The COVID-19 pandemic has created a public health crisis. Because SARS-CoV-2 can spread from individuals with presymptomatic, symptomatic, and asymptomatic infections, the reopening of societies and the control of virus spread will be facilitated by robust population screening, for which virus testing will often be central. After infection, individuals undergo a period of incubation during which viral titers are too low to detect, followed by exponential viral growth, leading to peak viral load and infectiousness and ending with declining titers and clearance. Given the pattern of viral load kinetics, we model the effectiveness of repeated population screening considering test sensitivities, frequency, and sample-to-answer reporting time. These results demonstrate that effective screening depends largely on frequency of testing and speed of reporting and is only marginally improved by high test sensitivity. We therefore conclude that screening should prioritize accessibility, frequency, and sample-to-answer time; analytical limits of detection should be secondary.

The COVID-19 pandemic has created a public health crisis. Because SARS-CoV-2 can spread from individuals with pre-symptomatic, symptomatic, and asymptomatic infections, the re-opening of societies and the control of virus spread will be facilitated by robust surveillance, for which virus testing will often be central. After infection, individuals undergo a period of incubation during which viral titers are usually too low to detect, followed by an exponential growth of virus, leading to a peak viral load and infectiousness, and ending with declining viral levels and clearance. Given the pattern of viral load kinetics, we model surveillance effectiveness considering test sensitivities, frequency, and sample-to-answer reporting time. These results demonstrate that effective surveillance, including time to first detection and outbreak control, depends largely on frequency of testing and the speed of reporting, and is only marginally improved by high test sensitivity. We therefore conclude that surveillance should prioritize accessibility, frequency, and sample-to-answer time; analytical limits of detection should be secondary.

SummaryA dominant histopathological feature in neuromuscular diseases including amyotrophic lateral sclerosis and inclusion body myopathy is cytoplasmic aggregation of the RNA-binding protein TDP-43. Although rare protein-misfolding mutations in TDP-43 often cause protein aggregation, most patients do not have a TDP-43 mutation suggesting aggregates of wild-type TDP-43 arise by an unknown mechanism. Here we show TDP-43 is an essential protein for normal skeletal muscle formation that unexpectedly forms cytoplasmic, amyloid-like oligomeric assemblies, termed myo-granules, during skeletal muscle regeneration in mice and humans. Myo-granules bind mRNAs encoding sarcomeric proteins and are cleared as myofibers mature. Although myo-granules occur during normal skeletal muscle regeneration, myo-granules can seed TDP-43 amyloid fibrils in vitro, and are increased in a mouse model of inclusion body myopathy. Therefore, heightened assembly or decreased clearance of functionally normal myo-granules could be the source of cytoplasmic TDP-43 aggregates common to neuromuscular disease.