Table 3

Main categories of risk factors and biomarkers associated with suspected acute respiratory infection by category of risk and strength of each association

Main categories of risk factors and biomarkers assessed	Association identified	Strength	Confounders	Variables adjusted for (confounders/ multivariable model)	Study
Demographic factors
Younger athletes in the illness prone group	Yes	+	–	No/No	Gleeson et al 102
Age	No	000	Performance level, sex, training phase and load, season	Yes/Yes	Svendsen et al 56
Gender	No	000	Time, age, sex, training centre, and competition level	Yes/Yes	Hellard et al 57
Gender	No	0	–	No/No	He et al 101
Sport (type and level of participation)
Participating in endurance sports	Yes	++	Sex, type of sport	Yes/No	Edouard et al 105
Participating in athletics compared with other Paralympic sports	Yes	+	–	No/No	Schwellnus et al 107
Completing a marathon	No	0	–	No/No	Furusawa et al 98
Being at a less competitive level	Yes	+++	Performance level, sex, training phase and load, season	Yes/Yes	Svendsen et al 56
Being at a less competitive level	Yes	+++	Age, sex, competition level, season	Yes/Yes	Hellard et al 13
Training and competition factors
Increased training load	Yes	+++	Age, sex, competition level, season	Yes/Yes	Hellard et al 13
		+++	Time, age, sex, training centre, and competition level	Yes/Yes	Hellard et al 57
		+	–	No/No	Moreira et al 96
		+	–	No/No	Rama et al 47
		+	–	No/No	Gleeson et al 102
		+	–	No/No	Fricker et al 66
		+	–	No/No	Leicht et al 97
		+	–	No/No	Yamauchi et al 108
		+	–	No/No	Hausswirth et al 100
		+	–	No/No	Ikonen et al 103
		+	–	No/No	Milanez et al 84
		+	–	No/No	Gleeson et al 102
	No	000	Performance level, sex, training phase and load, season	Yes/Yes	Svendsen et al 56
		0	–	No/No	Dressendorfer et al 106
		0	–	No/No	Neville et al 9
Increased training intensity	Yes	+	–	No/No	Brisola et al 97
Increased training intensity	No	0	–	No/No	Dressendorfer et al 106
Increased training intensity – lower incidence	Yes	+++	Performance level, sex, training phase and load, season	Yes/Yes	Svendsen et al 56
Increased strength and speed training	Yes	+++	Age, sex, competition level, season	Yes/Yes	Hellard et al 13
Increased strength and speed training	No	000	Performance level, sex, training phase and load, season	Yes/Yes	Svendsen et al 56
Increased training monotony	Yes	+++	Performance level, sex, training phase and load, season	Yes/Yes	Svendsen et al 56
Endurance preparation phase	Yes	+++	Performance level, sex, training phase, and load, season	Yes/Yes	Svendsen et al 56
Tapering phase – lower incidence	Yes	+++	Performance level, sex, training phase and load, season	Yes/Yes	Svendsen et al 56
Tapering phase – lower incidence	Yes	+++	Age, sex, competition level, season	Yes/Yes	Hellard et al 13
Competition period	Yes	+++	Gender, age, sport types	Yes/Yes	Schwellnus et al 69
	Yes	+	–	No/No	Brisola et al 99
	No	000	Age, sex, competition level, season	Yes/Yes	Hellard et al 13
	No	000	Time, age, sex, training centre, and competition level	Yes/Yes	Hellard et al 57
Nutritional factors
Reduced serum (vitamin-D)	Yes	+++	Baseline values, time effect, exercise	Yes/Yes	Hanstock et al 27
Vitamin D supplementation – lower incidence	Yes	+	–	No/No	He et al 101
Lower intake of arginine and alanine amino acids during the overreaching phase	Yes	+	–	No/No	Ikonen et al 103
Environmental/exposure factors
Winter	Yes	+++	Performance level, sex, training phase and load, season	Yes/Yes	Svendsen et al 56
		+++	Age, sex, competition level, season	Yes/Yes	Hellard et al 13
		+	–	No/No	Fahlman and Engels104
