Genetic, immunological, and clinical description of pediatric patients with recessive inborn errors of type I IFN immunity and COVID-19 pneumonia
| Patient . | Gene . | Gender . | Age (yr) . | Ethnicity/residence . | COVID-19 pneumonia severity . | Systemic inflammation . | Other viral infections . | Other infections and clinical history . | Outcome . | Publication . | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P1 | STAT2 | AR | S613F/Q685X (LOF/LOF) | M | 12 | Middle East/Turkey | Critical | Yes | Aseptic meningitis and Kawasaki disease after MMR vaccination at the age of 1 yr; recurrent severe influenza pneumonia requiring hospitalization since the age of 2 yr | Survived | This report | |
| P2 | TYK2 | AR | P216fs/P216fs (LOF) | F | 2 | Middle East/Turkey | Moderate | Hospitalized for infection of VZV vaccine at the age of 2 yr | Hospitalized for sepsis during the neonatal period; Admitted to ICU twice for fever and dyspnea before 5 mo old, diagnosed with Kawasaki disease at the age of 11 mo | Survived | This report | |
| P3 | TYK2 | AR | P216fs/P216fs (LOF) | M | 4 | Middle East/Turkey | Critical | Admitted to ICU for influenza pneumonia at 3 yr; no adverse reaction to MMR vaccination | Hospitalized for sepsis during the neonatal period | Survived | This report | |
| P4 | TYK2 | AR | P216fs/P216fs (LOF) | M | 9 | Middle East/Turkey | Critical | No adverse reaction to MMR vaccination | Recurrent bronchitis requiring hospital admission and inhaler therapy | Survived | This report | |
| P5 | TLR7 | XR | I174R/Y (LOF) | M | 12 | Europe/Belgium | Severe | No adverse reaction to MMR vaccination | Survived | This report | ||
| P6 | TLR7 | XR | N75H/Y (LOF) | M | 7 | Middle East/Turkey | Severe | No adverse reaction to MMR vaccination | Survived | Asano et al. (2021) | ||
| P7 | TLR7 | XR | N75H/Y (LOF) | M | 12 | Middle East/Turkey | Severe | No adverse reaction to MMR vaccination | Survived | Asano et al. (2021) | ||
| P8 | TLR7 | XR | D244Y/Y (LOF) | M | 13 | Middle East/Turkey | Critical | No adverse reaction to MMR vaccination | Survived | Asano, et al. (2021) | ||
| P9 | TLR7 | XR | D244Y/Y (LOF) | M | 5 | Middle East/Turkey | Moderate | No adverse reaction to MMR vaccination | Survived | Asano et al. (2021) | ||
| P10 | TLR7 | XR | H781L/Y (LOF) | M | 13 | Middle East/France | Critical | No adverse reaction to MMR vaccination | Survived | Asano et al. (2021) | ||
| P11a | TLR7 | XR | L372M/Y (LOF) | M | 7 | Middle East/Iran | Critical | No adverse reaction to MMR vaccination | Recurrent fever, upper respiratory tract infections and otitis media, pneumonia, since the age of 1 yr; diagnosed with failure to thrive, splenomegaly, anemia, and thrombocytopenia, osteomyelitis of the hip, since the age of 4 yr; diagnosed with hyper IgM syndrome since the age of 5 yr, and received IVIG since then | Survived | Asano et al. (2021); Abolhassani et al. (2021) | |
| P12 | IFNAR1 | AR | H263fs/H263fs (LOF) | F | 3 | Middle East/Iran | Critical | Yes | No adverse reaction to MMR vaccination | Chronic severe chronic sinusitis and oral thrush since the age of 8 mo; severe mucormycosis of the nose and paranasal sinuses since the age of 2 yr | Deceased | Abolhassani et al. (2022) |
| C1 | TLR7 | XR | H782D/Y (Neutral) | M | 53 | Europe/Brazil | Asymptomatic | |||||
| C2 | IFIH1 | AR | Q415K/Q415K (Neutral) | F | 50 | North Africa/France | Asymptomatic | |||||
| C3 | IRF7 | AR | L128M/L128M (Neutral) | M | 44 | Southeast Asia/Singapore | Asymptomatic | |||||
