California's COVID-19 Vaccine Equity Policy: Cases, Hospitalizations, And Deaths Averted In Affected Communities.

In March 2021, California implemented a vaccine equity policy that prioritized COVID-19 vaccine allocation to communities identified as least advantaged by an area-based socioeconomic measure, the Healthy Places Index. We conducted quasi-experimental and counterfactual analyses to estimate the effect of this policy on COVID-19 vaccination, case, hospitalization, and death rates. Among prioritized communities, vaccination rates increased 28.4 percent after policy implementation. Furthermore, an estimated 160,892 COVID-19 cases, 10,248 hospitalizations, and 679 deaths in the least-advantaged communities were averted by the policy. Despite these improvements, the share of COVID-19 cases, hospitalizations, and deaths in prioritized communities remained elevated. These estimates were robust in sensitivity analyses that tested exchangeability between prioritized communities and those not prioritized by the policy; model specifications; and potential temporal confounders, including prior infections. Correcting for disparities by strategically allocating limited resources to the least-advantaged or most-affected communities can reduce the impacts of COVID-19 and other diseases but might not eliminate health disparities.

Rates of SARS-CoV-2 transmission between and into California state prisons.

Correctional institutions are a crucial hotspot amplifying SARS-CoV-2 spread and disease disparity in the U.S. In the California state prison system, multiple massive outbreaks have been caused by transmission between prisons. Correctional staff are a likely vector for transmission into the prison system from surrounding communities. We used publicly available data to estimate the magnitude of flows to and between California state prisons, estimating rates of transmission from communities to prison staff and residents, among and between residents and staff within facilities, and between staff and residents of distinct facilities in the state's 34 prisons through March 22, 2021. We use a mechanistic model, the Hawkes process, reflecting the dynamics of SARS-CoV-2 transmission, for joint estimation of transmission rates. Using nested models for hypothesis testing, we compared the results to simplified models (i) without transmission between prisons, and (ii) with no distinction between prison staff and residents. We estimated that transmission between different facilities' staff is a significant cause of disease spread, and that staff are a vector of transmission between resident populations and outside communities. While increased screening and vaccination of correctional staff may help reduce introductions, large-scale decarceration remains crucially needed as more limited measures are not likely to prevent large-scale disease spread.

Aligning staff schedules, testing, and isolation reduces the risk of COVID-19 outbreaks in carceral and other congregate settings: A simulation study.

COVID-19 outbreaks in congregate settings remain a serious threat to the health of disproportionately affected populations such as people experiencing incarceration or homelessness, the elderly, and essential workers. An individual-based model accounting for individual infectiousness over time, staff work schedules, and testing and isolation schedules was developed to simulate community transmission of SARS-CoV-2 to staff in a congregate facility and subsequent transmission within the facility that could cause an outbreak. Systematic testing strategies in which staff are tested on the first day of their workweek were found to prevent up to 16% more infections than testing strategies unrelated to staff schedules. Testing staff at the beginning of their workweek, implementing timely isolation following testing, limiting test turnaround time, and increasing test frequency in high transmission scenarios can supplement additional mitigation measures to aid outbreak prevention in congregate settings.

Reframing Optimal Control Problems for Infectious Disease Management in Low-Income Countries.

Optimal control theory can be a useful tool to identify the best strategies for the management of infectious diseases. In most of the applications to disease control with ordinary differential equations, the objective functional to be optimized is formulated in monetary terms as the sum of intervention costs and the cost associated with the burden of disease. We present alternate formulations that express epidemiological outcomes via health metrics and reframe the problem to include features such as budget constraints and epidemiological targets. These alternate formulations are illustrated with a compartmental cholera model. The alternate formulations permit us to better explore the sensitivity of the optimal control solutions to changes in available budget or the desired epidemiological target. We also discuss some limitations of comprehensive cost assessment in epidemiology.

Somewhere to go: assessing the impact of public restroom interventions on reports of open defecation in San Francisco, California from 2014 to 2020.