Autumn – lower incidence	Yes	+++	Team home country, season, intercontinental travel and duration in a specific travel stage of the tournament.	Yes/Yes	Schwellnus et al 67
Exposure to training at high altitude >1500 masl	Yes	+++	Performance level, sex, training phase and load, season	Yes/Yes	Svendsen et al 56
Longer International travelling	Yes	+++	Performance level, sex, training phase and load, season	Yes/Yes	Svendsen et al 56
Longer International travelling	Yes	+++	Team home country, season, intercontinental travel and duration in a specific travel stage of the tournament.	Yes/Yes	Schwellnus et al 67
Increased psychological stress	Yes	+	–	No/No	Moreira et al 96
Increased psychological stress	No	0	–	No/No	Milanez et al 84
Poor sleep quality	Yes	+	–	No/No	Hausswirth et al 100
Household family exposure	No	000	Performance level, sex, training phase and load, season	Yes/Yes	Svendsen et al 56
Immune/haematological risk factors and biomarkers
Prior respiratory tract infections	Yes	+++	Age, sex, competition level, season	Yes/Yes	Hellard et al 13
Higher rates of expression of EBV-DNA in saliva (viral reactivation)	Yes	+	–	No/No	Gleeson et al 33
	No	0	–	No/No	Yamauchi et al 108
Lower CD56 +cell counts (neutrophil cell marker)	Yes	+	–	No/No	Rama et al 47
Higher CD56bright:CD56 dim ratio	Yes	+	–	No/No	Rama et al 47
Lower salivary-IgA concentration	Yes	+	–	No/No	Gleeson et al 33
	Yes	+	–	No/No	Fahlman and Engels104
	No	0	–	No/No	Gleeson et al 102
	No	0	–	No/No	Leicht et al 97
Larger decrease in salivary (IgA) across training weeks	Yes	+	–	No/No	Milanez et al 84
Reduced pre-training salivary (IgA)	Yes	+	–	No/No	Neville et al 83
Reduced pre-training salivary (IgA)	Yes	+	–	No/No	Milanez et al 84
Reduced salivary-IgA secretion rate	Yes	+	–	No/No	Gleeson et al 102
		+	–	No/No	Fahlman and Engels104
		+	–	No/No	Yamauchi et al 108
		+	–	No/No	Neville et al 83
		+	–	No/No	Milanez et al 84
	No	0	–	No/No	Leicht et al 97
Genetic risk score for predisposition to pro-inflammatory cytokine responses	Yes	+	–	No/No	Gleeson et al 33
High expression IFN-ɣ genotype	Yes	+	–	No/No	Gleeson et al 33
Higher IFN-ɣ production in illness prone athletes	Yes	+	–	No/No	Gleeson et al 102
Higher IFN-ɣ production in illness prone athletes	No	0	–	No/No	Gleeson et al 9
TNF-α production	No	0	–	No/No	Gleeson et al 102
IL-1ra cytokine genotypes	No	0	–	No/No	Gleeson et al 33
IL-1β production	No	0	–	No/No	Gleeson et al 102
Higher IL-2 production	Yes	+	–	No/No	Gleeson et al 9
Higher IL-2 production	Yes	+	–	No/No	Gleeson et al 102
Higher IL-4 cytokine production	Yes	+	–	No/No	Gleeson et al 9
	Yes	+	–	No/No	Gleeson et al 102
	No	0	–	No/No	Gleeson et al 33
High expression IL-6 (CC) and IFNɣ (AA) genotypes	Yes	+	–	No/No	Gleeson et al 33
Higher IL-6 production	No	0	–	No/No	Gleeson et al 102
Higher IL-8 production	No	0	–	No/No	Gleeson et al 102
Higher expression IL-8 cytokine genotypes	No	0	–	No/No	Gleeson et al 33
Higher post exercise IL-10 production	Yes	+	–	No/No	Gleeson et al 102
Higher post exercise IL-10 production	Yes	+	–	No/No	Gleeson et al 9
Higher expression IL-10 cytokine genotypes	No	0	–	No/No	Gleeson et al 33
High expression IL-17 cytokine genotype	No	0	–	No/No	Gleeson et al 33
Higher plasma (IgM)	Yes	+	–	No/No	Gleeson et al 102
Plasma (IgA)	No	0	–	No/No	Gleeson et al 102
Plasma (IgG)	No	0	–	No/No	Gleeson et al 102

Strength of association, no association (0/00/000), + some association, ++ good association, +++ strong association.
AA, alpha amylase; EBV, Epstein-Barr virus; IL, interleukin; INF, interferon; masl, metre above sea level; TNF, tumour necrosis factor.