Patent Publication Number: US-2023149617-A1

Title: Methods of treating conditions

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Pat. Application No. 63/005,125, filed Apr. 3, 2020, and U.S. Provisional Pat. Application No. 63/019,675, filed May 4, 2020, the disclosures of which are incorporated herein by reference in their entirety. 
    
    
     FIELD 
     The present disclosure relates to a method of treating conditions and/or diseases using blood irradiation. The present disclosure further relates to blood irradiation for the treatment of cytokine storm syndrome, autoimmune diseases, and infectious diseases, for modulation of the immune system, and for other purposes. 
     BACKGROUND 
     Currently, there is a great need for the development of new treatments that are effective against infections, particularly against viral infections which are associated with high morbidity and mortality, and which impact on sizable populations. Treatments currently available are inadequate or ineffective in large proportions of infected patients. 
     A well-known family of pathogenic viruses are the Coronaviruses. Coronaviruses (Order Nidovirales, family Coronaviridae, Genus Coronavirus) are enveloped positive-stranded RNA viruses that bud from the endoplasmic reticulum-Golgi intermediate compartment or the cis-Golgi network (Fischer, Stegen et al. 1998; Maeda, Maeda et al. 1999; Corse and Machamer 2000; Maeda, Repass et al. 2001; Kuo and Masters 2003). Coronaviruses infect humans and animals and it is thought that there could be a coronavirus that infects every animal. Per the Center for Disease Control and Prevention (CDC), coronaviruses are named for the crown-like spikes on their surface and comprise four main sub-groupings known as alpha, beta, gamma, and delta., examples of which include: 229E (alpha coronavirus), NL63 (alpha coronavirus), OC43 (beta coronavirus), HKU1 (beta coronavirus)). Other human coronaviruses are MERS-CoV (the beta coronavirus that causes Middle East Respiratory Syndrome, or MERS), SARS-CoV (the beta coronavirus that causes severe acute respiratory syndrome, or SARS), and SARS-CoV-2 (the novel coronavirus that causes coronavirus disease 2019, or COVID-19). People around the world commonly get infected with human coronaviruses 229E, NL63, OC43, and HKU1. Sometimes coronaviruses that infect animals can evolve and make people sick and become a new human coronavirus. Three recent examples of this are SARS-CoV-2, SARS-CoV, and MERS-CoV. (cdc.gov/coronavirus/types.html; February 2020). 
     Two human coronaviruses, 229E and OC43, are known to be the major causes of the common cold and can occasionally cause pneumonia in older adults, neonates, or immunocompromised patients (Peiris, Lai et al. 2003). Animal coronaviruses can cause respiratory, gastrointestinal, neurological, or hepatic diseases in their host (Peiris, Lai et al. 2003). Several animal coronaviruses are significant veterinary pathogens (Rota, Oberste et al. 2003). 
     Although coronaviruses were first identified decades ago, they only received notoriety in 2003 when one of their members was identified as the etiological agent of severe acute respiratory syndrome (SARS). Since then, MERS-CoV and SARS-CoV-2 have become substantial health concerns, with SARS-CoV-2 causing a global pandemic that began in 2019. Previously these viruses were known mainly to be important agents of respiratory and enteric infections of domestic and companion animals and to cause approximately 15% of all cases of the common cold. 
     In general, coronaviruses are well known and most of those who are diagnosed with it recover completely with no complications after receiving the needed supportive therapy. However, in some of the patients who are infected, serious complications can develop affecting the respiratory system, immune system, organs, and other body systems. Coronaviruses can cause death, especially among the elderly, in patients with chronic respiratory and/or cardiac conditions, and in immunocompromised patients. 
     To improve the prospect of treating and preventing viral infections, such as coronavirus infections, there is an on-going need to identify treatments capable of mitigating various aspects of respiratory viral infection. 
     SUMMARY 
     The present disclosure generally relates to a method for the therapeutic or prophylactic treatment of a subject patient having or being at risk of cytokine storm syndrome or other diseases by the extracorporeal administration of blood irradiation (BI) to blood of a patient or other donor. 
     In some embodiments, the invention relates to a method of treating a patient having or being at risk of cytokine storm syndrome. The treatment involves removing a portion of blood from the patient, exposing the portion of blood to ultraviolet radiation, and replacing the exposed portion of blood into the patient. The treatment improves a treatment outcome of the cytokine storm syndrome. 
     In some embodiments, the invention relates to a method of treating a patient having or being at risk of cytokine storm syndrome. The treatment involves removing a portion of blood from a donor, exposing the portion of blood to ultraviolet radiation, and placing the exposed portion of blood into the patient. The treatment improves a treatment outcome of the cytokine storm syndrome. 
     In some embodiments, the invention relates to a method of treating a patient having or being at risk of autoimmune disease. The treatment involves removing a portion of blood from a donor, exposing the portion of blood to ultraviolet radiation, and placing the exposed portion of blood into the patient. The treatment improves a treatment outcome of autoimmune disease. 
     In some embodiments, the invention relates to a method of treating a patient having or being at risk of an infectious disease. The treatment involves removing a portion of blood from a donor, exposing the portion of blood to ultraviolet radiation, and placing the exposed portion of blood into the patient. In some aspects, the patient develops an immune response against the infectious disease and/or the causative agent of the infectious disease. 
     In some embodiments, the invention relates to a method of modulating leukocytes in a patient. The treatment involves removing a portion of blood from a donor, exposing the portion of blood to ultraviolet radiation, and placing the exposed portion of blood into the patient. The treatment improves a treatment outcome of a disease. 
     In some embodiments, the invention relates to a method of treating a patient having or being at risk of COVID-19. The treatment involves removing a portion of blood from a donor, exposing the portion of blood to ultraviolet radiation, and placing the exposed portion of blood into the patient. The treatment improves a treatment outcome of COVID-19. 
     In some embodiments, the patient has, had, or is at risk of cytokine storm syndrome. 
     In some aspects, the cytokine storm syndrome is associated with a condition selected from the group consisting of viral, bacterial, parasitic or fungal infection, acute respiratory distress syndrome, trauma, reaction to a blood transfusion, reaction to a medication, graft vs. host disease, gastric aspiration, sepsis, hemophagocytic lymphohistiocytosis, autoimmune disease, and combinations. 
     In some aspects, the condition is a respiratory viral infection by a virus selected from the group consisting of influenza virus, coronavirus, hantavirus, cytomegalovirus, herpesvirus, varicella virus, rhinovirus, parainfluenza virus, human metapneumovirus, adenovirus, respiratory syncytial virus, Ebstein-Barr virus, Dengue virus, West Nile virus, Western and Eastern equine encephalitis viruses, polio, chikungunya variola virus, Ebola virus, and orthopoxvirus. In some aspects, the respiratory viral infection is infection by a coronavirus, which in some aspects is SARS-CoV-2. 
     In certain embodiments, the step of removing involves removing between about 0.1% and about 20%, between about 1% and about 20%, or between about 5% and about 15% of the blood of the patient. In certain aspects, between about 1.0 and about 5.0 milliliters of blood are removed per kilogram of body weight of the patient. 
     The type of ultraviolet radiation is, in some embodiments, UVA, UVB, UVC, near ultraviolet, middle ultraviolet, far ultraviolet, hydrogen Lyman-alpha, vacuum ultraviolet, or extreme ultraviolet. In some aspects, the ultraviolet radiation is UVA, UVB, and/or UVC. 
     In some aspects, the radiation is ionizing radiation. In some aspects, the radiation is molecularly damaging radiation. In certain aspects, the radiation is particle radiation, and, in some aspects, the particle radiation is selected from the group consisting of alpha radiation, beta radiation, neutron radiation, positron radiation, and proton radiation. In certain aspects, the radiation is electromagnetic radiation, and, in some aspects, the radiation has a wavelength less than about 380 nm. In some aspects, the type of radiation is ultraviolet radiation selected from the group of UVA, UVB, UVC, near ultraviolet, middle ultraviolet, far ultraviolet, hydrogen Lyman-alpha, vacuum ultraviolet, extreme ultraviolet, and combinations thereof, and, in certain aspects the radiation is ultraviolet radiation selected from the group of UVA, UVB, UVC, and combinations thereof. In certain aspects, the radiation has a wavelength less than about 10 nm, and, in some aspects, the radiation has a wavelength less than about 10 pm. In some aspects, the radiation comprises γ-rays. 
     In some embodiments, the blood is exposed to radiation at a dosage of a dosage sufficient to elicit an improved treatment outcome. 
     In some embodiments, the treatment outcome is selected from the group consisting of reduced viral load, reduced risk of cytokine storm syndrome, reduced severity of cytokine storm syndrome, reduced risk of sepsis, reduced severity of sepsis, and reduced severity of autoimmune disease. In certain aspects, the treatment outcome is reduced viral load. In some aspects, the viral load in the portion of blood is reduced by about 100%, at least about 99%, at least about 95%, at least about 90%, at least about 80%, at least about 70%, at least about 60%, at least about 50%, at least about 40%, at least about 30%, at least about 20%, or at least about 10%. In some aspects, the treatment outcome is risk of cytokine storm syndrome. In some aspects, the risk of cytokine storm syndrome in the patient after placing the exposed portion of blood into the individual is reduced by about 100%, by at least about 99%, by at least about 95%, by at least about 90%, by at least about 80%, by at least about 70%, by at least about 60%, by at least about 50%, by at least about 40%, by at least about 30%, by at least about 20%, or by at least about 10%. In some aspects, the severity of cytokine storm syndrome is determined by blood levels of a protein selected from the group consisting of an interleukin, a chemokine, a colony-stimulating factor, a tumor necrosis factor, and combinations thereof. The severity of cytokine storm syndrome is, in some aspects, determined by blood levels of IL-2, IL2R, IL-6, IL-7, IL-8, IL-10, IL-1β, IL-1RA, IL-12, IL-17, TNF-α, GSCF, IP10, MCP1/CCL2, CCL5, CXCL9, IP-10/CXCL10, MIG protein/CXCL9, MIP1A, CSF3R, IFNγ, IFNAR1, IFNGR1, CD58,TNFα, and combinations thereof. In some aspects, the severity of cytokine release is determined by absence of or deceased severity of a symptom. Such symptoms are, in some aspects, lung injury, fever, swelling, edema, redness, fatigue, nausea, and/or sepsis. 
     In certain embodiments, the treatment outcome is severity of autoimmune disease. In some aspects, the severity of autoimmune disease is determined by absence of or deceased severity of a symptom. Such symptoms include fatigue, joint pain, joint swelling, skin problems, vascular inflammation, vascular problems, myocarditis, arrhythmias, nerve problems, abdominal pain, digestive problems, fever, and/or swollen glands. 
     In some embodiments, the patient has or had a condition selected from the group consisting of viral, bacterial, parasitic or fungal infection, acute respiratory distress syndrome, trauma, reaction to a blood transfusion, reaction to a medication, graft vs. host disease, gastric aspiration, sepsis, hemophagocytic lymphohistiocytosis, autoimmune disease, and combinations thereof. In some embodiments, the donor has or had a condition selected from the group consisting of viral, bacterial, parasitic or fungal infection, acute respiratory distress syndrome, trauma, reaction to a blood transfusion, reaction to a medication, graft vs. host disease, gastric aspiration, sepsis, hemophagocytic lymphohistiocytosis, autoimmune disease, and combinations thereof. In some embodiments the condition is an infection by an unknown microorganism or unknown types of microorganism. 
     In some embodiments, the autoimmune disease is selected from the group consisting of Crohn’s disease, eczema, psoriasis, psoriatic arthritis, rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, myocarditis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes mellitus, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, Graves’s disease, and myasthenia graves 
     Some embodiments include further treating the portion of blood. The further treatment in some aspects involves contacting the blood with a compound selected riboflavin, psoralens, amotosalen HCl, porphyrins, photosensitizers, chlorophyll derivatives, light-sensitive agents, UV-activated nucleic acid replication inhibitors, dyes (such as such as neutral red, methylene blue, acridine, toluidines, flavine (acriflavine hydrochloride) and phenothiazine derivatives), coumarins, quinolones, quinones, and anthroquinones. 
     In some embodiments, the methods cause downregulation of the patient’s immune system. In some aspects, the downregulation of the patient’s immune system is caused by inactivating, attenuating, or downregulating white blood cell activity of the patient. In some aspects, the downregulation of the patient’s immune system is caused by inactivating, attenuating, or downregulating white blood cells in the portion of blood. In certain aspects, the downregulation of the patient’s immune system is caused by inactivating, attenuating, or downregulating deleterious cytokine activity in the portion of blood and/or in the patient. 
     In some embodiments, the leukocytes are selected from the group consisting of neutrophils, eosinophils, basophils, macrophages, B cells, and T cells. In some aspects, the T cells are selected from the group consisting of CD4+ T cells, CD8+ T cells, helper T cells, cytotoxic T cells, memory T cells, regulatory T cells, natural killer T cells, mucosal associated invariant T cells, and gamma delta T cells. 
     In some embodiments, there is a vaccine-like effect caused by embodiments of the invention. In some aspects, the radiation creates antigens in the portion of blood. In certain embodiments, the antigens induce an immune response in the patient against an infectious agent. 
     In some embodiments, the patient is the donor. 
     In some embodiments, the patient has, had, or is at risk of having an infection caused by at least one multi-drug resistant organism. In some embodiments, the donor has, had, or is at risk of having an infection caused by at least one multi-drug resistant organism. 
    