BACKGROUND: Open defecation due to a lack of access to sanitation facilities remains a public health issue in the United States. People experiencing homelessness face barriers to accessing sanitation facilities, and are often forced to practice open defecation on streets and sidewalks. Exposed feces may contain harmful pathogens posing a significant threat to public health, especially among unhoused persons living near open defecation sites. The City of San Francisco's Department of Public Works implemented the Pit Stop Program to provide the unhoused and the general public with improved access to sanitation with the goal of reducing fecal contamination on streets and sidewalks. The objective of this study was to assess the impact of these public restroom interventions on reports of exposed feces in San Francisco, California. METHODS: We evaluated the impact of various public restroom interventions implemented from January 1, 2014 to January 1, 2020 on reports of exposed feces, captured through a 311 municipal service. Publicly available 311 reports of exposed feces were spatially and temporally matched to 31 Pit Stop restroom interventions at 27 locations across 10 San Francisco neighborhoods. We conducted an interrupted time-series analysis to compare pre- versus post-intervention rates of feces reports near the restrooms. RESULTS: Feces reports declined by 12.47 reports per week after the installation of 13 Pit Stop restrooms (p-value = 0.0002). In the same restrooms, the rate of reports per week declined from the six-month pre-intervention period to the post-intervention period (slope change = -0.024 [95% CI = -0.033, -0.014]). In a subset of restrooms, where new installations were made (Mission and Golden Gate Park), and in another subset of restrooms where restroom attendants were provided (Mission, Castro/Upper Market, and Financial District/South Beach), feces reports also declined. CONCLUSIONS: Increased access to public toilets reduced feces reports in San Francisco, especially in neighborhoods with people experiencing homelessness. The addition of restroom attendants also appeared to have reduced feces reports in some neighborhoods with PEH. These interventions should be audited for implementation quality, observed utilization data, and user experience at the neighborhood level in order to tailor sanitation interventions to neighborhood-specific needs.

Quantitative reverse transcription PCR assay to detect a genetic marker of pyrethroid resistance in Culex mosquitoes.

Pyrethroid insecticides are widely used to control mosquitoes that transmit pathogens such as West Nile virus (WNV) to people. Single nucleotide polymorphisms (SNP) in the knockdown resistance locus (kdr) of the voltage gated sodium channel (Vgsc) gene in Culex mosquitoes are associated with knockdown resistance to pyrethroids. RNAseq was used to sequence the coding region of Vgsc for Culex tarsalis Coquillett and Culex erythrothorax Dyar, two WNV vectors. The cDNA sequences were used to develop a quantitative reverse transcriptase PCR assay that detects the L1014F kdr mutation in the Vgsc. Because this locus is conserved, the assay was used successfully in six Culex spp. The resulting Culex RTkdr assay was validated using quantitative PCR and sequencing of PCR products. The accuracy of the Culex RTkdr assay was 99%. The L1014F kdr mutation associated with pyrethroid resistance was more common among Cx. pipiens than other Culex spp. and was more prevalent in mosquitoes collected near farmland. The Culex RTkdr assay takes advantage of the RNA that vector control agencies routinely isolate to assess arbovirus prevalence in mosquitoes. We anticipate that public health and vector control agencies may employ the Culex RTkdr assay to define the geographic distribution of the L1014F kdr mutation in Culex species and improve the monitoring of insecticide resistance that will ultimately contribute to effective control of Culex mosquitoes.

Modeling scenarios for mitigating outbreaks in congregate settings.

The explosive outbreaks of COVID-19 seen in congregate settings such as prisons and nursing homes, has highlighted a critical need for effective outbreak prevention and mitigation strategies for these settings. Here we consider how different types of control interventions impact the expected number of symptomatic infections due to outbreaks. Introduction of disease into the resident population from the community is modeled as a stochastic point process coupled to a branching process, while spread between residents is modeled via a deterministic compartmental model that accounts for depletion of susceptible individuals. Control is modeled as a proportional decrease in the number of susceptible residents, the reproduction number, and/or the proportion of symptomatic infections. This permits a range of assumptions about the density dependence of transmission and modes of protection by vaccination, depopulation and other types of control. We find that vaccination or depopulation can have a greater than linear effect on the expected number of cases. For example, assuming a reproduction number of 3.0 with density-dependent transmission, we find that preemptively reducing the size of the susceptible population by 20% reduced overall disease burden by 47%. In some circumstances, it may be possible to reduce the risk and burden of disease outbreaks by optimizing the way a group of residents are apportioned into distinct residential units. The optimal apportionment may be different depending on whether the goal is to reduce the probability of an outbreak occurring, or the expected number of cases from outbreak dynamics. In other circumstances there may be an opportunity to implement reactive disease control measures in which the number of susceptible individuals is rapidly reduced once an outbreak has been detected to occur. Reactive control is most effective when the reproduction number is not too high, and there is minimal delay in implementing control. We highlight the California state prison system as an example for how these findings provide a quantitative framework for understanding disease transmission in congregate settings. Our approach and accompanying interactive website (https://phoebelu.shinyapps.io/DepopulationModels/) provides a quantitative framework to evaluate the potential impact of policy decisions governing infection control in outbreak settings.

