Pumilio/FBF (PUF) proteins are a highly conserved family of translational regulators. The Drosophila PUF protein, Pumilio, is crucial for germline establishment and fertility. In mammals, primordial folliculogenesis is a key process that establishes the initial cohort of female mammalian germ cells prior to birth, and this primordial follicle pool is a prerequisite for female reproductive competence. We sought to understand whether PUF proteins have a conserved role in mammals during primordial folliculogenesis and female reproductive competency. In mammals, two homologs of Pumilio exist: Pumilio 1 (Pum1) and Pum2. Here, we report that PUMILIO (PUM) 1 plays an important role in the establishment of the primordial follicle pool, meiosis, and female reproductive competency, whereas PUM2 does not have a detectable function in these processes. Furthermore, we show that PUM1 facilitates the transition of the late meiotic prophase I oocyte from pachytene to diplotene stage by regulating SYCP1 protein. Our study reveals an important role of translational regulation in mammalian female germ cell development.

Background Structural racism has driven and continues to drive policies that create the social, economic, and community factors resulting in residential segregation, lack of access to adequate healthcare, and lack of employment opportunities that would allow economic mobility. This results in overall poorer population health for minoritized people. In 2020, Black and Hispanic/Latinx communities throughout the United States, including the state of Illinois, experienced disproportionately high rates of COVID-19 cases and deaths. Public health officials in Illinois implemented targeted programs at state and local levels to increase intervention access and reduce disparities. Methods To quantify how disparities in COVID outcomes evolved through the epidemic, data on SARS-CoV-2 diagnostic tests, COVID-19 cases, and COVID-19 deaths were obtained from the Illinois National Electronic Disease Surveillance System for the period from March 1 to December 31, 2020. Relative risks of COVID-19 cases and deaths were calculated for Black and Hispanic/Latinx vs. White residents, stratified by age group and epidemic interval. Deaths attributable to racial/ethnic disparities in incidence and case fatality were estimated with counterfactual simulations. Results Disparities in case and death rates became less drastic after May 2020, but did not disappear, and were more pronounced at younger ages. From March to May of 2020, the risk of a COVID-19 case for Black and Hispanic/Latinx populations was more than twice that of Whites across all age groups. The relative risk of COVID-19 death reached above 10 for Black and Hispanic/Latinx individuals under 50 years of age compared to age-matched Whites in the early epidemic. In all Illinois counties, relative risk of a COVID-19 case was the same or significantly increased for minoritized populations compared to the White population. 79.3 and 86.7% of disparities in deaths among Black and Hispanic/Latinx populations, respectively, were attributable to differences in age-adjusted incidence compared to White populations rather than differences in case fatality ratios. Conclusions Racial and ethnic disparities in the COVID-19 pandemic are products of society, not biology. Considering age and geography in addition to race/ethnicity can help to identify the structural factors driving poorer outcomes for certain groups. Studies and policies aimed at reducing inequalities in disease exposure may reduce disparities in mortality more than those focused on drivers of case fatality.

Background Availability of SARS-CoV-2 testing in the United States (U.S.) has fluctuated through the course of the COVID-19 pandemic, including in the U.S. state of Illinois. Despite substantial ramp-up in test volume, access to SARS-CoV-2 testing remains limited, heterogeneous, and insufficient to control spread. Methods We compared SARS-CoV-2 testing rates across geographic regions, over time, and by demographic characteristics (i.e., age and racial/ethnic groups) in Illinois during March through December 2020. We compared age-matched case fatality ratios and infection fatality ratios through time to estimate the fraction of SARS-CoV-2 infections that have been detected through diagnostic testing. Results By the end of 2020, initial geographic differences in testing rates had closed substantially. Case fatality ratios were higher in non-Hispanic Black and Hispanic/Latino populations in Illinois relative to non-Hispanic White populations, suggesting that tests were insufficient to accurately capture the true burden of COVID-19 disease in the minority populations during the initial epidemic wave. While testing disparities decreased during 2020, Hispanic/Latino populations consistently remained the least tested at 1.87 tests per 1000 population per day compared with 2.58 and 2.87 for non-Hispanic Black and non-Hispanic White populations, respectively, at the end of 2020. Despite a large expansion in testing since the beginning of the first wave of the epidemic, we estimated that over half (50–80%) of all SARS-CoV-2 infections were not detected by diagnostic testing and continued to evade surveillance. Conclusions Systematic methods for identifying relatively under-tested geographic regions and demographic groups may enable policymakers to regularly monitor and evaluate the shifting landscape of diagnostic testing, allowing officials to prioritize allocation of testing resources to reduce disparities in COVID-19 burden and eventually reduce SARS-CoV-2 transmission.

