Which immunodeficiency syndromes or cell types are prone to viral infections in children?

Immunodeficiency Syndromes and Cell Types Prone to Viral Infections in Children

Children with T-cell immunodeficiencies are most vulnerable to severe viral infections, followed by those with combined T-cell and B-cell defects, while isolated B-cell deficiencies primarily increase susceptibility to specific viral pathogens like enteroviruses. 1

T-Cell Immunodeficiencies: Highest Risk Category

T-cell defects represent the most critical vulnerability to viral infections because cytotoxic T cells are essential for controlling viral replication and clearing infected cells. 2

Severe Combined Immunodeficiency (SCID)

• SCID patients face life-threatening risk from all viral pathogens, including vaccine-derived viruses, respiratory viruses, and herpesviruses. 1
• Respiratory viral infections, particularly paramyxoviruses (RSV, parainfluenza), cause severe pneumonitis with 59% mortality in SCID patients requiring bone marrow transplantation. 3
• All live viral vaccines are absolutely contraindicated in SCID patients until complete immune reconstitution is documented. 1
• Profound lymphopenia (<100 cells/mm³) predicts progression from upper to lower respiratory tract disease. 1

Complete DiGeorge Syndrome

• Similar risk profile to SCID due to absent T-cell function. 1
• All live viral and bacterial vaccines must be avoided prior to immune reconstitution. 1

DOCK-8 Deficiency

• Patients develop severe complications from live viral vaccines, including central nervous system vasculopathy from vaccine-strain varicella. 1

Combined T-Cell and B-Cell Deficiencies

Common Variable Immunodeficiency (CVID)

• Dual vulnerability: impaired antibody responses plus variable T-cell defects increase susceptibility to multiple viral pathogens. 1
• Chronic norovirus infection causes significant morbidity with prolonged viral shedding. 4
• Rare cases of CNS enteroviral infections occur, particularly with severe hypogammaglobulinemia. 1
• Herpesviruses may drive inflammatory complications in a subset of patients. 4

B-Cell (Antibody) Deficiencies

X-Linked Agammaglobulinemia (XLA)

• Specific predilection for enteroviral infections, including vaccine-derived poliovirus causing CNS disease. 1
• Chronic enteroviral meningoencephalitis represents a characteristic infectious syndrome. 5
• Prolonged excretion of vaccine-derived poliovirus poses transmission risk to others. 4
• Oral poliovirus vaccine is absolutely contraindicated; close contacts must receive inactivated polio vaccine only. 1

Selective IgA Deficiency and IgG Subclass Deficiencies

• Generally tolerate viral infections well; all vaccines including live viral vaccines are considered safe. 1

Phagocytic Cell Disorders

Chronic Granulomatous Disease (CGD)

• Primarily susceptible to bacterial and fungal infections, but severe viral infections can occur. 1
• One death from RSV infection documented among immunocompromised children. 1
• Live viral vaccines can be administered, but live bacterial vaccines (BCG) are contraindicated. 6

Complement Deficiencies

• Not significantly prone to viral infections; primarily increase susceptibility to neisserial (bacterial) infections. 5
• All vaccines, including live viral vaccines, can be safely administered. 7

Immunocompromised States (Secondary Immunodeficiency)

Children Receiving Chemotherapy

• Severe RSV disease occurs at all ages with higher mortality rates compared to immunocompetent children. 8
• Viral shedding is significantly prolonged, particularly with RSV. 8
• Giant-cell pneumonia from RSV documented in children with leukemia. 8
• Adenovirus can cause disseminated disease including pneumonia despite antiviral therapy. 3

Hematopoietic Stem Cell Transplant (HSCT) Recipients

• Lymphopenia (<100 cells/mm³) is the critical predictor of progression to severe lower respiratory tract disease. 1
• Four of five deaths from RSV infection in one series occurred in allogeneic HSCT recipients. 1
• No viral clearance occurs without successful T-cell engraftment, regardless of antiviral therapy. 3

Solid Organ Transplant Recipients

• RSV infection can progress to respiratory failure, though mortality appears lower than in HSCT recipients. 1

Critical Clinical Pearls

Respiratory Syncytial Virus (RSV)

• Nasopharyngeal aspirate is the ideal specimen for diagnosis and monitoring; virus appears in bronchoalveolar lavage only with lower respiratory tract infection. 3
• Paramyxoviruses (RSV, parainfluenza) cause the most severe viral pneumonitis, worsening post-BMT. 3

Rhinovirus

• Generally causes only coryza in immunodeficient children (82% asymptomatic or mild). 3
• Severe disease occurs only when additional lung pathology is present. 3

Adenovirus

• Can cause disseminated disease in severely immunocompromised children despite antiviral therapy. 3

Hospital-Acquired Infections

• Over 50% of immunocompromised children acquire RSV nosocomially; strict infection control is essential. 8

Common Pitfalls to Avoid

• Do not assume all immunodeficiencies carry equal viral infection risk: T-cell defects are most critical, while complement deficiencies pose minimal viral susceptibility. 1, 5
• Do not overlook lymphocyte counts: absolute lymphocyte count <100 cells/mm³ predicts severe progression of respiratory viral infections. 1
• Do not delay immune evaluation in children with severe or unusual viral infections: undiagnosed immunodeficiency may be present. 2
• Do not give live vaccines to household contacts of SCID patients: only oral poliovirus must be avoided; all other live vaccines create protective herd immunity. 1