Deletion of platelet CLEC-2 decreases GPIbα-mediated integrin αIIbß3 activation and decreases thrombosis in TTP.

Microvascular thrombosis in patients with thrombotic thrombocytopenic purpura (TTP) is initiated by GPIbα-mediated platelet binding to von Willebrand factor (VWF). Binding of VWF to GPIbα causes activation of the platelet surface integrin αIIbß3. However, the mechanism of GPIbα-initiated activation of αIIbß3 and its clinical importance for microvascular thrombosis remain elusive. Deletion of platelet C-type lectin-like receptor 2 (CLEC-2) did not prevent VWF binding to platelets but specifically inhibited platelet aggregation induced by VWF binding in mice. Deletion of platelet CLEC-2 also inhibited αIIbß3 activation induced by the binding of VWF to GPIbα. Using a mouse model of TTP, which was created by infusion of anti-mouse ADAMTS13 monoclonal antibodies followed by infusion of VWF, we found that deletion of platelet CLEC-2 decreased pulmonary arterial thrombosis and the severity of thrombocytopenia. Importantly, prophylactic oral administration of aspirin, an inhibitor of platelet activation, and therapeutic treatment of the TTP mice with eptifibatide, an integrin αIIbß3 antagonist, reduced pulmonary arterial thrombosis in the TTP mouse model. Our observations demonstrate that GPIbα-mediated activation of integrin αIIbß3 plays an important role in the formation of thrombosis in TTP. These observations suggest that prevention of platelet activation with aspirin may reduce the risk for thrombosis in patients with TTP.

Mitigating outbreaks in congregate settings by decreasing the size of the susceptible population.

While many transmission models have been developed for community spread of respiratory pathogens, less attention has been given to modeling the interdependence of disease introduction and spread seen in congregate settings, such as prisons or nursing homes. As demonstrated by the explosive outbreaks of COVID-19 seen in congregate settings, the need for effective outbreak prevention and mitigation strategies for these settings is critical. Here we consider how interventions that decrease the size of the susceptible populations, such as vaccination or depopulation, impact the expected number of infections due to outbreaks. Introduction of disease into the resident population from the community is modeled as a branching process, while spread between residents is modeled via a compartmental model. Control is modeled as a proportional decrease in both the number of susceptible residents and the reproduction number. We find that vaccination or depopulation can have a greater than linear effect on anticipated infections. For example, assuming a reproduction number of 3.0 for density-dependent COVID-19 transmission, we find that reducing the size of the susceptible population by 20% reduced overall disease burden by 47%. We highlight the California state prison system as an example for how these findings provide a quantitative framework for implementing infection control in congregate settings. Additional applications of our modeling framework include optimizing the distribution of residents into independent residential units, and comparison of preemptive versus reactive vaccination strategies.

L-SIGN is a receptor on liver sinusoidal endothelial cells for SARS-CoV-2 virus.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a pandemic. Severe disease is associated with dysfunction of multiple organs, but some infected cells do not express ACE2, the canonical entry receptor for SARS-CoV-2. Here, we report that the C-type lectin receptor L-SIGN interacted in a Ca2+-dependent manner with high-mannose-type N-glycans on the SARS-CoV-2 spike protein. We found that L-SIGN was highly expressed on human liver sinusoidal endothelial cells (LSECs) and lymph node lymphatic endothelial cells but not on blood endothelial cells. Using high-resolution confocal microscopy imaging, we detected SARS-CoV-2 viral proteins within the LSECs from liver autopsy samples from patients with COVID-19. We found that both pseudo-typed virus enveloped with SARS-CoV-2 spike protein and authentic SARS-CoV-2 virus infected L-SIGN-expressing cells relative to control cells. Moreover, blocking L-SIGN function reduced CoV-2-type infection. These results indicate that L-SIGN is a receptor for SARS-CoV-2 infection. LSECs are major sources of the clotting factors vWF and factor VIII (FVIII). LSECs from liver autopsy samples from patients with COVID-19 expressed substantially higher levels of vWF and FVIII than LSECs from uninfected liver samples. Our data demonstrate that L-SIGN is an endothelial cell receptor for SARS-CoV-2 that may contribute to COVID-19-associated coagulopathy.

