Table 5 Potential risk factors for disease severity

Sex

Odds ratio for severe disease 3.68 for men compared to women (multivariable regression) [36]

Odds ratio for invasive mechanical ventilation 2.83 for men compared to women (multivariable regression) [37]

Females less likely to be admitted to ICU, require mechanical ventilation, or die; odds ratio 0.61 (multivariable logistic regression) [31]

Sex distribution similar in severe and non-severe disease (descriptive) [30, 49]

Sex distribution similar in severe and non-severe disease (statistical test) [23, 26, 28, 29, 32, 34, 38, 39, 41,42,43,44, 48,49,50]

Sex distribution similar in severe and non-severe disease (multivariable regression) [19, 20]

Age

Average^a 61 years severe disease, 45 otherwise (statistical test) [38]

Average^a 61 years severe disease, 52 years moderate disease (statistical test) [23]

Average^a 56 years severe disease, 44 years mild disease (statistical test) [39]

Median 67 years acute respiratory distress syndrome, 52 severe, 45 mild (statistical test) [42]

Median 64 years severe patients, 52 years otherwise (statistical test) [48]

Mean 61 years severe, otherwise 40 (statistical test) [50]

Median 71 years SpO₂ < 90%, 37 years SpO₂ ≥ 90% (statistical test) [43]

Median 66 years patients in ICU, 51 otherwise (statistical test) [41]

Median 54 years patients in ICU, 41 otherwise (statistical test) [26]

65 years and over 3.26 times the hazard rate of ARDS than those under 65 (univariable regression) [44]

Age associated with ICU admission, odds ratio 1.06 but unclear for what categorisation of age (multivariable regression) [20]

Distribution of age did not differ by disease severity (descriptive) [30, 34, 49]

Distribution of age did not differ by disease severity (statistical test) [28, 29, 32]

Confidence interval for effect of age (categorisation unclear) crosses the null (multivariable regression) [37]

Mean 56 years severe disease, 45 years mild disease; odds ratio 1.06 but unclear categorisation of age (multivariable regression) [36]

Mean 63 years severe disease, 41 years mild disease; odds ratio 1.08 but unclear categorisation of age (multivariable regression) [19]

Older individuals more likely to be admitted to ICU, require mechanical ventilation, or die; odds ratio 1.05, categories of age unclear (multivariable logistic regression) [31]

Ethnicity

76.3% of individuals receiving basic respiratory support were White versus 65.6% receiving advanced respiratory support; Asian and Black ethnicities appear most at risk of severe disease (England, Northern Ireland and Wales; descriptive) [30]

Distribution of disease severity similar across ethnic groups (Chinese, Malay, Indian, other – with small numbers in groups other than Chinese; study in Singapore; descriptive) [26]

Deprivation

Distribution across deprivation categories similar (descriptive) [30]

Pregnancy

Distribution in pregnant and non-pregnant individuals similar across disease severity (descriptive) [30]

Smoking

100% of current smokers had severe disease, but only six individuals smoked [50]

Distribution in current and non-current smokers similar across disease severity (descriptive), only three individuals smoked [39]

Distribution in current and non-current smokers similar across disease severity (statistical test); small numbers who smoked [29]

Distribution in historical/current and non-smokers similar across disease severity (statistical test) [36, 48]

Body mass index

≥35 kg/m² risk factor versus < 25 kg/m² for invasive mechanical ventilation; odds ratio 7.36. Results for other strata cross the null (multivariable regression) [37]

Increasing body mass index increased risk; odds ratio 1.17 (categorisation unclear) [19]

Distribution of disease severity similar across body mass index categories (descriptive) [30]

Any/other comorbidity

Presence of comorbidity more common among those with severe disease (statistical test) [39, 41, 48, 50]

Distribution with and without condition similar across disease severity (statistical test) [23, 29, 36]

Distribution with and without comorbidities not otherwise considered in the study similar across disease severity (statistical test) [50]

Distribution with and without condition similar across disease severity (multivariable regression) [20]

Cardiovascular disease/chronic heart disease/coronary heart disease

Presence of comorbidity more common among those with severe disease (descriptive) [39]

Presence of comorbidity more common among those with severe disease (statistical test) [19, 36, 41, 43, 50]

Distribution with and without condition similar across disease severity (descriptive) [30, 44]

Distribution with and without condition similar across disease severity (statistical test) [29, 48]

Hypertension

Presence of comorbidity more common among those with severe disease (statistical test) [41, 43, 50]

Hazard ratio of ARDS 1.82 in those with the condition versus those without (univariable regression) [44]

Odds ratio of severe disease 2.71 in those with the condition versus those without (multivariable regression) [36]

Odds ratio of being admitted to ICU, require mechanical ventilation, or die 1.89 in those with the condition versus those without (multivariable regression) [31]

Distribution with and without condition similar across disease severity (descriptive) [39]

