- Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. Authors found enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, authors experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. Human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.
- Rethinking Covid-19 Test Sensitivity — A Strategy for Containment
The Food and Drug Administration (FDA) and the scientific community are currently almost exclusively focused on test sensitivity, a measure of how well an individual assay can detect viral protein or RNA molecules. For an effective Covid filter that will stop this pandemic, we need tests that can enable regimens that will capture most infections while they are still infectious. These tests exist today in the form of rapid lateral-flow antigen tests, and rapid lateral-flow tests based on CRISPR gene-editing technology are on the horizon. Such tests are cheap (<$5), can be produced in the tens of millions or more per week, and could be performed at home, opening the door to effective Covid filter regimens. Lateral-flow antigen tests do not have an amplification step, so their analytic limits of detection are 100 or 1000 times higher than that of the benchmark test, but that is largely inconsequential if the goal is to identify people who are currently transmitting virus. SARS-CoV-2 is a virus that grows quickly inside the body, so by the time a benchmark PCR test becomes positive, the virus is well into exponential growth. At that point, it is probably hours, not days, before the virus grows by orders of magnitude, reaching the detection thresholds of currently available cheap and rapid point-of-care tests. It is after this point, when people would have positive results on both tests, that they would be expected to become infectious
- Adolescent with COVID-19 as the Source of an Outbreak at a 3-Week Family Gathering — Four States, June–July 2020
There is increasing evidence that children and adolescents can efficiently transmit SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1–3). During July–August 2020, four state health departments and CDC investigated a COVID-19 outbreak that occurred during a 3-week family gathering of five households in which an adolescent aged 13 years was the index and suspected primary patient; 11 subsequent cases occurred.