Table 3. Sex differences across various classes of pathogens (virus, bacteria, worms, parasites, fungi) for humans and mouse/rodent models.

Pathogen prevalence and incidence, pathogen loads and disease severity, and mouse models exhibiting sex bias with infection or disease are shown in each column. Information regarding hormonal or genetic influences on the sex bias is provided (when available) for each pathogen.

	Pathogen	Pathogen Prevalence and Incidence	Pathogen Intensity/Load; Resulting Disease Severity	Mouse Models & Sex Biased Mechanisms/Pathways
VIRUS	Coronaviruses; SARS-CoV; SARS-CoV-2	Males have higher incidence1-10	Adult males (45-79yrs) have higher mortality5,6 9 Females more likely to be diagnosed with Long Covid syndrome11,12	Male mice are more susceptible to SARS-CoV infection13-15 Male mice have increased accumulation of inflammatory macrophages and neutrophils in lung (SARS-CoV)3,13 Estrogen receptor signaling is protective after SARS-CoV-infection13,16 SARS-CoV-2 entry receptor Ace2 is biallelically expressed in females, which might reflect its dual role in mediating viral replication vs renin-angiotensin-aldosterone system 4,17
	Influenza	Infant males and older adult males have increased incidence18-23	Males (pre-pubescent, elderly) have high mortality.19,23 Females (pre-menopausal; pregnancy) also have high mortality18,24-26	Male mice have greater disease severity and this increases with age27 Female mice have greater mortality28 Female mice are more protected following influenza vaccination29,30 Low levels of testosterone in male mice correlate with poorer protection27,31-33 but estriol protects female mice from severe disease and decreases influenza replication34,35
	Hepatitis A	Males have more hospitalizations36	Males have higher mortality36	n/a
	Hepatitis C	Similar incidence rates between males and females37	Males have greater disease severity (HCV-associated cirrhosis) 37 Females more likely to clear virus37	n/a
	West Nile Virus	Higher percentage of affected males in this case study38	Similar initial viremia38 Females have more symptoms38 Males have longer lived cytokine response38 Males have increased mortality38 Males more likely to develop neuroinvasive disease38	n/a
	Human Immunodeficiency Virus (HIV)	Females have higher incidence 39 Females have higher levels of immune activation and interferon signature gene expression40	Females have lower viral loads in early stages of infection (but comparable in advanced stage)40,41 No sex difference with disease progression or clinical outcomes	Male-to-female transmission appears more efficient than female-to-male transmission42
	HCMV	Females (post-puberty pre-menopausal) have higher incidence of HCMV seroprevalence43		n/a
	Herpes Simplex Virus (HSV)	Females have higher prevalence44,45		Female mice more susceptible to infection28 Female mice have higher HSV titers in brain tissue28 Higher mortality in male mice46 Ovariectomy of female mice or estrogen treatment of male mice eliminated sex differences after infection28 Sex-biased survival differences depend on type I IFN signaling and DAP12 signaling28
	Coxsackievirus			Male mice have increased mortality28,47 Males develop more severe cardiac inflammation due to Th1 response47 Females are more resistant; exhibit predominantly Th2 responses47
	Ebola		Males have higher mortality48	n/a
	Measles	Females (age 45-64) have higher incidence49; Males (age 0-45) have higher incidence50	Females (ages 0-49) have higher mortality, particularly post-puberty pre-menopausal49.	n/a
	Respiratory Syncytial Virus (RSV)	Males have higher incidence51,52, but a metanalysis of acute respiratory infections in Africa did not identify sex as a factor in RSV prevalence53	Males have higher rates of hospitalizations51	Male neonatal mice have higher viral gene expression after RSV infection, and delayed viral resolution54 After early-life RSV infection, male mice exposed to allergen have severe allergic exacerbation (female mice are protected). TSLP pathway (which impacts IFN-beta production) alters male immune environment after neonatal infection54
BACTERIA	Heliobactor pylori	Males have greater H. Pylori sero-prevalence55,56 Infection has a male bias55	Males have more severe inflammation, atrophy, and intestinal metaplasia57	Male mice are more susceptible Males have higher colonization levels for babA virualence factor of H. pylori58 Male mice treated with estradiol produce less IFN-gamma and IL-1-beta, and increased IL-10 and Th2 associated IgG1 levels58 Estrogen is protective against gastric lesions; ovarectomy increases severity of gastritis and gastric cancer58
	Pseudomonas aeruginosa	Males have higher prevalence	Female CF patients have worse disease prognosis59	Female mice more susceptible to infection60 Females mount strong inflammatory response in lungs60 Estradiol upregulates expression of secretory leucoprotease which inhibits Tlr-dependent IL-8 release in bronchial epithelial cells during P.aeruginosa infection
	Salmonella	Higher incidence rates in male children for salmonellosis (up to age 15) 61 Females have higher incidence rates (ages 15–44 and 45–64)		n/a