    
     DETAILED DESCRIPTION 
     Unless otherwise defined herein, scientific and technical terms used in this application shall have the meanings that are commonly understood by those of ordinary skill in the art. Generally, nomenclature used in connection with, and techniques of, chemistry, molecular biology, cell and cancer biology, immunology, microbiology, pharmacology, and protein and nucleic acid chemistry, described herein, are those well-known and commonly used in the art. 
     All publications, patents and published patent applications referred to in this application are specifically incorporated by reference herein. In case of conflict, the present specification, including its specific definitions, will control. 
     Respiratory viral infections are a major cause of illness and mortality, and respiratory viral infections are a major cause of hospitalization. The types of respiratory viral infection contemplated by the invention are not limited to infections caused by specific types of virus, e.g. to a specific family, genus, or species of virus. Examples of viruses contemplated by the invention are influenza virus, coronavirus, hantavirus, cytomegalovirus, herpesvirus, and orthopoxvirus. 
     Types of influenza include but are not limited to Influenza A, Influenza B, Influenza C, Influenza D and could include other types of influenza that do not yet exist or that have not been described or discovered. There are many types of Influenza A, which include but are not limited to H1N1, H2N2, H3N2, H5N1, H7N7, H1N2, H9N2, H7N2, H7N3, H10N7, H7N9, and H6N1. The naming conventions for influenza are well known in the art, and a person of skill in the art would know how new types of influenza would be named. 
     SARS-CoV-2 is an example of a coronavirus that frequently causes severe symptoms and death. SARS-CoV-2 infection causes the disease COVID-19, which is characterized by numerous respiratory and non-respiratory symptoms. Symptoms include cough, fever, chills, shortness of breath, difficulty breathing, muscle aches, body aches, loss of taste and/or smell, diarrhea, headache, fatigue, nausea, vomiting, nasal congestion, chest pain or pressure, confusion, low oxygen, and others. In some patients, COVID-19 can cause pneumonia and/or acute respiratory distress syndrome (ARDS). ARDS can be the result of cytokine storm syndrome. In some patients, even those with relatively mild disease symptoms can last for more than a month, or even more than two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve months. COVID-19 severity and progression can be measured using the World Health Organization’s eight point ordinal scale. World Health Organization. (2020). WHO R&amp;D Blueprint: novel Coronavirus: COVID-19 Therapeutic Trial Synopsis, Feb. 18, 2020, Geneva, Switzerland. World Health Organization. 
     Types of parainfluenza include but are not limited to Human parainfluenza virus type 1 (HPIV-1), type 2 (HPIV-2), type 3 (HPIV-3), type 4 (HPIV-4) and could include other types of parainfluenza that do not yet exist or that have not been described or discovered. 
     Hantaviruses belong to the bunyavirus family of viruses. There are 5 genera within the family: bunyavirus, phlebovirus, nairovirus, tospovirus, and hantavirus. Each is made up of negative-sensed, single-stranded RNA viruses. All these genera include arthropod-borne viruses, with the exception of hantavirus, which is rodent-borne. Hantaviruses can also infect humans. Hantaviruses could also include other types of parainfluenza that do not yet exist or that have not been described or discovered. 
     Types of cytomegalovirus include but are not limited to  Aotine betaherpesvirus ,  Cebine betaherpesvirus ,  Cercopithecine betaherpesvirus ,  Human betaherpesvirus ,  Macacine betaherpesvirus ,  Macacine betaherpesvirus ,  Mandrilline betaherpesvirus ,  Panine betaherpesvirus ,  Papiine betaherpesvirus ,  Papiine betaherpesvirus ,  Saimiriine betaherpesvirus , and could include other types of parainfluenza that do not yet exist or that have not been described or discovered. 
     Herpes viruses include but are not limited to HHV-1(Herpes simplex virus-1 (HSV-1)), HHV-2 (Herpes simplex virus-2 (HSV-2)), HHV-3 (Varicella zoster virus (VZV)), HHV-4 (Epstein-Barr virus (EBV) Lymphocryptovirus), HHV-5 (Cytomegalovirus (CMV)), HHV-6A and 6B (Roseolovirus) HHV-7, HHV-8 (Kaposi’s sarcoma-associated herpesvirus (KSHV)), CeHV-1 (Cercopithecine herpesvirus 1, (monkey B virus)), MuHV-4 (Murid herpesvirus 68 (MHV-68)). There are many other types of known herpes viruses, and herpes viruses could also include other types of parainfluenza that do not yet exist or that have not been described or discovered. 
     Orthopoxviruses include but are not limited to smallpox, cowpox, horsepox, camelpox, and monkeypox. Orthpoxviruses could also include other types of parainfluenza that do not yet exist or that have not been described or discovered. 
     The methods of the invention can be used to treat cytokine storm syndrome, regardless of what causes or caused the cytokine storm. For example, a cytokine storm can be caused by respiratory viral, bacterial, parasitic or fungal infection, acute respiratory distress syndrome, trauma, reaction to a blood transfusion, reaction to a medication, graft vs. host disease, gastric aspiration, sepsis, hemophagocytic lymphohistiocytosis, other causes, and combinations thereof. Types of bacteria contemplated by the invention include but are not limited to  Staphylococcus  species,  Streptococcus  species,  Pseudomonas aeruginosa ,  Bacteroides  species,  Clostridium perfringens ,  Enterococus  species,  Klebsiella  species,  Escherichia coli ,  Pneumococcus  species,  Listeria monocytogenes ,  Fusobacterium ,  Peptococcus ,  Peptostreptococcus ,  Enterobacter ,  Hemophilus influzenae ,  Proteus ,  Leptospira ,  Burkholderia mallei ,  Burkholderia pseudomallei ,  Brucellosis ,  Coxiella burnetti ,  Vibrio  species,  Francisella tularensis ,  Neisseria meningitides ,  Mycoplasma pneumoniae ,  Mycobacterium avium ,  Mycobacterium avium  subsp.  paratuberculosis , and others. 
     Types of parasites and protozoans contemplated by the invention include but are not limited to  Pneumocystis  species,  toxoplasmosis , malaria ( Plasmodium  species),  Entamoeba histolytica ,  Schistosoma mansoni ,  Trypanosoma  species,  Leischmania  species, and others. Parasites include but are not limited to protozoa (e.g. Sarcodina, Mastigophora, Ciliophora, Sporozoa, and others), helminths (e.g. platyhelminths, acanthocephalins, nematodes, and others), ectoparaisites (e.g. arthropods, and others), and others. 
     Types of fungus contemplated by the invention include but are not limited to  Cryptococcus neoformans ,  Blastomyces dermatitidis ,  Histoplasma capsulatum ,  Candida  species,  Aspergillus ,  Coccidioides immitis ,  Paracoccidioides brasiliensis ,  Sporothrix schenckii ,  Rhizopus ,  Rhizomucor ,  Mucor ,  Absidia  ( Licthemia ), and others. 
     In some cases, pathogenic microorganisms cannot be easily eradicated by the use of existing antimicrobial drugs as these microorganisms may acquire resistance to drugs, or the drugs may pose undesirable side effects to varying degrees to patients. As a result, known antibiotics, antivirals, antifungals, and antiparasitics have not been entirely satisfactory in terms of their activity, behavior in the body, safety, or ability to suppress drug-resistant organisms. 
     The present invention contemplates the treatment and/or prevention of infections by drug resistant organisms, especially those cause bacteria, fungi, viruses, and parasites. Drug resistant organisms can be resistant to one or more drugs. For example, multi-drug resistant organisms can be multi-drug resistant bacteria, multi-drug resistant viruses, multi-drug resistant fungi, multi-drug resistant parasites, and/or other multi-drug resistant organisms. 
     In some embodiments, the bacterium is selected from the group consisting of  Acinetobacter baumanii ,  Burkholderia cepacia ,  Bacterioides fragilis ,  Chlamydia trachomatis ,  Citrobacter freundii ,  Campylobacter jejuni ,  Escherichia coli ,  Enterobacter aerogenes ,  Enterobacter cloacae ,  Haemophilus   inf b,  Helicobacter pylori ,  Klebsiella oxytoca ,  K .  pneumonia  (MDR/CRE),  Legionella pneumophila ,  Neisseria meningitides ,  Neisseria gonorrhoeae ,  Pseudomonas aeruginosa ,  Salmonella typhi ,  paratyphi ,  typhimurium ,  Serratia marcescens ,  Shigella flexneri ,  Stenotrophomonas maltophilia ,  Yersinia pseudotuberculosis ,  Bacillus subtilis ,  Clostridium neoformans ,  C .  difficile ,  C .  perfringens ,  Corynebacterium  spp,  Enterococcus faecalis ,  Enterococcus faecium , vancomycin-resistant Enterococci (VRE),  Listeria monocytogenes ,  Mycobactrium avium ,  M .  tuberculosis ,  M .  leprae ,  Nocardia farcinica ,  P .  acnes ,  Staphylococcus aureus , methicillin-susceptible  Staphylococcus aureus  (MSSA), methicillin-resistant  Staphylococcus aureus  (MRSA),  Staphylococcus epidermidis ,  Streptococcus pyogenes , Strep Group A, Strep Group B (agalactiae) and Strep Group C. 
     In some embodiments, the bacterium is an antibiotic-resistant bacterium. In some embodiments, the bacterium is a multi-drug resistant bacterium. In certain embodiments, the antibiotic-resistant bacterium or the multi-drug resistant bacterium is selected from the group consisting of  Acinetobacter baumanii ,  Escherichia coli ,  Klebsiella oxytoca ,  K .  pneumonia  (MDR/CRE),  Pseudomonas aeruginosa ,  C .  difficile , vancomycin-resistant Enterococci (VRE) and methicillin-resistant  Staphylococcus aureus  (MRSA). 
     In some embodiments, the fungus is selected from the group consisting of  Aspergillus  spp,  Blastomyces ,  Candida albicans ,  glabrata ,  guilliermondii ,  krusei ,  parapsilosis ,  tropicalis Cryptococcus ,  Fusarium  spp.,  Mucor  spp.,  Saccharomyces , and  Pneumocystis jirovecii  ( carinii ). In some embodiments, the virus is selected from the group consisting of Dengue virus, Ebola virus, EBV, Hepitis A virus, Hepitis B virus, Hepitis C virus, Hepitis D virus, HIV, HSV 1, HSV 2, Cytomegalovirus (CMV), Influenza A virus, Marburg virus, Human respiratory syncytial virus (RSV), SARS-CoV, West Nile virus, Human papillomavirus (HPV), Human rhinoviruses (HRVs), and Zica virus. 
     In some embodiments, the parasite is selected from the group consisting of  Cryptosporidium ,  Leishmania ,  Malaria ,  Schistosoma ,  Trichomonasm  and  Trypanosoma . 
     In some embodiments, the pathogen is a mycoplasma. In certain embodiments, the mycoplasma is selected from the group consisting of  M .  pneumoniae ,  M .  hominis  and  M .  orale . 
     The present invention also contemplates the treatment of autoimmune disease. Autoimmune diseases are characterizing by the immune system of a patient recognizing the patient’s own body as foreign, causing the patient’s own immune system to inappropriately attacking the patient’s own body. The present invention now recognizes that modulation of a patient’s immune system, for example by blood irradiation can be used to treat certain aspects of autoimmune disease. Modulation of the immune system can be accomplished by modulating immune, bone marrow, and/or blood cells. Modulation of the immune system can also involve autologous and/or allogeneic bone marrow transplantation, including bone marrow transplantation with or without myeloablation. 
     Autoimmune diseases include but are not limited to Crohn’s disease, eczema, psoriasis, psoriatic arthritis, rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, myocarditis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes mellitus, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, multiple sclerosis Graves’s disease, and myasthenia graves. Further autoimmune diseases are listed in Table 1.  
     
