Influenza viral infection is a risk factor for severe illness in COVID-19 patients: a nationwide population-based cohort study

Figures & data

Figure 1. The influenza-positive group was classified into five subgroups according to history of influenza infection within 1 year, 1–2 years, 2–3 years before the onset of the COVID-19 pandemic.

Figure 2. Distribution and flow chart of influenza and SARS-CoV-2 patients in a nationwide Korean cohort.

Table 1. Demographic characteristics of patients in the Korean nationwide cohort who underwent SARS-CoV-2 testing.

	COVID-19-negative (n = 245,788)	COVID-19-positive (n = 28,338)
Age, years	47.16 ± 23.40	46.02 ± 21.92
<65	198,105 (80.6)	22,755 (80.3)
≥65	47,683 (19.4)	5,583 (19.7)
Sex
Male	121,629 (49.5)	13,936 (49.2)
Female	124,159 (50.5)	14,402 (50.8)
Socioeconomic status
High	81,802 (33.3)	8,851 (31.2)
Low	163,986 (66.7)	19,487 (68.8)
Underlying diseases
History of angina	32,808 (13.3)	2,873 (10.1)
History of cancer	36,979 (15.0)	3,275 (11.6)
History of congestive heart failure	26,398 (10.7)	2,108 (7.4)
History of chronic kidney disease	32,710 (13.3)	3,155 (11.1)
History of myocardial infarction	8,911 (3.6)	945 (3.3)
History of diabetes mellitus	49,911 (20.3)	4,849 (17.1)
History of hypertension	71,725 (29.2)	7,144 (25.2)
History of chronic lung disease	59,998 (24.4)	5,818 (20.5)
History of chronic liver disease	21,722 (8.8)	2,158 (7.6)
Influenza infection	50,346 (20.5)	4,003 (14.1)

Data are presented as mean ± SD or number (%).

Table 2. Propensity score-matched baseline characteristics associated with severe illness from COVID-19 infection

	Influenza-negative (n = 4,003)	Influenza-positive (n = 4,003)	SMD
Age, years			0.038
≥ 65	524 (13.1)	544 (13.6)
<65	3,479 (86.9)	3,459 (86.4)
Sex			0.005
Male	1,860 (46.5)	1,869 (46.7)
Female	2,143 (53.5)	2,134 (53.3)
Socioeconomic status			0.007
Low	2,680 (66.9)	2,694 (67.3)
High	1,323 (33.1)	1309 (32.7)
Underlying diseases
History of angina	268 (6.7)	317 (7.9)	0.047
History of cancer	318 (7.9)	398 (9.9)	0.07
History of congestive heart failure	226 (5.6)	267 (6.7)	0.043
History of chronic kidney disease	326 (8.1)	385 (9.6)	0.052
History of myocardial infarction	107 (2.7)	131 (3.3)	0.035
History of diabetes mellitus	408 (10.2)	493 (12.3)	0.067
History of hypertension	623 (15.6)	700 (17.5)	0.052
History of chronic lung disease	1,153 (28.8)	1,192 (29.8)	0.021
History of chronic liver disease	259 (6.5)	307 (7.7)	0.047
Severe illness from COVID-19	192 (4.8)	260 (6.5)	0.074
Adjusted OR*	1 (reference)	1.29 (1.04 - 1.59)

Data are presented as mean ± SD or number (%). SMD, standardized mean difference.

* Adjusted by age, sex, socioeconomic status, and underlying diseases.

Figure 3. Propensity score-matched association between influenza and severe clinical outcomes of COVID-19 in patients who tested positive for SARS-CoV-2. Sensitivity analysis was performed according to 1) matching ratio, 2) matching variables (minimally: age + sex + demography, 3 underlying diseases: minimally + HTN + DM + CKD matching, 4 underlying diseases: minimally + HTN + DM + CKD + lung diseases matching, 5 underlying diseases: minimally + HTN + DM + CKD + lung diseases + liver diseases matching, fully matching: minimally + HTN + DM + CKD + lung diseases + liver diseases + cardiac diseases (CHF + angina + MI) matching). (Abbreviations: HTN, hypertension; DM, diabetes mellitus; CKD, chronic kidney disease; CHF, congestive heart failure; MI, myocardial infarction).

Table 3. Propensity score-matched adjusted ORs for the risk of severe illness from COVID-19 in patients with previous influenza infection

	No influenza (n = 4,003)	Previous influenza infection before COVID-19 (n = 4,003)
		Within 1 year (n = 1,760)	1–2 years (n = 1,129)	2–3 years (n = 1,114)
Event of severe illness from COVID-19	260 (6.5%)	143 (8.1%)	48 (4.3%)	69 (6.2%)
Adjusted OR*	1 (reference)	1.54 (1.20-1.98)	1.19 (0.84-1.70)	1.00 (0.73-1.37)
P-value		< 0.001	0.328	1.000
E-value		2.45	1.00	1.00

Data are presented as number (%) or odds ratios (95% confidence interval).

* Adjusted by age, sex, socioeconomic status, and underlying diseases.

Figure 4. Sensitivity analysis was performed according to 1) matching ratio, 2) matching variables (minimally: age + sex + demography, 3 underlying diseases: minimally + HTN + DM + CKD matching, 4 underlying diseases: minimally + HTN + DM + CKD + lung diseases matching, 5 underlying diseases: minimally + HTN + DM + CKD + lung diseases + liver diseases matching, fully matching: minimally + HTN + DM + CKD + lung diseases + liver diseases + cardiac diseases (CHF + angina + MI) matching). (Abbreviations: HTN, hypertension; DM, diabetes mellitus; CKD, chronic kidney disease; CHF, congestive heart failure; MI, myocardial infarction)

Data availability statement

The datasets analyzed in this study are stored in the Korean National Health Insurance claim-based database. The data will be made available for research on reasonable request and with permission from the National Health Insurance Service (NHIS) (NHIS-2022-1-382).