More than 40% of the deaths recorded in the first wave of the SARS-CoV-2 pandemic were linked to nursing homes. Not only are the residents of long-term care facilities (LTCFs) typically older and more susceptible to endemic infections, the facilities' high degree of connection to wider communities makes them especially vulnerable to local COVID-19 outbreaks. In 2008, in the wake of the SARS-CoV-1 and MERS epidemics and anticipating an influenza pandemic, we created a stochastic compartmental model to evaluate the deployment of non-pharmaceutical interventions (NPIs) in LTCFs during influenza epidemics. In that model, the most effective NPI by far was a staff schedule consisting of 5-day duty periods with onsite residence, followed by an 4-to-5 day off-duty period with a 3-day quarantine period just prior to the return to work. Unlike influenza, COVID-19 appears to have significant rates of pre-symptomatic transmission. In this study, we modified our prior modeling framework to include new parameters and a set of NPIs to identify and control the degree of pre-symptomatic transmission. We found that infections, deaths, hospitalizations, and ICU utilization were projected to be high and largely irreducible, even with rigorous application of all defined NPIs, unless pre-symptomatic carriers can be identified and isolated at high rates. We found that increasingly rigorous application of NPIs is likely to significantly decrease the peak of infections; but even with complete isolation of symptomatic persons, and a 50% reduction in silent transmission, the attack rate is projected to be nearly 95%.

Before the first zygotic division, the nuclear envelopes of the maternal and paternal pronuclei disassemble, allowing both sets of chromosomes to be incorporated into a single nucleus in daughter cells after mitosis. We found that in Caenorhabditis elegans, partial inactivation of the polo-like kinase PLK-1 causes the formation of two nuclei, containing either the maternal or paternal chromosomes, in each daughter cell. These two nuclei gave rise to paired nuclei in all subsequent cell divisions. The paired-nuclei phenotype was caused by a defect in forming a gap in the nuclear envelopes at the interface between the two pronuclei during the first mitotic division. This was accompanied by defects in chromosome congression and alignment of the maternal and paternal metaphase plates relative to each other. Perturbing chromosome congression by other means also resulted in failure to disassemble the nuclear envelope between the two pronuclei. Our data further show that PLK-1 is needed for nuclear envelope breakdown during early embryogenesis. We propose that during the first zygotic division, PLK-1-dependent chromosome congression and metaphase plate alignment are necessary for the disassembly of the nuclear envelope between the two pronuclei, ultimately allowing intermingling of the maternal and paternal chromosomes.