       
         
          TABLE 1
           
               
               
               
               
             
               
                 List of autoimmune diseases 
               
             
            
               
                 Achalasia 
                 Devic’s disease (neuromyelitis optica) 
                 Lyme disease chronic 
                 Pyoderma gangrenosum 
               
               
                 Addison’s disease 
                 Discoid lupus 
                 Meniere’s disease 
                 Raynaud’s phenomenon 
               
               
                 Adult Still’s disease 
                 Dressler’s syndrome 
                 Microscopic polyangiitis (MPA) 
                 Reactive Arthritis 
               
               
                 Agammaglobulinemia 
                 Endometriosis 
                 Mixed connective tissue disease (MCTD) 
                 Reflex sympathetic dystrophy 
               
               
                 Alopecia areata 
                 Eosinophilic esophagitis (EoE) 
                 Mooren’s ulcer 
                 Relapsing polychondritis 
               
               
                 Amyloidosis 
                 Eosinophilic fasciitis 
                 Mucha-Habermann disease 
                 Restless legs syndrome (RLS) 
               
               
                 Ankylosing spondylitis 
                 Erythema nodosum 
                 Multifocal Motor Neuropathy (MMN) or MMNCB 
                 Retroperitoneal fibrosis 
               
               
                 Anti-GBM/Anti-TBM nephritis 
                 Essential mixed cryoglobulinemia 
                 Multiple sclerosis 
                 Rheumatic fever 
               
               
                 Antiphospholipid syndrome 
                 Evans syndrome 
                 Myasthenia gravis 
                 Rheumatoid arthritis 
               
               
                 Autoimmune angioedema 
                 Fibromyalgia 
                 Myositis 
                 Sarcoidosis 
               
               
                 Autoimmune dysautonomia 
                 Fibrosing alveolitis 
                 Narcolepsy 
                 Schmidt syndrome 
               
               
                 Autoimmune encephalomyelitis 
                 Giant cell arteritis (temporal arteritis) 
                 Neonatal Lupus 
                 Scleritis 
               
               
                 Autoimmune hepatitis 
                 Giant cell myocarditis 
                 Neuromyelitis optica 
                 Scleroderma 
               
               
                 Autoimmune inner ear disease (AIED) 
                 Glomerulonephritis 
                 Neutropenia 
                 Sjögren’s syndrome 
               
               
                 Autoimmune myocarditis 
                 Goodpasture’s syndrome 
                 Ocular cicatricial pemphigoid 
                 Sperm &amp; testicular autoimmunity 
               
               
                 Autoimmune oophoritis 
                 Granulomatosis with Polyangiitis 
                 Optic neuritis 
                 Stiff person syndrome (SPS) 
               
               
                 Autoimmune orchitis 
                 Graves’ disease 
                 Palindromic rheumatism (PR) 
                 Subacute bacterial endocarditis (SBE) 
               
               
                 Autoimmune pancreatitis 
                 Guillain-Barre syndrome 
                 PANDAS 
                 Susac’s syndrome 
               
               
                 Autoimmune retinopathy 
                 Hashimoto’s thyroiditis 
                 Paraneoplastic cerebellar degeneration (PCD) 
                 Sympathetic ophthalmia (SO) 
               
               
                 Autoimmune urticaria 
                 Hemolytic anemia 
                 Paroxysmal nocturnal hemoglobinuria (PNH) 
                 Takayasu’s arteritis 
               
               
                 Axonal &amp; neuronal neuropathy (AMAN) 
                 Henoch-Schonlein purpura (HSP) 
                 Parry Romberg syndrome 
                 Temporal arteritis/Giant cell arteritis 
               
               
                 Baló disease 
                 Herpes gestationis or pemphigoid gestationis (PG) 
                 Pars planitis (peripheral uveitis) 
                 Thrombocytopenic purpura (TTP) 
               
               
                 Behcet’s disease 
                 Hidradenitis Suppurativa (HS) (Acne Inversa) 
                 Parsonage-Turner syndrome 
                 Tolosa-Hunt syndrome (THS) 
               
               
                 Benign mucosal pemphigoid 
                 Hypogammalglobulinemia 
                 Pemphigus 
                 Transverse myelitis 
               
               
                 Bullous pemphigoid 
                 IgA Nephropathy 
                 Peripheral neuropathy 
                 Type 1 diabetes 
               
               
                 Castleman disease (CD) 
                 IgG4-related sclerosing disease 
                 Perivenous encephalomyelitis 
                 Ulcerative colitis (UC) 
               
