Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia
Bibliographic record
Abstract
X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4-dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8-207.8, P < 0.001). The patients' susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".