In managing COVID-19 with non-pharmaceutical interventions, occupancy of intensive care units (ICU) is often used as an indicator to inform when to intensify mitigation and thus reduce SARS-CoV-2 transmission, strain on ICUs, and deaths. However, ICU occupancy thresholds at which action should be taken are often selected arbitrarily. We propose a quantitative approach using mathematical modeling to identify ICU occupancy thresholds at which mitigation should be triggered to avoid exceeding the ICU capacity available for COVID-19 patients. We used a stochastic compartmental model to simulate SARS-CoV-2 transmission and disease progression, including critical cases that would require intensive care. We calibrated the model for the United States city of Chicago using daily COVID-19 ICU and hospital census data between March and August 2020. We projected ICU occupancies from September to May 2021 under two possible levels of transmission increase. The effect of combined mitigation measures was modeled as a decrease in the transmission rate that took effect when projected ICU occupancy reached a specified threshold. We found that mitigation did not immediately eliminate the risk of exceeding ICU capacity. Delaying action by 7 days increased the probability of exceeding ICU capacity by 10-60% and this increase could not be counteracted by stronger mitigation. Even under modest transmission increase, a threshold occupancy no higher than 60% was required when mitigation reduced the reproductive number Rt to just below 1. At higher transmission increase, a threshold of at most 40% was required with mitigation that reduced Rt below 0.75 within the first two weeks after mitigation. Our analysis demonstrates a quantitative approach for the selection of ICU occupancy thresholds that considers parameter uncertainty and compares relevant mitigation and transmission scenarios. An appropriate threshold will depend on the location, number of ICU beds available for COVID-19, available mitigation options, feasible mitigation strengths, and tolerated durations of intensified mitigation.

In non-pharmaceutical management of COVID-19, occupancy of intensive care units (ICU) is often used as an indicator to inform when to intensify mitigation and thus reduce SARS-CoV-2 transmission, strain on ICUs, and deaths. However, ICU occupancy thresholds at which action should be taken are often selected arbitrarily. We propose a quantitative approach using mathematical modeling to identify ICU occupancy thresholds at which mitigation should be triggered to avoid exceeding the ICU capacity available for COVID-19 patients and demonstrate this approach for the United States city of Chicago. We used a stochastic compartmental model to simulate SARS-CoV-2 transmission and disease progression, including critical cases that would require intensive care. We calibrated the model using daily COVID-19 ICU and hospital census data between March and August 2020. We projected various possible ICU occupancy trajectories from September 2020 to May 2021 with two possible levels of transmission increase and uncertainty in core model parameters. The effect of combined mitigation measures was modeled as a decrease in the transmission rate that took effect when projected ICU occupancy reached a specified threshold. We found that mitigation did not immediately eliminate the risk of exceeding ICU capacity. Delaying action by 7 days increased the probability of exceeding ICU capacity by 10–60% and this increase could not be counteracted by stronger mitigation. Even under modest transmission increase, a threshold occupancy no higher than 60% was required when mitigation reduced the reproductive number Rt to just below 1. At higher transmission increase, a threshold of at most 40% was required with mitigation that reduced Rt below 0.75 within the first two weeks after mitigation. Our analysis demonstrates a quantitative approach for the selection of ICU occupancy thresholds that considers parameter uncertainty and compares relevant mitigation and transmission scenarios. An appropriate threshold will depend on the location, number of ICU beds available for COVID-19, available mitigation options, feasible mitigation strengths, and tolerated durations of intensified mitigation.