               
                 Celiac disease 
                 Immune thrombocytopenic purpura (ITP) 
                 Pernicious anemia (PA) 
                 Undifferentiated connective tissue disease (UCTD) 
               
               
                 Chagas disease 
                 Inclusion body myositis (IBM) 
                 POEMS syndrome 
                 Uveitis 
               
               
                 Chronic inflammatory demyelinating polyneuropathy (CIDP) 
                 Interstitial cystitis (IC) 
                 Polyarteritis nodosa 
                 Vasculitis 
               
               
                 Chronic recurrent multifocal osteomyelitis (CRMO) 
                 Juvenile arthritis 
                 Polyglandular syndromes type I, II, III 
                 Vitiligo 
               
               
                 Churg-Strauss Syndrome (CSS) or Eosinophilic Granulomatosis (EGPA) 
                 Juvenile diabetes (Type 1 diabetes) 
                 Polymyalgia rheumatica 
                 Vogt-Koyanagi-Harada Disease 
               
               
                 Cicatricial pemphigoid 
                 Juvenile myositis (JM) 
                 Polymyositis 
                   
               
               
                 Cogan’s syndrome 
                 Kawasaki disease 
                 Postmyocardial infarction syndrome 
                   
               
               
                 Cold agglutinin disease 
                 Lambert-Eaton syndrome 
                 Postpericardiotomy syndrome 
                   
               
               
                 Congenital heart block 
                 Leukocytoclastic vasculitis 
                 Primary biliary cirrhosis 
                   
               
               
                 Coxsackie myocarditis 
                 Lichen planus 
                 Primary sclerosing cholangitis 
                   
               
               
                 CREST syndrome 
                 Lichen sclerosus 
                 Progesterone dermatitis 
                   
               
               
                 Crohn’s disease 
                 Ligneous conjunctivitis 
                 Psoriasis 
                   
               
               
                 Dermatitis herpetiformis 
                 Linear IgA disease (LAD) 
                 Psoriatic arthritis 
                   
               
               
                 Dermatomyositis 
                 Lupus 
                 Pure red cell aplasia (PRCA) 
                   
               
            
           
         
       
     
     Blood cells can be in whole blood or in a sub-population of cells in whole blood. Subpopulations of cells in whole blood include platelets, red blood cells (erythrocytes), platelets and white blood cells (i.e., peripheral blood leukocytes, which are made up of neutrophils, lymphocytes, eosinophils, basophils and monocytes). These five types of white blood cells can be further divided into two groups, granulocytes (which are also known as polymorphonuclear leukocytes and include neutrophils, eosinophils and basophils) and mononuclear leukocytes (which include monocytes and lymphocytes). Lymphocytes can be further divided into T cells, B cells and NK cells. Peripheral blood cells are found in the circulating pool of blood and not sequestered within the lymphatic system, spleen, liver, or bone marrow. Other cells are present in blood that can be isolated. Types of leukocytes include naive B cells, memory B cells, plasma cells, CD8 T cells, naive CD4 T cells, CD4 memory RO unactivated T cells, CD4 memory RO activated T cells, follicular helper T cells, regulatory T cells, gamma delta T cells, unstimulated NK cells, stimulated NK cells, monocytes, macrophages M0, macrophages M1, macrophages M2, unstimulated dendritic cells, stimulated dendritic cells, unstimulated mast cells, stimulated mast cells, eosinophils, and neutrophils. 
     Blood can be fractionated to yield various preparations of blood fractions. Blood fractions include but are not limited to red blood cells, white blood cells, platelets, and plasma. Other blood fractions include but are not limited to albumin, clotting factors, colony stimulating factors, cryoprecipitate, erythropoietin (EPO), Factor I, Factor II, fibrinogen/fibrin, hemoglobin-based oxygen carriers, immunoglobulins, interferon, interleukin, prothrombin, Rh Factor, sealants, and thrombin. A blood fraction can also be a fraction that includes an infectious agent, for example a fraction enriched with, relative to whole blood, bacteria, virus, fungus, parasite, or combinations thereof. A fraction can also contain completely or incompletely purified or isolated bacteria, virus, fungus, parasite, or combinations thereof. The present invention contemplates irradiation of whole blood and/or one or more blood fractions. 
     Herein, “portion” refers to an amount of whole blood or to a fraction of whole blood. The invention contemplates irradiation of a whole portion of blood, a percentage or amount of a portion of blood, a fraction of a portion of blood, a component from a portion of blood, or combinations thereof. The invention contemplates placing into a patient a whole portion of blood, a percentage or amount of a portion of blood, a fraction of a portion of blood, a component from blood, or combinations thereof. 
     The invention contemplates the removal of a portion of blood from a patient and/or donor and irradiation of the portion of blood, which includes a/the whole portion of blood, a/the percentage or amount of a portion of blood, a/the fraction of a portion of blood, a/the component from a portion blood, or combinations thereof. A fraction and/or a component, for example an infectious agent, can be removed from the portion of blood, irradiated, and placed into a/the patient. After removal from blood, for example a/the portion of blood, an infectious agent can be cultured, expanded, or otherwise increased or decreased in quantity, size, health, infectivity, contagiousness, reproductive capacity, virulence, lethality, purity, and/or other measures of infectious agent characteristics prior to being irradiated and then placed into a/the patient. For example, an infectious agent (e.g. a bacterium, virus, fungus, and/or parasite) can be isolated from a portion of blood and cultured to increase in number, and then the agent can be irradiated and placed into a/the patient. Alternatively, an agent can be irradiated prior to being taken from the portion of blood and placed into a/the patient. The whole infectious agent or one or more pieces of the agent can be placed into a/the patient. For example, an agent can be irradiated, and then antigens from the irradiated agent can be enriched in purity and then placed into a/the patient. These procedures are expected to induce an immune response in a/the patient, as in the vaccine-like effect described herein, and/or to have other effects. 
     Vaccines are used to protect a patient from a disease, oftentimes an infectious and/or microbial disease or cancer. Vaccines induce a protective immunological response in a patient such that resistance to new infection will be enhanced and/or the clinical severity of the disease reduced. Vaccines typically work by presenting antigens from a target, for example a target organism or cancer cell, to a patient’s immune system. The patient’s immune system recognizes the antigen(s) and mounts a protective response caused by the antigen(s) that confers resistance to the target. The present infection contemplates the use of blood irradiation to induce a vaccine-like effect in a patient. 
     The vaccine-like effect of the present invention involves the use of radiation to create antigens in the blood of a patient, against which antigens the patient’s immune system can mount an immunological response. For example, the blood of a patient can be irradiated so as to induce damage to blood components, such as blood cells, or other materials in the blood, for example viruses or bacteria. Irradiation can induce damage in a potential target to cause the exposure and/or formation of antigens that can be used by the patient’s immune system to stimulate and mount a response to protect against the target. Irradiation can also induce the exposure and/or formation, of antigens through means other than damage. 
     Ultraviolet blood irradiation (UBI)—originally the Knott technique—has been used in the United States since 1928 for the successful extracorporeal treatment of microbial infections. Over the years there have been scientific arguments concerning the mechanism by which UBI works and the consensus appears to be that some organisms are killed and a stimulated immune system then protects the patient by clearing the remaining organisms from the body. 
     Ultraviolet (UV) blood irradiation (UBI) therapy may be administered by a device called a Knott HEMO-IRRADIATOR®, for example as disclosed in Knott’s U.S. Pat. No. 2,308,516. UBI therapy raises the resistance of the host and is therefore able to control many disease processes. A fundamental effect of UBI is to enhance the biochemical and physiological defenses of the body by the introduction of UV energy into the blood stream. 
     Such treatment is intravenously applied by irradiating blood with a controlled amount of UV energy in the accepted therapeutic band. This produces a rapid detoxifying effect with subsidence of toxic symptoms. Venous oxygen is increased in patients with depressed blood oxygen values. Of special interest is that a rapid rise in resistance to acute or chronic viral and bacterial infection occurs. Minimal harmful effects have been observed with UBI therapy in cases of viral infections, hepatitis, bacterial infections, hypoxemia and many other illnesses, especially blood-related infections. 
     The Knott technique of blood irradiation (approved by the American Blood Irradiation Society) has achieved the following physiologic objectives: (1) increases the blood oxygen level; (2) increases phagocytosis; (3) relieves toxemia; (4) decreases edema; and (5) controls nausea and vomiting. 
     In some embodiments of the present invention, treatment generally consists of withdrawing from 1.0 to 1.5 cc of blood per pound of body weight from the patient, and, by use of the Knott HEMO-IRRADIATOR®, or similar device, exposing the blood to radiant energy between the wave lengths of 2,000 and 12,000 angstroms units as it passes through the irradiation unit at a predetermined flow rate. The blood is returned to the patient through the needle used for the initial venipuncture. Treatment requires from 30-45 minutes. Outpatients rest fifteen minutes, after which time they may resume whatever activity is permitted. 
     Various parameters of the above treatment protocol can be adjusted. For example, the volume of blood used can be from 1 to 5 milliliters per kilogram of blood, or 1 to 4, or 1 to 3, or 1 to 2, or 2 to 4, or 2 to 3, or about 1, or about 2, or about 3, or about 4, or about 5 milliliters of blood per kilogram of body weight. Various types of ultraviolet light are suitable for UBI procedures of the present invention. For example, the types of ultraviolet light contemplated by the invention include those in Table 2.  
     