Distribution with and without condition similar across disease severity (statistical test); one study with small numbers with the condition [23, 29, 42, 48]

Confidence interval in presence and absence of condition crosses the null (multivariable regression) [19]

Confidence interval in presence and absence of condition crosses the null (multivariable regression, result borderline) [37]

Diabetes

Presence of comorbidity more common among those with severe disease (descriptive) [39]

Presence of comorbidity more common among those with severe disease (statistical test) [19, 36, 41, 43, 50]

Hazard ratio of ARDS 2.34 in those with the condition versus those without (univariable regression) [44]

Odds ratio of being admitted to ICU, require mechanical ventilation, or die 2.21 in those with the condition versus those without (multivariable regression) [31]

Distribution with and without condition similar across disease severity (statistical test); small numbers with condition [23]

Distribution with and without condition similar across disease severity (statistical test) [29, 48]

Distribution with and without condition similar across disease severity (statistical test, borderline result) [42]

Confidence interval in presence and absence of condition crosses the null (multivariable regression) [37]

Respiratory/pulmonary disease

Distribution with and without condition similar across disease severity (descriptive) [30, 39]

Asthma

Distribution with and without condition similar across disease severity (statistical test); small numbers with condition [43]

Chronic obstructive pulmonary disease (COPD)

Presence of comorbidity more common among those with severe disease (descriptive); small numbers with condition [39]

Presence of comorbidity more common among those with severe disease (statistical test); both studies have small numbers with the condition [41, 50]

Odds ratio of being admitted to ICU, require mechanical ventilation, or die 3.40 in those with the condition versus those without (multivariable regression) [31]

Distribution with and without condition similar across disease severity (statistical test); small numbers with condition [29, 43, 48]

Pulmonary tuberculosis

Distribution with and without condition similar across disease severity (statistical test); small numbers with condition [48]

Malignancy

Presence of comorbidity more common among those with severe disease (statistical test); small numbers with condition [39]

Presence of comorbidity more common among those with severe disease (statistical test) [36, 42, 50]

Presence of comorbidity more common among those with severe disease (multivariable analysis) [31]

Distribution with and without condition similar across disease severity (descriptive) [30]

Distribution with and without condition similar across disease severity (statistical test) [41]

Distribution with and without condition similar across disease severity (statistical test); small numbers with condition [19, 29, 43]

Cerebrovascular disease

Presence of comorbidity more common among those with severe disease (statistical test) [41]

Arrhythmia

Distribution with and without condition similar across disease severity (statistical test); small numbers with the condition [48]

Cerebral infarction

Distribution with and without condition similar across disease severity (statistical test) [42]

Stroke

Distribution with and without condition similar across disease severity (statistical test); small numbers with condition [48]

Aorta sclerosis

Distribution with and without condition similar across disease severity (statistical test); small numbers with condition [48]

Chronic kidney disease/renal issues

Presence of comorbidity more common among those with severe disease (statistical test) [42]

Distribution with and without condition similar across disease severity (descriptive) [30]

Distribution with and without condition similar across disease severity (statistical test); small numbers with the condition [41]

Chronic renal disease/insufficiency

Distribution with and without condition similar across disease severity (statistical test); one study has small numbers of patients with the condition [36, 48]

Chronic liver disease

Distribution with and without condition similar across disease severity (descriptive), sometimes small numbers with condition [19, 30, 39]

Distribution with and without condition similar across disease severity (statistical test) [36, 41]

Distribution with and without condition similar across disease severity (statistical test); small numbers with condition [29, 50]

Fatty liver and abnormal liver function

Distribution with and without condition similar across disease severity (statistical test) [48]

Hyperlipidaemia

Distribution with and without condition similar across disease severity (statistical test) [48]

Dyslipidemia

Confidence interval in presence and absence of condition crosses the null (multivariable regression) [37]

Chronic gastritis/gastric ulcer

Distribution with and without condition similar across disease severity (statistical test) [48]

Cholelithiasis

Distribution with and without condition similar across disease severity (statistical test) [48]

Urolithiasis

Distribution with and without condition similar across disease severity (statistical test); small numbers with condition [48]

Thyroid diseases

Distribution with and without condition similar across disease severity (statistical test); small numbers with the condition [48]

Electrolyte imbalance

Presence of comorbidity more common among those with severe disease (statistical test); small numbers with condition [48]

Agglomerative disease

Distribution with and without condition similar across disease severity (descriptive); small numbers with the condition [39]

Immunocompromised

Distribution with and without condition similar across disease severity (descriptive) [30]

Chronic hepatitis

Distribution with and without condition similar across disease severity (statistical test); small numbers with condition [43]

HIV

Distribution with and without condition similar across disease severity (statistical test); small numbers with condition [41]

Living without assistance

Distribution with and without condition similar across disease severity (descriptive) [30]