Kupffer cell receptor CLEC4F is important for the destruction of desialylated platelets in mice.

The liver has recently been identified as a major organ for destruction of desialylated platelets. However, the underlying mechanism remains unclear. Kupffer cells, which are professional phagocytic cells in the liver, comprise the largest population of resident tissue macrophages in the body. Kupffer cells express a C-type lectin receptor, CLEC4F, that recognizes desialylated glycans with an unclear in vivo role in mediating platelet destruction. In this study, we generated a CLEC4F-deficient mouse model (Clec4f-/-) and found that CLEC4F was specifically expressed by Kupffer cells. Using the Clec4f-/- mice and a newly generated platelet-specific reporter mouse line, we revealed a critical role for CLEC4F on Kupffer cells in mediating destruction of desialylated platelets in the liver in vivo. Platelet clearance experiments and ultrastructural analysis revealed that desialylated platelets were phagocytized predominantly by Kupffer cells in a CLEC4F-dependent manner in mice. Collectively, these findings identify CLEC4F as a Kupffer cell receptor important for the destruction of desialylated platelets induced by bacteria-derived neuraminidases, which provide new insights into the pathogenesis of thrombocytopenia in disease conditions such as sepsis.

School closures reduced social mixing of children during COVID-19 with implications for transmission risk and school reopening policies.

School closures may reduce the size of social networks among children, potentially limiting infectious disease transmission. To estimate the impact of K-12 closures and reopening policies on children's social interactions and COVID-19 incidence in California's Bay Area, we collected data on children's social contacts and assessed implications for transmission using an individual-based model. Elementary and Hispanic children had more contacts during closures than high school and non-Hispanic children, respectively. We estimated that spring 2020 closures of elementary schools averted 2167 cases in the Bay Area (95% CI: -985, 5572), fewer than middle (5884; 95% CI: 1478, 11.550), high school (8650; 95% CI: 3054, 15 940) and workplace (15 813; 95% CI: 9963, 22 617) closures. Under assumptions of moderate community transmission, we estimated that reopening for a four-month semester without any precautions will increase symptomatic illness among high school teachers (an additional 40.7% expected to experience symptomatic infection, 95% CI: 1.9, 61.1), middle school teachers (37.2%, 95% CI: 4.6, 58.1) and elementary school teachers (4.1%, 95% CI: -1.7, 12.0). However, we found that reopening policies for elementary schools that combine universal masking with classroom cohorts could result in few within-school transmissions, while high schools may require masking plus a staggered hybrid schedule. Stronger community interventions (e.g. remote work, social distancing) decreased the risk of within-school transmission across all measures studied, with the influence of community transmission minimized as the effectiveness of the within-school measures increased.

Heightened activation of embryonic megakaryocytes causes aneurysms in the developing brain of mice lacking podoplanin.

During early embryonic development in mammals, including humans and mice, megakaryocytes (Mks) first originate from primitive hematopoiesis in the yolk sac. These embryonic Mks (eMks) circulate in the vasculature with unclear function. Herein, we report that podoplanin (PDPN), the ligand of C-type lectin-like receptor (CLEC-2) on Mks/platelets, is temporarily expressed in neural tissue during midgestation in mice. Loss of PDPN or CLEC-2 resulted in aneurysms and spontaneous hemorrhage, specifically in the lower diencephalon during midgestation. Surprisingly, more eMks/platelets had enhanced granule release and localized to the lower diencephalon in mutant mouse embryos than in wild-type littermates before hemorrhage. We found that PDPN counteracted the collagen-1-induced secretion of angiopoietin-1 from fetal Mks, which coincided with enhanced TIE-2 activation in aneurysm-like sprouts of PDPN-deficient embryos. Blocking platelet activation prevented the PDPN-deficient embryo from developing vascular defects. Our data reveal a new role for PDPN in regulating eMk function during midgestation.