       
         
          TABLE 2
           
               
               
               
               
             
               
                 Types of ultraviolet light 
               
               
                 Name 
                 Abbreviation 
                 Wavelength (nm) 
                 Photon energy (eV) 
               
             
            
               
                 Ultraviolet A 
                 UVA 
                 315-400 
                 3.10-3.94 
               
               
                 Ultraviolet B 
                 UVB 
                 280-315 
                 3.94-4.43 
               
               
                 Ultraviolet C 
                 UVC 
                 100-280 
                 4.43-12.4 
               
               
                 Near ultraviolet 
                 NUV 
                 300-400 
                 3.10-4.13 
               
               
                 Middle ultraviolet 
                 MUV 
                 200-300 
                 4.13-6.20 
               
               
                 Far ultraviolet 
                 FUV 
                 122-200 
                 6.20-10.16 
               
               
                 Hydrogen 
                 H Lyman-α 
                 121-122 
                 10.16-10.25 
               
               
                 Vacuum ultraviolet 
                 VUV 
                 10-200 
                 6.20-124 
               
               
                 Extreme ultraviolet 
                 EUV 
                 10-121 
                 10.25-124 
               
            
           
         
       
     
     UBI is useful to treat various aspects of viral infection, for example to reduce viral load or reduce the risk and/or severity of cytokine storm syndrome. Cytokine storm syndrome is also known as a cytokine storm or cytokine storm syndrome. Cytokine storm syndrome is a dangerous condition caused by some types of virus, for example influenza (e.g. H5N1 influenza and H1N1 influenza) and coronavirus (e.g. SARS-CoV-2, SARS-CoV, and MERS-CoV). Cytokine storm syndrome is a systemic inflammatory response syndrome, so called because it involves massive release of cytokines, that can lead to serious injury to a patient or death. In some embodiments, cytokine storm syndrome is determined by the following three criteria: 1) elevated circulating cytokine levels, 2) acute systemic inflammatory symptoms, and 3) either secondary organ dysfunction (often renal, hepatic, or pulmonary) due to inflammation beyond that which could be attributed to a normal response to a pathogen (if a pathogen is present), or any cytokine-driven organ dysfunction (if no pathogen is present). Examples of cytokines are provided in Table 3. 
     During a cytokine storm, inflammatory mediators, for example pro-inflammatory cytokines such as Interleukin-1 (IL1), Interleukin-6 (IL6), tumor necrosis factor-alpha (TNF-alpha), oxygen free radicals, and coagulation factors are released by the immune cells of the body. Cytokine storm severity and progression can be measured by levels of cytokines, for example those in Table 3.  
     
       
         
          TABLE 3
           
               
               
               
               
               
               
               
               
               
             
               
                 List of cytokines 
               
               
                 UniProt Entry 
                 UniProt Entry name 
                 Gene names 
                 UniProt Entry 
                 UniProt Entry name 
                 Gene names 
                 UniProt Entry 
                 UniProt Entry name 
                 Gene names 
               
             
            
               
                 Q16663 
                 CCL15_HUMAN 
                 CCL15 MIP5 NCC3 SCYA15 
                 P05013 
                 IFNA6_HUMAN 
                 IFNA6 
                 P32970 
                 CD70_HUMAN 
                 CD70 CD27L CD27LG TNFSF7 
               
               
                 P13501 
                 CCL5_HUMAN 
                 CCL5 D17S136E SCYA5 
                 P32881 
                 IFNA8_HUMAN 
                 IFNA8 
                 P34820 
                 BMP8B_HUMAN 
                 BMP8B BMP8 
               
               
                 P04141 
                 CSF2_HUMAN 
                 CSF2 GMCSF 
                 Q8IU54 
                 IFNL1_HUMAN 
                 IFNL1 IL29 ZCYTO21 
                 Q9UBH0 
                 I36RA_HUMAN 
                 IL36RN FIL1D IL1F5 IL1HY1 IL1L1 IL1RP3 UNQ1896/ PRO4342 
               
               
                 P09919 
                 CSF3_HUMAN 
                 CSF3 C17orf33 GCSF 
                 Q9Y4X3 
                 CCL27_HUMAN 
                 CCL27 ILC SCYA27 
                 P13232 
                 IL7_HUMAN 
                 IL7 
               
               
                 Q96DZ9 
                 CKLF5_HUMAN 
                 CMTM5 CKLFSF5 
                 O00626 
                 CCL22_HUMAN 
                 CCL22 MDC SCYA22 A-152E5.1 
                 P15248 
                 IL9_HUMAN 
                 IL9 
               
               
                 P16619 
                 CL3L1_HUMAN 
                 CCL3L1 D17S1718 G0S19-2 SCYA3L1; CCL3L3 
                 Q8IZV2 
                 CKLF8_HUMAN 
                 CMTM8 CKLFSF8 
                 Q8IZJ0 
                 IFNL2_HUMAN 
                 IFNL2 IL28A ZCYTO20 
               
               
                 Q99731 
                 CCL19_HUMAN 
                 CCL19 ELC MIP3B SCYA19 
                 Q96FZ5 
                 CKLF7_HUMAN 
                 CMTM7 CKLFSF7 
                 P01566 
                 IFN10_HUMAN 
                 IFNA10 
               
               
                 P13500 
                 CCL2_HUMAN 
                 CCL2 MCP1 SCYA2 
                 O60565 
                 GREM1_HUMAN 
                 GREM1 CKTSF1B1 DAND2 DRM PIG2 
                 P01579 
                 IFNG_HUMAN 
                 IFNG 
               
               
                 Q16627 
                 CCL14_HUMAN 
                 CCL14 NCC2 
                 O14793 
                 GDF8_HUMAN 
                 MSTN GDF8 
                 Q8TAD2 
                 IL17D_HUMAN 
                 IL17D UNQ3096/ PRO21175 
               
               
                 Q9UBD9 
                 CLCF1_HUMAN 
                 CLCF1 BSF3 CLC NNT1 
                 O43927 
                 CXL13_HUMAN 
                 CXCL13 BCA1 BLC SCYB13 
                 Q9UHD0 
                 IL19_HUMAN 
                 IL19 ZMDA1 
               
               
                 P22003 
                 BMP5_HUMAN 
                 BMP5 
                 Q9NPF7 
                 IL23A_HUMAN 
                 IL23A SGRF UNQ2498/ PRO5798 
                 Q9P0M4 
                 IL17C_HUMAN 
                 IL17C UNQ561/P RO1122 
               
               
                 Q7Z5Y6 
                 BMP8A_HUMAN 
                 BMP8A 
                 P02775 
                 CXCL7_HUMAN 
                 PPBP CTAP3 CXCL7 SCYB7 TGB1 THBGB1 
                 Q9UHF5 
                 IL17B_HUMAN 
                 IL17B IL20 NIRF ZCYTO7 UNQ516/P RO1031 
               
               
                 O95813 
                 CER1_HUMAN 
                 CER1 DAND4 
                 Q07325 
                 CXCL9_HUMAN 
                 CXCL9 CMK MIG SCYB9 
                 P015 83 
                 IL1A_HUMAN 
                 IL1A IL1F1 
               
               
                 P49771 
                 FLT3L_HUMAN 
                 FLT3LG 
                 Q9H293 
                 IL25_HUMAN 
                 IL25 IL17E UNQ3120/ PRO 10272 
                 Q9NZH7 
                 IL36B_HUMAN 
                 IL36B IL1F8 IL1H2 
               
               
                 P15514 
                 AREG_HUMAN 
                 AREG AREGB SDGF 
                 Q8NEV9 
                 IL27A_HUMAN 
                 IL27 IL27A IL30 
                 O00175 
                 CCL24_HUMAN 
                 CCL24 MPIF2 SCYA24 
               
               
                 Q99616 
                 CCL13_HUMAN 
                 CCL13 MCP4 NCC1 SCYA13 
                 Q6EBC2 
                 IL31_HUMAN 
                 IL31 
                 P29459 
                 IL12A_HUMAN 
                 IL12A NKSF1 
               
               
                 Q9NRJ3 
                 CCL28_HUMAN 
                 CCL28 SCYA28 
                 O95760 
                 IL33_HUMAN 
                 IL33 C9orf26 IL1F11 NFHEV 
                 P14174 
                 MIF_HUMAN 
                 MIF GLIF MMIF 
               
               
                 015444 
                 CCL25_HUMAN 
                 CCL25 SCYA25 TECK 
                 Q9UHA7 
                 IL36A_HUMAN 
                 IL36A FIL1E IL1E IL1F6 
                 Q86WN2 
                 IFNE_HUMAN 
                 IFNE IFNE1 UNQ360/P RO655 
               
               
                 P27539 
                 GDF1_HUMAN 
                 GDF1 
                 Q8NHW4 
                 CC4L_HUMAN 
                 CCL4L1 CCL4L LAG1 SCYA4L1; CCL4L2 CCL4L SCYA4L2 
                 P20809 
                 IL11_HUMAN 
                 IL11 
               
               
                 P28799 
                 GRN_HUMAN 
                 GRN 
                 P12643 
                 BMP2_HUMAN 
                 BMP2 BMP2A 
                 Q1L6U9 
                 MSMP_HUMAN 
                 MSMP PSMP 
               
               
                 O95390 
                 GDF11_HUMAN 
                 GDF11 BMP 11 
                 O95393 
                 BMP10_HUMAN 
                 BMP 10 
                 P01562 
                 IFNA1_HUMAN 
                 IFNA1; IFNA13 
               
               
                 P41273 
                 TNFL9_HUMAN 
                 TNFSF9 
                 O00585 
                 CCL21_HUMAN 
                 CCL21 SCYA21 UNQ784/P RO1600 
                 P01568 
                 IFN21_HUMAN 
                 IFNA21 
               
               
                 P13236 
                 CCL4_HUMAN 
                 CCL4 LAG1 MIP1B SCYA4 
                 P19876 
                 CXCL3_HUMAN 
                 CXCL3 GRO3 GROG SCYB3 
                 K9M1U5 
                 IFNL4_HUMAN 
                 IFNL4 
               
               
                 Q9UBR5 
                 CKLF_HUMAN 
                 CKLF CKLF1 HSPC224 UNQ410/P RO772 
                 P42830 
                 CXCL5_HUMAN 
                 CXCL5 ENA78 SCYB5 
                 P05231 
                 IL6_HUMAN 
                 IL6 IFNB2 
               
