| Population name | van der Made |
| Genome | GRCh37 |
| Consortium | Radboud University Medical Center,Nijmegen, Netherlands |
| Super population | EUR, AFR |
| Population description | 2 pairs of brothers with no previous chronic disease presented in hospital with COVID-19 associated respiratory insufficiency. Pair 1 -Caucasian ancestry, required ICU and mechanical ventilation with one death. Pair 2- African ancestry requiring ICU and mechanical ventilation. |
| Population origin | North Western Europe |
| Case population size | 4 |
| Control population size | 0 |
| Comorbidities | none |
| Mean / median age | 26 years median age |
| Sex | Male |
| Severity | Critical |
| Sample source | Nasopharyngeal swab |
| Method | Rapid whole-exome sequencing was performed. DNA samples were processed using the Human Core Exome Kit and extended RefSeq targets (Twist Biosciences). Librarieswere prepared according to the manufacturers’ protocols. All DNAsampleswere sheared using a Covaris R230 ultrasonicator (Covaris), subsequently followed by 2 × 150– base pair paired-end sequencing on a Novaseq 6000 instrument (Illumina). |
| Bioinformatics | Downstream processing was performed using an automated data analysis pipeline that included Burrows- Wheeler Aligner mapping, Genome Analysis Toolkit variant calling, and custom-made annotation. Exome analysis of the affected brothers families was also performed to check segregation of all rare filtered variants in the respective index patients. |
| Imputation details | - |
| Limitations | The case series precludes drawing conclusions regarding causality between the rare loss-of-function TLR7 variants and the pathogenesis of severe COVID-19. The functional experiments with IFN-? measurements lacked statistical significance, possibly due to the limited number of replications and controls included in this study. |