BACKGROUND: Structural racism has driven and continues to drive policies that create the social, economic, and community factors resulting in residential segregation, lack of access to adequate healthcare, and lack of employment opportunities that would allow economic mobility. This results in overall poorer population health for minoritized people. In 2020, Black and Hispanic/Latinx communities throughout the United States, including the state of Illinois, experienced disproportionately high rates of COVID-19 cases and deaths. Public health officials in Illinois implemented targeted programs at state and local levels to increase intervention access and reduce disparities. METHODS: To quantify how disparities in COVID outcomes evolved through the epidemic, data on SARS-CoV-2 diagnostic tests, COVID-19 cases, and COVID-19 deaths were obtained from the Illinois National Electronic Disease Surveillance System for the period from March 1 to December 31, 2020. Relative risks of COVID-19 cases and deaths were calculated for Black and Hispanic/Latinx vs. White residents, stratified by age group and epidemic interval. Deaths attributable to racial/ethnic disparities in incidence and case fatality were estimated with counterfactual simulations. RESULTS: Disparities in case and death rates became less drastic after May 2020, but did not disappear, and were more pronounced at younger ages. From March to May of 2020, the risk of a COVID-19 case for Black and Hispanic/Latinx populations was more than twice that of Whites across all age groups. The relative risk of COVID-19 death reached above 10 for Black and Hispanic/Latinx individuals under 50 years of age compared to age-matched Whites in the early epidemic. In all Illinois counties, relative risk of a COVID-19 case was the same or significantly increased for minoritized populations compared to the White population. 79.3% and 86.7% of disparities in deaths among Black and Hispanic/Latinx populations, respectively, were attributable to differences in age-adjusted incidence compared to White populations rather than differences in case fatality ratios. CONCLUSIONS: Racial and ethnic disparities in the COVID-19 pandemic are products of society, not biology. Considering age and geography in addition to race/ethnicity can help to identify the structural factors driving poorer outcomes for certain groups. Studies and policies aimed at reducing inequalities in disease exposure will reduce disparities in mortality more than those focused on drivers of case fatality.

Public health indicators typically used for COVID-19 surveillance can be biased or lag changing community transmission patterns. The United States city of Chicago opportunistically investigated whether sentinel surveillance of recently symptomatic individuals receiving outpatient diagnostic testing for SARS-CoV-2 could accurately assess the instantaneous reproductive number R(t) and provide early warning of changes in transmission. Patients tested at community-based diagnostic testing sites between September 2020 and June 2021, and reporting symptom onset within four days preceding their test, formed the sentinel population. R(t) calculated from sentinel cases agreed well with R(t) from other indicators. Retrospectively, trends in sentinel cases did not precede trends in COVID-19 hospital admissions by any identifiable lead time. In deployment, sentinel surveillance held an operational recency advantage of nine days over hospital admissions. The promising performance of opportunistic sentinel surveillance suggests that deliberately designed outpatient sentinel surveillance would provide robust early warning of increasing transmission.

Background Availability of SARS-CoV-2 testing in the United States (U.S.) has fluctuated through the course of the COVID-19 pandemic, including in the U.S. state of Illinois. Despite substantial ramp-up in test volume, access to SARS-CoV-2 testing remains limited, heterogeneous, and insufficient to control spread. Methods We compared SARS-CoV-2 testing rates across geographic regions, over time, and by demographic characteristics (i.e., age and racial/ethnic groups) in Illinois during March through December 2020. We compared age-matched case fatality ratios and infection fatality ratios through time to estimate the fraction of SARS-CoV-2 infections that have been detected through diagnostic testing. Results By the end of 2020, initial geographic differences in testing rates had closed substantially. Case fatality ratios were higher in non-Hispanic Black and Hispanic/Latino populations in Illinois relative to non-Hispanic White populations, suggesting that tests were insufficient to accurately capture the true burden of COVID-19 disease in the minority populations during the initial epidemic wave. While testing disparities decreased during 2020, Hispanic/Latino populations consistently remained the least tested at 1.87 tests per 1000 population per day compared with 2.58 and 2.87 for non-Hispanic Black and non-Hispanic White populations, respectively, at the end of 2020. Despite a large expansion in testing since the beginning of the first wave of the epidemic, we estimated that over half (50-80%) of all SARS-CoV-2 infections were not detected by diagnostic testing and continued to evade surveillance. Conclusions Systematic methods for identifying relatively under-tested geographic regions and demographic groups may enable policymakers to regularly monitor and evaluate the shifting landscape of diagnostic testing, allowing officials to prioritize allocation of testing resources to reduce disparities in COVID-19 burden and eventually reduce SARS-CoV-2 transmission.