               
                 P22362 
                 CCL1_HUMAN 
                 CCL1 SCYA1 
                 O95715 
                 CXL14_HUMAN 
                 CXCL14 MIP2G NJAC SCYB14 PSEC0212 UNQ240/P RO273 
                 Q9NZH8 
                 IL36G_HUMAN 
                 IL36G IL1E IL1F9 IL1H1 IL1RP2 UNQ2456/ PRO5737 
               
               
                 Q9BXJ3 
                 C1QT4_HUMAN 
                 C1QTNF4 CTRP4 
                 O75610 
                 LFTY1_HUMAN 
                 LEFTY 1 LEFTB LEFTYB UNQ278/P RO317 
                 P10147 
                 CCL3_HUMAN 
                 CCL3 G0S19-1 MIP1A SCYA3 
               
               
                 Q96MX0 
                 CKLF3_HUMAN 
                 CMTM3 CKLFSF3 
                 P55107 
                 GDF10_HUMAN 
                 GDF10 BMP3B 
                 Q92583 
                 CCL17_HUMAN 
                 CCL17 SCYA17 TARC 
               
               
                 Q8IZ96 
                 CKLF1_HUMAN 
                 CMTM1 CKLFSF1 
                 Q6KF10 
                 GDF6_HUMAN 
                 GDF6 BMP 13 GDF16 
                 P51671 
                 CCL11_HUMAN 
                 CCL11 SCYA11 
               
               
                 P22004 
                 BMP6_HUMAN 
                 BMP6 VGR 
                 P40933 
                 IL15_HUMAN 
                 IL15 
                 Q14116 
                 IL18_HUMAN 
                 IL18 IGIF IL1F4 
               
               
                 Q9Y258 
                 CCL26_HUMAN 
                 CCL26 SCYA26 UNQ216/P RO242 
                 Q14213 
                 IL27B_HUMAN 
                 EBI3 IL27B 
                 Q96QR1 
                 SG3A1_HUMAN 
                 SCGB3A1 HIN1 PNSP2 UGRP2 UNQ629/P RO1245 
               
               
                 Q8TAZ6 
                 CKLF2_HUMAN 
                 CMTM2 CKLFSF2 
                 P05113 
                 IL5_HUMAN 
                 IL5 
                 O43557 
                 TNF14_HUMAN 
                 TNFSF14 HVEML LIGHT UNQ391/P RO726 
               
               
                 P43026 
                 GDF5_HUMAN 
                 GDF5 BMP14 CDMP1 
                 P10145 
                 IL8_HUMAN 
                 CXCL8 IL8 
                 P48061 
                 SDF1_HUMAN 
                 CXCL12 SDF1 SDF1A SDF1B 
               
               
                 015467 
                 CCL16_HUMAN 
                 CCL16 ILINCK NCC4 SCYA16 
                 P05112 
                 IL4_HUMAN 
                 IL4 
                 P32971 
                 TNFL8_HUMAN 
                 TNFSF8 CD30L CD30LG 
               
               
                 Q99988 
                 GDF15_HUMAN 
                 GDF15 MIC1 PDF PLAB PTGFB 
                 P01574 
                 IFNB_HUMAN 
                 IFNB 1 IFB IFNB 
                 O43508 
                 TNF12_HUMAN 
                 TNFSF12 APO3L DR3LG UNQ181/P RO207 
               
               
                 P58499 
                 FAM3B_HUMAN 
                 FAM3B C21orf11 C21orf76 PRED44 UNQ320/P RO365 
                 P29460 
                 IL12B_HUMAN 
                 IL12B NKSF2 
                 Q9Y275 
                 TN13B_HUMAN 
                 TNFSF13B BAFF BLYS TALL1 TNFSF20 ZTNF4 UNQ401/P RO738 
               
               
                 P12645 
                 BMP3_HUMAN 
                 BMP3 BMP3A 
                 P08700 
                 IL3_HUMAN 
                 IL3 
                 P80098 
                 CCL7_HUMAN 
                 CCL7 MCP3 SCYA6 SCYA7 
               
               
                 P13497 
                 BMP1_HUMAN 
                 BMP1 PCOLC 
                 Q9UK05 
                 GDF2_HUMAN 
                 GDF2 BMP9 
                 O75888 
                 TNF13_HUMAN 
                 TNFSF13 APRIL TALL2 ZTNF2 UNQ383/P RO715 
               
               
                 P80162 
                 CXCL6_HUMAN 
                 CXCL6 GCP2 SCYB6 
                 P09341 
                 GROA_HUMAN 
                 CXCL1 GRO GRO1 GROA MGSA SCYB1 
                 P40225 
                 TPO_HUMAN 
                 THPO MGDF 
               
               
                 Q13007 
                 IL24_HUMAN 
                 IL24 MDA7 ST16 
                 O60383 
                 GDF9_HUMAN 
                 GDF9 
                 Q969D9 
                 TSLP_HUMAN 
                 TSLP 
               
               
                 Q9NPH9 
                 IL26_HUMAN 
                 IL26 AK155 
                 Q7Z4P5 
                 GDF7_HUMAN 
                 GDF7 
                 P43490 
                 NAMPT_HUMAN 
                 NAMPT PBEF PBEF1 
               
               
                 P19875 
                 CXCL2_HUMAN 
                 CXCL2 GRO2 GROB MIP2A SCYB2 
                 Q16552 
                 IL17_HUMAN 
                 IL17A CTLA8 IL17 
                 Q86YJ6 
                 THNS2_HUMAN 
                 THNSL2 
               
               
                 Q8WWZ1 
                 IL1FA_HUMAN 
                 IL1F10 FIL1T IL1HY2 IL38 FKSG75 UNQ6119/ PRO20041 
                 P29965 
                 CD40L_HUMAN 
                 CD40LG CD40L TNFSF5 TRAP 
                 P01374 
                 TNFB_HUMAN 
                 LTA TNFB TNFSF1 
               
               
                 P02778 
                 CXL10_HUMAN 
                 CXCL10 INP10 SCYB10 
                 P05015 
                 IFN16_HUMAN 
                 IFNA16 
                 P48023 
                 TNFL6_HUMAN 
                 FASLG APT1LG1 CD95L FASL TNFSF6 
               
               
                 014625 
                 CXL11_HUMAN 
                 CXCL11 ITAC SCYB 11 SCYB9B 
                 P05014 
                 IFNA4_HUMAN 
                 IFNA4 
                 Q6UWK7 
                 GP15L_HUMAN 
                 GPR15L C10orf99 UNQ1833/ PRO3446 
               
               
                 Q9H2A7 
                 CXL16_HUMAN 
                 CXCL16 SCYB16 SRPSOX UNQ2759/ PRO6714 
                 Q16619 
                 CTF1_HUMAN 
                 CTF1 
                 P02776 
                 PLF4_HUMAN 
                 PF4 CXCL4 SCYB4 
               
               
                 Q9NYY1 
                 IL20_HUMAN 
                 IL20 ZCYTO10 UNQ852/P RO1801 
                 O95972 
                 BMP15_HUMAN 
                 BMP15 GDF9B 
                 Q96PD4 
                 IL17F_HUMAN 
                 IL17F 
               
               
                 Q9HBE4 
                 IL21_HUMAN 
                 IL21 
                 P06744 
                 G6PI_HUMAN 
                 GPI 
                 P55000 
                 SLUR1_HUMAN 
                 SLURP 1 ARS 
               
               
                 Q9GZX6 
                 IL22_HUMAN 
                 IL22 ILTIF ZCYTO18 UNQ3099/ PRO 10096 
                 Q96S42 
                 NODAL_HUMAN 
                 NODAL 
                 Q7Z5A7 
                 TAFA5_HUMAN 
                 TAFA5 FAM19A5 UNQ5208/ PRO34524 
               
               
                 P60568 
                 IL2_HUMAN 
                 IL2 
                 P78556 
                 CCL20_HUMAN 
                 CCL20 LARC MIP3A SCYA20 
                 P50591 
                 TNF10_HUMAN 
                 TNFSF10 APO2L TRAIL 
               
               
                 P24001 
                 IL32_HUMAN 
                 IL32 NK4 TAIF 
                 Q8IZ19 
                 IFNL3_HUMAN 
                 IFNL3 IL28B IL28C ZCYTO22 
                 Q9UNG2 
                 TNF18_HUMAN 
                 TNFSF18 AITRL GITRL TL6 UNQ149/P RO175 
               
               
                 Q6ZMJ4 
                 IL34_HUMAN 
                 IL34 C16orf77 
                 P80075 
                 CCL8_HUMAN 
                 CCL8 MCP2 SCYA10 SCYA8 
                 O95150 
                 TNF15_HUMAN 
                 TNFSF15 TL1 VEGI 
               
               
                 Q9P0W0 
                 IFNK_HUMAN 
                 IFNK UNQ6124/ PRO20084 
                 Q9NR23 
                 GDF3_HUMAN 
                 GDF3 UNQ222/P RO248 
                 P78423 
                 X3CL1_HUMAN 
                 CX3CL1 FKN NTT SCYD1 A-152E5.2 
               
               
                 Q9H772 
                 GREM2_HUMAN 
                 GREM2 CKTSF1B2 DAND3 PRDC 
                 P12644 
                 BMP4_HUMAN 
                 BMP4 BMP2B DVR4 
                 P01375 
                 TNFA_HUMAN 
                 TNF TNFA TNFSF2 
               
               
                 P01584 
                 IL1B_HUMAN 
                 IL1B IL1F2 
                 P01567 
                 IFNA7_HUMAN 
                 IFNA7 
                 Q06643 
                 TNFC_HUMAN 
                 LTB TNFC TNFSF3 
               
               
                 O00292 
                 LFTY2_HUMAN 
                 LEFTY2 EBAF LEFTA LEFTYA TGFB4 PSEC0024 
                 Q14005 
                 IL16_HUMAN 
                 IL16 
                 014788 
                 TNF11_HUMAN 
                 TNFSF11 OPGL RANKL TRANCE 
               