The COVID-19 Symptom to Isolation Cascade in a Latinx Community: A Call to Action.

BACKGROUND: Rapid coronavirus disease 2019 (COVID-19) diagnosis and isolation of infectious persons are critical to stopping forward transmission, and the care cascade framework can identify gaps in the COVID-19 response. METHODS: We described a COVID-19 symptom to isolation cascade and barriers among symptomatic persons who tested polymerase chain reaction positive for severe acute respiratory disease coronavirus 2 (SARS-CoV-2) at a low-barrier testing site serving a low-income Latinx community in San Francisco. Steps in the cascade are defined as days from symptom onset to test, test to result, and result to counseling on self-isolation. We examined SARS-CoV-2 cycle threshold (Ct) values to assess the likelihood of infectiousness on the day of testing and during missed isolation days. RESULTS: Among 145 persons, 97% were Latinx and 81% had an income of <$50 000. The median time from symptom onset to isolation (interquartile range [IQR]) was 7 (5-10) days, leaving a median (IQR) of 3 (0-6) days of isolation. Eighty-three percent had moderate to high levels of virus (Ct <33), but by disclosure 23% were out of their isolation period. The longest intervals were symptom onset to test (median [IQR], 4 [2-9] days) and test to results notification (median [IQR], 3 [2-4] days). Access to a test site was the most common barrier to testing, and food and income loss was the most common barrier to isolation. CONCLUSIONS: Over half of the 10-day isolation period passed by the time of disclosure, and over a fifth of people were likely outside the window of infectiousness by the time they received results. Improvements in test access and turnaround time, plus support for isolation, are needed for epidemic control of SARS-CoV-2 in highly impacted communities.

Modelled effects of prawn aquaculture on poverty alleviation and schistosomiasis control.

Recent evidence suggests that snail predators may aid efforts to control the human parasitic disease schistosomiasis by eating aquatic snail species that serve as intermediate hosts of the parasite. Potential synergies between schistosomiasis control and aquaculture of giant prawns are evaluated using an integrated bio-economic-epidemiologic model. Combinations of stocking density and aquaculture cycle length that maximize cumulative, discounted profit are identified for two prawn species in sub-Saharan Africa: the endemic, non-domesticated Macrobrachium vollenhovenii, and the non-native, domesticated Macrobrachium rosenbergii. At profit maximizing densities, both M. rosenbergii and M. vollenhovenii may substantially reduce intermediate host snail populations and aid schistosomiasis control efforts. Control strategies drawing on both prawn aquaculture to reduce intermediate host snail populations and mass drug administration to treat infected individuals are found to be superior to either strategy alone. Integrated aquaculture-based interventions can be a win-win strategy in terms of health and sustainable development in schistosomiasis endemic regions of the world.

Prenatal and early-life exposure to the Great Chinese Famine increased the risk of tuberculosis in adulthood across two generations.

Global food security is a major driver of population health, and food system collapse may have complex and long-lasting effects on health outcomes. We examined the effect of prenatal exposure to the Great Chinese Famine (1958-1962)-the largest famine in human history-on pulmonary tuberculosis (PTB) across consecutive generations in a major center of ongoing transmission in China. We analyzed >1 million PTB cases diagnosed between 2005 and 2018 in Sichuan Province using age-period-cohort analysis and mixed-effects metaregression to estimate the effect of the famine on PTB risk in the directly affected birth cohort (F1) and their likely offspring (F2). The analysis was repeated on certain sexually transmitted and blood-borne infections (STBBI) to explore potential mechanisms of the intergenerational effects. A substantial burden of active PTB in the exposed F1 cohort and their offspring was attributable to the Great Chinese Famine, with more than 12,000 famine-attributable active PTB cases (>1.23% of all cases reported between 2005 and 2018). An interquartile range increase in famine intensity resulted in a 6.53% (95% confidence interval [CI]: 1.19-12.14%) increase in the ratio of observed to expected incidence rate (incidence rate ratio, IRR) in the absence of famine in F1, and an 8.32% (95% CI: 0.59-16.6%) increase in F2 IRR. Increased risk of STBBI was also observed in F2. Prenatal and early-life exposure to malnutrition may increase the risk of active PTB in the exposed generation and their offspring, with the intergenerational effect potentially due to both within-household transmission and increases in host susceptibility.

