disease outcomes in this study.
The association was stronger in males, older age, and those with hypertension.
Initially there was a concern that people on statins may be at increased risk of infection or more severe disease, as statins have been shown to increase ACE2 expression in animals and may promote the activation of the inflammatory pathway in acute respiratory distress syndrome. However, so far, studies do not support this hypothesis, and studies have shown a protective effect (lower risk of mortality or severe disease). Findings from the American Heart Association’s COVID-19 Cardiovascular Disease Registry report that patients taking statins prior to hospitalisation had substantially lower odds of death, primarily among individuals with a history of cardiovascular disease and/or hypertension.
Surgical mortality and complications may be 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.
People with blood group A may be at increased risk for infection and mortality, and people with blood group B may be at increased risk for infection; however, evidence is limited.
There is no evidence for an association between blood group AB and the risk of infection. Blood group O appears to be protective against infection; however, evidence is of low/very low quality. People who are Rh-positive were more vulnerable to infection compared with those who were Rh-negative.
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. The SARS-CoV-2 receptor-binding domain directly binds the blood group A antigen expressed on respiratory epithelial cells, directly linking blood group A and SARS-CoV-2.
There is limited evidence that gut and lung microbiota dysfunction may be implicated in the pathogenesis of COVID-19.
Patients appear to have a depletion of beneficial commensals (e.g., Eubacterium ventriosum, Eubacterium rectale, Faecalibacterium prausnitzii, Roseburia and Lachnospiraceae taxa) and an overgrowth of opportunistic pathogens (e.g., Clostridium hathewayi, Actinomyces viscosus, Bacteroides nordii) during hospitalisation. Associations between gut microbiota composition, levels of cytokines, and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in disease severity, possibly via modulating host immune responses. Gut dysbiosis after disease resolution may contribute to persistent symptoms.
Climate and latitude: higher temperatures may slow the progression of the epidemic based on low-certainty evidence and limited studies; however, climate variables alone don’t explain most of the variability in disease transmission. Temperature, humidity, wind speed, ultraviolet light, and latitude may play a role in the epidemic, but further research is required.
Residence in urban or deprived areas: limited evidence suggests that the prevalence was greater in people living in urban areas compared with people living in rural areas, and in people living in more deprived areas compared with people living in less deprived areas.
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