               
                 P01569 
                 IFNA5_HUMAN 
                 IFNA5 
                 Q6UX52 
                 IL40_HUMAN 
                 C17orf99 IL40 UNQ464/P RO809 
                 P23510 
                 TNFL4_HUMAN 
                 TNFSF4 TXGP1 
               
               
                 Q9NZH6 
                 IL37_HUMAN 
                 IL37 FIL1Z IL1F7 IL1H4 IL1RP1 
                 P15018 
                 LIF_HUMAN 
                 LIF HILDA 
                 Q6UX27 
                 VSTM1_HUMAN 
                 VSTM1 UNQ3033/ PRO9835 
               
               
                 P55773 
                 CCL23_HUMAN 
                 CCL23 MIP3 MPIF1 SCYA23 
                 P01571 
                 IFN17_HUMAN 
                 IFNA17 
                 Q9UBD3 
                 XCL2_HUMAN 
                 XCL2 SCYC2 
               
               
                 P01570 
                 IFN14_HUMAN 
                 IFNA14 
                 P05000 
                 IFNW1_HUMAN 
                 IFNW1 
                 P47992 
                 XCL1_HUMAN 
                 XCL1 LTN SCYC1 
               
               
                 P01563 
                 IFNA2_HUMAN 
                 IFNA2 IFNA2A IFNA2B IFNA2C 
                 P35225 
                 IL13_HUMAN 
                 IL13 NC30 
                 Q12904 
                 AIMP1_HUMAN 
                 AIMP 1 EMAP2 SCYE1 
               
               
                 P22301 
                 IL10_HUMAN 
                 IL10 
                 P13725 
                 ONCM_HUMAN 
                 OSM 
                 P09603 
                 CSF1_HUMAN 
                 CSF1 
               
               
                 P18075 
                 BMP7_HUMAN 
                 BMP7 OP1 
                 P10451 
                 OSTP_HUMAN 
                 SPP1 BNSP OPN PSEC0156 
                   
               
               
                 P55774 
                 CCL18_HUMAN 
                 CCL18 AMAC1 DCCK1 MIP4 PARC SCYA18 
                 P10720 
                 PF4V_HUMAN 
                 PF4V1 CXCL4V1 SCYB4V1 
               
            
           
         
       
     
     Cytokine storms have the potential to cause significant damage to body tissues and organs. For example, occurrence of cytokine storms in the lungs can cause an accumulation of fluids and immune cells, for example macrophages, in the lungs, and eventually block the body’s airways thereby resulting in respiratory distress and even death. 
     It is important to be able to prevent, control, or mitigate the occurrence of the cytokine storm. There are existing or conventional techniques associated with preventing, controlling, or mitigating the occurrence of the cytokine storm (and unwanted inflammation in general). For example, it has been reported that TNF inhibitors may be useful for facilitating the control of cytokine storms and for reducing adverse reactions caused by the occurrence of cytokine storms within the body. In addition, research has suggested that angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs), may have clinical utility for controlling or down-regulating cytokine storms, and for reducing inflammation, within the body. Corticosteriods and non-steroidal anti-inflammatory drugs (NSAIDS) have also been employed in an attempt to treat patients experiencing cytokine storms. In addition, suggested therapeutic agents for treating influenza-type viral infections include antibodies to the influenza virus neuraminidase. 
     However, the effectiveness and safety of many conventional techniques associated with the prevention, control, or mitigation of cytokine storms within the body have not been comprehensively or adequately verified. In addition, many conventional anti-influenza treatments (e.g. anti-viral or anti-influenza drugs) have associated undesirable side effects when consumed by a patient. Such undesirable side effects include nausea, vomiting, and toxicity. Furthermore, there is an increasing problem of developed resistance to many conventional anti-viral (e.g. anti-influenza) drugs. Accordingly, new or enhanced approaches for at least one of preventing, controlling, or mitigating cytokine storms may be useful for improving public health. Furthermore, new compositions or techniques providing anti-influenza or anti-inflammatory properties may also be useful for improving public health. 
     In some embodiments of the invention, multiple UBI treatments are administered. For example, UBI treatments can be administered every day, every other day, two times a week, three times a week, four times a week, five times a week, six times a week, about once every ten days, about once every two weeks, about once every three weeks, about once every four weeks, or at other intervals. 
     Other types of radiation can also be used in the present invention, for example γ radiation. There are many types of radiation. Of particular use for the invention is molecularly damaging radiation. Molecularly damaging radiation can be ionizing radiation or lower energy radiation that is not ionizing but does induce other types of molecular damage. For example, non-ionizing radiation can cause the formation of free radicals that can damage biological molecules. Non-ionizing radiation can also induce the formation of pyrimidine dimers in nucleic acid molecules, and radiation can also heat biological molecules. Near ultraviolet radiation and radiation in the visible spectrum can cause molecular damage, including free radical and pyrimidine dimer formation, and longer wavelength radiation, for example microwave radiation can heat molecules. 
     Radiation can be particle radiation or electromagnetic radiation. Types of particle radiation include alpha particles, beta particles, protons, helium ions, HZE ions, certain electrons, photons, neutrons, neutrinos, mesons, muons, and others. Electromagnetic radiation consists of electromagnetic waves (or the wave quanta, photons), which can have varied but interrelated wavelengths, frequencies, and energies. Frequency is inversely proportional to wavelength, according to the equation: 
     
       
         
           
             v 
             = 
             f 
             λ 
           
         
       
     
      where v is the speed of the wave (c, the speed of light in a vacuum, when in a vacuum or less than c in other media), f is the frequency and λ is the wavelength. A photon has an energy, E, proportional to its frequency, f, by 
     
       
         
           
             E 
             = 
             h 
             f 
             = 
             h 
             c 
             / 
             λ 
           
         
       
     
      where h is Planck’s constant, λ is the wavelength and c is the speed of light in a vacuum. Higher energies tend to be more damaging to molecules than lower energies. 
     High energy radiation has low wavelengths. UV radiation is a type of ionizing radiation, with properties depicted in Table 2, that has lower wavelength and higher energy than radiation in the form of visible light. Ionizing radiation in the form of UV radiation is particularly appropriate for certain embodiments of the invention. γradiation has lower wavelength and higher energy than UV radiation and is a particularly appropriate form of radiation for certain embodiments of the invention. X-ray radiation is another form of low wavelength, high energy electromagnetic radiation that is historically distinguished from γradiation, also electromagnetic radiation. X-rays can be distinguished from γradiation by their source or their wavelengths, frequencies, and energies. X-rays are emitted by electrons outside of the nucleus, while γrays are emitted by the nucleus. However, X-ray radiation and γradiation have overlapping wavelengths, frequencies, and energies and are both appropriate radiation for certain embodiments of the invention. Most X-rays have wavelengths of 10 picometers (pm) to 10 nanometers (nm), and γ rays can be described as radiation with wavelengths less than about 10 pm. Radio, microwave, infrared, and optical radiation are also appropriate for certain embodiments of the invention. The properties of certain types of radiation are depicted in Table 4.  
     
       
         
          TABLE 4
           
               
               
               
               
             
               
                 Wavelengths, frequencies, and energies of types of radiation 
               
               
                   
                 Wavelength (m) 
                 Frequency (Hz) 
                 Energy (J) 
               
             
            
               
                 Radio 
                 &gt; 1 × 10 -1 
 
                 &lt;3 × 10 9 
 
                 &lt; 2 × 10 -24 
 
               
               
                 Microwave 
                 1 × 10 -3  - 1 × 10 -1 
 
                 3 × 10 9  - 3 × 10 11 
 
                 2 × 10 -24 - 2 × 10 -22 
 
               
               
                 Infrared 
                 7 × 10 -7  - 1 × 10 -3 
 
                 3 × 10 11 -4 × 10 14 
 
                 2 × 10 -22  - 3 × 10 -19 
 
               
               
                 Optical 
                 4 × 10 -7  - 7 × 10 -7 
 
                 4 × 10 14  - 7.5 × 10 14 
 
                 3 × 10 -19  - 5 × 10 -19 
 
               
               
                 UV 
                 1 × 10 -8  -4 × 10 -7 
 
                 7.5 × 10 14  - 3 × 10 16 
 
                 5 × 10 -19  - 2 × 10 -17 
 
               
               
                 X-ray 
                 1 × 10 -11  - 1 × 10 -8 
 
                 3 × 10 16  - 3 × 10 19 
 
                 2 × 10 -17  - 2 × 10 -14 
 
               
               
                 Gamma-ray 
                 &lt; 1 × 10 -11 
 
                 &gt;3 × 10 19 
 
                 &gt;2 × 10 -14 
 
               
            
           
         
       
     