Proximal colon-derived O-glycosylated mucus encapsulates and modulates the microbiota.

Colon mucus segregates the intestinal microbiota from host tissues, but how it organizes to function throughout the colon is unclear. In mice, we found that colon mucus consists of two distinct O-glycosylated entities of Muc2: a major form produced by the proximal colon, which encapsulates the fecal material including the microbiota, and a minor form derived from the distal colon, which adheres to the major form. The microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells. In turn, O-glycans on proximal colon-derived Muc2 modulate the structure and function of the microbiota as well as transcription in the colon mucosa. Our work shows how proximal colon control of mucin production is an important element in the regulation of host-microbiota symbiosis.

Optimal Modeling: an Updated Method for Safely and Effectively Eliminating Curvature During Penile Prosthesis Implantation.

OBJECTIVES: To assess outcomes of a variant of traditional modeling ("optimal modeling," OM) in patients with residual curvature following prosthesis implantation. METHODS: We performed a retrospective review of all patients who underwent penile implant insertion. Patients with >30° of residual curvature after cylinder placement and inflation underwent OM and were compared 1:1 to a demographically-matched cohort who received implantation without ancillary straightening. Optimal modeling was performed by forcibly bending the erect penis in the direction opposite the point of maximal curvature while maintaining glanular pressure to prevent urethral injury. This was performed for 90-second intervals for as many cycles as necessary to achieve <15° curvature. RESULTS: Eighty patients were included in the final analysis; 40 (50.0%) underwent optimal modeling while 40 (50.0%) did not need additional straightening following surgery. The mean premodeling curvature was 47.8° (range 30°-90°) while post-modeling curvature improved to a mean of 10.6° (range 0°-30°, P < .001); 87.5% of patients had <15° of residual curvature. Patients in the OM cohort experienced longer operative times (82.7 vs 75.8 min, P = .15). No patient in either group experienced an intraoperative or postoperative complication at a mean follow-up of 29.9 months. CONCLUSION: Although many prosthetic urologists forego manual modeling in cases of moderate-severe penile curvature, our contemporary series shows it to be both safe and effective. OM may preclude the need for more time-consuming and complex surgical procedures.

The effect of school closures and reopening strategies on COVID-19 infection dynamics in the San Francisco Bay Area: a cross-sectional survey and modeling analysis.

Background Large-scale school closures have been implemented worldwide to curb the spread of COVID-19. However, the impact of school closures and re-opening on epidemic dynamics remains unclear. Methods We simulated COVID-19 transmission dynamics using an individual-based stochastic model, incorporating social-contact data of school-aged children during shelter-in-place orders derived from Bay Area (California) household surveys. We simulated transmission under observed conditions and counterfactual intervention scenarios between March 17-June 1, and evaluated various fall 2020 K-12 reopening strategies. Findings Between March 17-June 1, assuming children <10 were half as susceptible to infection as older children and adults, we estimated school closures averted a similar number of infections (13,842 cases; 95% CI: 6,290, 23,040) as workplace closures (15,813; 95% CI: 9,963, 22,617) and social distancing measures (7,030; 95% CI: 3,118, 11,676). School closure effects were driven by high school and middle school closures. Under assumptions of moderate community transmission, we estimate that fall 2020 school reopenings will increase symptomatic illness among high school teachers (an additional 40.7% expected to experience symptomatic infection, 95% CI: 1.9, 61.1), middle school teachers (37.2%, 95% CI: 4.6, 58.1), and elementary school teachers (4.1%, 95% CI: -1.7, 12.0). Results are highly dependent on uncertain parameters, notably the relative susceptibility and infectiousness of children, and extent of community transmission amid re-opening. The school-based interventions needed to reduce the risk to fewer than an additional 1% of teachers infected varies by grade level. A hybrid-learning approach with halved class sizes of 10 students may be needed in high schools, while maintaining small cohorts of 20 students may be needed for elementary schools. Interpretation Multiple in-school intervention strategies and community transmission reductions, beyond the extent achieved to date, will be necessary to avoid undue excess risk associated with school reopening. Policymakers must urgently enact policies that curb community transmission and implement within-school control measures to simultaneously address the tandem health crises posed by COVID-19 and adverse child health and development consequences of long-term school closures.