	Chlamydia trachomatis; Chlamydia pneumoniae	Males have greater prevalence (C. pneumoniae)62 Females have higher prevalence (C. trachomatis)63	Males have higher levels of C. pneumoniae64 Females have higher infection rates because they are more likely to be screened (C.trachomatis)65 Estrogen levels correlate with chlamydial load64 Chlamydia-induced arthritis more common in men66	n/a
	Brucella spp.	Males have higher incidence67 No sex bias with prevalence	Males more likely to develop Brucellosis68	n/a
	Borrelia burgdorferi (Lyme disease)	Males have higher incidence (USA 1992-1998)69 Females >45 greater incidence (Sweden 1992-1993)70,71 Females more likely to be re-infected after 5 years.	Males have more hospitalizations and likelihood for disseminated disease72 Lyme neuroborreliosis is more common in female patients73 Females have increased production of IFN-gamma, IL-4, IL6, IL-10, TNF-alpha70	Male mice have more infected tissues and higher spirochete loads74
	Mycobacterium tuberculosis	Males have higher incidence (male/female 1.7)75	Males exhibit higher mortality rates (global)76 Pregnancy increases risk of disease complications77 Females usually have less symptoms64	Male mice have accelerated disease progression, increased morbidity and mortality78 Males have higher M. tuberculosis loads78 Testosterone treatment increases susceptibility to infection
	Mycoplasma pulmonis			Male mice more susceptible79 Male mice develop more severe disease in lung parenchyma79 Removal of reproductive organs reduced disease severity79
	Coxiella burnettii	Males have higher incidence80	Human males more likely to become sympotomatic with Q fever (symptoms include fever, granulomatous hepatitis, myocarditis, pericarditis, pneumonia)64,80 Pregnancy increases risk for persistent infections, and impaired immunity negatively impacts pregnancy64	Male mice have higher bacterial loads64 Estrogen treatment of ovariectomized mice reduces bacterial loads and granulomas81 C. burnetti infection results in sex-specific gene expression profiles: males upregulate IL-10 and interferon-gamma production; females exhibt altered expression of circadian rhythm genes.82
	Campylobacter spp.	Males have higher incidence64		Males are more susceptible to infection and colonization83 Males have higher shedding rates
	Clostridiodes difficile	Females have higher incidence84 Females have increased risk of recurrent infection57	Increased disease severity in pregnant and peripartum females84	Progesterone and estrogen intermediates can inhibit spore germination in mice57
	Listeria monocytogenes	Females have higher incidence rates of invasive listeriosis85 Pregnant females have higher incidence64 Among older individuals, males have 2-4 higher incidence rates85	Pregnant females and older males have greater incidences of invasive disease85 Older males have increased fatality rates85	Female mice more susceptible to infection and exhibit greater lethality86 Females have higher bacterial load; Infected females have increased IL-10, which inhibits Th1 differentiation and Th1-derived cytokines86 Estrogen treatment reduced IL-12, IFN-gamma, TNF-alpha; increased IL-4 and IL-10; reduced monocytes and lymphocyte accumulation at infection87
	Legionella pneumophila	Males have higher incidence	Males more likely to develop legionellosis and males more likely to have poor prognosis64	n/a
	Leptospira spp.	Males have higher incidence64		n/a
	Francisella tularensis	Males have higher incidence65		No sex difference with susceptibility Vaccinated female mice are more resistant to infection, with lower bacterial burdens, less tissue inflammation, and less proinflammatory cytokine production, and more Ft-specific antibodies in serum and lung85
	Escherichia coli	Females have higher incidence64		No sex difference with enterohemorrhagic E.coli disease in mice
	Treponema pallidum (syphilis)	Males have higher incidence88,89		n/a
	Neisseria gonorrhea	Males have higher incidence64 Infected males may also have increased expression of gonococcal antimicrobial resistance genes90	Most females lack symptoms64 Complications in males include epididymitis, infertility, prostatitis, seminal vesiculitis91 Elevated progesterone promotes gonococcal infection (human cervical epithelial cells)	Estrogen treated mice have increased susceptibility to gonococcal infection92
	Streptococcus pneumoniae	Males have higher incidence for all types of pneumonia64 Males (pre-puberty) have higher incidence	Males have greater hospitalization rates and increased mortality64 Males more frequently diagnosed with Legionellosis (1.7:5 male to female)93	Male mice are more susceptible & have more severe disease94 Males exhibit increased pro-inflammatory cytokines (IL-6, IL-17A, IFN-gamma)94 Estrogen is protective, regulating macrophage activity (for pneumococcal pneumonia)95
	Yersinia enterocolitica	Males have higher incidence for Yersiniosis96	Males have higher levels of IgG4 antibodies for Yersinia outer membrane proteins, which is associated with anti-inflammatory response that is resistant to treatment57	n/a
	Sepsis: Staphylococcus, Escherichia coli, Pseduomonas, etc	Males have higher rates of sepsis and septic shock65 Males more likely to develop sepsis after trauma or surgery65	Conflicting results for a sex bias with mortality97	Male mice develop greater inflammatory response, producing more pro-inflammatory cytokines64 Males have more severe sepsis-induced cardiac dysfunction85 Estrogen is protective, and female mice produced protective antibodies in response to estrogen; estrogen-driven antibodies were maternally transferrable to offspring98