     The foregoing methods can be administered in combination with suitable drugs as combination therapies. In each case, the method of treatment of the invention can be administered prior to, at the same time as, or after the administration of a drug for treatment of the condition. In accordance with the methods of the present invention, more than one compound or composition may be co-administered with one or more other compounds, such as known anti-viral compounds or molecules as well as antibiotics, chloroquine, hydroxychloroquine, known drugs for treating pneumonia, an analgesic (such as lidocaine or paracetoamol), an anti-inflammatory (such as bethamethasone, non-steroid anti-inflammatory drugs (NSAIDs), acetaminophen, ibuprofen, naproxen), and/or other suitable drugs. 
     The foregoing methods can also be administered with further treatment of the portion of blood removed from the patient. For example, the portion of blood can be contacted with a compound selected from riboflavin, psoralens, amotosalen HCl, porphyrins, photosensitizers, chlorophyll derivatives, light-sensitive agents, UV-activated nucleic acid replication inhibitors, dyes (such as such as neutral red, methylene blue, acridine, toluidines, flavine (acriflavine hydrochloride) and phenothiazine derivatives), coumarins, quinolones, quinones, and anthroquinones. The compound and portion of blood can then be irradiated with UV to inactivate pathogens. Other treatments of the portion of blood are also possible. 
     The foregoing methods can be used to inactivate white blood cells in the portion of blood removed from the patient and/or in the total blood of the patient. Without intending to be bound by theory, exposing blood to UV radiation can have multiple effects. The effects can be killing, weakening, and/or inactivating pathogens, downregulation of the immune system, inactivating, attenuating, and/or downregulating white blood cell activity. 
     The foregoing methods can be used wherein the patient’s own blood is irradiated and placed back into the patient (autologous) or wherein a donor, who is not the patient, is the source of a portion of blood that is placed into the patient (allogeneic). 
     EXAMPLES 
     Example 1 
     A patient with a respiratory viral infection, for example a patient with SARS-CoV-2, is treated with ultraviolet blood irradiation (UBI). The UBI is administered by a variation of the Knott Hemo-irradiator that is compliant with modern safety standards. 
     First, a portion of blood is removed from the patient. The amount of blood removed is based on the patient’s body weight or blood volume. For example, 3.3 milliliters of blood per kilogram of body weight is removed from the patient. The blood is mixed with heparin to prevent clotting, though under certain circumstances, a person of skill in the art might conclude that the heparin is not necessary or should not be used. For example, a patient with recent hemorrhage might not need heparin due to a risk of bleeding. 
     The blood is then exposed to ultraviolet light using the irradiator. The irradiator exposes the blood to ultraviolet light with wavelengths between 200 and 400 nanometers. The blood flows through the chamber of the irradiator at a flow rate of 30 milliliter per minute, thereby exposing the blood to the desired amount of ultraviolet radiation. The irradiated blood is then placed back into the patient at the fastest safe infusion rate. 
     The irradiated blood causes a reduction of the viral load in the patient and/or a reduction in the risk and/or severity of cytokine storm syndrome. 
     Additional rounds of UBI treatment are conducted under appropriate circumstances. 
     Example 2 
     A patient with a respiratory viral infection, for example a patient with SARS-CoV-2, is treated with ultraviolet blood irradiation (UBI). A portion of blood is removed from the patient and treated with molecularly damaging radiation, such as UV radiation or γradiation. The radiation damages the virus in the portion of blood, causing the exposure of viral antigens. The damage can expose many different types of antigens, including antigens derived from viral proteins, RNA, DNA, modifications to viral components (e.g. posttranslational modifications of viral proteins, posttranscriptional modifications to RNA, and/or others), and other types of antigens. The patient’s immune system recognizes the viral antigens created by the radiation and stimulates an immune response against the virus, causing the patient’s immune system to attack the virus. This is a vaccine-like effect that protects the patient from disease. 
     Example 3 
     A pandemic caused by SARS-CoV-2 has led to an illness termed COVID-19 with significant ongoing morbidity and increasing fatalities (174,336) with a preliminary mortality rate of about 6.9% (Apr. 21, 2020/ https://coronavirus.jhu.edu/map.html). COVID-19 presents with a spectrum of disease from mild and self-limited to severe progressive pneumonia, multiorgan failure, and death. One likely culprit of the high mortality is cytokine storm syndrome (CSS) but no effective therapies exist. In the late 1940s and 1950s ultraviolet blood irradiation (UBI) was safely used to treat over 60,000 patients including those with bacterial and viral infections. With the advent of penicillin in the 1940s and polio vaccine in the 1950s UBI may have been replaced by these and additional antibiotics in subsequent years. This study tests the safety and efficacy of the Mirasol® device (currently used in blood transfusion safety to reduce pathogens in donated blood) to treat hospitalized patients with COVID-19. Using UV light with riboflavin added to whole blood inactivates bacterial, viral and parasitic pathogens, including SARS-CoV-2, also inactivating white blood cells that propagate CSS. 
     Goals: In hospitalized patients with Covid-19 approximately 450 cc of whole blood will be treated with riboflavin and UV light (Mirasol® device) then retransfusing in an autologous manner, UV blood irradiation (UBI) will cause decreasing cytokine storm, improving illness severity, improve hypoxemia and development of SARS-CoV-2 antibody titers. By acutely inactivating leukocytes, destroying a small proportion of pathogen and shifting the O 2  dissociation curve to the left, improvements over 1, 3 and 7 days in levels of serum biomarkers of CSS, clinical illness severity scores, the PaO 2 /FiO 2  ratio will occur and generate antibody titers to SARS-CoV-2 at 14 days. 
     Implications: UBI with riboflavin for the treatment of viral-associated cytokine storm, along with an improvement in clinical illness severity will be a novel therapeutic approach to combat the harmful effects of SARS-CoV-2 infection and also other infectious and non-infectious illnesses resulting from overwhelming inflammatory responses leading to shock and/or acute respiratory distress syndrome (ARDS) with cytokine storm syndrome (CSS). 
     Inclusion Criteria:
     Provision of signed and dated informed consent form consistent with ICH-GCP   Informed consent can be provided by patient or legally authorized representative   Male or female hospitalized patients age &gt;_ 18 years   Hospitalized for confirmed active Covid-19 infection by PCR or IgM to SARS-CoV-2 in preceding 72 hours; OR PCR positive sample ≥72 hours previous but progressive disease suggestive of ongoing SARS-CoV-2 infection   Lung involvement confirmed by chest imaging   ≤14 days since illness onset   Willingness to participate in trial arm they select 1. UBI intervention, blood draws, symptom reporting, 14 d antibodies and 30 day follow up phone call or visit if inpatient status, 2. No UBI intervention, blood draws, symptom reporting, 14 d antibodies and 30 day follow up phone call or visit if inpatient status.   

     Exclusion Criteria:
     Physician makes decision that trial involvement is not in patient’s best interest or any condition that prevents following the trial protocol safely   Inability to have or successful placement of 16 gauge iv placed for blood collection if no central or midline catheter access present   Allergy to riboflavin   Life expectancy &lt; 48 hours   History of pulseless electrical activity in previous 48 hours.   Pregnancy/breast feeding   100% FiO2 requirement when proned   Use of 2 vasopressors at maximum dosage or 3 total vasopressors   Hemoglobin &lt; 10.0 mg/dL   Hyperkalemia with serum potassium currently &gt; 5.0 mEq/L   Active bleeding in previous 48 hours   System fibrinolytic use in previous 48 hours   Requirement for renal replacement therapy initiated and ongoing during current hospitalization (i.e. hemodialysis, CVVH, SLED)   Major injury or surgery needed (e.g. bowel perforation, diverticulitis) at Investigator’s judgment   History of saddle or submassive pulmonary embolus in previous 7 days   History of intracranial hemorrhage or stroke in preceding 7 days or unresolved intracranial hemorrhage   History of advanced hepatic liver disease (Child Pugh C), variceal bleeding, spontaneous bacterial peritonitis, or hepatic encephalopathy   AST, ALT &gt; 5 × upper limit of normal at time of consent   Current history of non-resected metastatic solid tumor on chemotherapy   Anticipated need for sulfa antibiotic, dapsone or sulfasalazine in the 5 days following UBI intervention   History of porphyria   Severe pulmonary hypertension requiring intravenous vasoactive medication   Patients not able to understand or follow trial procedures including completion of self-administered questionnaires   
   Anticipated transfer or discharge from hospital in next 72 hours.   

     Outcomes:
     Primary-Safety 
   1. The cumulative incidence of severe adverse events   
   Secondary-Efficacy metrics
   1. Time to clinical recovery.   2. Time to improve by 2 points on clinical severity ordinal 7-point scale.   3. Changes in clinical illness severity scores (i.e., SOFA, APACHE II, SIC, NEWS2)   4. Changes in serum biomarkers of inflammation and cytokine storm (i.e. ferritin, hs-CRP, IL-6, LDH, D-dimer)   5. Changes in oxygenation measured by PaO2/FiO2 ratio   6. Using a modified flu-iiQ™ validated patient-reported outcomes measure (PROM) to assess clinical improvement.   
   

     Study Protocol Timeline:
     Stage 1: n=10 
   For safety monitoring no more than 1 enrolled per day between 0800-1700 M-F across illness severity spectrum (floor, IMC, ICU).   
   Stage 2: n= 15 
   If no significant adverse safety signals from Phase 1 and Safety Monitoring Committee agrees, proceed with same protocol enrolled between hours of 0800-1700 M-F   
   Stage 3: n=75 
   If no significant adverse safety signals from Phase 2, Safety Monitoring Committee agrees and blood bank/phlebotomy comfortable with the study and Mirasol® device use 7 days/week.   
   

     Results: In the current pandemic of Covid-19 triggering CSS and hypoxemia, after treatment with UBI and riboflavin using the MIRASOL® device and ~ 450 cc of a Covid-19 patient’s blood then autologously retransfusing the blood into the same patient, the following results will occur:
     1. Use of the Mirasol® device and riboflavin with autologous transfusion of this treated whole blood is safe in hospitalized patients with Covid-19.   2. The time to clinical recovery will improve.   3. Time to improve by 2 points on clinical severity ordinal 7-point scale will improve.   4. The clinical illness severity will decrease in the ensuing 1-30 days measured by clinical illness severity scores (i.e. SOFA, APACHE II, SIC, NEWS2).   5. Via leukocyte inactivation it will decrease the CSS as demonstrated by a reduction in serum biomarkers of CSS at days 1, 3 and 7 following treatment.   6. Via shift of the hemoglobin O2 dissociation curve to the left will lead to an acute improvement in hypoxemia quantified by the PaO2/FiO2 ratio at designated time intervals.   7. Via viral disruption and reintroduction of the inactivated pathogen components it will improve the antibody formation response quantified by antibody titers to SARS-CoV-2 at 14 days.   

     Variations, modifications, and other implementations of what is described herein will occur to those of ordinary skill without departing from the spirit and the scope of the invention. Accordingly, the invention is not to be limited only to the preceding illustrative description. Each of the embodiments of the invention may be combined individually or in combination with one or more other embodiments of the invention. 
     Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, numerous equivalents to the compounds, compositions, and methods of use thereof described herein. Such equivalents are considered to be within the scope of the invention. 
     The contents of all references, patents and published patent applications cited throughout this Application, as well as their associated figures are hereby incorporated by reference in their entirety.