Life-threatening Infection in Humans: from Epidemiological Analysis to Molecular Genetics

Inclusion Criteria: * Obtained informed consent; * Otherwise healthy patient on admission Infectious episode: * life-threatening caused by known or unknown etiologic agent including viruses, bacteria, mycobacteria or mycetes (in case of lack of microbiologic isolate if clinical, laboratory, histopathologic and radiologic data, justify an infectious origin) * or caused by vaccine strains of attenuated vaccines such as Measles, Mumps, Rubella, Yellow Fever. * or caused by viruses, bacteria, mycobacteria or mycetes with features suggestive of congenital deficiency of immunity, the clinical pictures below refer to known conditions potentially associated with congenital errors of innate immunity Viral susceptibility: * ARDS caused by influenza virus type A, Sars-Cov2 * Life-threatening enterovirus rhomboencephalitis * Life-threatening infection by VZV, CMV, EBV, Rhinovirus, Respiratory Syncytial Virus * HSV encephalitis * Fulminant hepatitis from HAV * Kaposi\'s sarcoma from HHV8 * Beta-HPV infections such as: epidermodysplasia verruciformis, mucocutaneous carcinoma,recurrent/diffuse skin warts,, papillomatosis. Susceptibility to pyogenic bacteria: * At least one life-threatening infection or two episodes of invasive infectionsin otherwise healthy patients, either systemic (bacteremia) or focal (pneumonia, meningitis, arthritis, osteomyelitis, deep brain/peritoneal/hepatosplenic/muscle abscesses) * At least two episodes of disseminated or severe staphylococcal muco-cutaneous infections in otherwise healthy patients: decalvant folliculitis, pustules, furunculosis, blepharitis, lymphadenitis, abscesses Susceptibility to Tropherymawhipplei: \- Whipple\'s disease Susceptibility to Mycobacteria: * Life-threatening , recurrent, or persistent infections with tuberculous or nontuberculous mycobacteria in otherwise healthy patients * Post-vaccinal BCG-osis from attenuated M. Bovis strain Susceptibility to mycetes: * Chronic muco-cutaneous candidiasis Invasive fungal infections of sinuses, lungs, CNS, bones, joints, liver, spleen, and mucocutaneous membranes by Coccidioides, Paracoccidiodes, Cryptococcus, Histoplasma, Pneumocystis, Aspergillus, Talaromyces, Mucormycetes, or Blastomyces * Invasive candidiasis of brain, eyes, heart, bone, and blood in the absence of central catheters * Blood dissemination of fungal pathogens (except for candidiasis from central access) * Persistent positive fungal culture after adequate therapy in terms of drug susceptibility, dosage and duration * Deep infection with dermatophytes (Microsporum, Epidermophyton, Tricophyton) at dermal and lymph node level * Infection with rare yeasts (Geotrichum, Kodamaea, Malassezia/Rhodotorula, Saccharomyces, Trichosporon) or rare molds (AureobasidiumChrysosporium, Corynesprora, Exophiala, Geosmithia, Ochroconis, Paecilomyces, Phellinus, Phialophora, Rhizopus, Scopulariopsis) Other: -All infectious diseases not included in the list whose natural history differs from that expected for the identified pathogen with regard to severity, recurrence, and persistence of the disease, if the condition is not otherwise explainable by the patient\'s acquired risk factors. Exclusion Criteria: * Patients with nonimmunological diseases, secondary immunodeficiencies, nonpharmacological iatrogenic factors, immunosuppressive drug therapies