WORMS	Pork tapeworm (Taenia solium) Neurocysticercosis	Females have higher incidence in some countries (Nigeria, Tanzania, Guatemala)99 Females have more transitional cysts in brain (Ecuador)100 No sex difference with incidence in Vietnam99	Female patients have greater number of transitional cysts100	Estrogen increases parasite loads and androgens decrease loads in mice, either acting directly on the worm’s reproduction or by altering host’s immune response to favor Th2 or Th1 pathways (Taenia crassiceps)101
	A. Lumbricoides	Females have higher incidence102		n/a
	Schistosoma masoni	Males have higher prevalence for infection103		Female and castrated male mice have greater morbidity after Schistosoma infection104 Female mice have higher worm loads104 Testosterone is protective for Schistosoma mansoni infections; female mice treated with testosterone had reduced worm burdens (if treated before infection)104
PARASITES	Plasmodium falciparum (malaria)		Male patients have greater disease severity105	n/a
	Cryptosporidium	Males have higher incidence106	Male patients have greater incidence of hospitalizations107	n/a
	Entamoeba histolytica (amoebiasis)	Asymtopmatic infection rates are the same across sexes108	Invasive amebiasis predominantly affects males; males have higher rates of invasive disease108 Males have higher incidence of hepatic amebiasis109	Testosterone treatment induces proinflammatory responses in mouse (& human) classical monocytes, with increased production of CXCL1 and TNF109
	Leishmania	Males have higher incidence even when accounting for exposure110 Adult males have higher incidence of cutaneous leishmaniasis111 Childhood cutaneous leishmaniasis does not exhibit a sex bias112 Males have higher incidence and greater risk ratio of visceral leishmaniasis113 No sex bias for childhood cutaneous leishmaniasis114	Male patients exhibit higher rates of treatment failure and adverse effects110	Male mice have higher parasite burdens following infection (L.infantum)115 Male mice express higher levels of IL-10 and TNF after infection and exhibit greater disease severity115 Male mice (BALB/c congenic strains) are more susceptible to subcutanteous L.major, and exhibit more severe disease110,116 Female mice heal small lesions following L. Mexicana infection, yet male mice exhibit persistent lesions, dependent on IL-4 levels117 Male hamsters have increased disease severity and parasite burden with L. viannia infection. Testosterone-treated female animals had larger lesions than untreated females. Disease severity correlated with increased expression of IL-4, IL-10, and TGF-beta118 X-linked Cxcr3 is biallelically expressed in T cells of female mice and contributes to increased cytokine production119
	Toxoplasma gondii		Sex differences with infection-induced behavioral changes and personality shifts120	Female mice are more susceptible to infection and have higher cyst burdens121 Female mice exhibit higher mortality after acute infection121 Male mice produce higher TNF-alpha after day 10 of infection; female mice mortality did not correlate with lower TNF-alpha levels. Male mice produce higher IFN-gamma and IL-10 early during infection121
FUNGI	Aspergillus fumigatus	Males have higher incidence (invasive pulmonary aspergillosis)122 Male bias with prevalence, incidence and severity123 Males more susceptible to infection123		Female mice have higher levels of immune components (antibody titers, neutrophil eosinophil, and lymphocyte cells) after infection124
	Cryptococcus neoformans	Males have higher incidence125 Males more affected than females125		Female mice express more cytokines in plasma and increased expression of TNF-alpha, interferon-gamma in spleen126 Increased lethality for young male mice126 Survival and fungal loads are similar between male and female mice126
	Paracoccidioides brasiliensis	Males have greater incidence (10:1 male to female, Latin America)127	Male patients have faster disease progression128	Male mice are more susceptible129 Macrophages from infected female mice exhibit greater fungicidal activity, with higher nitric oxide production129 Estrogen is protective following P. brasiliensis infection, as castrated male treated with estradiol have higher levels of IFN-gamma and lower levels of IL-10 compared to normal males. Ovariectomized female mice treated with testosterone produce less IFN-gamma and more IL-10 compared to normal female mice after infection129
	Microsporum, Trichophyton, epigermophyton (Tinea or Dermatophytosi)	Males have higher incidence 130		n/a
	Candida albicans	Females have higher incidence (oral candidiasis)131 Females have higher incidence (candida onychomycosis), with 3/4 females (childbearing age) infected at least once in their life; and 1/10 females having a recurring event131	Male patients with seropositivity for C.albicans have increased odds for schizopherenia132 Female patients with seropositivity for C.albicans have increased odds for lower cognitive scores132	n/a