| Patient . | Gene . | Gender . | Age (yr) . | Ethnicity/residence . | COVID-19 pneumonia severity . | Systemic inflammation . | Other viral infections . | Other infections and clinical history . | Outcome . | Publication . | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P1 | STAT2 | AR | S613F/Q685X (LOF/LOF) | M | 12 | Middle East/Turkey | Critical | Yes | Aseptic meningitis and Kawasaki disease after MMR vaccination at the age of 1 yr; recurrent severe influenza pneumonia requiring hospitalization since the age of 2 yr | Survived | This report | |
| P2 | TYK2 | AR | P216fs/P216fs (LOF) | F | 2 | Middle East/Turkey | Moderate | Hospitalized for infection of VZV vaccine at the age of 2 yr | Hospitalized for sepsis during the neonatal period; Admitted to ICU twice for fever and dyspnea before 5 mo old, diagnosed with Kawasaki disease at the age of 11 mo | Survived | This report | |
| P3 | TYK2 | AR | P216fs/P216fs (LOF) | M | 4 | Middle East/Turkey | Critical | Admitted to ICU for influenza pneumonia at 3 yr; no adverse reaction to MMR vaccination | Hospitalized for sepsis during the neonatal period | Survived | This report | |
| P4 | TYK2 | AR | P216fs/P216fs (LOF) | M | 9 | Middle East/Turkey | Critical | No adverse reaction to MMR vaccination | Recurrent bronchitis requiring hospital admission and inhaler therapy | Survived | This report | |
| P5 | TLR7 | XR | I174R/Y (LOF) | M | 12 | Europe/Belgium | Severe | No adverse reaction to MMR vaccination | Survived | This report | ||
| P6 | TLR7 | XR | N75H/Y (LOF) | M | 7 | Middle East/Turkey | Severe | No adverse reaction to MMR vaccination | Survived | Asano et al. (2021) | ||
| P7 | TLR7 | XR | N75H/Y (LOF) | M | 12 | Middle East/Turkey | Severe | No adverse reaction to MMR vaccination | Survived | Asano et al. (2021) | ||
| P8 | TLR7 | XR | D244Y/Y (LOF) | M | 13 | Middle East/Turkey | Critical | No adverse reaction to MMR vaccination | Survived | Asano, et al. (2021) | ||
| P9 | TLR7 | XR | D244Y/Y (LOF) | M | 5 | Middle East/Turkey | Moderate | No adverse reaction to MMR vaccination | Survived | Asano et al. (2021) | ||
| P10 | TLR7 | XR | H781L/Y (LOF) | M | 13 | Middle East/France | Critical | No adverse reaction to MMR vaccination | Survived | Asano et al. (2021) | ||
| P11a | TLR7 | XR | L372M/Y (LOF) | M | 7 | Middle East/Iran | Critical | No adverse reaction to MMR vaccination | Recurrent fever, upper respiratory tract infections and otitis media, pneumonia, since the age of 1 yr; diagnosed with failure to thrive, splenomegaly, anemia, and thrombocytopenia, osteomyelitis of the hip, since the age of 4 yr; diagnosed with hyper IgM syndrome since the age of 5 yr, and received IVIG since then | Survived | Asano et al. (2021); Abolhassani et al. (2021) | |
| P12 | IFNAR1 | AR | H263fs/H263fs (LOF) | F | 3 | Middle East/Iran | Critical | Yes | No adverse reaction to MMR vaccination | Chronic severe chronic sinusitis and oral thrush since the age of 8 mo; severe mucormycosis of the nose and paranasal sinuses since the age of 2 yr | Deceased | Abolhassani et al. (2022) |
| C1 | TLR7 | XR | H782D/Y (Neutral) | M | 53 | Europe/Brazil | Asymptomatic | |||||
| C2 | IFIH1 | AR | Q415K/Q415K (Neutral) | F | 50 | North Africa/France | Asymptomatic | |||||
| C3 | IRF7 | AR | L128M/L128M (Neutral) | M | 44 | Southeast Asia/Singapore | Asymptomatic | |||||
M, male; F, female.
Patient also carries a homozygous deleterious ATM mutation (Y2371X).