Table 4.

Studies reporting the burden of hospitalizations and ER visits among patients aged ≥ 65 years with existing comorbidities

	Country	Author	Key clinical outcome(s)
Hospitalizations	USA	Owusu, 2020 [82]	Mean annual rate of influenza-related hospitalization was higher among patients with diabetes mellitus [276 (95% CI 230–330) per 100,000 population] than without [181 (95% CI 150–217) per 100,000 population]
		Near, 2020 [80]	The rate of influenza-related hospitalizations was higher among older patients [≥ 65 (9.4%] vs ≥ 75 years (25.7%)] The rate of influenza-related hospitalizations among patients aged ≥ 65 increased to 27.4% when patients presented with pre-existing COPD or CHF
		Matias, 2017 [61]	Between 1997 and 2009, annual mean hospitalization rates among patients aged 65–74 years and ≥ 75 years were 256 (SD 91, range 83–385) and 589 (SD 216, range: 173–864), per 100,000 population, respectively During the study period, hospitalization rate across the low- and high-risk cohorts was higher among patients aged ≥ 75 years compared to patients aged 65–74 years The highest hospitalization rate across risk and age groups was incurred by influenza A(H3N2)
		Young-Xu, 2017 [81]	The mean annual rate of influenza-attributed hospitalization was 71 (95% CI 60–83) per 100,000 Patients were stratified into high- and low-risk groups, with those defined as high risk having had at least one diagnosis code for chronic cardiac, pulmonary, renal, metabolic, liver, neurological diseases, diabetes, hemoglobinopathies, immunosuppressive conditions, or malignancy assigned during the influenza season The mean annual rate of influenza-attributed hospitalizations was higher in the high-risk group of patients [144 (95% CI 121–167) per 100,000 population] than the low-risk group [0 (95% CI 0–1) per 100,000] Of note, the high- and low-risk group sample sizes were 2029 and 4, respectively
	China	Chair, 2020 [35]	Between 1997 and 2017, 1199 patients were admitted for heart failure within 12 months of influenza-associated hospitalization The aOR for heart failure-related admittance was 1.1 (95% CI 1.0–1.2)
	England	Cromer, 2014 [70]	Patients with an acute respiratory illness code and with ICD-10 codes in other diagnostic fields for conditions indicated for seasonal influenza vaccination were flagged as being in a clinical risk group Among adults aged ≥ 65 years, being in a risk group increased the hospital admission rate by 1.8-fold (from 0.5 to 0.8/1000). Average annual admissions in those at clinical risk vs not at clinical risk were 368,489 vs 53,254, respectively
ER visits	USA	Near, 2020 [83]	The presence of comorbidities in patients with influenza is associated with an increased rate of ER visits The proportion of patients visiting the ER with CKD stage 5/ESRD/dialysis and influenza was higher than CKD stage 5/ESRD/dialysis only (60 vs 28%, p < 0.5). Similar trends were observed for influenza with and without CAD (37 vs 14%, p < 0.5), COPD (44 vs 18%, p < 0.5), CHF (49 vs 23, p < 0.5)
Mortality	Spain	Soldevila, 2020 [71]	The comorbidity reported to result in the highest proportion of influenza deaths was congestive heart failure [50% (OR 2.5; 95% CI 1.5–4.2)]
	China	Qi, 2020 [77]	The annual influenza-associated mortality rate in patients with influenza A(H3N2) and B, and underlying COPD was 7.9 per 100,000 population (95% CI 6.3–9.5) and 23.1 per 100,000 population (95% CI 22.3–24.0), respectively The annual influenza-associated mortality rate in patients with influenza A(H3N2) and B, and underlying ischemic heart disease was 5.5 per 100,000 population (95% CI 4.5–6.5) and 11.1 per 100,000 population (95% CI 10.6–11.6), respectively

aOR adjusted odds ratio, CAD coronary artery disease, CHF congestive heart failure, CI confidence interval, CKD chronic kidney disease, COPD chronic obstructive pulmonary disorder, ER emergency room, ESRD end-stage renal disease, ICD-10 International Classification of Disease 10th edition, OR odds ratios, SD standard deviation